Brazilian Journal of Cardiovascular Surgery 29.4 by Revista Brasileira de Cirurgia Cardiovascular

29.4 OCTOBER/DECEMBER 2014

REVISTA BRASILEIRA DE CIRURGIA CARDIOVASCULAR | BRAZILIAN JOURNAL OF CARDIOVASCULAR SURGERY

VOL. 29 Nยบ 4 OCTOBER/DECEMBER 2014

Agende esta data e garanta sua presença no SBCCV 2015

Educação Médica

26a 28 de março de 2015

frente às novas tecnologias

S BCC V

CONGRESSO DA SOCIEDADE BRASILEIRA

DE CIRURGIA CARDIOVASCULAR

5º Simpósio de Enfermagem em Cirurgia Cardiovascular 5º Simpósio de Fisioterapia em Cirurgia Cardiovascular 4º Congresso Acadêmico em Cirurgia Cardiovascular

26 a 28 de março de 2015 • Curitiba • Paraná • Brasil

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Você tem quatro bons motivos para participar deste evento: 1 PROGRAMA Através de palestras, mesas redondas e cursos avançados vamos discutir, debater e compartilhar experiências sobre a atualização profissional frente às novas tecnologias.

2 HANDS ON Uma estratégia de ensino-aprendizagem, que permite a interação entre o expert e os cirurgiões que desejam dominar novas tecnologias de comprovada eficácia, mas com baixas taxas de adoção, e os novos procedimentos com um domínio ainda restrito, mas em fase de expansão na prática clínica.

PROMOÇÃO Sociedade Brasileira de Cirurgia Cardiovascular

anúncio sbccv 2015.indd 1

3 PALESTRANTES A programação, como de hábito, vai reunir especialistas de reconhecido mérito acadêmico, destacando presenças nacionais e internacionais.

ORGANIZAÇÃO

(51) 3061.2959 inscricoes@abev.com.br www.abev.com.br

4 TEMAS LIVRES Uma oportunidade de divulgar e compartilhar a sua produção científica e ensaio clínico inovador através da discussão de temas importantes para os cirurgiões cardiovasculares. Partilhe sua experiência e contribua para o avanço da nossa especialidade médica.

AGÊNCIA OFICIAL

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29/08/14 13:47

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RBCCV REVISTA BRASILEIRA DE CIRURGIA CARDIOVASCULAR

EDITOR/EDITOR Prof. Dr. Domingo M. Braile - PhD São José do Rio Preto - SP - Brasil domingo@braile.com.br

BRAZILIAN JOURNAL OF CARDIOVASCULAR SURGERY

EDITORES ANTERIORES/FORMER EDITORS • Prof. Dr. Adib D. Jatene PhD - São Paulo (BRA) [1986-1996] • Prof. Dr. Fábio B. Jatene PhD - São Paulo (BRA) [1996-2002]

EDITOR EXECUTIVO EXECUTIVE EDITOR Ricardo Brandau Pós-graduado em Jornalismo Científico - S. José do Rio Preto (BRA) brandau@sbccv.org.br

ASSESSORA EDITORIAL/EDITORIAL ASSISTANT Rosangela Monteiro Camila Safadi PhD - São Paulo (BRA) S. José do Rio Preto (BRA) rosangela.monteiro@incor.usp.br camila@sbccv.org.br

EDITORES ASSOCIADOS/ASSOCIATE EDITORS • Antônio Sérgio Martins • Gilberto Venossi Barbosa • José Dario Frota Filho • José Teles de Mendonça • Luciano Cabral Albuquerque • Luis Alberto Oliveira Dallan • Luiz Felipe Pinho Moreira

Botucatu (BRA) Porto Alegre (BRA) Porto Alegre (BRA) Aracaju (BRA) Porto Alegre (BRA) São Paulo (BRA) São Paulo (BRA)

• Manuel Antunes • Mario O. Vrandecic Peredo • Michel Pompeu B. Oliveira Sá • Paulo Roberto Slud Brofman • Ricardo C. Lima • Ulisses A. Croti • Walter José Gomes

Coimbra (POR) Belo Horizonte (BRA) Recife (BRA) Curitiba (BRA) Recife (BRA) S.J. Rio Preto (BRA) São Paulo (BRA)

EDITOR DE ESTATÍSTICA/STATISTICS EDITOR • Orlando Petrucci Jr.

Campinas (BRA)

CONSELHO EDITORIAL/EDITORIAL BOARD • Adolfo Leirner • Adolfo Saadia • Alan Menkis • Alexandre V. Brick • Antônio Carlos G. Penna Jr. • Bayard Gontijo Filho • Borut Gersak • Carlos Roberto Moraes • Christian Schreiber • Cláudio Azevedo Salles • Djair Brindeiro Filho • Eduardo Keller Saadi • Eduardo Sérgio Bastos • Enio Buffolo • Fábio B. Jatene • Fernando Antônio Lucchese • Gianni D. Angelini • Gilles D. Dreyfus • Ivo A. Nesralla • Jarbas J. Dinkhuysen • José Antônio F. Ramires • José Ernesto Succi • José Pedro da Silva • Joseph A. Dearani

São Paulo (BRA) Buenos Aires (ARG) Winnipeg (CAN) Brasília (BRA) Marília (BRA) Belo Horizonte (BRA) Ljubljana (SLO) Recife (BRA) Munique (GER) Belo Horizonte (BRA) Recife (BRA) Porto Alegre (BRA) Rio de Janeiro (BRA) São Paulo (BRA) São Paulo (BRA) Porto Alegre (BRA) Bristol (UK) Harefield (UK) Porto Alegre (BRA) São Paulo (BRA) São Paulo (BRA) São Paulo (BRA) São Paulo (BRA) Rochester (USA)

VERSÃO PARA O INGLÊS/ENGLISH VERSION • Fernando Pires Buosi • Maria Carolina Zuppardo • Marcelo Almeida

• Joseph S. Coselli • Luiz Carlos Bento de Souza • Luiz Fernando Kubrusly • Mauro Paes Leme de Sá • Miguel Barbero Marcial • Milton Ary Meier • Nilzo A. Mendes Ribeiro • Noedir A. G. Stolf • Olivio Alves Souza Neto • Otoni Moreira Gomes • Pablo M. A. Pomerantzeff • Paulo Manuel Pêgo Fernandes • Paulo P. Paulista • Paulo Roberto B. Évora • Pirooz Eghtesady • Protásio Lemos da Luz • Reinaldo Wilson Vieira • Renato Abdala Karam Kalil • Renato Samy Assad • Roberto Costa • Rodolfo Neirotti • Rui M. S. Almeida • Sérgio Almeida de Oliveira • Tomas A. Salerno

Houston (USA) São Paulo (BRA) Curitiba (BRA) Rio de Janeiro (BRA) São Paulo (BRA) Rio de Janeiro (BRA) Salvador (BRA) São Paulo (BRA) Rio de Janeiro (BRA) Belo Horizonte (BRA) São Paulo (BRA) São Paulo (BRA) São Paulo (BRA) Ribeirão Preto (BRA) Cincinatti (USA) São Paulo (BRA) Campinas (BRA) Porto Alegre (BRA) São Paulo (BRA) São Paulo (BRA) Cambridge (USA) Cascavel (BRA) São Paulo (BRA) Miami (USA)

ÓRGÃO OFICIAL DA SOCIEDADE BRASILEIRA DE CIRURGIA CARDIOVASCULAR DESDE 1986 OFFICIAL ORGAN OF THE BRAZILIAN SOCIETY OF CARDIOVASCULAR SURGERY SINCE 1986

ENDEREÇO/ADDRESS

Sociedade Brasileira de Cirurgia Cardiovascular

Rua Afonso Celso, 1178 • Vila Mariana • Fone: 11 3849-0341. Fax: 11 5096-0079. Cep: 04119-061 • São Paulo, SP, Brasil E-mail RBCCV: revista@sbccv.org.br • E-mail SBCCV: sbccv@sbccv.org.br • Site SBCCV: www.sbccv.org.br • Sites RBCCV: www.scielo.br/rbccv / www.rbccv.org.br (também para submissão de artigos)

Publicação trimestral/Quarterly publication Edição Impressa - Tiragem: 250 exemplares (*)

REVISTA BRASILEIRA DE CIRURGIA CARDIOVASCULAR (Sociedade Brasileira de Cirurgia Cardiovascular) São Paulo, SP - Brasil. v. 119861986, 1: 1,2 1987, 2: 1,2,3 1988, 3: 1,2,3 1989, 4: 1,2,3 1990, 5: 1,2,3 1991, 6: 1,2,3 1992, 7: 1,2,3,4 1993, 8: 1,2,3,4 1994, 9: 1,2,3,4 1995, 10: 1,2,3,4

2006, 21: 1 [supl] 2006, 21: 1,2,3,4 2007, 22: 1 [supl] 2007, 22: 1,2,3,4 2008, 23: 1 [supl] 2008, 23: 1,2,3,4 2009, 24: 1 [supl] 2009, 24: 1,2,3,4 2009, 24: 2 [supl] 2010, 25: 1,2,3,4

1996, 11: 1,2,3,4 1997, 12: 1,2,3,4 1998, 13: 1,2,3,4 1999, 14: 1,2,3,4 2000, 15: 1,2,3,4 2001, 16: 1,2,3,4 2002, 17: 1,2,3,4 2003, 18: 1,2,3,4 2004, 19: 1,2,3,4 2005, 20: 1,2,3,4

2010, 25: 1 [supl] 2011, 26: 1,2,3,4 2011, 26: 1 [supl] 2012, 27: 1,2,3,4 2012, 27: 1 [supl] 2013, 28: 1,2,3,4 2013, 28: 1 [supl] 2014, 29: 1,2,3,4 2014, 29: 1 [supl]

ISSN 1678-9741 - Publicação on-line ISSN 0102-7638 - Publicação impressa RBCCV 44205

CDD 617.4105 NLM18 WG 168

(*) ASSOCIAÇÃO PAULISTA DE BIBLIOTECÁRIOS. Grupo de Bibliotecários Biomédicos. Normas para catalogação de publicações seriadas nas bibliotecas especializadas. São Paulo, Ed. Polígono, 1972

INDEXADA EM • Thomson Scientific (ISI) http://science.thomsonreuters.com • PubMed/Medline www.ncbi.nlm.nih.gov/sites/entrez • SciELO - Scientific Library Online www.scielo.br • Scopus www.info.scopus.com • LILACS - Literatura Latino-Americana e do Caribe em Ciências da Saúde. www.bireme.org • LATINDEX -Sistema Regional de Información en Línea para Revistas Cientificas de America Latina, el Caribe, España y Portugal www.latindex.uam.mx

• ADSAUDE - Sistema Especializado de Informação em Administração de Saúde www.bibcir.fsp.usp.br/html/p/pesquisa_em_ bases_de_dados/programa_rede_adsaude • Index Copernicus www.indexcopernicus.com • Google scholar http://scholar.google.com.br/scholar • EBSCO www2.ebsco.com/pt-br

SOCIEDADE BRASILEIRA DE CIRURGIA CARDIOVASCULAR

BRAZILIAN SOCIETY OF CARDIOVASCULAR SURGERY DEPARTAMENTO DE CIRURGIA DA SOCIEDADE BRASILEIRA DE CARDIOLOGIA DEPARTMENT OF SURGERY OF THE BRAZILIAN SOCIETY OF CARDIOLOGY

“Valorizando o profissional em prol do paciente” DIRETORIA 2014 - 2015 Presidente: Vice-Presidente: Secretário Geral: Tesoureiro: Diretor Científico:

Marcelo Matos Cascudo (RN) Fábio Biscegli Jatene (SP) Henrique Murad (RJ) Eduardo Augusto Victor Rocha (MG) Rui M.S. Almeida (PR)

Conselho Deliberativo:

Bruno Botelho Pinheiro (GO) Henrique Barsanulfo Furtado (TO) José Pedro da Silva (SP) Luciano Cabral Albuquerque (RS) Ricardo de Carvalho Lima (PE)

Editor da Revista: Editor do Site: Editores do Boletim:

Domingo Marcolino Braile (SP) João Carlos Ferreira Leal (SP) Walter José Gomes (SP) Domingo Marcolino Braile (SP) Orlando Petrucci (SP) Luciano Cabral Albuquerque (RS) Fernando Ribeiro Moraes Neto (PE)

Presidentes das Regionais Afiliadas Norte-Nordeste: Rio de Janeiro: São Paulo: Minas Gerais: Centro-Oeste: Rio Grande do Sul: Paraná: Santa Catarina:

Vinícius José da Silva Nina (MA) Marcelo Sávio da Silva Martins Rubens Tofano de Barros Rodrigo de Castro Bernardes Jorge Luiz França de Vasconcelos (MS) Marcela da Cunha Sales Luiz César Guarita Souza Milton de Miranda Santoro

Departamentos DCCVPED: DECAM: DECA: DECEM: DEPEX: DECARDIO: DBLACCV: ABRECCV:

Luiz Fernando Canêo (SP) Juan Alberto Cosquillo Mejia (CE) Cláudio José Fuganti (PR) Eduardo Keller Saadi (RS) Alexandre Ciappina Hueb (SP) José Carlos Dorsa V. Pontes (MS) Leila Nogueira Barros (SP) Paulo Marcelo Barbosa Mesquita (SP)

SOCIEDADE BRASILEIRA DE CIRURGIA CARDIOVASCULAR BRAZILIAN SOCIETY OF CARDIOVASCULAR SURGERY E-mail: revista@sbccv.org.br Sites: www.scielo.br/rbccv www.rbccv.org.br

REVISTA BRASILEIRA DE CIRURGIA CARDIOVASCULAR

ISSN 1678-9741 - On-line ISSN 0102-7638 - Printed RBCCV 44205

Impact Factor: 0,632

BRAZILIAN JOURNAL OF CARDIOVASCULAR SURGERY Rev Bras Cir Cardiovasc, (São José do Rio Preto, SP - Brazil) oct/dec - 2014;29(4) 473-676

CONTENTS/SUMÁRIO EDITORIAL/EDITORIAL Adib Domingos Jatene (1929 – 2014) Adib Domingos Jatene (1929 – 2014) Domingo M. Braile.................................................................................................................................................................................. I IN MEMORIAM/MEMÓRIA 1578 Adib Jatene: June 4, 1929 - November 14, 2014 Adib Jatene: 04 de junho de 1929 - 14 de novembro de 2014 Domingo M. Braile, Enio Buffolo........................................................................................................................................................473 ORIGINAL ARTICLES/ARTIGOS ORIGINAIS 1579 New contribution to the study of ventricular remodeling and valve rings in dilated cardiomyopathy: anatomical and histological evaluation Nova contribuição ao estudo do remodelamento ventricular e dos anéis valvares na cardiomiopatia dilatada: avaliação anátomohistopatológica Moise Dalva, Aristides Tadeu Correia, Natalia de Freitas Jatene, Paulo Hilário Nascimento Saldiva, Fabio Biscegli Jatene............478 1580 Risk factors of atheromatous aorta in cardiovascular surgery Fatores de risco de ateromatose da aorta em cirurgia cardiovascular Fernando A. Atik, Isaac Azevedo Silva, Claudio Ribeiro da Cunha....................................................................................................487 1581 Aortic Center: specialized care improves outcomes and decreases mortality Centro de Tratamento da Aorta: a especialização reduz complicações e mortalidade Marcela da Cunha Sales, José Dario Frota Filho, Cristiane Aguzzoli, Leonardo Dornelles Souza, Álvaro Machado Rösler, Eraldo Azevedo Lucio, Paulo Ernesto Leães, Mauro Ricardo Nunes Pontes, Fernando Antonio Lucchese..................................................494 1582 Comparison of two surgical techniques for creating an acute myocardial infarct in rats Comparação de duas técnicas cirúrgicas para criar um infarto agudo do miocárdio em ratos Luiz Guilherme Achcar Capriglione, Fabiane Barchiki, Gabriel Sales Ottoboni, Nelson Itiro Miyague, Paula Hansen Suss, Carmen Lúcia Kuniyoshi Rebelatto, Cláudia Turra Pimpão, Alexandra Cristina Senegaglia, Paulo Roberto Brofman...................................505 1583 Risk factors for mortality of patients undergoing coronary artery bypass graft surgery Fatores de risco para mortalidade de pacientes submetidos à revascularização miocárdica Carlos Alberto dos Santos, Marcos Aurélio Barboza de Oliveira, Antônio Carlos Brandi, Paulo Henrique Husseini Botelho, Josélia de Cássia Menin Brandi, Marcio Antonio dos Santos, Moacir Fernandes de Godoy, Domingo Marcolino Braile..................................513 1584 Very short cycles of postconditioning have no protective effect against reperfusion injury. Experimental study in rats Ciclos muito curtos de pós-condicionamento não protegem contra lesão de reperfusão. Estudo experimental em ratos Ricardo Kenithi Nakamura, Carlos Henrique Marques dos Santos, Luciana Nakao Odashiro Miiji, Mariana Sousa Arakaki, Cristiane Midori Maedo, Maurício Érnica Filho, Pedro Carvalho Cassino, Elenir Rose Jardim Cury Pontes...................................................521 1585 Hybrid treatment of aortic arch disease Tratamento híbrido das doenças do arco aórtico Patrick Bastos Metzger, Fabio Henrique Rossi, Samuel Martins Moreira, Mario Issa, Nilo Mitsuru Izukawa, Jarbas J. Dinkhuysen, Domingos Spina Neto, Antonio Massamitsu Kambara........................................................................................................................527

1586 Evaluation of variables responsible for hospital mortality in patients with rheumatic heart disease undergoing double valve replacement Avaliação de variáveis responsáveis pela mortalidade hospitalar em pacientes portadores de doença reumática submetidos à dupla troca valvar André Maurício Souza Fernandes, Gustavo Maltez de Andrade, Rafael Marcelino Oliveira, Gabriela Tanajura Biscaia, Francisco Farias Borges dos Reis, Cristiano Ricardo Macedo, Andre Rodrigues Durães, Roque Aras Junior..............................................................537 1587 Graft pathology at the time of harvest: impact on long-term survival Patologia do enxerto no momento da coleta: impacto na sobrevida a longo prazo Shi-Min Yuan, Yun Li, Yan Hong Ben, Xiao Feng Cheng, Da Zhu Li, De Min Li, Hua Jing.............................................................543 1588 Effectiveness of the endotracheal tube cuff on the trachea: physical and mechanical aspects Eficácia do balonete do tubo endotraqueal sobre a traqueia: aspectos físicos e mecânicos Maira Soliani Del Negro, Gilson Barreto, Raíssa Quaiatti Antonelli, Tiago Antônio Baldasso, Luciana Rodrigues de Meirelles, Marcos Mello Moreira, Alfio José Tincani........................................................................................................................................................552 1589 Influence of valve prosthesis type on early mortality in patients undergoing valve surgery A influência da escolha da prótese valvar sobre a mortalidade intra-hospitalar no pós-operatório em pacientes submetidos à cirurgia valvar Andre Mauricio S. Fernandes, Felipe da Silva Pereira, Larissa Santana Bitencourt, Agnaldo Viana Pereira Neto, Gabriel Barreto Bastos, André Rodrigues Durães, Roque Aras Jr, Igor Nogueira Lessa...........................................................................................................559 1590 Distribution of saphenous vein valves and its pratical importance Distribuição das válvulas da veia safena magna e sua importância prática Isabella Batista Martins Portugal, Igor de Lima Ribeiro, Célio Fernando de Sousa-Rodrigues, Rodrigo Freitas Monte-Bispo, Amauri Clemente da Rocha...............................................................................................................................................................................564 1591 The effect of gender on the early results of coronary artery bypass surgery in the younger patients’ group O efeito do gênero sobre os resultados iniciais da cirurgia de revascularização do miocárdio em grupo de pacientes mais jovens Hasan Uncu, Mehmet Acipayam, Levent Altinay, Pinar Doğan, Isil Davarcı, İbrahim Özsöyler.......................................................569 1592 Carotid endarterectomy in awake patients: safety, tolerability and results Endarterectomia de carótida em pacientes acordados: segurança, tolerabilidade e resultados Célio Teixeira Mendonça, Jerônimo A. Fortunato Jr., Cláudio A. de Carvalho, Janaina Weingartner, Otávio R. M. Filho, Felipe F. Rezende, Luciane P. Bertinato..............................................................................................................................................................574 1593 Nebivolol in preventing atrial fibrillation following coronary surgery in patients over 60 years of age Nebivolol na prevenção da fibrilação atrial após a cirurgia coronária em pacientes acima de 60 anos de idade Nevzat Erdil, Murat Kaynak, Köksal Dönmez, Olcay Murat Disli, Bektas Battaloglu.......................................................................581 1594 Pleural subxyphoid drain confers better pulmonary function and clinical outcomes in chronic obstructive pulmonary disease after off-pump coronary artery bypass grafting: a randomized controlled trial Dreno pleural subxifoide confere melhor função pulmonar e resultados clínicos na doença pulmonar obstrutiva crônica após cirurgia de revascularização miocárdica sem circulação extracorpórea: ensaio clínico controlado e randomizado Solange Guizilini, Marcela Viceconte, Gabriel Tavares da M. Esperança, Douglas W. Bolzan, Milena Vidotto, Rita Simone L Moreira, Andréia Azevedo Câncio, Walter J Gomes..........................................................................................................................................588 1595 Comparative trial of the use of antiplatelet and oral anticoagulant in thrombosis prophylaxis in patients undergoing total cavopulmonary operation with extracardiac conduit: echocardiographic, tomographic, scintigraphic, clinical, and laboratory analysis Estudo comparativo entre o uso do antiagregante plaquetário e do anticoagulante oral na profilaxia de trombose em pacientes submetidos à operação cavopulmonar total com tubo extracardíaco: análise ecocardiográfica, angiotomográfica, cintilográfica, laboratorial e clínica Cristiane Felix Ximenes Pessotti, Marcelo Biscegli Jatene, Ieda Biscegli Jatene, Patricia Marques Oliveira, Fabiana Moreira Passos Succi, Valeria de Melo Moreira, Rafael Willian Lopes, Simone Rolim Fernandes Fontes Pedra.......................................................595 REVIEW ARTICLES/ARTIGOS DE REVISÃO 1596 Therapeutic options to minimize allogeneic blood transfusions and their adverse effects in cardiac surgery: A systematic review Opções terapêuticas para minimizar transfusões de sangue alogênico e seus efeitos adversos em cirurgia cardíaca: Revisão sistemática Antonio Alceu dos Santos, José Pedro da Silva, Luciana da Fonseca da Silva, Alexandre Gonçalves de Sousa, Raquel Ferrari Piotto, José Francisco Baumgratz....................................................................................................................................................................606

1597 Anomalous origin of coronary artery: taxonomy and clinical implication Origem anômala da artéria coronária: taxonomia e implicação clínica Shi-Min Yuan.......................................................................................................................................................................................622 1598 S100 and S100ß: biomarkers of cerebral damage in cardiac surgery with or without the use of cardiopulmonary bypass S100 e S100ß: biomarcadores de dano cerebral em cirurgia cardíaca com ou sem o uso de circulação extracorpórea Shi-Min Yuan.......................................................................................................................................................................................630 BRIEF COMMUNICATIONS/COMUNICAÇÕES BREVES 1599 Saccular aneurysm formation of the descending aorta associated with aortic coarctation in an infant Formação de aneurismas saculares da aorta descendente associados com coarctação aórtica em criança Arda Ozyuksel, Emir Canturk, Aygun Dindar, Atif Akcevin...............................................................................................................642 1600 A variant technique for the surgical treatment of left ventricular aneurysms Variante técnica para o tratamento cirúrgico de aneurismas do ventrículo esquerdo Paulo Roberto Barbosa Evora, Paulo Victor Alves Tubino, Luis Gustavo Gali, Lafaiete Alves Junior, Cesar Augusto Ferreira, Solange Bassetto, Antônio Carlos Menardi, Alfredo José Rodrigues, Walter Vilella de Andrade Vicente.......................................................645 HOW TO DO IT/COMO EU FAÇO 1601 Implantation of transcatheter aortic valve prosthesis through the ascending aorta concomitant with coronary artery bypass grafting without cardiopulmonary bypass Implante de prótese valvar aórtica transcateter através da aorta ascendente concomitante com revascularização do miocárdio sem circulação extracorpórea João Carlos Ferreira Leal, Luis Ernesto Avanci, Achilles Abelaira Filho, Thiago Faria Almeida, Domingo Marcolino Braile.........650 1602 How to perform a coronary artery anastomosis in complete endoscopic fashion with robotic assistance Como realizar anastomose coronariana totalmente endoscópica com assistência robótica Leonardo Secchin Canale, Johannes Bonatti.......................................................................................................................................654 1603 Right-sided reverse T composite arterial grafting to complete revascularization of the right coronary artery Enxerto arterial composto reverso em T do lado direito para completar a revascularização da artéria coronária direita Mathias H. Aazami, Mohammad Abbasi-Teshnizi, Shahram Amini, Nasim Sadat Lotfinejad............................................................657 1604 Surgical treatment of a giant left ventricular aneurysm - A case report Tratamento cirúrgico do aneurisma gigante de ventrículo esquerdo - Relato de caso Gustavo Alves Schaitza, José Rocha Faria Neto, Julio Cesar Francisco, Cristiana Pellegrino Baena, Helcio Giffhorn, Bruna Olandoski, Leanderson Franco de Meira, Luiz César Guarita-Souza....................................................................................................................663 LETTERS TO THE EDITOR/CARTAS AO EDITOR 1605 Comments on "Impact of type of procedure and surgeon on EuroSCORE operative risk validation" Kyriakos Spiliopoulos, Oliver Deutsch, Walter Eichinger, Brigitte Gansera......................................................................................667 1606 Reply to the editor on “Impact of type of procedure and surgeon on EuroSCORE operative risk validation” Fernando A. Atik, Claudio Ribeiro da Cunha......................................................................................................................................668 Reviewers BJCVS 29.4/Revisores RBCCV 29.4..............................................................................................................................669

Printed in Brazil

Graphic design and layout: Heber Janes Ferreira

Editorial

Adib Domingos Jatene (1929-2014) Adib Domingos Jatene (1929-2014)

Domingo M. Braile1

DOI: 10.5935/1678-9741.20140123

BJCVS in English In a landmark decision, the members of the Brazilian Society of Cardiovascular Surgery (BSCVS) approved at a meeting held during the Brazilian Cardiology Congress in Brasília, that from 2015 the Brazilian Journal of Cardiovascular Surgery (BJCVS) will be published exclusively in English, the lingua franca of science in modern times. This is an important step not only for the consolidation of our journal on the international scenario, but also an incentive so that cardiac surgeons and allied professionals who submit manuscripts to BJCVS can improve themselves in the English language. I thank colleagues and Board of BSCVS for their efforts to make this change a reality. This new dynamic will also accelerate availability on the Scielo and other databases, giving greater visibility and enabling the latest articles can be read and certainly cited with positive impact on Impact Factor, a fact crucial to the evolution of our publication in the concert of nations. As a matter of workflow, Scielo makes available its edition in both languages together. As the Portuguese version was ready before, due to the print edition, there was a great period of time until the two versions were available. Although on its website (www.rbccv.org.br) this problem does not occur, the SciELO is responsible for distributing the files to the PubMed and this delay just makes the articles were accessible on that database only months after completion, an incompatible situation with the necessary agility in these days of instant communication. Regarding manuscripts, for those already sent in Portuguese, following approval for publication, the author will be asked to send the English version. If not, the version will be made by the translators team of BJCVS, with the costs being borne by the authors, as already stated in Rules for Authors. So that the process can be streamlined and the publication occurs in less time, it is essential that the manuscripts are submitted in English, with quality compatible with international levels of scientific language.

rofessor Adib Domingos Jatene, indelible mark of pioneering spirit, honesty, wisdom and accurate surgical technique, left this life on the 14th of November. It saddened the entire Brazilian nation, impoverished without his striking and distinguished presence, always dedicated to healing the heart of ill patients and Brazil’s flaws. It especially dismayed cardiovascular surgeons, who have him as a paradigm and exemplary teacher. He was Chairman of the Department of Cardiovascular Surgery; Founding member and President of the Brazilian Society of Cardiovascular Surgery (BSCVS); one of the founders and first Chief Editor of the Brazilian Journal of Cardiovascular Surgery (BJCVS) back in 1982, implementing the journal inception in 1986. Certainly, as Socrates, Professor Jatene is not dead! He will live on his mission of great physician, dedicated teacher, inventor, class leader, competent administrator in higher academic and government positions, and exemplary citizen. The legacy left by the thousands of disciples who he formed, and friends who had the privilege to live with him over the 85 years of his fruitful existence is eternal, therefore, his lessons will continue to be propagated throughout the ages in a chain of ideas and dignified conduct of the great leaders of national and international opinion. Read more about life and the role of Dr. Adib Jatene in Brazilian cardiovascular surgery from page 473. Dr. Raul Rabelo Also, Dr. Raul Corrêa Rabelo, from Belo Horizonte, MG, left us on November 12, after 68 years. He was one of the most outstanding figures in the history of Brazilian cardiovascular surgery, leaving a great legacy and an example of dignity and perseverance to all those who had the privilege to live with him. He was an active member of the Board of the Brazilian Society of Cardiovascular Surgery in managements 1990-1992 and 1992-1994.

Rev Bras Cir Cardiovasc | Braz J Cardiovasc Surg

We have some important points to consider: a- Essentially, all journals in our area, even in Germany, France, Italy, Japan, China, India, Turkey etc. are published in English, so that we cannot stay out of the competition, with articles in English of poor quality. b- BJCVS is one of the few Open Access journals which does not charge the authors the high sums charged by counterparts to publish the articles, so the collaboration of colleagues to invest in a good standard of translation will guarantee the success of the BJCVS and the researchers themselves. The Editorial Board will keep in its staff reliable translators for checking the quality of language. If necessary, the translation will be rejected and the study will not be published, while not in accordance with established standards. We count on understanding of all, so that the future of BJCVS is of full rise for the conquest of most readers, to publicize their studies in their quotations so that we do not have the frustration we had the last evaluation at Thomson Reuters on which our Impact Factor fell by 35%. c- We hope these measures grow back above the levels we’ve ever had. The Editorial Board of BJCVS is available to answer any questions by any means available. It is not our wish harm colleagues, but offer them the opportunity to count on a disclosure body in the level of greatness of our Brazilian Society of Cardiac Surgery.

up a subject little discussed, but very important: less known publications have been responsible for the publication of articles of great impact. Bohannon cites a study from Google Scholar (“Rise of the Rest: The Growing Impact of Non-Elite Journals”[2]), which shows that in 1995 only 27% of the citations were from articles published in journals outside the “elite” (the ten most cited journals). In 2013, this proportion rose to 47%! Although experts pointed to a few restrictions on the study of Google Scholar, as not differentiate the types of articles, as well as factors such as the growing number of journals and open access repositories, there is no denying that these figures show a trend change, which needs be observed. These facts make us very hopeful. Since I took over as Editor-in-Chief of BJCVS in 2002, I have emphasized the importance of expanding the journal’s horizons. Publishing in English and with the trend towards decentralization of the international flow of articles, we can attract more and better studies, which will give the necessary scientific visibility to our journal. PubMed Central BJCVS overcame another step in the admission process to PubMed Central. We were approved in the technical evaluation and we are looking forward now for the analysis of documents and the banner we sent so that we can finally be accepted in this important database. There is no deadline for the publication of the results, we hope to give soon more good news for our readers.

Bimonthly Another novelty is that the BJCVS will change from quarterly to bimonthly (one edition every two months), a change that aims to streamline the flow of articles. Since today our journal has a large number of submissions, some manuscripts, as approved, have long waiting time to be published. To minimize this problem, preventing damage to the authors and the journal itself, it was adopted, as in a large number of competitors, the online publication “Ahead of Print”, providing the study on our site (http://www.rbccv.org. br/publication-proofs) already with the attribution of the DOI that allows proof of article precedence, as well as its quotation. Even so, our interest has always been to publish as many studies as possible, as quickly as possible. Unfortunately, space limitations and the high costs of print publishing (printing, postage) prevent this expansion occurs, maintaining the current number of issues per year. To get a faster flow, it is important for authors and reviewers comply strictly with the time limits.

CNPq As we have done every year, we ask the CNPq the grant of Editorial Support for 2015. In 2014, after several years without the capital, we received R$30.000,00, an amount below the journal’s needs, but important to cover some costs. I hope we are again among the journals chosen, and that the amount may be greater. CME The following items are available for testing of Continuing Medical Education (CME) in this issue: “Risk factors of atheromatous aorta in cardiovascular surgery” (p. 487), “Very short cycles of postconditioning have no protective effect against reperfusion injury. Experimental study in rats” (p. 521), “Carotid endarterectomy in awake patients: safety, tolerability and results” (p. 574) and “Therapeutic options to minimize allogeneic blood transfusions and their adverse effects in cardiac surgery: A systematic review” (p. 606). I remember the CME, in addition to be a useful tool to test and update knowledge, worth 0.5 linear in Proof of Title of BSCVS, if the reader has answered all the questions of tests available from volumes 28.4 to 29.3.

Small but important The article “Uprising: Less prestigious journals publishing greater share of high-impact papers”, by John Bohannon[1], published in the Newsletter of Science in October, brought

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2015 I conclude this editorial thanking the sponsors, who believe in the journal’s quality, the authors, reviewers, the Editorial Board and BSCVS, which through its members and Directors has always supported us over the years. To all, Merry Christmas and a great 2015! My warmest regards!

REFERENCES

1. Bohannon J. Uprising: Less prestigious journals publishing greater share of high-impact papers [Acesso 15 Out 2014]. Disponível em: http://news.sciencemag.org/scientific-community/2014/10/ uprising-less-prestigious-journals-publishing-greater-share-highimpact 2. Achiara A, Verstak A, Suzuki H, Henderson S, Iakhiaev M, Lin CCY, et al. Rise of the Rest: The Growing Impact of Non-Elite Journals [Acesso 12 Nov 2014]. Disponível em: http://arxiv.org/ pdf/1410.2217.pdf

Editor-in-Chief BJCVS

III

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SOCIEDADE BRASILEIRA DE CIRURGIA CARDIOVASCULAR BRAZILIAN SOCIETY OF CARDIOVASCULAR SURGERY E-mail: revista@sbccv.org.br Sites: www.scielo.br/rbccv www.rbccv.org.br

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Braile DM & Buffolo E - Adib Jatene: June 4, 1929/November 14, 2014 IN MEMORIAM

Adib Jatene: June 4, 1929 November 14, 2014 Adib Jatene: 4 de junho de 1929 14 de novembro de 2014

Domingo M. Braile1, MD, PhD; Enio Buffolo2, MD, PhD

DOI: 10.5935/1678-9741.20140124

RBCCV 44205-1578

Professor Adib Domingos Jatene, indelible mark of pioneering spirit, honesty, wisdom and accurate surgical technique, left this life on the 14th of November. It saddened the entire Brazilian nation, impoverished without his striking and distinguished presence, always dedicated to healing the heart of ill patients and Brazil’s flaws. Certainly, as Socrates, Professor Jatene is not dead! He will live on his mission of great physician, dedicated teacher, inventor, class leader, competent administrator in higher academic and government positions and an exemplary citizen. The legacy left by the thousands of disciples who he formed, and friends who had the privilege to live with him over the 85 years of his fruitful existence is eternal, therefore, his lessons will continue to be propagated throughout the ages in a chain of ideas and dignified conduct of the great leaders of national and international opinion. It should serve as an example the trajectory of this person whose motto was be helpful to others, without that it may cost him any effort, therefore, it was of his nature the desire to serve the nation, to the best of his great director capacity. Born in the wilds of the Amazon, in the state of Acre, in Xapuri, still today a frontier of civilization in the pristine forest breast. Founded in 1902 by Brazilian it was the focus of the revolution of which resulted in the incorporation of this Bolivian territory to Brazil. Adib was the son of Lebanese immigrants who in search of Eldorado, braved the unknown in the early twentieth century, going to live in the jungle. His father, Domingos Jatene, was rubber trader, the white gold (Latex) extracted from native rubber trees.

Professor Adib Jatene personally operated more than 20,000 patients. In one of his forays into thick woods, he returned with high fever and jaundice. In a few days he died! At that time Adib was two years old. He lived there until he was 10, when his mother, with the other children, moved to the State of Minas Gerais, in the city of Uberlândia, where civilization was already present.

Editor-in-Chief of Brazilian Journal of Cardiovascular Surgery E-mail: domingo@braile.com.br 2 Full Professor of Cardiac Surgery at Escola Paulista de Medicina - Universidade Federal de São Paulo 1

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This experience had a great influence on the young man’s character, marking his desire to help the needy. In 1947 with the desire to study engineering or medicine he moved to Sao Paulo, the State Capital. In 1948 he enters the School of Medicine, University of São Paulo, which traced his career and destiny. It was his wish to specialize in Public Health and return to his hometown in Acre. In 1951 on the medical fourth year he starts working on the group of Professor Euríclides de Jesus Zerbini, a pioneer of global heart surgery. At that time he acts as scrub in the first open surgery to correct Mitral Stenosis, held by Professor Zerbini at the Hospital of the FMUSP. He enchants by the Cardiac Surgery, abandons the idea to specialize in public health and returns to the Acre! He graduated physician in 1953 at age 23. He performs specialization under Zerbini advice in 1954. He marries Aurice Biscegli Jatene.

He was admired by his assistants, among them Professor E.J.Zerbini and Professor Adib Jatene, their substitutes in the evolution of their brilliant careers. With the full support of this eminent professor; Zerbini, with great civic spirit and own ideas about inventions and innovations, encouraged his assistants to create equipment for heart surgery, here in Brazil. With this vision was created at the Hospital of the University of São Paulo, one workshop to begin this journey into the future. It received the pompous name of “Artificial Heart Workshop” Showing his penchant for equipment construction, Professor Adib showed all his ability developing improved CPB machines, oxygenators, heat exchangers, thermometers etc. meeting the needs not only in Brazil but also in South America nations. Some models were shipped to Europe, with great acceptance. Professor Adib Jatene was fundamental in the evolution of Cardiac Surgery group at Clinics Hospital between 1957 and 1961, when he moved to the incipient “Cardiology Institute of the State of São Paulo”, a government institution headed by a cardiologist also ahead of his time: Professor Dante Pazzanese, a pioneer in many fields of specialty. With much justice today the Institute takes his name. In the new house, Jatene developed his creativity and competence as expert surgeon, trainer of brilliant disciples and creator of many important inputs for the development of Cardiac Surgery, advancing by leaps and bounds to its consolidation. At this time of great challenges Jatene already created in 1962 another workshop to manufacture equipments: Experimental Workshop, precursor of Adib Jatene Foundation (1984). Just as an example we mention some of the achievements of this institution: Artificial Heart Valves, Starr Edwards type, just two years after the original be developed. It was used for many years, with even better performance than the imported equipment; defibrillators; pacemaker, which allowed us to advance in this field without any lags behind the developed countries. CPB machines, with important technological additions in relation to the primitive; concentric, stainless steel and compact Bubble oxygenators. With advent of the hollow membranes, the workshop developed the first Brazilian membrane oxygenator, marketed worldwide by a national company. Other equipment were adding to these, some more simple as aspirators of various types and models, as well as surgical instruments not marketed in the country. It developed a tilting disc valve which resulted in an international patent. Since the dawn Professor Jatene invested in the research of implantable artificial mechanical hearts, an idea that never left, until the last days of his life when he worked (always accompanied by the best technicians and engineers) in developing another model incorporating appreciable technical advances.

Dr. Adib Jatene and wife Aurice, companion of every hour for more than half a century. He moves to Uberaba in 1955 as Professor of Topographic Anatomy and cardiothoracic surgeon. Endowed with great skill, he attends a machine shop, impressed with his “masters” by the ease they manufactured products for surgery using the right tools. Thus, he developed a heart lung machine and a disc oxygenator, which was he performed experimental heart surgery in dogs and was ahead of his time! In 1957 Professor Zerbini, sensing the potential of Jatene invites him to return to the Hospital of the FMUSP. At this time, as his assistant. The atmosphere was effervescent in the 1st Surgical Clinic, whose professor was the flagship Professor Alípio Correa Netto, humble in his greatness, immune to jealousy, he was creator of a large number of specialties, which began their differentiation in those years.

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Braile DM & Buffolo E - Adib Jatene: June 4, 1929/November 14, 2014

The latest models were implanted in calves, showing adequate performance.It may seem to be an exaggeration to emphasize these qualities of a surgeon with the carat of Professor Jatene, but this made all the difference for the development of cardiac surgery in Brazil, now 200 centers and 100 thousand surgeries per year, covering from north to south and from east to west throughout the country. It was not what happened in most developing countries, which preferred to import the equipment. This made all the difference representing the embryo of the Brazilian industry in the cardiovascular area, which besides supplying the domestic market, exports to many countries, creating quality jobs. The connection of Professor Adib with the University never ceased to exist. In 1983, with the retirement of his master, Professor Zerbini, Jatene wins memorable contest and becomes professor of cardiovascular surgery at the venerable educational institution, now fitted in a modern unit, INCOR, with more than 600 beds and the latest equipment, exclusively dedicated to teaching, research and medical and surgical treatment of cardiac patients. Jatene always stood out in this new challenge, implementing his way to work for results. He was Director of the Medical School from 1990 to 1994, the position of high relevance for a teacher with many merits. He retired from INCOR and USP in 1999 as Emeritus Professor, after having been dedicated to his alma mater for 16 years! Jatene’s retirement meant little in relation to his surgical activity. Besides all the activities in public governmental organizations, Professor Adib at the invitation of the Syrian Sanatorium Association takes over in 1986 as its Director. Today HCor is a large complex Hospital, with special focus of activity in Cardiac Surgery. Jatene continued his activities as a surgeon in this hospital, non-profit, which allowed him to continue in full activity by 2014, along with their children who, like him, are also Cardiac Surgeons: Fábio Jatene, Professor, University of São Paulo (INCOR), Marcelo Jatene, Associate Professor, responsible for Children’s Heart Surgery also at the University of São Paulo (INCOR) and his daughter Ieda Jatene, Pediatric Cardiologist. In his fruitful existence Professor Jatene personally operated more than 20,000 patients and under his leadership the teams who led operated more than 100,000 heart diseases. He is the author and co-author of about 800 scientific studies published in national and international literature In surgical field Jatene had impactful contributions: In 1962 implanted the first aortic valve manufactured in Brazil. In 1970 he performed the first coronary artery bypass grafting, having had a conspicuous contribution in this field. On May 8, 1975 Jatene surprised the scientific world for having operated the first patient with a new technique he described as Anatomic correction of transposition of the great arteries: it became known as “Jatene’s operation”. This pioneering technique was responsible for the advent of a new subspecialty: The Heart Surgery of Neonates,

with all framework of its complexity during surgery and after surgery, providing further development of Surgical Intensive Care Units specialized in neonates. The subspecialty crystallized new specialists: Cardiac surgeons and Infant Neonatologists with specific training in the area.

Dr. Adib Jatene and their children, cardiac surgeons like him, Fabio, Ieda and Marcelo. Today, thousands of patients benefit from this operation and these achievements, which returns the cardiac anatomy to critically ill newborns. In 1984 he received the prestigious title of “Honorary Member of the American Association for Thoracic Surgery”. In 1985 he was “Honorary Guest” of the American Association for Thoracic Surgery. On this occasion he presented the study on reconstruction of the left ventricle in patients with ventricular aneurysm. This technique was innovative in this field, and the concept of ventricular reconstruction for the treatment of aneurysms and heart failure. ASSOCIATIVE ACTIVITY 1981 Chairman of the Department of Cardiovascular Surgery of the Brazilian Society of Cardiology 1984 Founder and first President of the Brazilian Society of Cardiovascular Surgery 1985 President of the Brazilian Society of Cardiology. 1986 President of the International Society for Cardiovascular Surgery 1986 First Editor of the Brazilian Journal of Cardiovascular Surgery. AWARDS AND COMMENDATIONS 1989 Titular Member of the National Academy of Medicine. 1998 “Honorary Fellow” of the American Surgical Association. 2002 “Honorary Felloswship” of the European Association for CardioThoracic Surgery. 2003 “Golden Hippocrates International Prize for Excellency in Medicine” at Horev Medical Center (Haifa-Israel).

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Braile DM & Buffolo E - Adib Jatene: June 4, 1929/November 14, 2014

2003 Award “Talal El Zein” by the Mediterranean Association of Cardiology and Cardiac Surgery. 2006 Award “Fundação Conrado Wessel de Medicina 2005”. 2007 “Seven Wise Men of the World in Cardiovascular Surgery”. 2008 Knowledge Medal Award, Category Managers/ Researchers by the Ministry of Development, Industry and Foreign Trade. 2011 “Bakulev Award for Cardiovascular Surgery” (Moscow). 2012 “Commendation Sérgio Arouca” for the ethical performance and social commitment to Medicine. Member of 32 scientific societies in many parts of the world. He received 178 Titles and Honors of various countries, of which we cite only the most important. PUBLISHED BOOKS: -Cardiomioplastia Dinâmica no Brasil. São Paulo Ed. Atheneu, 1999 -Medicina, Saúde e Sociedade Ed. Atheneu, 2005 -Cartas a um Jovem Médico Elsevier, Ed. Campus, 2007 -40 Anos de Medicina O que mudou? Ed. Saberes, 2011

Dr. Adib Jatene and Aurice during tribute.

PUBLIC LIFE Believing in the scope of Public Health, even apolitical, he assumed government positions. 1979-1982 State Secretary of Health of São Paulo in the Government of Paulo Maluf. Designed to 490 health centers and 40 Hospitals for the Greater São Paulo. 1992 Minister of Health in the management of Fernando Collor. 1996-1998 Minister of Health in the management of Fernando Henrique Cardoso. Dr. Fábio Jatene and Aurice Biscegli Jatene: family together.

PERSONAL ACTIVITIES When young, Adib was a good sportsman, during college he was much in demand for the competitions of the famous Mac-Med, a dispute, now centennial, between the Mackenzie and Medicine Course of USP. He excelled in many sports, especially in rowing in competitions in Rio Tietê. He continued throughout his life to work out. He also had artistic sensibility, and especially fond of Modern Art Week artists, such as Di Cavalcanti, Alfredo Volpi and Tarsila do Amaral, among many others that adorned his well selected collection. By its Amazonian origin, he took a great love for the land, he immensely enjoyed his own farms, dedicating to the most diverse cultures. He had greater preference for livestock, being a creator of the first magnitude, quite prized for his Nelore cattle herds, which he was also an interested connoisseur.

conditions. If you are able to do you create the conditions." ● "I never discuss problem, there are people who are lost in the discussion of the problem. I just discuss solution." ● "The secret is to find the way. And research is to find the way." ● "What kills is not the work, but the rage!" ● "Envy, vanity and excessive nervousness are bad for the heart."

ADIB JATENE THINKER AND APHORIST ● "I am against this saying - I don’t do because I have no

● "I never complain. The present is fantastic."

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● "The doctor’s role is to alleviate the suffering and distress of the people. In this profession, universal values such as faith, love and solidarity, must be above private interests." ● "The biggest problem of poor people is they do know only other poor people. There’s no one for them!" He leaves a copy family: His wife Aurice, four children: Fábio, Marcelo, Ieda (doctors) and Iara (architect), husbands and daughters, ten grandchildren and four great-grandchildren. The children Ieda, Marcelo and Fábio (doctors) and Iara (architect).

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Dalva M, et al.ORIGINAL - New contribution to the study of ventricular remodeling and ARTICLE valve rings in dilated cardiomyopathy: anatomical and histological evaluation

New contribution to the study of ventricular remodeling and valve rings in dilated cardiomyopathy: anatomical and histological evaluation Nova contribuição ao estudo do remodelamento ventricular e dos anéis valvares na cardiomiopatia dilatada: avaliação anátomo-histopatológica

Moise Dalva1, MD, PhD; Aristides Tadeu Correia2; Natalia de Freitas Jatene1; Paulo Hilário Nascimento Saldiva3, MD, PhD; Fabio Biscegli Jatene1, MD, PhD

DOI: 10.5935/1678-9741.20140064

RBCCV 44205-1579

Abstract Introduction: Idiopathic dilated cardiomyopathy causes great impact but many aspects of its pathophysiology remain unknown. Objective: To evaluate anatomical and histological aspects of hearts with idiopathic dilated cardiomyopathy and compare them to a control group, evaluating the behavior of the perimeters of the atrioventricular rings and ventricles and to compare the percentage of collagen and elastic fibers of the atrioventricular rings. Methods:Thirteen hearts with cardiomyopathy and 13 normal hearts were analysed. They were dissected keeping the ventricular mass and atrioventricular rings, with lamination of segments 20%, 50% and 80% of the distance between the atrioventricular groove and the ventricular apex. The sections were subjected to photo scanning, with measurement of perimeters. The atrioventricular rings were dissected and measured digitally to evaluate their perimeters, later being sent to the pathology

laboratory, and stained by hematoxylin-eosin, picrosirius and oxidized resorcin fuccin. Results: Regarding to ventricles, dilation occurs in all segments in the pathological group, and the right atrioventricular ring measurement was higher in idiopathic dilated cardiomyopathy group, with no difference in the left side. With respect to collagen, both sides had lower percentage of fibers in the pathological group. With respect to the elastic fibers, there was no difference between the groups. Conclusion: There is a change in ventricular geometry in cardiomyopathy group. The left atrioventricular ring does not dilate, in spite of the fact that in both ventricles there is lowering of collagen.

Instituto do Coração da Hospital das Clínicas daFaculdade de Medicina da Universidade de São Paulo, InCor-HCFMUSP, São Paulo, SP, Brazil. 2 Surgical Anatomical Museum of Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, InCor-HCFMUSP, São Paulo, SP, Brazil. 3 Pathology Department of the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, InCor-HCFMUSP, São Paulo, SP, Brazil.

Correspondence address: Moise Dalva Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo InCor-HCFMUSP Rua Dr. Enéas de Carvalho Aguiar, 44 – Cerqueira César – São Paulo, SP, Brazil - Zip Code: 05403-000 E-mail: moise.dalva@gmail.com

Descriptors: Heart. Mitral Valve. Tricuspid Valve. Cardiomyopathy, Dilated.

This study was carried out at Hospital das Clínicas of the Faculdade de Medicina da Universidade de São Paulo, InCor-HCFMUSP, São Paulo, SP, Brazil.

Article received on December 29th, 2013 Article accepted on March 16th, 2014

No financial support.

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Dalva M, et al. - New contribution to the study of ventricular remodeling and valve rings in dilated cardiomyopathy: anatomical and histological evaluation

Objetivo: Avaliar aspectos anatomo-histológicos de corações com CMDId comparando-os a corações normais, com medidas perimetrais dos anéis atrioventriculares direito (AVD) e esquerdo (AVE) e dos ventrículos direito (VD) e esquerdo (VE) e a porcentagem de fibras colágenas e elásticas dos anéis. Métodos: Foram avaliados 13 corações de cadáveres portadores de CMDId e 13 corações normais, que foram dissecados mantendo-se os anéis atrioventriculares e a massa ventricular, com laminação em segmentos correspondentes a 20%, 50% e 80% da distância entre o sulco atrioventricular e o ápice ventricular. Os cortes foram submetidos à digitalização fotográfica, sendo comparadas as medidas. Os anéis foram dissecados, medidos e enviados ao laboratório de anatomia patológica, sendo realizadas colorações por meio de hematoxilina-eosina, picrossírius e resorcina fuccina oxidada. Resultados: Com relação aos ventrículos, no grupo CMDId ocorre dilatação nos segmentos apical, equatorial e basal. A medida do AVD foi maior no grupo CMDId, não havendo diferença no AVE entre os grupos. Com relação ao percentual de fibras colágenas, há diminuição no grupo CMDId em relação ao grupo normal. Com relação às fibras elásticas, não houve diferença entre os grupos. Conclusão: Ocorre alteração da geometria ventricular com dilatação no grupo CMDId. Na CMDId observou-se aumento no perímetro do AVD. Não se observou aumento do perímetro do AVE. Houve diminuição percentual na área total de colágeno tanto no AVD quanto no AVE em corações com CMDId.

Abbreviations, acronyms and symbols RVR LVR CAPPesq DCM idDCM iscDCM DistAV-AP

Right ventricular ring Left ventricular ring Ethics Committee for Research Project Analysis Dilated cardiomyopathy Idiopathic dilated cardiomyopathy Ischemic dilated cardiomyopathy Distance of atrioventricular groove to the left ventricular apex SD Standard deviation USP University of São Paulo HCFMUSP Clinics Hospital of the Faculty of Medicine, University of São Paulo HE hematoxylin-eosin CHF congestive heart failure INCOR Heart Institute ISFC International Society and Federation of Cardiology MAGPs Microfibrils associated with glycoproteins MMPs Metalloproteinases RFO Weigert Resorcin-fuchsin with previous oxidation by oxone SPSS Statiscal package for the social sciences SVOC Coroner’s Service of São Paulo USA United States of America WHO World Health Organization

Resumo Introdução: A cardiomiopatia dilatada idiopática (CMDId) é causadora de grande impacto, porém aspectos de sua fisiopatologia são desconhecidos.

Descritores: Coração. Valva Mitral. Valva Tricúspide. Cardiomiopatia Dilatada.

INTRODUCTION

despite this relevant fact, the rings expansion mechanism is not completely understood[2-4]. The presence of valvular insufficiency may contribute to increased morbidity in heart valve disease patients[5] or those presenting a DCM of various etiologies[6]. There is a tendency to consider the valve tissues as inert, because of its simple histological structure and sparse cell population, however, this fact seems less reasonable in light of the huge mechanical load imposed on these structures throughout life and the consequent need for maintenance of its tissue integrity at the cost of balance between collagen production and degradation[7]. Although the presence of myocytes and coronary circulation are capital for the functioning of the heart as a pump, the components of the extracellular matrix (ECM), particularly the collagen fibers of types I and III are recognized as fundamental to the maintenance of the cardiac cycle[8]. Among its many functions, the most important are to provide structural framework for myocytes and vessels as well as provide the body resistance and resilience properties, providing systolic and diastolic tone, helping the heart to maintain its conformation[8-12].

Congestive heart failure (CHF) is the entity causing major impact in terms of morbidity and mortality, and its main cause is dilated cardiomyopathy (DCM), which in its various etiologies, constitute a serious public health problem, with an estimated prevalence of 4-8 cases per 100,000 people per year and an estimated incidence of 36.5 per 100,000 people[1]. The key pathophysiological aspect of such entities is the severe systolic dysfunction caused by the loss of efficiency of the heart to act as hydraulic pump. Although myocellular component is present in an important way, other mechanisms such as the remodeling and activation of the renin-angiotensin-aldosterone system are factors contributing to the perpetuation of the presentation[1]. Ventricular remodeling characterized by both right and left morphogeometrical changes, provides vicious cycle of functional deterioration, since the heart loses its original anatomical conformation, which is critical to its efficiency. In this context, the valve insufficiency caused primarily by expansion of the atrioventricular rings is of paramount importance[1], but

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The breakdown of these fibers may occasionally persist even after removal of the underlying disease in many situations. In patients with disease of the mitral valve with secondary tricuspid insufficiency, there can be no normalization of tricuspid regurgitant flow even with the correction of mitral valve disease[13]. This fact raises controversy in the literature about the real necessity of repair of the tricuspid valve ring when it is secondarily dilated[13], and to what extent the non-standardization of reflux may be associated with irreversible histological changes in atrioventricular rings. This fact is of crucial importance, given the fact that about half of patients with mitral valve disease requiring surgery presents significant tricuspid insufficiency[14]. The authors who advocate not performing repair insist on the fact that the correction of mitral lesion leads to normalization of the afterload of the right ventricle by reducing the pressure of the pulmonary vascular bed[15]. In contrast, those who advocate the realization of repair of the tricuspid ring support the fact that the ring expansion cannot be naturally reversible in advanced cases, despite the total correction of the mitral valve[16,17]. This fact could possibly be due to microscopic structural changes in the atrioventricular rings with occurrence of collagenolysis and replacement of collagen fibers for tissue of other nature, compromising its integrity. The anatomical concept that the fibrous skeleton of the heart does not dilate has been refuted[2,3,18], and its enlargement has been proved in cases of severe heart failure due to dilated cardiomyopathy of ischemic (iscDCM) or nonchagasic idiopathic (idDCM) etiologies[2,3]; however, it does not exist in the literature comparative histological study of right and left atrioventricular rings in cases of idDCM in light of this new concept. At the same time, available knowledge about the role played by ECM in terms of control and regulation of this process is still scarce so that there is broad field of research being done in this area.

(SVOC-USP), and dilated hearts from the Anatomic Pathology Laboratory of the Heart Institute of the Clinics Hospital, University of São Paulo (InCor-HC USP). A total of 26 specimens were grouped as follows: Group 1 - (idDCM) Composed of 13 hearts from individuals with idDCM Group 2 - (NORMAL) Composed of 13 hearts from individuals without cardiomyopathy and considered normal After collection, samples were fixed in formalin, followed by removal of large vessels and the atria, leaving only the atrioventricular rings and ventricular mass. After the steps of preparation and assessment of parts, cross-sections of ventricular mass were performed, starting from the atrioventricular groove towards the apex of the heart (DistAV-AP). The cross-sections were performed at a level corresponding to 80% (baseline), 50% (equatorial) and 20% (apical) from this distance, following being photographed with a digital camera (Sony, model Cyber Shot DSC W 200) which was set at a table through a bucky 15 cm distally from the parts. The images were transferred to a computer where measurements were performed with the software Image Tool, (Department of Dental Diagnostic Science of the University of Texas Health Science Center, San Antonio, USA). All parts were photographed next to a rule which served as a reference for measurements. After the completion of the photographs, the right and left atrioventricular rings were completely dissected, but were not separated, keeping them together by the central fibrous body. The rings were placed in boxes and sent to the pathology department, following being waxed and laminated, and performed histological sections of 5 micrometers thick and used the following staining methods: • Hematoxylin-eosin (HE) - Standard coloring in pathology services, and is used for identification of technical artifacts and histopathological changes that eventually could compromise analysis by other methods. • Picrosirius - coloring used to study collagen fibers. • Weigert’s resorcinol-fuchsin with previous oxidation by oxone (RFO) - coloring used to study elastic fibers Quantitative morphometric analysis was performed by means of digital image analysis using system consisting of optical microscope Leyca DMR (Leyca Microsystems Wetzlar Gmb H, Germany) connected to a computer by a video camera. Histological sections of the right and left atrioventricular rings were photographed at 15 points randomly selected from an increase of 100 times, and the captured images were analyzed using the software Image Pro Plus version 4.1 (Media Cybernetics - Silver Spring, MD, USA) that quantifies the area occupied by fibers and then quantifies the total area, and then it was possible to calculate the percentage of collagen and elastic fibers of each photographed spot. For each ring was used the percentage average of the fibers of the fifteen points photographed.

Objective The aims of this study are: 1-Evaluating and comparing the perimeters of the right and left ventricles in different segments and right and left atrioventricular rings in normal hearts and patients with IdDCM. 2- Comparing the percentage by area of collagen and elastic fibers of the right and left atrioventricular rings between the normal hearts and patients with idDCM. METHODS The design of this study was initially submitted to and approved by the Institutional Research Ethics Committee. Material Specimens of normal and dilated hearts were studied. Normal hearts came from the Coroner’s Service of São Paulo

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After obtaining the macroscopic data, comparisons of the average ventricular circumference of each segment were performed (apical and basal Equatorial) between idDCM and normal groups and the right and left ventricles as well as comparisons of means of ventricular perimeter between each segment (Apical, Equatorial and Basal) within each group (idDCM and NORMAL). The perimeters of the right and left atrioventricular rings were also compared. Regarding the microscopic data, the average of the percentages comparisons were performed by area of collagen and elastic fibers of the right and left atrioventricular rings between each group ( idDCM and NORMAL). Regarding the statistics, descriptive analyzes were performed, presenting means along with the related standard deviations (Âą SD) and minimum and maximum values. The assumptions of normal distribution in each group and the homogeneity of variances between groups were assessed, respectively, with the Shapiro-Wilk test and the Levene test. The inferential analysis for ventricular perimeter was performed using analysis of variance (ANOVA) for repeated measures to compare the means of each segment between the groups (intergroup factor). The t test was used to evaluate the average perimeters of the right and left atrioventricular rings and the mean percentage of elastic and collagen fibers of the rings. The descriptive and inferential

statistical analyzes were performed using SPSS version 13 (SPSS 13.0 for Windows). RESULTS One of the objectives was to assess the perimeters of the right and left ventricles (apical, equatorial and basal segments) for each group ( idDCM and NORMAL), but the point for section of the apical segment (20%) did not include the right ventricular cavity of hearts from idDCM the NORMAL groups and in most cases. Thus, in the right ventricles of the hearts from idDCM and NORMAL groups were analyzed only the perimeters of the equatorial and basal segments. Descriptive data for variables of right ventricle perimeters (equatorial and basal segments) and left (apical, equatorial and basal segments) for each group are presented in Tables 1 and 2 and the descriptive results for the perimeters of variables of right and left atrioventricular rings for each group are presented in Tables 3 and 4. The descriptive results for the variables percentages by area of collagen fibers of the right and left atrioventricular rings for each group are shown in Tables 5 and 6, and the descriptive results for the variables percentages by area of elastic fibers of the right and left atrioventricular rings for each group are presented in Tables 7 and 8.

Table 1. Descriptive measures of equatorial and basal perimeter variables in idDCM and NORMAL (mm) right ventricle groups. Groups idDCM

NORMAL

Segment Equatorial

N 13

Mean 170.812

Standard deviation 44.60938

Minimum 84.36

Maximum 242.99

Basal

223.339

29.03743

190.58

287.34

Equatorial

112.66

20.58866

74.78

142.72

Basal

173.38

24.82283

123.59

216.54

idDCM: Idiopathic dilated cardiomyopathy

Table 2. Descriptive measures of variables apical, equatorial and basal perimeter in idDCM and NORMAL (mm) left ventricle groups. Groups idDCM

NORMAL

Segment Apical Equatorial Basal

N 13 13 13

Mean 101.5862 191.3458 181.9777

Standard deviation 38.23844 30.37638 35.22137

Minimum 56.34 146.81 140.39

Maximum 180.79 254.45 261.37

Apical Equatorial Basal

13 13 13

59.93 120.3235 116.6919

18.70348 17.89946 15.00732

23.62 93.17 93.42

86.57 144.8 143.5

idDCM: Idiopathic dilated cardiomyopathy

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Table 3. Descriptive measures of variables RVR ring perimeter in idDCM groups and Normal (mm). Groups idDCM NORMAL

N 13 13

Mean 120.1915 104.0046

Standard deviation 15.33305 13.88195

Minimum 94.85 75.77

Maximum 141.78 128.89

RVR=Right ventricular ring; idDCM: Idiopathic dilated cardiomyopathy

Table 4. Descriptive measures of variables LVR perimeter in idDCM and Normal (mm) groups. Groups idDCM NORMAL

N 12 13

Mean 108.3233 97.2723

Standard deviation 13.76889 16.40091

Minimum 87.35 69.02

Maximum 128.01 118.09

RVR=Right ventricular ring; idDCM: Idiopathic dilated cardiomyopathy

Table 5. Descriptive measures of variables collagen fibers of RVR in idDCM and NORMAL groups (percentage). Groups idDCM NORMAL

N 13 13

Mean 19.2332 38.5756

Standard deviation 14.19502 21.51783

MĂinimum 1.51 13.43

Maximum 60.73 88.89

RVR=Right ventricular ring; idDCM: Idiopathic dilated cardiomyopathy

Table 6. Descriptive measures of variables collagen fibers of LVR in idDCM and NORMAL groups (percentage). Groups idDCM NORMAL

N 13 13

Mean 22.0962 38.4603

Standard deviation 12.85746 14.75941

Minimum 1.44 14.85

Maximum 59.55 59.55

LVR=Left ventricular ring; idDCM: Idiopathic dilated cardiomyopathy

Table 7. Descriptive measures of variables elastic fibers of RVR in idDCM and NORMAL groups (percentage). Groups idDCM NORMAL

N 13 13

Mean 19.5032 17.5873

Standard deviation 11.33865 13.42513

Minimum 8.12 0.29

Maximum 45.4 43.46

RVR=Right ventricular ring; idDCM: Idiopathic dilated cardiomyopathy

Table 8. Descriptive measures of variables of elastic fibers of LVR in idDCM and NORMAL groups (percentage). Groups idDCM NORMAL

N 13 13

Mean 21.0929 18.1184

Standard deviation 11.16968 13.63213

Minimum 7.13 1.26

Maximum 43.78 50.78

LVR=Left ventricular ring; idDCM: Idiopathic dilated cardiomyopathy

In the mean comparison analysis of right ventricular perimeters of equatorial and basal segments between NORMAL and idDCM groups, statistically significant differences were found (P<0.05) in all studied segments. In the mean comparison analysis of the right atrioventricular perimeters of the rings between idDCM and NORMAL groups statistically significant difference was found (P<0.05).

In the mean comparison analysis of left ventricular apical perimeters of equatorial and basal segments between idDCM and NORMAL groups, statistically significant differences were found (P<0.05) in all segments. The results of the Post-Hoc test with Bonferroni correction for multiple comparisons showed statistically significant differences for all comparisons, except with respect to the com-

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parison between equatorial and basal ventricular perimeters. In the mean comparison of the perimeters analysis of left atrioventricular rings between the idDCM and NORMAL groups, there was no significant statistical difference (P> 0.05). In the mean comparison analysis of the collagen fibers of the right and left atrioventricular rings between the idDCM and NORMAL groups, there was a statistically significant difference (P<0.05). In the mean comparison analysis of the elastic fibers of the right and left atrioventricular rings between the idDCM groups and NORMAL, there was no statistically significant difference (P>0.05).

responsible for the remodeling mechanism, with decreased contractile efficiency. This discrepancy results seem to be related in part to the methodology used and partly due to the fact that collagen may take different forms in the case of normal myocardial collagen or fibrosis. Although myocardial ECM changes have already been investigated in cases of idDCM, two factors remain unknown, namely any modification of the histological composition of the ECM of right and left atrioventricular rings and the behavior of the collagen fibers in terms of balance among its production, degradation and organization. These facts motivated the present study. From a macroscopic point of view, it was noted that there dilatation in both ventricles of the idDCM group, albeit with distinct morphology, since the expansion of the RVR accompanies the expansion of the equatorial and basal ventricular segments, contrary to what happens in LVR which presents no significant expansion compared to the control group, although there was dilation of equatorial and basal segments at left. In relation to LVR, these findings confirm the results of Juliani[22] and Hueb et al.[2,3], who claim to not be the degree of left ventricular dilation that determines the degree of dilation of the mitral ring, since they occur independently. This statement has always been a matter of controversy in the literature. In a study that examined the measure of LVR in 102 hearts, 78 of which had left ventricular dilation, Bulkley & Roberts[23] conclude that the isolated expansion of the left ventricular rarely causes failure in the left atrioventricular valve. They mention that the contrary affirmative has long been regarded as true, as postulated by great names of cardiology, as Flint and Osler in books dated end of the nineteenth century. The association of left atrioventricular valve insufficiency increases the morbidity and mortality of patients with CHF caused by idDCM[1]. Although often seen as secondary only to ventricular remodeling and it is therefore classified as â&#x20AC;&#x153;functionalâ&#x20AC;?, recent studies indicate that possibly there are intrinsic components to the valve structure as a whole that acting differently can be responsible for the observed failure[4,6]. The valve leaflets, although considered to be only inert, because apparently they are not committed in cases of idDCM, contrary to what happens in other types of valvular regurgitation, present their own characteristics that must be taken into account, such as afferent and efferent innervation, intrinsic contractile properties, and spatial orientation of collagenous fibers that allows optimal distribution of mechanical stress, so that the remodeling of the leaflets possibly plays an intrinsic role in the genesis of valve failure, as demonstrated by Timek et al.[4] in experimental study in sheep. This fact comes against the results observed in our study, since there was no statistically significant dilation of the LVR, which seems to confirm the fact that it is not only the possible expansion of the ring that

DISCUSSION The medical understanding of the CHF has undergone substantial change since the first records of this entity, which can be traced in writings attributed to Hippocrates, and we can identify its historical evolution, which progressed in symmetry with the advancement of scientific knowledge[19]. From a functional standpoint, the loss of pumping function occurs due to energy dissipation, a fact derived from mechanisms as increased heart weight, ventricular dilation, and thrombi in the heart chambers and dilation of atrioventricular rings[1]. The ECM had its role reviewed in the genesis of idDCM. Initially, its components were taken as part of passive support in which the myocytes are intertwined, but recent studies point to the fact that these components play an active role in all phases of the normal cardiac cycle, for giving the heart fundamental properties such as resistance, resilience and elasticity, with consequent amendment of these features in pathological cardiac cycle, whose main characteristic is ventricular remodeling, which can be observed in macroscopic and microscopic level[8,20]. The normal myocardial collagen comprises predominantly Type I (corresponding to about 80% of the total collagen mass) and III, which form a three dimensional network structure which includes valves, chordae tendineae and perivascular interstitial collagenous components, which is organized in bundles. They are called epimisium (which covers each muscle fiber individually), perimysium (covering myocytes groups) and endomysium (found between each myocyte)[8]. Regarding the behavior of the collagen fibers in cardiomyopathies, studies show conflicting results, and there may be increased[21] or decrease[20] of the collagenous component as well as breakdown of normal structure. Weber et al.[8], in histological study analyzing three hearts of patients who died due to idDCM, reported that there was a decrease of type I collagen (tougher) and increased collagen type III (less resistant) compared to the normal pattern and loss of normal functional architecture of collagenous fibers. They found that the increase in the less resistant collagen is likely

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causes failure. The fact that there was dilation statistically significant of the RVR may optionally be associated to a lack of a full collagenous ring around the right atrioventricular orifice, unlike what occurs on the left side, where this hole is effectively surrounded by strong collagenous ring, which may reduce the propensity for ring dilation. According Juliani[22], there was cross left ventricular dilation in idDCM, which is mainly caused by changes in the baseline and equatorial segments. The fact that dilation of LVR can be a significant component of the ventricular remodeling process because anatomically the ring is part of the ventricle containing it, and because of its non-expansion may not occur changes in ventricular anatomic configuration, with tapering of its superior portion. This fact occurs only at left because at right occurs dilation of the basal, equatorial and RVR segments, a fact that gives rise to a different ventricular conformation and morphology of the wider top. These findings seem to corroborate the results of Hueb[3], who observed the fact that impairment of RVR valve accompanies the enlargement of the right ring, which does not occur on the left. The proportionality between the different types of collagen seems to represent major role in maintaining normal geometric conformation of the heart[8]. Although the amount of total collagen in the myocardium may increase, due mainly to the replacement of such fibers by scar tissue, with a consequent functional breakdown, there appears to be evidence points to the fact that the ECM of myocardium composition may vary according to the anatomic location. Gunja-Smith et al.[24] in study comparing 8 hearts with idDCM extracted from heart transplant recipients, with 12 normal hearts, stated emphatically that “it deals with a simplification to assume that every heart has a similar composition.” In this study, we assessed the ECM regarding its collagenous and elastic components exclusively in the region of the atrioventricular rings. As far as we know, there is no similar study in literature, a reason that can possibly explain the inconsistencies found with respect to the total amount of collagen, because in this study we noted, under microscopic inference analysis, that the percentage amount of total collagen fibers was significantly lower in idDCM group relative to the control group in both atrioventricular rings.

participants, since the only available were effectively used in the study. This limitation may eventually be overcome from studies in animal models, since there are already developed models for this purpose. Microscopic analysis was limited by issues relating to staining methods used, especially in relation to the study of elastic fibers. Staining with the use of resorcin-fuchsin oxidized allows evaluating the totality of the elastic fibers present, but it does not adequately provide for differentiation between three different types of such fibers (oxytalan, elastic and mature). Studies with use of alternative colors, such as Verhoeff method for exclusive coloring mature elastic fibers and Weigert resorcin-fuchsin, for recognizing the mature and elastic fibers may help elucidate the elastic behavior of the system qualitatively and not only quantitative. Regarding the collagen fibers, the methodology used allowed the quantification of the total fibers present, however, it did not allow the differentiation of different types of fibers present, so that it could not be assessed the quantity of the collagen studied that was composed of healing material and fibrosis. In the present study, there was the aim to investigate the variation of the total quantity of collagen and elastic fibers in different anatomic regions of the heart, which could lead to the confirmation of the hypothesis that the ECM structure varies according to the anatomical region, presenting a standard of increase of some structures and decrease in others. Final considerations The anatomical variation of the atrioventricular ring in terms of presence of ECM has been demonstrated. Angelini et al.[25] analyzed after autopsy the left atrioventricular junction in 13 subjects, 7 of them free of heart disease and 6 patients with mitral valve prolapse and concluded that except for the intertrigonal distance, where lies the mitral-aortic continuity, there is great ECM array arrangement, with the presence of variable size fibrous portions permeating areas where atrial myocardium and the ventricular myocardium are located, and further found that the amount of collagen in the ring ranged thick and easily identifiable portions and also thin portions. This same hypothesis was raised by Juliani[22], who in anatomical study that examined 43 human hearts, 18 of them from deceased patients by idDCM, when establishing the independence of the left atrioventricular ring dilatation with respect to dilation of ventricular segments, postulated that “One hypothesis would be that the forming tissue of the mitral ring is richer in fibrous matrix, particularly the region of shortest inter-trigonal distance, than the ventricular muscle, so even suffering the “pressure” of ventricular dilation, in addition to being subject the same etiologic agents that determine the left ventricular dilation in idDCM and iscDCM, its rate of expansion occurs differently.”

Study limitations With regard to the selection of the sample, although we had calculated the power to explain any change found in macroscopic terms such as above 80%, it was not possible to calculate it in microscopic terms, since there are no studies in the literature about the specific change in EMC of atrioventricular rings in idDCM that would serve as the basis to a similar calculation. The possibility of a pilot study was not contemplated by the impossibility of obtaining more

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CONCLUSION

4. Antoniali F, Braile DM, Potério GMB, Costa CE, Lopes MM, Ribeiro GCA, et al. Proporção entre os segmentos do anel da valva tricúspide normal: um parâmetro para realização de anuloplastia valvar. Braz J Cardiovasc Surg. 2006;21(3): 262-71.

The results showed that: 1) There was an increase of ventricular perimeters in idDCM group compared to the normal group at right and left in different segments evaluated. The perimeter of the RVR was higher in idDCM group compared to the NORMAL group, with no significant difference in relation to LVR between the two groups. 2) With regard to the percentage by area of collagen fibers, the right and left atrioventricular rings showed lower percentage of fibers in idDCM group compared to the control group. Regarding the percentage by area of elastic fibers, there was no difference between groups.

5. Matsuyama K, Matsumoto M, Sugita T, Nishizawa J, Tokuda Y, Matsuo T. Predictors of residual tricuspid regurgitation after mitral valve surgery. Ann Thorac Surg. 2003;75(6):1826-8. 6. Breda JR, Palma JHA, Teles CA, Branco JNR, Catani R, Buffolo E. Miocardiopatia terminal com insuficiência mitral secundária: tratamento com implante de prótese e remodelamento interno do ventrículo esquerdo. Braz J Cardiovasc Surg. 2006;21(3):283-8. 7. Henney AM, Parker DJ, Davies MJ. Collagen byosinthesis in normal and abnormal human heart valves. Cardiovasc Res. 1982;16(11):624-30.

Authors’ roles & responsibilities MD

ATC

NFJ PANS FBJ

8. Weber KT. Cardiac interstitium in health and disease: the fibrillar collagen network. J Am Coll Cardiol. 1989;13(7):1637-52.

Analysis and/or interpretation of data, statistical analysis, final approval of the manuscript, conception and design of the study, implementation of operations and/or experiments, manuscript writing or critical review of its contents Analysis and/or interpretation of data, statistical analysis, final approval of the manuscript, conception and design of the study, implementation of operations and/or experiments, manuscript writing or critical review of its contents Implementation of operations and/or experiments Conception and design, manuscript writing or critical review of its contents Analysis and/or interpretation of data, final approval of the manuscript, study design, manuscript writing or critical review of its contents

9. Montes GS, Junqueira LC. The use of the Picrosirius-polarization method for the study of the biopathology of collagen. Mem Inst Oswaldo Cruz. 1991;86(Suppl 3):1-11. 10. Melo ECM, Lemos M, Ximenes Filho JA, Sennes LU, Saldiva PHN, Tsuji DH. Distribution of collagen in the lamina propria of the human vocal fold. Laryngoscope. 2003;113(12):2187-91. 11. Buhler RB, Sennes LU, Mauad T, Melo EC, Silva LF, Saldiva PH. Collagen fiber and versican distribution within the lamina propria of fetal vocal folds. Laryngoscope. 2008;118(2):371-4. 12. Sakae FA, Imamura R, Sennes LU, Mauad T, Saldiva PH, Tsuji DH. Disarrangement of collagen fibers in Reinke’s edema. Laryngoscope. 2008;118(8):1500-3. 13. Sagie A, Schwammenthal E, Padial LR, Vasquez de Prada JA, Weyman AE, Levine RA. Determinants of functional tricuspid regurgitation in incomplete tricuspid valve closure: Doppler color flow study of 109 patients. J Am Coll Cardiol. 1994;24(2): 446-53. 14. Dreyfus GD, Corbi PJ, Chan KM, Bahrami T. Secondary tricuspid regurgitation or dilatation: which should be the criteria for surgical repair? Ann Thorac Surg. 2005;79(1):127-32.

REFERENCES 1. Hare JM. The dilated, restrictive and infiltrative cardiomyopathies. In. Libby P, Bonow RO, Mann DL, Zipes DP, eds. Braunwald’s heart disease: a textbook of cardiovascular medicine. 8th ed. Philadelphia: Saunders Elsevier; 2008. p.1739-62.

15. Braunwald NS, Ross J Jr, Morrow AG. Conservative management of tricuspid regurgitation in patients undergoing mitral valve replacement. Circulation. 1967;35(4 Supp):I63-9.

2. Hueb AC, Jatene FB, Moreira LFP, Pomerantzeff PMA, Mioto BM, Chabelmann RC, et al. Estudo comparativo do anel valvar mitral e do ventrículo esquerdo na cardiomiopatia dilatada. Rev Bras Cir Cardiovasc. 2001;16(4):354-63.

16. Cohen SR, Sell JE, McIntosh CL, Clark RE. Tricuspid regurgitation in patients with acquired, chronic, pure mitral regurgitation. II. Nonoperative management, tricuspid valve annuloplasty, and tricuspid valve replacement. J Thorac Cardiovasc Surg. 1987;94(4):488-97.

3. Hueb AC, Jatene FB, Moreira LF, Pomerantzeff PM, Kallás E, Oliveira SA. Ventricular remodeling and mitral valve modifications in dilated cardiomyopathy: new insights from anatomic study. J Thorac Cardiovasc Surg. 2002;124(6):1216-24.

17. Groves PH, Lewis NP, Ikram S, Maire R, Hall RJ. Reduced exercise capacity in patients with tricuspid regurgitation after

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successful mitral valve replacement for rheumatic mitral valve disease. Br Heart J. 1991;66(4):295-301. 18. McCarthy PM. Does the intertrigonal distance dilate? Never say never. J Thorac Cardiovasc Surg. 2002;124(6):1078-9.

22. Juliani PS. Avaliação morfogeométrica do ventrículo esquerdo e do anel valvar mitral na cardiomiopatia dilatada isquêmica ou idiopática: estudo comparativo computadorizado [Tese de doutorado]. São Paulo: Faculdade de Medicina, Universidade São Paulo; 2008.

19. Katz AM. The ’’modern’’ view of heart failure: how did we get here? Circ Heart Fail. 2008;1(1):63-71.

23. Bulkley BH, Roberts WC. Dilatation of mitral annulus. A rare cause of mitral regurgitation. Am J Med. 1975;59(4):457-63.

20. Spinale FG. Myocardial matrix remodeling and the matrix metalloproteinases: influence on cardiac form and function. Physiol Rev. 2007;87(4):1285-342.

24. Gunja-Smith Z, Morales AR, Romanelli R, Woessner JF Jr. Remodeling of human myocardial collagen in idiopathic dilated cardiomyopathy. Role of metalloproteinases and pyridinoline cross-links. Am J Pathol. 1996;48(5):1639-48.

21. Nunes VL, Ramires FSA, Pimentel WS, Fernandes F, Ianni BM, Mady C. O papel do acúmulo de colágeno no interstício miocárdico na sobrevida dos pacientes com cardiomiopatia dilatada idiopática e chagásica. Arq Bras Cardiol. 2006;87(6):757-62.

25. Angelini A, Ho SY, Anderson RH, Davies MJ, Becker AE. A histological study of the atrioventricular junction in hearts with normal and prolapsed leaflets of the mitral valve. Br Heart J. 1988;59(6):712-6.

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Atik FA, et al.ORIGINAL - Risk factorsARTICLE of atheromatous aorta in cardiovascular surgery

Risk factors of atheromatous aorta in cardiovascular surgery Fatores de risco de ateromatose da aorta em cirurgia cardiovascular

Fernando A. Atik1, MD; Isaac Azevedo Silva1, MD; Claudio Ribeiro da Cunha1, MD

DOI 10.5935/1678-9741.20140058

RBCCV 44205-1580

Abstract Objective: To determine the prevalence and profile of ascending aorta or aortic arch atheromatous disease in cardiovascular surgery patients, its risk factors and its prognostic implication early after surgery. Methods: Between January 2007 and June 2011, 2042 consecutive adult patients were analyzed, with no exclusion criteria. Atheromatous aorta diagnosis was determined intraoperatively by surgeon palpation of the aorta. Determinants of atheromatous aorta, as well as its prognostic implication were studied by multivariate logistic regression. Results: Prevalence of atheromatous aorta was 3.3% (68 patients). Determinants were age > 61 years (OR= 2.79; CI95%= 2.43 - 3.15; P<0.0001), coronary artery disease (OR=3.1; CI95%=2.8 - 3.44; P=0.002), hypertension (OR=2.26; CI95%=1.82 - 2.7; P=0.03) and peripheral vascular disease (OR=3.15; CI95%= 2.83 - 3.46; P=0.04). Atheromatous aorta was an independent predictor of postoperative cerebrovascular accident (OR=3.46; CI95%=3.18 - 3.76; P=0.01). Conclusion: Although infrequent, the presence of atheromatous aorta is associated with advanced age, hypertension, coronary artery disease and peripheral vascular disease. In those patients, a more detailed preoperative and intraoperative assessment of the aorta is justified, due to greater risk of postoperative cerebrovascular accident.

Resumo Objetivo: Determinar a prevalência e as características de ateromatose da aorta ascendente e/ou arco aórtico em cirurgia cardiovascular, os fatores de risco de sua ocorrência e a implicação prognóstica imediata da mesma. Métodos: No período de janeiro de 2007 a junho de 2011, 2042 pacientes adultos consecutivos foram analisados, sem critérios de exclusão. A detecção de ateromatose da aorta foi realizada por meio de palpação durante o ato operatório. Os fatores de risco de ateromatose da aorta e a sua implicação prognóstica foram determinados por regressão logística multivariada. Resultados: A prevalência de ateromatose da aorta foi de 3,3% (68 pacientes). Os fatores de risco foram a idade > 61 anos (OR= 2,79; IC95%= 2,43 - 3,15; P<0,0001), doença arterial coronária (OR=3,1; IC95%=2,8 - 3,44; P=0,002), hipertensão arterial sistêmica (OR=2,26; IC95%=1,82 - 2,7; P=0,03) e doença vascular periférica (OR=3,15; IC95%= 2,83 - 3,46; P=0,04). A ateromatose da aorta foi preditor independente da ocorrência de acidente vascular cerebral no pós-operatório (OR=3,46; IC95%=3,18 - 3,76; P=0,01). Conclusão: Embora infrequente, a presença de ateromatose da aorta tem maior ocorrência de acordo com a idade, com a presença de hipertensão arterial sistêmica, doença arterial coronária e doença vascular periférica. Nestas situações, é justificada investigação pré e intraoperatória mais detalhada, pois a presença de ateromatose determina maior chance de acidente vascular cerebral no pós-operatório.

Descriptors: Atherosclerosis. Aorta. Thoracic Surgery. Cardiovascular Surgical Procedures.

Descritores: Aterosclerose. Aorta. Cirurgia Torácica. Procedimentos Cirúrgicos Cardiovasculares.

Instituto de Cardiologia do Distrito Federal (IC-DF), Brasília, DF, Brazil.

Correspondence address: Fernando Antibas Atik Instituto de Cardiologia do Distrito Federal Estrada Parque Contorno do Bosque s/n - Cruzeiro Novo – Brasília, DF, Brasil – Zip Code: 70658-700 E-mail: atikf@mac.com

This study was carried out at Instituto de Cardiologia do Distrito Federal (IC-DF), Brasília, DF, Brazil.

Article received on October 3rd, 2013 Article accepted on March 24th, 2014

No financial support.

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the Research Ethics Commission under the protocol number 069883/2013, in accordance with the Helsinki rules. The surgeries were isolated coronary artery bypass grafting (CABG) in 911 patients (44.6%), isolated valve surgeries in 561 (27.5%) and combined surgeries in 400 patients (19.6%), and other procedures in 170 (8, 3%). Other procedures were composed of congenital disease in adult surgeries in 84 patients (4.1%), isolated aorta surgeries in 45 patients (2.2%) and miscellaneous surgeries in the rest. Of the patients that we identified the atheromatous aorta, 47 (69%) underwent isolated CABG, 5 (7%) valve operation and the rest of the combined operations (24%). Cardiopulmonary bypass was not used in 15 (32%) patients of those who underwent isolated CABG. On the other hand, it was used in all submitted to other operations. The decision regarding the performance of surgery from diagnosis of atheromatosis was the surgeonâ&#x20AC;&#x2122;s discretion. The aorta is no longer handled entirely in 16% of patients. Changes in cannulation site occurred in 79% of patients, change of clamping site in 69% and change in proximal anastomoses or aortotomy in 59%. The aortic replacement under deep hypothermic circulatory arrest was performed in 16% of patients.

Abbreviations, acronyms and symbols CABG LC LV NYHA

Coronary artery bypass grafting Left coronary Left ventricle New York Heart Association

INTRODUCTION The presence of atheromatous disease of the thoracic aorta is a known complicating factor in patients undergoing cardiovascular surgery, since it determines changes in intraoperative planning, and increases the risk for increased morbidity and mortality[1]. The correlation between atherosclerosis in the coronary arteries and other arterial sites have been extensively documented[2,3], especially in the carotid arteries[4]. In turn, patients with atherosclerosis of the carotid arteries also have a higher rate of atheromatous thoracic aorta[5]. On the other hand, atheromatosis of the thoracic aorta is common in the elderly, and population studies[6,7] found that these patients have a higher prevalence of cardiovascular events and stroke. Although this evidence demands a more careful monitoring in risk groups, there are no national data on the subject. Knowledge of the prevalence and atheromatous aorta risk factors may provide greater predictability of its occurrence and prognosis. They can also lead to therapeutic changes that aim to minimize the operative risk. The aim of this study are to determine the prevalence and characteristics of atheromatous ascending aorta and/or aortic arch in patients undergoing cardiovascular surgery in a Brazilian center, the risk factors for its occurrence and its immediate prognostic implications.

Statistical analysis Categorical variables were expressed as frequencies and percentages and continuous by mean and standard deviation. Continuous variables with heterogeneous distribution were expressed by medians and confidence intervals relating to one standard deviation. When comparing the pre- and intraoperative characteristics of morbidity and mortality events between the groups, the chi-square test, Fisher exact test, Studentâ&#x20AC;&#x2122;s t test were used when indicated. Multivariate logistic regression was used to determine the risk of atheromatosis and its prognostic implications factors in the occurrence of death, stroke and acute renal failure. Variables significantly (P <0.05) related to each of the events by univariate analysis were retained. Then, stepwise backward logistic regression was used in the construction of multivariate models. Calibration and discrimination of the models were determined by the Hosmer-Lemeshow test and the analysis of the ROC curve (receiver-operating characteristic), respectively.

METHODS

RESULTS

From January 2007 to June 2011, 2042 consecutive adult patients underwent cardiovascular surgery. The mean age was 57.4Âą15 years (range 16 years to 87 years) and 1168 (57.2%) were male. All patients were studied, with no exclusion criteria. Pre-, intra- and post-operative of the patients were prospectively collected and stored in an electronic database. The diagnosis of atheromatous aorta was performed by its palpation during surgery by the surgeon, and the collection of data took into account the full account of the surgeon in relation to atheromatosis characteristics. The study was approved by

Prevalence and descriptive atheromatosis The atheromatous ascending aorta and/or aortic arch were diagnosed by the surgeon during surgery in 68 patients, which corresponds to 3.3% of the total. The intraoperative findings were isolated calcified plate bounded by 35%, extensive or multiple plate calcified in 33% and porcelain aorta by 32%. Given these findings, various types of impact emerged: impossibility of any manipulation of the aorta in 33.3%, cannulation failure

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in 9.7%, clamping impossibility 4.2% and impossibility of cannulation and clamping 2.8%. In the remaining half of the patients, there was possibility of cardiopulmonary bypass with changes in local cannulation, clamping and proximal anastomoses.

group compared to the control. In addition, there was a higher frequency of involvement of other arterial territories in atheromatous aorta group, for example, coronary artery disease, especially when associated with left main coronary artery obstruction and peripheral vascular disease. There was an association trend between obstructive carotid artery disease and aortic atheromatosis. Multivariate analysis identified independent risk factors for atheromatous disease of the aorta in the study population (Table 2), as the age older than 61 years (OR=2.79; 95% CI 2.43 to 3.15; P<0.0001), the presence of coronary artery disease (OR=3.1; 95% CI 2.8 to 3.44; P=0.002), hypertension (OR=2.26; 95% CI 1.82 to 2.7; P=0.03) and peripheral vascular disease (OR=3.15; 95% CI 2.83 to 3.46; P=0.04).

Risk factors of ateromatose In Table 1 are described the differences found between the control group and atheromatosis by univariate analysis as regards demographics, comorbity and risk factors widely recognized for cardiovascular surgery. Thus, the older age in the atheromatosis group was particularly significant (65.8±9.7 years versus 54.3±15 years, P<0.0001). Still, all of atherosclerosis risk factors occurred more frequently in atheromatosis

Table 1. Preoperative characteristics of patients with and without atheromatous aorta who underwent cardiovascular surgery.

Demographics Age (years) Male Weight (kg) Height (cm) Previous cardiac surgery Functional class (NYHA) I II III IV Coronary artery disease Acute coronary syndrome Myocardial infarction <30d Trunk lesion LC Number of affected vessels 1 2 3 LV ejection fraction Pulmonary hypertension Carotid disease Risk factors Arterial hypertension Diabetes mellitus Dyslipidemia Smoking Comorbidities Prior stroke Atrial fibrillation Peripheral vascular disease Endocarditis Creatinine Serum hemoglobin

Atheromatosis (N=68)

Control (N=1974)

65.8±9.7 45 (66.2%) 70.1±12.8 164±10 2 (2.9%)

54.3±15 1123 (56.9%) 68.2±14.2 170±27 219 (11.1%)

<0.0001 0.12 0.31 0.87 0.03

48 (70.6%) 13 (19.1%) 6 (8.8%) 1 (1.5%) 59 (86.8%) 16 (23.5%) 9 (13.2%) 17 (25%)

1015 (51.6%) 570 (29%) 327 (16.6%) 56 (2.8%) 1103 (55.9%) 371 (18.8%) 253 (12.8%) 200 (10.1%)

3 (4.4%) 16 (23.5%) 40 (58.8%) 57.7±11.7 0 3 (4.4%)

96 (4.9%) 208 (10.5%) 799 (40.5%) 58.8±13.2 157 (8%) 34 (1.7%)

59 (86.8%) 26 (38.2%) 33 (48.5%) 11 (16.2%)

1185 (60.2%) 460 (23.4%) 675 (34.3%) 145 (7.4%)

<0.0001 0.004 0.01 0.007

5 (7.3%) 2 (2.9%) 4 (5.9%) 0 1.09±0.9 13.3±1.8

103 (5.2%) 226 (11.5%) 25 (1.3%) 58 (2.9%) 1.3±1 13.5±1.9

0.44 0.02 0.001 0.15 0.08 0.52

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0.03 <0.001 0.34 0.92 <0.0001 0.08 0.53 0.01 0.1

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Table 2. Multivariate analysis of risk factors for atheromatous aorta in patients undergoing cardiovascular surgery. Variable Atheromatosis† Intercept

Estimate±SE

3.24±0.33

<0.0001

Age > 61 years

0.51±0.13

<0.0001

DAC

0.57±0.19

0.002

SAH

0.41±0.19

0.03

Peripheral vascular disease

0.57±0.28

0.04

CI 95%

2.79

2.43 – 3.15

3.1

2.8 – 3.44

2.26

1.82 – 2.7

3.15

2.83 – 3.46

† Hosmer-Lemeshow test, P=0.09; C-statistic 0.77, CAD=coronary artery disease, Hypertension. CAD=coronary artery disease; SH=systemic arterial hypertension

Table 3. Morbidity and mortality data in patients with and without aortic atheromatosis undergoing cardiovascular surgery. Atheromatosis (N=68) 12 (17.6%) 7 (10.4%) 10 (14.7%) 13 (19.1%) 12 (17.6%) 6 (8.9%) 3 (2; 5) 15 (8; 25)

Hospital mortality Stroke Myocardial infarction Sepsis Acute renal failure Prolonged mechanical ventilation Intensive care unit stay (days) Length of stay (days)

Control (N=1974) 114 (5.7%) 44 (2.2%) 96 (4.8%) 136 (6.9%) 81 (4.1%) 44 (2.2%) 2 (2; 4) 11 (7; 19)

P <0.0001 <0.0001 0.0003 0.0001 <0.0001 0.0005 0.24 0.03

Table 4. Multivariate analysis of the occurrence of stroke in patients undergoing cardiovascular surgery. Estimate±SE

Intercept

-0.31±0.65

0.64

Atheromatosis

0.62±0.24

0.01

Ejection fraction

2.84±0.99

0.004

Functional class IV

1.35±0.4

0.0007

Variable Atheromatosis†

CI 95%

3.46

3.18 – 3.76

9.42

1.98 – 42.6

3.86

1.93 – 5.35

† Hosmer-Lemeshow test, P=0.9; C-statistic 0.7

Prognostic implications Table 3 shows the impact of atheromatous aorta in hospital mortality and major morbidity outcomes by univariate analysis. 1There was a higher hospital mortality and higher incidence of stroke, sepsis, myocardial infarction, acute renal failure, prolonged mechanical ventilation and longer hospital stay in patients with atheromatous aorta compared to the

control. Regarding the multivariate analysis, the presence of atheromatous aorta was an independent predictor of the occurrence of stroke in the postoperative period (OR=3.47; 95% CI 3.18 to 3.76; P=0.01), as documented in Table 4. There was no correlation in the analysis of risk factors, including the presence of atheromatous aorta and hospital mortality or acute renal failure in the postoperative period.

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It was not identified a greater risk of stroke according to the type of the atheromatous disease in the aorta. Patients with porcelain aorta had the same risk as other patients with delimited atherosclerotic plaques (12.5% vs. 9.5%, P=0.87). Also, avoiding manipulation of the aorta did not prevent the occurrence of cerebral complications (9% vs. 10.2%, P=0.91), as well as changing the cannulation site (P=0.61), clamping (P=0.12) or using circulatory arrest (P=0.9).

its use is associated with high cost for the health system. It can, however, be used in the groups at the most risk prior to surgery[13]. During surgery, the surgeon palpates traditionally the aorta to diagnose aortic atheromatosis. However, Wareing et al.[10] studied more than 500 patients and found palpation be imprecise and it was detected only 38% of positive diagnoses on ultrasound. The best imaging method is the epiaortic ultrasound[16,17] performed intraoperatively with high-resolution transducers which measure the wall and the lumen of the aorta in the various segments. Precise informations regarding the pathological features of the aorta have implications for the management of cardiopulmonary bypass, myocardial and cerebral protection and surgical planning, in order to minimize unwanted embolism microparticle atheroma, especially to the brain. Our study and others[1,18] showed that the presence of atheromatous aorta is an independent risk factor in the development of stroke postoperatively, with absolute risk by about 10%, a risk consistent in several series. Blauth et al.[12] reviewed the autopsy findings of 221 patients undergoing cardiac surgery. It was revealed that cerebral embolism occurred in 37% of patients with atherosclerosis of the aorta, compared to only 2% of those who had not. Van der Linden et al.[19] showed that the kind of impairment of the aorta has a differential risk of stroke. In our experience, we could not corroborate the findings of this latest study of higher risk related to the type of involvement, including as regards the porcelain aorta. The various types of surgical strategy are possible to be performed, as shown in our experience, and there is no consensus in the literature regarding the best strategy. These include the revascularization with composite arterial grafts under cardiopulmonary bypass without aortic clamping, changes on the site of cannulation, clamping and proximal anastomoses, up to the aortic replacement under total circulatory arrest with deep hypothermia. However, none of these approaches is capable of preventing the risk of displacement of atheromatous particles. Itâ&#x20AC;&#x2122;s intuitive to state that avoiding any manipulation of the aorta is advised in the presence of atheromatosis. However, this strategy is not possible in all cases, particularly the need for combined surgeries involving the heart valves and thoracic aorta. There are also some data from observational studies[1,8,10-12,14] suggesting that the change in operative tactics to minimize the risk of complications, although the morbidity remain higher than usual. We could not find in our superiority experience any approach to minimizing the risk of cerebral complications. Both off-pump surgery without manipulation of the aorta showed the same stroke rates than patients undergoing surgery with CPB. Attempts to change the site of cannulation, clamping, performance of proximal anastomoses or aortotomy did not

DISCUSSION This observational study aimed at exploring atheromatous ascending aorta and/or aortic arch in a group of consecutive adult patients undergoing cardiovascular surgery. Despite the prevalence is relatively low in this population, it is consistent with other[8] literature series. The prevalence could be higher if our population was older, since there was direct relationship between age and the presence of atheromatosis. Davila-Roman et al.[9] found important atheromatous ascending aorta in approximately one third of patients older than 80 years who underwent cardiovascular surgery. The increase in life expectancy of the Brazilian population will certainly determine a higher incidence of patients with this problem being treated for cardiovascular surgery. In addition to age, it was identified that the main atherosclerosis risk factors[5] are the same related to atheromatous aorta by univariate analysis. However, only hypertension was considered an independent risk factor in the multivariate analysis. In the latter, other factors found in our series were coronary artery disease and peripheral vascular disease, reinforcing the coexistence of atherosclerotic involvement in different arterial territories. Most studies in the [10-12] literature considers as risk factors for aortic atheromatosis the obstructive carotid artery disease, abdominal aortic aneurysm, left main coronary artery obstruction, diabetes mellitus and hypertension. The calcified aortic stenosis and chronic renal failure are still other risk factors involved[13]. Looking critically, preoperative patient characteristics have little predictive value, since most of the patients referred to the cardiovascular surgery has such features, which therefore requires more accurate assessments. In our experience, such evaluations are performed infrequently and dependent on the doctorâ&#x20AC;&#x2122;s suspicion level. The importance of completing the diagnosis in order to enable the best possible surgical planning. Traditional image tests that can identify the atheromatous aorta are inaccurate, as the chest X-ray or cardiac catheterization. Transesophageal echocardiography[14] is better than the previous ones, however, presents image acquisition limitations in the distal ascending aorta and proximal aortic arch, frequently used sites for cannulation and clamping. Computed tomography[15] is an excellent test to detect atheromatous aorta, however, it has disadvantages in relation to the use of radiation and

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reduce this risk. Neither the replacement of the aorta under total circulatory arrest with deep hypothermia reached the same benefit, although not carrying additional risk. Cardiac surgery with aortic manipulation guided by epiaortic ultrasound has uncertain clinical value. Clinical studies have detected low cerebral embolization by transcranial Doppler[20] and improved neuropsychological performance[21,22], but it has not been demonstrated lower stroke rates. In a patient with porcelain aorta, carrier or aorta valve disease requiring surgery, most surgeons hesitate to perform complicated surgical procedures involving total circulatory arrest and aortic replacement in elderly patients who often already has other operative risk factors, which opens the possibility of transapical aortic valve replacement when indicated[23]. On the other hand, if the proposed surgery would be isolated CABG, performing it without cardiopulmonary bypass and without manipulation of the aorta seems to be a more appropriate strategy when possible[24]. It should be noted that our experience does not corroborate such conduct, nor there is strong evidence in the literature to support them up to this point.

REFERENCES 1. Gillinov AM, Lytle BW, Hoang V, Cosgrove DM, Banbury MK, McCarthy PM, et al. The atherosclerotic aorta at aortic valve replacement: surgical strategies and results. J Thorac Cardiovasc Surg 2000;120(5):957-63. 2. Yamamoto H, Shavelle D, Takasu J, Lu B, Mao SS, Fisher H, et al. Valvular and thoracic aortic calcium as a marker of the extent and severity of angiographic coronary artery disease. Am Heart J. 2003;146(1):153-9. 3. Budoff MJ, Nasir K, Mao S, Tseng PH, Chau A, Liu ST, et al. Ethnic differences of the presence and severity of coronary atherosclerosis. Atherosclerosis. 2006;187(2):343-50. 4. Folsom AR, Kronmal RA, Detrano RC, O’Leary DH, Bild DE, Bluemke DA, et al. Coronary artery calcification compared with carotid intima-media thickness in the prediction of cardiovascular disease incidence: the Multi-Ethnic Study of Atherosclerosis (MESA). Arch Intern Med. 2008;168(12):1333-9. 5. Takasu J, Budoff MJ, O’Brien KD, Shavelle DM, Probstfield JL, Carr JJ, et al. Relationship between coronary artery and descending thoracic aortic calcification as detected by computed tomography: the Multi-Ethnic Study of Atherosclerosis. Atherosclerosis. 2009;204(2):440-6.

Study limitations This is an observational study, with the limitations inherent to its design. We used palpation of the aorta as a diagnostic method of atheromatosis, which certainly reduced the prevalence. The use of epiaortic ultrasound should be the standard of our service. The limited number of patients and the very different approaches adopted by surgeons in the presence of atheromatous hamper determining the impact of the change of intraoperative tactic in the results of morbidity and mortality. For this reason, this was not listed as objective of this study. A multicenter study of more robust number of patients facing this purpose would be interesting to be developed.

6. Witterman JC, Kannel WB, Wolf PA, Grobbee DE, Hofman A, D’Agostino RB, et al. Aortic calcified plaques and cardiovascular disease (the Framingham Study). Am J Cardiol 1990;66(15):1060-4. 7. Hollander M, Hak AE, Koudstaal PJ, Bots ML, Grobbee DE, Hofman A, et al. Comparison between measures of atherosclerosis and risk of stroke: the Rotterdam study. Stroke. 2003;34(10):2367-72. 8. Zingone B, Gatti G, Spina A, Rauber E, Dreas L, Forti G, et al. Current role and outcomes of ascending aortic replacement for severe nonaneurysmal aortic atherosclerosis. Ann Thorac Surg. 2010;89(2):429-34.

CONCLUSION

9. Dávila-Román VG, Kouchoukos NT, Schechtman KB, Barzilai B. Atherosclerosis of the ascending aorta is a predictor of renal dysfunction after cardiac operations. J Thorac Cardiovasc Surg. 1999;117(1):111-6.

Although infrequent, the presence of atheromatous aorta has higher incidence according to age, with the presence of hypertension, coronary artery disease and peripheral vascular disease. In these situations, it is justified pre- and intraoperative more detailed research, because the presence of atheromatous determines greater chance of stroke postoperatively.

10. Wareing TH, Davila-Roman VG, Barzilai B, Murphy SF, Kouchoukos NT. Management of the severely atherosclerotic ascending aorta during cardiac operations. A strategy for detection and treatment. J Thorac Cardiovasc Surg. 1992;103(3):453-62. 11. Mills NL, Everson CT. Atherosclerosis of the ascending aorta and coronary artery bypass. Pathology, clinical correlates, and operative management. J Thorac Cardiovasc Surg. 1991;102(4):546-53.

Authors' roles & responsibilities FAA IAS CRC

Data collection, statistical analysis, data interpretation and writing of the manuscript Manuscript writing Manuscript review

12. Blauth CI, Cosgrove DM, Webb BW, Ratliff NB, Boylan M, Piedmonte MR, et al. Atheroembolism from the ascending aorta.

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An emerging problem in cardiac surgery. J Thorac Cardiovasc Surg. 1992;103(6):1104-11.

aorta and new ischemic brain lesions after conventional coronary bypass graft surgery. Stroke. 2004;35(9):e356-8.

13. Nishi H, Mitsuno M, Tanaka H, Ryomoto M, Fukui S, Miyamoto Y. Who needs preoperative routine chest computed tomography for prevention of stroke in cardiac surgery? Interact Cardiovasc Thorac Surg. 2010;11(1):30-3.

19. van der Linden J, Hadjinikolaou L, Bergman P, Lindblom D. Postoperative stroke in cardiac surgery is related to the location and extent of atherosclerotic disease in the ascending aorta. J Am Coll Cardiol; 2001;38(1):131-5.

14. Katz ES, Tunick PA, Rusinek H, Ribakove G, Spencer FC, Kronzon I. Protruding aortic atheromas predict stroke in elderly patients undergoing cardiopulmonar bypass: experience with intraoperative transesophageal echocardiography. J Am Coll Cardiol. 1992;20(1):70-7.

20. Borger MA, Taylor RL, Weisel RD, Kulkarni G, Benaroia M, Rao V, et al. Decreased cerebral emboli during distal aortic arch cannulation: a randomized clinical trial. J Thorac Cardiovasc Surg. 1999;118(4):740-5. 21. Goto T, Baba T, Yoshitake A, Shibata Y, Ura M, Sakata R. Craniocervical and aortic atherosclerosis as neurologic risk factors in coronary surgery. Ann Thorac Surg. 2000;69(3):834-40.

15. Takeda Y, Hoshiga M, Tatsugami F, Morinaga I, Takehara K, Hotchi J, et al. Clinical significance of calcification in ascending aorta as a marker for the requirement of coronary revascularization. J Atheroscler Thromb. 2009;16(4):346-54.

22. Hammon JW Jr, Stump DA, Kon ND, Cordell AR, Hudspeth AS, Oaks TE, et al. Risk factors and solutions for the development of neurobehavioral changes after coronary artery bypass grafting. Ann Thorac Surg. 1997;63(6):1613-8.

16. Zingone B, Rauber E, Gatti G, Pappalardo A, Benussi B, Dreas L, et al. The impact of epiaortic ultrasonography scanning on the risk of perioperative stroke. Eur J Cardiothorac Surg. 2006;29(5):720-8.

23. Kempfert J, Van Linden A, Linke A, Schuler G, Rastan A, Lehmann S, et al. Transapical aortic valve implantation: therapy of choice for patients with aortic stenosis and porcelain aorta? Ann Thorac Surg. 2010;90(5):1457-61.

17. Davila-Roman VG, Barzilai B, Wareing TH, Murphy SF, Kouchoukos NT. Intraoperative ultrasonography evaluation of the ascending aorta in 100 consecutive patients undergoing cardiac surgery. Circulation. 1991;84(5 Suppl):III47-53.

24. MejĂa OA, Lisboa LA, Puig LB, Moreira LF, Dallan LA, Jatene FB. On-pump? or off-pump? Impact of risk scores in coronary artery bypass surgery. Rev Bras Cir Cardiovasc. 2012;27(4):503-11.

18. Djaiani G, Fedorko L, Borger M, Mikulis D, Carroll J, Cheng D, et al. Mild to moderate atheromatous disease of the thoracic

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Sales MC, et ORIGINAL al. - Aortic Center: specialized care improves outcomes and ARTICLE decreases mortality

Aortic Center: specialized care improves outcomes and decreases mortality

Centro de Tratamento da Aorta: a especialização reduz complicações e mortalidade

Marcela da Cunha Sales1, MD, MsC; José Dario Frota Filho1, MD; Cristiane Aguzzoli1, MD; Leonardo Dornelles Souza1, MD; Álvaro Machado Rösler1, BMD; Eraldo Azevedo Lucio1, MD, DSc; Paulo Ernesto Leães1, MD, DSc; Mauro Ricardo Nunes Pontes1,2, MD, DSc; Fernando Antônio Lucchese1, MD, LD

DOI: 10.5935/1678-9741.20140122

RBCCV 44205-1581

Abstract Objective: To compare in-hospital outcomes in aortic surgery in our cardiac surgery unit, before and after foundation of our Center for Aortic Surgery (CTA). Methods: Prospective cohort with non-concurrent control. Foundation of CTA required specialized training of surgical, anesthetic and intensive care unit teams, routine neurological monitoring, endovascular and hybrid facilities, training of the support personnel, improvement of the registry and adoption of specific protocols. We included 332 patients operated on between: January/2003 to December/2007 (before-CTA, n=157, 47.3%); and January/2008 to December/2010 (CTA, n=175, 52.7%). Baseline clinical and demographic data, operative variables, complications and in-hospital mortality were compared between both groups. Results: Mean age was 58±14 years, with 65% male. Group CTA was older, had higher rate of diabetes, lower rates of COPD and HF, more non-urgent surgeries, endovascular procedures, and aneurysms. In the univariate analysis, CTA had lower mortality (9.7 vs. 23.0%, P=0.008), which occurred consistently across different diseases and procedures. Other outcomes which were reduced in CTA included lower rates of reinterventions (5.7 vs 11%, P=0.046), major complications (20.6 vs. 33.1%, P=0.007), stroke (4.6 vs. 10.9%, P=0.045) and sepsis (1.7 vs. 9.6%, P=0.001),

as compared to before-CTA. Multivariable analysis adjusted for potential counfounders revealed that CTA was independently associated with mortality reduction (OR=0.23, IC 95% 0.08 – 0.67, P=0.007). CTA independent mortality reduction was consistent in the multivariable analysis stratified by disease (aneurysm, OR=0.18, CI 95% 0.03 – 0.98, P=0.048; dissection, OR=0.31, CI 95% 0.09 – 0.99, P=0.049) and by procedure (hybrid, OR=0.07, CI 95% 0.007 – 0.72, P=0.026; Bentall, OR=0.18, CI 95% 0.038 – 0.904, P=0.037). Additional multivariable predictors of in-hospital mortality included creatinine (OR=1.7 [1.1-2.6], P=0.008), urgent surgery (OR=5.0 [1.5-16.7], P=0.008) and thoracoabdominal aneurysm (OR=24.6 [3.1-194.1], P=0.002). Conclusions: Thoracic aorta surgery in specialized center was associated with lower incidence of complications and all-cause mortality as compared to usual care.

Cardiovascular Surgery Division, Hospital São Francisco, Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, RS, Brazil. 2 Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil.

Correspondence address: Marcela da Cunha Sales Rua Carvalho Monteiro, 252, apto 1201 - Bairro Petrópolis, Porto Alegre, RS, Brazil Zip code: 90470-100 E-mail: mcsales@terra.com.br

Descriptors: Aortic surgery. Specialized care. Surgical outcomes. Inpatient mortality. Resumo Objetivo: Comparar desfechos intrahospitalares em pacientes submetidos a cirurgia da aorta torácica e toracoabdominal, antes e após a constituição do Centro Especializado de Tratamento da Aorta (CTA).

Work carried out at Hospital São Francisco, Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, RS, Brazil and Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil.

Article received on February 10th, 2011 Article accepted on August 24th, 2014

No financial support.

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de aneurismas e cirurgias eletivas; e mais procedimentos endovasculares que o pré-CTA. Na análise univariada, o grupo CTA mostrou redução de mortalidade (9,7% x 23,0%, P=0,008), que foi consistente nos diferentes subgrupos estratificados por patologia e por procedimento. O grupo CTA teve também redução de reoperações (5,7% x 11%, P=0,046), complicações maiores (20,6% x 33,1%, P=0,007), acidente vascular cerebral (4,6% x 10,9%, P=0,045) e sepse (1,7% x 9,6%, P=0,001), comparado ao pré-CTA. Na análise multivariada, o CTA se associou de forma independente a redução de mortalidade hospitalar (OR=0,23, IC 95% 0,08 - 0,67, P=0,007). A redução de mortalidade do CTA também ocorreu na análise estratificada por patologia (cirurgias de aneurisma, OR=0,18, IC 95% 0,03 - 0,98, P=0,048; cirurgias de dissecção, OR=0,31, IC 95% 0,09 - 0,99, P=0,049) e por procedimento (híbridos, OR=0,07, IC 95% 0,007 - 0,72, P=0,026; Bentall, OR=0,18, IC 95% 0,038 – 0,904, P=0,037). Também foram preditores independentes de mortalidade a creatinina pré-operatória (OR=1,7, IC 95% 1,1-2,6, P=0,008), a cirurgia de urgência (OR=5,0, IC 95% 1,5-16,7, P=0,008) e o aneurisma toracoabdominal (OR=24,6, IC 95% 3,1-194,1, P=0,002). Conclusão: O tratamento cirúrgico de patologias da aorta torácica e toracoabdominal em centro especializado, em comparação ao tratamento usual, se associou a menor incidência de complicações e mortalidade global.

Abbreviations, acronyms & symbols AAA AMI ARF CABG CAD COPD CPB CRF CTA CVA DM ICU

Abdominal aortic aneurysms Acute myocardial infarction Acute renal failure Coronary artery bypass grafting Coronary artery disease Chronic obstructive pulmonary disease Circulatory bypass Chronic renal failure Center for Aortic Surgery Cerebrovascular accident Diabetes mellitus Intensive Care Unit

Métodos: Coorte prospectiva com controle não contemporâneo. A criação do CTA envolveu treinamento cirúrgico especializado, sala híbrida, monitorização neurológica, capacitação de pessoal de apoio, aperfeiçoamento dos registros e uso de protocolos específicos. Foram incluídos 332 pacientes operados em 2 períodos: janeiro/2003 a dezembro/2007 (pré-CTA, n=157, 47,3%); e janeiro/2008 a dezembro/2010 (CTA, n=175, 52,7%). As características demográficas, clínicas, dados cirúrgicos, complicações e mortalidade hospitalar foram comparados nos 2 grupos. Resultados: A idade média foi 58±14 anos, com 65% sexo masculino. O grupo CTA teve idade, prevalência de diabete (DM) e glicemia maiores; menor prevalência de doença pulmonar obstrutiva crônica e insuficiência cardíaca; maior proporção

Descritores: Cirurgia de aorta. Centro especializado. Desfechos cirúrgicos. Mortalidade hospitalar.

INTRODUCTION

(IRAD), a consortium of specialized centers in 12 countries that aims to study the etiology, clinical findings, treatment and hospital outcomes of patients with aortic dissection[9]. Specialized aortic centers have also been created, aiming to systematize the medical and surgical treatment by the best evidence, taking into account parameters such as the extent of aortic involvement, the underlying pathology, the need for anticoagulation and life expectancy[10]. These centers have multiplied, serving patients with complex pathologies that require sophisticated surgical techniques and high-tech prostheses[11]. In the management of abdominal aortic aneurysms (AAA), strategies of regionalization of care have been implemented, directing patients to specialized centers with high volume (> 50 cases per year). Surgical outcomes in these centers have been better than low-volume centers, with 20-30% reduction in complications and in-hospital mortality[12]. In thoracic aortic pathologies in general, however, there is no studies evaluating the outcomes, complications and mortality of surgery in specialized centers, compared to non-specialized centers[13,14]. Therefore, the aim of this study is to evaluate the impact of surgical treatment of the thoracic and thoracoabdominal aortic diseases in specialized center (CTA) on hospital outcomes, complications and mortality compared to treatment in a non-specialized center.

The assessment and management of aortic pathologies impose multiple challenges. Aneurysms are usually asymptomatic, with slow growth and may develop distal thromboembolism, rapid expansion and rupture, with catastrophic evolution. Dissections have high early mortality, with mortality rate up to 1-2% per hour[1]. The diagnosis is complex, requiring integration with multiple clinical imaging studies (echocardiography, CT angiography, MRI and aortography). The initial clinical management is critical for limiting the spread of disease, and surgical planning is complex, including endovascular and hybrid procedures and new forms of neurological monitoring and protection[2,3]. Evidence has supported the concept that complex surgery should be performed in high-volume centers of care to improve outcomes in these patients[4]. Accordingly, there is evidence that highly complex surgeries such as esophagectomies[5], resection of lung neoplasms[6], duodenopancreatectomies[7], and endarterectomy[8], performed in centers with high surgical volume, result in reduction of morbidity and mortality. The challenges and complexities presented by aortic surgery have stimulated the creation of multicenter registries, such as the International Registry of Acute Aortic Dissections

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METHODS

(AMI), reoperation for bleeding, acute visceral or lower limb ischemia, or paraplegia).

Patients Between January/2003 and December/2010, 332 adults consecutively underwent thoracic/thoracoabdominal aortic surgery and were divided into two periods: pre-CTA (January/2003 to December/2007) and CTA (January/2008 to December/2010). The mean age was 58Âą14 years; 65% male.

Statistical analysis Continuous variables with normal distribution were described using mean Âą SD and compared using Studentâ&#x20AC;&#x2122;s t test. The non-normal continuous variables underwent log transformation or have been described using the median and interquartile range, and compared with the Mann-Whitney test. Categorical variables were described as proportions (%) and compared with the chi-square test. In univariate analysis, the outcomes were compared between groups using chi-square test with Yates correction. A stratified analysis was performed by subgroups, trying to detect heterogeneity of effect in subgroups of interest (mortality by pathology and by procedure), using a test-variable interaction effect, using the P value of <0.05. To exclude confounding (variability of mortality by other factors over time, unrelated to CTA), a sensitivity analysis was performed by evaluating separately the evolution of the annual mortality in the pre-CTA period, followed by the CTA period; then the mortality between the two periods was compared using chi-square with correction for multiple comparisons. Univariate analysis of factors associated with mortality was performed using chi-square test for categorical variables and t test or Mann-Whitney test for continuous variables. Using multivariate analysis (logistic regression), the adjusted comparison of mortality was performed in the two groups, and the independent effect of predictor variables - covariates associated with outcome (P<0.1) in univariate analysis - on hospital outcomes was evaluated[18]. The discrimination ability of the logistic model was assessed using the area under the ROC curve (receiver operating characteristics curve); calibration was assessed using the Hosmer-Lemeshow test. The model was tested for the presence of multicollinearity and its predictive value was determined. All analyzes were performed using SPSS 17.0 (Statistical Package for Social Science, Chicago, IL) software. Statistical significance was confirmed when P<0.05. The project was approved by the Research Ethics Committee (No. N2094/09), and all patients signed a written informed consent.

CTA The constitution of the CTA involved: 1. surgical training in specialized centers (national and international); 2. improvements in infrastructure (hybrid room, C-arc, intraoperative echocardiography, neurological monitoring, reform of the Intensive Care Unit (ICU), new postoperative protocols of care); 3. Training of personnel (anesthetists, diagnostic services, perfusionists); 4. Research activities (improvement of records and databases, publication of results); 5. standardization of care and use of evidence-based guidelines[15,16]. These procedures take place between November/2007 and January/2008. Design Prospective observational study with a non-contemporaneous control (historical), comparing in-hospital outcomes in patients undergoing thoracic and thoracoabdominal aortic surgery before and after the creation of the CTA. Patient evaluation and surgical treatment Preoperative imaging studies included CT angiography using multidetector scanner (Model Aquilion, Toshiba, New York, USA). The images were post-processed with three-dimensional reconstruction, allowing surgical planning and measurement of aortic diameters. Magnetic resonance angiography or contrast angiography were rarely used. Preoperative transesophageal echocardiography was used in emergency situations. All patients were assessed by a group of surgeons who analyzed the surgical options and planned the surgery. The surgical procedures performed included the Bentall surgery, replacement of the aortic root with interposition of a Dacron graft, aortoplasty, implantation of endovascular prosthesis (stent) and hybrid procedures, using standard techniques[10,11,17]. After surgery, patients were transferred to the ICU in mechanical ventilation.

RESULTS

Variables Demographic, clinical, laboratory and preoperative echocardiographic variables, the location of the aneurysm, the type of dissection, the operative data and the procedure performed were prospectively collected. The primary outcome was in-hospital mortality. Secondary outcomes included major complications, reoperation rate and ICU stay. Major complication included cerebrovascular accident (CVA), acute renal failure (ARF), acute myocardial infarction

332 patients who had undergone surgery for diseases of the thoracic and thoracoabdominal aorta between January/2003 and December/2010 were included (pre-CTA, January 2003-December 2007, n=157, 47.3%; CTA, January 2008-December 2010, n=175, 52.7%). Cases included 175 aneurysms (52.7%), and 150 dissections (45.2%). Approximately 85% of patients were hypertensive, 41.6% were smokers, 31% had CHF, 20.6% chronic obstructive pulmonary disease (COPD), 21% coronary artery dis-

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ease (CAD), 17% chronic renal failure (CRF) and 7,3% had diabetes mellitus (DM) (Table 1). Regarding aneurysms, the most common location was the ascending aorta, with a similar rate in both groups (46 patients (68.0%) in the pre-CTA group and 68 (62.1%) in CTA - P>0.05). We also found, with a similar percentage between groups, aneurysms of the descending aorta, with 10 patients (14.9%) in the pre-CTA group and 11 patients (10.1%) on CTA, and thoracoabdominal aortic aneurysms with 6 patients (9.0%) in pre-CTA group and 13 patients (11.8%) of the CTA group (P>0.05 for all comparisons). Regarding dissections, there was also similar distribution between the two groups: the acute type A dissections amounted

83% (74 patients) of the pre-CTA group and 73% (45 patients) of the CTA group; type B acute aortic dissection amounted 17% (15 patients) of pre-CTA group and 24% (16 patients) of CTA group (P>0.05 for both comparisons). Patients from CTA group (Table 1) were older (P=0.01), with a higher prevalence of DM (P=0.005), higher blood glucose (P=0.001) lower prevalence of COPD (P=0.037) and HF (P=0.005) and higher proportion of aneurysms than dissections (P=0.001), shorter circulatory arrest (P<0.001), less urgent surgeries (P<0.001), more hybrid (P=0.023) and endovascular (P=0.024) procedures. The proportion of Bentall surgeries and aortoplasties was similar in the 2 groups.

Table 1. Baseline clinical characteristics and operative variables according to the group. N (%) Age (years) Male gender n (%) Disease Aneurysm Dissection Coarctation Penetrating ulcer Previous CV surgery High blood pressure Diabetes Chronic kidney disease Myocardial infarction Cerebrovascular disease Smoking COPD Carotid disease Heart failure Hemoglobin (mg/dl) Creatinine (mg/dl) Glucose (mg/dl) Body mass index (kg/m2) Aortic size (mm) Urgent surgery Bypass time (min) Ischemia time (min) Circulatory arrest (min) Procedure Aortic root replacement Bentall Endovascular Hybrid Aortoplasty Concomitant procedures None CABG Valve surgery CABG + valve surgery

Overall 332 58±14 214 (64%)

Before-CTA 157 (47.3%) 56±13 105 (49%)

CTA 175 (52.7%) 60±15 109 (51%)

175 (52.7%) 150 (45.2%) 3 (0.9%) 3 (0.9%) 54 (23.2%) 197 (84.5%) 17 (7.3%) 40 (17.2%) 16 (6.9%) 23 (9.9%) 97 (41.6%) 48 (20.6%) 8 (3.4%) 71 (31.7%) 12.6±2.0 1.44±1.14 104±29 25.7±4.6 60.5±16.1 85 (25.6%) 147±56 82±36 29±17.5

65 (41.4%) 91 (58.0%) 1 (0.6%) 0 (0%) 12 (19.7%) 48 (78.7%) 0 (0%) 13 (21.3%) 6 (9.8%) 8 (13.1%) 31 (50.8%) 18 (29.5%) 0 (0%) 28 (45.9%) 12.5±2.1 1.42±1.22 94±20 25.5±3.5 66.9±14.2 56 (35.7%) 144±51 78±37 38±14

110 (62.9%) 59 (33.7%) 2 (1.1%) 3 (1.7%) 42 (24.4%) 149 (86.6%) 17 (9.9%) 27 (15.7%) 10 (5.8%) 15 (8.7%) 66 (38.4%) 30 (17.4%) 8 (4.7%) 43 (26.4%) 12.6±1.9 1.44±1.1 110±31 25.7±4.8 58.6±16.2 29 (16.6%) 148±62 85±35 18±14

105 (31.6%) 96 (28.9%) 50 (15.1%) 71 (21.4%) 8(2.6%)

53 (33.8%) 48 (30.6%) 13 (8.3%) 38 (24.2%) 5 (3.2%)

52(29.7%) 48(27.4%) 37(21.1%) 33(18.9%) 3(1.7%)

279 (84%) 30 (9.0%) 14 (4.2%) 5 (1.5%)

135 (86%) 14 (8.9%) 6 (3.8%) 2 (1.3%)

144 (82.3%) 16 (9.1%) 8 (4.5%) 3 (1.7%)

P 0.013 0.224 <0.001 0.285 0.104 0.005 0.209 0.215 0.226 0.062 0.037 0.084 0.005 0.636 0.938 <0.001 0.777 0.006 <0.001 0.532 0.110 <0.001

0.024

0.772

CABG=coronary artery bypass graft; COPD=chronic obstructive pulmonary disease; CTA=Center for the Treatment of Aorta

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Procedures Primary procedures included aortic root replacement with Dacron graft (105 patients, 31.6%), Bentall surgery (96 patients, 28.9%), endovascular repair (50 patients, 15.1%), hybrid procedure (71 patients, 21.4%), and direct aortoplasty (8 patients, 2.4%). Tirone surgery was performed in 1 patient. Concomitant procedures were performed in 16% of patients, with similar distribution between the groups; CABG (9.0%), valve surgery (4.2%), and combined surgery (coronary artery bypass and valve surgery, 1.5%) predominated. There was no difference between groups in the rate of associated procedures. The surgeries were performed urgently in 25.6% of patients, and were more common in the pre-CTA group (35.7%) than in the CTA group (16.6%, P<0.001).

Fig. 1 - Complications and mortality in groups Before-CTA and CTA.

In subgroup analyzes stratified by timing of surgery (urgent vs. non-urgent surgery) (Figure 2), the CTA group showed a numerical reduction of mortality in urgent surgery (27.6% vs. 35.7%), without reaching statistical significance (P=0.158). There was also a significant reduction in mortality in elective procedures (6.9% vs. 15.8%, P=0.034). In subgroup analyzes stratified by disease (Figure 2 and 3A), CTA group had reduced mortality in aneurysms in general (6.9% vs. 16.7%, P=0.043), in aneurysms of the ascending aorta (1.4% vs. 6.5%, P=0.048) and associations of > 2 aneurysms (20.0% vs. 100%, P=0.04).

Univariate analysis In-hospital morbidity and mortality The overall unadjusted mortality was 16.3% (54 patients). Major complications occurred in 88 patients (26.5%), and 27 patients suffered reoperation (8.2%). The average length of ICU stay was 5.2 days; the average hospital stay was 14.7 days. The most common complications are postoperative bleeding (17.2%), arrhythmias (11.1%), pneumonia (7.2%), stroke (7.5%) and sepsis (5.4 %). The CTA group had lower in-hospital mortality in univariate analysis compared to the pre-CTA (9.7% vs. 23%, P=0.002) (Figure 1). The CTA also had a lower incidence of complications (38.9% vs 56.7%, P=0.001) and major complications (20.6% vs 33.1%, P=0.007) (Figure 1 and Table 2). There was also a reduction in length of stay in the ICU in CTA group (4.8±8.4 days vs. 6.4±7.2 days, P=0.001).

Fig. 2 - Mortality according to urgency and to disease subgroups.

Table 2. Postoperative outcomes according to the group. Reintervention Complications Major complications ICU LOS (days) Hospital time (days) Stroke Myocardial infarction PO bleeding Acute kidney injury Mediastinitis AV block Arrhytmia Pneumonia Sepses Low cardiac output Pleural effusion Myocardial ischemia

Overall 27 (8.2%) 157 (47.3%) 88 (26.5%) 5.2±8.2 14.7±13.9 25 (7.5%) 6 (1.8%) 57 (17.2%) 7 (2.1%) 6 (1.8%) 8 (2.4%) 37 (11.1%) 24 (7.2%) 18 (5.4%) 17 (5.1%) 13 (3.9%) 2 (0.6%)

Before-CTA 17 (10.9%) 89 (56.7%) 52 (33.1%) 6.4±7.2 14.4±12.8 17 (10.9%) 3 (1.9%) 32 (20.4%) 3 (1.9%) 3 (1.9%) 2 (1.3%) 15 (9.6%) 15 (9.6%) 15 (9.6%) 8 (5.1%) 5 (3.2%) 0 (0%)

CTA 10 (5.7%) 68 (38.9%) 36 (20.6%) 4.8±8.4 14.8±14.2 8 (4.6%) 3 (1.7%) 25 (14.3%) 4 (2.3%) 3 (1.7%) 6 (3.4%) 22 (12.6%) 9 (5.1%) 3 (1.7%) 9 (5.1%) 8 (4.6%) 2 (1.1%)

P 0.046 0.001 0.007 0.001 0.651 0.045 0.605 0.083 0.560 0.605 0.180 0.243 0.090 0.001 0.592 0.359 0.277

ICU=intensive care unit; CTA=Center for the treatment of aorta; AV=atrioventricular; LOS=lenght of stay; PO=postoperative

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Fig. 3 - A) Subgroup analysis showing overall, procedure- disease-, and urgency-stratified mortality; B) Sensitivity analysis, comparing mortality by year in Before-CTA group, in CTA group, and mean annualized mortality between the 2 groups.

In the repair of thoracoabdominal aneurysms, there was a reduction in mortality, without reaching statistical significance (30.8% vs. 50.0%, P=0.378). In aneurysms of arch and descending aorta, the number of surgical cases was low and there were no deaths, precluding comparison between groups. In patients undergoing surgery for acute type A aortic dissection, there was no significant reduction in mortality in the CTA group (17.7% vs. 25.7%, P=0.238), and the analysis stratified by the involvement of the aortic arch did not change this outcome. In acute type B dissections, however, there was a reduction of mortality in the CTA group compared to pre-CTA (18.7% vs. 37.5%, P=0.038). In stratified analysis by procedure (Figure 3A) the CTA group showed reduced mortality in hybrid procedures (15.2% vs 39.5%, P=0.023) and in the Bentall surgery (4.2% vs 18.8%, P=0.025). In urgent/emergency surgeries and in the aortic root replacement surgeries, the CTA group showed reduced mortality, without reaching statistical significance (27.6% vs 35.7%, P=0.338, and 13.5 vs 20%, 8%, P=0.321, respectively). In the endovascular treatment, mortality was similar in the 2 groups (10.8% vs 7.7%, P=0.611). In the sensitivity analysis to assess the evolution of annual mortality (Figure 3B), mortality within the pre-CTA (20032007) period remained between 17.6% and 30% (annualized average 23%), with no significant variation in the period (P=0.580). In CTA period (2008-2010), the annual mortality was between 7.7% and 13.5% (annualized average 9.7%), also with no variation within the period (P=0.594). However, comparing the annualized mortality between the two periods, a statistically significant reduction in the CTA group (P=0.002) appeared, suggesting that the reduction in mortality has not occurred by seasonal variation, gradual decrease over time,

or improvements in other factors not related to the CTA, but by the direct effect of the creation of the CTA. In the specific complications (Table 2), the CTA group had lower incidence of reoperation (P=0.046), stroke (P=0.045) and sepsis (P=0.001). The increased incidence of postoperative bleeding (14.3% vs. 20.4%) and pneumonia (5.1% vs. 9.6%) also had a reduced number without reaching statistical significance. Factors associated with mortality The baseline and operative risk factors associated with in-hospital death in the univariate analysis were: CTA, group (dissections), location of the aneurysm (thoracoabdominal and aneurysms associations), urgent surgery, reoperation, age, hemoglobin, creatinine, increased aortic diameter and CPB time (Table 3). Multivariable Analysis Independent predictors of mortality Multivariate logistic regression (Table 4) was performed to evaluate whether specialized treatment in CTA was an independent predictor of mortality reduction. Logistic regression allows defining which variables are independently related to the outcome after simultaneous adjustment for all potential confounders[18]. The multivariate model included covariates associated with mortality in univariate analysis; thus, any association between the CTA and the primary outcome have occurred regardless of baseline differences between groups[19]. The prevalence of diabetes mellitus, COPD and heart failure; ejection fraction, and the rate of endovascular procedures were not associated with outcome in the univariate analysis, so they were not included in the multivariate model.

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Table 3. Univariate analysis of baseline characteristics and operative variables associated with in-hospital mortality after aortic surgery. Survivals Deaths P Group 0.008 Before-CTA 121 (77.1%) 36 (22.9%) CTA 157 (89.7%) 17 (9.7%) Disease Group 0.002 I (Aneurysms/coarctation) 161 (89.9%) 16 (8.9%) II (Dissection/ulcer) 117 (76.5%) 35 (22.9%) Aneurysm location <0.001 Ascending aorta 110 (96.5%) 4 (3.5%) Aortic arch 4 (100%) 0 (0%) Descending aorta 20 (95.2%) 1 (4.8%) Thoracoabdominal 12 (63.2%) 5 (26.3%) Aneurysm association 4 (44.4%) 5 (55.6%) Abdominal aorta 11 (91.7%) 5 (8.3%) Type of dissection 0.160 A 91 (67.1%) 27 (22.9%) B 24 (72.7%) 8 (24.2%) Urgent 57 (20.5%) 28 (52.8%) <0.001 Reintervention 16 (5.7%) 11 (20.7%) 0.001 Age (years) 58±14 62±11 0.032 Hemoglobin (mg/dL) 12.7±1.9 11.9±2.4 0.065 Creatinine (mg/dL) 1.3±0.8 2.2±2.2 0.053 Aortic size 59.1±15.2 73.3±19.4 0.002 Bypass time (min) 138±47 180±58 <0.001

Table 4. Multivariable analysis showing predictors of in-hospital mortality after aortic surgery. N (%) Adjusted OR 95% CI P Period 0.007 Before-CTA 1.0 Reference 65 (34.5) CTA 0.23 0.08-0.67 123 (65.5) Aneurysm location Ascending aorta 66 (58.9) 1.0 Reference Thoracoabdominal 15 (13.4) 24.59 3.11 - 194.1 0.002 Descending aorta 5.83 0.89 - 37.9 0.065 6 (5.3) Urgent surgery 5.04 1.52 - 16.75 0.008 33 (17.5) Age 188 (100) 1.04 0.99 - 1.09 0.079 Creatinine 188 (100) 1.73 1.15 - 2.60 0.008 Independent predictors of in-hospital death in multivariable analysis are marked in bold letters. Logistic regression model was adjusted for the following covariates: period (CTA), aneurysm location, disease, type of dissection, reintervention, hemoglobin, aortic size and bypass time. OR=odds ratio; 95%CI=95% confidence interval.

A multivariate analysis was also performed to assess the impact of the CTA (compared to pre-CTA) on hospital mortality stratified by pathology (aneurysms and dissections) and procedure (Table 5). This analysis showed that the CTA group had reduced mortality in both aortic aneurysms (odds ratio=0.18, 95% CI 0.034 to 0.983, P=0.048) and in the dissection (odds ratio=0.31, 95% CI 0.094 - 0.99, P=0.049), even after multivariate adjustment; similarly, reduced mortality occurred in hybrid procedures (odds ratio=0.07, 95% CI 0.007 to 0.726, P=0.026) and in the Bentall surgery (odds ratio=0.18, 95% CI 0.038 to 0.904, P=0.037) after multivariate adjustment.

In the univariate analysis, there was no association of the following variables with death: gender, disease, previous cardiac surgery, high blood pressure, diabetes, chronic kidney failure, myocardial infarction, previous stroke, coronary artery disease, smoking, COPD, carotid disease, liver disease, heart failure, type of procedure, concomitant procedure, glucose, body mass index, left atrial volume, left ventricular diastolic diameter, ejection fraction

Table 5. Multivariable analysis showing independent association of CTA with reduction of in-hospital mortality. stratified according to group (aneurysms and dissections) and by procedure. Disease/Procedure Adjusted OR IC 95% P Aneurysms 0.18 0.034 – 0.983 0.048 a Dissections 0.31 0.094 – 0.99 0.049 b Hybrid procedure 0.07 0.007 – 0.726 0.026 c Bentall procedure 0.18 0.038 – 0.904 0.037 d

The logistic regression model showed that the surgery in specialized center (CTA) led to a 77% reduction of in-hospital mortality compared to the pre-CTA period, with an odds ratio = 0.23 (95% CI 0.07 to 0.67, P=0.007). Other independent predictors of death were thoracoabdominal aneurysm surgery, with an odds ratio = 24.6 (95% CI 3,1 to 194, P=0.002); urgent surgery, with an odds ratio = 5.0 (95% CI 1.5 to 16.7, P=0.008); and preoperative creatinine, with an odds ratio = 1.7 (95% CI 1.1-2.6, P=0.008); for each 0.1mg/dL increase in preoperative creatinine, the risk of death increased by 7.3%. These factors are independently associated with hospital mortality, even after adjustment for possible confounding factors. The predictive characteristics of the multivariate model were as follow: overall accuracy of 90% for predicting hospital mortality; explains 40% of the variability in the outcome of hospital death (Nagelgerke R square=0.391); very good discriminatory power (area under the ROC curve=0.824); have a good fit (Hosmer-Lemeshow test for goodness-of-fit: P=0.184), and shows stability and absence of significant multicollinearity.

a. Model adjusted for: previous cardiac surgery, urgency, age, chronic kidney disease, aortic size. b. Model adjusted for: diabetes, smoking, urgency, previous cardiac surgery. c. Adjusted for: disease, urgency, creatinine, age; d. Model adjusted for: disease, urgency, age, creatinine, heart failure. OR=odds ratio; 95%CI=95% confidence interval

DISCUSSION In the present study, the thoracic aortic surgery in a specialized center (CTA) decreased the rate of complications (stroke, sepsis, bleeding) and was independently associated with lower in-hospital mortality after thoracic and thoracoabdominal aortic surgeries (reduction ~77%). There was a reduction of in-hospital mortality in CTA in subgroups stratified by disease

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(in aneurysms, especially of the ascending aorta and in more than one segment; in acute dissections, especially type B) and by procedure (hybrid procedures, Bentall). In addition to surgery in non-specialized center, baseline creatinine, urgent surgery and thoracoabdominal aneurysms were also independent predictors of in-hospital death. Aortic surgeries are complex, have high morbidity and mortality, and require great care and preparation to ensure favorable outcomes[20-22]. In the most complex diseases the effect of specialized interventions on clinical outcomes is more relevant[23]. Therefore, it is expected that specialized centers in thoracic aortic surgeries may obtain the best results. There is already evidence of efficacy of this strategy in the pathologies of the infrarenal aorta[12,24]. Specialized centers in aortic surgery with high surgical volume have reported good results in thoracic aortic surgery. However, these results do not reflect the reality of all centers. Thus, multicenter registries including non-specialized centers have reported increased morbidity and mortality, especially for high-risk cases. Indirectly, this suggests that patients with high surgical risk patients present better outcomes in specialized centers[25,26]. This study objectively confirms this notion, showing a reduction of clinically relevant outcomes after thoracic aortic surgery (in-hospital mortality, complications, reoperations, stroke and sepsis). The outcomes described herein for the CTA group are comparable to those described in reports of case series undergoing surgery in large centers specialized in aortic surgery. In a series of 597 patients undergoing the Bentall surgery, overall mortality was 3.8%[27], similar to what was reported in our study (4.2%), and consistent with recommendations to specialized centers (mortality 1-5%)[14]. Regarding endovascular treatment, in a report of 400 cases, the mortality rate was 6.5%[28], comparable to our group (7.7%). On the other hand, the outcomes reported for pre-CTA group are similar to those described in multicenter registries that include non-specialized centers. In a cohort study of 12,573 patients with thoracic aortic aneurysms[29], the authors reported mortality for urgent surgery of 46%, even higher than that reported by us in the pre-CTA group (35.7%). The mortality rate for endovascular repair was 6.1% (elective), similar to reported in our pre-CTA group (10.3%); in urgent surgery, the mortality was 28%, comparable to our data (25%). An important finding was revealed by the sensitivity analysis that evaluated the evolution of annual mortality. During the period 2003-2010, there was a significant reduction in mortality (P=0.008). This reduction did not occurred in 2003-2007 period, where mortality was stable (annualized average: 23%). This reduction also didnÂ´t occur in the period 2008-2010, where the mortality remained stable (annualized average: 9.7%). This analysis confirms that there was no reduction of outcomes only by gradual improvement in care or progressive incorporation of new techniques. Finally, comparing mortality

among pre-CTA vs. CTA period, there was a significant reduction (P=0.002), showing clearly that the improvement in outcomes occurred exactly at the transition between the two periods. Considering that our service has performed aortic surgery for over 15 years, one can say that the improvement in outcomes was not due to the impact of the learning curve or increased surgical volume, but due to the specialization[21,22]. The improved outcomes reported herein repeated consistently in different subgroups of patients, in multivariate analysis adjusted for baseline differences and comorbidities. The CTA group had independent mortality reduction in aneurysms, dissections and also in hybrids procedures and Bentall surgeries. Thus, we can confirm that the lowest mortality occurred by the beneficial effect of specialization of the center, and not by the differences in the baseline clinical variables between pre-CTA and CTA patients. There is only one study in the literature directly comparing outcomes in thoracic aortic surgery at high-volume centers (> 80 surgeries in 3 years) with lower volume centers (<80 surgeries in three years); this study retrospectively evaluates the data from the Virginia Cardiac Surgery Quality Initiative (VCSQI)[30]. However, unlike the present study, the authors evaluate only the thoracic aortic aneurysms and exclude emergency surgeries. More than 500 elective aortic aneurysm surgeries were performed in high-volume centers and 216 surgeries in low-volume centers. In-hospital mortality was 3.8% for high-volume centers compared with 8.3% in low-volume centers (P=0.01). This difference demonstrated in the univariate analysis was tested after multivariate adjustment. For this, the authors performed the same multivariable logistic regression that we did, and they showed that elective surgery for thoracic aortic aneurysm in high-volume centers was an independent predictor of reduced mortality, with an odds ratio=0.41 (95% CI 0.18 to 0.92, P=0.03, 59% reduction). In our study, unselected thoracic aortic surgery at the CTA also reduced in-hospital mortality (odds ratio=0.23 (95% CI 0.08 to 0.67, P=0.007, 77% reduction). It is noteworthy the fact that hospital mortality for elective thoracic aortic aneurysms of our CTA group (n=84, mortality 3.8%) was equal to the mortality of high-volume centers of the aforementioned study (3.8%), and mortality for aneurysms of our pre-CTA group (n=54, mortality 7.4%) was slightly better than the mortality of low-volume centers (8.3%). A more recent study[31] aimed to compare surgical outcomes in patients with type A acute aortic dissection, before and after installation of a multidisciplinary program in thoracic aortic surgery (â&#x20AC;&#x153;TASPâ&#x20AC;?). In this study, the post-TASP group also had several baseline differences when compared to the pre-TASP group: it had a lower rate of infarction, fewer emergency surgeries, less concomitant procedures, shorter CPB and circulatory arrest, a higher percentage of patients undergoing selective cerebral perfusion, and more use of VIIa factor postoperatively. The results showed a very important

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reduction in mortality in the post-TASP group compared to pre-TASP group (from 33.9% to 2.8%, P=0.002). The authors didnÂ´t perform any kind of multivariate analysis to adjust the results for differences in baseline characteristics; they only compared the pre-TASP and post-TASP mortalities with their predicted mortality by Rampaldi Score, which is a score that still lacks external validation. In contrast, in the present study, we performed a rigorous multivariate adjustment to avoid confounding caused by differences in baseline characteristics between the groups; in addition, we assessed the effect of CTA in a broader group of patients including dissections, aneurysms and different types of procedures. Multiple aspects may explain the improved outcomes in specialized centers in aortic surgery. It has been shown that performing highly specialized procedures with high surgical volumes generates expertise by repetition[32]. Specific technology used by trained staff creates operational efficiency, economy in scale and greater cost-effectiveness[33]. In addition, trained and specialized teams can quickly add new technologies and scientific advances to patient care with improved outcomes[34]. Our study has limitations. Our patients were not randomized for allocation in the pre-CTA or CTA groups. Therefore, unmeasured baseline differences between groups may be present, with a potential impact on the estimate of the effect of the intervention. However, it seems inappropriate to randomize patients to surgery in non-specialized center, precluding the use of treatment strategies which are part of the best current therapy (and included here as part of the CTA strategy), because it would be unethical and could add risk to patients. Therefore, our study used a non-contemporaneous (historical) control group. This strategy has been questioned for possible selection bias (differences in baseline characteristics or disease severity) and bias by variation of other factors associated with outcome[35,36]. More recently, however, it has been shown that studies with historical controls, conducted carefully and accurately, can provide important evidence about benefits and harms of interventions, especially when there is effect plausibility, poor prognosis with usual treatment or risk of worse outcomes in patients not treated with the intervention under test[37,38]. Quality criteria and requirements for using historical controls have been proposed[39,40]. They include: collecting data in a blinded way (our data collection was prospective and blind); including patients with the same eligibility during the entire period (all treated patients with aortic disease in our hospital were eligible to allocation, and conditions of referral from other facilities were stable over the period); maintaining stable strategies of treatment over time (surgical techniques and perioperative care were similar throughout the study); using similar diagnostic methods (CT angiography of the aorta, aortography and transesophageal echocardiography were available for the whole period); indicating surgery at the same stage of evolution (we met surgical indications of relevant

guidelines and avoided comparing outcomes between groups undergoing surgery in different stages of disease progression); and rigorous multivariate adjustment (we used multivariate logistic regression with adjustment for all covariates associated with outcome)[39,40]. If performed with such care, studies with historical controls have enabled major advances in relevant diseases[41-45], also having influenced health policies of several countries[41-43]. The implications of the reported findings are potentially relevant. It is essential that new studies confirm our findings, and enable additional analyzes, by determining the cost-effectiveness of CTA strategy. It is also important to determine if there is a positive impact on long-term outcomes. Nevertheless, these data may be an important stimulus for new surgical groups to create specialized centers, offering patients positive results as demonstrated herein. The allocation of public resources supporting the creation of new centers may be needed to ensure the availability of aortic centers in many hospitals and cities, expanding this strategy and reducing adverse outcomes. In conclusion, surgical treatment of thoracic and thoracoabdominal aortic diseases in specialized center (aortic center) was associated with lower rates of complications and in-hospital mortality. Further studies will be required to confirm these data and to assess the cost-effectiveness and long-term outcomes.

Authorsâ&#x20AC;&#x2122; roles & responsibilities MCS Author JDFF Coauthor CA Coauthor LDS Coauthor AMR Coauthor EAL Coauthor PEL Coauthor MRNP Coauthor FAL Coauthor

REFERENCES 1. Hirst AE Jr, Johns VJ Jr, Kime SW Jr. Dissecting aneurysm of the aorta: a review of 505 cases. Medicine (Baltimore). 1958;37(3):217-79. 2. Elefteriades JA, Farkas EA. Thoracic aortic aneurysm clinical pertinent controversies and uncertainties. J Am Coll Cardiol. 2010;55(9):841-57. 3. Svensson LG, Kouchoukos NT, Miller DC, Bavaria JE, Coselli JS, Curi MA, et al; Society of Thoracic Surgeons Endovascular Surgery Task Force. Expert consensus document on the treatment of descending thoracic aortic disease using endovascular stentgrafts. Ann Thorac Surg. 2008;85(1 Suppl):S1-41.

502

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Sales MC, et al. - Aortic Center: specialized care improves outcomes and decreases mortality

Rev Bras Cir Cardiovasc 2014;29(4):494-504

4. Birkmeyer JD, Siewers AE, Finlayson EV, Stukel TA, Lucas FL, Batista I, et al. Hospital volume and surgical mortality in the United States. N Engl J Med. 2002;346(15):1128-37.

Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine. J Am Coll Cardiol. 2010;55(14):e27-e-129.

5. Verhoef C, van der Weyer R, Schaapveld M, Bastiaannet E, Plukker JT. Better survival in patients with esophageal cancer after surgical treatment in university hospitals: a plea for performance by surgical oncologists. Ann Surg Oncol. 2007;14(5):1678-87.

15. Albuquerque LC, Braile DM, Palma JH, Gomes WJ, Buffolo E. Diretrizes para o tratamento cirúrgico das doenças da aorta da Sociedade Brasileira de Cirurgia Cardiovascular. Rev Bras Cir Cardiovasc. 2007;22(2):137-59.

6. Cheung MC, Hamilton K, Sherman R, Byrne MM, Nguyen DM, Franceschi D, et al. Impact of teaching facility status and high-volume centers on outcomes for lung cancer resection: an examination of 13,469 surgical patients. Ann Surg Oncol. 2009;16(1):3-13.

16. Erbel R, Alfonso F, Boileau C, Dirsch O, Eber B, Haverich A, et al; Task Force on Aortic Dissection, European Society of Cardiology. Diagnosis and management of aortic dissection. Eur Heart J. 2001;22(18):1642-81.

7. Eppsteiner RW, Csikesz NG, McPhee JT, Tseng JF, Shah SA. Surgeon volume impacts hospital mortality for pancreatic resections. Ann Surg. 2009;249(4):635-40.

17. Coselli JS, LeMaire SA. Descending and thoracoabdominal aortic aneurysms. In: Cohn LH, ed. Cardiac surgery in the adult. 3rd ed. New York: McGraw-Hill; 2008. p.1277-98.

8. Cowan JA Jr, Dimick JB, Thompson BG, Stanley JC, Upchurch GR Jr. Surgeon volume as an indicator of outcomes after carotid endarterectomy: an effect independent of specialty practice and hospital volume. J Am Coll Surg. 2002;195(6):814-21.

18. Chan YH. Biostatistics 202: logistic regression analysis. Singapore Med J. 2004;45(4):149-53.

9. Hagan PG, Nienaber CA, Isselbacher EM, Bruckman D, Karavite DJ, Russman PL, et al. The International Registry of Acute Aortic Dissection (IRAD): new insights into an old disease. JAMA. 2000;283(7):897-903.

19. Katz MH. Multivariable analysis: a primer for readers of medical research. Ann Intern Med. 2003;138(8):644-50. 20. Hatswell EM. Abdominal aortic aneurysm surgery, Part I: An overview and discussion of immediate perioperative complications. Heart Lung. 1994;23(3):228-39.

10. Reece TB, Green GR, Kron IL. Aortic dissection. In: Cohn LH, ed. Cardiac surgery in the adult. 3rd ed. New York: McGraw-Hill; 2008. p.1195-222.

21. Pereira WM, Frota Filho JD, Sales M, Delatorre N, Leães PE, Blacher C, et al. “Stent” auto-expansível nas dissecções da aorta tipo B. Rev Bras Cir Cardiovasc. 1999;14(3):207-14.

11. Kouchoukos NT, Bavaria JE, Coselli JS, De la Torre R, Ikonomidis JS, Karmy-Jones RC, et al. Guidelines for credentialing of practitioners to perform endovascular stent-grafting of the thoracic aorta. J Thorac Cardiovasc Surg. 2006;131(3):530-2.

22. Pereira WM, Lobo R, Sales M, Tanaka N, Portugal LEV, Flores LAV, et al. Tratamento das afecções da aorta com a primeira geração de stents auto-expansíveis. Rev Bras Cir Cardiovasc 2001;16(3):218-25.

12. Hill JS, McPhee JT, Messina LM, Ciocca RG, Eslami MH. Regionalization of abdominal aortic aneurysm repair: evidence of a shift to high-volume centers in the endovascular era. J Vasc Surg. 2008;48(1):29-36.

23. Ronellenfitsch U, Rössner E, Jakob J, Post S, Hohenberger P, Schwarzbach M. Clinical Pathways in surgery: should we introduce them into clinical routine? A review article. Langenbecks Arch Surg. 2008;393(4):449-57.

13. Williams OD. Quality of care versus provider volume: does one lead to the other? Med Care. 2003;41(10):1127-8.

24. Troëng T. Volume versus outcome when treating abdominal aortic aneurysm electively: is there evidence to centralize? Scand J Surg. 2008;97(2):154-9.

14. Hiratzka LF, Bakris GL, Beckman JA, Bersin RM, Carr VF, Casey DE Jr, et al; American College of Cardiology Foundation/ American Heart Association Task Force on Practice Guidelines; American Association for Thoracic Surgery; American College of Radiology; American Stroke Association; Society of Cardiovascular Anesthesiologists; Society for Cardiovascular Angiography and Interventions; Society of Interventional Radiology; Society of Thoracic Surgeons; Society for Vascular Medicine. 2010 ACCF/AHA/AATS /ACR/ASA/SCA/SCAI/ SIR/STS/SVM Guidelines for the diagnosis and management of patients with thoracic aortic disease. A Report of the American College of Cardiology Foundation/American Heart Association

25. Rigberg DA, McGory ML, Zingmond DS, Maggard MA, Agustin M, Lawrence PF, et al. Thirty-day mortality statistics underestimate the risk of repair of thoracoabdominal aortic aneurysms: a statewide experience. J Vasc Surg. 2006;43(2):217-22. 26. Knipp BS, Deeb GM, Prager RL, Williams CY, Upchurch GR Jr, Patel HJ. A contemporary analysis of outcomes for operative repair of type A aortic dissection in the United States. Surgery. 2007;142(4):524-8.

503

Rev Bras Cir Cardiovasc | Braz J Cardiovasc Surg

Sales MC, et al. - Aortic Center: specialized care improves outcomes and decreases mortality

Rev Bras Cir Cardiovasc 2014;29(4):494-504

27. Etz CD, Bischoff MS, Bodian C, Roder F, Brenner R, Griepp RD, et al. The Bentall procedure: is it the gold standard? A series of 597 consecutive cases. J Thorac Cardiovasc Surg. 2010;140(6 Suppl):S64-70.

traditional ways of assessing evidence. [Acesso em: 25/6/2011]. Disponível em: http://www.politics.co.uk/opinion-formers/ royal-college-of-physicians/article/royal-college-of-physicianssir-michael-rawlins-attacks-trad

28. Lee WA, Daniels MJ, Beaver TM, Klodell CT, Raghinaru DE, Hess PJ Jr. Late outcomes of a single-center experience of 400 consecutive thoracic endovascular aortic repairs. Circulation. 2011;123(25):2938-45.

38. Cranberg L. Do retrospective controls make clinical trials “inherently fallacious?” Br Med J. 1979;2(6200):1265-6. 39. Baker SG, Lindeman KS, Kramer BS. The paired availability design for historical controls. BMC Med Res Methodol. 2001;1:9.

29. Goodney PP, Travis L, Lucas FL, Fillinger MF, Goodman DC, Cronenwett JL, et al. Survival after open versus endovascular thoracic aortic aneurysm repair in an observational study of the Medicare population. Circulation. 2011;124(24):2661-9.

40. Caro J, Payne K, Khan Z, Daley W. The use of historical controls to enable actual practice comparisons for prospective observational studies. ISPOR-International Society of Pharmaco economics and Outcomes Research 8th Annual European Congress Nov 2005.

30. Gazoni LM, Speir AM, Kron IL, Fonner E, Crosby IK. Elective thoracic aortic aneurysm surgery: better outcomes from highvolume centers. J Am Coll Surg. 2010;210(5):855-9.

41. Humar A, Kumar D, Preiksaitis J, Boivin G, Siegal D, Fenton J, et al. A trial of valganciclovir prophylaxis for cytomegalovirus prevention in lung transplant recipients. Am J Transplant. 2005;5(6):1462-8.

31. Andersen ND, Ganapathi AM, Hanna JM, Williams JB, Gaca JG, Hughes GC. Outcomes of acute type a dissection repair before and after implementation of a multidisciplinary thoracic aortic surgery program. J Am Coll Cardiol. 2014;63(17):1796-803.

42. Buist MD, Moore GE, Bernard SA, Waxman BP, Anderson JN, Nguyen TV. Effects of a medical emergency team on reduction of incidence of and mortality from unexpected cardiac arrests in hospital: preliminary study. BMJ. 2002;324(7334):387-90.

32. Casalino LP, Devers KJ, Brewster LR. Focused factories? Physician-owned specialty facilities. Health Aff (Millwood). 2003;22(6):56-67.

43. Olsen AH, Njor SH, Vejborg I, Schwartz W, Dalgaard P, Jensen MB, et al. Breast cancer mortality in Copenhagen after introduction of mammography screening: cohort study. BMJ. 2005;330(7485):220.

33. Leung GM. Hospitals must become “focused factories” BMJ. 2000;320(7239):942-3. 34. Crean KW. Accelerating innovation in information and communication technology for health. Health Aff (Millwood). 2010;29(2):278-83.

44. Martling AL, Holm T, Rutqvist LE, Moran BJ, Heald RJ, Cedemark B. Effect of a surgical training programme on outcome of rectal cancer in the County of Stockholm. Stockholm Colorectal Cancer Study Group, Basingstoke Bowel Cancer Research Project. Lancet. 2000;356(9224):93-6.

35. Sacks H, Chalmers TC, Smith H Jr. Randomized versus historical controls for clinical trials. Am J Med. 1982;72(2):233-40. 36. Altman DG, Bland JM. Statistics notes. Treatment allocation in controlled trials: why randomise? BMJ. 1999;318(7192):1209.

45. Fakhry SM, Trask AL, Waller MA, Watts DD; IRTC Neurotrauma Task Force. Management of brain-injured patients by an evidencebased medicine protocol improves outcomes and decreases hospital charges. J Trauma. 2004;56(3):492-9.

37. Royal College of Physicians: Sir Michael Rawlins attacks

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Capriglione LGA, et al. - Comparison of two surgical techniques for creating ORIGINAL ARTICLE an acute myocardial infarct in rats

Comparison of two surgical techniques for creating an acute myocardial infarct in rats Comparação de duas técnicas cirúrgicas para criar um infarto agudo do miocárdio em ratos

Luiz Guilherme Achcar Capriglione1, MsC; Fabiane Barchiki1, MsC; Gabriel Sales Ottoboni1, MsC; Nelson Itiro Miyague1, PhD; Paula Hansen Suss1, PhD; Carmen Lúcia Kuniyoshi Rebelatto1, PhD; Cláudia Turra Pimpão1, PhD; Alexandra Cristina Senegaglia1, PhD; Paulo Roberto Brofman1, PhD

DOI: 10.5935/1678-9741.20140075

RBCCV 44205-1582

Abstract Objective: To perform a comparative assessment of two surgical techniques that are used creating an acute myocardial infarc by occluding the left anterior descending coronary artery in order to generate rats with a left ventricular ejection fraction of less than 40%. Methods: The study was completely randomized and comprised 89 halothane-anaesthetised rats, which were divided into three groups. The control group (SHAM) comprised fourteen rats, whose left anterior descending coronary artery was not occluded. Group 1 (G1): comprised by 35 endotracheally intubated and mechanically ventilated rats, whose left anterior descending coronary artery was occluded. Group 2 (G2): comprised 40 rats being manually ventilated using a nasal respirator whose left anterior descending coronary artery was occluded. Other differences between the two techniques include the method of performing the thoracotomy and removing the pericardium in order to expose the heart, and the use of different methods and suture types for closing the thorax. Seven days after surgery, the cardiac function of all surviving rats was determined by echocardiography. Results: No rats SHAM group had progressed to death or had left ventricular ejection fraction less than 40%. Nine of the

16 surviving G1 rats (56.3%) and six of the 20 surviving G2 rats (30%) had a left ventricular ejection fraction of less than 40%. Conclusion: The results indicate a tendency of the technique used in G1 to be better than in G2. This improvement is probably due to the greater duration of the open thorax, which reduces the pressure over time from the surgeon, allowing occlusion of left anterior descending coronary artery with higher accuracy.

Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, PR, Brazil.

Correspondence address: Paulo Roberto Brofman Pontifícia Universidade Católica do Paraná Rua Imaculada Conceição, 1155 - Prado Velho, Curitiba, PR Brazil - Zip code:80215-901 E-mail: paulo.brofman@pucpr.br

Descriptors: Myocardial infarction. Echocardiography. Models, Cardiovascular. Resumo Objetivo: Realizar uma avaliação comparativa de duas técnicas cirúrgicas que são usadas para criar um infarto agudo do miocárdio pela oclusão da artéria coronária descendente anterior esquerda, a fim de gerar ratos com uma fração de ejeção ventricular esquerda inferior a 40%. Métodos: O estudo foi completamente randomizado e composto por 89 ratos anestesiados com halotano, que foram divididos dentro de três grupos. O grupo controle (SHAM) composto por 14 ratos, cuja artéria coronária descendente anterior esquerda não foi ocluída. Grupo 1 (G1): composto por 35 ratos intubados

This study was carried out at Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, PR, Brazil. Financial support from Conselho Nacional de Desenvolvimento Científico e Tecnológico-CNPq

Article received on October 31th, 2013 Article accepted on May 26th, 2014

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lizando um respirador nasal, cuja artéria coronária descendente anterior esquerda foi ocluída. Outras diferenças entre as duas técnicas incluem o método de realizar a toracotomia e remover o pericárdio, a fim de expor o coração, e o uso de diferentes métodos e tipos de sutura para fechar o tórax. Sete dias após a cirurgia, a função cardíaca de todos os ratos sobreviventes foi determinada por ecocardiografia. Resultados: Nenhum rato do grupo SHAM foi a óbito ou teve fração de ejeção ventricular esquerda menor que 40%. Nove dos 16 ratos sobreviventes do G1 (56,3%) e seis dos 20 ratos sobreviventes do G2 (30%) tiveram uma fração de ejeção ventricular esquerda inferior a 40%. Conclusão: Os resultados indicam uma tendência da técnica utilizada no G1 ser melhor do que a do G2. Esta melhora deve-se provavelmente à maior duração do tórax aberto, o que reduz a pressão de tempo sobre o cirurgião, permitindo uma oclusão da artéria coronária descendente anterior esquerda com maior acurácia.

Abbreviations, acronyms & symbols AMI Acute myocardial infarction EDA End diastolic area EDV End diastolic volume ESA End systolic area ESV End systolic volume G1 Group 1 G2 Group 2 HR Heart rate IM Intramuscular IP Intraperitoneal LADCA Left anterior descending coronary artery LVEF Left ventricular ejection fraction SD Standard deviation SHAM Control group

endotraquealmente e ventilados mecanicamente, cuja artéria coronária descendente anterior esquerda foi ocluída. Grupo 2 (G2): constituído por 40 ratos sendo ventilados manualmente uti-

Descritores: Infarto do miocárdio. Ecocardiografia. Modelos Cardiovasculares.

INTRODUCTION

left ventricular ejection fraction (LVEF) of less than 40%. The consequent on cardiac function in these rats was assessed using echocardiography.

Cell therapy has been proposed as a future therapy for myocardial diseases, and the efficacy of the different types of cell therapy for cardiomyopathies has been investigated in rats with experimental acute myocardial infarction (AMI)[1]. Two different surgical techniques for creating an AMI in rats have been described in the medical science literature. Both techniques have four common steps: a lateral thoracotomy through the left fourth intercostal space, removal of the pericardium, permanent occlusion of the left anterior descending coronary artery (LADCA), and closure of the thorax. However, the techniques differ in terms of (a) the need for endotracheal intubation, (b) the type of ventilatory support, (c) the duration of the open-chest surgery, and (d) visualisation of the myocardial infarction after occlusion of the LADCA artery. The first technique, which was initially described by Johns & Olson[2], is simple, does not require sophisticated equipment, and is still widely used by other investigators[3-6]. In this technique, the animal can be nasally ventilated using a respirator because of the duration of open thorax is short, thereby eliminating the need for endotracheal intubation. In the second technique, which is also commonly used by investigators[1,7], the animals are obligatorily intubated and are mechanically ventilated in the positive end-expiratory pressure mode because the duration of open thorax is longer than that of the first technique. Other differences between the two techniques include the method of performing the thoracotomy and removing the pericardium in order to expose the heart, and the use of different methods and suture types for closing the open thorax. The aim of this study was to compare two different surgical methods for creating an AMI in order to generate rats with a

METHODS Animals This animal study and the procedures detailed herein were reviewed and approved by the Local Ethics Committee on Animal Research (Identification numbers: PUCPR 180 and 540). The study comprised 89 male 100-day-old albino Wistar rats (Rattus norvegicus) (mean weight 348.6 grams ±24.3 (standard deviation (SD)]. The rats were obtained from the central animal facility of the Pontifícia Universidade Católica do Paraná, Curitiba, Brazil, which has an in-house breeding programme. The rats were housed in open-top polypropylene cages (41cm x 34cm x 16cm (height)) in groups of three or four rats/cage in a temperature- (18-21C°) and humidity-controlled (55-65% relative humidity) environment with a 12-hour light-dark cycle, and had ad libitum access to a standard rodent chow (NUVITAL®, Colombo, Paraná, Brazil) and water. The bedding (pine wood shavings, Inbrasfama, São José dos Pinhais, Paraná, Brazil) in each cage was changed daily. A comparative experimental study was performed. After a 2-day acclimatization period, the rats were randomly divided by lot of cages into three groups according to the surgical procedure that they underwent. An AMI was created in 35 rats of the Group 1 (G1) and 40 rats of the Group 2 (G2) by two different surgical methods (see later). Group 3 (SHAM) comprised fourteen rats, used as control of the experiment, in which ones the AMI was not created. The methods of anaes-

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thesia, thoracotomy, and exposure of the heart and LADCA in these fourteen SHAM rats were identical to those that were done in the G2 rats (see later). In the SHAM rats, the LADCA was not occluded after placing 4-0 silk thread around the exposed vessel.

~4% halothane in 100% oxygen in a glass induction chamber (Chiarorn. Brazil). The rats were not endotracheally intubated, and the anaesthesia was maintained by ~2% halothane in 100% oxygen (~350 ml/minute) using a facial mask. Halothane delivery to the anaesthetised rats was not continuous: it was stopped at the time of LADCA occlusion or when the rat was at the desired depth of anaesthesia. The rats were manually ventilated at ~70-80 breaths/minute and a minute volume of ~175-200 ml/min during the thoracotomy and in the immediate postoperative period using a nasal respirator that was adapted[7] (Figure 1).

Anaesthesia Full details of the anaesthetic protocols for the two groups of rats are presented in Table 1. For G1 rats, the rats were first pre-medicated by intraperitoneal (IP) injections of 1.25mg/ kg diazepam (Valium®, 5 mg/ml, Teuto, Goiás, Brazil) and 12.5 mg/kg ketamine (Vetanarcol®, 50 mg/ml, Laboratórios König S.A., Avellaneda, Argentina), and an intramuscular (IM) injection of 5 mg/kg meperidine (Dolosal®, 50 mg/ml, Cristália, São Paulo, Brazil). Five minutes after the injections, anaesthesia was induced by ~4% halothane (Tanohalo®, Cristália, São Paulo, Brazil) in 100% oxygen in a glass induction chamber (Chiarorn, Brazil). Each rat was then endotracheally intubated, and their anaesthesia was maintained by ~2% halothane vaporized in 100% oxygen (~150 ml/minute) in a semi-closed breathing circuit. Halothane delivery to the anaesthetised rats was not continuous: it was stopped at the time of LADCA occlusion or when the rat was at the desired depth of anaesthesia. Each rat was mechanically ventilated using a ventilator (Harvard model 683 small animal ventilator, Harvard Apparatus, MA, USA), which was set 70-80 breaths/ minute and a minute volume of 175-200 ml/min. For G2 rats, different pre-medication and anaesthesia protocols were used because the duration of the surgery was shorter than that of the G1 rats. In this group, the rats were first pre-medicated by an IM injection of 5 mg/kg meperidine. Five minutes after the injection, anaesthesia was then induced by

Fig. 1 - Nasal respirator for manual ventilation of the G2 rats during the thoracotomy and occlusion of the left anterior descending branch of the left coronary artery. *Group 2 (G2)

Table 1. Details of the pre-medication and anaesthetic protocols and the peri-and post-operative medications of the two groups of rats in whom an acute myocardial infarction (AMI) was created. Anaesthesia Protocol Inhalation Anaesthesia Dissociative Anaesthesia Muscle Relaxant Intraoperative Analgesic Postoperative Analgesics

Antibiotic Anticholinergic* Diuretic* Positive Inotrope*

Group 1 (n =35) Halothane (vaporizer) Ketamine 12.5mg/kg IP Diazepam 1.25mg/kg IP Meperidine 5mg/kg IM Morphine 1mg/kg SC, three times per day for 48 hours Flunixin 2.5mg/kg SC, once a day for 48 hours Enrofloxacin 10mg/kg IM, once daily for 4 days Atropine 40µg/kg IM Furosemide 1-4mg/kg IM Adrenaline 0.04-0.2mg/kg IM

Group 2 (n=40) Halothane (facial mask) not given not given Meperidine 5mg/kg IM Morphine 1mg/kg SC, three times per day for 48 hours Flunixin 2.5mg/kg SC, once a day for 48 hours Enrofloxacin 10mg/kg IM, once daily for 4 days Atropine 40µg/kg IM Furosemide 1-4mg/kg IM Adrenaline 0.04-0.2mg/kg IM

IM=intramuscular route of administration; IP= intraperitoneal route of administration; SC=subcutaneous route of administration; n=sample size. (*) Rats which developed adverse cardio-respiratory and renal effects following the creation of an AMI were treated with atropine, furosemide and adrenaline, if necessary

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The body temperature of the rats during the surgery and while they recovered from anaesthesia was maintained by keeping them on a heated table (MASTER DIGITAL SA300®, Ch@mpion/Electronics, France). Post-operative pain was relieved for 48 hours after surgery using flunixin and morphine, whose doses and route and frequency of administration are given in Table 1. Rats which developed adverse cardio-respiratory and renal effects following creation of the AMI were treated with atropine, furosemide, adrenaline, if necessary, and the specific details of each drug’s dose and route of administration are also listed in Table 1. Surgical creation of an AMI Before surgery, the surgical site was prepared by presurgical shaving and skin antisepsis using 95% alcohol and 2% chlorhexidine gluconate. In the G1 rats, the thoracotomy was performed through the left fourth intercostal space after surgically separating the latissimus dorsi and pectoral muscles. The intercostal space was kept open using a 7-cm Alm self-retaining retractor in order to visualize the beating heart. The pericardium was then removed using a sterile flexible cotton-tipped rod. After exposing the heart, which was not exteriorized, the LADCA was first identified, and then occluded 2 mm from its origin between the left atrial edge and the pulmonary artery sulcus using 7-0 polypropylene thread. The thorax was then closed in two layers with simple interrupted 4-0 monofilament nylon sutures. In the G2 rats, the latissimus dorsi and pectoral muscles were first separated prior to thoracotomy, which was performed through either the left fourth intercostal space. A continuous cotton thread was then placed around the surgical incision before opening the chest and exposing the heart in order to facilitate rapid closure of the open thorax immediately following occlusion of the LADCA (Figure 2). The thorax was opened using 16-cm thoracic Crile forcepsand in the sequence it was applied a lateral compression to the right thorax to physically tear the pericardium exteriorizing the heart. After exteriorizing the heart, the LADCA was occluded 2 mm from its origin by ligating the artery between the pulmonary artery and the left atrial auricle with 4-0 silk thread. Silk thread was used to occlude the artery because it has a higher tensile strength than 7-0 polypropylene thread, thereby making it less likely to break when occluding the artery. The entire procedure was rapidly performed in order to ensure a high survival rate of the rats. The thorax was closed immediately after occlusion of the LADCA. Each rat was returned to its home cage when it was fully recovered from the anaesthesia and surgery, and kept under the identical conditions that were described in the “Animals” subsection.

Fig. 2 - The route of the continuous cotton thread that is placed around the surgical incision before opening the chest in the G2 rats. * Group 2 (G2), Skin (A), latissimus dorsal muscle (B), pectoral muscle (C), skin (D), skin (E) of the other incision edge, pectoral muscle (F), latissimus dorsal muscle (G), and skin (H), 4th intercostal space (I)

SHAM rats and all surviving G1 and G2 rats was performed seven days after surgery. For this purpose, the rats were sedated by an IM injection of 50 mg/kg ketamine and 5mg/kg xylazine (Rompun®, 20 mg/ml, Bayer S.A., São Paulo, Brazil). When sedated, their thoracic hair was removed by shaving, and they were placed in the dorsal decubitus position with the body slightly inclined to the left. Two-dimensional transthoracic echocardiography was performed using a multi-frequency linear-array ultrasound transducer (15L6, bandwidth 15 MHz, Philips Ultrasound, USA) whose output was recorded on a Hewlett Packard Sonos 5500 Ultrasound System. Ejection fraction (LVEF), end systolic volume (ESV), end diastolic volume (EDV), end systolic area (ESA), and end diastolic area (EDA) of the left ventricle were determined from the images using Simpson’s method[8]. The heart rate (HR) of these rats was simultaneously measured by an electrocardiograph that was incorporated into the ultrasound system. All echocardiographic measurements were performed using the same equipment and were repeated three times by the same examiner. The results are represented as the mean of three independent measurements. After the echocardiographic examination, the rats were then returned to their home cages, where they were kept for thirty days under the identical conditions that were described in the “Animals” subsection. The rats were also followed-up daily for clinical signs of illness and behavioural problems, such as aggression or stereotypic behaviours. After 30 days, the rats were humanely killed without the presence of other

Echocardiography Echocardiographic examination was performed by an experienced professional, without the knowledge of the groups formed. An echocardiographic examination of the fourteen

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rats by an overdose of halothane after being placed in the glass induction chamber that was used to induce anaesthesia. After confirmation of death, each rat was necropsied.

The normal distribution of the samples was assessed by the Kolmogorov-Smirnov test. Means of echocardiographic parameters as well as the duration of anesthesia and surgery were compared using the test of ONE-WAY (ANOVA) followed by Bonferroni test. The chi-square test for proportions was used to determine whether the mortality rates in the SHAM, G1 and G2 groups were different from each other. The Fisher exact test was used to determine differences in proportions between groups SHAM, G1 and G2 for the occurrence of LVEF less than 40%. Data are presented as mean±SD, the level of statistical significance was set at 5% (α=0.05).

Histopathology of the hearts After euthanasia, the heart of each rat from the G1, G2, and SHAM groups was removed for histopathological analysis. For this purpose, the hearts were fixed in a 10% neutral buffered formalin solution (Biotec, Labmaster, Pinhais-PR) for 24 hours. Histological sections of the heart were prepared for haematoxylin and eosin (H&E) and Masson trichrome staining by standard procedures using a commercial kit (Easy Path®, Bio-Optica Milano S.P.A., Milan, Italy). Briefly, the formalin-maintained samples were washed in tap water, dehydrated using an ascending alcohol series, and then embedded in paraffin blocks. Sections (5-µm thick) were cut, mounted on glass slides, hydrated using distilled water, and then stained. H&E staining was performed in order to locate the infarction and Masson trichrome staining was used to assess collagen deposition in the infarct.

RESULTS The entire duration of anaesthesia and surgery was significantly longer (P<0.0001) in the G1 rats than in the G2 rats (Table 2). None of the fourteen SHAM rats died after surgery, and each SHAM rats had a LVEF that was greater than 40% (Table 2). Specifically, the values of the five echocardiographic measurements in these rats were 61.67±7.23% for LVEF, 0.59±0.07 ml for EDV, 0.23±0.05 ml for ESV, 1.09±0.08 cm2 for EDA, and 0.59±0.08 cm2 for ESA, statistically different in the G1 and G2 (Table 3). Nineteen G1 rats (54.3%) and 20 G2 rats (50%) died during the first 24 hours after surgery, and the mortality rates in the two groups were not significantly different (Table 2).

Statistical analysis The echocardiographic measurements of all surviving G1 and G2 rats, whose LVEF was less than 40% and the rats SHAM group were compared and statistically analysed using a computerized statistical software programme (Prism version 5.0 for Windows, GraphPad Software Inc., CA, USA).

Table 2. Comparison of the duration of the anesthetic-surgical procedure and the percentage of rats with ejection fraction of the left ventricle (LVEF) less than 40% between G1, G2 and SHAM groups. Number of Operated Rats G1: n=35 G2: n=40 SHAM: n=14

Duration in minutes of the Number of surviving anaesthesia and surgery rats 24 hours (mean ± standard deviation) after surgery 14.6±0.1a 16 5.5±0.2b 20 14

Mortality Rate (%) 54.3a 50.0a 0b

Number (%) of surviving rats whose LVEF <40% 56.3a 30ab 0b

n=sample size; different letters between rows = P<0.05, and is the significance of the difference between the groups

Table 3. Comparison of the means of echocardiographic measurements between the groups SHAM and G2, G1. Variables G1 (n=9) G2 (n=6) SHAM (n=14) P value

LVEF (%) 28,0 ±9,2a 26,5 ±6,1a 61.6 ±7.2b 0,0001

ESV (mL) 0,54 ±0,12a 0,55 ±0,12a 0.23 ± 0.05b 0,0001

EDV (mL) 0,74 ±0,09a 0,74 ±0,13a 0.59 ±0.07b 0,0007

ESA (cm2) 1,12 ±0,35a 1,01 ±0,12a 0.59 ± 0.08b 0,0001

EDA (cm2) 1,23 ±0,1a 1,23 ±0,11a 1.0 ±0.08b 0,0022

HR (bpm) 258,4 ±41,6a 255,2 ±40,2a 227,3 ± 34,8a >0,05

LVEF=ejection fraction of the left ventricle; ESV=end systolic volume; EDV=end diastolic volume; ESA=end systolic area; EDA=end diastolic area; HR=heart rates; bpm=beats per minute. Different letters between rows: significant difference (P<0.05)

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The propensity for complications during surgery, namely pulmonary atelectasis and haemorrhage, was higher in the G2 rats than in the G1 rats. In contrast, the propensity for post-operative complications, namely respiratory depression, heart failure, and pulmonary oedema, was higher in the G1 rats than in the G2. The main causes of death in the G1 and G2 rats were cardiac dilation, heart failure, and pulmonary oedema. Nine of the 16 surviving G1 rats (56.3%) and six of the 20 surviving G2 rats (30%) had a LVEF of less than 40%. The proportion of rats with a LVEF of less than 40% in the groups G1 and G2 was not significantly different from each other (P=0.176). The proportion of rats with LVEF less than 40% was significantly higher in G1 compared to SHAM group (P=0.014), but there

was no difference in this rate between the G2 and SHAM group (P=0.0743), (Table 2). Overall, 25.7% of all G1 rats and 15% of all G2 rats had a LVEF of less than 40%. Table 3 shows the comparison of the means of echocardiographic measurements between the groups SHAM and G2, G1. The mean values of each echocardiographic measurement in the nine G1 rats were not significantly different from those in the six G2 rats. Histopathological analysis of hearts from the ten SHAM rats revealed preserved cardiac muscle tissue (Figure 3). Histological analysis of hearts from both the G1 and G2 rats revealed the presence of an organized transmural infarct with fibrosis and intense collagen deposits in the free wall of the left ventricle (Figure 3).

Fig. 3 - Panoramic photomicrographs of the cross-sections of the heart from a SHAM rat (A), a G1 rat (B), and a G2 rat (C). *In the G1 and G2 rats, a transmural infarct is observed on the free wall of the left ventricle.Â Haematoxylin and eosin staining of cardiac tissue from a SHAM rat (A1) in which no myocardial infarct was observed, the myocardium is preserved and no histological alterations in cardiac microarchitecture were found. Haematoxylin and eosin staining of cardiac tissue in a G1 rat (B1) and a G2 rat (C1) shows an organized area of cicatricial collagen (Coll) in the transmural infarct of remanescent muscle fibres (F). Masson trichrome staining of cardiac tissue from a SHAM rat (A2), a G1 rat (B2), and a G2 rat (C2) in which the muscle fibres are stained red and the collagen is stained blue

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DISCUSSION

in a decrease in LVEF with an increase in end systolic and end diastolic volume of the left ventricle. This process results in ventricular dilatation and an increase in diastolic tension[10,12]. We found no significant differences in the echocardiographic measurements of the G1 and G2 rats whose LVEF were less than 40%. However, when comparing the two surgical techniques for creating the AMI, the technique that was used in the G2 rats is more advantageous than that used in the G1 rats in terms of (a) the duration of the surgical procedure, (b) the need for specific rodent equipment or instrumentation, (c) the healing process, as measured by the low incidence of suture breakdown, and the reduced time of the complete closure of the surgical wound and removal of the sutures, and (d) the extent of acoustic shadowing in the echocardiographic evaluation. Nonetheless, the surgical technique that was used for creating the AMI in the G1 rats does have some advantages over that used for creating the AMI in the G2 rats. Firstly, the rate of operative complications, such as the frequency of pulmonary atelectasis and haemorrhage, is lower. Secondly, the use of a flexible cotton-tipped rod enables easier removal of the pericardium. Thirdly, the risk of cardiac rupture is lower because the heart is not exteriorized as in the G1. Finally, the duration of the open thorax is longer, which reduces the time pressure on the surgeon. Our study has several limitations. The techniques showed are the most practiced, but the low rate of severely infarcted rats remains a limitation of this experimental model. Due to this limitation, the power of the statistical test used to analyze the proportion of LVEF less than 40% between the groups was low (0.35). To increase the power of the test, we would have a greater number of samples in each group, making the statistical results of this analysis more reliable, but for ethical reasons this was not done. A second limitation of our study was the necessity of sedate the rats with ketamine and xylazine for echocardiographic examination. This sedative mixture not only affects the HR, but also decreases cardiac contractility[15]. Although the doses of ketamine and xylazine were identical for all rats, we used minimal doses in order to immobilize the rats for the examination. Echocardiographic measurements were also performed in the fourteen SHAM rats, which were also sedated by the identical doses of ketamine and xylazine. We found that the values of these measurements were higher than those in the rats with an AMI. Accordingly, we concluded that the changes in the echocardiographic measurements that were found in the rats with an AMI are due to the presence of the AMI and not to the sedatives.

The mortality rate in the G1 and G2 during the first 24 hours following surgery in this study was between 50-55%, and this rate is similar to that reported (40-65%) in other studies[3,9]. Zomoff et al.[10] reported that the cardiac remodelling that occurs after AMI is associated with a high prevalence of cardiac rupture, arrhythmias, and the formation of aneurysms. Other investigators have reported that arrhythmias, such as sustained ventricular tachycardia and ventricular fibrillation, are the principal cause of death in rats with an experimentally-induced AMI[9,11]. Although there was no statistical difference between groups, we found that the number of G1 rats with a LVEF of less than 40% was greater than found in the group G2. We attribute this increased to the duration of the surgical procedure that was used to create the AMI. The resultant number of rats with a LVEF of less than 40% is also determined by several intrinsic and extrinsic factors. The intrinsic determinants include the ratâ&#x20AC;&#x2122;s age and lineage, individual variations in the anatomy of the coronary artery, and individual physiological factors. On the age of the rat, spontaneous improvement in systolic function and ventricular volume can occur within 30 days after creation of an AMI in young rats[12]. Hence, adult rats whose ages of the approximately 150 days and have a body weight of approximately 350 grams are preferred for creating the experimental AMI[12]. The extrinsic determinants include the site of the occlusion, which is dependent of the surgeonâ&#x20AC;&#x2122;s experience and skill in occluding the LADCA. If the LADCA is occluded close to its origin, the size of the infarct will be large and the mortality rate can be as high as 100%[13]. Kissin et al.[14] has also reported that the prolonged duration (three hours) of halothane-induced anaesthesia can influence the onset of postoperative deleterious effects and could cause postoperative death in rats with an experimentally-induced AMI. Specifically, they showed that increasing the duration of halothane anaesthesia after creation of the AMI causes prolonged hypotension and increases the size of the myocardial infarction. Then, it is possible that, beyond the surgery, the duration of halothane-induced anaesthesia accounted for the higher propensity for a severe left ventricular dysfunction in the G1 rats than in the G2 rats. However, in a mild form, as in this study the difference in anaesthesia time between groups was only nine minutes. In our study, histopathological examination of the hearts of all rats with a LVEF of less than 40% revealed that these hearts had histopathological characteristics that were similar to those that have been reported by others[3,4]. Specifically, we found that the infarcted hearts were dilated, and this dilation was associated with a reduced thickness of the free wall of the left ventricle with intense collagen deposits. According to Fishbein et al.[4], these cardiac alterations in the G1 and G2 rats probably occur about 21 days after creation of the experimental AMI. Consequently, cardiac muscle tissue loss results

CONCLUSION Both surgical techniques can be used to create an AMI in order to generate rats with a LVEF of less than 40%. However, our results indicate a tendency of the technique used G1 to

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be better than G2. This improvement is probably due to the greater duration of the open thorax, which reduces the time pressure on the surgeon, allowing a LADCA occlusion with greater accuracy.

6. Louzada RA, Oliveira PF, Cavalcanti-de-Albuquerque JP, Cunha-Carvalho L, Baldanza MR, Kasai-Brunswick TH, et al. Granulocyte-colony stimulating factor treatment of chronic myocardial infarction. Cardiovasc Drugs Ther. 2010;24(2):121-30. 7. Yu Y, Zhan ZH, Wei SG, Chu Y, Weiss RM, Heistad DD, et al. Central gene transfer of interleukin-10 reduces hypothalamic inflammation and evidence of heart failure in rats after myocardial infarction. Circ Res. 2007;101(3):304-12.

Authorsâ&#x20AC;&#x2122; roles & responsibilities LGAC FB GSO NIM PHS CLKR CTP ACS PRB

Study design, anesthetic and surgical procedures, handling and care of animals, interpretation of results and writing Histopathological analysis, handling and care of animals, interpretation of results Anesthetic and surgical procedures and interpretation of results Echocardiographic examination Preparation of images and discussion Histopathological analysis and interpretation of results Statistical analysis Study design, revision of the manuscript and final approval Orientation for study design and final approval

8. Schiller NB, Foster E. Analysis of left ventricular systolic function. Heart. 1996;75(6 Suppl 2):17-26. 9. Opitz CF, Mitchell GF, Pfeffer MA, Pfeffer JM. Arrhythmias and death after coronary artery occlusion in the rat. Continuous telemetric ECG monitoring in conscious, untethered rats. Circulation. 1995;92(2):253-61. 10. Zornoff LA, Paiva SA, Duarte DR, Spadaro J. Ventricular remodeling after myocardial infarction: concepts and clinical implications. Arq Bras Cardiol. 2009;92(2):150-64.

REFERENCES

11. Li Y, Kloner RA. Is there a gender difference in infarct size and arrhythmias following experimental coronary occlusion and reperfusion? J Thromb Thrombolysis. 1995;2(3):221-5.

1. Senegaglia AC, Barboza LA, Dallagiovanna B, Aita CA, Hansen P, Rebelatto CL, et al. Are purified or expanded cord bloodderived CD133+ cells better at improving cardiac function? Exp Biol Med (Mywood). 2010;235(1):119-29. 2. Johns TN, Olson BJ. Experimental myocardial infarction. I. A method of coronary occlusion in small animals. Ann Surg. 1954;140(5):675-82.

12. Pabis FC, Miyague NI, Francisco JC, Woitowicz V, Carvalho KA, Faria-Neto JR, et al. Echocardiographic assessment of myocardial infarction evolution in young and adult rats. Arq Bras Cardiol. 2008;91(5):321-6.

3. Zornoff LA, Paiva SA, Minicucci MF, Spadaro J. Experimental myocardium infarction in rats: analysis of the model. Arq Bras Cardiol. 2009;93(4):434-40.

13. Pfeffer MA, Pfeffer JM, Fishbein MC, Fletcher PJ, Spadaro J, Kloner RA, et al. Myocardial infarct size and ventricular function in rats. Circ Res. 1979;44(4):503-12.

4. Fishbein MC, Maclean MB, Maroko PR. Experimental myocardial infarction in the rat: qualitative and quantitative changes during pathologic evolution. Am J Pathol. 1978;90(1):57-70.

14. Kissin I, Stanbridge R, Bishop SP, Reves JG. Effect of halothane on myocardial infarct size in rats. Can Anaesth Soc J. 1981;28(3):239-43.

5. Pimentel EB, de Moraes AC, Forechi L, Machado RC, Baldo MP, Mill JG. Kinetics of the electrocardiographic changes after permanent coronary occlusion in rats: Relationship with infarct size. Pathophysiology. 2012;19(4):277-81.

15. Stein AB, Tiwari S, Thomas P, Hunt G, Levent C, Stoddard MF, et al. Effects of anesthesia on echocardiographic assessment of left ventricular structure and function in rats. Basic Res Cardiol. 2007;102(1):28-41.

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Santos CA, etORIGINAL al. - Risk factors for mortality of patients undergoing coronary ARTICLE artery bypass graft surgery

Risk factors for mortality of patients undergoing coronary artery bypass graft surgery Fatores de risco para mortalidade de pacientes submetidos à revascularização miocárdica

Carlos Alberto dos Santos1, MD, PhD; Marcos Aurélio Barboza de Oliveira1, MD, MsC; Antônio Carlos Brandi1, MD; Paulo Henrique Husseini Botelho1, MD; Josélia de Cássia Menin Brandi1, MD; Marcio Antônio dos Santos1, MD; Moacir Fernandes de Godoy1, MD, PhD; Domingo Marcolino Braile1, MD, PhD

DOI10.5935/1678-9741.20140073

RBCCV 44205-1583

Abstract Introduction: Coronary artery bypass grafting is a safe procedure performed worldwide with low rates of mortality and morbidity in general population. Objective: To investigate risk factors for mortality of patients undergoing coronary artery bypass grafting coronary artery bypass grafting surgery. Methods: A total of 1,628 consecutive patients undergoing on-pump coronary artery bypass grafting were retrospectively studied from December 1999 to February 2012. Data analysis involved paired Student t test, Mann-Whitney test and Fisher’s exact test for the categorical data. Logistic regression, Odds Ratio and 95%CI were used for definition of risk factors for mortality. Results: Of a total of 1,628 patients undergoing on-pump coronary artery bypass grafting, 141 (8.7%) died. The following risk factors for mortality were identified after logistic regression: dialysis (OR=7.61; 95%CI 3.58-16.20), neurologic dysfunction type I (OR=4.42; 95%CI 2.48-7.81), use of IABP (OR=3.38; 95%CI 1.98-5.79), cardiopulmonary bypass time (OR=3.09; 95%CI 2.04-4.68), serum creatinine on admission and peak values > 0.4mg/dL (OR=2.67; 95%CI 1.79-4.00), age > 65 years (OR=2.31; 95%CI 1.55-3.44), and time between

hospital admission and and surgical procedure (OR=1.53; 95%CI 1.03-2.27). Conclusion: Dialysis, type I neurologic dysfunction, use of IABP, cardiopulmonary bypass time (>115 minutes), serum creatinine on admission and peak values>0.4mg/dL, age > 65 years and time between hospital admission and surgical procedure were considered as risk factors for mortality in patients undergoing on-pump coronary artery bypass grafting surgery.

Faculdade de Medicina de São José do Rio Preto (FAMERP), São José do Rio Preto, SP, Brazil.

Correspondence address: Carlos Alberto dos Santos Faculdade de Medicina de São José do Rio Preto Av. Brigadeiro Faria Lima, 5416 - Vila São Pedro - São José do Rio Preto, SP, Brasil – Zip Code: 15090-000 E-mail: carlosburi@terra.com.br

Descriptors: Risk Factors. Myocardial Revascularization. Mortality. Resumo Introdução: Cirurgia de revascularização do miocárdio é um procedimento seguro realizado em todo o mundo com taxas baixas de mortalidade e morbidade na população geral. Objetivo: Estudar fatores de risco para mortalidade de pacientes submetidos à revascularização miocárdica com circulação extracorpórea. Métodos: Foram estudados retrospectivamente e de forma consecutiva 1.628 pacientes submetidos à revascularização com circulação extracorpórea no período de dezembro de 1999 a fevereiro

This study was carried out at Hospital de Base of the Faculdade de Medicina de São José do Rio Preto (FAMERP), São José do Rio Preto, SP, Brazil.

Article received on February 14th, 2014 Article accepted on May 25th, 2014

There was no financial support.

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Resultados: Do total de 1.628 pacientes submetidos à cirurgia de revascularização do miocárdio com circulação extracorpórea, 141 (8,7%) foram a óbito. Após regressão logística, foram identificados como fatores de risco para mortalidade as variáveis diálise (OR=7,61; IC 95% 3,58-16,20), lesão neurológica tipo I (OR = 4,42; IC 95% 2,48-7,81), uso de BIA (OR=3,38; IC 95% 1,98-5,79), tempo de CEC (OR = 3,09; IC 95% 2,04-4,68), creatinina pico - admissão > 0,4 mg/dL (OR=2,67; IC 95% 1,794,00), idade > 65 anos (OR=2,31; IC 95% 1,55-3,44) e tempo entre admissão hospitalar e procedimento cirúrgico (OR = 1,53; IC 95% 1,03-2,27). Conclusão: Diálise, lesão neurológica tipo I, uso de balão intra-aórtico, tempo de circulação extracorpórea (> 115 minutos), creatinina pico-admissão > 0,4 mg/dL, idade > 65 anos e tempo entre admissão hospitalar e procedimento cirúrgico foram considerados como fatores de risco para mortalidade em pacientes submetidos à cirurgia de revascularização do miocárdio com circulação extracorpórea.

Abbreviations, acronyms and symbols AF AKIN BMI CABG CAD CI CPB FAMERP HB IAB ICU OR P ROC SIRS STS SUS

Atrial fibrillation Acute Kidney Injury Network Body mass index Coronary Artery Bypass Grafting Coronary artery disease Confidence interval Cardiopulmonary bypass Faculdade de Medicina de São José do Rio Preto Hospital de Base Intra-aortic balloon Intensive Care Unit Odds Ratio significance level Receiver Operating Characteristics Systemic inflammatory response syndrome Society of Thoracic Surgeons Unified Health System

de 2012. A análise de dados foi efetuada por meio dos testes t de Student não pareado, Mann-Whitney e exato de Fisher para dados categóricos. Regressão logística, Odds Ratio e IC95% foram utilizados para definição de fatores de risco para mortalidade.

Descritores: Fatores de Risco. Revascularização Miocárdica. Mortalidade.

INTRODUCTION

The CABG is the most practiced cardiac surgery in our country, most of which performed by Unified Health System (SUS) both in public hospitals as in philanthropic or private [10]. In the period 2005 to 2007 63,272 CABG were performed in Brazil, with a mortality rate of 6.2%[10] higher than in countries like the United States (2.9%)[11] and Canada (1.7%) [12], probably due to the high prevalence of cardiovascular risk factors among Brazilian who underwent CABG[13]. Currently, there is a higher prevalence of poor cardiac conditions and associated comorbidities[14]. The CABG mortality rate may have variation depending on several factors related to pre-, peri- and postoperative. Postoperative variables as length of stay in intensive care unit, atrial fibrillation, acute kidney injury, neurological damage type I and dialysis are related to increased postoperative mortality[14-17]. Considering the importance of CABG in the correction of myocardial ischemia consequent to the obstruction of the coronary arteries, seeking for the relief of symptoms, improved quality of life, patient return to work, as well as increased life expectancy, we can justify this research, because long-term studies on preoperative, intraoperative and postoperative that

Cardiovascular diseases are the leading causes of death in the population, including cerebrovascular, cardiac ischemic, hypertensive diseases, atherosclerosis, rheumatic fever and other heart diseases. According to the World Health Organization data in 2008 there were 17.3 million deaths worldwide[1], and 7.3 million were due to coronary artery disease (CAD)[2]. In Brazil, in 2009 totaled 209,029 admissions for CHD patients, occurring 12,619 deaths with a mortality rate of 6.04%[3]. The treatment of CAD may be clinical/medical or surgical. Despite advances in medical therapy and PCI, coronary artery bypass grafting (CABG) is a safe procedure performed worldwide with low rates of mortality and morbidity in the general population[4] and it is still excellent option for treatment of obstructive CAD[5], even in diabetic patients[6], the elderly[7] and in patients with low left ventricular ejection fraction[8]. In addition, the CABG can control the persistent ischemia and progression to acute myocardial infarction, in addition to provide symptomatic relief and prevent ischemic complications[9].

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can influence the mortality of patients undergoing CABG with CPB are scarce. Furthermore, it is important to note that all cardiac surgeries were performed by the same team and in a university hospital, with medical residency program in cardiovascular surgery. The aim of this research was to study risk factors for mortality in the postoperative period in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass (CPB), considering preoperative, intraoperative and postoperative variables and its influence on mortality.

Table 1. Descriptive statistics for pre-, intra- and postoperative variables in patients undergoing CABG from December/1999 to February/2012 (n=1.628). Variable mean sd median min max age (years) 60.7 9.4 61 25 91 BMI (Kg/m2) 27 4.2 26.6 15.3 49.3 time of surgery-admission 6.2 5.8 4 0 38 (d) 4.1 5.2 2 0 30 Ucor stay up to 30 days (d) Creatinine peak - Intake 0.4 0.7 0.1 -0.2 7.5 (mg/dL) Total of grafts 2.7 0.7 3 1 5 CPB time (min) 94.4 25.5 92 24 218

METHODS 1,674 patients undergoing cardiac surgery for coronary artery bypass grafting with cardiopulmonary bypass (CPB) were retrospectively and consecutively studied, regardless of gender and race at Hospital de Base (HB), São José do Rio Preto, from December/1999 to February/2012. This study was approved by the Research Ethics Committee under opinion 454,518 of 11/12/2013. Of these, 46 (2.7%) were excluded because of failure in the information record in their forms. Patient data were reviewed prospectively by collecting in computerized system. Were considered as exclusion criteria patients undergoing OPCAB or associated with other cardiac surgery (valvular, ventricular aneurysms, acquired ventricular septal defects, congenital heart diseases) or vascular, in addition to CABG and who died during the intraoperative period. Data from each patient were obtained in perfusion records of Cardiac Surgery Service of Hospital de Base, including demographic or non-cardiac variables such as gender, age and body mass index (BMI), whereas cardiac variables included time between hospital admission and surgery, use of intraaortic balloon (IAB), cardiopulmonary bypass (CPB) time, total number of grafts, acute atrial fibrillation, respiratory infections, creatinine peak-admission (mg/dL), dialysis, deep surgical site infection (mediastinitis), neurological damage type I, length of stay in the coronary unit up to 30 days and 30-day mortality. Were defined as postoperative variables: Creatinine peak-admission (mg/dL): change in serum creatinine defined as the difference between admission creatinine in the Intensive Care Unit (ICU) and the highest value obtained during the stay on this unit. Cardiac arrhythmias: acute atrial fibrillation lasting longer than 1 hour. Pulmonary complications: tracheal reintubation due to respiratory failure due to mechanical changes of the ventilation or respiratory infection. Mediastinitis: mediastinal secretion associated with clinical signs (fever, chest pain) and laboratory (leukocytosis) of infection with or without sternal instability and with secretions culture and positive blood culture. Type I neurological

Table 2. Percentage distribution of pre- and postoperative variables in patients undergoing CABG from December/1999 to February/2012 (n=1.628). Variables N (%) N (%) M F Gender 1125 (69.1) 503 (30.9) Presence Absence IAB 114 (7) 1514 (93) Acute FA 141 (8.7) 1487 (91.3) PC 227 (14.4) 1351 (85.6) Dialysis 40 (2.5) 1588 (97.5) mediastinitis 25 (1.5) 1603 (98.5) neurological lesions I 71 (4.4) 1557 (95.6) N=number of subjects; M=male; F=female; PC=pulmonary complications; IAB=intra-aortic balloon; AF=atrial fibrillation

lesion: new and persistent deficit focal motor, coma, seizures or brain damage. Deaths: mortality from all causes within 30 days. Statistical Analysis The data were submitted to normality KolmogorovSmirnov test and, subsequently, the parametric analysis by the Student t test or unpaired nonparametric Mann-Whitney test and Fisher’s exact test for categorical data. Numerical variables were submitted to the ROC curve for definition of the cutoff point of each in relation to death in the postoperative period. Logistic regression, odds ratio (OR) and 95% CI were used to define risk factors for mortality in the postoperative period. For other tests, P<0.05 was considered significant. We used the program of statistical calculations GraphPad InStat version 3.00 (GraphPad Software, San Diego, California, United States).

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RESULTS

Table 3. Descriptive statistics for pre-, intra- and postoperative variables in patients undergoing CABG who died from December/1999 to February/2012 (n=141). Variables Mean sd Median Min Max age (years) 65.89 8.96 66 35 91 BMI (Kg/m2) 26.46 4.89 26.22 15.27 40.35 time of surgery-admission (d) 7.28 6.59 6 0 38 Ucor stay up to 30 days (d) 6.09 7.15 2 0 29 Creatinine peak -Intake (mg/dL) 1.07 1.28 0.6 0 6.3 Total of grafts 2.80 0.74 3 1 4 CPB time (min) 108.58 33.01 101 24 191 sd=standard deviation; min=minimum value; max=maximum value; BMI=body mass index; d=day; Ucor=coronary unit; CPB=cardiopulmonary bypass

The results for the preoperative, intraoperative and postoperative variables found in patients undergoing onpump CABG (n=1,628) are in Tables 1 and 2. The most common included males (69.1%), pulmonary complications (14.4%), acute atrial fibrillation (8.7%) and use of intra-aortic balloon (7%). Analytical Variables in Patients who died Of the 1,628 patients undergoing CABG with CPB, 141 (8.7%) died. The results for the preoperative, intraoperative and postoperative found in these patients are shown in Tables 3 and 4. The main were male (67%), pulmonary complications (40%), use of intra-aortic balloon (21%) and neurological damage type I (19%). Variables influencing the mortality The results of the ROC curve for age, time between hospital admission and surgery, creatinine peak-admission and CPB time are shown in Figure 1. Age (years) showed cutoff value of 65.128, sensitivity 54%, specificity 69%, and area under the curve of 0.670 (95% CI 0.620 to 0.721). With respect to the time between hospital admission and surgery (days) the cutoff value was 5.016, sensitivity 54%, specificity of 59% and area under the curve of 0.558 (95% CI 0.506 to 0.609). The change in creatinine peak-admission (mg/dL) showed cutoff of 0.400, sensitivity 57%, specificity 82%, and area under the curve of 0.682 (95% CI 0.631 to 0.732). The CPB time (min) showed cutoff value of 115.18, sensitivity 38%, specificity of 84% and area under the curve of 0.640 (95% CI 0.589 to 0.691). Analyzing risk factors for mortality in patients undergoing CABG with CPB (Table 5), it was observed that the relative risk of patients who used BIA go to death is 238% higher than those who did not need that type of device for ventricular assistance (OR=3.38, 95% CI 1.98 to 5.79; P<0.0001). Regarding the need for dialysis, the relative risk of death in patients in need of such treatment in the postoperative period is 661% higher than those not undergoing dialysis (OR=7.61, 95% CI 3.58 to 16.20; P<0.0001). In patients with neurological injury type I, the relative possibility of death is 342% higher than those without such lesions (OR=4.42, 95% CI 2.48 to 7.81; P<0.0001). Considering the age of the patients, the relative chance of subjects > 65 years to die is 131% higher than those <65 years (OR=2.31, 95% CI 1.55 to 3.44; P<0.0001). The analysis of time between hospital admission and surgery showed that the relative risk of death is 53% higher than when this time was > 5 days (OR=1.53, 95% CI 1.03 to 2.27; P=0.0352).

Table 4. Percentage distribution of pre- and postoperative variables in patients undergoing CABG who died from December/1999 to February/2012 (n=141). Variables N (%) N (%) M F Gender 95 (67) 46 (33) Presense Absence IAB 30 (21) 111 (79) Acute AF 23 (16) 118 (84) PC 56 (40) 85 (60) Dialysis 23 (16) 118 (84) mediastinitis 6 (4) 135 (96) Neurological lesions I 27 (19) 114 (81) N=number of individuals; M=male; F=female; IAB=intra-aortic balloon; AF=atrial fibrillation; CP=pulmonary complications

Table 5. Results of the logistic regression risk factors for mortality in patients undergoing CABG from December/1999 to February/2012 (n=1.628). Risk factors OR CI 95% P IAB 3.38 1.98-5.79 <0.0001* Dialysis 7.61 3.58-16.20 <0.0001* Neurological lesions I 4.42 2.48-7.81 <0.0001* Diabetes 1.38 0.92-2.08 0.1168 age > 65 years 2.31 1.55-3.44 <0.0001* BMI > 23,4 Kg/m2 0.67 0.43-1.05 0.0807 time of surgery-admission 1.53 1.03-2.27 0.0352* > 5 days Creatinine peak - Intake > 2.67 1.79-4.00 <0.0001* 0.4 mg/dL CPB time >115 min 3.09 2.04-4.68 <0.0001* OR=odds ratio; CI=confidence interval; N=number of individuals; M=male; F=female; IAB=intra-aortic balloon; AF=atrial fibrillation; BMI=body mass index; UCor=Coronary Unit; CPB = cardiopulmonary bypass; *statistically significant

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Fig. 1 - ROC curves (receiver operating characteristics) of age, time between hospital admission and surgery, cardiopulmonary bypass time and creatinine peak-admission for death up to 30 days.

Regarding change in serum creatinine (peak-admission), the relative risk of death is 167% higher when this variation is â&#x2030;Ľ0.4 mg/dL (OR=2.67, 95% CI 1.79 to 4.00; P<0.001). As for the CPB time, the relative risk of death is 209% higher when it is above 115 minutes (OR=3.09, 95% CI 2.04 to 4.68; P<0.001).

(OR=2.67), age> 65 years (OR=2.31) and time between hospital admission and surgery (OR=1.53). In this research, the mortality rate was 8.7%, close to that recorded by DATASUS for CABG, or that is, 7%[18]. In the period 2005-2007, Piegas et al.[10] analyzed 63,272 CABG surgeries performed in 191 hospitals and found that the mortality rate was 6.2%. Cadore et al.[14], investigating 2,809 patients undergoing CABG alone or combined with valve replacement reported that the mortality rate was 10%. It is noteworthy that the performance of combined surgery increases the risk of mortality. These mortality rates are higher than in countries like the United States (2.9%)[11] and Canada (1.7%)[12], possibly due to the high prevalence of cardiovascular risk factors among Brazilian who underwent CABG[13]. On the other hand, the comparison of surgical results in national centers for European and North American centers is inadequate, because both the registration of the Society of Thoracic Surgeons (STS)

DISCUSSION This study identified seven risk factors for mortality in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass. In patients who died, the most common variables included male, pulmonary complications, use of intra-aortic balloon and type I neurological lesion. After logistic regression, risk factors for mortality were as follows: dialysis (OR=7.61 ), neurological damage type I (OR=4.42), use of intra-aortic balloon (OR=3.38), cardiopulmonary bypass time (OR=3.09), creatinine peak - Intake> 0.4 mg/dL

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as the UK Cardiac Surgical Register are volunteers, while DATASUS is administrative. In this study, the peak-admission creatinine ≥ 0.4 mg/ dL was considered a risk factor for death. This finding was similar to that found by Machado et al.[15] who studied 817 patients with acute kidney injury (AKI), and found that the creatinine peak-admission ≥0.3 mg/dl was an independent predictor of death in 30 days after on-pump CABG. However, these authors used the criterion proposed by Acute Kidney Injury Network (AKIN) classification, or that is, percentage increase (≥ 50%) or absolute (≥ 0.3 mg/dL) of serum creatinine characterizes AKI. In this research, the value of creatinine peak-admission ≥ 0.4 mg/dL was considered as the cutoff point for death by the ROC curve. The assessment of renal function by serum creatinine in patients undergoing CABG with CPB is essential because even a subclinical increase is considered independent predictor of death within 30 days after CABG in patients with normal renal function or preoperative renal injury[19]. In addition, AKI after CABG is common complication that increases the length of hospital stay and ICU and is associated with high morbidity and mortality rates[16,20] with prognostic importance. Of the 1,628 patients undergoing CABG with CPB, 40 (2.5%) required dialysis postoperatively. The need for dialysis is observed in up to 30.6% of cases[16,20,21]. Yehia et al.[21], assessing 104 patients undergoing CABG, found that 41.3% of them developed AKI after surgery, requiring dialysis in up to 9.6%, mainly in those with preoperative renal injury. Santos et al.[16] found that of 223 patients undergoing CABG with CPB, dialysis was required in 4.9% of them. In this series, of 40 patients requiring dialysis postoperatively, 23 (57.5%) died, close to the mortality rate recorded by Santos et al.[16] and Chertow et al.[20] 63 6% (n=223) and 63.7% (n=460), respectively. Despite this proximity, the comparison between the studies is complex because it is related to the number and characteristics of hospitals involved in each study, patient profiles and sample size. The relative risk of death in patients requiring dialysis postoperatively was significantly higher (OR=7.61, 95% CI 3.58 to 16.20; P<0.0001). This finding is consistent with the literature. According Chertow et al.[20] the need for dialysis increases by 7.9 times the odds ratio of death among these patients. When there is severe renal injury enough to require dialysis, a sharp increase in mortality occurs[20]. Therefore, the identification of preoperative risk factors for AKI may contribute to the use of preventive strategies to minimize risk and improve treatment of this injury. In this series, age> 65 years was considered a risk factor for mortality. This finding was similar to that found by Rocha et al.[22] in patients aged ≥ 70 years. Naughton et al.[23] studied 3,683 patients undergoing CABG and found that age ≥ 75 years was an independent risk factor for mortality within 30

days. However, Aikawa et al.[4] investigating the impact of CABG on 253 elderly patients, found that age ≥ 65 years was not associated with death variable. Considering the increased prevalence of CAD with age[24], it is possible that an increasing number of elderly patients are candidates to CABG in the coming years. Therefore, a careful assessment of cardiac and non-cardiac variables during pre-, intra- and post-operative patients over 65 years is necessary because age can be associated with other severe comorbidities such as renal and neurological injuries in the postoperative period. In this study, the CPB time was identified as a risk factor for mortality. The average time in patients undergoing CABG was 94.4 min. In the literature, this time varies from 65.8 to 120 min[13,16,24]. In patients who died, the mean CPB time was higher (118.58 min), confirming the findings of Oliveira et al.[13]. The relative risk of death is 209% higher when the CPB time is higher than 115 minutes (OR=3.09, 95% CI 2.04 to 4.68; P <0.001). A major concern related to cardiopulmonary bypass is systemic inflammatory response syndrome (SIRS), characterized by clinical changes in ventricular function, lung and kidney, coagulation disorders, susceptibility to infections, abnormal vascular permeability and fluid accumulation in the interstitium, leukocytosis, vasoconstriction and hemolysis[25]. It is noteworthy that despite these changes, the body’s ability to reverse this situation, and the use of corticosteroids, an effective alternative in reducing the systemic effects caused by the release of cytokines during and after CPB[26], can reduce morbidity and mortality rate. On the other hand, the CPB substitutes the cardiopulmonary functions, seeks to maintain cell integrity, structure, function and metabolism of organs and individual systems, enabling more complex and longer surgeries[27] such as coronary artery bypass grafting. In this study, the patients studied (n=1,628) 4.4% had neurological damage type I. This finding was consistent with the two largest series in the literature that assessed more than 16,000 patients undergoing CABG with incidences of 2 to 4.6%[28,29]. In our country, Guaragna et al.[17] assessing 1,760 patients undergoing CABG with CPB found this lesion in 3% of them. Among the patients who died (n=141), 19% had neurological injury type I. This result is consistent with previous studies that showed high mortality (13-41%) in patients who have had this injury after CABG[30]. The relative risk of death in patients with type I neurological injury postoperatively was significantly higher (OR=4.42, 95% CI 2.48 to 7.81; P<0.0001). This finding was similar to that observed by Guaragna et al.[17], and the relative risk of death was 4.6 times higher in patients with this injury. Considering the severity of this type of injury in postoperative patients undergoing CABG with CPB, some preventive

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measures can be adopted as an individualized management strategy for patients with previous cerebrovascular disease, including minimal manipulation of the aorta and maintenance of the highest pressure gradient during CPB. Among the 141 patients undergoing CABG with CPB who died, 21% of them used intra-aortic balloon. This rate was consistent with the literature. In a review of 27 years of IAB use by the Massachusetts General Hospital, mortality among patients who received IAB ranged from 13.6 to 35%[31]. According to Christenson et al.[32], the preoperative prophylactic use of IAB has great value to prevent trans- and postoperative complications. In this sample, the relative likelihood of patients who used this type of device for ventricular assistance to die was significantly high. The use of IAB is related to the existence of low left ventricular ejection fraction and or severe coronary lesions, indicating poor heart condition, which can increase morbidity and mortality rate in patients undergoing CABG with CPB. In patients who died, the median time between hospital admission and surgery was 6 days. Oliveira et al.[13] found that mortality was higher among patients with time of preoperative stay less than 3 days. Importantly, the hospital stay before surgery may be related to the clinical severity, suggesting an advanced degree of coronary involvement that may result in increased morbidity and mortality rate in the postoperative period. As limitations of the study we should mention that it is not randomized. In addition, the influence of preoperative, intraoperative and postoperative mortality of patients undergoing CABG with CPB needs more long-term scientific research. The clinical importance of the results obtained herein reinforces the multidisciplinary approach in patients undergoing coronary artery bypass grafting, especially in the postoperative period. The identification of risk factors for mortality is critical, since this knowledge can support interventions aimed at the planning and execution of new preventive strategies, and minimizing the complications associated with this surgery. This information may also be used as an important care quality indicator in the postoperative period, in this case provided by SUS.

Authors' roles & responsibilities CAS

Analysis and / or interpretation of data, final approval of the manuscript, study design, conduct of operations and/or experiments, manuscript writing or critical review of its content MABO Analysis and/or interpretation of data, statistical analysis, manuscript writing or critical review of its content ACB Conduct of operations and/or experiments, manuscript writing or critical review of its content PHHB Conception and design of the study, implementation of operations and/or experiments JCMB Analysis and/or interpretation of data, final approval of the manuscript MAS Final approval of the manuscript, design and study design, manuscript writing or critical review of its content MFG Analysis and/or interpretation of data, statistical analysis, study design DMB Analysis and/or interpretation of data, final approval of the manuscript, manuscript writing or critical review of its content

REFERENCES 1. World Health Organization. Global status report on noncommunicable diseases 2010. Geneva: World Health Organization; 2011. 2. World Health Organization. Global atlas on cardiovascular disease prevention and control. Geneva: World Health Organization; 2011. 3. Brasil. Ministério da Saúde. Datasus. Banco de dados do Sistema Único de Saúde. Brasília: Ministério da Saúde; 2010. Disponível em: http://www.datasus.org.br 4. Aikawa P, Cintra AR, Leite CA, Marques RH, Silva CT, Afonso MS, et al. Impact of coronary artery bypass grafting in elderly patients. Rev Bras Cir Cardiovasc. 2013;28(1):22-8. 5. Dallan LAO, Jatene FB. Revascularização miocárdica no século XXI. Rev Bras Cir Cardiovasc 2013;28:137-44. 6. Stevens LM, Carrier M, Perrault LP, Hébert Y, Cartier R, Bouchard D, et al. Influence of diabetes and bilateral internal thoracic artery grafts on long-term outcome for multivessel coronary artery bypass grafting. Eur J Cardiothorac Surg. 2005;27(2):281-8.

CONCLUSION

7. Kieser TM, Lewin AM, Graham MM, Martin BJ, Galbraith PD, Rabi DM, et al. Outcomes associated with bilateral internal thoracic artery grafting: the importance of age. Ann Thorac Surg. 2011;92(4):1269-75.

In patients undergoing coronary artery bypass grafting with cardiopulmonary bypass who died, the more frequent preoperative, intraoperative and postoperative variable were male, pulmonary complications, use of intra-aortic balloon and neurological damage type I. Dialysis, neurological damage type I, use of intra-aortic balloon, CPB time (> 115 minutes), creatinine peak-admission> 0.4 mg/dL, age> 65 years and time between hospital admission and surgery were identified as risk factors for mortality in the postoperative period.

8. Galbut DL, Kurlansky PA, Traad EA, Dorman MJ, Zucker M, Ebra G. Bilateral internal thoracic artery grafting improves long-term survival in patients with reduced ejection fraction: a propensity-matched study with 30-year follow-up. J Thorac Cardiovasc Surg. 2012;143(4):844-853. 9. Sussenbach CP, Guaragna JC, Castagnino RS, Piccoli J, Albuquerque LC, Goldani MA, et al. Unstable angina does not increase

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mortality in coronary artery bypass graft surgery. Rev Bras Cir Cardiovasc. 2013;28(3):391-400.

21. Yehia M, Collins JF, Beca J. Acute renal failure in patients with pre-existing renal dysfunction following coronary artery bypass grafting. Nephrology (Carlton). 2005;10(6):541-3.

10. Piegas LP, Bittar OJNV, Haddad N. Cirurgia de revascularização miocárdica: resultados do Sistema Único de Saúde. Arq Bras Cardiol. 2009;93(5):555-60.

22. Rocha AS, Pittella FJ, Lorenzo AR, Barzan V, Colafranceschi AS, Brito JO, et al. Age influences outcomes in 70-year or older patients undergoing isolated coronary artery bypass graft surgery. Rev Bras Cir Cardiovasc. 2012;27(1):45-51.

11. Hannan EL, Wu C, Ryan TJ, Bennett E, Culliford AT, Gold JP, et al. Do hospital and surgeons with higher coronary artery bypass graft surgery volumes still have lower risk-adjusted mortality rates? Circulation. 2003;108(7):795-801.

23. Naughton C, Feneck RO, Roxburgh J. Early and late predictors of mortality following on-pump coronary artery bypass graft surgery in the elderly as compared to a younger population. Eur J Cardiothorac Surg. 2009;36(4):621-7.

12. Cartier R, Bouchout O, El-Hamamsy I. Influence of sex and age on long-term survival in systematic off-pump coronary artery bypass surgery. Eur J Cardiothorac Surg. 2008;34(4):826-32.

24. Rodrigues AJ, Evora PRB, Bassetto S, Alves Júnior L, Scorzoni Filho A, Araújo WF, et al. Fatores de risco para lesão renal aguda após cirurgia cardíaca. Rev Bras Cir Cardiovasc. 2009;24(4):441-6.

13. Oliveira EL, Westphal GA, Mastroeni MF. Características clínicodemográficas de pacientes submetidos a cirurgia de revascularização do miocárdio e sua relação com a mortalidade. Rev Bras Cir Cardiovasc. 2012;27(1):52-60.

25. Hall RI, Smith MS, Rocker G. The systemic inflammatory response to cardiopulmonary bypass: pathophysiological, therapeutic, and pharmacological considerations. Anesth Analg. 1997;85(4):766-82.

14. Cadore MP, Guaragna JCVC, Anacker JFA, Albuquerque LC, Bodanese LC, Piccoli JCE, et al. Proposição de um escore de risco cirúrgico em pacientes submetidos à cirurgia de revascularização miocárdica. Rev Bras Cir Cardiovasc. 2010;25(4):447-56.

26. Inaba H, Kochi A, Yorozu S. Suppression by methylprednisolone of augmented plasma endotoxin-like activity and interleukin-6 during cardiopulmonary bypass. Br J Anaesth. 1994;72(3):348-50.

15. Machado MN, Miranda RC, Takakura IT, Palmegiani E, Santos CA, Oliveira MA, et al. Acute kidney injury after on-pump coronary artery bypass graft surgery. Arq Bras Cardiol. 2009;93(3):247-52.

27. Souza MHL, Elias DO. Fundamentos de extracorpórea. Rio de Janeiro: Centro Editorial Alfa Rio; 1995.

16. Santos FO, Silveira MA, Maia RB, Monteiro MD, Martinelli R. Acute renal failure after coronary artery bypass surgery with extracorporeal circulation: incidence, risk factors, and mortality. Arq Bras Cardiol. 2004;83(2):150-4.

28. Stamou SC, Hill PC, Dangas G, Pfister AJ, Boyce SW, Dullum MK, et al. Stroke after coronary artery bypass: incidence, predictors, and clinical outcome. Stroke. 2001;32(7):1508-13. 29. Bucerius J, Gummert JF, Borger MA, Walther T, Doll N, Onnasch JF, et al. Stroke after cardiac surgery: a risk factor analysis of 16,184 consecutive adult patients. Ann Thorac Surg. 2003;75(2):472-8.

17. Guaragna JCVC, Bolsi DC, Jaeger CP, Melchior R, Petracco JB, Facchi LM, et al. Preditores de disfunção neurológica maior após cirurgia de revascularização miocárdica isolada. Rev Bras Cir Cardiovasc. 2006;21(2):173-9. 18. Ribeiro AL, Gagliardi SP, Nogueira JL, Silveira LM, Colosimo EA, Lopes do Nascimento CA. Mortality related to cardiac surgery in Brazil, 2000-2003. J Thorac Cardiovasc Surg. 2006;131(4):907-9.

30. Roach GW, Kanchuger M, Mangano CM, Newman M, Nussmeier N, Wolman R, et al. Adverse cerebral outcomes after coronary bypass surgery. Multicenter Study of Perioperative Ischemia Research Group and the Ischemia Research and Education Foundation Investigators. N Eng J Med. 1996;335(25):1857-63.

19. Tolpin DA, Collard CD, Lee VV, Virani SS, Allison PM, Elayda MA, et al. Subclinical changes in serum creatinine and mortality after coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2012;143(3):682-8.

31. Torchiana DF, Hirsch G, Buckley MJ, Hahn C, Allyn JW, Akins CW, et al. Intraaortic balloon pumping for cardiac support: trends in practice and outcome, 1968-1995. J Thorac Cardiovasc Surg. 1997;113(4):758-64.

20. Chertow GM, Levy EM, Hammermeister KE, Grover F, Daley J. Independent association between acute renal failure and mortality following cardiac surgery. Am J Med. 1998;104(4):343-8.

32. Christenson JT, Simonet F, Schmuziger M. The effect of preoperative intra-aortic balloon pump support in high risk patients requiring myocardial revascularization. J Cardiovasc Surg (Torino). 1997;38(4):397-402.

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Nakamura RK,ORIGINAL et al. - Very short cycles of postconditioning have no protective ARTICLE effect against reperfusion injury. Experimental study in rats

Very short cycles of postconditioning have no protective effect against reperfusion injury. Experimental study in rats Ciclos muito curtos de pós-condicionamento não protegem contra lesão de reperfusão. Estudo experimental em ratos

Ricardo Kenithi Nakamura1, MD; Carlos Henrique Marques dos Santos1, PhD; Luciana Nakao Odashiro Miiji2, PhD; Mariana Sousa Arakaki1, MD; Cristiane Midori Maedo1; Maurício Érnica Filho1; Pedro Carvalho Cassino1; Elenir Rose Jardim Cury Pontes1, PhD

DOI 10.5935/1678-9741.20140088

RBCCV 44205-1584

Abstract Introduction: Ischemic postconditioning has been recognized as effective in the prevention of reperfusion injury in situations of ischemia and reperfusion in various organs and tissues. However, it remains unclear what would be the best way to accomplish it, since studies show great variation in the method of their application. Objective: To assess the protective effect of ischemic postconditioning on ischemia and reperfusion in rats undergoing five alternating cycles of reperfusion and ischemia of 30 seconds each one. Methods: We studied 25 Wistar rats distributed in three groups: group A (10 rats), which underwent mesenteric ischemia (30 minutes) and reperfusion (60 minutes); Group B (10 rats), undergoing ischemia (30 minutes) and reperfusion (60 minutes), intercalated by postconditioning (5 alternating cycles of reperfusion and ischemia of 30 seconds each one); and group C - SHAM (5 rats), undergoing only laparotomy and manipulation of mesenteric artery. All animals underwent resection of an ileum segment for histological analysis. Results: The mean lesions degree according to Chiu et al. were: group A, 2.77, group B, 2.67 and group C, 0.12. There was no difference between groups A and B (P>0.05).

Conclusion: Ischemic postconditioning was not able to minimize or prevent the intestinal tissue injury in rats undergoing ischemia and reperfusion process when used five cycles lasting 30 seconds each one.

Faculdade de Medicina da Universidade Federal de Mato Grosso do Sul, Campo Grande, MS, Brazil.

Correspondence address: Carlos Henrique Marques dos Santos Universidade Federal de Mato Grosso do Sul Rua 15 de novembro, 1859 - Vila Esportiva - Campo Grande, MS, Brazil – Zip code: 79020-300 E-mail: chenriquems@yahoo.com.br

Descriptors: Ischemia. Reperfusion Injury. Ischemic Postconditioning. Mesenteric Vascular Occlusion. Rats. Resumo Introdução: O pós-condicionamento isquêmico tem sido reconhecido como eficaz na prevenção das lesões de reperfusão em situações de isquemia e reperfusão em vários órgãos e tecidos. Entretanto, não está ainda claro qual seria a melhor maneira de realizá-lo, já que as publicações mostram grande variação de método no seu emprego. Objetivo: Avaliar o efeito protetor do pós-condicionamento isquêmico na isquemia e reperfusão intestinal em ratos, através de cinco ciclos alternados de 30 segundos de isquemia e 30 segundos de reperfusão. Métodos: Foram estudados 25 ratos Wistar, distribuídos em três grupos: grupo A (10 ratos), em que se realizou isquemia (30 minutos) e reperfusão (60 minutos) mesentérica; grupo B (10

Pathology Devision, Universidade Federal de São Paulo, São Paulo, SP, Brazil. 2

This study was carried out at Faculdade de Medicina da Universidade Federal de Mato Grosso do Sul (Famed-UFMS), Campo Grande, MS, Brazil.

Article received on March 14th, 2014 Article accepted on July 1st, 2014

No financial support.

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Resultados: As médias dos graus de lesão tecidual segundo a classificação de Chiu et al. foram: no grupo A, 2,77; no grupo B, 2,67; e no grupo C, 0,12. A diferença entre o resultado do grupo A com o resultado do grupo B não teve significância estatística (P>0,05). Conclusão: O pós-condicionamento isquêmico não foi capaz de minimizar ou prevenir a lesão tecidual intestinal de ratos submetidos ao processo de isquemia e reperfusão mesentérica quando utilizados cinco ciclos com duração de 30 segundos cada.

Abbreviations, acronyms & symbols IPo IPr ROS

Ischemic postconditioning Ischemic preconditioning Reactive oxygen species

ratos), isquemia e reperfusão, seguidos de pós-condicionamento isquêmico com 5 ciclos alternados de reperfusão e reoclusão, de 30 segundos cada; e grupo C (5 ratos), controle (SHAM). Ao final, ressecou-se um segmento do intestino delgado para análise histológica. Avaliaram-se os resultados pela classificação de Chiu et al. e procedeu-se ao tratamento estatístico.

Descritores: Pós-Condicionamento Isquêmico. Isquemia. Reperfusão. Oclusão Vascular Mesentérica. Ratos.

Some intestinal surgeries, especially resection and transplantation are usually held by temporary occlusion of mesenteric vessels to prevent bleeding. This knowledge has led many researchers to develop a method to minimize the damage caused by reperfusion. In 2003, Zhao et al.[2] presented the concept of ischemic postconditioning (IPo), which consists in performing one or more short cycles of reperfusion followed by one or more short cycles of ischemia, immediately after the ischemic phase and before establishment of permanent reperfusion. In an experimental model, there is already evidence of a protective effect of IPo on the intestinal mucosa of rats undergoing mesenteric ischemia and reperfusion[5]. And recently, IPo was able to minimize the severity of liver injury in rats undergoing ischemia and reperfusion through 3 cycles of ischemia and reperfusion of two minutes[6]. Several published experiments analyzed the effects of IPo in other organs and tissues, among them we can mention Darling et al.[7] in which the IPo was able to minimize the area of myocardial infarction in rabbits; Tang et al.[8] demonstrated the effectiveness of IPo in the prevention of coronary lesions resulting from the ischemia and reperfusion in rats, since the ischemia time did not exceed 45 minutes; Huang et al.[3] have shown that the IPo was preventing tissue damage in the spinal cord of rats subjected to ischemia and reperfusion; Santos et al.[9] showed that the ICRP and IPo was able to minimize tissue injury in the intestinal mucosa of rats undergoing ischemia and reperfusion process. However, Bretz et al.[10] in 2010, published a study in rabbits, showing that postconditioning performed with four cycles of 30 seconds reperfusion and 30 seconds of reocclusion during the initial four minutes of reperfusion, showed no statistical significance on degree of necrosis of the intestinal mucosa.

INTRODUCTION Since 1986, when Parks & Granger[1] demonstrated the harmful effects of toxic reactive oxygen species (ROS) produced during reperfusion, much research has been developed in search of an experimental model that could minimize this process in order to reduce cell and organ ischemia and reperfusion damage[2,3]. With the acquired knowledge on the pathophysiology of this process seems to be the way to complement reperfusion techniques already developed, such as ischemic preconditioning (IPr) - consisting of short and repeated episodes of ischemia before the ischemic event itself, and ischemic postconditioning (IPo) - consisting of short and repeated episodes of reperfusion, post-ischemia established, and prior to reperfusion period. But unfortunately they did not alter significantly the mortality of mesenteric ischemia. The process of ischemia has been studied for many years and the knowledge on pathophysiology still faces some dilemmas. It is known that in any situation of ischemia, reperfusion also occurs, which is an important factor in the deterioration of the clinical picture, leading to local and systemic damage due to predisposition to the formation of oxygen free radicals and other substances responsible for the direct tissue damage, proven by Parks & Granger[1]. Probably, the best results previously published in controlling the production of ROS were obtained with the IPr, as numerous publications that followed Murry et al.[4], including ischemia and reperfusion. However, little practical and clinically applicable to situations in IPr, for example, acute abdomen, mesenteric vascular ischemia, since the time of diagnosis, there is already ischemia. It is for this reason that the IPo has increased interest in this aspect, since, if proven its effectiveness there were many clinical situations with the possibility of applying this method.

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Thus, although there is much evidence of the effectiveness of IPo, it is not yet determined what would be the best method of developing it, how many cycles, the duration of each cycle, if there are differences when used for bowel or other organs, etc. Thus, considering the current evidence of the value of IPo to minimize tissue damage resulting from ischemia and reperfusion, it becomes of paramount importance, and the aim of this study was to assess the effectiveness of IPo accomplished through five cycles of ischemia and reperfusion with five short cycles of ischemia and reperfusion.

Surgical procedure After anesthetization, it was performed the trichotomy and placement of the animal on the operating table in the supine position, with all four members in abduction. The rats underwent midline longitudinal laparotomy of approximately four centimeters, exteriorization of the small intestine, identification and dissection of the cranial mesenteric artery. In the IR group, the cranial mesenteric artery was occluded by atraumatic vascular clamp that remained for 30 minutes (ischemic phase). After placement of the clamp, the small intestine was repositioned in the abdominal cavity and the wound closed with continuous skin suture with 4-0 monofilament nylon suture (mononylon速). After the ischemic phase, the abdominal wall was opened again by removing the suture and the vascular clamp was removed too, initiating reperfusion phase, lasting 60 minutes. The abdomen was closed again by continuous skin suture until the end of the experiment (Figure 1). In IPo group, there was a phase of ischemia (30 minutes) and reperfusion (60 minutes). Preceding the reperfusion, ischemic postconditioning was then performed by five cycles of reperfusion (removal of atraumatic vascular clamp of the cranial mesenteric artery) lasting 30 seconds each one, interspersed by with five cycles of ischemia (re-occlusion of the cranial mesenteric artery by atraumatic vascular clamp), also lasting 30 seconds each one (Figure 1).

Objective To assess the protective effect of IPo on ischemia and reperfusion in rats by five alternating cycles of 30 seconds of reperfusion and 30 seconds of ischemia. METHODS The study was approved by the Ethics Committee on Animal Experimentation of the Federal University of Mato Grosso do Sul and was based on ethical principles defended by the Brazilian College of Animal Experimentation. Animals Studied Twenty-five rats (Rattus norvegicus) of Wistar lineage, adults, males, weighing 270-350 grams, with an average of 305 grams, from the vivarium of the Federal University of Mato Grosso do Sul. The rats were housed individually in cages where temperatures were maintained between 21oC and 24oC, with automatic alternation of light and dark periods of 12 hours, and received diet and water ad libitum. Constituted groups The animals were distributed into three groups: Ischemia-reperfusion (IR) group, with 10 animals, undergoing 30 minutes of ischemia and 60 minutes of reperfusion; group Ischemic postconditioning (IPo), with 10 animals, in which were performed five cycles of 30 seconds of reperfusion inserted by five cycles of 30 seconds of ischemia, immediately after ischemia period (30 minutes) and before reperfusion (60 minutes); and control group (SHAM), with five animals. They had undergone only laparotomy and manipulation of mesenteric cranial artery.

Fig. 1 - Schematic figure showing the times of ischemia and reperfusion in both groups.

After completing the reperfusion in both groups, the abdominal wall was opened again by removing the suture and a segment of 1cm of ileum was resected, five centimeters proximal to ileum-cecal valve, for subsequent histological analysis and classification according to Chiu et al.[11]. In the SHAM group, it was performed only incision of the abdominal wall, bowel exposure, followed by its closure by continuous skin suture with 4-0 nylon. Ninety minutes later it was resected a segment of ileum, as explained above. All the animals were euthanized by anesthetic depth.

Anesthesia The animals were weighed on an electronic precision balance and anesthetized with an intraperitoneal injection of 2:1 solution of Hydrochloride of Ketamine (Cetamin速), 50 mg/ ml, and Hydrochloride of Xylazine (Xilazin速) 20mg/ml, respectively, at a dose of 0.1ml/100g.

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Histopathological study The resected bowel segments, after fixation in formaldehyde solution 10%, were submitted to histological processing (hematoxylin-eosin) and examined under light microscopy by a pathologist without prior knowledge about this group within each rat, and were classified according to the degree of tissue injury second Chiu et al.[11]. • Grade 0: no mucosal changes. • Grade 1: well-formed villi without cell lysis or inflammatory process, however, with formation of Grünhagen subepithelial space. • Grade 2: presence of cell lysis, formation of Grünhagen subepithelial space and increased spacing between the villi. • Grade 3: destruction of the free portion of the villi, presence of dilated capillaries and inflammatory cells. • Grade 4: structural destruction of the villi, with only some outline, formed by inflammatory cells and necrotic material, with hemorrhage and basal glandular ulceration. • Grade 5: destruction of the entire mucosa, no longer any glandular structure was observed, but only amorphous material deposited on the submucosa.

Fig. 2 - Results of the histological analysis of the injury degree of the intestinal mucosa of rats according to Chiu et al.11 DISCUSSION The protective mechanism of IPo in ischemia and reperfusion process is still not entirely clear, but there is evidence that IPo may be related to a significant decrease in the levels of malondialdehyde and products related to lipid peroxidation. These observations suggest a reduction in the production of ROS and less injury mediated by oxidants with IPo[1-9]. The peak production of ROS occurs between the first and seventh minutes after the beginning of reperfusion, although these substances are detectable in later periods. An abundant production of ROS during this initial phase of reperfusion has been implicated as the primary factor in the pathogenesis of tissue injury[12]. The IPo acts at this stage, probably reducing the production of ROS by the gradual release of oxygen to tissue[13]. Santos et al.[14] proposed IPo evaluation using cycles of mesenteric ischemia and reperfusion (three alternate cycles of two minutes each one) after 30 minutes of ischemia and preceding 60 minutes of reperfusion. The results showed a protective effect of IPo. However, in 2010, Bretz et al.[10] published a study which aim was to determine whether IPo could actually mitigate the injury caused by ischemia and reperfusion process. Six rabbits were distributed into control, IR and IPo groups. Ischemia was induced for 45 minutes of occlusion of the segment of jejunal artery, followed by two hours of reperfusion. The IPo was performed with four cycles of 30 seconds of reperfusion and 30 seconds of reocclusion during the initial four minutes of reperfusion. The histopathological evaluation was performed by a single observer and there was no significant difference in necrosis degree between the groups[10]. We have to keep in mind the small sample of this research. Despite this, it was the first publication demonstrating a bad result of IPo before our study. Common among these publications, we can observe that the cycle duration of IPo is shorter than most of the articles[15]. It could be the reason of IPo doesn’t work against

Statistical Analysis The results were analyzed statistically by applying the non-parametric Kruskal-Wallis test, considering significant level of P<0.05. The BioStat 5.4 software was used. RESULTS After histological analysis of the injury degree of the intestinal mucosa according Chiu et al.[11], we have found the following results (Table 1 and Figure 2).

Table 1. Results of the histological analysis of the injury degree of the intestinal mucosa of rats according to Chiu et al.11. Rats Mucosa lesion degree Group IR Group IPo Group SHAM 1 2 1 1 2 4 4 2 3 3 3 1 4 2 3 1 5 2 3 1 6 3 2 7 3 3 8 3 2 9 2 3 10 4 3 Average 2.77 2.67 0.12 Obs: The P value between IR and IPo was >0.05; between IR and SHAM was <0.05, and between IPo and SHAM was <0.05

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reperfusion lesion, and we need more researches observing the cycles duration to prove this hypothesis. However, recently Rosero et al.[16] had shown a different result. They had realized three different protocols of postconditioning in rats undergoing mesenteric ischemia and reperfusion, and had observed that shorter cycles offered better protection against reperfusion lesion. Despite this confrontable result, the ischemia period utilized was 60 minutes, different of our period, with 30 minutes. That’s the biggest problem when we analyzed the literature: a great variation of methods of development of ischemia, reperfusion and postconditioning, hindering a confrontation of existing articles. Sengui et al.[17] also demonstrated better result with short cycles of postconditioning. They had utilized three and six cycles of IPo in rats submitted to mesenteric ischemia and reperfusion and obtained better result with six cycles, but both were better than control group. Again we have to observe that they utilized different periods of ischemia and reperfusion when compared with our research (30 minutes of ischemia, 120 minutes of reperfusion). Postconditioning had also shown effectiveness in other experimental models of ischemia and reperfusion, like spinal cord[18], kidney[19] and brain[20]. It was also analyzed in humans. Staat et al.[21] reported its beneficial effect by performing intermittent reperfusion during angioplasty in patients with acute myocardial infarction, having observed reduction in myocardial injury. Loukogeorgakis et al.[22] performed an experimental study in humans that caused transient upper limb ischemia followed by reperfusion, also observing protective effect of IPo.

2. Zhao ZQ, Corvera JS, Halkos ME, Kerendi F, Wang NP, Guyton RA, et al. Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning. Am J Physiol Heart Circ Physiol. 2003;285(2):H579-88. 3. Huang H, Zhang L, Wang Y, Yao J, Weng H, Wu H, et al. Effect of ischemic post-conditioning on spinal cord ischemic-reperfusion injury in rabbits. Can J Anaesth. 2007;54(1):42-8. 4. Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation. 1986;74(5):1124-36. 5. Santos CHM, Gomes OM, Pontes JCDV, Miiji LNO, Bispo MAF. Post-conditioning: preliminary results of this new option in the treatment of mesenteric ischemia and reperfusion. Cardiovasc Sci Forum. 2007;2(2):13-24. 6. Santos CHM, Pontes JCDV, Miiji LNO, Nakamura DI, Galhardo CAV, Aguena SM. Postconditioning effect in the hepatic ischemia and reperfusion in rats. Acta Cir Bras. 2010;25(2):163-8. 7. Darling CE, Jiang R, Maynard M, Whittaker P, Vinten-Johansen J, Przyklenk K. Postconditioning via stuttering reperfusion limits myocardial infarct size in rabbit hearts: role of ERK1/2. Am J Physiol Heart Circ Physiol. 2005;289(4):H1618-26. 8. Tang XL, Sato H, Tiwari S, Dawn B, Bi Q, Li Q, et al. Cardioprotection by postconditioning in conscious rats is limited to coronary occlusions <45 min. Am J Physiol Heart Circ Physiol. 2006;291(5):H2308-17.

CONCLUSION

9. Dos Santos CH, Pontes JC, Gomes OM, Miiji LN, Bispo MA. Evaluation of ischemic postconditioning effect on mesenteric ischemia treatment: experimental study in rats. Rev Bras Cir Cardiovasc. 2009;24(2):150-6.

Ischemic postconditioning was not able to minimize or prevent the intestinal tissue injury in rats undergoing ischemia and reperfusion process when used five cycles of reperfusion and ischemia lasting 30 seconds each one.

10. Bretz B, Blaze C, Parry N, Kudej RK. Ischemic postconditioning does not attenuate ischemia-reperfusion injury of rabbit small intestine. Vet Surg. 2010;39(2):216-23.

Authors’ roles & responsibilities RKN CHMS LNOM MSA CMM MEF PCC ERJCP

11. Chiu CJ, Mcardle AH, Brown R, Scott HJ, Gurd FN. Intestinal Mucosal Lesion in Low-Flow States. I. A morphological, hemodynamic, and metabolic reappraisal. Arch Surg. 1970;101(4):478-83.

Conception and design of the study; manuscript writing and review Final approval of the manuscript; conception and design of the study; manuscript writing and review Analysis and/or interpretation of data Performing of operations and/or experiments Performing of operations and/or experiments Performing of operations and/or experiments Performing of operations and/or experiments Statistical analysis

12. Sun HY, Wang NP, Kerendi F, Halkos M, Kin H, Guyton RA, et al. Hypoxic postconditioning reduces cardiomyocyte loss by inhibiting ROS generation and intracellular Ca2+ overload. Am J Physiol Heart Circ Physiol. 2005;288(4):1900-8.

REFERENCES

13. Lim SY, Davidson SM, Hausenloy DJ, Yellon DM. Preconditioning and postconditioning: the essential role of the mitochondrial permeability transition pore. Cardiovasc Res. 2007;75(3):530-5.

1. Parks DA, Granger DN. Contributions of ischemia and reperfusion to mucosal lesion formation. Am J Physiol. 1986;250(6 Pt 1):G749-53.

14. Santos CH, Gomes OM, Pontes JCDV, Miiji LNO, Bispo MAF. Tratamento da isquemia mesentérica pelo pós-condicionamento isquêmico. Rev Bras Colo-proctol. 2008;28(2):187-92.

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15. Zhao ZQ, Corvera JS, Halkos ME, Kerendi F, Wang NP, Guyton RA, et al. Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning. Am J Physiol Heart Circ Physiol. 2003;285(2):H579-88.

19. Liu X, Chen H, Zhan B, Xing B, Zhou J, Zhu H, et al. Attenuation of reperfusion injury by renal ischemic postconditioning: the role of NO. Biochem Biophys Res Commun. 2007;359(3):628-34. 20. Rehni AK, Singh N. Role of phosphoinositide 3-kinase in ischemic postconditioning-induced attenuation of cerebral ischemia-evoked behavioral deficits in mice. Pharmacol Rep. 2007;59(2):192-8.

16. Rosero O, Onody P, Stangl R, Turoczi Z, Fulop A, Garbaisz D, et al. Postconditioning of the small intestine: which is the most effective algorithm in a rat model? J Surg Res. 2014;187(2):427-37.

21. Staat P, Rioufol G, Piot C, Cottin Y, Cung TT, Lâ&#x20AC;&#x2122;Huillier I, et al. Postconditioning the human heart. Circulation. 2005;112(14):2143-8.

17. Sengul I, Sengul D, Guler O, Hasanoglu A, Urhan MK, Taner AS, et al. Postconditioning attenuates acute intestinal ischemiareperfusion injury. Kaohsiung J Med Sci. 2013;29(3):119-27.

22. Loukogeorgakis SP, Panagiotidou AT, Yellon DM, Deanfield JE, MacAllister RJ. Postconditioning protects against endothelial ischemia-reperfusion injury in the human forearm. Circulation. 2006;113(7):1015-9.

18. Huang H, Zhang L, Wang Y, Yao J, Weng H, Wu H, et al. Effect of ischemic postconditioning on spinal cord ischemic-reperfusion injury in rabbits. Can J Anaesth. 2007;54(1):42-8.

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Metzger PB, et al. - Hybrid ARTICLE treatment of aortic arch disease ORIGINAL

Hybrid treatment of aortic arch disease Tratamento híbrido das doenças do arco aórtico

Patrick Bastos Metzger1, MD; Fabio Henrique Rossi2, MD, PhD; Samuel Martins Moreira3, MD; Mario Issa4, MD, PhD; Nilo Mitsuru Izukawa5, MD, PhD; Jarbas J. Dinkhuysen6, MD, PhD; Domingos Spina Neto7, MD; Antônio Massamitsu Kambara8, MD, PhD

RBCCV 44205-1585

DOI: 10.5935/1678-9741.20140056 Abstract Introduction: The management of thoracic aortic disease involving the ascending aorta, aortic arch and descending thoracic aorta are technically challenging and is an area in constant development and innovation. Objective: To analyze early and midterm results of hybrid treatment of arch aortic disease. Methods: Retrospective study of procedures performed from January 2010 to December 2012. The end points were the technical success, therapeutic success, morbidity and mortality, neurologic outcomes, the rate of endoleaks and reinterventions. Results: A total of 95 patients treated for thoracic aortic diseases in this period, 18 underwent hybrid treatment and entered in this study. The average ages were 62.3 years. The male was present in 66.7%. The technical and therapeutic success was 94.5% e 83.3%. The perioperative mortality rate of 11.1%. There is any death during one-year follow-up. The reoperation rates were 16.6% due 2 cases of endoleak Ia

and one case of endoleak II. There is any occlusion of anatomic or extra anatomic bypass during follow up. Conclusion: In our study, the hybrid treatment of aortic arch disease proved to be a feasible alternative of conventional surgery. The therapeutic success rates and reinterventions obtained demonstrate the necessity of thorough clinical follow-up of these patients in a long time. Descriptors: Blood Vessel Prosthesis Implantation. Cerebral Revascularization. Aortic Aneurysm, Thoracic. Aneurysm, Dissecting. Aortic Diseases. Resumo Introdução: O manejo das doenças da aorta torácica que envolvem a aorta ascendente, arco aórtico e aorta torácica descendente constituem um desafio técnico e é uma área em constante desenvolvimento e inovação. Objetivo: Analisar os resultados iniciais e a médio prazo do tratamento híbrido das doenças do arco aórtico.

Hospital Salvalus (HS), São Paulo, SP, Brazil. Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil and Instituto Dante Pazzanese de Cardiologia (IDPC), São Paulo, SP, Brazil.

Faculdade de Medicina da Universidade de São Paulo (FMUSP), SP, Brasil, Instituto Dante Pazzanese de Cardiologia (IDPC), São Paulo, SP, Brazil and Hospital Salvalus (HS), São Paulo, SP, Brazil. 2 Faculdade de Medicina da Universidade de São Paulo (FMUSP), SP, Brasil and Seção Médica de Cirurgia Vascular e Centro de Intervenções Endovasculares (CIEV) of Instituto Dante Pazzanese de Cardiologia (IDPC), São Paulo, SP, Brazil. 3 Seção Médica de Radiologia e Centro de Intervenções Endovascular (CIEV) of Instituto Dante Pazzanese de Cardiologia (IDPC), São Paulo, SP, Brazil. 4 Secretaria da Saúde do Estado de São Paulo, São Paulo, SP, Brasil and Departament of Aorta Deseases of Instituto Dante Pazzanese de Cardiologia (IDPC), São Paulo, SP, Brazil 5 Seção Médica de Cirurgia Vascular e do Centro de Intervenções of Instituto Dante Pazzanese de Cardiologia (IDPC), São Paulo, SP, Brazil. 6 Faculdade de Medicina da Universidade de São Paulo (FMUSP), SP, Brazil and Instituto Dante Pazzanese de Cardiologia (IDPC), São Paulo, SP, Brazil.

Work performed at Instituto Dante Pazzanese de Cardiologia (IDPC), São Paulo, SP, Brazsil and Hospital Salvalus (HS), São Paulo, SP, Brazil. No financial support. Correspondence address: Patrick Bastos Metzger Rua Dr. Dante Pazzanese, 500 - Vila Mariana, São Paulo, SP, Brazil – Zip Code: 04012-909 E-mail: patrickvascular@gmail.com Article received on January 27th, 2014 Article accepted on March 3rd, 2014

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Métodos: Estudo retrospectivo de procedimentos realizados no período de janeiro de 2010 a dezembro de 2012, em que foram analisados o sucesso técnico e terapêutico, a morbimortalidade, os desfechos neurológicos, a taxa de vazamentos e de reintervenções. Resultados: Em um total de 95 pacientes tratados por doenças da aorta torácica no período, 18 realizaram o tratamento híbrido e adentraram neste estudo. A idade média foi de 62,3 anos. O sexo masculino esteve presente em 66,7%. O sucesso técnico e terapêutico foi de 94,5% e 83,3%, respectivamente. A mortalidade perioperatória foi de 11,1%. Não houve óbito durante o acompanhamento de 1 ano. A taxa de rein-

tervenção foi de 16,6%, devido a 2 casos de endoleak tipo Ia e um caso de endoleak tipo 2. Não foi observada oclusão dos enxertos anatômicos ou extra-anatômicos durante o período de seguimento. Conclusão: O tratamento híbrido das doenças do arco aórtico demonstrou ser uma alternativa viável à cirurgia convencional. As taxas de sucesso terapêutico e de reintervenções demonstram a necessidade do seguimento clínico rigoroso desses pacientes a longo prazo. Descritores: Implante de Prótese Vascular. Revascularização Cerebral. Aneurisma da Aorta Torácica. Aneurisma Dissecante. Doenças da Aorta.

INTRODUCTION

METHODS Type of study This is a retrospective, longitudinal and observational study carried out in two reference centers for cardiovascular diseases, from January 2010 to December 2012, with a total of 18 patients undergoing hybrid repair of aortic arch disease.

The management of patients with thoracic aortic diseases involving the ascending aorta, aortic arch and descending thoracic aorta are a technical challenge and is an area in constant development and innovation[1,2]. Traditionally, the total surgical repair of the aortic arch demand a period of deep hypothermic circulatory arrest, which can cause high rates of perioperative morbimortality[1-3]. The supra-aortic trunk derivations followed by the endovascular aortic repair is a less invasive alternative for the treatment of this serious condition, having been reported in several clinical trials, systematic reviews and recent meta-analyzes[3-5]. The total endovascular repair of the aortic arch has been a promising method in the last two decades, however, there is information divergence in the literature on the safety of the short-and-medium-term technique, patient selection criteria, in addition, little is known about the material durability and the long-term method[5-8]. The data available in the literature of different types of treatment are the result of small case series with heterogeneous samples and limited follow-up of patients[9]. Therefore, the ideal method for the treatment of aortic arch disease is still a matter of intense debate. The objective of this study is to analyze the results in the short and medium term of a consecutive series of patients undergoing hybrid treatment of the aortic arch disease having as the outcomes studied the technical and therapeutic success, perioperative morbimortality and 1 year after the treatment, neurological outcomes after 30 days, the leak rate and reintervention during the follow-up period.

Inclusion and exclusion criteria The study included patients of both sexes, with or without thoracic symptoms, with indications for aortic correction by: 1. Thoracic aortic aneurysms with a diameter greater than 60 mm or acute complicated Stanford type B aortic dissections (AAD), with inadequate proximal anchor zones (length <2 cm and/or presence of thrombus or calcified plaques greater than 50% of the circumference of the proximal colon) 2. Aortic arch pseudoaneurysm. 3. Penetrating ulcers of the aortic arch and thoracic aorta with a diameter of more than 2 cm and a depth of 1 cm without proximal anchor zones. 4. True aneurysms of the aortic arch (TAAA). 5. Chronic type A aortic dissection. The study excluded patients with: proximal aortic neck fixation with extention greater than 20 mm, diameter of external iliac arteries smaller than 7 mm, serum creatinine greater than 2.0 mg/dl or creatinine clearance less than 30 ml/min. Patients who underwent endovascular repair of thoracic aortic aneurysm and those who did not undergo the supra-aortic trunk revascularization were excluded from the present study. The evaluation of cardiac and/or anesthetic risk was not considered in the inclusion or exclusion.

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Fig. 1 - Angiotomography with multiplanar and three-dimensional reconstruction. A: Axial section demonstrating the dissection of the left subclavian artery origin. B: Larger diameter of the aorta. C: Sagittal section. D: Superior mesenteric artery originating from the true light. E: Involvement of the abdominal aorta. F: Dissection at the level of the left iliac artery. G: Three-dimensional reconstruction of the left anterior oblique. H: Threedimensional reconstruction of the right anterior oblique.

The treatment planning was performed with angiotomography in all patients, and the pre-operative arteriogram was an optinal diagnostic method. All scans were reconstructed in OSIRIX速 MD software 3D mode (three-dimensional) and MPR mode (multiplanar reconstruction), and then the diameters, angles and extensions of the proximal aortic neck were obtained (Figure 1). Surgical technique The extension of the supra-aortic trunks revascularization was scheduled after the angiotomography evaluation of proximal anchoring zones and stratified using the Ishimaru & Mitchell classification[10] (Figure 2): Zone 0: Revascularization of 3 or 4 supra-aortic vessels with median sternotomy (Figure 3A). Zone 1: Carotid-carotid graft with retropharyngeal tunneling or anterior to the trachea associated with the subclavian artery revascularization by transposition or carotid-subclavian graft (Figure 3B). Zone 2: Subclavian artery revascularization byb transposition or carotid-subclavian graft (Figure 3C). Endovascular technique All procedures were performed in the catheterization laboratory of the Endovascular Intervention Center (CIEV) of Dante Pazzanese Carfiology Institute and Salvalus Hospital, by the same group of vascular, cardiovascular surgeons and interventional radiologists.

Fig. 2 - Anchoring zones of the thoracic aneurysm according to Ishimaru and Mitchell classification. In diseases that affect the Zones 0-2, revascularization procedures of the supra-aortic trunks are needed.

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Fig. 3 - Carotid-left subclavian graft with prosthesis anchoring in Zone 2. A=Angiotomography in axial section showing massive thoracic aneurysm without proximal landing zone. B=Three-dimensional reconstruction of pre-implanted stents. C=Digital subtraction angiotomography with endoprosthesis anchoring in Zone 2 and carotid-suclavian patent graft. D=Three-dimensional angiographic reconstruction after stent implantation without leaks.

Outcomes and definitions The primary outcome analyzed were defined as follows: 1 - Technical Success: When the derivation of the supra-aortic trunks was carried out in a previously planned manner; the objective to release the stent in the affected area has been achieved, even in the presence of leaks or other events that could adversely influence the evolution of aortic disease. 2 - Therapeutic Success: The stent deployment occurred without type I and/or III endoleak, or other complications that would affect the favorable development of aortic disease, preserving the patency of the supra-aortic trunk revascularizations. 3 - Perioperative Mortality: Number of deaths registered within the first 30 days after the procedure. 4 - Neurological morbidity in the first 30 days: ischemic cerebrovascular accident (ICVA) and paraplegia secondary to spinal cord ischemia. 5 - Mortality during the one-year-follow-up period.

The patients were treated under inhalation general anesthesia. Antibiotic prophylaxis was performed with 1.5 g of cefuroxime at the anaesthetic induction time. The approach was preferably carried out through the common femoral artery by unilateral open surgical dissection. As it was unsuccessful, we decided to approach the external iliac artery using a retroperitoneal approach. Radiographic control was performed with Siemens® Artis Flat Panel device or in hybrid room with Siemens® Artis zeego Hybrid device. The devices used were: Valiant® (Medtronic Inc, Santa Rosa, Calif), Zenith TX2® (Cook, Bloomington, Ind), Tag® (WL Gore & Assoc, Flagstaff, Ariz), Relay® (Bolton Medical, Sunrise, Fla). The diameters of the stents ranged from 10% to 20% depending on the aortic disease that has to be treated. In cases of true aneurysms, we used an oversize of 20% and in the case of dissection, 10% to 15%. The drainage of cerebrospinal fluid was carried out in selected cases depending on the extent of coverage of the aorta or presence of previous aortic surgeries. In patients where the prostheses were implanted in Zone 0, tachycardia induced by temporary pacemaker was used. In cases of implantation in zone 1 and 2, permissive hypotension was used for accurate endoprosthesis deployment. Intraoperative angiography was performed in all patients. The immediate postoperative period was performed in an intensive care unit in all cases.

RESULTS In the period from January 2010 to December 2012, 95 endovascular correction of thoracic aortic diseases were performed, in which 18 patients underwent hybrid fix consecutively. The demographic characteristics, comorbidities and treatment indications are described in Table 1. The mean age was 62.3±8.3 years, with prevalence of males. The patients were asymptomatic in 13 cases (72.2%), and they were diagnosed in routine examinations findings. Hypertension was present in all patients. Among the present comorbidities, we found a high incidence of chronic obstructive pulmonary disease (COPD) (44.4%) and ischemic heart disease (27.8%). We also observed that 2 patients underwent previous correction of aortic aneurysm (11.1%) and 1 underwent endovas-

Postoperative follow-up Patients were followed up with outpatient evaluation on the 15th, 30th, 180th, and 360th days after the correction. After the first year, the consultations were held annually. The control with angiotomography was performed on the 30th and 360th days of the follow-up period. Ultrasound - Doppler (USG-D) was performed on the 30th and 180th days and annually in order to evaluate the patency of the supra-aortic grafts.

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cular repair of abdominal aortic aneurysm. (Table 1) Most of the indications for hybrid treatment were: true aneurysms of the aortic arch and descending thoracic aorta with colon anchoring <2 cm or unfavorable (Table 1). Most patients were electively treated (72.2%), with the hybrid treatment staged in two phases. Five patients with type A dissection or complicated acute B dissection underwent emergency surgery with surgical and endovascular treatment at the same time. Inhalation general anesthesia was used in all cases with selective cerebrospinal fluid drainage. The techniques used for the supra-aortic trunk revascularizations are described in Table 2. Eight anatomical grafts were performed (total revascularization of the aortic arch) and 10 extra-anatomic grafts (left-right carotid-carotid grafts and/or grafts or left carotid-subclavian transposition). All anatomical grafts were made with bifurcated and/ or straight Dacron prosthesis.The extra-anatomic bridges were performed using PTFE annealed 6 or 8 with retropharyngeal tunneling in 2 cases and 1 case of tunneling anterior to the trachea. Regarding the left subclavian carotid bridges, 7 transpositions of subclavian artery and 3 carotid-subclavian grafts. One of the patients have had previous correction of the ascending aorta, thus, we performed a graft of the ascending aorta-brachiocephalic trunk associated with carotid-carotid graft, and then, a vascular plug implantation in the origin of the brachiocephalic trunk and endovascular aortic repair with stent implantation in Zone 0. In this case, intentional occlusion of the left subclavian artery was performed after confirmation of patency and dominance of the right vertebral artery (Figure 3). Venous, lymphatic or neurological lesions were not observed during the intra-and postoperative period. During the one-year-followup period, there were no occlusions or hemodynamically significant stenoses in the anatomical or extra-anatomic grafts (Figures 4 and 5). The revascularizations requiring the segment exchange of the ascending aorta were performed with total cardiac arrest and cardiopulmonary bypass, as in cases where only the supra-aortic revascularization was used, the proximal anastomosis was performed by partial aortic clamping without interruption flow. The cervical anastomoses were marked with radiopaque material in order to facilitate the endoprosthesis implantation. All aortic accesses were performed by conventional median sternotomy. Cervical access via supraclavicular incision and/or unilateral or bilateral anterior cervical were used depending on the desired type of supra-aortic revascularization. The technical success was achieved in 94.5%, in other words, we were able to perform the programmed supra-aortic graft in 17 patients and, insert the stent into the desired position.

Table 1. Clinical data (n=18). Value (%) Characteristics population Mean age (years) Male Symptomatic disease True TAA Pseudoaneurysms AAA Acute type B dissection Acute type A dissection Chronic type A dissection Diabetes Mellitus Hypertension Dyslipidemia Smoking Chronic renal failure Ischaemic heart disease Chronic Obstructive Pulmonary Disease Prior aortic surgery Cerebrovascular accident Congestive heart failure

n=18 62.3Âą8.3 12 (66.7%) 5 (27.8%) 6 (33.3%) 1 (5.5%) 4 (22.2%) 2 (11.1%) 3 (16.6%) 2 (11.1%) 6 (33.3%) 18 (100%) 12 (66.7%) 12 (66.7%) 1 ( 5.5%) 5 (27.8%) 8 (44.4%) 3 (16.7%) 0 4 (22.2%)

TAA= thoracic aortic aneurysm; AAA= aortic arch aneurysm; Stanford type A and B classification

Table 2. Technical details of 18 supra-aortic trunk revascularizations. Technical details Staged procedures Zone 0

Number of events (%) 13 (72.2%) 8 (44.4%)

Revascularization description 2 Ao-Ao bridges + BCT revascularization + LCC + Sbc 5 Ao-BCT bridges + AoLCC + Sbc 1 Ao-BCT bridge (single carotid aortic trunk) + BCT proximal embolization

Zone 1

4 (22.2%)

3 RCC-LCC bridges + Sbc transposition 1 Sbc-LCC transposition (single carotid trunk)

Zone 2

6 (33.3%)

3 Sbc-LCC transposition 3 Sbc-LCC bridges

15 patients used endoprosthesis 3 patients used two endoprostheses

Numbers of endoprostheses used

Ao-Ao=aorto-aortic; BCT=brachiocephalic trunk; LCC=left common carotid artery; Sbc=subclavian artery; RCC=Right commom carotid artery

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Fig 4 - Carotid-carotid graft associated with transposition of the left subclavian artery and stent-graft implantation in Zone 1. A: Angiotomography in sagittal section with thoracic aneurysm without proper anchoring zone in Zone 2 due to extreme proximity between the left carotid and the left subclavian arteries. B: Angiotomography in axial section showing massive thoracic aneurysm. C: Angiotomography with volume reconstruction. D: Supra-aortic trunk revascularizatoins with carotid-carotid graft associated with transposition of the left subclavian artery. E: Aortography before stent implantation with patency of anatomical extra grafts. F: Aortography after stent implantation demonstrating the aortic stent in Zone 1, no leaks and patency of supra-aortic trunks.

Therapeutic success was 83.3%, in other words, the prosthesis was inserted in 15 patients without leaks or other complications that would jeopardize the favorable evolution of the intervention. The therapeutic failure causes were the type I leak in two cases and one death in the intraoperative period during a correction of Stanford type A dissection, which evolved with retrograde dissection and aortic rupture with cardiac tamponade. The in-hospital postoperative complication rate was 27.7%, as follows: two ischemic neurological injuries (11.1%), two cases of pulmonary complications (11.1%) and one case of acute renal failure (5, 5%) (Table 3). The perioperative mortality was 11.1%. The two deaths occurred due to retrograde type A dissection: one by rupture and acute cardiac tamponade during the endovascular treatment and another by left coronary trunk dissection and acute myocardial infarction on the 8th day after surgery (Table 4). There were no deaths after the 30-day-follow-up period. The primary leak rate was 16.6%, with the type I endoleak in two cases and type II in one case. No cases of type III leaks

and stent migration during follow-up were observed. The reintervention rate after one year was 16.7% due to the treatment of type I and II leaks in a satisfactory manner (Table 4). The annual survival during our follow-up period was 89.9%. The stent devices used were: in seven cases (38.9%) Zenith TX2速 (Cook Medical, Bloomington, INC, USA), in six cases (33.3%) Tag速 (Gore Medical, Flagstaff, AZ, USA) in three cases (16.6%) Valiant速 (Medtronic, Minneapolis, MN, USA), and in two cases (11.1%) Relay速 (Bolton Medical, Sunrise, Fla). We used a total of 21 stents. The average time of endovascular procedure was 65 min (ranging from 48 to 151 minutes), the average time of the supra-aortic trunk revascularization was 196 minutes and the mean hospital stay was 9.7 days, with a 10-day variation. The mean follow-up time was 13 months (5-22 months). DISCUSSION The improvement of endovascular techniques and the association to surgical revascularization of the supra-aortic

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Fig. 5 - Brachiocephalic ascending aorta graft associated with carotid-carotid graft placement of vascular plug and aortic endoprosthesis implantation in Zone 0. Intentional occlusion of left subclavian artery. A=Brachiocephalic ascending aorta surgical graft. B=Preoperative arteriography showing patency of brachiocephalic trunk ascending aorta and right-left carotid-carotid artery. C=Stent implantation in Zone 0 and subtraction arteriograph via right subclavian artery demonstrating type 2 leak coming from the brachiocephalic trunk with left subclavian artery filling. D=Implantation of 22 mm vascular plug in the ostium of the brachiocephalic trunk. E=Arteriography control without type 2 leak F=Thoracic aortography without leaks and with disconnection of native supra-aortic trunks

Table 3. Intra-and perioperative complications (n = 18). Number of events (%) Outcomes Sample n=18

Table 4. Primary leak data (n = 18). Number of events (%) Endoleak types

Intraoperative complications Peripheral embolization Femoral lesion Cardiac tamponade Intra-hospital complications Paraplegia Pulmonary complications ICVA Acute renal failure Acute myocardial infarction Death

Total Type IA Type IB Type II Type III Type IV Reintervention rate

0 0 1 (5.5%) 1 (5.5%) 2 (11.1%) 1 (5.5%) 1 (5.5%) 1 (5.5%) 2 (11.1%)

ICVA=Ischemic cerebrovascular accident

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Sample n=18 3 (16.6%) 2 (11.1%) 0 1 (5.5%) 0 0 3 (16.6%)

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trunks allowed its application in aortic arch diseases, territory in which the conventional surgical treatment can bring high morbimortality rates[11]. Systematic reviews and recent clinical studies have confirmed the benefits of endovascular method over conventional surgery in this aortic segment[1-3,7,11-13]. A suitable anchoring zone in which there is at least 2 cm of healthy aortic extension is required for proper stent implantation, thereby preventing type I endoleak and maintaining the prosthesis durability for a long period[14]. For patients with unfavorable proximal colon, the supra-aortic trunk revascularizations, with the advanced endovascular aortic device for healthy aortic zones, make the treatment of this disease feasible, avoiding the conventional surgical procedure that requires circulatory arrest and deep hypothermia. The mortality of the conventional surgical procedure on the aortic arch varies 0.9 9.3% even in centers with a large number of surgery[3,15,16]. However, according to data from the National Inpatient Sample Database and Medicare Provider Analysis and Reviewer, that better reflect the global reality, mortality rates range from 15 to 20%[17-20]. Despite the invasiveness of the hybrid technique, its degree of morbidity can be minimized by using shorter aortic clamping or partial clamping techniques when you need to advance the prosthesis to Zone 0. In cases where a suitable landing colon can be obtained in Zones 1 and 2, the procedures staged without aortic clamping with the use of extra-anatomic grafts should be used[2,3]. We obtained a technical success rate of 94.5% and a therapeutic success rate. The technical success rate was influenced by intraoperative death, while the therapeutic success rate was influenced by the presence of type IA endoleaks, generating a primary leak rate of 16.6%. Both type IA leaks were treated with the advancement of a second larger diameter endoprosthesis with the leak fully sealed, whereas the type II leak through the subclavian artery was embolized using a spring, which generated a reintervention rate of 16.6%. Moulakakis et al.[1] reported a technical success rate of 92.8%, with a similar leak rate of 16.6%, which were mostly type I endoleaks. The authors explain this data due to the presence of retrograde type A dissection in 4.5% of their patients with the advancement of the stent to Zone 0[1]. Currently, the late results of the hybrid treatment of the aortic arch are not well known, with the most studies reporting a follow-up period of 15 to 18 months[6,21]. These data are extremely scarce and heterogeneous when the endoleaks are specifically evaluated. This rate varies in the literature from 0 to 15%, and the long-term data leaks are virtually absent[4,8,21]. Czerny et al.[4] in a recent study of transcontinental record data including 66 patients with complete revascularization of the aortic arch and a mean follow-up period of 25 months, only one late endoleak type IB and a 5-year survival of 96% was observed by the researchers. On the other hand, Vallejo et al.[6] in a series of 38 hybrid repair of the aortic arch, with

a mean follow-up perid of 28 months, found four type I and two type II endoleaks[6]. Bavaria et al.[8] in a 30-month-follow-up period, did not observe the presence of type I or III leaks. In our study, we observed the presence of late type I, II and III leaks during the mean follow-up period of 13 months. The population of our study showed high risk for conventional surgery due to the high prevalence of chronic obstructive pulmonary disease (50%) and ischemic heart disease (38.9%), and 5 of these patients were treated on an emergency basis due to complicated acute type A a or type B dissections, so our mortality rate in a 30-day-follow-up period was 11.1%. One patient died during the intraoperative period due to progression of retrograde type A dissection with aortic rupture and cardiac tamponade and another patient died on the 8th postoperative day due to the progression of type A dissection with retrograde left coronary trunk involvement and acute myocardial infarction. Brazilian authors reported a mortality rate of 16.7% in the perioperative period using the same technique[2]. A recent meta-analysis published in 2013, with 956 patients analyzed, obtained a perioperative mortality rate of 11.9%[1]. However, smaller case series have been published with mortality rates ranging between 3-6%[3,11]. The neurological injury rates in the literature range from 4% to 12%[11]. When we separate ICVA of the spinal cord from permanent paraplegia, we observed rates of 7.6% and 3.6% respectively, in the meta-analytic study by Moulakakis et al.[1]. In our region, we observed an ICVA rate of 5.5%. This occurred during the advancement of the stent to Zone 0. The occurrence of neurological outcome is directly related to the quality of the native aorta, with the unfavorable characteristics the presence of plaques and thrombi in the aortic segment[22]. Low ICVA rate found by Shirakawa et al.[11] in their clinical study with 40 patients and a follow-up of 15.5 months, is justified by the author due to careful preoperative selection of patients with angiotomography, evaluating the endoprosthesis implantation conditions in the ascending aorta. When a healthy aorta was found, the hybrid treatment was performed[11]. We had a case of spinal cord ischemia in a patient who previously had an open repair of the ascending aorta and prior endovascular repair of infrarenal abdominal aortic aneurysm. This patient had paraplegia signals on the 3rd postoperative day, therefore immediate fluid drainage was performed, however, this individual remained with permanent paraplegia as a sequel. Spinal cord ischemia is directly related to aortic coverage area and the aortic clamping time[1,3,23], thus, spinal cord ischemia rates in hybrid procedures are lower when compared to the open aortic corrections, since the aortic coverage area in hybrid procedures is smaller, as well as the clamping time. In this patient, the area of previous aortic management to the hybrid procedure favored this complication. As for the postoperative complications, we highlight the low incidence of pulmonary complications (11.1%). Two

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patients had prolonged weaning and associated pulmonary infection being treated in the intensive care unit for a long period, but they evolved satisfactorily. The main clinical morbidity in the postoperative period of open and hybrid treatment of thoracic aortic diseases are pulmonary and cardiac complications. The rates of these complications were 19.7% and 6%, respectively, in the meta-analysis published in 2013[1]. In our study, we had one death due to acute myocardial infarction caused by retrograde dissection with left main coronary artery involvement. Despite the large number of COPD patients in our study, the low rate of pulmonary complications is explained due to strict stratification and preoperative clinical training, as well as intensive care dedicated to adequate cardiopulmonary rehabilitation. The retrograde type A dissection is a complication described in the open and endovascular repair of the native ascending aorta[1,7,21]. When assessing the clinical studies for the presence of this complication, it is observed that the data are published in relation to all treated sample, with an absolute rate of 3.8% in the most recent meta-analysis published; however, when observing only the native ascending aorta at risk, we obtain higher rates of this complication. In the study published by Andersen et al.[7], a similar incidence of 3.4% is reported in a series of 87 patients with hybrid aortic arch repair. However, the authors report that the real rate should be 11.1% (3 of 27 cases) when they includ only patients with native ascending aorta at risk of this complication[3,7]. We had two cases of retrograde type A dissection in 16 native ascending aorta (12.5%). New techniques with the full endovascular management of aortic arch aneurysms using branched and fenestrated stents are under development. The first clinical study is being conducted and, therefore, little is known about the medium and long term results of this technique[24]. Endovascular procedures using the Snorkel and ChaminĂŠ techniques, although feasible, they expose the patient to type I endoleak and retrograde type A dissection[25].

The treatment success rates and required reinterventions in the various segments of the aortic arch treated demonstrate the need for rigorous follow-up of these long-term patients.

Authorsâ&#x20AC;&#x2122; roles & responsibilities PBM

FHR SMM MI NMI JJD DSN AMK

Analysis and/or interpretation of data, statistical analysis, final approval of the manuscript, conception and design of the study, operations and/or experiments, manuscript writing or critical review of its contents Final approval of the manuscript, operations and/or experiments, manuscript writing or critical review of its contents Final approval of the manuscript, operations and/or experiments Final approval of the manuscript, operations and/or experiments Final approval of the manuscript, operations and/or experiments Final approval of the manuscript, operations and/or experiments Operations and/or experiments Final approval of the manuscript, operations and/or experiments, manuscript writing or critical review of its contents

REFERENCES 1. Moulakakis KG, Mylonas SN, Markatis F, Kotsis T, Kakisis J, Liapis CD. A systematic review and meta-analysis of hybrid aortic arch replacement. Ann Cardiothorac Surg. 2013;2(3):247-60.

Study limitations Due to the small number of cases, the heterogeneous group of patients and types of procedures performed, as well as the short follow-up period, the comparison between the techniques and the relationship with their outcomes limit the results of our study. Lasty, the accuracy of the results may be affected by retrospective analysis of data.

2. Ingrund JC, Nasser F, Jesus-Silva SG, Limaco RP, Galastri FL, Burihan MC, et al. Hybrid procedures for complex thoracic aortic diseases. Rev Bras Cir Cardiovasc. 2010;25(3):303-10. 3. De Rango P, Cao P, Ferrer C, Simonte G, Coscarella C, Cieri E, et al. Aortic arch debranching and thoracic endovascular repair. J Vasc Surg. 2014;59(1):107-14.

CONCLUSION

4. Czerny M, Weigang E, Sodeck G, Schmidli J, Antona C, Gelpi G, et al. Targeting landing zone 0 by total arch rerouting and TEVAR: midterm results of a transcontinental registry. Ann Thorac Surg. 2012;94(1):84-9.

In our study, the hybrid treatment of aortic arch disease proved to be a technically feasible alternative with short and medium term results. The involvement of the ascending aorta by type A dissection and the need to implant in Zone 0 had a higher rate of acute neurological events and retrograde type A dissection.

5. Cao P, De Rango P, Czerny M, Evangelista A, Fattori R, Nienaber C, et al. Systematic review of clinical outcomes in hybrid procedures for aortic arch dissections and other arch diseases. J Thorac Cardiovasc Surg. 2012;144(6):1286-300.

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6. Vallejo N, Rodriguez-Lopez JA, Heidari P, Wheatley G, Caparrelli D, Ramaiah V, et al. Hybrid repair of thoracic aortic lesions for zone 0 and 1 in high-risk patients. J Vasc Surg. 2012;55(2):318-25.

rebral perfusion in the era of endovascular aortic repair. J Thorac Cardiovasc Surg. 2013;145(3 Suppl):S72-7. 17. Sachs T, Pomposelli F, Hagberg R, Hamdan A, Wyers M, Giles K, et al. Open and endovascular repair of type B aortic dissection in the Nationwide Inpatient Sample. J Vasc Surg. 2010;52(4):860-6.

7. Andersen ND, Williams JB, Hanna JM, Shah AA, McCann RL, Hughes GC. Results with an algorithmic approach to hybrid repair of the aortic arch. J Vasc Surg. 2013;57(3):655-67.

18. Cowan JA Jr, Dimick JB, Henke PK, Huber TS, Stanley JC, Upchurch GR Jr. Surgical treatment of intact thoracoabdominal aortic aneurysms in the United States: hospital and surgeon volume-related outcomes. J Vasc Surg. 2003;37(6):1169-74.

8. Bavaria J, Vallabhajosyula P, Moeller P, Szeto W, Desai N, Pochettino A. Hybrid approaches in the treatment of aortic arch aneurysms: postoperative and midterm outcomes. J Thorac Cardiovasc Surg. 2013;145(3 Suppl):S85-90.

19. Patel VI, Mukhopadhyay S, Ergul E, Aranson N, Conrad MF, Lamuraglia GM, et al. Impact of hospital volume and type on outcomes of open and endovascular repair of descending thoracic aneurysms in the United States Medicare population. J Vasc Surg. 2013;58(2):346-54.

9. Benedetto U, Melina G, Angeloni E, Codispoti M, Sinatra R. Current results of open total arch replacement versus hybrid thoracic endovascular aortic repair for aortic arch aneurysm: a meta-analysis of comparative studies. J Thorac Cardiovasc Surg. 2013;145(1):305-6.

20. Chikwe J, Cavallaro P, Itagaki S, Seigerman M, Diluozzo G, Adams DH. National outcomes in acute aortic dissection: influence of surgeon and institutional volume on operative mortality. Ann Thorac Surg. 2013;95(5):1563-9.

10. Mitchell RS, Ishimaru S, Ehrlich MP, Iwase T, Lauterjung L, Shimono T, et al. First International Summit on Thoracic Aortic Endografting: roundtable on thoracic aortic dissection as an indication for endografting. J Endovasc Ther. 2002;9(Suppl 2):II98-105.

21. Lotfi S, Clough RE, Ali T, Salter R, Young CP, Bell R, et al. Hybrid repair of complex thoracic aortic arch pathology: long-term outcomes of extra-anatomic bypass grafting of the supra-aortic trunk. Cardiovasc Intervent Radiol. 2013;36(1):46-55.

11. Shirakawa Y, Kuratani T, Shimamura K, Torikai K, Sakamoto T, Shijo T, et al. The efficacy and short-term results of hybrid thoracic endovascular repair into the ascending aorta for aortic arch pathologies. Eur J Cardiothorac Surg. 2014;45(2):298-304.

22. Metzger PB, Novero ER, Rossi FH, et al. Evaluation of preoperative computed tomography angiography in association with conventional angiography versus computed tomography angiography only, in the endovascular treatment of aortic diseases. Radiol Bras. 2013;46(5):265-72.

12. Novero ER, Metzger PB, Obregon J, Marco VLA, Rossi FH, Moreira SM. Endovascular treatment of thoracic aortic diseases: a single center result analysis. Radiol Bras. 2012;45(5):251-8. 13. Metzger PB, Fontes DCC, Novero ER, Marco VLA, Moreira SM, Rossi FH, et al. Tratamento endovascular da dissecção crônica de aorta tipo B complicada. Rev Bras Cardiol Invasiva. 2012;20(2):184-90.

23. Fioranelli A, Razuk Filho A, Castelli Júnior V, Karakhanian W, Godoy JM, Caffaro RA. Mortality within the endovascular treatment in Stanford type B aortic dissections. Rev Bras Cir Cardiovasc. 2011;26(2):250-7.

14. Cho JS, Haider SE, Makaroun MS. US multicenter trials of endoprostheses for the endovascular treatment of descending thoracic aneurysms. J Vasc Surg. 2006;43(Suppl A):12A-9A.

24. Schoder M, Lammer J, Czerny M. Endovascular aortic arch repair: hopes and certainties. Eur J Vasc Endovasc Surg. 2009;38(3):255-61.

15. Patel HJ, Nguyen C, Diener AC, Passow MC, Salata D, Deeb GM. Open arch reconstruction in the endovascular era: analysis of 721 patients over 17 years. J Thorac Cardiovasc Surg. 2011;141(6):1417-23.

25. Gehringhoff B, Torsello G, Pitoulias GA, Austermann M, Donas KP. Use of chimney grafts in aortic arch pathologies involving the supra-aortic branches. J Endovasc Ther. 2011;18(5):650-5.

16. Iba Y, Minatoya K, Matsuda H, Sasaki H, Tanaka H, Kobayashi J, et al. Contemporary open aortic arch repair with selective ce-

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Fernandes AMS, et al. - Evaluation ORIGINAL ARTICLEof variables responsible for hospital mortality in patients with rheumatic heart disease undergoing double valve replacement

Evaluation of variables responsible for hospital mortality in patients with rheumatic heart disease undergoing double valve replacement Avaliação de variáveis responsáveis pela mortalidade hospitalar em pacientes portadores de doença reumática submetidos à dupla troca valvar

André Maurício Souza Fernandes1, MsC; Gustavo Maltez de Andrade2; Rafael Marcelino Oliveira2; Gabriela Tanajura Biscaia2; Francisco Farias Borges dos Reis2, MsC, PhD; Cristiano Ricardo Macedo1, MsC; Andre Rodrigues Durães1, PhD; Roque Aras Junior1, PhD

DOI 10.5935/1678-9741.20140044

RBCCV 44205-1586

Abstract Objective: To describe the hospital mortality and associated clinical and echocardiographic variables in patients with rheumatic disease who underwent double valve replacement surgery. Methods: This is a cross sectional descriptive study of mortality, performed in a referral hospital in Salvador, Bahia. Records from patients with rheumatic disease who underwent double valve replacement surgery during the years 2007-2011 were analyzed. Results: The studied sample comprises 104 patients and 60 (57.7%) were male. The mean age was 38.04±14.45. Sixty five bioprostheses and 38 mechanical prostheses were used in these patients at the time of surgery. There were statistically significant differences between the two groups, when we analyzed the following variables: the mean age (36.30±13.03 vs. 45.35±17.8 years-old, P=0.011), mean hemoglobin (11.10±2.19 vs. 9.22±2.26 g/dL, P=0.002), mean hematocrit (34.22±5.86 vs. 28.44±6.62%, P<0.001). New York Heart Association functional class III and IV (NYHA) (P=0.022) was statistically associated with mortality. Conclusion: We concluded that the mean hemoglobin/hematocrit level and the NYHA functional class was the major variables

associated to the mortality among these patients. Based on these data one may concern about the patient best moment for surgery and the patient hemoglobin level.

1. Universidade Federal da Bahia (UFBA), Salvador, BA, Brazil. 2. Escola Bahiana de Medicina e Saúde Pública, Salvador, BA, Brazil.

Correspondence address: Gustavo Maltez de Andrade Hospital Ana Nery, Escola Bahiana de Medicina e Saúde Pública Rua Saldanha Marinho, S/N - Caixa D’água - Salvador, BA, Brazil Zip code: 40320-010 E-mail: maltezgustavo@yahoo.com.br

Descriptors: Rheumatic Fever. Heart Valve Diseases. Hospital Mortality. Preoperative Period. Resumo Objetivo: Descrever a mortalidade hospitalar em pacientes reumáticos submetidos à cirurgia de dupla troca valvar e sua relação com variáveis clínicas e ecocardiográficas. Métodos: Trata-se de um estudo de corte transversal. Foram estudados pacientes maiores que 18 anos, com valvopatia reumática que foram submetidos à cirurgia de DTV do período de janeiro de 2007 a dezembro de 2011 no Hospital Ana Nery Salvador - Bahia. A coleta de dados se deu por meio de consulta aos prontuários dos pacientes. Resultados: Foram estudados 104 pacientes, 60 (57,7%) eram do sexo masculino. A média de idade da população estudada foi de 38,04±14,45 anos. Foram utilizadas 65 próteses biológicas e 38 próteses metálicas. Houve diferença estatisticamente significante entre os grupos comparados, pacientes que obtiveram alta versus pacientes que foram a óbito, em relação às seguintes

This study was carried out at Hospital Ana Nery, Salvador, BA, Brazil and Escola Bahiana de Medicina e Saúde Pública, Salvador, BA, Brazil.

Article received on September 22nd, 2013 Article accepted on January 13th, 2014

No financial support.

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9,22±2,26 g/dL, P=0,002); média do hematócrito, (34,22±5,86 vs. 28,44±6,62%, P<0,001). As classes funcionais III e IV (New York Heart Association) estiveram associadas estatisticamente com a mortalidade (P=0.022). Conclusão: Os dados encontrados no estudo apresentam uma população pouco estudada na qual os principais achados foram a média do nível de hemoglobina/hematócrito e classe funcional NYHA. Deve se levar em conta esses dados para a escolha do melhor momento de cirurgia para essa população.

Abbreviations, acronyms & symbols AR CPB MR NYHA RF

Aortic regurgitation Cardiopulmonary bypass Mitral regurgitation New York Heart Association Rheumatic fever

variáveis: média de idade dos pacientes que receberam alta para casa e foram a óbito, respectivamente (36,30±13,03 vs. 45,35±17,8, P=0,011); média de hemoglobina, (11,10±2,19 vs.

Descritores: Febre Reumática. Doenças das Valvas Cardíacas. Mortalidade Hospitalar. Período Pré-Operatório.

INTRODUCTION

performed, followed by cannulation of the ascending aorta for cardioplegia, using hypothermia (32oC) as a protective strategy, followed by cardiopulmonary bypass (CPB). In the presence of AR, the Aorta was opened and then injected the cardioplegic solution into the coronary ostium. For those patients without AR, the cardioplegic solution was injected directly into the aortic root. Afterwards, the left atrium was opened to perform the mitral and aortic valve replacement, in this respective order, with mechanical or biological prostheses as indicated. Statistical analysis was performed with SPSS (Version 17.0). Variables were tested for normality using the One Sample Test Kolmogorov-Smirnov and the appropriate statistical test was applied according to its distribution. Continuous variables were described as mean ± standard deviation. Continuous variables with normal distribution were compared using Student’s t-test. Asymmetrical distribution variables were analyzed by the Mann-Whitnney test, and their depiction was done by their median, maximum and minimum values. Categorical variables were described by their frequencies and analyzed with the Chi-square test. The level of statistical significance in this study was 5% (P<0.05). This study was approved by the institutional review board of the Ana Nery Hospital (protocol 59/10).

Rheumatic fever (RF) is a major public health problem, especially in developing countries[1]. Valvular heart disease accounts for a significant portion of cardiovascular hospital admissions in Brazil. Unlike most developed countries, its main cause is RF, responsible for 70% of the cases[2]. During the acute phase of the disease, mitral regurgitation (MR) is the most frequent impairment, followed by aortic regurgitation (AR). Obstructive valve lesions usually do not occur in the early stages of the RF. Recurrence of the acute phase of rheumatic heart disease increases the long term risk of permanent heart injuries and may cause multiple valves lesions[3]. Therefore, patients with rheumatic valve disease tend to have multiple valve lesions: either due to rheumatic valve involvement (stenosis and/or regurgitation) or secondary to ventricle dilation, leading to mitral or tricuspid insufficiency. Surgical treatment is usually focused at the most severe valve lesion. However, double valve replacement surgery is being performed more frequently nowadays as an attempt to achieve better quality of life and to improve cardiovascular hemodynamics, reducing mortality among these patients[2,4]. Present literature lacks data on clinical or echocardiographic variables associated to in-hospital mortality in rheumatic patients undergoing double valve replacement surgery. Thus, this study aims to assess which of these determinants has impact in this population.

RESULTS This study sample was composed by 104 patients who underwent double valve replacement surgery between January 2007 and December 2011. The mean age±standard deviation was 38.04±14.45 years. Clinical and epidemiological characteristics of the study population are shown in Table 1. In the study population, 100% of the patients underwent mitral and aortic valve replacement. This surgery was associated with another surgical procedure in only 30.8% of cases. The postoperative hospitalization period ranged from one day to a maximum of 56 days (median 13 days). The aortic and mitral valves were the most affected in this study population, but the tricuspid and pulmonary valves were also impaired, as follows. Three patients presented mild tricus-

METHODS This is a cross-sectional retrospective study including all rheumatic patients admitted to the Ana Neri Hospital, Salvador, BA, Brazil, older than 18 years old, that underwent double valve replacement surgery from January 2007 to December 2011. Medical records were reviewed and evaluated for data collection. The surgical procedure was performed with the patient in the dorsal decubitus position, with a central arterial line to monitor the mean arterial pressure and a central venous line. Median sternotomy and systemic heparinization (0.4 mg/Kg) were

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Table 1. Clinical and epidemiological characteristics of the study population. Salvador, 2007-2011.

pid stenosis and one patient had moderate tricuspid stenosis. Two patients presented with mild pulmonary regurgitation and one patient presented with severe insufficiency. No patients presented pulmonary stenosis (Figure 1). The left atrium was analyzed through echocardiography in 96 patients, ranging from a minimum of 33 mm until 129 mm (median 53 mm). The left atrium size was not associated with hospital mortality (P=0.785). The left ventricle diameters and left ventricular systolic function were also not associated with mortality (Table 2), as well as the degree of valve lesion. When considering two distinct groups, those who were discharged after surgery and those who died during hospital stay, some statistically significant differences can be noticed: their mean age, respectively (36.30±13.03 vs. 45.35±17.8 years old, P=0.011), mean hemoglobin (11.10±2.19 vs. 9.22±2.26 g/dL, P=0.002); and mean hematocrit (34.22±5.86 vs. 28.44±6.62 %, P<0.001). Comparisons of gender, city of origin, body mass index, diabetes mellitus, hypertension, atrial fibrillation, class of heart failure, urea, creatinine, previous cardiac surgery and kind of prosthesis between the groups and outcomes are presented in Table 3. The anoxia time was 129±30 minutes, CPB time was 163±40 minutes, and the total time of surgery was 305±66 minutes. The comparison between the mean anoxia time, CPB time, and total surgical time in both hospital outcomes (death x discharge) were, respectively, 149.17±40.99 and 123.99±24.125 (P=0.001), 185.53±54.597 and 157.34±34.623 (P=0.006), 350.29 and 295.23±56.692±63.983 (P=0.002).

Characteristics Sex (n=104) Man Woman Origin (n=104) Capital Interior Body Mass Index (n=97) Underweight Normal Overweight Obesity Grade 1 Diabetes Mellitus (n=104) Present Absent Systemic Arterial Hypertension (n=104) Present Absent Chagas Disease (n=104) Present Absent Atrial Fibrillation before DVRS (n=100) Yes No Class of Heart Failure NYHA (n=94) Class I Class II Class III Class IV Previous cardiac surgery (n=100) Yes No Type of prosthesis (n=103) Biological Metallic Hospital outcome (n=104) Death Discharged home

Nº

60 44

57.7 42.3

34 70

32.7 67.3

8 67 18 4

8.2 69.1 18.6 4.1

3 101

2.9 97.1

50 54

48.1 51.9

0 104

0 100

28 72

2 36 33 23

2.1 38.3 35.1 24.5

38 62

65 38

63.1 36.9

20 84

19.2 80.8

DISCUSSION Five clinical variables were associated with mortality during the hospitalization of rheumatic patients who underwent double valve replacement surgery: age, hemoglobin, hematocrit, diabetes mellitus and NYHA functional class (New York Heart Association (NYHA) functional classification of heart failure).

DVRS- Double valve replacement surgery; NYHA- New York Heart Association.

Fig. 1 - Distribution of studied patients by valvular’s injury degree of. Salvador 2007-2011. *MI=Mitral Regurgitation; **MS=Mitral Stenosis; ***AoR=Aortic Regurgitation; ****AoS=Aortic Stenosis; *****TI=Tricuspid Regurgitation

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Table 2. Average of echocardiography’s measurements of normal distribution in the study population and average’s comparison on hospital outcome. Salvador, 2007-2011. ECO LVDD (n=92)

Global average 63.73±15.77

LVSD (n=91)

42.81±12.56

EF (n=94)

60.74±12.27

PASP (n=63)

58.63±22.19

Outcome Discharged home Death Discharged home Death Discharged home Death Discharged home Death

Average 63.52±13.5 64.65±23.89 43.53±12.50 39.71±12.76 60.78±11.51 60.56±15.92 57.38±22.14 64.55±22.49

P Value 0.792 0.261 0.948 0.335

LVDD=Left Ventricular Diastolic Diameter; LVSD=Left Ventricular Systolic Diameter; EF=Ejection Fraction; ECO=Echocardiographic Measurements; PASP=Pulmonary Artery Systolic Pressure Table 3. Clinical and epidemiological characteristics and comparison between groups of hospital outcome. Variable Sex (n=104) Man Woman Origin (n=104) Capital Interior Body Mass Index (n=97) Normal Not normal Diabetes Mellitus (n=104) Present Absent Arterial Hypertension (n=104) Present Absent Atrial Fibrillation (n=100) Present Absent Class of HF NYHA (n=94) I or II III or IV Urea (n=97) Normal Not normal Creatinine (n=99) Normal Not normal Previous cardiac surgery (n=100) Yes No Type of prosthesis (n=103) Biological Metallic

Discharged Home Nº %

Nº

48 36

46.2 34.6

12 8

25 59

24 56.7

9 11

56 26

57.7 26.8

11 4

1 83

1 79.8

2 18

37 47

35.6 45.2

13 7

20 60

8 12

35 41

37.2 43.6

3 15

55 23

56.7 23.7

9 10

65 15

65.7 15.2

12 7

29 51

9 11

50 33

48.5 32

15 5

Death

% 11.5 7.7 8.7 10.6 11.3 4.1 1.9 17.3 12.5 6.7 8 12 3.2 16 9.3 10.3 12.1 7.1 9 11 14.6 4.9

P value 0.816 0.192 0.698 0.034 0.092 0.181 0.022 0.056 0.088 0.471 0.219

HF NYHA=Class of Heart Failure New York Heart Association

The double valve replacement surgery is a risk factor for death independent of preoperative data[5], mainly due to longer duration of surgery, CPB and aortic clamping[2,6,7]. The mortality rate in the study population was 19.2%.

Despite elevated when compared to other referral centers in developed countries, different socioeconomic profiles and different access to health between developed and developing countries lead to a comparison limitation[8,9].

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In this study population, 59.6% of patients had functional New York Heart Association (NYHA) class III or IV, and 24.5% were in NYHA functional class IV. No other study has a number of patients in a so severe functional class. Studies with low mortality rates show a maximum of 8% of the population with NYHA functional class IV[8,10]. The lowest mortality rate was 0.7% presented by a study which had only 0.5% of patients in NYHA functional class IV[11] and NYHA functional class IV has been presented as an independent risk factor for operative mortality in double valve replacement surgery. Possibly, this is due to an increased release of proinflammatory vasodepressive cytokines in NYHA functional class IV[12]. Patient with advanced heart failure presents a state of chronic inflammation, especially in episodes of decompensation, generating greater degree of difficulty and complications during the surgical technique performing[12]. Preoperative anemia is associated with increased morbidity and mortality among patients undergoing cardiac surgery[13]. Patients with lower hemoglobin levels and preoperative hematocrit are more likely to be transfused, and the use of blood derivates bags is an independent risk factor for mortality and clinical complications such kidney failure, infections, and cardiac complications, pulmonary and neurological in the first thirty postoperative days[14,15]. Studies evaluating mortality in patients undergoing double valve replacement not present data on hemoglobin and hematocrit preoperatively patients[9-11]. This prevents a proper comparison of the results of this study which showed hemoglobin and hematocrit significantly lower in patients who had hospital death. The magnitude of the effect of anemia in the preoperative surgical double valve replacement as well as the optimal management of these patients lack of data in literature. The mean age of patients who died was 45.35Âą17.8 years. Age as a mortality predictor in cardiac surgery is described in the literature as one of the main risk factors in most scores[15-22]. However, it should be noted that each score has its own cut-off point from which the surgical risk is established. The EuroSCORE indicates that there is an increased risk of death above 60 years old and one point is given for every 5 additional years[16,17]. A previous study states that patients who were at least 50 years old had higher in-hospital mortality, regardless of the valve surgery performed: aortic or mitral valve replacement, double valve replacement, with or without coronary bypass revascularization[23]. This study shows a higher surgical risk among those with a lower mean age when compared to previously published data, since it is a more complex surgery in critically ill patients. Therefore, existing scores in the literature may not be suitable for predicting the actual risk for this specified population. It is possible that the relative risk with age is established at a lower age range for this group of patients. Some clinical variables assessed in this study showed no influence on in-hospital mortality. Some are part of major

risk scores for mortality risk in heart surgery, such as: female gender, previous cardiac surgery and serum creatinine[16,19]. However, most studies evaluated these variables in all types of cardiac surgeries, not specifically double valve replacement. Otherwise, one study that presented independent risk factors for double valve replacement surgery, also found no influence of the variables mentioned above. It is noteworthy that most of these studies were conducted in major medical centers of the United States and Europe. This demonstrates the need to develop scores of preoperative risk in populations with different socioeconomic characteristics. Echocardiographyâ&#x20AC;&#x2122;s measurements of the left ventricle compared between the two groups of patients (who were discharged home and who died) were not statistically significant, in agreement with previously published data[7]. Because they are variables characteristic of chronic disease, it seems possible that a certain degree of adaptation to the hemodynamic status may occur, with no impact on in-hospital mortality. However, it is necessary to investigate the influence of these variables on morbidity and mortality in a long term way. The study has quite few limitations. It was a single center study, which may cause bias due to the restricted population size, limiting extrapolation of data to other populations. CONCLUSION This study is remarkable for highlighting the value of age, hemoglobin, hematocrit, diabetes mellitus and NYHA functional class as possible variables associated to in-hospital mortality of rheumatic patients undergoing double valve replacement surgery. A precise cut off point in the hemoglobin value to determine and predict mortality risk should be studied in order to improve the therapeutic management of patients who will undergo double valve replacement. Furthermore, early indication of heart valve surgeries may avoid a delayed procedure at an advanced stage of the disease. Therefore, new prospective studies in national territory are needed to compare mortality rates between different Brazilian centers, enabling an advance in the management of this disease that still represents a serious public health problem.

Authorsâ&#x20AC;&#x2122; roles & responsibilities AMSF GMA RMO GTB FFBR CRM ARD RAJ

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Planning and writing of the manuscript Collection and analysis of data and writing of the manuscript; statistical analysis; conception and design of the study; completion of the operations and/or experiments Collection and analysis of data Collection and analysis of data Interpretation and review of the manuscript Interpretation and review of the manuscript Review of the manuscript and approval of final version Review of the manuscript and approval of final version

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REFERENCES

production of tumor necrosis factor-α in advanced congestive heart failure. Am J Cardiol. 2001;88(5):578-81.

1. Barbosa PJB, Müller RE, Latado AL, Achutti AC, Ramos AIO, Weksler C, et al. Diretrizes Brasileiras para Diagnóstico, Tratamento e Prevenção da Febre Reumática da Sociedade Brasileira de Cardiologia, da Sociedade Brasileira de Pediatria e da Sociedade Brasileira de Reumatologia. Arq Bras Cardiol. 2009;93(3 supl.4):1-18.

13. LaPar DJ, Crosby IK, Ailawadi G, Ad N, Choi E, Spiess BD, et al.; Investigators for the Virginia Cardiac Surgery Quality Initiative. Blood product conservation is associated with improved outcomes and reduced costs after cardiac surgery. J Thorac Cardiovasc Surg. 2013;145(3):796-803.

2. Tarasoutchi F, Montera MW, Grinberg M, Barbosa MR, Piñeiro DJ, Sánchez CRM, et al. Diretriz Brasileira de Valvopatias - SBC 2011 / I Diretriz Interamericana de Valvopatias - SIAC 2011. Arq Bras Cardiol. 2011;97(5 supl.3):1-67.

14. Hajjar LA, Vincent JL, Galas FR, Nakamura RE, Silva CM, Santos MH, et al. Transfusion requirements after cardiac surgery: the TRACS randomized controlled trial. JAMA. 2010:304(14);1559-67.

3. Peixoto A, Linhares L, Scherr P, Xavier R, Siqueira SL, Pacheco TJ, et al. Febre reumática: revisão sistemática. Rev Soc Bras Clin Med. 2011;9(3):234-8.

15. Bhaskar B, Dulhunty J, Mullany DV, Fraser JF. Impact of blood product transfusion on short and long-term survival after cardiac surgery: more evidence. Ann Thorac Surg. 2012;94(2):460-7.

4. Okuyama H, Hashimoto K, Kurosawa H, Tanaka K, Sakamoto Y, Shiratori K. Midterm results of the Manouguian double valve replacement: comparison with standard double valve replacement. J Thorac Cardiovasc Surg. 2005;129(4):869-74.

16. Roques F, Nashef SA, Michel P, Gauducheau E, de Vincentiis C, Baudet E, et al. Risk factors and outcome in European cardiac surgery: analysis of the EuroSCORE multinational database of 19030 patients. Eur J Cardiothorac Surg. 1999;15(6):816-22.

5. Edwards MB, Taylor KM. Is 30-day mortality an adequate outcome statistic for patients considering heart valve replacement? Ann Thorac Surg. 2003;76(2):482-5.

17. Nashef SA, Roques F, Michel P, Gauducheau E, Lemeshow S, Salamon R. European system for cardiac operative risk evaluation (EuroSCORE). Eur J Cardiothorac Surg. 1999;16(1):9-13.

6. Laffey JG, Boylan JF, Cheng DC. The systemic inflammatory response to cardiac surgery: implications for the anesthesiologist. Anesthesiology. 2002;97(1):215-52.

18. Roques F, Gabrielle F, Michel P, De Vincentiis C, David M, Baudet E. Quality of care in adult heart surgery: proposal for a self-assessment approach based on a French multicenter study. Eur J Cardiothorac Surg. 1995;9(8):433-9.

7. Brandão CMA, Pomerantzeff PMA, Souza LR, Tarasoutchi F, Grimberg M, Oliveira SA. Fatores de risco para mortalidade hospitalar nas reoperações valvares. Rev Bras Cir Cardiovasc. 2002;17(3):236-41.

19. Pons JM, Granados A, Espinas JA, Borras JM, Martin I, Moreno V. Assessing open heart surgery mortality in Catalonia (Spain) through a predictive risk model. Eur J Cardiothorac Surg. 1997;11(3):415-23.

8. Talwar S, Mathur A, Choudhary SK, Singh R, Kumar AS. Aortic valve replacement with mitral valve repair compared with combined aortic and mitral valve replacement. Ann Thorac Surg. 2007;84(4):1219-25.

20. Tu JV, Jaglal SB, Naylor CD. Multicenter validation of a risk index for mortality, intensive care unit stay, and overall hospital length of stay after cardiac surgery. Steering Committee of the Provincial Adult Cardiac Care Network of Ontario. Circulation. 1995;91(3):677-84.

9. McGonigle N, Jones JM, Sidhu P, Macgowan S. Concomitant mitral valve surgery with aortic valve replacement: a 21-year experience with a single mechanical prosthesis. J Cardiothorac Surg. 2007;2:24.

21. Parsonnet V, Dean D, Bernstein AD. A method of uniform stratification of risk for evaluating the results of surgery in acquired adult heart disease. Circulation. 1989;79(6 Pt 2):I3-I12.

10. Gillinov AM, Blackstone EH, Cosgrove DM 3rd, White J, Kerr P, Marullo A, et al. Mitral valve repair with aortic valve replacement is superior to double valve replacement. J Thorac Cardiovasc Surg. 2003;125(6):1372-87.

22. Higgins TL, Estafanous FG, Loop FD, Beck GJ, Blum JM, Paranandi L. Stratification of morbidity and mortality outcome by preoperative risk factors in coronary artery bypass patients. JAMA. 1992;267(17):2344-8.

11. Ho HQ, Nguyen VP, Phan KP, Pham NV. Mitral valve repair with aortic valve replacement in rheumatic heart disease. Asian Cardiovasc Thorac Ann. 2004;12(4):341-5.

23. Hannan EL, Racz MJ, Jones RH, Gold JP, Ryan TJ, Hafner JP, et al. Predictors of mortality for patients undergoing cardiac valve replacements in New York State. Ann Thorac Surg. 2000;70(4):1212-8.

12. Grossman GB, Rohde LE, Clausell N. Evidence for peripheral

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Yuan SM, et al. - Graft pathology at the time of harvest: impact on long-term ORIGINAL ARTICLE survival

Graft pathology at the time of harvest: impact on long-term survival Patologia do enxerto no momento da coleta: impacto na sobrevida a longo prazo

Shi-Min Yuan1, MMed, PhD; Yun Li2, MD, PhD; Yan Hong Ben3,RN; Xiao Feng Cheng3, MMed,MD; Da Zhu Li4, MD; De Min Li3, MMed, PhD; Hua Jing3, MMed, MD

DOI 10.5935/1678-9741.20140118

RBCCV 44205-1587

Abstract Objective: This study aims to present the graft pathology at the time of harvest and its impact on long-term survival. Methods: The remnants of the bypass grafts from 66 consecutive patients with coronary artery disease receiving a coronary artery bypass grafting were investigated pathologically, and pertinent predictive risk factors and survival were analyzed. Results: Medial degenerative changes with or without intimal proliferation were present in 36.8%, 37.8% and 35.6% of left internal mammary artery (IMA), radial artery and saphenous vein grafts. There were 2 (3.0%) hospital deaths and 9 (14.1%) late deaths. Multinomial logistic regression revealed left IMA pathological changes, dyslipidemia, history of percutaneous transluminal coronary angioplasty/stent deployment and Y-graft were significant predictive risk factors negatively influencing the patients’ long-term survival. Kaplan-Meier survival analysis revealed that the long-term survival of patients with left IMA pathological changes were significantly reduced compared with those without (74.1% vs. 91.4%, P=0.002); whereas no differences were noted in long-term survivals between patients with and without pathological changes of the radial arterial or saphenous vein grafts. Conclusion: Pathological changes may be seen in the bypass graft at the time of harvest. The subtle ultrastructural modifi-

cations and the expressions of vascular tone regulators might be responsible for late graft patency. The pathological changes of the left IMA at the time of harvest rather than those of the radial artery or saphenous vein graft affect significantly longterm survival. Non-traumatic maneuver of left IMA harvest, well-controlled dyslipidemia and avoidance of using composite grafts can be helpful in maintaining the architecture of the grafts.

The First Hospital of Putian, Teaching Hospital, Fujian Medical University, Putian, People's Republic of China. 2 Department of Thoracic Surgery, Provincial Hospital Affiliated to Shandong University, Ji'nan, Shandong Province, People's Republic of China. 3 Department of Cardiothoracic Surgery, Jinling Hospital, School of Clinical Medicine, Nanjing University, Jiangsu Province, People's Republic of China. 4 First Department of Surgery, Fourth People’s Hospital of Lu’an, Lu'an, Anhui Province, People's Republic of China.

No financial support.

Descriptors: Coronary Artery Bypass. Pathology. Survival Analysis. Mammary Arteries. Resumo Objetivo: Este estudo tem como objetivo apresentar a patologia do enxerto no momento da coleta e do impacto na sobrevida a longo prazo. Métodos: Os remanescentes de pontes de safena de 66 pacientes consecutivos com doença arterial coronária que receberam uma cirurgia de revascularização coronariana foram investigados patologicamente, e os fatores de risco preditivos e a sobrevivência foram analisados. Resultados: Alterações degenerativas da artéria medial, com ou sem proliferação da íntima estavam presentes em 36,8%, 37,8% e 35,6% de pontes da artéria torácica interna esquerda

Correspondence address: Shi-Min Yuan Longdejing Street, 389 - Chengxian District, Putian, Fujian Province, People’s Republic of China E-mail: shi_min_yuan@yahoo.com

This study was carried out at Jinling Hospital, School of Clinical Medicine, Nanjing University, Jiangsu Province; and First Hospital of Putian, Teaching Hospital, Fujian Medical University, Putian, Fujian Province, People’s Republic of China.

Article received on July 20th, 2014 Article accepted on October 12th, 2014

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alterações patológicas da ATIE foi significativamente reduzida em comparação com aqueles sem (74,1% vs. 91,4%, P=0,002), considerando que não foram observadas diferenças na sobrevivência de longo prazo entre pacientes com e sem alterações patológicas dos enxertos da artéria radial ou de veia safena. Conclusão: As alterações patológicas podem se desenvolver na revascularização no momento da coleta. As modificações ultraestruturais sutis e as expressões de reguladores do tônus vascular podem ser responsáveis pela patência tardia do enxerto. As alterações patológicas da ATIE no momento da coleta, em vez do enxerto da artéria radial ou da veia safena, podem afetar significativamente a sobrevida de longo prazo. Manobra não traumática da ATIE na coleta, bom controle da dislipidemia e para evitar uso de enxertos compostos pode ser útil na manutenção da arquitetura dos enxertos.

Abbreviations, acronyms & symbols CABG eNOS IMA LAD RA SVG

Coronary artery bypass grafting Endothelial nitric oxide synthase Left internal mammary artery Left anterior descending coronary artery Radial artery Saphenous vein graft

(ATIE), artéria radial e veia safena. Houve dois (3,0%) óbitos hospitalares e nove (14,1%) óbitos tardios. A regressão logística multinomial revelou que alterações patológicas na ATIE, dislipidemia, história de angioplastia/stent implantação coronariana transluminal percutânea e Y-enxerto foram significativos fatores de risco preditivos que influenciam negativamente a sobrevivência a longo prazo dos pacientes. Análise de sobrevida de KaplanMeier revelou que a sobrevivência a longo prazo de pacientes com

Descritores: Ponte de Artéria Coronária. Patologia. Análise de Sobrevida. Artéria Torácica Interna.

INTRODUCTION

The patient demographics and the extents of coronary lesions by coronary angiography were listed in Tables 1 and 2.

The left internal mammary artery (IMA) has gained popularity as an arterial graft for coronary artery bypass grafting (CABG) as it provides the gold standard left IMA-left descending coronary artery (LAD) bypass[1]. The radial artery (RA) has become a graft of choice for CABG since its first clinical use by Carpentier in 1971[2]. The graft flow patterns have been evaluated in several studies intraoperatively[3] or postoperatively[4]. Even though the RA graft showed better flow than the IMA and saphenous vein graft (SVG)[3], the patency of the RA graft was inferior to that of the IMA and SVGs[5]. The RA has been recommended to be anastomosed to the circumflex artery or right coronary artery[6]. Use of the RA graft may improve patients’ survival and decrease the incidence of cardiac-related events within the first postoperative years[7]. The low morbidity rate associated with the RA has urged the use of this conduit as a supplement of the right IMA in the IMA-to-LAD bypass[7]. However, controversies still exist on the graft choices in CABG. The pathological changes of bypass grafts at the time of harvest have not been frequently investigated and the relations between the pathology and graft patency and long-term survival are scanty. The present study was designed to evaluate the graft pathology at the time of harvest and its impact on long-term survival.

Harvesting Conventional harvesting of the IMA (pedicled), RA and SVG were applied in all patients. Specimens The remnants of the grafts were collected at the completion of CABG from these 66 consecutive patients. The samples were cut into 1 mm3 in size and immersed in 10% methanal solution in appropriate bottles for pathological inspections. Hematoxylin and Eosin staining was performed on 4 μm paraffin-embedded sections. The pathological changes of the grafts were observed and evaluated by an experienced pathologist. Definitions Pathologies of the grafts are classified as: normal, proliferation and degeneration (of the smooth muscle cells), degeneration (of the intima), atherosclerosis, calcification, vascular wall hemorrhage and inflammatory cell infiltration, uneven vascular wall thickness and varicose (of the SVG). Proliferation is defined as remarkable growth of vascular cells either in the intima or smooth muscle cells. Destructive changes present in the vascular cells are termed as degeneration. A form of arteriosclerosis is characterized by the deposition of atheromatous plaques containing cholesterol and lipids on the innermost layer of the vessel walls. Vessels permeated with calcium are defined as calcification.

METHODS Patients’ information From 2004 to 2011, 66 patients with coronary artery disease receiving CABG had their remnants of bypass grafts for pathological inspections. There were 55 males and 11 females with a mean age of 68.3±8.1 (range: 50-84; median, 73） years. No difference was found in patient age between males and females (68.8±7.9 years, vs. 65.8±9.0 years, P=0.2608).

Ethics This study complies with the Declaration of Helsinki. Informed consent was obtained from each patient and the Institutional Ethics Committee has approved the research protocol.

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Table 1. Patient demographics. Variables Sex, male/female Age, year Course of disease Major symptom, n (%) Chest pain/chest distress Shortness of breath Palpitation Upper abdominal discomfort Associated disorder, n (%) Pacemaker Cerebral infarction Pyelonephritis Others Comorbiditiy, n (%) Hypertension Diabetes mellitus Dyslipidemia Alcohol Smoker New York Heart Association class Cardiovascular agent, n (%) Angiotensin converting enzyme inhibitor ß-blocker Calcium channel antagonist Diuretics Vasodilator Statin Myocardial infarction, n (%) Acute myocardial infraction Non-ST segment elevation myocardial infarction Non-Q wave myocardial infarction Percutaneous transluminal coronary angioplasty/stent, n (%) Coronary artery disease, n (%) 2-vessel disease 3-vessel disease Left main+1-vessel disease Left main+2-vessel disease Left main+3-vessel disease Coronary stenosis on angiography, % Left main coronary artery Left anterior descending artery Circumflex artery Right coronary artery Hospitalization, day Postoperative complications, n (%)

Results (n=66) 55/11 68.3±8.1 (range, 50-84) 5.9±7.6 year (range, 1 day-30 year)

48 (72.7) 6 (9.1) 10 (15.2) 2 (3.0)

3 (4.6) 6 (9.1) 1 (1.5) 1 (1.5)

58 (87.9) 16 (24.2) 7 (10.6) 9 (13.6) 21 (31.8) 2.2±0.4 (range, 2-3)

11 (16.7) 16 (24.2) 27 (40.9) 13 (19.7) 17 (25.8) 2 (3.0) 24 (36.4) 20 (30.3) 3 (4.6) 1 (1.5) 5 (7.6)

9 (13.6) 27 (40.9) 2 (3.0) 2 (3.0) 26 (39.4)

61.8±21.8 (range, 20-95) (n=30) 91.0±11.4 (range, 70-100) (n=58) 87.5±14.9 (range, 30-100) (n=52) 84.0±19.2 (range, 20-100) (n=51) 22.0±15.5 (range, 3-70) (n=66) 4 (6.1)

Table 2. Number or extent of the coronary lesions. Coronary artery

No lesion n (%) Left main coronary artery 35 (53.0) Left anterior descending coronary artery 1 (1.5) Circumflex artery 8 (12.1) Right coronary artery 7 (10.6)

Solitary n (%) 26 (39.4) 20 (30.3) 19 (28.8) 12 (18.2)

2 n (%) 3 (4.6) 11 (16.7) 12 (18.2) 5 (7.6)

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Long lesion n (%) 0 (0) 8 (12.1) 4 (6.1) 9 (13.6)

Diffuse lesion n (%) 1 (1.5) 16 (24.2) 12 (18.2) 17 (25.8)

Not recorded n (%) 1 (1.5) 4 (6.1) 4 (6.1) 5 (7.6)

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Statistics Data were expressed as mean ± standard deviation. Unpaired t-test was made for intergroup comparisons of the quantitative data. Fisher exact test and logistic regression analysis were performed for the postoperative outcomes and the pathology of the grafts. Patients’ survival was evaluated with Kaplan-Meier survival analysis. A two-tailed P value of <0.05 was considered of significance.

56 (75.7%), the first diagonal branch in 1 (1.4%), sequentially LAD and first diagonal branch in 8 (10.8%) and the great cardiac vein for the purpose of venous arterialization in 1 (1.4%) patient, respectively. An RA graft was used in 51 (77.3%) patients, bypassed to the first diagonal branch in 6 (11.8%), LAD in 1 (2.0%), intermediate artery in 1 (2.0%), circumflex artery in 1 (2.0%), obtuse marginal branch in 23 (45.1%) and posterior descending artery in 19 (37.3%) patients, respectively. They were in a sequential fashion in 4 (7.8%) patients (one RA graft for two distal anastomoses in each patient), a Y-graft in 2 (3.9%) patients and an independent graft in 41 (80.4%) patients. The 2 right IMA grafts were bypassed to the intermediate artery and right coronary artery, respectively. Of the 236 grafts, 161 (68.2%) remnants were collected and inspected pathologically. There were 57 (35.4%) left IMAs, 45 (28.0%) RAs and 59 (36.7%) SVGs. Types of grafts used did not differ between gender. The dimensions of the lumens of the three grafts were all within normal ranges. The lengths and lumen diameters of the SVG were larger than those of the IMAs and RAs, however, no statistical differences were noted (Table 3). Of this patient setting, half of the patients had normal graft vessels as evidenced by histological observations (Table 4). The prevalence of pathological changes did not reach a statistical significance between the IMA, RA and venous grafts (47.4% vs. 46.7% vs. 45.8%, χ2=0.0, P=0.985). The prevalence of the medial degeneration did not differ between the three grafts, either (36.8% vs. 37.8% vs. 35.6%, χ2=0.1, P=0.973). The microscopic views of the grafts were shown in Figure 1. There were 2 hospital deaths with an early mortality of 3.0%. Two patients were lost for follow-up. The remaining 62 patients were followed up for an average of 30.2±8.8 (range, 6.9-55; median, 15.8) months. Twenty-four patients had coronary angiography examined during follow-up, 1 (4.2%) patient had left IMA and 1 (4.2%) patient had RA graft occlusion requiring reoperations and 2 (8.3%) patients had SVG occlusion warranting a reintervention by percutaneous angioplasty. There were 9 (14.1%) late deaths due to heart dysfunction (n=3), acute myocardial infarction (n=2), renal failure (n=2), malignant cancer (n=1) and unknown reason (n=1).

RESULTS The CABG procedures were performed under CPB in 55 (83.3%), off-pump in 10 (15.2%) and a stepped off-pump and beating heart revascularization under CPB in 1 (1.5%) patient, respectively. Ten (15.2%) patients had a secondary procedure during the operations including mitral valve replacement or repair in 5 (50%), aortic valve replacement, left ventricular pseudoaneurysmectomy, left ventricular pseudoaneurysmectomy with mitral valve repair, left ventricular pseudoaneurysmectomy with the aid of intraaortic balloon pump and intraaortic balloon pump alone in 1 (10%) patient each. There were totally 236 grafts bypassed in 66 patients with a mean of 3.6±0.9 (range: 2-5; median, 3) grafts per patient including 103 (43.6%) SVGs, 57 (24.2%) RAs, 74 (31.4%) left IMAs (inclusive of all distal anastomoses of the sequential grafts) and 2 (0.8%) right IMAs. A sequential graft was performed in 34 (51.5%) patients, a Y-graft in 2 (3.0%) patients and only independent grafts in the remaining 30 (45.5%) patients. The donor vessels for the LAD were left IMA in 63 (96.9%), RA in 1 (1.5%) and SVG in 1 (1.5%), respectively (χ2=177.4, P=0.0000). The coronary arteries receiving an SVG were left main coronary artery in 1 (1.0%), LAD in 1 (1.0%), the first diagonal branch in 21 (20.4%), intermediate artery in 3 (2.9%), circumflex artery in 1 (1.0%), obtuse marginal branch in 41 (39.8%), right coronary artery in 5 (4.9%), posterior descending artery in 26 (25.2%) and posterior left ventricular branch in 4 (3.9%), totaling 103 grafts. Apart from one (1.0%) bypassed to the left main coronary artery, there were 25 (24.3%), 42 (40.8%) and 35 (34.0%) SVGs grafted to the LAD, circumflex and RCA systems, respectively (χ2=6.4, P=0.0399). The receipt vessels of the left IMA were LAD in

Table 3. Measurements of the inspected remnants of the grafts. Pathology Lenght (cm) Lumen diameter (cm)

Saphenous vein graft (n=59) 4.9±3.4 (range, 0.4-9) (n=42) 0.4±0.1 (0.2-0.9) (n=54)

Left internal mammary artery (n=57) 2.1±1.1 (range, 0.5-5) (n=38) 0.3±0.1 (range, 0.1-0.5) (n=40)

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Radial artery (n=45) 2.7±1.7 (range, 0.5-5) (n=33) 0.4±0.1 (range, 0.2-0.8) (n=36)

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Table 4. Pathology of the inspected remnants of the grafts. Pathology Normal Proliferation and degeneration of smooth muscle cells Intimal degeneration Atherosclerosis Calcification Vascular wall hemorrhage & inflammatory cell infiltration Uneven vascular wall thickness Varicose (saphenous vein)

Left internal mammary artery (n=57) n (%) 30 (52.6) 21 (36.8) 2 (3.5) 2 (3.5) 1 (1.8) 1 (1.8) ---

Radial artery (n=45) n (%) 24 (53.3) 17 (37.8) 3 (6.7) 0 (0) 1 (2.2) 0 (0) ---

Saphenous vein graft (n=59) n (%) 32 (54.2) 21 (35.6) 1 (1.7) 0 (0) 0 (0) 0 (0) 3 (5.1) 2 (3.4)

Kaplan-Meier survival analysis revealed that the long-term survival of the patients with left IMA pathological changes was significantly reduced in comparison with those without (74.1% vs. 91.4%, P=0.002) and that the pathological changes of the radial arterial or saphenous vein graft were unlikely to significantly affect patientsâ&#x20AC;&#x2122; long-term survival (Figures 2-4). DISCUSSION The left IMA-LAD graft is appraised for its promising patency rate and patients' long-term survival[8]. The left IMA is usually used to bypass the anterior circulation and the RA graft, to bypass the coronary arteries of the inferior or the lateral territory[9]. Recent randomized

Fig. 1 - Microspcopic views of the grafts: (A) saphenous vein grafts with normal structures; (B) saphenous vein grafts showing medial degenerative changes with intimal proliferation; (C) radial arterial grafts with normal structures; (D) radial arterial grafts with medial degenerative changes with intimal proliferation; (E) internal mammary arteries with roughly normal structures; and (F) internal mammary arteries with mild degeneration of the media with intimal proliferation. Hematoxylin and Eosin staining Ă&#x2014; 200 Fig. 2 - Kaplan-Meier analysis revealed that the pathological changes of the left internal mammary graft artery were a risk factor that negatively influenced the survival rate. The long-term survival rate was 83.9%, 74.1% and 91.4% for overall and patients with and without pathological changes of the left internal mammary artery. LIMA=Left internal mammary artery; With=With pathological changes; Without=Without pathological changes

Multinomial logistic regression revealed that pathology of the left IMA (P=0.017), the presence of dyslipidemia (P=0.033), history of percutaneous transluminal coronary angioplasty/stent deployment (P=0.001) and Y-graft (P=0.006) were significant predictive risk factors of long-term survival.

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ROOBY trial proved that off-pump CABG was associated with lower patency for arterial and venous graft conduits than on-pump CABG[10]. Superior long-term survival rate was observed in the on-pump CABG than in the off-pump CABG patients[11-13]. Clinical observations revealed that the RA grafts had a lower patency rate (51.3%) than the left IMAs (90.3%) or the SVGs (64.0%)[4]. At a mean of 7.7±1.5 year follow-up after CABG, RAs had much lower functional (12.0% vs. 19.7%, P=0.03) and complete graft occlusion rates (8.9% vs. 18.6%, P=0.002) compared with the SVGs[14]. Hata et al.[15] reported that the cumulative graft patency rates at 8 years were 74.3% for the RA and 64.7% for the SVG, respectively. RA patency rate varied with territory and bypass modes, with 79.4% in the left circumflex coronary artery, 72.7% in the LAD and 50% in the right coronary artery; the occlusion rate was 20.0% among free grafts, 18.2% among sequential grafts and 20.0% among composite grafts[16]. The RA patency rate showed a gender predilection, which was higher in men than in women (38.9% vs. 56.1%, P=0.025) at a mean follow-up of 565±511 days[17]. Non-severe stenosis of the target coronary arteries can be a potential risk factor leading to a higher diffuse narrowing rate of the RA grafts in comparison to the SVGs[9]. Several studies agreed that the history of open heart surgery or percutaneous coronary intervention can be a significant risk factor of increased mortality[18,19]. Severe congestive heart failure, advanced age, postinfarction myocardial rupture, cardiogenic shock, CPB, pulmonary hypertension and increased creatinine can be the risk factors of in-hospital mortality[20]. Long-term mortality was also associated with female gender, non-Hispanic black race, small body surface area, extreme body mass index values, left main coronary disease, multivessel disease, reduced ejection fraction, history of myocardial infarction, unstable hemodynamic state/shock and the presence of comorbidities[21]. The research of graft pathology started from the 1970’s. By light microscopy, minimal to moderate mediointimal fibrosis and graft occlusion due to recent thrombosis were noted in 31.7% (13/41) grafts early (<20 days) and old thrombus, intimal leiomyocellular proliferation, or intimal phlebosclerosis were noted in 19.5% (8/41) patients in the late group (3-39 months); whereas a vein graft showed atherosclerotic changes[22]. A histological study of the SVGs showed grade 1 to 2 intimal proliferation in the early group (14 days) and grade 2 to 3 or even grade 4 intimal proliferation in the late group (34 months) in all grafts[23]. In a prospective study involving 365 consecutive patients undergoing isolated CABG, significant lesions in the SGVs were observed in 71 (19.5%) patients[24]. Structures of the SVG, particularly the tunica media and smooth muscle cells had a significant impact on the late outcome after CABG[25]. In patients with postoperative coronary

Fig. 3 - Kaplan-Meier analysis revealed that pathological changes of the radial artery graft were not a significant risk factor affecting the survival rate. The long-term survival rate was 83.6%, 82.9% and 85.0% for overall, patients with and without pathological changes of the radial artery. RA= Radial artery; With= With pathological changes; Without= Without pathological changes

Fig. 4 - Kaplan-Meier analysis revealed that the pathological changes of the saphenous vein graft were not a significant risk factor affecting the survival rate. The long-term survival rate was 83.6%, 78.9% and 91.3% for overall, patients with and without pathological changes of the saphenous vein. SVG= Saphenous vein graft; With= With pathological changes; Without= Without pathological changes

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artery disease progression and severe venous graft disease, tunica media thickening was noted, and it was taken as a risk factor for late venous graft failure[25]. In recent years, graft pathology has been carried out in deep-going ways concerning ultrastructural and signaling pathway studies. Saphenous tunica media thickening and chunky smooth muscle cell nuclei were identified as independent risk factors for graft disease[24]. High lipid exposure may be prone to early graft failure especially of the vein graft[26]. Morphometric studies of the RA disclosed mild or moderate intimal hyperplasia but no medial calcification in both young and elderly patients[27]. Matrix vesicles and calcifications were frequently present in the media of both the RA and IMA[28]. Fewer endothelial denudations, similar medial lipid deposition and submicroscopic calcification were observed in the RA comparing to other arteries[28]. The higher proliferative potential of the smooth muscle cells and more actively secretory status of endothelial cells of the RA enhance the remodeling process and predispose a reduced long-term patency[28]. In diabetic patients, the foam cells and tendency of migration from the smooth muscle cells to the intima were more frequently observed in the RA than in non-diabetic patients as observed by electron microscopy[29]. Chronic hypoxia increases the activity of vascular endothelial growth factor, a potent mitogenic molecule for the smooth muscle cells[30]. Li et al.[31] discovered that platelet-derived growth factor, another potent mitogenic molecule, is active exclusively in the epithelioid-like smooth muscle cells isolated from the human IMA but not in the spindle-like cells. Endothelial nitric oxide synthase (eNOS) type III was expressed in the intima of the IMA, RA and SVG and in the media of the IMA and RA. However, the IMA showed a higher intensity of eNOS type III expression, particularly within the media. This may provide an histologic explanation for the better results of the IMA graft[32]. Increased expressions of eNOS in the intima and media were also observed in the RA grafts irrespective of patients’ age[27]. A recent study revealed that Gas6/Axl pathway cytokines are more expressed in the left IMA than in other arteries, indicating that the IMAs were more resistant to atherosclerotic changes[33]. Independent predictors of late RA graft failure were native coronary stenosis <75% and peripheral vascular disease. Independent predictors of late SV graft failure were use of only one anti-platelet agent and low-density/high-density lipoprotein cholesterol ratio >2.5[15]. The vasa vasorum of the veins is more pronounced than in the arteries and hence the vasa vasorum plays an important role in enhancing SVG patency when harvested along with surrounding tissue for restoring medial blood flow from the nutrient microvessels[34]. Upregulated inflammation biomarkers including scavenger receptors A

and B, toll-like receptors 2 and 4, platelet endothelial cell adhesion molecule, vascular cell adhesion molecule and intercellular cell adhesion molecule have been noted in the SVGs and were thus taken as a possible mechanism of graft failure[35]. An increased expression of cytokeratin 8 and weak expressions of calponin in the tunica media of the SVGs might be useful markers of unfavorable longterm prognosis in CABG patients[36]. The skeletonization of the IMA with an ultrasonic scalpel had no deleterious effect on the endothelium. All IMA specimens showed a completely confluent endothelium, and no endothelial injury was observed by a scanning electron microscopic study[37]. A metal clamp can cause serious intimal injury which disrupts the internal elastic lamina, and thus should be avoided for the temporary clamping of the skeletonized IMA. A fibrous jay clamp, however, hardly ever causes intimal injury, and its clinical use for the temporary clamping of the ultrasonically skeletonized IMA is therefore recommended[37]. Retention of perivascular tissue on the SVG prepared for CABG by “no-touch” technique protects against distension-induced damage, preserves vessel morphology and maintains eNOS activity[38]. In no-touch vessels, eNOS is highly expressed as compared with conventionally harvested ones[39]. The RAs harvested by “no-touch” technique are associated with better preservation of the endothelial cells warranting a long-term patency[28]. In the present study, the dimensions of the lumens of the three grafts were within normal ranges, with reference to their normal limits of 3.1 to 8.5 mm[40], 2.1 mm[41] and 2.6 mm[42] for the SVG, IMA and RA, respectively, as reported in the literature. Pathologically, over half of the patients had normal graft vessels; while others showed medial degenerative changes with or without intimal proliferation accounting for 35.6%, 36.8% and 37.8% in three grafts, respectively. In line with previous reports[11,19], the present study revealed left IMA pathological changes, dyslipidemia, history of PTCA/stent and Y-graft were significant predictive risk factors negatively influencing the patients’ long-term survival. The nonrandomized nature and the limitations in patient selection were likely to be the major drawbacks of this study. A multicenter study in the future would be helpful in obtaining more accurate results. CONCLUSION Pathological changes may develop in bypass graft at the time of harvest. The subtle ultrastructural modifications and the expressions of the vascular tone regulator might be the underlying causes responsible for late graft patency. The pathological changes of the left IMA at the time of harvest rather than those of the RA or SVG affect significantly pa-

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tients' long-term survival. Non-traumatic maneuver of IMA harvest, well-controlled dyslipidemia and avoidance of using composite grafts can be helpful in maintaining the architecture of the IMA graft and may therefore improve the long-term outcomes of the patients.

CT, Dacey LJ, et al. Use of the internal mammary artery graft and in-hospital mortality and other adverse outcomes associated with coronary artery bypass surgery. Circulation. 2001;103(4):507-12. 9. Desai ND, Cohen EA, Naylor CD, Fremes SE; Radial Artery Patency Study Investigators. A randomized comparison of radialartery and saphenous-vein coronary bypass grafts. N Engl J Med. 2004;351(22):2302-9. 10. Hattler B, Messenger JC, Shroyer AL, Collins JF, Haugen SJ, Garcia JA, et al; Veterans Affairs Randomized On/Off Bypass (ROOBY) Study Group. Off-Pump coronary artery bypass surgery is associated with worse arterial and saphenous vein graft patency and less effective revascularization: Results from the Veterans Affairs Randomized On/Off Bypass (ROOBY) trial. Circulation. 2012;125(23):2827-35.

Authors’ roles & responsibilities SMY YL YHB XFC DZL DML HJ

Main Author Carrying out operations and/or experiments Carrying out operations and/or experiments Carrying out operations and/or experiments Carrying out operations and/or experiments Carrying out operations and/or experiments Carrying out operations and/or experiments

11. Shroyer AL, Grover FL, Hattler B, Collins JF, McDonald GO, Kozora E, et al; Veterans Affairs Randomized On/Off Bypass (ROOBY) Study Group. On-pump versus off-pump coronaryartery bypass surgery. N Engl J Med. 2009;361(19):1827-37. 12. Kim JB, Yun SC, Lim JW, Hwang SK, Jung SH, Song H, et al. Long-term survival following coronary artery bypass grafting: off-pump versus on-pump strategies. J Am Coll Cardiol. 2014;63(21):2280-8.

REFERENCES 1. Karthik S, Fabri BM. Left internal mammary artery usage in coronary artery bypass grafting: a measure of quality control. Ann R Coll Surg Engl. 2006;88(4):367-9.

13. Filardo G, Grayburn PA, Hamilton C, Hebeler RF Jr, Cooksey WB, Hamman B. Comparing long-term survival between patients undergoing off-pump and on-pump coronary artery bypass graft operations. Ann Thorac Surg. 2011;92(2):571-7.

2. Carpentier A, Guermonprez JL, Deloche A, Frechette C, DuBost C. The aorta-to-coronary radial artery bypass graft. A technique avoiding pathological changes in grafts. Ann Thorac Surg. 1973;16(2):111-21.

14. Deb S, Cohen EA, Singh SK, Une D, Laupacis A, Fremes SE; RAPS Investigators. Radial artery and saphenous vein patency more than 5 years after coronary artery bypass surgery: results from RAPS (Radial Artery Patency Study). J Am Coll Cardiol. 2012;60(1):28-35.

3. Goel P, Dubey S, Makker A, Kohli VM. Evaluation of coronary artery bypass grafts by intraoperative transit time flow measurement. Ind J Thorac Cardiovasc Surg. 2003;19(2):108-12.

15. Hata M, Yoshitake I, Wakui S, Unosawa S, Kimura H, Hata H, et al. Long-term patency rate for radial artery vs. saphenous vein grafts using same-patient materials. Circ J. 2011;75(6):1373-7.

4. Pizzuto F, Voci P, Mariano E, Puddu PE, Aprile A, Romeo F. Evaluation of flow in the left anterior descending coronary artery but not in the left internal mammary artery graft predicts significant stenosis of the arterial conduit. J Am Coll Cardiol. 2005;45(3):424-32.

16. Crusco F, Antoniella A, Papa V, Menzano R, Di Lazzaro D, Di Manici G, et al. Midterm follow-up of patients receiving radial artery as coronary artery bypass grafts using 16-detector-row CT coronary angiography. Radiol Med. 2007;112(4):538-49.

5. Khot UN, Friedman DT, Ellis SG. Radial-artery coronary bypass grafts. N Engl J Med. 2005;352(9):941-2; author reply 941-2.

17. Khot UN, Friedman DT, Pettersson G, Smedira NG, Li J, Ellis SG. Radial artery bypass grafts have an increased occurrence of angiographically severe stenosis and occlusion compared with left internal mammary arteries and saphenous vein grafts. Circulation. 2004;109(17):2086-91.

6. Ennker J, Wanner M, Gehle P, Ennker IC, Rosendahl U. Postoperative evaluation of radial artery grafts for coronary artery bypass grafting by transit-time Doppler flow measurements. Thorac Cardiovasc Surg. 2001;49(6):365-8.

18. Wu C, Camacho FT, Wechsler AS, Lahey S, Culliford AT, Jordan D, et al. Risk score for predicting long-term mortality after coronary artery bypass graft surgery. Circulation. 2012;125(20):2423-30.

7. Acar C, Cook RC. Letter regarding article by Khot et al, "Radial artery bypass grafts have an increased occurrence of angiographically severe stenosis and occlusion compared with left internal mammary arteries and saphenous vein grafts". Circulation. 2005;111(1):e6-9.

19. Shahian DM, O’Brien SM, Sheng S, Grover FL, Mayer JE, Jacobs JP, et al. Predictors of long-term survival after coronary artery bypass grafting surgery: results from the Society of Thoracic

8. Leavitt BJ, O’Connor GT, Olmstead EM, Morton JR, Maloney

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Surgeons Adult Cardiac Surgery Database (the ASCERT study). Circulation. 2012;125(12):1491-500.

32. Gaudino M, Toesca A, Maggiano N, Pragliola C, Possati G. Localization of nitric oxide synthase type III in the internal thoracic and radial arteries and the great saphenous vein: a comparative immunohistochemical study. J Thorac Cardiovasc Surg. 2003;125(6):1510-5.

20. Mejía OA, Lisboa LA, Tiveron MG, Santiago JA, Tineli RA, Dallan LA, et al. Coronary artery bypass grafting in acute myocardial infarction: analysis of predictors of in-hospital mortality. Rev Bras Cir Cardiovasc. 2012;27(1):66-74.

33. Lee CH, Shieh YS, Tsai CS, Hung YJ, Tsai YT, Lin CY. Expression of growth arrest-specific protein 6 and Axl molecules in the left internal mammary artery of patients undergoing coronary artery bypass grafting. J Clin Pathol. 2014;67(6):506-11.

21. Hannan EL, Racz MJ, Walford G, Jones RH, Ryan TJ, Bennett E, et al. Long-term outcomes of coronary-artery bypass grafting versus stent implantation. N Engl J Med. 2005;352(21):2174-83.

34. Dreifaldt M, Souza DS, Dashwood MR. Comparable patencies of the radial artery and right internal thoracic artery or saphenous vein beyond 5 years: results from the Radial Artery Patency and Clinical Outcomes trial. J Thorac Cardiovasc Surg. 2010;140(3):727-8.

22. Thiene G, Valente ML, Miazzi P, Casarotto D, Bortolotti U, Gallucci V. [Pathology of the aorto-coronary bypass by autologous saphenous vein (author's transl)]. G Ital Cardiol. 1979;9(6):549-56. 23. Lawrie GM, Lie JT, Morris GC Jr, Beazley HL. Vein graft patency and intimal proliferation after aortocoronary bypass: early and longterm angiopathologic correlations. Am J Cardiol. 1976;38(7):856-62.

35. Khaleel MS, Dorheim TA, Duryee MJ, Durbin HE Jr, Bussey WD, Garvin RP, et al. High-pressure distention of the saphenous vein during preparation results in increased markers of inflammation: a potential mechanism for graft failure. Ann Thorac Surg. 2012;93(2):552-8.

24. Perek B, Malinska A, Stefaniak S, Ostalska-Nowicka D, Misterski M, Zabel M, et al. Predictive factors of late venous aortocoronary graft failure: ultrastructural studies. PLoS One. 2013;8(8):e70628. 25. Davies AH. Vein factors that affect the outcome of femorodistal bypass. Ann R Coll Surg Engl. 1995;77(1):63-6.

36. Perek B, Malińska A, Ostalska-Nowicka D, Puślecki M, Ligowski M, Misterski M, et al. Cytokeratin 8 in venous grafts: a factor of unfavorable long-term prognosis in coronary artery bypass grafting patients. Cardiol J. 2013;20(6):583-91.

26. Zhu YY, Hayward PA, Hare DL, Reid C, Stewart AG, Buxton BF. Effect of lipid exposure on graft patency and clinical outcomes: arteries and veins are different. Eur J Cardiothorac Surg. 2014;45(2):323-8.

37. Yoshikai M, Ito T, Kamohara K, Yunoki J. Endothelial integrity of ultrasonically skeletonized internal thoracic artery: morphological analysis with scanning electron microscopy. Eur J Cardiothorac Surg. 2004;25(2):208-11.

27. Shen LZ, Chen XJ, Chen X, Xu M, Wang LM, Jiang YS. [The morphometry and eNOS expression of radial artery in elderly patients with coronary atherosclerotic heart disease]. Zhonghua Wai Ke Za Zhi. 2010;48(11):825-9.

38. Dashwood MR, Savage K, Tsui JC, Dooley A, Shaw SG, Fernández Alfonso MS, et al. Retaining perivascular tissue of human saphenous vein grafts protects against surgical and distension-induced damage and preserves endothelial nitric oxide synthase and nitric oxide synthase activity. J Thorac Cardiovasc Surg. 2009;138(2):334-40.

28. Wang HY, Meng Y, Lou XJ, Chu Y, Xu XL, Sun HS, et al. [Comparative study on the ultrastructures of radial and internal mammary arteries used for coronary artery bypass grafting]. Zhonghua Bing Li Xue Za Zhi. 2005;34(8):528-32.

39. Tsui JC, Souza DS, Filbey D, Karlsson MG, Dashwood MR. Localization of nitric oxide synthase in saphenous vein grafts harvested with a novel "no-touch" technique: potential role of nitric oxide contribution to improved early graft patency rates. J Vasc Surg. 2002;35(2):356-62.

29. Zou L, Chen XJ, Xu M, Chen W, Wang LM, Huang FH, et al. [Comparative study on the ultrastructure of radial artery in elderly patients underwent coronary artery bypass grafting with diabetes mellitus]. Zhonghua Wai Ke Za Zhi. 2011;49(12):1109-13.

40. Fazan VP, Borges CT, Da Silva JH, Caetano AG, Filho OA. Superficial palmar arch: an arterial diameter study. J Anat. 2004;204(4):307-11.

30. Hubbell MC, Semotiuk AJ, Thorpe RB, Adeoye OO, Butler SM, Williams JM, et al. Chronic hypoxia and VEGF differentially modulate abundance and organization of myosin heavy chain isoforms in fetal and adult ovine arteries. Am J Physiol Cell Physiol. 2012;303(10):C1090-103.

41. Canham PB, Finlay HM, Boughner DR. Contrasting structure of the saphenous vein and internal mammary artery used as coronary bypass vessels. Cardiovasc Res. 1997;34(3):557-67.

31. Li S, Fan YS, Chow LH, Van Den Diepstraten C, van Der Veer E, Sims SM, et al. Innate diversity of adult human arterial smooth muscle cells: cloning of distinct subtypes from the internal thoracic artery. Circ Res. 2001;89(6):517-25.

42. Han S, Yoon SY, Park JM. The anatomical evaluation of internal mammary vessels using sonography and 2-dimensional computed tomography in Asians. Br J Plast Surg. 2003;56(7):684-8.

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Del Negro MS, et al. - Effectiveness ORIGINAL ARTICLEof the endotracheal tube cuff on the trachea: physical and mechanical aspects

Effectiveness of the endotracheal tube cuff on the trachea: physical and mechanical aspects Eficácia do balonete do tubo endotraqueal sobre a traqueia: aspectos físicos e mecânicos

Maira Soliani Del Negro1; Gilson Barreto2, MD; Raíssa Quaiatti Antonelli1; Tiago Antônio Baldasso1; Luciana Rodrigues de Meirelles1, MD, PhD; Marcos Mello Moreira1, PhD; Alfio José Tincani1, MD, MsC, PhD

DOI 10.5935/1678-9741.20140096

RBCCV 44205-1588

Abstract Introduction: The inflation pressure of the endotracheal tube cuff can cause ischemia of the tracheal mucosa at high pressures; thus, it can cause important tracheal morbidity and tracheal microaspiration of the oropharyngeal secretion, or it can even cause pneumonia associated with mechanical ventilation if the pressure of the cuff is insufficient. Objective: In order to investigate the effectiveness of the RUSCH® 7.5 mm endotracheal tube cuff, this study was designed to investigate the physical and mechanical aspects of the cuff in contact with the trachea. Methods: For this end, we developed an in vitro experimental model to assess the flow of dye (methylene blue) by the inflated cuff on the wall of the artificial material. We also designed an in vivo study with 12 Large White pigs under endotracheal intubation. We instilled the same dye in the oral cavity of the animals, and we analyzed the presence or not of leakage in the trachea after the region of the cuff after their deaths (animal sacrifice). All cuffs were inflated at the pressure of 30 cmH2O. Results: We observed the passage of fluids through the cuff in all in vitro and in vivo experimental models. Conclusion: We conclude that, as well as several other cuff

models in the literature, the RUSCH® 7.5 mm tube cuffs are also not able to completely seal the trachea and thus prevent aspiration of oropharyngeal secretions. Other prevention measures should be taken.

Faculdade de Ciências Médicas da Universidade Estadual de Campinas (FCM/Unicamp), Campinas, SP, Brazil. 2 Centro Médico de Campinas (CMC), Campinas, SP, Brazil.

Correspondence address: Alfio José Tincani Universidade Estadual de Campinas-Unicamp/Cidade Universitária Zeferino Vaz - Departamento de Cirurgia Rua Tessália Vieira de Camargo, 126 – Barão Geraldo – Campinas, SP, Brazil - Zip code: 13083-970 Mail box 6111 E-mail: tincani@unicamp.br

Descriptors: Thoracic Duct. Thoracic Wall. Tracheal Stenosis. Respiratory Aspiration of Gastric Contents. Suction. Resumo Introdução: A pressão de insuflação do balonete (cuff) do tubo endotraqueal tanto pode causar isquemia de mucosa traqueal em pressões elevadas, e assim ocasionar morbidade traqueal importante, quanto pode causar microaspiração traqueal de secreção de orofaringe ou, ainda, ocasionar pneumonia associada à ventilação mecânica, caso a pressão do balonete seja insuficiente. Objetivo: A fim de investigar a eficácia do balonete do tubo endotraqueal RUSCH® 7,5mm, este estudo foi desenhado para investigar aspectos físicos e mecânicos do balonete em contato com a traqueia. Métodos: Para isto, foi desenvolvido modelo experimental in vitro para avaliar o escoamento de corante (azul de metileno)

This study was carried out at Universidade Estadual de Campinas (FCM/ Unicamp), Campinas, SP, Brazil.

Article received on July 30th, 2013 Article accepted on July 24th, 2014

No financial support.

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pós-região do balonete. Todos os balonetes foram insuflados na pressão de 30 cmH2O. Resultados: Houve passagem de fluidos pelo balonete em todos os modelos experimentais in vitro e in vivo. Conclusão: Podemos concluir que, assim como diversos outros modelos de balonetes na literatura, balonetes do tubo RUSCH® 7,5mm também não são capazes de vedar completamente a traqueia e com isso prevenir aspiração de secreções orofaríngeas. Outras medidas para a prevenção devem ser tomadas.

Abbreviations, acronyms & symbols ICU IMV OTI PAMV

Intensive care unit Invasive mechanical ventilation Orotracheal intubation Pneumonia associated with mechanical ventilation

pelo balonete insuflado na parede de material artificial. Também foi desenhado estudo in vivo com 12 porcos da raça Large-White sob intubação endotraqueal. Foi instilado o mesmo corante na cavidade oral do animal e após óbito (sacrifício do animal) foi analisada a presença ou não de vazamento deste na traqueia

Descritores: Tubos Torácicos. Parede Torácica. Estenose Traqueal. Aspiração Respiratória de Conteúdos Gástricos. Sucção.

INTRODUCTION

such as tracheitis, tracheomalacia, tracheal stenosis, among others[2,5,9-11]. This concern with the quality of the seal of the cuff is justified because of the risk of microaspiration occurring in critical patients under prolonged OTI, which, associated with a weakened immune system, lead to a high incidence of pneumonia associated with mechanical ventilation (PAMV), responsible for high morbidity and mortality and high hospital costs[12].

The orotracheal intubation (OTI) procedure is used in cases in which invasive mechanical ventilation (IMV) is required, such as in intensive care units (ICU) and some general anesthesia. The first reported use of OTI was described by Dobel[1]. Although it is a routine medical procedure, the OTI can bring numerous complications, including dental fractures, esophageal intubation, selective lung intubation, bronchoaspiration, tracheal injury, mucosal lesions and tracheal stenosis[2-4]. The morbidity associated with OTI is attributed to factors such as size of the tube, pressure of the cuff, movement of the tube or accidental extubation[5,6]. The main goals of the OTI are to ensure the pulmonary gas exchange through IMV and protect the airway from the bronchoaspiration of oral and gastric contents. For this purpose, the endotracheal tube has a cuff that is permanently inflated after intubation on its distal end, isolating and protecting the airway from the digestive pathway[1,3,5]. Tubes and cuffs of various materials and models are in constant improvement in search for a “perfect” model, as the pressure of the endotracheal tube cuff must be able to ensure the passage of adequate pressure volume, through mechanical ventilation, and it must also be sufficient to prevent aspiration of secretions that accumulate on the cuff and, at the same time, cannot compromise the tracheal perfusion. A minimum pressure of 20 cmH2O is recommended so that the aspiration of secretions above the cuff and pneumonia associated to mechanical ventilation can be prevented[7]. The upper limit of the pressure of the cuff associated with the impairment of the tracheal capillary perfusion varies in the literature between 30 and 50 mmHg[8]. This limit is important because excess pressure in the cuff, although apparently increasing the seal with the trachea wall to prevent aspiration, can compromise not only the tracheal perfusion, but can increase the chance of complications in the long term,

Objectives The primary objective of this study was to analyze the effectiveness of the endotracheal tube seal of the RUSCH® cuff on the trachea (at the upper limit of pressure in the cuff: 30 cmH2O) and obtain the physical and mechanical aspects related to the prevention of the flow of secretions. The secondary objective of the study was to measure the actual area that the cylindrical cuff has contact with the tracheal mucosa. METHODS Study Design The design of the experimental study has two aspects: in vitro and in vivo. We used 7.5 mm endotracheal tubes (RUSCH®) in both studies, as they are the most widely used tubes in adults. The measures described have been carried out with the use of a caliper with precision to one-hundredth of a millimeter (Mitutoyo® 530 series), and the data were rounded to the decimal for purposes of calculations. The pressure of the cuff was measured with a precision manometer, VBM® model. Description of the in vitro experiment: WE used the body of a 10 mL plastic syringe as a trachea model, since it has a diameter that approaches the trachea of an adult. The 7.5 mm orotracheal tube was introduced in the trachea model and its cuff was then inflated to the pressure

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of 30 cmH2O confirmed by the manometer. Direct measures were carried out for diameter, perimeter and area of contact of the cuff with the wall of the syringe. The sealing capacity of the cuff to prevent the flow of secretion was tested by applying 3ml of methylene blue diluted in 10 ml of water through the upper portion of the body of the syringe and observing if there was passage of the liquid through the outside of the cuff. The experiment was repeated twenty times and the values recorded. The dye was chosen as a qualitative marker of leakage (microaspiration); thus, there was no concern in measuring the amount of secretion leaked in this study. Description of the in vivo experiment: The experiment was approved by the Committee of Ethics in Animal Experimentation of the Institute of Biology of the University of Campinas (Unicamp), protocol number 2612-1. We used 12 Large White pigs (weighting approximately 30 kg). The animals were already being used for other experimental studies (which did not involve the cardiopulmonary system, aiming at the non-interference on the results, and were used because of ethical issues). The pressure in the cuff was measured with the manometer shortly after intubation and throughout the experiment; when necessary, we adjusted it to 30 cmH2O. For each animal, we injected 3 ml of methylene blue diluted in 10 ml of water into the oral right rima. After remaining in IMV for 3 to 6 hours, the animals were sacrificed with intravenous potassium chloride, and, without being extubated, the trachea was carefully open so that we could visualize the presence or absence of methylene blue below the region where the cuff was inflated (aspiration of contents).

Fig.1 - Cross-sectional area of the tube (A) demonstrates its outer ring and inner cuff. Item B corresponds to the format of the trachea and its perimeter. (C) Cross-sectional area of the endotracheal tube adapted to the tracheal lumen with redundancy channels formed, which can allow the passage of fluids.

Perimeter: considering a circular cross-section in the cuff, the perimeter would be given by the following formula: perimeter = 2 x pi x radius, with a radius of 15.45 mm, obtained by dividing the diameter (30.90mm). Therefore, the perimeter found for the cuff was 97.08 mm (2 x 3.1416 x 15.45). Area of contact of the cuff with the trachea: we measured it through its central portion, parallel to the tracheal wall with the inflated cuff. The contact area of 2.20 mm can be obtained by multiplying the perimeter by the longitudinal extension. Therefore, the area of contact of the cuff was obtained by the formula: area = width x length. That is, area = 20.00 mm x 97.08mm = 213.58mm2 or 21.36cm2. Mass of weight over the area: an atmospheric pressure (atm) is defined as equivalent to the application of 10 tons in an area of 1m2 or 10,000 Kg per 10,000 cm2, or even 1 atm corresponds to 1kg per cm2 of force. Extrapolating these data for the pressure of the cuff on the wall of the trachea, we must consider a cuff inflated to the pressure of 30 cmH2O or 0.03 atmospheric pressure units with contact area of the cuff of 21.36 cm in a 7.5 mm tube. The mass of the section of the trachea in contact with the cuff is given by: 1000 gr/cm2 = 1 atm x 0.03 atm = X gr (X gr = 1000 X 0.03 = 30 gr per cm2), with a contact area of 21.36 cm2 between the cuff and the wall of the trachea; in the area of contact with the cuff, we have a mass equivalent to 30 gr x 21.36 cm2 = 640.8 gr of weight on the trachea.

RESULTS The in vitro study Test of in vitro Instillation of Methylene Blue By externally instilling methylene blue in the upper portion of the inflated balloon, we observed the immediate leakage of the liquid around it (Figure 1). At the end of four minutes of experiment, there was the passage of all the fluid injected in all artificial models. Direct measurements In the analysis of 20 endotracheal tubes, we reached a cuff diameter of 30.90 mm (29.82 to 31.15). The length of the cuff surface parallel to the tube was 2.20 mm (2.00-2.30). Indirect Measurements Pressure Effect Diameter: for the 7.5 mm endotracheal tube, with the pressure in the cuff equivalent to 30cmH2O (or 0.03 atmospheric pressure unit), we found the average measure of its diameter as 30.90 mm.

Contact surface effect Perimeter of the cuff: The average measure of the diameter of a trachea varies with age, gender and race. Himalstein

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& Gallaguer[13] measured, in autopsies, the tracheal diameter of 100 men without any known tracheobronchial abnormalities. Based on these data, we used the mean sagittal diameter of trachea of 16.9 mm[14]. The human trachea measures approximately 12 cm in length, ranging from 9 to 16 cm. Its external diameter measures 23 mm laterally and 18 mm in the anterior-posterior diameter[15], based on the mean internal measurement of 17 mm for an adult, which is obtained applying the formula to calculate the perimeter (2 x pi x radius), with radius equal to 8.5 mm, obtained by dividing the tracheal diameter of 53.41 mm. In comparison with the 7.5 mm endotracheal tube, we have that the perimeter of the inflated cuff at a pressure of 30 cmH2O is 97.08 mm.

There is a uniform distension of the cuff when it is inflated, which does not occur inside the trachea. During the in vitro performance of the experiment, we observed the formation of recesses on the surface of the cuff studied, named “longitudinal channels”. Results of the in vivo study After the sacrifice of the animals with IV KCl, the tracheae were carefully extracted with a margin of 4 cm above and 4 cm below the location of the cuff. Of the 12 pigs studied, there was a bluish dyeing of the mucosa after the cuff (just below it) in 100% of the observed tracheas. As this was a qualitative analysis, the amount of secretion leaked was not measured (Figure 2).

Difference between the measures of the perimeters of the cuff (7.5 mm tube) and the trachea It is given through the subtraction of the perimeter of the cuff from the tracheal perimeter. Therefore, Δ of area = 97.08 – 53.41 = 43.67 mm or 4.37 cm. This means that the inflated cuff measuring 97.08 mm needs to be accommodated within another tube (trachea) that measures only 53.41 mm. After the inflation of the cuff with 0.03 atm pressure, there is a redundancy of 4.37 cm of the plastic that makes up the cuff inside the trachea. Therefore, we conclude that the cuff does not behave the same way inside and outside the trachea.

DISCUSSION The main result of the in vitro study was the maximum leakage of the injected solution in less than 7 minutes. Similar results were found in the study of Dave et al.[13] with similar study design, in which there was the passage of all the liquid injected at the superior part of the artificial trachea above the cuff on all PVC pipes without prior lubrication. The passage (leakage) of secretions after the cuff is a phenomenon that is known and already described in patients under OTI with tubes with high-volume and low pressures. This finding can be explained by the formation of longitudinal channels on the surface of the cuff, which were recognized as responsible for the passage of this secretion, even with the inflated cuff at appropriate pressures[14]. These longitudinal channels are formed from the redundancies of the inflated cuff plastic, which form “tunnels,” with virtual light, which communicate the region just above the cuff with the region just below it, thus allowing the passage of secretions through the cuff [11,14-18]. Longitudinal channels in the wall of the cuff were observed in this in vitro study. And, according to similar studies[16], the result found can also be explained by the formation of these channels. In the in vitro study, we also found secretion in the trachea below the cuff in all animals studied, which corroborates the hypothesis of occurrence of longitudinal channels present in the in vivo study, even with pressures in the upper limit of the safe range against ischemia of the tracheal mucosa (30 cmH2O). A possible solution to ease the passage of secretions by longitudinal channels would be the elevation of the pressure of the cuff. However, concerns in relation to the possible damage caused by this situation are widely discussed, as well as the prolonged permanence of the orotracheal tube. Extrapolating to the clinical setting, the complications to the patients requiring prolonged IMV can be worrisome[19-22]. Some authors consider the maximum pressure of the inflation of the cuff as 25 cmH2O (18.40 mmHg) so that the

Fig. 2 - Porcine trachea isolated with a tracheal tube with cuff (*) inflated at 30cmH2O pressure. The blue dye was introduced in the (proximal) upper region of the inflated cuff. After four minutes, the dye had leaked around the cuff (arrow).

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capillary perfusion can be adequate[5,23]. If pressures greater than 25-30 mmHg are maintained for a certain time, damage can be caused. If a continuous pressure equal to or higher than 67.5 cmH2O (50 mmHg) is applied against the trachea during 15 minutes, the epithelium, tracheal membrane and cartilage can be destroyed. Thus, there must be a strict and frequent control of this pressure by the constant and continued measurement through a manometer. According to Marjot[24], a 38mmHg pressure in the cuff causes the obstruction of blood flow in the mucosa, and the pressure of the cuff must remain lower than 30mmHg to avoid this risk. Other authors[2,5,6,9,19,20] claim that damage caused to the trachea is inevitable when the pressure in the cuff is higher than the perfusion pressure of the tracheal mucosa (20-35 mmHg); however, there is also the concern about insufficient inflation, which is also harmful, since the aspiration of oropharyngeal or gastric contents may occur. Traumas to the trachea, such as destruction of the epithelium, ulceration, stenosis, dilation and rupture, are associated to the sum of the pressure exerted by the cuff on the tracheal mucous membrane, intubation time and contact area of the cuff with the trachea[21]. For some authors[2,3], the pressure from the side walls is limited at 30 cmH2O or 22 mmHg. Luna et al.[4] reported cases of patients who suffered swelling and rupture of the trachea despite the careful monitoring of the pressure of the cuff. According to the authors, the pressure in the cuff should not exceed 25 mmHg in patients with IMV that use a cannula with high-volume and low pressure. They also claim that the exact capillary pressure is not known, since it is impossible to measure it in normal conditions. On the other hand, the authors mention two known methods to calculate the capillary pressure of the trachea with approximate pressure of 25 mmHg and indirect functional measurement of the capillary pressure of approximately 17 mmHg[25,26]. An injury caused by the pressure of the inflated cuff under the lining of the tracheal mucosa leads (in less than 48 hours) to varying degrees of inflammation and edema of the epiglottis and vocal cords[23,24]. Experimental studies demonstrate ulceration, even necrosis, of the larynx in the cases of use greater than 48 hours[21]. Similarly, lower pressures were tested, such as 10cmH2O, resulting in important leakages of oropharyngeal secretions[27]. An appropriate limit for the minimum acceptable pressure so there is no microaspiration is still discussed, and the pressure of 25 cmH2O was suggested by Lomholt et al.[28] as the minimum to prevent it. This study has some limitations. In the in vitro model, although the diameter is similar to that of an adult trachea, the wall of the trachea is not rigid as the body of the syringe. The viscosity of the methylene blue is also not exactly the same as the oropharyngeal secretion. However, the characteristic of viscosity and composition of the secretions vary greatly

between patients (e.g. different comorbidities, medications with anti-drooling effect, presence of vomiting, infection of the oral cavity and even enteral diet). For this reason, we chose to use only methylene blue. We also did not compare the use of positive expiratory pressure or lubricants around the cuff in this study. According to Lucangelo et al.[14], positive expiratory pressure may slow secretion leakage in in vitro models, and Young et al.[29] also showed that the rate of secretion leakage by the cuff is inversely proportional to the pressure of the cuff, varying with different positive expiratory pressures. Authors such as Blunt et al.[30] and Sanjay et al.[31] developed in vitro models to evaluate the effectiveness of using gel lubricants to fill the longitudinal channels and thus prevent or slow the leakage of secretion by the cuff. However, Dave et al.[13] say that this effect is transient and is lost in 24-120 hours. The authors also suggest that, to assess the quality of the seal of the cuff, the static in vitro models may be more suitable without using artifacts such as positive expiratory pressure or lubricants, because the difference between the effectiveness of the seals is more evident without this interference. A limitation of the in vivo model consists in the fact that we could have checked the pressure of the cuff at shorter time intervals in order to evaluate pressure change over time, since a pressure less than 25 cmH2O would be responsible for the leakage of fluids. On the other hand, intermittent measurements of the pressure of the cuff, with greater intervals, are closer to the routines in Intensive Care Units. CONCLUSION Similar to other works regarding the quality of the seal of the cuff, there was the passage of fluid in this study both in the in vitro and in vivo models for the cuff inflated with pressures considered as ideal. Given this result, we can conclude that inflated cuffs with pressure regarded as ideal to prevent the ischemia of the tracheal mucosa are not able to completely seal the trachea against aspiration of oropharyngeal secretions, which may pose risks to patients intubated or under general anesthesia in lengthy surgeries. Different models of endotracheal tubes and cuff measures and formats, such as continuous supraglottic aspiration, have been used; however, an ideal model is yet to emerge. While the ideal cuff is not developed, it is of great importance to take all precautions for the prevention of microaspiration, as well as the optimization of the time of intubation. Conflict of Interest The authors have no conflicts of interest. The choice for RUSCH速 tubes occurred because of its use in the Service where the study was conducted. No materials were donated for the completion of the study.

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12. Joseph NM, Sistla S, Dutta TK, Badhe AS, Parija SC. Ventilator-associated pneumonia: a review. Eur J Intern Med. 2010;21(5):360-8.

Authorsâ&#x20AC;&#x2122; roles & responsibilities MSDN GB RQA TAB LRM MMM AJT

Execution, analysis, writing and editing Preparation, supervision, execution, analysis, writing and editing Preparation, execution, analysis and writing Preparation, execution, analysis and writing Analysis and/or interpretation of data, conception and study design, conduct of procedures and/or experiments Preparation, supervision, execution, analysis, writing and editing Preparation, supervision, execution, analysis, writing and editing

13. Dave MH, Koepfer N, Madjdpour C, Frotzler A, Weiss M. Tracheal fluid leakage in benchtop trials: comparison of static versus dynamic ventilation model with and without lubrication. J Anesth. 2010;24(2):247-52. 14. Lucangelo U, Zin WA, Antonaglia V, Petrucci L, Viviani M, Buscema G, et al. Effect of positive expiratory pressure and type of tracheal cuff on the incidence of aspiration in mechanically ventilated patients in an intensive care unit. Crit Care Med. 2008;36(2):409-13.

REFERENCES

15. Young PJ, Burchett K, Harvey I, Blunt MC. The prevention of pulmonary aspiration with control of tracheal wall pressure using a silicone cuff. Anaesth Intensive Care. 2000;28(6):660-5.

1. Dobell AR. The origins of endotracheal ventilation. Ann Thorac Surg. 1994;58(2):578-84. 2. Mehta S. Tracheal tube cuff pressure. Anaesthesia. 1989;44(12):1001-2.

16. Dave MH, Frotzler A, Spielmann N, Madjdpour C, Weiss M. Effect of tracheal tube cuff shape on fluid leakage across the cuff: an in vitro study. Br J Anaesth. 2010;105(4):538-43.

3. Mehta S, Mickiewicz M. Pressure in large volume, low pressure cuffs: its significance, measurement and regulation. Intensive Care Med. 1985;11(5):267-72.

17. Pavlin EG, VanNimwegan D, Hornbein TF. Failure of a high-compliance low-pressure cuff to prevent aspiration. Anesthesiology. 1975;42(2):216-9.

4. Luna CM, Legarreta G, Esteva H, Laffaire E, Jolly EC. Effect of tracheal dilatation and rupture on mechanical ventilation using a low-pressure cuff tube. Chest. 1993;104(2):639-40.

18. Macrae W, Wallace P. Aspiration around high-volume, low-pressure endotracheal cuff. Br Med J (Clin Res Ed). 1981;283(6301):1220.

5. Bernhard WN, Yost L, Turndorf H, Danziger F. Cuffed tracheal tubes--physical and behavioral characteristics. Anesth Analg. 1982;61(1):36-41.

19. Windsor HM, Shanahan MX, Cherian K, Chang VP. Tracheal injury following prolonged intubation. Aust N Z J Surg. 1976;46(1):18-25.

6. Nordin U. The trachea and cuff-induced tracheal injury. An experimental study on causative factors and prevention. Acta Otolaryngol Suppl. 1977;345:1-71.

20. Lewis FR Jr, Schiobohm RM, Thomas AN. Prevention of complications from prolonged tracheal intubation. Am J Surg. 1978;135(3):452-7.

7. Sole ML, Su X, Talbert S, Penoyer DA, Kalita S, Jimenez E, et al. Evaluation of an intervention to maintain endotracheal tube cuff pressure within therapeutic range. Am J Crit Care. 2011;20(2):109-17.

21. Servin SO, Barreto G, Martins LC, Moreira MM, Meirelles L, Neto JA, et al. Atraumatic endotracheal tube for mechanical ventilation. Rev Bras Anestesiol. 2011;61(3):311-9.

8. Benumof JL, Cooper SD. Quantitative improvement in laryngoscopic view by optimal external laryngeal manipulation. J Clin Anesth. 1996;8(2):136-40.

22. Lima LC, Avelar SF, Westphal FL, Lima ILQ. Lung nodule, tracheal stenoses and coronary disease: how to approach when are all associated to? Rev Bras Cir Cardiovasc. 2007;22(3):359-61.

9. Keller C, Brimacombe J, Boehler M, Loeckinger A, Puehringer F. The influence of cuff volume and anatomic location on pharyngeal, esophageal, and tracheal mucosal pressures with the esophageal tracheal combitube. Anesthesiology. 2002;96(5):1074-7.

23. Conti M, Pougeoise M, Wurtz A, Porte H, Fourrier F, Ramon P, et al. Management of postintubation tracheobronchial ruptures. Chest. 2006;130(2):412-8.

10. Cooper JD, Grillo HC. The evolution of tracheal injury due to ventilatory assistance through cuffed tubes: a pathologic study. Ann Surg. 1969;169(3):334-48.

24. Marjot R. Pressure exerted by the laryngeal mask airway cuff upon the pharyngeal mucosa. Br J Anaesth. 1993;70(1):25-9. Erratum in: Br J Anaesth. 1993;70(6):711.

11. Seegobin RD, van Hasselt GL. Endotracheal cuff pressure and tracheal mucosal blood flow: endoscopic study of effects of four large volume cuffs. Br Med J (Clin Res Ed). 1984;288(6422):965-8.

25. PetĂĄk F, Janosi TZ, Myers C, Fontao F, Habre W. Impact of elevated pulmonary blood flow and capillary pressure on lung responsiveness. J Appl Physiol (1985). 2009;107(3):780-6.

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26. Iglesias JL, LaNoue JL, Rogers TE, Inman L, Turnage RH. Physiologic basis of pulmonary edema during intestinal reperfusion. J Surg Res. 1998;80(2):156-63.

29. Young PJ, Pakeerathan S, Blunt MC, Subramanya S. A lowvolume, low-pressure tracheal tube cuff reduces pulmonary aspiration. Crit Care Med. 2006;34(3):632-9.

27. Dullenkopf A, Gerber A, Weiss M. Fluid leakage past tracheal tube cuffs: evaluation of the new Microcuff endotracheal tube. Intensive Care Med. 2003;29(10):1849-53.

30. Blunt MC, Young PJ, Patil A, Haddock A. Gel lubrication of the tracheal tube cuff reduces pulmonary aspiration. Anesthesiology. 2001;95(2):377-81.

28. Lomholt N. A device for measuring the lateral wall cuff pressure of endotracheal tubes. Acta Anaesthesiol Scand. 1992;36(8):775-8.

31. Sanjay PS, Miller SA, Corry PR, Russell GN, Pennefather SH. The effect of gel lubrication on cuff leakage of double lumen tubes during thoracic surgery. Anaesthesia. 2006;61(2):133-7.

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Fernandes AMS, et al. - Influence of valve prosthesis type on early mortality ORIGINAL ARTICLE in patients undergoing valve surgery

Influence of valve prosthesis type on early mortality in patients undergoing valve surgery A influência da escolha da prótese valvar sobre a mortalidade intra-hospitalar no pós-operatório em pacientes submetidos à cirurgia valvar

André Mauricio S. Fernandes1, MD, MsC; Felipe da Silva Pereira1; Larissa Santana Bitencourt1, MD; Agnaldo Viana Pereira Neto1, MD; Gabriel Barreto Bastos1; André Rodrigues Durães1, MD, PhD; Roque Aras Jr1, MD, PhD; Igor Nogueira Lessa1, MD

DOI 10.5935/1678-9741.20140035

RBCCV 44205-1589

Abstract Objective: To evaluate the influence of the type of prosthesis in-hospital mortality in the post-operative period in patients who had valve replacement. Methods: A cross-sectional data, such as gender, origin, age, etiology, echocardiograph data, the type of surgery performed and the prosthesis used in cases of valve replacement were analyzed retrospectively. Results: We reviewed 353 charts of patients who underwent valve replacement surgery. The mean age was 41.87±17.9 years. Regarding gender, 52.8% were female. As for the origin, 61.1% came from small cities within the state. Of all patients, 58.5% suffered from rheumatic disease. Assessing the type of prosthesis implanted, 70% held replace by bioprosthesis and 30% metallic. The hospital mortality in this study was 11%, with no significant difference between the types of prosthesis utilized. Conclusion: The type of implant used had no effect on in-hospital mortality.

Resumo Objetivo: Avaliar a influência do tipo de prótese na mortalidade intra-hospitalar no período de pós-operatório imediato nos pacientes que fizeram substituição de válvula. Métodos: Estudo transversal, em que dados, como sexo, origem, idade, etiologia, dados ecocardiográficos, o tipo de cirurgia realizada e da prótese utilizada em casos de substituição de válvula foram analisadas retrospectivamente. Resultados: Foram revisados 353 prontuários de pacientes que realizaram cirurgia de troca valvar. A idade média foi de 41,87±17,9 anos. Em relação ao gênero, 52,8% eram do sexo feminino. Quanto à origem, 61,1% vieram de cidades do interior do estado. Do total de pacientes, 58,5% eram portadores da doença reumática. Avaliando o tipo de prótese implantada, 70% realizou troca por bioprótese e 30% metálica. A mortalidade hospitalar desse estudo foi de 11%, não havendo diferença significativa entre o tipo de prótese utilizada. Conclusão: O tipo de prótese utilizada não influenciou na mortalidade intra-hospitalar.

Descriptors: Mortality. Heart Valve Diseases. Heart Valve Prosthesis.

Descritores: Mortalidade. Doenças das Valvas Cardíacas. Próteses Valvulares Cardíacas.

Hospital Ana Nery (HAN), Salvador, BA, Brazil.

Correspondence address: Felipe da Silva Pereira Rua Saldanha Marinho - Caixa d’Água - Salvador, BA, Brazil Zip Code: 40320-010 E-mail: fs.pereira@globomail.com

This study was carried out at Hospital Ana Nery (HAN), Salvador, BA, Brazil.

Article received on August 20th, 2013 Article accepted on December 11th,2013

No financial support.

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Fernandes AMS, et al. - Influence of valve prosthesis type on early mortality in patients undergoing valve surgery

There are few studies evaluating the mortality in patients with heart valve disease. The focus of this study is to evaluate the impact of the choice of prosthesis on in-hospital mortality rate in patients with rheumatic and non-rheumatic heart disease who underwent surgical valve replacement.

Abbreviations, acronyms and symbols MS RD SD SPSS

Ministry of Health (acronym in Portuguese) Rheumatic Disease Standard Deviation Statistical Package for the Social Sciences

METHODS Analytical cross-sectional study with convenience sampling of patients who underwent valve replacement surgery during a period of three years at Ana Nery Hospital, Salvador, Bahia, Brazil. All data were obtained from medical records. Data analysis was performed based on the guidelines for reporting morbidity and mortality after cardiac valve interventions[9]. Thirty-five patients were excluded for lack of recorded data; thus, the total sample was 353. Data were analyzed using SPSS version 17.0. Continuous variables had their normality tested with the Kolmogorov-Smirnov test. To compare the means, the T test was used for normally distributed variables. The chi-square test was used to compare categorical variables. The p value adopted as statistically significant was Pâ&#x2030;¤0.05. The project was approved by the Ethics Committee of Ana Nery Hospital under the 59/10 protocol.

INTRODUCTION Valvular heart disease is a major public health problem. Since the 50s, the prevalence of valve disease in developed countries has been varying from rheumatic etiology to degenerative valve disease[1]. In the early twentieth century, rheumatic disease (RD) was a major cause of morbidity and mortality among young people in developed and developing countries[2,3], affecting them in a similar way. This pattern changed due to several factors, including early diagnosis, appropriate treatment of RD and also due to increased life expetancy leading to valve disease in older individuals. Rheumatic disease, even nowadays, has a high prevalence in developing countries such as Brazil, which is an important cause of cardiovascular disease and is responsible for high costs to the public health system. According to data provided by MS, during the year 2011, there were 5,512 hospital admissions due to acute rheumatic fever and 8,127 presenting with rheumatic valvular disease[4]. The postoperative in-hospital mortality rate is very variable, mostly due to the severity of hospitalized patients and the degree of experience of the surgical team. According to other studies, the mortality rate varies between 1% and 15%[1,5-8]. After 40 years of experience with valve replacement surgery in the country, the decision by the most appropriate type of prosthesis to be implanted in surgery is still controversial and sometimes complicated, especially for patients coming from rural areas or small towns. There is not an ideal substitute. There is a low risk of thromboembolic events and bleeding in the use of bioprosthesis, but its durability is short. On the other hand, the metallic prosthesis may offer longer duration, but with greater risk for such events [9]. Marchand et al.[10] and MyKen et al.[11] demonstrated satisfactory progress in the survival of patients after 14 and 15 years, respectively, bioprosthesis structural dysfunction free in both atrioventricular and aortic site.

RESULTS The total sample studied was 353 patients undergoing valve replacement surgery, and 73 of these were submitted to valve replacement and valvuloplasty. The male sex represented 49.6% (n=175) of them and 50.4% (n=178) were female. The age of the study population ranged from 6 to 82 years and the average age was 41.87Âą17.9 years. We observed a greater number of individuals from the contryside or rural areas (n=216, 61.2%) compared to the capital (n=137, 38.8%) (demographic data - Table 1). We also observed a total of 698 affected valves, 282 (40.4%) were mitral, 214 (30.7%) aortic, 183 (26.2%) tricuspid and 19 (2.7%) were pulmonary valves. Among them, 53 (7.6%) showed stenosis, 461 (66%) had insufficiency and 184 (26.4%) had double lesion. The patients were also divided according to their main mechanism of valve lesion: 204 (57.8%) had rheumatic disease as the main cause for valve disease and 134 (38%) had valvular disease due to other causes, such as prolapse, secondary to ischemia or degenerative disease, and 15 (4.2%) had no definite etiology. Regarding the type of prosthesis used, 70% (n=247) were replaced by bioprosthesis and 30% (n=106) by metal prosthesis. The preference to use bioprostheses was observed in all age groups (Figure 1).

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Table 1. Demographics Classification Gender Male Female Age 0-20 years 21-30 years 31-40 years 41-50 years 51-60 years > 60 years Etiology of valvular heart disease Rheumatic disease Non-rheumatic disease Lost data Prosthesis Bioprosthesis Metallic prosthesis Affected valve Mitral valve Aortic valve Mitral and aortic valve

175 178

49.6 50.4

40 68 53 74 50 68

11.3 19.3 15 21 14.2 19.2

204 134 15

57.8 38 4.2

247 106

70 30

194 98 61

55 27.8 17.2

Fig. 1 - Distribution of valve prostheses by age.

The overall mortality was 11% (n=39), and we did not observe difference between the type of prosthesis on overall mortality. The mortality caused by mechanical valve in comparison with bioprosthesis was 30.7% (n=12) x 69.3% (n=27), respectively, P=0.915. When analyzing only patients with rheumatic disease, we could not also observe a statistically significant difference in mortality rates between the metal prosthesis x bioprosthesis, 33.3% (n=3) x 66.7% (n=6), respectively, P=0.586. The mean age ± SD for the patients who died was 54.49±21.9 years, versus 41.19±16.8 years of those who were discharged, P=0.000 (Figure 2). Among the patients who died, 33 were submitted to only one valve replacement. Therefore, there was no impact of the double valve replacement on mortality. In relation to the location of valve replacement surgery, the results are shown in Figure 3.

Fig. 2 - Number of deaths vs. Age group.

DISCUSSION There was a high prevalence of rheumatic valve disease (58.5%) in this study, and these data are consistent with previous data on rheumatic disease, which is a major cause of heart disease in developing countries[10]. There was no effect on mortality regarding the type of implant used in valve replacement surgery.

Fig. 3 - Number of deaths vs. Valve site.

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The postoperative mortality rate is very variable and is influenced by many factors, such as multiple replacement valve, affected site, reoperation and presence of other associated procedures. This study demonstrated a 10.6% mortality rate, which is in agreement with the literature data ranging from 1% to 15%[12,13]. The average age of patients who died was 54.4±21.5 years, higher than the total study sample (40.40±16.8 years), P=0.001. This difference is probably due to valves with more severe lesions, associated or not with higher presence of comorbidities in older population, since there was no association between the type of prosthesis and mortality when age was taken into consideration. Patients who underwent mitral valve replacement had a higher mortality, regardless of the type of prosthesis used. This finding is consistent with what is reported in the literature[7,14,15]. The impact of the choice of valve prosthesis for patients who have rheumatic etiology has not been established. The use of bioprosthesis in this population influences the late mortality, since it may be a new procedure after a few years, a previous study shows mortality similar to the first surgery (1% to 15%)[16]. However, Cen et al.[17] published in 2001 that the choice of the type of implanted prosthesis did not statistically interfere in survival of patients undergoing valve replacement in 10 years. In our study, we observed that victims of rheumatic sequel were young adults, especially women, resulting in socio-economic repercussions as increased costs of public health and the reduction of labor input. This study shows that the most frequent injury was the valve regurgitation (66.2%) followed by double lesion (25.9%) and stenosis (7.9%), in disagreement with the literature where it is shown a prevalence of stenotic lesions . However, this is a difficult comparison to make due to the scarcity of data on the prevalence of specific lesions, especially in rheumatic disease[18]. It is generally very difficult to assess these patients due to poor adherence to treatment, since their families need to take long trips, dealing with cost of food and stay, in a scenario of a limited family budget. Unfortunately, this is a negative milestone for the treatment with impact on the choice of the prosthesis and possible consequences for a later outcome[19]. The higher prevalence of bioprosthesis in the present study can be justified by the large number of countryside patients without adequate specialized medical services, a fact that often leads to poor adherence to treatment and prevent the institution from anticoagulant therapy. The type of prosthesis did not have influence on in-hospital mortality in the study population, however, it can be considered an important prognostic factor for late mortality in patients suffering from valvular diseases with high

prevalence of rheumatic etiology. Therefore, cohort studies with similar populations, especially in developing countries, should be encouraged. Authors’ roles & responsibilities AMSF FSP LSB AVPN GBB ARD RAJ INL

Main author Co-author, collection of material, statistical analysis Co-author Co-author, references research Medical record survey, collection of material, co-author Co-author, references research Co-author, references research Co-author, references research

REFERENCES

1. Iung B, Vahanian A. Epidemiology of valvular heart disease in the adult. Nat Rev Cardiol. 2011;8(3):162-72. 2. Soler-Soler J, Galve E. Worldwide perspective of valve disease. Heart. 2000;83(6):721-5. 3. Vahanian A, Baumgartner H, Bax J, Butchart E, Dion R, Filippatos G, et al; Grupo de Trabajo sobre el Tratamiento de las Valvulopatías de la Sociedad Europea de Cardiología. Guidelines on the management of valvular heart disease. Rev Esp Cardiol. 2007;60(6):1e-50e. 4. Brasil. Ministério da Saúde. DATASUS. Informações de Saúde. Mortalidade, 2011. Brasília: Ministério da Saúde;2012. 5. Feguri GR, Macruz H, Bulhões D, Neves A, Castro RM, Fonseca L, et al. Aortic valve replacement with different types of prosthesis: are there differences in the outcomes during hospital phase? Rev Bras Cir Cardiovasc. 2008;23(4):534-41. 6. Almeida AS, Picon PD, Wender OC. Outcomes of patients subject to aortic valve replacement surgery using mechanical or biological prostheses. Rev Bras Cir Cardiovasc. 2012;26(3):326-37. 7. Stassano P, Di Tommaso L, Monaco M, Iorio F, Pepino P, Spampinato N, et al. Aortic valve replacement: a prospective randomized evaluation of mechanical versus biological valves in patients ages 55 to 70 years. J Am Coll Cardiol. 2009;54(20):1862-8. 8. Astor BC, Kaczmarek RG, Hefflin B, Daley WR. Mortality after aortic valve replacement: results from a nationally representative database. Ann Thorac Surg. 2000;70(6):1939-45. 9. Pomerantzeff PM, Brandão CM, Cauduro P, Puig LB, Grinberg M, Tarasoutchi F, et al. Fisics-Incor bovine pericardial bioprostheses: 15 year results. Heart Surg Forum. 1998;1(2):130-5.

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10. Marchand MA, Aupart MR, Norton R, Goldsmith IR, Pelletier LC, Pellerin M, et al. Fifteen-year experience with the mitral Carpentier-Edwards PERIMOUNT pericardial bioprosthesis. Ann Thorac Surg. 2001;71(5 Suppl):S236-9.

15. Silberman S, Oren A, Dotan M, Merin O, Fink D, Deeb M, et al. Aortic valve replacement: choice between mechanical valves and bioprostheses. J Card Surg. 2008;23(4):299-306. 16. Brandão CMA, Pomerantzeff PMA, Souza LR, Tarasoutchi F, Grimberg M, Oliveira SA. Fatores de risco para mortalidade hospitalar nas reoperações valvares. Rev Bras Cir Cardiovasc. 2002;17(3):236-41.

11. Mykén P, Bech-Hanssen O, Phipps B, Caidahl K. Fifteen years follow up with the St. Jude Medical Biocor porcine bioprosthesis. J Heart Valve Dis. 2000;9(3):415-22. 12. Pomerantzeff PM, Barbosa GV, de Sousa Filho BS, Brandão CM, Ribeiro EJ, Costa FD, et al. Guidelines for surgery in heart valve diseases. Arq Bras Cardiol. 2004;82(Suppl 5):22-33.

17. Cen YY, Glower DD, Landolfo K, Lowe JE, Davis RD, Wolfe WG, et al. Comparison of survival after mitral valve replacement with biologic and mechanical valves in 1139 patients. J Thorac Cardiovasc Surg. 2001;122(3):569-77.

13. Bottio T, Rizzoli G, Caprili L, Testolin L, Thiene G, Gerosa G. Biological versus mechanical aortic prosthesis? A nineteen-year comparison in a propensity-matched population. J Heart Valve Dis. 2005;14(4):493-500.

18. Fernandes AM, Bitencourt LS, Lessa IN, Viana A, Pereira F, Bastos G, et al. Impact of socio-economic profile on the prosthesis type choice used on heart surgery. Rev Bras Cir Cardiovasc. 2012;27(2):211-6.

14. Filsoufi F, Chikwe J, Castillo JG, Rahmanian PB, Vassalotti J, Adams DH. Prosthesis type has minimal impact on survival after valve surgery in patients with moderate to end-stage renal failure. Nephrol Dial Transplant. 2008;23(11):3613-21.

19. Gus I, Zaslavsky C, Seger JM, Strehl Machado R. Epidemiology of rheumatic fever. A local study. Arq Bras Cardiol. 1995;65(4):321-5.

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Portugal IBM,ORIGINAL et al. - Distribution of saphenous vein valves and its pratical ARTICLE importance

Distribution of saphenous vein valves and its pratical importance Distribuição das válvulas da veia safena magna e sua importância prática

Isabella Batista Martins Portugal1; Igor de Lima Ribeiro1; Célio Fernando de Sousa-Rodrigues1, PhD; Rodrigo Freitas Monte-Bispo1, MsC; Amauri Clemente da Rocha1, MsC

DOI 10.5935/1678-9741.20140038

RBCCV 44205-1590

Abstract Objective: Among the veins used as a graft in myocardial revascularizations and ends, great saphenous vein is the most used. Knowing the presence and location of valves has great importance when evaluating the surgical anatomy of the great saphenous vein. Despite major surgical application and many works involving great saphenous vein, the number of valves present in it from the saphenous hiatus to the medial epicondyle of the femur is still described inaccurately. The objective of this study is to quantify the valves of the great saphenous vein from the saphenous hiatus to the medial epicondyle of the femur to determine the best portion of the great saphenous vein to perform revascularization surgeries. Methods: This is a crosssectional observational study in which it was analyzed great saphenous vein extracted from 30 cadavers. It was measured the length of the veins; (diameter) at its proximal, middle and distal, quantifying the number of valves in each one and the total number of valves at the great saphenous vein. Results: The frequency of valves in the great saphenous vein taken from the medial epicondyle of the femur to the saphenous hiatus was 4.82, ranging between 2 and 9. Moreover, there is a

significant difference in the number of valves in the proximal and distal relative to the average. Conclusion: the median and distal portions of the saphenous vein in the thigh, are the best options for the realization of bridges due to the fact that these portions have fewer valves which therefore would tend to decrease the risk of complications connected with the valves in these grafts.

Universidade Estadual de Ciências da Saúde de Alagoas (UNCISAL), Maceió, AL, Brazil.

Correspondence address: Isabella Batista Martins Portugal Department of Descriptive and Topographic Anatomy Universidade Estadual de Ciências da Saúde de Alagoas (UNCISAL) Rua Doutor Jorge de Lima, 113 - Trapiche da Barra, Maceió, AL, Brazil Zip code: 57010-382 E-mail: isabellabmportugal@gmail.com

Descriptors: Venous Valves. Saphenous Vein. Myocardial Revascularization. Resumo Objetivo: Dentre as veias empregadas para revascularizações do miocárdio e de extremidades, a veia safena magna é a mais utilizada. Conhecer a presença e localização de válvulas é de grande importância quando se avalia a anatomia cirúrgica da veia safena magna. Apesar de grande aplicação cirúrgica e de muitos trabalhos envolvendo a veia safena magna, o número de válvulas presente nela desde o hiato safeno até o epicôndilo medial do fêmur ainda é descrito de forma imprecisa. O objetivo

This study was carried out at Universidade Estadual de Ciências da Saúde de Alagoas (UNCISAL), Maceió, AL, Brazil. Financial support: Scientific Initiation scholarship funded by Fundação de Amparo à Pesquisa do Estado de Alagoas (FAPEAL) from April/2012 to March/2013.

Article received on July 15th, 2013 Article accepted on December 2nd, 2013

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Portugal IBM, et al. - Distribution of saphenous vein valves and its pratical importance

Foram realizadas as medidas das variáveis do comprimento das veias; (diâmetro) em suas porções proximal, média e distal; quantificação do número de válvulas nestas e número de válvulas total na veia safena magna. Resultados: A frequência de válvulas da veia safena contadas desde o epicôndilo medial do fêmur até o hiato safeno foi de 4,82, podendo variar entre 2 e 9. Além disso, houve diferença significante do número de válvulas da porção proximal em relação à média e distal. Conclusão: As porções média e distal da veia safena magna na coxa são as melhores opções para a realização de pontes em decorrência do fato destas porções terem menor quantidade de válvulas o que, portanto, tenderia a diminuir o risco de complicações relacionadas as válvulas nestes enxertos.

Abbreviations, acronyms & symbols CPB DM GSV LCS LITA MAA UNCISAL

Cardiopulmonary bypass Mean diameter Great Saphenous Vein Left coronary system Left internal thoracic artery Without ascending aorta State University of Health Sciences of Alagoas

do presente trabalho é quantificar as válvulas da veia safena magna desde o hiato safeno até o epicôndilo medial do fêmur para determinar a melhor porção da veia safena magna para a realização de cirurgias de revascularização. Métodos: Este é um estudo transversal e observacional em que foram analisadas veias safena magna extraídas de 30 cadáveres.

Descritores: Válvulas Venosas. Revascularização Miocárdica. Veia Safena.

INTRODUCTION

role of valves, the saphenofemoral junction, for example, is to prevent the flow of popliteal[4], or femoral veins. This vein begins above the medial malleolus, ascends obliquely, and passes postero - medially to the medial condyle of the tibia and femur and along the medial aspect of the thigh through the saphenous gap[5]. It has numerous valves that are irregularly distributed throughout its length[6]. The GSV has 10 to 12 valves, which are more numerous than the leg at the thigh. These valves are usually located just below the veins sections[7]. The blood drained by the venous system of the lower limbs flows back to the heart through the thick veins and is maintained by unidirectional valves, usually bicuspid, which close as its contents move toward the center vein[8]. Despite extensive surgical application and many works involving the GSV, the number of existing valves from the saphenous hiatus to the medial epicondyle of the femur is further described inaccurately. The objective of this study is to quantify the valves of the GSV from the saphenous hiatus until the medial epicondyle of the femur, dividing the GSV into three regions, comparing the number of valves between them and indicating the portion with fewer valves, thus determining the best portion GSV for performing CABG surgeries.

Among the materials used for revascularization, the veins can be used in various parts of the body. Among them, the great saphenous vein (GSV) is the first choice. Its use as an implant during coronary artery bypass surgery and lack of being affected by varicose disease has aroused the interest of researchers. This vessel remains an essential component in strategies for coronary artery bypass grafting in humans. The vessel is used alone or in combination with arterial grafts and has the advantage of being available autologous vascular tissue in most patients in need of such surgeries[1]. Its use in composite graft with the left internal thoracic artery (LITA) could allow complete revascularization of the left coronary system (LCS) without a cardiopulmonary bypass (CPB) and without ascending aorta (MAA) in order to reduce some risks and complications in the immediate postoperative period. The autologous saphenous vein also remains a nearly ideal prosthetic element be low the inguinal ligament. That, depending on the outcome of patients in the progression of atherosclerotic disease especially in the revascularization of the tibia arteries, because they tolerate more flow limit[2]. Knowledge of the presence and location of valves is of great importance when assessing the surgical anatomy of the GSV. Generally, the valves are located along the vein and immediately below the mouth of major tributaries. Almost always, one or two valves are present in its termination or mouth. The GSV has often an ostial or ostial valve and a subostial valve. Knowledge of the presence of these valves makes us better understand the pathophysiology of trunk varicose veins of the GSV, since insufficient ostia valves can cause the appearance of these anomalies[3]. Another important

METHODS In the transversal method and observational study, great saphenous veins were taken from 30 cadavers during autopsies at Alagoas Services and analyzed. These veins were excluded from the corpses with disorders that brought certainty to the study, namely anemia, varicose veins, previous surgery, deformities, obesity and mellitus diabetes. After approval from the Ethics Committee in Research of the Universidade

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Estadual de Ciências da Saúde de Alagoas (UNCISAL), and the signing of consent from the statutory bodies responsible, we measured the lengths of the thighs and their diameters in their proximal, middle and distal portions. After this, the dissection of the GSV by traditional techniques was performed by making a long single incision along the venous path from the saphenous hiatus to the medial epicondyle of the femur (Figure 1). The ends of the veins were labeled with cotton thread at the proximal long and short on the distal. They were then identified and stored in a refrigerator.

and 4.78 mm from the right, the left middle portion was 4.05 mm right and 3.86 mm, DM left distal portion is 3.42 mm and 3.23 mm from the right. Analysis of the distribution of valves between the portions of the veins was performed by ANOVA with Tukey post-test. In both the left and the right, there was no significant difference in the number of valves between the middle and distal portions. However, there was significant difference in the number of valves in the proximal and distal relative to the average. Analysis of the distribution of valves between the left and right proximal portions was made by the student’s t test and no significant result (P (bilateral)=0.64) with a confidence interval (95%) 0.33 to 0.53. The sample size is 30 for each side. Analysis of the distribution of valves between the mean left and right portions was made by the student’s t test, with no significant result (P (bilateral)=0.88) with a confidence interval (95%) 0.42 to 0.48. Analysis of the distribution valve between the left and right distal portions and was performed by the student’s t test showed no significant result (P (bilateral)=0.1966) with a confidence interval (95%) 0.59 to 0.12. A linear regression analysis of the number of valve relative to the thigh length, diameter, length of the thigh vein and vein diameter were not significant (P=0.08), with the multiple correlation coefficient 0.32. No statistical significance was related to gender (Table 2). The sample size was 21 saphenous veins in males and 9 in females, with 95 % confidence interval (Diff between averages): 1.37 to 1.66. The length of the saphenous vein from the medial epicondyle of the femur to the saphenous hiatus divided by the number of valves 68 mm in males and 59 mm in females. Sample distribution and number of valves per age group are shown in Table 3. The analysis of the distribution valves for age was performed using Pearson correlation. No significance was found between age and distribution of valves in both GSV left (r(Pearson)=0.2651, (P)=0.1567) and in the right (r (Pearson)=0.0806, (P)=0.6719).

Fig. 1 – Dissected great saphenous vein.

At The Laboratory of Descriptive and Topographic Anatomy of UNCISAL - Maceió (AL), the measurements of the variables of the length of the veins were performed; (diameter) at its proximal, middle and distal portions; quantification of the number of these valves and the total number of valves in the VSM. The measurements were made with the aid of tape measure and caliper manual mechanical METRICA®. RESULTS The average number of valves of the saphenous vein taken from the medial epicondyle of the femur to the saphenous hiatus is 4.82, and 4.77 in the left leg and 4.87 in the right. The analysis of the total number of valves in the GSV was performed by quantitative descriptive analysis with a sample of 60 veins, this being 30 from the right leg and 30 from the left, from 30 adult cadavers of both sexes. Of these cadavers, 21 were male and 9 female. All valves were observed to be bicuspid. The minimum amount found was 2 valves and maximum of 9. The average was 4.8167 with a maximum standard deviation of 1.6518 and minimum standard deviation 0.2132. The median of each portion is shown in Table 1. The value of the number of valves that occurred in more proximal portions was 2 and in other portions, 1. Comparing the mean diameter (DM) of the portions, it was found that the MD of the proximal portion of the left saphenous vein was 4.96 millimeters (mm)

Table 1. The amount allocated between the portions of the GSV. Portions GSV Proximal Medial Distal P-value Median (ID) Median (ID) Median (ID) Left 2.00 (1.7500)a 1.00 (1.0000)b 1.00 (1.0000)b 0.0004 Right 2.00 (0.0000)c 1.00 (1.0000)d 1.50 (1.0000)d 0.0016 GSV=Great saphenous vein; ID=Interqualitic Deviation Table 2. Distribution of the valves in relation to sex. Gender GSV Male Female Average (ID) Average (ID) Left 5.00 (3.0000) 4.00 (3.0000) Right 5.00 (2.0000) 5.00 (2.0000) GSV=Great saphenous vein; ID=Interqualitic Deviation

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Table 3. Distribution of, and the number of, valves per age group. MP Median (ID) Age range n Percent 25.0 4.00 (3.0000) 14.0 |— 36.0 4 13.33 % 47.0 4.00 (2.2500) 36.0 |— 58.0 6 20.00% 58.0 |— 80.0 69.0 9 30.00% 4.00 (2.5000) 91.0 5.00 (1.7500) 80.0|—102.0 11 36.67 %

reported subendothelial proliferation within a single valve when reviewing pathological changes in aortal-coronary grafts. Many of the studies cited in the study showed fibrosis of the venous valve as a cause of late segmental occlusion of venous grafts[5]. Considering the characteristics of GSV, Sarzaeem et al.[10] created a scoring system that takes into account the ramifications, varicosity, diameter and wall thickness of the GSV. Regarding the number of branches, which are directly related to the number of valves, GSV were classified as follows: [None, when there are no significant branches (1 point); Few, if there are three or less branches (2 points) or multiple, when more than three branches (3 points)]. In relation to the diameter when a vein segment is continuous, has an internal diameter of 3 mm to 5 mm, and progressively increases in proximal size is classified as normal (1 point). A vein segment with an internal diameter of more than 5 mm is classified as dilated (2 points). A vein segment with a lower inner diameter of 3 mm is classified as small (3 points). Three distinct described pathologic processes are well known to influence early or late failure of revascularization with GSV. During the first 30 days after surgery, up to 12 % of the grafts can become clogged, which is referred to as acute graft failure. Between one month and one year, neointimal hyperplasia (the accumulation of smooth muscle cells and extracellular matrix in the intimal compartment) can occur. Although this condition rarely leads to a clinically significant stenosis, it may provide the basis for developing atherosclerotic graft. After the first postoperative year, graft failure is delayed and can occur in the form of graft vascular disease (accelerated atherosclerosis), which is present in 17% of grafts after 6 years and in 46% of grafts after 11 years. In this study, 87.7 % of the grafts were potent at 1 year, similar percentages reported in other studies[10]. The GSV has 10 to 12 valves, which are more numerous in the leg than in relation to the thigh and are usually located just below the perforated veins[7]. The number of valves in the saphenous vein has been reported to be 8 to 20, with many being below the knee[8]. Other studies claim that there are between 7 and 9 valves in the saphenous vein with an average of 3.5 (when above the knee) and 4 on average are located below the knee[12]. Some authors found between 5 and 11 valves in the saphenous vein with an average of 5.2 above the knee and 3.8 below the knee[13]. The latter feature also results closer to those observed in the results of our research. The average number of valves in the saphenous vein taken from the medial epicondyle of the femur to the saphenous nerve gap is 4.82 valves, but may vary between 2 and 9.

MP=Midpoint of the sample; n=Frequency; ID=Interqualitic deviation (DIQ) of the sample

DISCUSSION The consensus is that the best graft for myocardial revascularization is the Magna Saphenous Vein. Among these, the most used is the left internal thoracic artery. As a second option, this is widely used for bypass surgeries. The presence of valves in this vein has not been a deterrent for utilization[1-4]. The widespread use of the autologous Saphenous Vein for direct myocardial revascularization procedures is mainly attributed to its easy and safe surgical removal, its almost ideal size and versatility, as well as their biological acceptance[9]. The use of GSV in myocardial revascularization has become a well established method of acceptance in the treatment of refractory angina and improved prognosis. GSV grafts remain potent for about 10 years. However, 15% of the first block and the constant presence of year[10] valves in this vein has not been a hindrance to use[1-4]. The permeability of the greater saphenous vein in the short and long term depends on several factors, such as high blood pressure, “distal coronary circulation” intramural ischemia, and progressive graft atherosclerosis. The human saphenous vein wall has a thin inner layer, separated from the support by a rudimentary internal elastic membrane. The wall consists of two distinct layers of muscle cells: a longitudinal inner layer mixed with collagen bundles and a circular outer layer. The adventitia is composed mainly of collagen bundles with scattered longitudinal fascicles of smooth muscle cells. Near the locations of the venous valves, the longitudinal layer muscle usually becomes thicker. The main finding in the histopathological study of GSV grafts is the intimal fibrosis layer, while in communication; only the longitudinal muscle layer was surrounded by sclerotic process. Although these lesions are generally considered to be an aging process, statistical analysis reveals that neither the inner or medial sclerosis is correlated to the age of patients[9]. Experimental evidence has shown that intact valves in veins, when reversed, can cause luminal narrowing, serve as a source of strength, and generate significant hemodynamic effects in coronary artery bypass grafts. Indeed, in a recent study, reversed arterialized vein grafts in an animal model of atherosclerosis. After 8 weeks, a significant thickening was observed in the gr afted distal wall of valves when compared with grafts without valves[11]. Spray & Roberts[6]

CONCLUSION We conclude that it is extremely important to know the segments with the highest number of valves in the saphenous

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vein allowing surgeons, when possible, to have an option to choose the most appropriate segments; in the average or distal portion of the saphenous magna vein in the thigh, due to the smaller amount of valves, therefore, tend to decrease the risk of complications related to these structures in grafts.

4. Caggiati A, Bergan JJ, Gloviczki P, Ekolof B, Allegra C, Partsch H; International Interdisciplinary Consensus Committee on Venous Anatomical Terminology. Nomenclature of the veins of the lower limb: extensions, refinements, and clinical application. J Vasc Surg. 2005;41(4):719-24.

ACKNOWLEDGMENTS

5. Bosher LP, Deck JD, Thubrikar M, Nolan SP. Role of the venous valve in late segmental occlusion of vein graft. J Surgical Res. 1979;26(4):437-46.

First I thank God for the gift of life, health, love and wisdom. The dear teachers Amauri Clemente Rocha, Celio Fernando de Sousa-Rodrigues and Rodrigo Freitas Monte-Bispo friendship, patience, understanding and essential academic orientation. To all the people who directly or indirectly contributed with care and attention during the formation of this work.

6. Spray TL, Roberts WC. Changes in saphenous veins used as aortocoronary bypass grafts. Am Heart J. 1977;94(4):500-16. 7. Moore HM, Gohel M, Davies AH. Number and location of venous valves within the popliteal and femoral veins: a review the literature. J Anatom. 2011; 219(4):439-43.

Authors’ roles & responsibilities IBMP ILR CFSR RFMB ACR

Participation in all phases of the experiment, since the dissection to the writing of article Participation in all phases of the experiment, since the dissection to the writing of article Participation in all phases of the experiment, since the dissection to the writing of article Participation in all phases of the experiment, since the dissection to the writing of article Participation in all phases of the experiment, since the dissection to the writing of article

8. Moore KL, Dalley AF. Anatomia Orientada para a Clínica. 5ª ed. Rio de Janeiro: Guanabara Koogan; 2006. p.534. 9. Thiene G, Miazzi P, Valsecchi M, Valente ML, Bortolotti U, Casarotto D, et al. Histological survey of the saphenous vein before its use as autologous aortocoronary bypass graft. Thorax; 1980;35(7):519-22. 10. Sarzaeem MR, Mandegar MH, Roshanali F, Vedadian A, Saidi B, Alaeddini F, et al. Scoring system for predicting saphenous vein graft patency in coronary artery bypass grafting. Tex Heart Inst J. 2010;37(5):525-30.

REFERENCES 1. Chaux A, Ruan MX, Fishbein MC, Shandhu M, Matloff JM. Influence of vein valves in the development of arteriosclerosis in venoarterial grafts in the rabbit. J Thorac Cardiovasc Surg. 1995;110(5):1381-9.

11. Tullis MJ, Primozich J, Strandness DE Jr. Detection of “functional” valves in reversed saphenous vein bypass grafts: identification with duplex ultrasonography. J Vasc Surg. 1997;25(3):522-7.

2. Lobo Filho JG, Lobo Filho HG, Mesquita FJC, Linhares Filho JPP. Enxerto composto de artéria torácica interna esquerda e veia safena magna: estudo angiográfico após oito anos. Rev Bras Cir Cardiovasc. 2010;25(1):118-21.

12. Gottlob R, May R. Venous Valves: Morphology, Function, Radiology, Surgery. Vienna: Springer-Verlag; 1986. p.16-24. 13. Brett MC, Hopkinson BR. Technique of in situ saphenous vein arterial bypass: can the valves help to locate the major venous tributaries? Anne R Coll Surg Eng. 1990;72(1):14-7.

3. Petroianu A. Anatomia cirúrgica. 1ª Ed. Rio de Janeiro: Guanabara Koogan; 1999. p.721.

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Uncu H, et al.ORIGINAL - The effect of gender on the early results of coronary artery ARTICLE bypass surgery in the younger patients' group

The effect of gender on the early results of coronary artery bypass surgery in the younger patients' group O efeito do gênero sobre os resultados iniciais da cirurgia de revascularização do miocárdio em grupo de pacientes mais jovens

Hasan Uncu1, MD; Mehmet Acipayam2, MD; Levent Altinay2, MD; Pinar Doğan1, MD; Isil Davarcı2, MD; İbrahim Özsöyler1, MD

DOI: 10.5935/1678-9741.20140050

RBCCV 44205-1591

Abstract Introduction: In this retrospective study, we aimed to determine the risk factors for coronary artery bypass surgery in patients under 45 years of age, and evaluate the early postoperative results and the effect of gender. Methods: A total of 324 patients under 45 years of age who undergone on-pump coronary artery bypass surgery between April 12, 2004 and January 10, 2012 were included to the study. Patients divided into groups as follows: Group 1 consisted of 269 males (mean age 41.3), Group 2 consisted of 55 females (mean age 41.6). Preoperative risk factors, intraoperative and postoperative data and early mortality rates of the groups were compared. Results: Smoking rate was significantly higher in Group 1. Diabetes mellitus incidence and body mass index were significantly higher in Group 2 (P values P=0.01; P=0.0001; P=0.04 respectively). The aortic cross-clamping and cardiopulmonary bypass time and number of grafts per patient were significantly higher in Group 1 (P values P=0.04; P=0.04; P=0.002 respectively). There were no deaths in either group. Conclusion: We found that gender has no effect on early mortality rates of the coronary bypass surgery patients under 45 years.

Resumo Introdução: Este estudo retrospectivo teve como objetivo determinar os fatores de risco para cirurgia de revascularização do miocárdio em pacientes com menos de 45 anos de idade e avaliar os resultados pós-operatórios precoces e o efeito do gênero. Métodos: Um total de 324 pacientes com menos de 45 anos de idade, que submeteram à cirurgia de revascularização miocárdica entre 12 de abril de 2004 e 10 de janeiro de 2012 foram incluídos no estudo. Os pacientes divididos em dois grupos: Grupo 1, composto por 269 homens (idade média 41,3 anos), Grupo 2, composto por 55 mulheres (idade média 41,6 anos). Fatores de risco pré-operatórios, dados intraoperatórios e pós-operatórios e mortalidade precoce dos grupos foram comparados. Resultados: A taxa de tabagismo foi significativamente maior no grupo 1. Incidência de diabetes mellitus e massa corporal foram significativamente maiores no grupo 2 (valor de P: P=0,01, P=0,0001, P=0,04, respectivamente). O pinçamento aórtico e tempo de circulação extracorpórea e número de enxertos por paciente foi significativamente maior no grupo 1 (valor de P: P=0,04, P=0,04, P=0,002, respectivamente). Não ocorreram mortes em ambos os grupos. Conclusão: O gênero não tem efeito sobre as taxas de mortalidade precoce dos pacientes de cirurgia de revascularização do miocárdio com menos de 45 anos.

Descriptors: Cardiopulmonary Bypass. Coronary Artery Bypass. Education, Medical.

Descritores: Ponte Cardiopulmonar. Ponte de Artéria Coronária. Educação Médica.

Adana Numune Training and Research Hospital Department of Cardiovascular Surgery, Adana, Turkey. 2 Mustafa Kemal University School Of Medicine, Department of Cardiovascular Surgery, Zülüflühan Köyü, Antakya, Hatay, Turkey.

Correspondence address: Isil Davarcı Mustafa Kemal University School Of Medicine, Department of Anesthesiology Zülüflühan Köyü, 31000, Antakya, Hatay, Turkey E-mail: sildavarci@gmail.com

This study was carried out at Mustafa Kemal University School Of Medicine, Department of Anesthesiology, Antakya, Hatay, Turkey.

Article received on November 7th, 2013 Article accepted on February 13th, 2014

No financial support.

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pre and postoperative data of the CABG surgery in 45 year old patients and younger aged male and female patients and aimed to determine the effect of gender on these parameters.

Abbreviations, acronyms & symbols ACC Aortic cross-clamping BMI Levels, body mass index CABG Coronary artery bypass graft CAD Atherosclerotic coronary artery disease COPD Chronic obstructive pulmonary disease CPB Cardiopulmonary bypass DM Diabetes mellitus HT Hypertension Htc Pre- and postoperative hematocrit ICU Intensive care unit LDL Low-density lipoprotein LIMA Left internal mammarian artery LMCA Left main coronary artery MI Myocardial infarction

METHOD Patient Selection In most of the studies, patients between 40 - 45 years of age are considered as “young”[2] so we decided to include the patients who were younger than 45 years in our study. A total of 324 patients were selected to be included to the study from the data pool of 5527 patients who underwent CABG surgery between April 12, 2004 and January 10, 2012 in Adana Numune Training and Research Hospital Fatma Kemal Timuçin Heart Center, Adana, Turkey. Off-pump CABG surgery, concomitant heart valve or aortic surgery, age over 45 years were criteria for exclusion.

INTRODUCTION Atherosclerotic coronary artery disease (CAD) is the leading cause of morbidity and mortality in the developed countries, and the World Health Organization estimate that it will be leading cause of death all over the world by the year 2020[1]. It primarily affects the 40 year and older population but younger males and females can also be affected[2]. In the autopsies of 760 accident, homicide or suicide victims aged between 15 and 34; it was founded that in 2% of the 15-19 year old males group there were advanced atheromas in the coronary arteries as well as there were no coronary lesions in the same aged females group[3]. In the same study, 20% of the 30-34 year old males group and 8% of the same aged females group had advanced coronary artery lesions[3]. In the 20-24 year old male group there were advanced coronary lesions in about 2% of the patients, but not in the female group. In the 25-29 year old male and female groups, the percentage of advanced coronary artery lesions were nearly the same (between 2 - 3%)[3]. Young patients who had suffered myocardial infarction (MI), usually have more than one risk factors related with CAD. In results of some studies, it is reported that 90 – 97% of the patients had one or more risk factors for atherosclerosis[2,4,5]. Smoking[2-7], family member with CAD[2,5,7], hypercholesterolemia[2,3,5-7], diabetes mellitus (DM)[2,4,5,7], hypertension (HT)[2,3,5-7], obesity[2,3,6,7] and other risk factors such as oral contraceptives in young females, cocaine addiction, etc[8] may act as etiological factors in younger patients for coronary atherosclerosis. As the incidence of CAD in younger patients increases, the coronary artery bypass graft (CABG) surgery practice increases in this population. It is known that CABG surgery can prolong the life time especially in patients with left main coronary artery (LMCA) or 3-vessel disease when compared to medical therapy[9]. There are many studies concerning the results of CABG surgery in younger patients and many different results are reported in these studies about the risk factors for CAD. In this retrospective study, we evaluated the

Patient groups Patients were divided into groups according to their gender. Group 1 consisted of 269 males (mean age 41.3) and Group 2 consisted of 55 females (mean age 41.6). All the patients were operated under standard cardiopulmonary bypass (CPB) circumstances. All the data of the following parameters of groups were compared: Smoking, diabetes mellitus, hypertension, chronic obstructive pulmonary disease (COPD), low-density lipoprotein (LDL) levels, body mass index (BMI), pre- and post-operative hematocrit (Htc), left internal mammarian artery (LIMA) graft utilization, the amount of blood product used, the length of intensive care unit (ICU) stay, aortic cross-clamping (ACC) and cardiopulmonary bypass time, inotropic agent administration, intra-aortic balloon pump (IABP) counter pulsation, preoperative ejection fraction (EF), postoperative drainage through chest tubes and mortality rates. Surgical procedure In the operating room, after electrocardiographically (ECG) and invasive blood pressure monitoring was set, general anesthesia protocol was followed. After median sternotomy and LIMA and saphenous vein graft harvesting, CPB was established with an ascending aortic and a single two stage right atrial cannula. After heparinization with bolus injection of 3 mg/kg of body weight heparin, cardiopulmonary bypass circuit was initiated with a roller pump and non-pulsatile flow technique. Moderate hemodilution (hematocrit value: 22 to 24%) and mild hypothermia (nasopharyngeal temperature: 32°C) were sustained during CPB. Pump flow rate during CPB was maintained at 2.4 l/m2/min and mean arterial blood pressure was sustained above 60 mmHg. A membrane oxygenator (Compactflo Evo, Dideco, Mirandola, Italy) was used for CPB. Pump prime was a volume of 1 liter of 0.9 % sodium chloride solution. Ante grade 10 ml/kg blood cardioplegia solution was administered through the aortic root cannula. After completion

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of each distal coronary anastomosis, 250 ml of cardioplegic solution was administered through the grafts. Ringer’s lactate solution at 4°C was used for topical cooling of the heart. Left internal mammary artery grafts were reconstructed to the left anterior descending arteries (LAD) as the final anastomosis in all patients. Proximal anastomoses were implemented under partial aortic clamping.

Graft counts in the groups were as follows (Group 1/ Group 2 respectively): One vessel 26/10 patients, two vessels 84/25 patients, three vessels 126/17 patients, four vessels 30/3 patients and five vessels 3/0 patients (Table 3). The ACC happened to be 37.7±15 mins and CPB time was 67.5±23.6 mins in Group 1 and they were 33.3±13 mins and 60.5±22.5 mins respectively in Group 2. The ACC and CPB time and graft counts per patient were significantly higher in Group 1 (P=0.04; P=0.04; P=0.002) (Table 3). The LIMA graft utilization rate was 86.4% in the study population. It was higher in Group 1 and it was statistically significant (88.5% in Group 1; 76.4% in Group 2; P=0.03) (Table 3). Inotropic agent support was needed for weaning from CPB in 46% of the patients. The EuroSCORE values of the patients were between 0 and 3. There was one patient that IABP support was needed for weaning from CPB in Group 1. No mortalities happened in either of the groups.

Preoperative data The mortality in the first post-operative 30-day period was used to compare the mortality rates of the groups. The total amount of hemorrhage through the mediastinal and thoracic drainage tubes until they were drawed was defined as mediastinal drainage. Re-operation for any reason (bleeding, cardiac tamponade, graft failure, etc) in the first postoperative 24 hour period was defined as postoperative revision. Other parameters were recorded as they were. Statistical Analysis All tests were performed using SPSS for Windows 13.0. Categorical values were expressed by numbers and percentages and the numerical values were expressed as mean±standart deviation. After normality tests were employed, Mann Whitney U test and chi-square (x2) test were used to compare groups. A P value less than 0.05 were accepted as significant.

Table 2. Clinic data of the groups.

Graft Count (mean) Preoperative Hct Postoperative Hct Blood transfusion (Unit) Inotropic support Ventilatory support (hr) Chest tube drainage (ml) ICU stay (days) In-hospital stay (days)

RESULTS The demographical data, risk factor distribution and co morbidities of the groups are shown in Table 1. Smoking rate was higher in Group 1, DM incidence and BMI were higher in Group 2 (P values P=0.01; P=0.0001; P=0.04 respectively). Age, HT and COPD incidence were not significantly different. There were no significant differences for the following data either: LDL levels, preoperative EF, Htc values, ventilator support duration, drainage through chest tubes, blood transfusion volumes, the length of ICU stay and length of hospital stay (Table 2).

Group 1 (n=269) 41.3±3.3 26.2±4.7 161 (59.9%) 117.5±44.2 53.3±7.2 59 (22%) 50 (19%) 11 (4%)

Group 2 (n=55) 41.6±3.8 27.7±5.1 22 (40%) 115.8±41.7 52.7±8.1 29 (53%) 16 (29%) 1 (2%)

Group 2 (n=55) 2.2±0.8 41.9±4.2 28.3±2.2 1.1±1.1 20 (36%) 3.8±1.7 420±178 1.18±0.3 4.2±0.4

P value 0.002 0.255 0.852 0.319 0.155 0.978 0.378 0.489 0.600

Hct=Hematocrit; ICU=Intensive care unit Table 3. Operative data of the groups. Graft Count Group 1 (n=269) Group 2 (n=55) One vessel 26 (10%) 10 (18%) Two vessels 84 (31%) 25 (45%) Three vessels 126 (47%) 17 (31%) Four vessels 30 (11%) 3 (5%) Five vessels 3 (1%) 0 ACC time (mins) 37.7±15 33.3±13.4 CPB time (mins) 67.5±23.6 60.5±22.5 IABP 0 1 (1.8%) LIMA 238 (88%) 42 (76%) AC C =Aor tic cros s -clam ping; C PB=C ardio-pu lmonary bypass; IABP=Intra-aortic balloon pump; LIMA=Left internal mammarian artery

Table 1. Demographic data of the groups and distribution of the risk factors. Age (mean) BMI Smoking LDL EF (%) DM HT COPD

Group 1 (n=269) 2.6±0.8 42.7±4.5 28.3±2.1 0.9±1.1 129 (48%) 3.8±1.4 443±174 1.14±0.3 4.3±0.4

P value 0.2 0.04 0.01 0.912 0.701 0.0001 0.098 0.698

DISCUSSION It is reported that sedentary life style, excessive consumption of fatty foods, smoking, HT, etc are more commonly seen in people with CAD[6]. These findings were confirmed in Framingham study and by observing the people with atherosclerotic

DM=Diabetes Mellitus; EF=Ejection fraction; HT=Hypertension; COPD=Chronic Obstructive Pulmonary Disease; LDL=Low Density Lipoprotein; BMI=Body mass index

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diseases in younger ages. But it is also shown that advanced coronary artery disease may occur without the previous habits and risk factors[6]. The coronary atherosclerosis is shown to be present in autopsy studies of the patients in their 20’s and some studies report that about 19% of males in their early 30’s have advanced coronary artery atherosclerosis (>40% stenos). Smoking, HT and dislipidemia are very important factors for premature CAD in young patients[6]. Besides that smoking is shown to be the main risk factor[2,6,8]. Kannel et al. [8] reported in Framingham study that smokers aged between 35 - 40 years have 3 times more relative risk of CAD according to non-smokers in the same age. Also the studies evaluating the results of younger age patient undergoing CABG surgeries showed high rates of smoking in their patient populations[7,9,10]. The smoking rate in our patient population was 56.5% and it was more common in males than females (P=0.007). In a study conducted in 1998, the smoking prevalence was in 62.8% of theTurkish male population and 24.3% in Turkish female population[11]. In our study, the smoking rate of males was similar to that data (59.9% vs. 62.8%) but it was remarkably higher in our female patient group (40% vs. 24.3%). Gu et al.[12] reported in their study that the most common etiology of mortality in diabetic patients younger than 40 years of age was CAD. Diabetics have 2 – 4 times higher risk of CAD according to non-diabetics[6]. It is not clear how the CAD progresses in young diabetic female patients despite the protective effect of estrogen[8]. Smoking and oral contraceptive administration together can increase mortality of CAD about 13.6 times[13]. Truncal obesity and high BMI are independent risk factors of mortality of CAD in females[8]. The DM incidence and BMI were found to be significantly higher in female patients in relation to males in our study (53% vs. 22%, P=0.0001; 27.7% vs. 26.2%; P=0.04 respectively). The results of CABG surgery are better in patients younger than 40 years. Five years survival rate is 92% and the 10 year survival rate is 86% but the same rates for the 65 years and older age population are 73% and 58%, respectively[14]. Rocha et al.[15] also reported that the in-hospital mortality of elderly patients was 8.9% in their study. In a meta-analyses Sá et al found no effect of gender, number of grafts and age on the outcomes[16]. The long term patency of internal mammarian artery (IMA) graft is better than saphenous vein graft so it is accepted to use IMA grafts for the LAD lesions in younger patients[17,18]. The utilization rate of LIMA graft is 86.4% in our study. It is significantly higher in Group 1 in relation to Group 2 (88.5%; 76.4% respectively; P=0.03). Wagner et al.[19] reported that they used LIMA grafts in all of the 126 patients under 40 years of age as well as 286 saphenous vein grafts (2.3 grafts per patient). Five of their patients needed IABP support and 1 patient needed left ventricle assist device. They reported their in-hospital mortality rate as 1.6% (2 patients)[17]. The graft count per patient in our study

was 2.6 and 2.2 for Group 1 and Group 2 respectively. ACC and CPB duration, graft count per patient and LIMA graft utilization rates were higher in Group 1 (P=0.002; P=0.04; P=0.04; P=0.03 respectively). IABP support was needed for one patient and 46% of the patients needed inotropic agent support in our study. No mortality happened in either group. CONCLUSION Smoking appears to be the most important risk factor for both males and females under 45 years although DM and high BMI appear to be remarkable for the female population. We found that gender does not affect the early mortality rates in younger age population and postoperative period is shorter than for older age patients. We can say that to achieve the higher long term survival rates, at least one arterial bypass graft should be used and risk factors especially smoking, DM and BMI should strictly be kept under control. Authors’ roles & responsibilities HU MA LA PD ID İÖ

Medical records survey, research director Reference check, statistic Research design Language control, research design Reference search, Languaage check Medical records survey

REFERENCES 1. Reddy KS, Yusuf S. Emerging epidemic of cardiovascular disease in developing countries. Circulation. 1998;97(6):596-601. 2. Navas-Nacher EL, Colangelo L, Beam C, Greenland P. Risk factors for coronary heart disease in men 18 to 39 years of age. Ann Inter Med. 2001;134(6):433-9. 3. McGill HC Jr, McMahan CA, Zieske AW, Tracy RE, Malcom GT, Herderick EE, et al. Association of coronary heart disease risk factors with microscopic qualities of coronary atherosclerosis in youth. Circulation. 2000;102(4):374-9. 4. Chouhan L, Hajar HA, Pomposiello JC. Comparison of thrombolytic therapy for acute myocardial infarction in patients aged < 35 and > 55 years. Am J Cardiol. 1993;71(2):157-9. 5. Hoit BD, Gilpin EA, Henning H, Maisel AA, Dittrich H, Carlisle J, et al. Myocardial infarction in young patients: an analysis by age subsets. Circulation. 1986;74(4):712-21. 6. Noeman A, Ahmad N, Azhar M. Coronary artery disease in young: Faulty life style or heredofamilial or both. Annals. 2007;13(2):162-4.

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7. Zehr KJ, Lee PC, Poston RS, Gillinov AM, Greene PS, Cameron DE. Two decades of coronary artery bypass graft surgery in young adults. Circulation. 1994;90(5 Pt 2):II133-9.

14. Egred M, Viswanathan G, Davis GK. Myocardial infarction in young adults. Postgrad Med J. 2005;81(962):741-5. 15. Rocha AS, Pittella FJ, Lorenzo AR, Barzan V, Colafranceschi AS, Brito JO, et al. Age influences outcomes in 70-year or older patients undergoing isolated coronary artery bypass graft surgery. Rev Bras Cir Cardiovasc. 2012;27(1):45-51.

8. Klein LW, Nathan S. Coronary artery disease in young adults. J Am Coll Cardiol. 2003;41(4):529-31. 9. Tokmakoğlu H, Kandemir Ö, Farsak B, Günaydın S, Yorgancıoğlu C, Zorlutuna Y. Coronary artery bypass surgery in young patients. Turkish J Thorac Cardiovasc Surg. 2002;10:1-4.

16. Sá MP, Ferraz PE, Escobar RR, Martins WN, Lustosa PC, Nunes Ede O, et al. Off-pump versus on-pump coronary artery bypass surgery: meta-analysis and meta-regression of 13,524 patients from randomized trials. Rev Bras Cir Cardiovasc. 2012;27(4):631-41.

10. French JK, Scott DS, Whitlock RM, Nisbet HD, Vedder M, Kerr AR, et al. Late outcome after coronary artery bypass graft surgery in patients < 40 years old. Circulation. 1995;92(9 Suppl):II14-9.

17. Ng WK, Vedder M, Whitlock RM, Milsom FP, Nisbet HD, Smith WM, et al. Coronary revascularisation in young adults. Eur J Cardiothorac Surg. 1997;11(4):732-8.

11. Şahin EM, Özer C, Çakmak H, Tunç Z, Taştan K, Can EN. Smoking status of medical students. Balkan Med J. 2007;24(3):209-12.

18. Wu HY, Hueng GG, Lee GC, Lee SG, Tsai CS. Coronary artery bypass surgery in a 24 year-old man: A case report and reviews of literature. J Med Sci. 1999;20(3):157-63.

12. Gu K, Cowie CC, Harris MI. Mortality in adults with and without diabetes in a national cohort of the U.S. Population, 1971-1993. Diabetes Care. 1998;21(7):1138-45.

19. Wagner J, Ennker J, Hetzer R. Characteristics of patients younger than 40 years of age operated for coronary artery disease. Herz. 1996;21(3):183-91.

13. Tanis BC. Oral contraceptives and the risk of myocardial infarction. Eur Heart J. 2003;24(5):377-80.

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Mendonça CT, et al. - Carotid endarterectomy in awake patients: safety, ORIGINAL ARTICLE tolerability and results

Carotid endarterectomy in awake patients: safety, tolerability and results Endarterectomia de carótida em pacientes acordados: segurança, tolerabilidade e resultados

Célio Teixeira Mendonça1, MD, PhD; Jerônimo A. Fortunato Jr.2, MD; Cláudio A. de Carvalho3, MD; Janaina Weingartner3, MD; Otávio R. M. Filho2; Felipe F. Rezende2; Luciane P. Bertinato2, MD

DOI 10.5935/1678-9741.20140053

RBCCV 44205-1592

Abstract Objective: To analyze the results of 125 carotid endarterectomies under loco-regional anesthesia, with selective use of shunt and bovine pericardium patch. Methods: One hundred and seventeen patients with stenosis ≥ 70% in the internal carotid artery on duplex-scan + arteriography or magnetic resonance angiography underwent 125 carotid endarterectomies. Intraoperative pharmacological cerebral protection included intravenous administration of alfentanil and dexametasone. Clopidogrel, aspirin and statins were used in all cases. Seventy-seven patients were males (65.8%). Mean age was 70.8 years, ranging from 48 to 88 years. Surgery was performed to treat symptomatic stenosis in 69 arteries (55.2%) and asymptomatic stenosis in 56 arteries (44.8%). Results: A carotid shunt was used in 3 cases (2.4%) due to signs and symptoms of cerebral ischemia after carotid artery clamping during the operation, and all 3 patients had a good outcome. Bovine pericardium patch was used in 71 arteries ≤ 6 mm in diameter (56.8%). Perioperative mortality was 0.8%: one patient

died from a myocardial infarction. Two patients (1.6%) had minor ipsilateral strokes with good recovery, and 2 patients (1.6%) had non-fatal myocardial infarctions with good recovery. The mean follow-up period was 32 months. In the late postoperative period, there was restenosis in only three arteries (2.4%). Conclusion: Carotid artery endarterectomy can be safely performed in the awake patient, with low morbidity and mortality rates.

Universidade Positivo, Curitiba, PR, Brazil; Hospital Marcelino Champagnat (PUC-PR), Curitiba, PR, Brazil; Hospital Nossa Senhora das Graças (HNSG), Curitiba, PR, Brazil; and Hospital VITA-Curitiba, Curitiba, PR, Brazil. 2 Universidade Positivo, Curitiba, PR, Brazil. 3 Hospital Universitário da Cruz Vermelha do Paraná/ Universidade Positivo, Curitiba, PR, Brazil; Hospital Marcelino Champagnat (PUC-PR), Curitiba, PR, Brazil; Hospital Nossa Senhora das Graças (HNSG), Curitiba, PR, Brazil; and Hospital VITA-Curitiba, Curitiba, PR, Brazil.

Correspondence address: Célio Teixeira Mendonça Rua Visconde do Rio Branco, 1717, 3 floor – Downtown Curitiba, PR, Brazil - Zip code: 80420-210 E-mail: celiotm@brturbo.com.br

Descriptors: Endarterectomy, Carotid. Anesthesia, Local. Stroke. Resumo Objetivo: Analisar os resultados de 125 endarterectomias carotídeas, realizadas sob anestesia loco-regional com uso seletivo de shunt e remendo de pericárdio bovino. Métodos: Cento e dezessete pacientes com estenose na artéria carótida interna ≥ 70% ao ecoDoppler colorido +

No financial support.

This study was carried out at Serviços de Cirurgia Vascular, Cirurgia Cardiovascular e Anestesiologia do Hospital Universitário da Cruz Vermelha do Paraná/Universidade Positivo (UP), Curitiba, PR, Brazil.

Article received on November 28th, 2013 Article accepted on March 2nd, 2014

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(2,4%) devido a sintomas de isquemia cerebral após a colocação do clampe carotídeo durante o ato cirúrgico, e os três pacientes tiveram boa evolução. Remendo de pericárdio bovino foi utilizado em 71 artérias ≤ 6 mm de diâmetro (56,8%). A mortalidade perioperatória foi de 0,8%: um paciente faleceu devido a infarto agudo do miocárdio. Dois pacientes (1,6%) tiveram infartos cerebrais isquêmicos ipsilaterais menores com boa recuperação, e 2 pacientes (1,6%) tiveram infartos do miocárdio não-fatais com boa recuperação. O tempo médio de seguimento foi de 32 meses. No pós-operatório tardio, houve reestenose significativa em apenas três artérias (2,4%). Conclusão: A endarterectomia carotídea no paciente acordado é uma técnica segura, sendo realizada com baixas taxas de morbimortalidade.

Abbreviations, acronyms & symbols CVAs Cerebrovascular accidents ECG Electrocardiogram EEG Electroencephalography MAP Mean arterial pressure

arteriografia ou angiorressonância magnética foram submetidos a 125 endarterectomias carotídeas. As medidas de proteção farmacológica intraoperatória incluíam a administração endovenosa de alfentanil e dexametazona. Clopidogrel, aspirina e estatinas eram utilizadas em todos os casos. Setenta e sete pacientes eram do sexo masculino (65,8%). A idade média foi de 70,8 anos, variando de 48 a 88 anos. A operação foi indicada por estenose sintomática em 69 artérias (55,2%), e por estenose assintomática em 56 artérias (44,8%). Resultados: O shunt de carótida foi necessário em 3 casos

Descritores: Endarterectomia das Carótidas. Anestesia Local. Acidente Vascular Cerebral.

INTRODUCTION Ischemic cerebrovascular accidents (CVAs) are the third most common cause of death in the United States[1]. Up to 52% of all ischemic cerebral infarctions are caused by extracranial atherosclerotic cerebrovascular disease, that is, by stenoses in the internal carotid arteries caused by cholesterol plaque attached to thrombus[2]; it is known that the prevalence of carotid artery stenosis is high in patients with coronary disease and hypertension[1]. The first carotid endarterectomy was performed by Dr. Michael E. DeBakey in 1953 (and published in 1959)[3]. After a period of initial enthusiasm, followed by another period of concern due to high rates of complications reported in the 1970s and 1980s[4], prospective and randomized studies with large number of patients have been performed in the United States and Europe to investigate more objectively which patients would benefit from this procedure[5-8]. These studies were published from 1995 to 2004, and demonstrated that carotid endarterectomy plus medical therapy were superior to medical therapy alone in preventing ischemic strokes and death in selected patients with hemodynamically significant stenosis (≥ 70%) in the internal carotid artery[5-8]. It is estimated that more than 103,000 carotid endarterectomies are performed each year in the United States[1] with the aim of preventing ischemic strokes. However, there are still controversies regarding the type of anesthesia, cerebral monitoring and cerebral protection during the surgery, the use of a patch in closing the carotid artery and the criteria to use a carotid artery shunt. The aim of this study is to describe and assess the results of carotid endarterectomy under loco-regional anesthesia, with selective use of a carotid artery shunt and bovine pericardium patch.

METHODS From April 1996 to November 2012, 125 consecutive carotid endarterectomies were performed on 117 patients under loco-regional anesthesia at the Vascular Surgery and Cardiovascular Surgery Services in the Red Cross University Hospital of Paraná, Curitiba. All patients were included in a prospective registry, and signed a written informed consent form before surgery. This study was approved by the Research Ethics Committee of the Positivo University. All patients received perioperative acetylsalicylic acid (325 mg/day), clopidogrel (75 mg/day) and statins (simvastatin 20 mg/day or rosuvastatin 10 mg/day). This medication was started 15 days before the procedure and maintained for 1 year or more. There were 8 bilateral procedures. Six of the bilateral carotid endarterectomies were performed with an interval ranging from 4 to 5 weeks and 2 were performed at a later date when the contralateral carotid artery became symptomatic. There were 77 male (65.8%) and 40 (34.2%) female patients. The mean age of patients was 70.8 years, ranging from 48-88 years. Comorbidities of this group of patients were: diabetes (n=99 or 84.6%), smoking (n=97 or 82.9%), hypertension (n=92 or 78.6%), peripheral artery disease (n=64 or 54.7%), dyslipidemia (n=63 or 53.8%), ischemic coronary artery disease (n=62 or 53%), chronic obstructive pulmonary disease (n=14 or 11.9%) and chronic renal failure (n=5 or 4.3%). The carotid arteries of all patients were assessed by color Doppler ultrasound along with digital subtraction angiography or magnetic resonance angiography with gadolinium. The arteriography and magnetic resonance were performed to confirm the presence of hemodynamically significant stenosis (seen on Doppler ultrasound) and to calculate the degree of stenosis. For this calculation, we used the method

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described in the NASCET study[7]. Carotid endarterectomy was indicated when the degree of stenosis in the internal carotid artery was greater than or equal to 70%. The surgery was indicated for symptomatic stenosis in 69 arteries (55.2%), and asymptomatic stenosis in 56 arteries (44.8%). The indications for operation are listed in Table 1. Among symptomatic patients, 42 had suffered transient ischemic attacks (33.6%), and 14 (11.2%) had experienced small cerebral infarcts. Thirteen patients (10.4%) had monocular blindness: 10 of them had experienced transient symptoms (amaurosis fugax), and 3 had permanent visual field defects. Three patients had total occlusion of the contralateral internal carotid artery. All asymptomatic lesions underwent surgery before coronary artery bypass grafting (31 cases), open repair of abdominal aortic aneurysms (14 cases), or major abdominal surgery (11 cases).

process and, after aspiration, 5 ml of solution was injected in each transverse process. The patient was maintained without sedation for improved neurological monitoring, and we used short-term opioids, such as alfentanil at a dose of 5 mg/kg if the patient had postural or emotional discomfort. The operating table was adjusted so that the patient stayed in a semi-upright position (at an angle of 45°). When necessary, sodium nitroprusside in a dosage of 0.05 micrograms per kilogram of body weight per minute was administered using an infusion pump in order to keep the mean arterial pressure (MAP) at the level of the measures that had been obtained in the pre-anesthetic assessment (MAP between 100 and 120 mmHg). Five minutes before placing the arterial clamps to do the carotid occlusion test (during 3 minutes), 5000 international units of unfractionated heparin were administered intravenously. Intraoperative cerebral monitoring consisted of neurological examination and observation for signs or symptoms of cerebral ischemia, such as changes in level of consciousness, seizures, slurred speech or motor deficit in the upper and lower limbs on the contralateral side of the body. The techniques used in our service were conventional carotid endarterectomy with primary closure and conventional endarterectomy with closure using a bovine pericardium patch (Figures 1-4). The carotid shunt was used when the patient under loco-regional anesthesia and undergoing cerebral monitoring showed symptoms of cerebral ischemia. At the end of the procedure a careful review of hemostasis was performed and heparin was not reversed. A continuous suction drain was inserted by contraincision, the incision was sutured in layers and the patient was taken to the intensive care unit.

Table 1. Indications for carotid endarterectomy (125 procedures). Signs and symptoms Transient ischemic attack Cerebral infarction Monocular blindness Transient (amaurosis fugax) Permanent visual field defect Asymptomatic carotid stenosis

N 42 14 13 10 3 56

% 33.6 11.2 10.4 44.8

The technique used by our anesthesiology service was superficial and deep cervical plexus block, seeking to provide conditions for neurological assessment of the patient during the procedure in the operating room since, in our view, consciousness is the best parameter to know whether the patient’s brain is suffering or not from ischemia. During pre-anesthetic assessment, we confirmed the possibility of performing the procedure and the patient was oriented regarding the loco-regional anesthesia. The patients were on continuous oxygen mask and were monitored with ECG, invasive blood pressure and strict control of heart rate; their brain function was monitored by the level of consciousness and motor activity in the upper and lower limb in the contralateral side of the body. Before loco-regional anesthesia, we administered a dose of 2 mg of dexamethasone intravenously. The superficial cervical plexus block was performed with subcutaneous injection of 5 to 10 ml of 0.5% ropivacaine along the posterior border of the sternocleidomastoid muscle. The deep cervical plexus block was performed with injection of the same anesthetic solution in the transverse processes of C2, C3, and C4 respectively located 2, 4 and 6 cm below the mastoid process, in a straight line drawn between the mastoid process and the C6 transverse process (Chassaignac’s tuber). The needle was inserted perpendicular to the skin up to the transverse

Fig. 1 - Surgical dissection: common carotid artery (yellow strip), external carotid artery (white strip) and internal carotid artery (red strip).

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Patients underwent neurological assessments looking for signs or symptoms of cerebral ischemia in the immediate postoperative period, on the seventh postoperative day, and 30, 90 and 180 days after the procedure; after this period, the neurological assessments were annual. In patients where neurological examination was abnormal, realization of Doppler ultrasound was indicated; in neurologically normal patients, the Doppler was performed 6 months after the surgery. When the Doppler ultrassound showed a hemodynamically significant stenosis, the patient underwent arteriography or magnetic resonance angiography to confirm the lesion. RESULTS The carotid endarterectomies were performed with loco-regional anesthesia in 117 patients undergoing 125 surgeries: no patient required conversion to general anesthesia. The carotid endarterectomy with conventional primary closure was used when the diameter of the internal carotid artery was > 6 mm[9,10] and was performed in 54 arteries (43.2%). When the diameter of the internal carotid artery was â&#x2030;¤ 6 mm, which was observed in 71 arteries (56.8%), the chosen technique was conventional endarterectomy and closure with an elliptical bovine pericardium patch[10]. The patch was used in 95% of female patients (n=38), and 42.8% of male patients (n=33). It was necessary to use intraoperative shunt in 3 cases (2.4%). The first patient had stenosis of approximately 80% in the carotid being operated, and contralateral carotid occlusion; its circle of Willis was complete, and he had mental confusion followed by contralateral motor deficit in the arm and leg during the crossclamping test of the carotid artery. The second patient had 70% stenosis in the carotid being operated and stenosis of approximately 10% in the contralateral carotid artery, with a complete circle of Willis, and presented motor deficit in the contralateral upper limb during removal of the atherosclerotic plaque. The third patient had stenosis of approximately 80% in the carotid being operated, and 20% in the contralateral carotid artery, and its circle of Willis showed absence of the anterior cerebral artery; this patient showed mental confusion and motor deficit in the contralateral arm and leg during the crossclamping test. In those 3 cases, the neurological symptoms disappeared immediately after insertion of the shunt and the patients had a normal outcome. The average crossclamping time of the internal carotid artery was 19 minutes, ranging between 13 and 31 minutes. Perioperative mortality was 0.8%: one patient died of an acute myocardial infarction on the 2nd day after the procedure. Two patients (1.6%), both symptomatic, had a small ipsilateral ischemic cerebral infarct with good recovery, and 2 patients (1.6%) had nonfatal myocardial infarction with good recovery. In three surgeries (2.4%) there was excessive bleeding through the drain, and the incision was reopened for

Fig. 2 - Arteriotomy of the internal carotid artery with a view of the cholesterol plaque.

Fig. 3 - Example of cholesterol plaque removed from the internal carotid artery.

Fig. 4 - Closing the internal carotid artery with elliptical patch of bovine pericardium.

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revision of hemostasis. The average hospital stay was 3 days (2-6 days). The average follow-up time was 32 months (6192 months). Doppler ultrasound follow-up was performed in all patients, and significant restenosis (stenosis ≥ 70%) was found in three arteries (2.4%); the 3 cases with significant restenosis after carotid endarterectomy underwent angioplasty with stent implantation in the carotid artery, with a good outcome. During the late postoperative period, there were no cases of ischemic stroke.

used: routine use of a shunt (in all patients), or some monitoring technique to differentiate patients who are at risk to develop an ischemic stroke and the need to use the shunt selectively. Historically, no monitoring technique showed good correlation with the neurological status of the awake patient, which is considered the “gold standard” (to which all other techniques should be compared). The main direct (electroencephalography, response to evoked potentials) and indirect methods (stump pressure of the internal carotid artery, transcranial Doppler) for the detection of cerebral ischemia during carotid crossclamping showed, at some point, low sensitivity or low specificity when compared to the neurological status of the awake patient[15-17]. Electroencephalography (EEG), despite being the most accurate and used method to monitor brain function, can lead to a high incidence on the use of shunt (up to 28%); in addition, the incidence of false negative and false positive results reported is 4.5% and 6.7%, respectively[18]. Another worrying fact is that intraoperative ischemic strokes have clearly occurred in the absence of any changes in EEG[18]. Lawrence et al.[19] demonstrated that the incidence in the use of shunts in patients operated under loco-regional anesthesia was approximately 4.5%, a result comparable to our study (incidence in the use of shunt of 2.4%). As the routine use of a carotid shunt may lead to an incidence of up to 3% of iatrogenic complications (such as embolization of air or cholesterol particles to the brain, and lesions of the carotid intima causing early thrombosis and late stenosis)[14], we opted for its selective use in our service. It has been shown that routine use of a bovine pericardial patch (and other materials such as polyester, polyurethane and autologous veins) to close the internal carotid artery is more effective than primary closure in decreasing the incidence of perioperative ischemic strokes, perioperative carotid thrombosis and late restenosis[20]. However, some surgeons believe that the use of a patch for closing the internal carotid arteriotomy may prolong the operative time and the clamping time, making the procedure technically more complex and may be unnecessary in certain patients[21,22]. In our service, we chose to use the patch in arteries of small diameter (≤ 6 mm), because we believe that they would have greater chances of having complications if they were closed primarily. Recently, Mannheim et al.[23] performed a randomized controlled study comparing 216 patients undergoing carotid endarterectomy with primary closure versus 206 patients who had their arteriotomies closed with patch; the incidence of restenosis >70% in this study were significantly lower in patients who received patch compared to patients with primary closure (2.2% versus 8.6%, P=0.01). In our study, where we used the patch selectively[10], the incidence of significant restenosis in the internal carotid artery after 32 months of mean

DISCUSSION The natural history of atherosclerotic carotid artery disease is very worrying. Roederer et al.[11] showed that in equal to or greater than 80% stenosis in the internal carotid artery, the incidence of ischemic symptoms or total occlusion of the affected artery was 46% in 12 months. Aldoori et al.[12] showed that in equal to or greater than 75% stenosis in the internal carotid artery, the incidence of ischemic cerebral infarction was 50% in 3 years, with a mortality rate of 83%. Despite carotid endarterectomy has shown its efficacy in preventing ischemic strokes in both symptomatic and asymptomatic patients with hemodynamically significant stenosis in the internal carotid artery[5-8], ischemic cerebral infarction is still the most feared complication after this surgery. For this reason, particular attention has been paid to technical details of this procedure, in particular the preservation and monitoring of brain function during the crossclamping of the internal carotid artery. Numerous nonrandomized studies have been performed trying to establish what the best anesthesia would be to perform the surgical treatment of carotid disease: general or loco-regional. Although several clinical studies have suggested potential advantages of loco-regional anesthesia[9], the only prospective randomized study comparing the two techniques was published recently, and concluded that the combined rates of cerebral infarction, myocardial infarction and perioperative death were similar for both techniques. However, the loco-regional anesthesia has shown better outcomes in patients who had occlusion of the contralateral internal carotid artery[13]. The main reason why loco-regional anesthesia is preferred in our service, in spite of general anesthesia, is the fact that we can observe the neurological status of the patient during carotid artery crossclamping[14]. The fact that a small but significant group of patients will present intolerance during crossclamping of the internal carotid artery, and consequently require the carotid shunt for cerebral protection during endarterectomy, causes a serious dilemma for surgeons who choose to perform this surgery using general anesthesia. In order to make sure that an unconscious patient will not suffer an ischemic stroke while the surgery is performed, one of two methods should be

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follow-up was 2.4%, and the incidence of perioperative carotid thrombosis was 0%. Regarding the use of hypnoanalgesics, alfentanil calms the patient, improves his tolerance to operation time, and does not hamper his responses to verbal commands of the surgical team. If the MAP increases during surgery (increase of arterial pressure up to 15% compared to the initial pressure of the patient, or MAP greater than 120 mmHg) we use sodium nitroprusside, because this medication provides an accurate and immediate control of the blood pressure. The use of corticosteroids (dexamethasone) before the surgery aims to inhibit cerebral edema caused by the mechanism of ischemia/reperfusion, which may compromise the outcome of carotid endarterectomy. When we assess our perioperative rates of ischemic stroke and death (1.6% and 0.8%), we found comparable results to the most recent prospective randomized study on this subject, recently published in the literature (CREST study)[24]. In the group undergoing carotid endarterectomy in the CREST study, the rates of ischemic stroke and death in the perioperative period were 2.3% and 0.3%, respectively. In the group of patients undergoing treatment of carotid stenosis with stenting in the CREST study, the rates of perioperative ischemic stroke were significantly higher when compared to the group undergoing carotid endarterectomy (4.1% versus 2.3%, P=0.01). Mas et al.[25] recently demonstrated in a multicenter, randomized prospective study, that the incidence of ischemic strokes and death in symptomatic patients with carotid stenosis ≥60% were significantly lower in patients undergoing endarterectomy when compared to patients undergoing stenting in carotid arteries. In this study, the incidence of ischemic strokes or death in 30 days was 3.9% after endarterectomy and 9.6% after stenting (P=0.01) and after a 6 months follow-up period, the incidence was 6.1% after endarterectomy and 11.7% after stenting (P=0.02). At the moment, due to a higher incidence of ischemic strokes when opting for stenting[24,25], carotid endarterectomy seems to be the most appropriate technique for treatment of extracranial atherosclerotic cerebrovascular disease. One limitation of this study was a retrospective analysis of data. On the other hand, we emphasize the fact that no patient in this series have been lost during the mean 32 months follow-up period.

Authors’ roles & responsibilities CTM

JAFJr CAC JW ORMF FFR LPB

Analysis and/or interpretation of data, statistical analysis, final approval of manuscript conception and study design, conduct of procedures and/or experiments, writing of the manuscript or review of its content Sudy design, analysis and interpretation of data, approval of final version of the manuscript study design, analysis and interpretation of data, approval of final version of the manuscript Study design, analysis and interpretation of data, approval of final version of the manuscript Data collection, analysis and interpretation of data; approval of the final version of the manuscript Data collection, analysis and interpretation of data; approval of the final version of the manuscript Study design, analysis and interpretation of data, approval of final version of the manuscript

REFERENCES

1. Rosamond W, Flegal K, Furie K, Go A, Greenlund K, Haase N, et al.; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics–2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2008;117(4):e25-146. 2. Pessin MS, Duncan GW, Mohr JP, Poskanzer DC. Clinical and angiographic features of carotid transient ischemic attacks. N Engl J Med. 1977;296(7):358-62. 3. DeBakey ME, Crawford ES, Cooley DA, Morris GC Jr. Surgical considerations of occlusive disease of innominate, carotid, subclavian, and vertebral arteries. Ann Surg. 1959;149(5):690710. 4. Dyken ML. Carotid endarterectomy studies: a glimmering of science. Stroke. 1986;17(3):355-8. 5. Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. JAMA. 1995;273(18):1421-8.

CONCLUSION

6. Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST). Lancet. 1998;351(9193):1379-87.

We conclude that in our service, carotid endarterectomy performed on awake patients with selective use of a shunt and bovine pericardium patch is a very well tolerated, safe and effective technique to treat internal carotid artery stenosis ≥70% in symptomatic and asymptomatic patients. This procedure can be performed with very low morbidity and mortality rates.

7. Barnett HJ, Taylor DW, Eliasziw M, Fox AJ, Ferguson GG, Haynes RB, et al. Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med. 1998;339(20):1415-25.

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8. Halliday A, Mansfield A, Marro J, Peto C, Peto R, Potter J, et al.; MRC Asymptomatic Carotid Surgery Trial (ACST) Collaborative Group. Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial. Lancet. 2004;363(9420):1491-502.

17. McCarthy WJ, Park AE, Koushanpour E, Pearce WH, Yao JS. Carotid endarterectomy. Lessons from intraoperative monitoring— a decade of experience. Ann Surg. 1996;224(3):297-307. 18. Stoughton J, Nath RL, MD, Abbott WM. Comparison of simultaneous electroencephalographic and mental status monitoring during carotid endarterectomy with regional anesthesia. J Vasc Surg. 1998;28(6):1014-21.

9. AbuRahma AF. Processes of care for carotid endarterectomy: surgical and anesthesia considerations. J Vasc Surg. 2009;50(4):921-33.

19. Lawrence PF, Alves JC, Jicha D, Bhirangi K, Dobrin PB. Incidence, timing, and causes of cerebral ischemia during carotid endarterectomy with regional anesthesia. J Vasc Surg. 1998;27(2):329-34.

10. Cikrit DF, Larson DM, Sawchuk AP, Thornhill C, Shafique S, Nachreiner RD, et al. Discretionary carotid patch angioplasty leads to good results. Am J Surg. 2006;192(5):e46-50.

20. AbuRahma AF, Robinson PA, Richmond BK. Reanalysis of factors predicting recurrent stenosis in a prospective randomized trial of carotid endarterectomy comparing primary closure and patch closure. Vasc Endovasc Surg. 2000;34(4):319-29.

11. Roederer GO, Langlois YE, Jager KA, Primozich LF, Beach KW, Phillips DJ, et al. The natural history of carotid arterial disease in asymptomatic patients with cervical bruits. Stroke. 1984;15(4):605-13.

21. Clagett GP, Patterson CB, Fisher DF Jr, Fry RE, Eidt JF, Humble TH, et al. Vein patch versus primary closure for carotid endarterectomy. A randomized prospective study in a selected group of patients. J Vasc Surg 1989;9(2):213-23.

12. Aldoori MI, Benveniste GL, Baird RN, Horrocks M, Fairgrieve J. Asymptomatic carotid murmur: ultrasonic factors influencing outcome. Br J Surg. 1987;74(6):496-9. 13. GALA Trial Collaborative Group, Lewis SC, Warlow CP, Bodenham AR, Colam B, Rothwell PM, Torgenson D, et al. General anaesthesia versus local anaesthesia for carotid surgery (GALA): a multicentre, randomised controlled trial. Lancet. 2008;372(9656):2132-42.

22. Al-Rawi PG, Turner CL, Waran V, Ng I, Kirkpatrick PJ. A randomized trial of synthetic patch versus direct primary closure in carotid endarterectomy. Neurosurgery. 2006;59(4):822-8. 23. Mannheim D, Weller B, Vahadim E, Karmeli R. Carotid endarterectomy with a polyurethane patch versus primary closure: a prospective randomized study. J Vasc Surg. 2005;41(3):403-7.

14. Santos PC, Fabri HA, Cunha CR, Martins CAC, Shinosaki JSM, Neves AS, et al. Endarterectomia de carótida em paciente acordado. Rev Bras Cir Cardiovasc. 2006; 21(1):62-7. 15. Ahn SS, Concepcion B. Intraoperative monitoring during carotid endarterectomy. Semin Vasc Surg. 1995;8(1):29-37.

24. Brott TG, Hobson RW 2nd, Howard G, Roubin GS, Clark WM, Brooks W, et al.; CREST Investigators. Stenting versus endarterectomy for treatment of carotid artery stenosis. N Engl J Med. 2010;363(1):11-23.

16. Rockman CB, Riles TS, Gold M, Lamparello PJ, Giangola G, Adelman MA, et al. A comparison of regional and general anesthesia in patients undergoing carotid endarterectomy. J Vasc Surg. 1996;24(6):946-56.

25. Mas JL, Chatellier G, Beyssen B, Branchereau A, Moulin T, Becquemin JP, et al.; EVA-3S Investigators. Endarterectomy versus stenting in patients with symptomatic severe carotid stenosis. N Engl J Med. 2006;355(16):1660-71.

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Erdil N, et al. ORIGINAL - Nebivolol inARTICLE preventing atrial fibrillation following coronary surgery in patients over 60 years of age

Nebivolol in preventing atrial fibrillation following coronary surgery in patients over 60 years of age Nebivolol na prevenção da fibrilação atrial após a cirurgia coronária em pacientes acima de 60 anos de idade

Nevzat Erdil1, PhD; Murat Kaynak1, MD; Köksal Dönmez1, MD; Olcay Murat Disli1, MD; Bektas Battaloglu1, MD

DOI 10.5935/1678-9741.20140078

RBCCV 44205-1593

Abstract Objective: Postoperative atrial fibrillation is a common complication after cardiac surgery, with an incidence as high as 20-50%. Increased age is associated with a significant increase in postoperative atrial fibrillation risk. This common complication is associated with higher morbidity and mortality rates. The aim of this study was to assess the efficacy of nebivolol in preventing atrial fibrillation following coronary artery bypass surgery in patients over 60 years of age. Methods: In this prospective randomized study, 200 patients who were candidates for elective coronary artery bypass surgery were divided into two groups. The first group was administered with nebivolol and the second group was administered with metoprolol. Treatment was initiated four days prior to surgery, and patients were monitored for atrial fibrillation until discharge. Forty-one patients recieved 50 mg metoprolol succinate daily, which was initiated minimum 4 days before surgery. Results: Demographic data were similar in both groups. The incidence of postoperative atrial fibrillation in both groups was similar, with no significant difference being identified [n=20 (20%); n=18 (18%), P=0.718; respectively]. There were not any mortality at both groups during study. Inotropic agent

requirement at ICU was similar for both groups [n=12 (12%), n=18 (18%), P=0.32]. Conclusion: We compared the effectiveness of nebivolol and metoprolol in decreasing the incidence of postoperative atrial fibrillation, and determined that nebivolol was as effective as metoprolol in preventing postoperative atrial fibrillation at patients. Nebivolol may be the drug of choice due to its effects, especially after elective coronary artery bypass surgery.

Inonu University Turgut Ozal Medical Center, Malatya, Turkey.

Correspondence address: Nevzat Erdil Inonu University Turgut Ozal Medical Center Division of Cardiac Surgery, Malatya, Turkey, 44280 E-mail: nevzatkutay@gmail.com

Descriptors: Coronary Artery Bypass. Atrial Fibrillation. Anti-Arrhythmia Agents. Drug Therapy. Resumo Objetivo: Pós-operatório fibrilação atrial é uma complicação comum após a cirurgia cardíaca, com uma incidência tão elevada quanto 20-50%. O aumento da idade está associado com elevação significativa no risco de pós-operatório da fibrilação atrial. Esta complicação comum é associada com taxas de morbidade e mortalidade. O objetivo deste estudo foi avaliar a eficácia do nebivolol na prevenção da fibrilação atrial após cirurgia de revascularização do miocárdio de pacientes acima de 60 anos de idade.

Work carried out at Inonu University Turgut Ozal Medical Center, Malatya, Turkey. No financial support.

Article received on January 7th, 2014 Article accepted on June 8th, 2014

No conflict of interest.

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pacientes receberam 50 mg de sucinato de metoprolol diário, que foi iniciado, no mínimo, 4 dias antes da cirurgia. Resultados: Os dados demográficos foram semelhantes nos dois grupos. A incidência de fibrilação atrial pós-operatória em ambos os grupos foi semelhante, com nenhuma diferença significativa sendo identificado [n=20 (20%); n=18 (18%), P=0,718; respectivamente]. Não houve mortalidade em ambos os grupos durante o estudo. A necessidade de agente inotrópico em UTI foi semelhante nos dois grupos [n=12 pessoas (12%), n=18 (18%), P=0,32]. Conclusão: Nós comparamos a eficácia do nebivolol e metoprolol na diminuição da incidência de fibrilação atrial no pós-operatório, e verificamos que nebivolol foi tão eficaz como metoprolol na prevenção de fibrilação atrial no pós-operatório em pacientes. Nebivolol pode ser a droga de escolha devido aos seus efeitos, especialmente depois da cirurgia revascularização do miocárdio.

Abbreviations, acronyms & symbols AF Atrial fibrillation CPB Cardiopulmonary bypass DVT Deep vein thrombosis ECG Electrocardiogram EuroSCORE (European) System For Cardiac Operative Risk Evaluation Score ICU Intensive care unit LMCA Left main coronary artery MI Myocardial infarction POAF Postoperative atrial fibrillation

Métodos: Neste estudo prospectivo e randomizado, duzentos pacientes candidatos à cirurgia de revascularização do miocárdio foram divididos em dois grupos. O primeiro grupo foi administrado com nebivolol e o segundo grupo, com metoprolol. O tratamento foi iniciado quatro dias antes da cirurgia, e os pacientes foram monitorados para fibrilação atrial até a alta. Quarenta e um

Descritores: Ponte de Artéria Coronária. Fibrilação Atrial. Antiarrítmicos. Quimioterapia.

INTRODUCTION

METHODS

Postoperative atrial fibrillation (POAF) is a commonly observed complication following cardiac surgery, with an incidence as high as 20-50% depending on the accepted definition of POAF and the methods used for detection[1,2]. Increasing age in patients undergoing cardiac surgery is associated with a significant increase in POAF risk[2,3]. This common complication contributes to higher morbidity and mortality rates among patients. Major outcomes associated with POAF include an increased incidence of stroke, longer hospitalization, increased hospital costs, and higher early and late mortality rates[1,4,5]. Prophylactic treatment is recommended due to the high incidence of POAF, especially if risk factors are present. Effective preventive and treatment strategies are important for reducing the undesirable effects of this complication. It has been previously demonstrated in several studies that beta-blockers are effective agents for preventing POAF. Beta-blockers have also been recommended for POAF prophylaxis in several meta-analyses[6,7]. Nebivolol is a selective beta-1 adrenergic receptor antagonist that differs from conventional beta-blockers in its ability to induce nitric oxide synthesis in the human endothelium. Tepliakov et al.[8] showed that nebivolol administration (1.25-5.0 mg/day) increased exercise tolerance, improved life quality, reduced IR index by 11.9%, and reduced triglyceride levels by 5.3% (which in turn lowered the risk of effects associated with diabetic atherogenic dyslipidemia). In this prospective randomized study, we investigated the effectiveness of nebivolol and metoprolol in decreasing the incidence of POAF. Patients in this study were selected among individuals above 60 years of age, as age is a major risk factor for POAF. There are no other studies in the literature regarding the effects of nebivolol in preventing POAF.

Following the approval of the Medical Faculty’s Ethics Committee (Reference Number: 2009/145), and after written informed consents were obtained from the patients; 200 patients over 60 years of age with coronary artery disease, who had been admitted to our clinic for elective coronary artery bypass grafting surgery, were included into our study. The study was performed according to a randomized, prospective, parallel-group, active controlled, open-label, single-blind study design. The patients were randomized into two groups, and the study procedures were carried out for a period of 4 days. All included patients were from an inpatient setting. Study subjects were randomly allocated into the NEB and MET treatment groups at the beginning of the study by using a random number generated by SAS. The patients were not stratified according to race and sex during the randomization process, which led to an unequal distribution of males and females between the two groups. At the beginning of the study 100 subjects were recruited in each group. Due to the withdrawal of consent, lost to follow-up and missing values of some outcome variables, the final sample size was 100 in the NEB group and 100 in the MET group. Group 1 was the nebivolol group, consisting of 100 patients (27 women and 73 men, mean age 67.2±7.6), while Group 2 was the metoprolol group, also consisting of 100 patients (34 women and 67 men, mean age 68.4±5.8). Patients who had previous beta-blocker or antiarrhythmic treatment, previous atrial fibrillation (AF), heart failure (ejection fraction ≤ 35%), sick sinus syndrome, atrioventricular block, permanent pacemaker, valvular surgery, peripheral vascular disease, hyperthyroidism, and emergency surgery were excluded from the study. In both groups, drugs use was started 4 days prior to surgery[9].

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Metoprolol was administered once daily at a dose of 50 mg, while nebivolol was administered once daily at a dose of 5 mg. Drug use was continued after extubation during the postoperative period. Dosages were adjusted according to the hemodynamic responses of the patients after coronary surgery. None of the patients withdrew from study due to the side effects of the drugs. Data was collected at the time of hospitalization, during the first postoperative day, and at the time of discharge. The primary end point of the study was new-onset AF until discharge. None of the patients in both groups presented serious bradycardia or hypotension. Atrial fibrillation was diagnosed when 12-lead ECG showed rapid oscillations or fibrillatory P waves that varied in size, shape, and timing, and which were associated with irregular QRS complexes. In this study, POAF was defined as AF of any duration during the postoperative period, with the AF diagnosis being based on the physician’s assessments. All Holter and ECG data were evaluated by two blinded cardiologists, and AF diagnosis was confirmed with the observation of (i) absent P wave prior to QRS complex, and (ii) irregular ventricular rhythm that continued for more than 5 minutes. In the event that POAF was identified, no further evaluations were performed, and the patient was started on an administration of amiodarone at a 150 mg bolus dose, followed by administration at 15 mg/kg/24 h infusion. After sinus rythm was achieved, the patient’s treatment was continued with oral amiodarone administration for a period of 30 days, with a 800 mg/day dose being administered during week 1, a 600 mg/day dose during week 2, a 400 mg/ day dose during week 3, and a 200 mg/day dose during week 4. ECG and 12-lead ECG were needed to confirm the 12-lead ECG findings. Patients who developed AF were treated with a standard protocol of anticoagulation and amiodarone. None of patients who developed AF required electrical cardioversion. All of the patients were discharged from the hospital with a sinus rhythm.

and cardiopulmonary bypass was established by cannulating the ascending aorta and right atrium. Heparin (3 mg/kg) was administered for anticoagulation. Activated clotting time was maintained for longer than 450 seconds, and a roller pump and non-pulsatile flow (2.4 L/m2/min) were used. The body was cooled to a core temperature between 32oC and 34oC when performing distal anastomosis, and the body was rewarmed to 36oC before weaning from cardiopulmonary bypass. Cold blood cardioplegia was delivered intermittently via antegrade and retrograde routes throughout the procedure. A final dose of “hot-shot” cardioplegia was delivered intermittently via antegrade and retrograde routes throughout the procedure. A final dose of “hot-shot” cardioplegia was administered immediately before the aorta was unclamped. An epicardial temporary pacemaker lead (FLEXON 3-0 temporary cardiac pacing lead, Syneture, Covidien, US) was placed on the right ventricle. Details of the surgical techniques used for complete revascularization solely by means of arterial grafts have been previously described[10]. The same protocol was applied for each case in which radial artery was used. Radial-artery harvesting was carried out simultaneously with left internal thoracic artery harvesting. Saphenous veins were harvested using conventional methods. The choice of graft material was left to the surgeon, but certain protocols were followed. Left internal thoracic artery was generally used as a graft for the left anterior descending artery; radial artery and saphenous vein graft conduits were used mainly to bypass vessels other than the left anterior descending artery; and only radial artery conduits were used to bypass vessels other than the left anterior descending artery in case they exhibited more than 70% stenosis. Outcome parameters A prospective study was performed for the relevant pre-operative, intraoperative and postoperative data of the study group. The specific pre- and intraoperative data obtained from each patient included the following: age and gender, history of hypertension, diabetes, smoking, obesity, hyperlipidemia, body surface area and body mass index (BMI), history of myocardial infarction (MI), the presence of unstable angina, prior percutaneous transluminal coronary angioplasty, the presence of carotid artery disease, left ventricular ejection fraction, the presence of left main coronary artery (LMCA) disease, additive EuroSCORE and the extent of coronary disease. The postoperative data that was collected included the number of grafts per operation, the graft types that were used (i.e., left internal mammary artery, radial artery or saphenous vein grafts), the cardiopulmonary bypass time, the aortic crossclamp time, the mechanical ventilation time, the requirement for inotropic or intra-aortic balloon pump support, presence of infection, re-exploration for bleeding or cardiac tamponade, the duration of stay in the intensive care unit (ICU), overall duration of hospital stay, and hospital mortality (defined as

Statistical analysis Data were analyzed using the Statistical Package for Social Sciences 16.0 (SPSS 16.0) for Windows (SPSS Inc., Chicago, IL). Data for patient characteristics and outcomes were expressed either as percentage of total or as mean±SD. The independent samples t-test was used for normally distributed continuous variables (expressed as mean±SD), while the Pearson chi-square, Yates’ corrected chi-square and Fisher’s exact tests were used for categorical variables, where applicable. The Mann Whitney U test was used for continuous variables such as age, BMI and EuroSCORE, which were not normally distributed. The results were assessed within 95% confidence, and a value of P<0.05 was considered as statistically significant. Surgical Procedure Patients were placed under general anesthesia, and conventional median sternotomy was performed. Each patient underwent on-pump coronary artery bypass grafting surgery,

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death in the first 30 days after coronary artery bypass grafting surgery). We further employed data regarding study design, baseline patient data, administered treatment and POAF incidence by entering them to an Excel spreadsheet that was standardized. POAF incidence was considered as the study’s primary outcome.

Table 1. Preoperative demographic data. Group 2 P-Value Group 1 Metoprolol Nebivolol 100 100 N 68.4 ± 5.8 0.21 67.2 ± 7.6 Mean Age 34 (34%) 0.36 27 (27%) Gender (Female) 46 (46%) 0.67 43 (43%) Previous MI 28 (28%) 0.64 31 (31%) Diabetes Mellitus 33 (33%) 0.21 25 (25%) Hypertension 45 (45%) 0.39 52 (52%) Smoking 8 (8%) 0.25 14 (14%) COPD 66 (66%) 0.24 58 (58%) Hypercholesterolemia 24 (24%) 0.9 25 (25%) Obesity 2 (2%) 0.49 0 (0%) Renal Dysfunction 26.6±4.4 0.574 26.9±4.1 BMI 4.1±2.28 0.072 3.55±2.02 EuroSCORE 1.75±0.16 0.274 1.78±0.16 BSA COPD=Chronic Obstructive Pulmonary Disease; BMI=Body Mass Index; BSA=Body Surface Area

RESULTS Two hundred patients (100 patients per group) were included into this study. The pre-operative demographic characteristics of the patients are summarized in Table 1 and Table 2. The mean age of the patients was 67.2±7.6 years in Group 1, and 68.4±5.8 years in Group 2. There were no significant differences between the groups with respect to gender distribution; the prevalence of chronic obstructive pulmonary disease; the frequency of previous percutaneous transluminal coronary angioplasty; the prevalence of hypertension, obesity (body mass index, ≥30 kg/m2), hyperlipidemia, smoking, diabetes mellitus, unstable angina, or LMCA disease; the ratio of patients with a history of MI; or the ratio of patients with carotid artery disease. There were also no statistical differences between the groups with respect to the mean number of diseased vessels, the mean left ventricular ejection fraction, or the EuroSCORE. Intraoperative and postoperative data that were collected included the number of grafts per operation, the types of grafts used (for example, left internal thoracic artery, radial artery, and venous grafts), the cardiopulmonary bypass (CPB) time, and the aortic cross-clamp time. Data collected regarding the postoperative outcomes included the mechanical ventilation time; the requirement for inotropic or intra-aortic balloon pump support; the development of atrial fibrillation or infective complications; the re-exploration for bleeding or cardiac tamponade; and the occurrence of major pleural effusions, superficial or deep-wound infections, and deep vein thrombosis (DVT). With regards to inotrope usage, hypoxemia and low cardiac output, no statistically significant differences were observed between the two groups. Similarly, there was also no statistically significant difference between Group 1 and Group 2 in any of the types of data described above (Table 3). Group I and Group II had similar durations of stay in the intensive care unit (2.6±0.7 vs. 2.5±0.9 days, respectively; P=0.559), durations of overall hospital stay (7.1±1.4 vs. 7.4±2.2 days, respectively; P=0.388) and ventilation times (7.3±2.5 vs. 7.2±2.9 hours, respectively; P=0.794), with no significant differences being identified between the two groups. In addition, no perioperative deaths occurred in any of these two groups. There was no significant difference in the incidence of POAF between Group I and Group II (20% vs. 18%, respectively; P=0.718). The incidence of inotropic agent requirement at ICU were also similar in both groups (12% in Group I vs. 18% in Group II, P=0.32) (Table 4).

Table 2. Preoperative demographic data (cardiac). Group 1 Nebivolol

Group 2 Metoprolol

P-Value

One Vessel

8 (8%)

1.000

Two Vessel

45 (47%)

50 (50%)

0.479

Three Vessel

47 (47%)

42 (42%)

0.477

Number of Diseased Vessels

8 (8%) 0.78 6 (6%) LMCA disease 71 (71%) 0.44 66 (66%) Right Coronary Disease 5 (5%) 0.28 10 (10%) Carotid artery disease 22 (22%) 0.13 13 (13%) Previous PTCA 50.9 ± 8.6 0.533 50.2 ± 8.1 Ejection fraction 17 (17%) 0.027 6 (6%) New MI 21 (21%) 0.19 13 (13%) Unstable Angina LMCA=Left Main coronary Artery Disease; PTCA=Percutaneous Transluminal Coronary Angioplasty; MI=Myocardial Infarction

Table 3. Operative data.

N Preoperative Mortality Complete arterial revascularization LIMA usage Radial Artery usage Mean distal bypass number Cross-clamp time (min) Perfusion time (min)

Group 1 Nebivolol 100 0

Group 2 Metoprolol 100 0

P-value

3 (3%) 96 (96%) 7 (7%) 2.40 ± 0.67 64.6 ± 16.5 74.7 ± 17.6

1 (1%) 95 (95%) 4 (4%) 2.38 ± 0.69 62.6 ± 15.7 74.2 ± 16.9

0.62 0.733 0.352 0.835 0.423 0.838

LIMA=Left Internal Mammarian artery

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observed that POAF led to a nearly two-fold increase in the hospital mortality and the 6-month mortality of patients. Increasing age is the most significant contributing factor to the risk of POAF[11,13,14]. Matthew et al.[18] determined in a recently conducted study that the incidence of POAF increased by nearly 75% for every decade of age, and that all patients above the age of 70 were at a high risk of POAF. Other factors that also increase the risk of POAF include previous episodes of AF, lower left ventricular ejection fraction, left atrial enlargement, valvular heart surgery, chronic obstructive pulmonary disease, chronic renal failure, diabetes mellitus, and rheumatic heart diseases[13,17,18]. Recent students have also suggested that obesity may be associated with a higher incidence of POAF in both patients with and without previous cardiac surgeries[19,20]. A variety of factors appear to be involved in the etiology of POAF, although the mechanistic relationship between these factors and POAF development has not yet been clearly identified. Several mechanisms that are potentially involved in POAF pathogenesis include pericardial inflammation, excessive catecholamine production, postoperative autonomic imbalance, and interstitial fluid mobilization. These factors may adversely affect atrial refractoriness and slow atrial conduction. The multiple re-entry wavelets caused by the dispersion of atrial refractoriness appear to be the underlying mechanism for the development of POAF[21]. In a meta-analysis performed recently by Crystal et al.[22], it was observed that, within the scope of 28 trials conducted with 4074 subjects, beta-blocker drugs demonstrated the highest magnitude of effect with an odds ratio (OR) of 0.3, and a 95% confidence interval (CI) of 02.26 to 0.49. In the meta-analysis of Burgess et al.[23], the authors reported that the use of beta-blocker drugs lead to a reduction in the incidence of POAF. According to the American College of Cardiology/American Heart Association and the European Society of Cardiology Guidelines for AF; pre-operative or early postoperative administration of beta-blockers for preventing AF after coronary artery bypass grafting surgery in patients without contraindications is a class-1 indication, with an evidence level of A[24]. Nebivolol is a third generation selective beta-1 adrenergic receptor antagonist that differs from conventional beta-blockers in its ability to induce nitric oxide synthesis in the endothelium[25]. The endothelium produces nitric oxide, which is a well-known vasodilator. Nebivolol has a high beta-1 adrenergic receptor selectivity, and can be used safely in patients with reduced cardiac functions. There are numerous studies discussing other properties of Nebivolol; however, based on our review of the literature, we believe that our study was the first to investigate the prophylactic use of nebivolol for POAF after coronary artery bypass surgery. Metoprolol is an important drug that was approved by the FDA in 1978. We chose metoprolol for comparison with

Table 4. Postoperative data.

Requirement for Inotropes IABP Ventilation time (hours) ICU stay (days) Surgical site infection Re-exploration for bleeding or tamponade Pleural effusion DVT Atrial Fibrillation Inotrope requirement in ICU Hospital Stay (days) IABP=Intra-aortic Balloon DVT=Deep Vein Thrombosis

Group 1 Nebivolol 11 (11%) 0 (0%) 7.3 ± 2.5 2.6 ± 0.7 1 (1%) 3 (3%)

Group 2 Metoprolol 22 (22%) 1 (1%) 7.2 ± 2.9 2.5 ± 0.9 1 (1%) 1 (1%)

P-value

3 (3%) 1 (1%) 20 (20%) 12 (12%)

0 (0%) 1 (1%) 18 (18%) 18 (18%)

0.24 1.000 0.718 0.32

0.057 1.000 0.794 0.559 1.000 0.62

7.4 ± 2.2 0.388 7.1 ± 1.4 Pump; ICU=Intensive Care Unit;

DISCUSSION The aim of this study was to investigate the effectiveness of nebivolol in the prophylaxis of postoperative atrial fibrillation (POAF) by comparing it with metoprolol, a medication whose effectiveness against atrial fibrillation is well-documented. Based on the study results, we identified no significant difference between nebivolol and metoprolol with regards to the effectiveness of POAF prophylaxis. POAF is observed in nearly 30% of patients who undergo isolated coronary artery bypass (CABG) surgery. This ratio increases to nearly 40% if replacement or repair of valves is performed during surgery, and to 50% in case combined procedures are performed. Considering that the age average of populations undergoing cardiac surgery is gradually increasing, and that the incidence of POAF is positively correlated with age, it is likely that these percentages will increase in the future. In most cases, POAF develops between the 2nd and 4th days that immediately follow surgery, with the highest incidence being observed on the 2nd day. The onset of POAF occurs before the 4th postoperative day in 70% of cases, and before the 6th postoperative day in 94% of cases[11]. POAF often manifests itself as a transient condition that is tolerated by most patients. However, POAF also has the potential to cause serious complications or even be fatal in certain patients – especially older patients and patients with certain ventricular dysfunctions[12] and mortality[13]. POAF was previously described as a potential cause of significant morbidity[14] that can lead to further postoperative complications such as thromboembolism[15], hemodynamic problems[16], ventricular dysrhythmias[17], and even to iatrogenetic effects due to inappropriate diagnosis and treatment of POAF. Moreover, POAF is known to increase nearly three times the incidence of perioperative stroke[13-17]. In a study conducted by Almassi et al. on 3855 cardiac surgery patients[14], it was

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nebivolol due to its safety and common use. Metoprolol has been used for the prevention and treatment of postoperative AF for decades. Thus, in this study we aimed to investigate the effectiveness of nebivolol in the prophylaxis of POAF by comparing it with metoprolol Radial arterial graft vasospasm is one of the most problematic complications following cardiac surgery. As mentioned before, nebivolol possesses a potent vasodilator effect on radial artery graft, and can increase the lumen diameter and protect the graft[26]. Furthermore, nebivolol is also known to improve sleep parameters, which contributes positively to the patients’ life quality[27]. Disturbance of normal sleep, in particular, may cause tiredness and lead to depression. This is most important for postoperative patients, who are emotionally vulnerable after surgery. Owing to its electrophysiological properties, and in a manner similar to other beta-blockers; nebivolol has the effect of increasing the ventricular fibrillation threshold. This effect allows nebivolol to reduce ventricular arrhythmia or drug-induced cardiomyopathy in various animal models. Nebivolol is also known to reduce the QT dispersions, which are associated with the risk of developing arrhythmias, and P-wave dispersions, which are associated with the risk of developing atrial fibrillation[28]. We believe that the results we obtained for nebivolol in our study – which were not significantly different than those for metoprolol – were ultimately the result of the effects and mechanisms described above. Previous experiments on ischemia and reperfusion injury[29] have also demonstrated the preventive and protective effects of nebivolol. In addition, it was shown that the administration of nebivolol in humans increased tolerance during exercise (in comparison to atenolol), as well as the time required for the onset of angina[30]. Nebivolol was also demonstrated to have a consistent effect in increasing coronary flow among individuals with ischemic and nonischemic heart diseases, which is believed to engender a decrease in the ischemic threshold of these individuals[31]. We believe that these effects that counter the damages associated with ischemia and ischemia-reperfusion will also allow nebivolol to be effective in the prevention and treatment of POAF. For ethical reasons, and also due to the relatively low number of patients in our study groups, we did not to include into the study design a control group without beta-blocker treatment. Unlike metoprolol, nebivolol does not have an IV form, which also represents a disadvantage.

this study; well-planned prospective and randomized studies with larger groups that evaluate other properties and features of nebivolol will be necessary to gain further information. The contribution of such studies on the body of knowledge regarding nebivolol’s effects will be significant. Authors’ roles & responsibilities NE MK KD OMD BB

Analysis and/or interpretation of data, statistical analysis, final approval of manuscript Final approval of manuscript, conception and study design, conduct of operations, and/or experiments Study design, conduct of operations, and/or experiments Analysis and/or interpretation of data, statistical analysis, final approval of the manuscript, conception and study design, conduct of operations, and/or experiments Conception and design of the study

REFERENCES

1. Creswell LL, Schuessler RB, Rosenbloom M, Cox JL. Hazards of postoperative atrial arrhythmias. Ann Thorac Surg. 1993;56(3):539-49. 2. Andrews TC, Reimold SC, Berlin JA, Antman EM. Prevention of supraventricular arrhythmias after coronary artery bypass surgery. A meta-analysis of randomized control trials. Circulation. 1991;84(5 Suppl):III236-44. 3. Nisanoglu V, Erdil N, Aldemir M, Ozgur B, Berat Cihan H, Yologlu S, et al. Atrial fibrillation after coronary artery bypass grafting in elderly patients: incidence and risk factor analysis. Thorac Cardiovasc Surg. 2007;55(1):32-8. 4. Aranki SF, Shaw DP, Adams DH, Rizzo RJ, Couper GS, VanderVliet M, et al. Predictors of atrial fibrillation after coronary artery surgery. Current trends and impact on hospital resources. Circulation. 1996;94(3):390-7. 5. Mathew JP, Parks R, Savino JS, Friedman AS, Koch C, Mangano DT, et al. Atrial fibrillation following coronary artery bypass graft surgery: predictors, outcomes, and resource utilization. Multicenter Study of Perioperative Ischemia Research Group. JAMA. 1996;276(4):300-6. 6. Zhu J, Wang C, Gao D, Zhang C, Zhang Y, Lu Y, et al. Metaanalysis of amiodarone versus β-blocker as a prophylactic therapy against atrial fibrillation following cardiac surgery. Intern Med J. 2012;42(10):1078-87.

CONCLUSION Metoprolol is a well-known and commonly preferred drug for the prevention of POAF. In this study, Nebivolol was determined to be as effective as metoprolol. Thus, it is possible to use nebivolol effectively for prophylaxis of POAF. Moreover, nebivolol’s characteristic properties may also result in additional benefits for elderly patients. Due to the limitations of

7. Zimmer J, Pezzullo J, Choucair W, Southard J, Kokkinos P, Karasik P, et al. Meta-analysis of antiarrhythmic therapy in the prevention of postoperative atrial fibrillation and the effect on hospital length of stay, costs, cerebrovascular accidents, and mortality in patients undergoing cardiac surgery. Am J Cardiol. 2003;91(9):1137-40.

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8. Tepliakov AT, Kuznetsova AV, Lukinov AV, Levshin AV. Effects of a superselective beta1-adrenoblocker nebivolol on the course of coronary heart disease and insulin resistance in patients with diabetes mellitus type 2 after coronary artery bypass grafting. Ter Arkh. 2007;79(12):38-43.

Champagne J, et al. Obesity and metabolic syndrome are independent risk factors for atrial fibrillation after coronary artery bypass graft surgery. Circulation. 2007;116(11 Suppl):I213-9. 21. Cox JL. A perspective of postoperative atrial fibrillation in cardiac operations. Ann Thorac Surg. 1993;56(3):405-9.

9. Imren Y, Benson AA, Zor H, Tasoglu I, Ereren E, Sinci V, et al. Preoperative beta-blocker use reduces atrial fibrillation in offpump coronary bypass surgery. ANZ J Surg. 2007;77(6):429-32.

22. Crystal E, Garfinkle MS, Connolly SS, Ginger TT, Sleik K, Yusuf SS. Interventions for preventing post-operative atrial fibrillation in patients undergoing heart surgery. Cochrane Database Syst Rev. 2004;(4):CD003611.

10. Nisanoglu V, Battaloglu B, Erdil N, Ozgur B, Aldemir M, Cihan HB. Complete myocardial revascularization using arterial grafts only in patients with unstable angina: impact on early outcome. Thorac Cardiovasc Surg. 2007;55(1):7-12.

23. Burgess DC, Kilborn MJ, Keech AC. Interventions for prevention of post-operative atrial fibrillation and its complications after cardiac surgery: a meta-analysis. Eur Heart J. 2006;27(23):2846-57.

11. Hernández-Romero D, Vílchez JA, Lahoz A, Romero-Aniorte AI, Orenes-Piñero E, Caballero L, et al. High-sensitivity troponin T as a biomarker for the development of atrial fibrillation after cardiac surgery. Eur J Cardiothorac Surg. 2014;45(4):733-8.

24. Fuster V, Rydén LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, et al; American College of Cardiology/American Heart Association Task Force on Practice Guidelines; European Society of Cardiology Committee for Practice Guidelines; European Heart Rhythm Association; Heart Rhythm Society. ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation. 2006;114(7):e257-354.

12. Wyse DG, Waldo AL, DiMarco JP, Domanski MJ, Rosenberg Y, Schron EB, et al; Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med. 2002;347(23):1825-33. 13. Mathew JP, Parks R, Savino JS, Friedman AS, Koch C, Mangano DT, et al; Atrial fibrillation following coronary artery bypass graft surgery: predictors, outcomes, and resource utilization. MultiCenter Study of Perioperative Ischemia Research Group. JAMA. 1996;276(4):300-6.

25. McNeely W, Goa KL. Nebivolol in the management of essential hypertension: a review. Drugs. 1999;57(4):633-51.

14. Almassi GH, Schowalter T, Nicolosi AC, Aggarwal A, Moritz TE, Henderson WG, et al. Atrial fibrillation after cardiac surgery: a major morbid event? Ann Surg. 1997;226(4):501-11.

26. Erdil N, Nisanoğlu V, Eroğlu T, Tüten R, Cihan HB, Kutlu R, et al. Choice of medication for radial artery vasodilation in patients awaiting coronary artery bypass grafting. Turk Gogus Kalp Dama. 2011;19(1):7-11.

15. Fuller JA, Adams GG, Buxton B. Atrial fibrillation after coronary artery bypass grafting. Is it a disorder of the elderly? J Thorac Cardiovasc Surg. 1989;97(6):821-5.

27. Toblli JE, DiGennaro F, Giani JF, Dominici FP. Nebivolol: impact on cardiac and endothelial function and clinical utility. Vasc Health Risk Manag. 2012:8:151-60.

16. Lauer MS, Eagle KA, Buckley MJ, DeSanctis RW. Atrial fibrillation following coronary artery bypass surgery. Prog Cardiovasc Dis. 1989;31(5):367-78.

28. Tuncer M, Fettser DV, Gunes Y, Batyraliev TA, Guntekin U, Gumrukchuoglu KhA, et al. Comparison of effects of nebivolol and atenolol on P-wave dispersion in patients with hypertension. Kardiologiia. 2008;48(4):42-5.

17. Creswell LL, Schuessler RB, Rosenbloom M, Cox JL. Hazards of postoperative atrial arrhythmias. Ann Thorac Surg. 1993;56(3):539-49. 18. Mathew JP, Fontes ML, Tudor IC, Ramsay J, Duke P, Mazer CD, et al; Investigators of the Ischemia Research and Education Foundation; Multicenter Study of Perioperative Ischemia Research Group. A multicenter risk index for atrial fibrillation after cardiac surgery. JAMA. 2004;291(14):1720-9.

29. Vandeplassche G, Lu HR, Wouters L, Flameng W, Borgers M. Normothermic ischemic cardiac arrest in the isolated working rabbit heart: effects of dl-nebivolol and atenolol. Basic Res Cardiol. 1991;86(1):21-31. 30. Van Bortel LM, van Baak MA. Exercise tolerance with nebivolol and atenolol. Cardiovasc Drugs Ther. 1992;6(3):239-47.

19. Zacharias A, Schwann TA, Riordan CJ, Durham SJ, Shah AS, Habib RH. Obesity and risk of new-onset atrial fibrillation after cardiac surgery. Circulation. 2005;112(21):3247-55.

31. Galderisi M, D’Errico A. Beta-blockers and coronary flow reserve: the importance of a vasodilatory action. Drugs. 2008;68(5):579-90.

20. Echahidi N, Mohty D, Pibarot P, Després JP, O’Hara G,

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Guizilini S, et ORIGINAL al. - Pleural subxyphoid drain confers better pulmonary function ARTICLE and clinical outcomes in chronic obstructive pulmonary disease after off-pump coronary artery bypass grafting: a randomized controlled trial

Pleural subxyphoid drain confers better pulmonary function and clinical outcomes in chronic obstructive pulmonary disease after off-pump coronary artery bypass grafting: a randomized controlled trial Dreno pleural subxifoide confere melhor função pulmonar e resultados clínicos na doença pulmonar obstrutiva crônica após cirurgia de revascularização miocárdica sem circulação extracorpórea: ensaio clínico controlado e randomizado

Solange Guizilini1, PhD; Marcela Viceconte2, PT; Gabriel Tavares da M. Esperança2, PT; Douglas W. Bolzan2, PhD; Milena Vidotto1, PhD; Rita Simone L Moreira2, PhD; Andréia Azevedo Câncio2, MsC; Walter J Gomes2, PhD

DOI 10.5935/1678-9741.20140047

RBCCV 44205-1594

Abstract Objective: To evaluate the lung function and clinical outcome in severe chronic obstructive pulmonary disease in patients undergoing off-pump coronary artery bypass grafting with left internal thoracic artery graft, comparing the pleural drain insertion in the intercostal versus subxyphoid region. Methods: A randomized controlled trial. Chronic obstructive pulmonary disease patients were randomized into two groups according pleural drain site: II group (n=27) - pleural drain in intercostal space; SI group (n=29) - pleural drain in the subxyphoid region. Spirometry values (Forced Vital Capacity - and Forced expiratory volume in 1 second) were obtained on preoperative and 1, 3 and 5 postoperative

days. Chest x-ray from preoperative until postoperative day 5 (POD5) was performed for monitoring respiratory events, such as atelectasis and pleural effusion. Pulmonary shunt fraction and pain score was evaluate preoperatively and on postoperative day 1. Results: In both groups there was a significant decrease of the spirometry values (Forced Vital Capacity and Forced expiratory volume in 1 second) until POD5 (P<0.05). However, when compared, SI group presented less decrease in these parameters (P<0.05). Pulmonary shunt fraction was significantly lower in SI group (P<0.05). Respiratory events, pain score, orotracheal intubation time and postoperative length of hospital stay were lower in the SI group (P<0.05).

Cardiology and Cardiovascular Surgery Discipline, São Paulo Hospital, Escola Paulista de Medicina, Department of Human Motion Sciences, Physical Therapy School – Universidade Federal de São Paulo, São Paulo, SP, Brazil.

Correspondence address: Solange Guizilini Universidade Federal de São Paulo (Unifesp) Rua Botucatu, 740 - Vila Clementino - São Paulo, SP, Brazil Zip code: 04023-062 E-mail: sguizilini@unifesp.br

Cardiology and Cardiovascular Surgery Discipline, São Paulo Hospital, Escola Paulista de Medicina, Universidade Federal de São Paulo (Unifesp), São Paulo, SP, Brazil. 2

No financial support.

This study was carried out at the São Paulo Hospital, Escola Paulista de Medicina, Federal University of São Paulo (Unifesp), São Paulo, SP, Brazil.

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Article received on October 24th, 2013 Article accepted on January13th, 2014

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Guizilini S, et al. - Pleural subxyphoid drain confers better pulmonary function and clinical outcomes in chronic obstructive pulmonary disease after off-pump coronary artery bypass grafting: a randomized controlled trial

em dois grupos de acordo com a posição do dreno pleural: grupo II (n=27) - dreno pleural intercostal; grupo IS (n=29) dreno pleural na região subxifóide. Os valores espirométricos (Capacidade Vital Forçada e Volume expiratório forçado no 1 segundo) foram obtidos no pré-operatório, e no 1º, 3º e 5º dias de pós-operatório. Foi realizada radiografia de tórax no préoperatório até o 5º dia pós-operatório (5PO) para monitoração de eventos respiratórios, como atelectasia e derrame pleural. A fração de shunt pulmonar e a escala de dor foram avaliadas no 1º dia pós-operatório. Resultados: Em ambos os grupos houve queda significativa dos valores espirométricos (Capacidade Vital Forçada e Volume expiratório forçado no 1 segundo) até o 5PO (P<0.05), porém, quando comparados, o grupo IS apresentou menor queda destes parâmetros (P<0.05). A fração de shunt pulmonar foi significativamente menor no grupo IS (P<0.05). Os eventos respiratórios, escala da dor, tempo de intubação orotraqueal e dias internação hospitalar no pós-operatório foram menores no grupo IS (P<0.05). Conclusão: Drenagem pleural subxifoide em pacientes com doença pulmonar obstrutiva crônica grave determinou melhor preservação e recuperação dos volumes e capacidades pulmonares, com menor fração de shunt pulmonar e melhores resultados clínicos no pós-operatório precoce de cirurgia de revascularização do miocárdio sem circulação extracorpórea.

Abbreviations, acronyms & symbols CABG COPD FEV1 FVC ITA OPCAB POD

Coronary artery bypass graft Chronic obstructive pulmonary disease Forced expiratory volume in 1 second Forced Vital Capacity Internal thoracic artery Off-pump coronary artery bypass grafting Postoperative day

Conclusion: Subxyphoid pleural drainage in severe Chronic obstructive pulmonary disease patients determined better preservation and recovery of pulmonary capacity and volumes with lower pulmonary shunt fraction and better clinical outcomes on early postoperative off-pump coronary artery bypass grafting. Descriptors: Pulmonary Disease, Chronic Obstructive. Respiratory Function Tests. Coronary Artery Bypass, Off-Pump. Resumo Objetivo: Avaliar a função pulmonar e os resultados clínicos em pacientes com doença pulmonar obstrutiva crônica grave submetidos à cirurgia de revascularização do miocárdio sem circulação extracorpórea, com enxerto da artéria torácica interna esquerda, comparando a inserção do dreno pleural intercostal versus subxifoide. Métodos: Estudo clínico, controlado e randomizado. Pacientes com doença pulmonar obstrutiva crônica foram randomizados

Descritores: Doença Pulmonar Obstrutiva Crônica. Testes de Função Respiratória. Ponte de Artéria Coronária sem Circulação Extracorpórea.

INTRODUCTION

function[6,7]. Our hypothesis is that reducing thoracic trauma in COPD patients underwent OPCAB could determine lower impairment to the lung function and better clinical results. Therefore, the aim of this study was to evaluate the pulmonary function and clinical outcomes in severe COPD patients, comparing pleural drain insertion site in intercostal space versus subxyphoid region after OPCAB using left ITA (LITA).

Chronic obstructive pulmonary disease (COPD) has been associated with increased morbidity and mortality in patients undergoing coronary artery bypass graft (CABG)[1]. Many studies showed that as higher severity degree of COPD is associated to longer mechanical ventilation time and length of stay in the hospital and, consequently, increased hospital costs[2]. Furthermore, severe COPD patients undergoing CABG have a worse prognosis and increased mortality rate at long-term, when compared to patients without COPD[3,4]. Several factors may influence pulmonary function and clinical results in patients undergoing CABG, such as: general anesthesia, sternotomy, cardiopulmonary bypass, internal thoracic artery (ITA) graft with pleurotomy and pleural drain[5]. Pleural drain insertion through intercostal space promotes higher thoracic trauma, increased pain and discomfort for the patient, leading to increased vulnerability to lung complications. In patients without COPD undergoing offpump CABG (OPCAB), the shift of pleural drain insertion to subxyphoid region reduces postoperative pulmonary dys-

METHODS This prospective randomized study was performed between December 2007 and March 2012 at the Cardiovascular Surgery Discipline, Sao Paulo and Pirajussara Hospitals of the Federal University of Sao Paulo, Sao Paulo, Brazil. The Institutional Human Ethics Committee approved the protocol and written informed consent was obtained from all patients. Patients study group Patients of both sexes, age between 35 and 75 years old, coronary disease confirmed by coronary angiography, under-

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going elective OPCAB using LITA, with an ejection fraction > 50%, and severe COPD were included in this study. We excluded patients unable to perform spirometry, with hemodynamic instability, intraoperative death, renal failure (creatinine >1.3 mg/dL), intact pleura, intraoperative complications requiring on-pump CABG conversion and patients who required additional analgesia. The subjects were randomized into two groups by computerized system according to pleural drain position and the secrecy was maintained by sealed, numbered and opaque envelopes: II group (n=27), pleural drain was inserted in the sixth intercostals space; and SI group (n=29), pleural drain in the subxyphoid position.

Anesthesia and ventilation management All patients received a standard anesthetic technique, induction with etomidate and midazolam, maintenance with sufentanil and isofluorane (0.5% to 1%) and were mechanically ventilated to maintain normocapnia, with a 50% inspired oxygen fraction without positive end-expiratory pressure. Intraoperative fluids were given according to the anesthetist discretion. Operative technique The OPCAB surgery was performed through a median sternotomy, using LITA complemented with additional saphenous vein grafts. The LITA was harvested in a skeletonized fashion. A heated water mattress was used to keep all patients normothermic throughout the operation. OPCAB has followed the pattern at our service. Briefly, with systemic heparinization to achieve an activated clotting time exceeding 250 seconds, occlusion of the coronary artery was accomplished by using a proximal soft silicone snare. The distal anastomosis was accomplished with a 7-0 running polypropylene suture. The vein top ends were then attached to the ascending aorta using side-bite clamping. An Octopus 3 (Medtronic, Inc, Minneapolis, MN) suction stabilizer was used in all cases. Before chest closure, and in the presence of left pleura opening, the site of pleural drain insertion was randomized. A soft tubular straight PVC drain (¼ inch) was inserted and exteriorized at the intersection of the sixth left intercostal space (Group II) or a curved one at the subxyphoid region and positioned in the left costophrenic sinus (Group SI). In all patients, a straight mediastinal drain was also placed via a subxyphoid approach.

Lung function assessment Spirometry records were obtained to evaluate the forced vital capacity (FVC) and the forced expiratory volume in 1 second (FEV1) on preoperative and postoperative days 1, 3, and 5 (POD1, POD3, POD5) by the same respiratory physiotherapist, using a portable espirometer (Spirobank G, MIR, Rome, Italy) according to the standards of the American Thoracic Society[8]. Chronic obstructive pulmonary disease was defined according to the criteria of the Global Initiative for Chronic Obstructive Lung Disease – GOLD, with presence of dyspnea (progressive and/or persistent), chronic cough or sputum production, and/or a history of exposure to risk factors for the disease (tobacco smoking, occupational dusts and chemical), and by spirometry with FEV1/FVC < 0.70. Furthermore, the severity of COPD was defined as described on Table 1[9].

Postoperative Management All patients were transferred to the intensive care unit (ICU) with orotracheal intubation, inspired oxygen fraction to keep arterial oxygen saturation above 90%, predicted tidal volume of 8 ml/kg, PEEP of 5 cmH2O and extubated according to ICU protocol. The drains (mediastinal and/or pleural) were routinely removed on POD2. During postoperative days, the patients were evaluated by the same physiotherapist and all patients were undergone to the same physical therapy program until hospital discharge (breathing exercises and early deambulation).

Table 1. Chronic obstructive pulmonary disease stage classification according to GOLD Guidelines. Stage I: mild COPD Stage II: moderate COPD Stage III: severe COPD Stage IV: very severe COPD

FEV1/CVF < 70% andFEV1 ≥ 80% FEV1/CVF < 70% and 50% ≤ FEV1< 80% FEV1/CVF < 70% and 30% ≤ FEV1< 50% FEV1/CVF < 70% and FEV1< 30%

COPD = Chronic obstructive pulmonary disease; FEV 1=Forced expiratory volume in 1 second; FVC=forced vital capacity; GOLD =Global Initiative for Chronic Obstructive Lung Disease

Clinical Outcomes All patients underwent to the same analgesic protocol administered during the postoperative period (100mg of tramadol chlorhydrate 4 times a day). Pain was evaluated and quantified by Visual Analogical Scale (VAS)[10] (0 = no pain to 10 = unbearable pain) on POD1 and before spirometry. Total orotracheal intubation time and length of hospital stay after surgery were also recorded. The patients were undergoing chest radiography on preoperative, POD1, POD3 and POD5 for monitoring respira-

Pulmonary shunt fraction was evaluated preoperatively and on POD1 using the software Oxygen Status Algorithm, (version 2.0; Mads & Ole Siggaard; Radiometer). This software needs the arterial blood gas and the fraction of inspired oxygen to calculate the percentage of blood that is not supplied by oxygen.

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tory events, like pleural effusion and atelectasis. The radiological evaluation was performed by the same radiologist, blinded to the study. The pleural effusion was deemed significant when exceeding the costophrenic angle. Atelectasis was acknowledged when a clear atelectasis radiologic shadow exceeded 15 mm in width, with linear atelectasis being disregarded in this study. Statistical analysis Data were expressed as mean ± standard deviation. The FVC, FEV1 were analyzed, and values are expressed as a percentage of the preoperative value considered as 100% the preoperative baseline value. Intragroup variables comparing pre versus postoperative values were evaluated by paired Student t tests and analysis of variance for repeated measures with the Newman-Keuls posttest. Differences between groups were analyzed by unpaired Student t test or the Mann-Whitney test, when necessary. The categoric data were analyzed by the Pearson chi-square test. Statistical analysis was performed with GraphPad Prism 3.0 software (GraphPad Software Inc, San Diego, CA). A value of P<0.05 was considered statistically significant.

Fig. 1 - Flow diagram of the progress through the phases of a randomized trial.

RESULTS Initially, 165 subjects were selected for this study, however, 95 were excluded in the pre- and intraoperative, 14 were lost to follow-up and 56 were actually analyzed according to Figure 1. Groups were homogeneous preoperatively in terms of age, gender, body mass index (BMI), preoperative pulmonary function, operative time, number of grafts per patients with no significant statistically differences, as shown in Table 2. No signs of preoperative myocardial infarction were detected in either group, as assessed by electrocardiographic changes or enzyme elevation. In the postoperative period, the both groups presented significant reduction in spirometric parameters (FVC and FEV1) until POD5 (P<0.05). However, when compared the values, the SI group presented lower impairment (Figure 2). The pulmonary shunt fraction increase in both groups, but was significantly lesser in SI group (0.24±0.03% versus 0.28±0.04%; P<0.001). In relation to respiratory events, lower incidence of atelectasis and pleural effusion was observed in SI group (atelectasis: 21±3.4% versus 25±0.1%; P=0.001 e pleural effusion: 22±2.4% versus 26±1.7%; P=0.003). The chest pain sensation was lesser in group SI than II group (4.6±3.4 versus 7.9±2.1, P=0.001). Moreover, the time of mechanical ventilation and the length of hospital stay was lower in SI group when compared to II group (13.98±1.4 hours versus 16.25±2.1 hours; P=0.001; 9.51±1.6 days versus 12.1±1.4 days; P<0.001).

Table 2. Baseline patient characteristics. Group II (N=27) Variables 59.22 ± 11.73 Age (years) Gender (n) 18/9 Male/ Female

Group SI (N=29) 56.66 ± 10.33

0.32

20/9

0.42

BMI (kg/m2)

24.52 ± 3.56

26.12± 4.61

0.24

Pulmonary function FVC (L) % predicted FEV1 (L) % predicted

3.27 ± 0.26 98.2 ± 21.70 1.40 ± 0.35 40.32 ± 7.22

3.51± 0.45 101.25 ± 25.24 1.37 ± 0.22 38.21 ± 9.07

0.39

0.03 ± 0.03

0.04 ± 0.02

0.10

314.8 ± 29.78 2.71 ± 0.42

309.4 ± 21.98 2.62 ± 0.77

0.33 0.39

Pulmonary shunt fraction (%) Surgery time (min) Grafts per patient (n)

0.32

Data are shown as mean ± standard deviation. BMI = body mass index; FEV1 = Forced expiratory volume in 1 second; FVC = forced vital capacity; II = intercostal insertion; SI = subxyphoid insertion.

DISCUSSION The results demonstrated that both groups presented impairment in pulmonary function in the early postoperative. However, the patients of SI group presented better pulmo-

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nary function and clinical outcomes when compared to II group. This data corroborate with findings by other studies with patients without COPD[5,11].

tensity[6,7,11]. Furthermore, Guizilini et al.[19] observed that the insertion of a chest tube in the subxyphoid region resulted in similar findings to CABG with intact pleura. COPD can also be considered a risk factor for development of pulmonary dysfunction in postoperative period of CABG. Fuster et al.[2] and Lizak et al.[20] compared postoperative outcomes of patients with and without COPD and observed that patients with COPD had a higher incidence of pulmonary complications and hospital stay, more pronounced in patients with severe COPD. Taking into account evidence that shifting the site of drain insertion to the subxyphoid region may be beneficial for the postoperative clinical outcomes, and the fact that patients with severe COPD have a higher risk of pulmonary complications in this period, this study aimed to answer the following question: Do patients with clinically severe COPD would benefit by shifting the drain position in the postoperative period of OPCAB using the LITA graft? For our knowledge, no randomized controlled trial has evaluated the impact of drain shifting in severe COPD patients undergoing OPCAB, which makes our proposal innovative and original. Previous studies compared the effectiveness of shifting the drain insertion site to the subxyphoid region and reported lesser lung function impairment[6,11,19]. These findings corroborate the results found in this study, reiterating the hypothesis that subxyphoid drain minimizes the dysfunction in postoperative period of OPCAB surgery, even in patients with severe COPD. Regarding the chest pain, patients with subxyphoid drain reported less intensity on VAS. The same result was reported in other studies with patients without COPD, which showed less pain when the chest tube was inserted in the subxyphoid region[6,11,21]. Similar outcomes were found in this study. Sensoz et al.[11] evaluated patients with COPD undergoing on-pump CABG by means of computed tomography. Patients who belonged to the group with pleural drain in subxyphoid region evolved with a lower incidence of atelectasis in postoperative period, corroborating the results found in this study. Hypoxemia is also an unavoidable consequence in CABG postoperative, regardless of surgical technique[5,6]. There are many causes of hypoxemia, abnormal diffusion, hypoventilation and shunt. In this study, the pulmonary shunt fraction was assessed on the first postoperative day, which was significantly lower in the subxyphoid group. These findings could be explained due to better preservation and recovery of FVC and consequently decrease of pulmonary fraction shunt, reflects the chest wall lesser degree of trauma in patients with pleural subxyphoid drain. Fuster et al.[2] associated severe COPD with higher incidence of pneumonia, sepsis and respiratory distress syndrome, longer ICU stay, and greater number of hospitalization days in the postoperative period of coronary revasculariza-

Fig. 2 - Pulmonary function test values on the POD1, 3 and 5, in percentage considering 100% preoperative baseline value. Data are shown as mean ± standard deviation. BMI=body mass index; FEV1=Forced expiratory volume in 1 second; FVC=forced vital capacity; II=intercostal insertion; SI=subxyphoid insertion.

The lung dysfunction in postoperative period after CABG is associated with intraoperative procedures. The use of general anesthesia[12], the sternotomy[13], cardiopulmonary bypass[5], ITA graft with consequent pleurotomy and necessity of pleural drain insertion make the pulmonary dysfunction unavoidable[14]. The use of ITA graft for coronary revascularization is associated with higher survival and less incidence of cardiovascular events when compared to saphenous vein graft[15]. The technique of skeletonized ITA dissection has been proved beneficial to reduce sternal complications or infections, due to better preservation of arterial branches supplying sternal and intercostal muscles[16]. Beyond reduction of blood supply, the manipulation of ITA may lead the opening of parietal pleura[17]. Consequently to pleurotomy, pleural drainage becomes mandatory. In the majority of the operations, the chest tube is inserted and exteriorized in the intercostal space, coming into contact with the periosteum and the parietal pleura, which are highly sensitive. Therefore, the use of intercostal chest tube can promote ventilatory-dependent pain, limiting deep inspiration, which leads to the adoption of an antalgic posture, immobilization and reduced lung volumes and capacities[18]. Recent studies have evaluated the postoperative clinical follow-up of patients undergoing CABG, with exteriorization of the drain in the subxyphoid region, and concluded that this strategy minimizes the pulmonary dysfunction in postoperative period, with better spirometric parameters, lower rate of atelectasis and pleural effusion, and lower pain in-

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tion. Saleh et al.[1] found that COPD severity is a significant prognostic marker in clinical outcomes after CABG. In this study, we found similar results; however the SI group presented shorter mechanical ventilation time and length of hospital stay, which may be reflected in reduced hospital costs, although this finding was not evaluated. This study has some limitations. The assessment of patients after surgery was not blind because of the possibility to visualize the drain position in the rib cage, with exception of radiological analyses; however the spirometry was performed according to ATS standardization to confirm the airflow limitation, by the same evaluator, reducing the evaluation bias. Furthermore, the sample size was limited by the tight inclusion criteria restricted to severe COPD. Considering the results of this study and others, it is clear that CABG elicits postoperatively pulmonary dysfunction and may exacerbate in the existence of comorbidities such as COPD. Drain shifting to the subxyphoid region is recommended for further decreasing trauma to the chest and can be an alternative to minimize the postoperative pulmonary dysfunction in this group of patients.

3. Nishiyama K, Morimoto T, Furukawa Y, Nakagawa Y, Ehara N, Taniguchi R, et al. Chronic obstructive pulmonary disease–an independent risk factor for long-term cardiac and cardiovascular mortality in patients with ischemic heart disease. Int J Cardiol. 2010;143(2):178-83. 4. Leavitt BJ, Ross CS, Spence B, Surgenor SD, Olmstead EM, Clough RA, et al.; Northern New England Cardiovascular Disease Study Group. Long-term survival of patients with chronic obstructive pulmonary disease undergoing coronary artery bypass surgery. Circulation. 2006;114(1 Suppl):I430-4 5. Guizilini S, Gomes WJ, Faresin SM, Bolzan DW, Alves FA, Catani R, et al. Evaluation of pulmonary function in patients following on- and off-pump coronary artery bypass grafting. Rev Bras Cir Cardiovasc 2005;20(3):310-6. 6. Guizilini S, Gomes WJ, Faresin SM, Carvalho ACC, Jaramillo JI, Alves FA, et al. Effects of the pleural drain site on the pulmonary function after coronary artery bypass grafting. Rev Bras Cir Cardiovasc. 2004;19(1):47-54. 7. Cancio AS, Guizilini S, Bolzan DW, Dauar RB, Succi JE, de Paola AA, et al. Subxyphoid pleural drain confers lesser impairment in respiratory muscle strength, oxygenation and lower chest pain after off-pump coronary artery bypass grafting: a randomized controlled trial. Rev Bras Cir Cardiovasc. 2012;27(1):103-9.

CONCLUSION Subxyphoid pleural drainage in severe COPD patients determined better preservation and recovery of pulmonary capacity and volumes with lower pulmonary shunt fraction and better clinical outcomes on early postoperative OPCAB.

8. American Thoracic Society. Standardization of spirometry. 1994 Update. Am J Respir Crit Care Med.1995;152(3):1107-36. 9. Vestbo J, Hurd SS, Agustí AG, Jones PW, Vogelmeier C, Anzueto A, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2013;187(4):347-65.

Authors’ roles & responsibilities SG MV GTME DWB MV RSLM AAC WJG

Data collection and manuscript preparation Data collection and manuscript preparation Data collection Data collection Statistical analysis and data collection Manuscript preparation Data collection Review of the manuscript

10. Symreng T, Gomez MN, Rossi N. Intrapleural bupivacaine v saline after thoracotomy--effects on pain and lung function--a double-blind study. J Cardiothorac Anesth. 1989;3(2):144-9. 11. Sensoz Y, Gunay R, Tuygun AK, Balci AY, Sahin S, Kayacioglu I, et al. Computed tomography evaluation of different chest tube sites for residual pleural volumes after coronary artery bypass surgery. Ann Saudi Med. 2011;31(4):383-6. 12. Hedenstierna G, Edmark L. The effects of anesthesia and muscle paralysis on the respiratory system. Intensive Care Med. 2005;31(10):1327-35.

REFERENCES 1. Saleh HZ, Mohan K, Shaw M, Al-Rawi O, Elsayed H, Walshaw M, et al. Impact of chronic obstructive pulmonary disease severity on surgical outcomes in patients undergoing non-emergent coronary artery bypass grafting. Eur J Cardiothorac Surg. 2012;42(1):108-13.

13. Guizilini S, Bolzan DW, Faresin SM, Alves FA, Gomes WJ. Ministernotomy in myocardial revascularization preserves postoperative pulmonary function. Arq Bras Cardiol. 2010;95(5):587-93. 14. Wynne R, Botti M. Postoperative pulmonary dysfunction in adults after cardiac surgery with cardiopulmonary bypass: clinical significance and implications for practice. Am J Crit Care. 2004;13(5):384-93

2. Fuster RG, Argudo JAM, Albarova OG, Sos FH, López SC, Codoñer MB, et al. Prognostic value of chronic obstructive pulmonary disease in coronary artery bypass grafting. Eur J Cardiothorac Surg. 2006;29(2):202-9.

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15. Rolla G, Fogliati P, Bucca C, Brussino L, Di Rosa E, Di Summa M, et al. Effect of pleurotomy on pulmonary function after coronary artery bypass grafting with internal mammary artery. Respir Med. 1994;88(6):417-20.

19. Guizilini S, Bolzan DW, Faresin SM, Ferraz RF, Tavolaro K, Cancio AA, et al. Pleurotomy with subxyphoid pleural drain affords similar effects to pleural integrity in pulmonary function after off-pump coronary artery bypass graft. J Cardiothorac Surg. 2012;7:11.

16. Berdajs D, ZĂźnd G, Turina MI, Genoni M. Blood supply of the sternum and its importance in internal thoracic artery harvesting. Ann Thorac Surg. 2006;81(6):2155-9.

20. Lizak MK, Nash E, ZakliczyĹ&#x201E;ski M, Sliwka J, Knapik P, Zembala M. Additional spirometry criteria predict postoperative complications after coronary artery bypass grafting (CABG) independently of concomitant chronic obstructive pulmonary disease: when is off-pump CABG more beneficial? Pol Arch Med Wewn. 2009;119(9):550-7.

17. Guizilini S, Gomes WJ, Faresin SM, Bolzan DW, Buffolo E, Carvalho AC, et al. Influence of pleurotomy on pulmonary function after off-pump coronary artery bypass grafting. Ann Thorac Surg. 2007;84(3):817-22.

21. Hagl C, Harringer W, Gohrbandt B, Haverich A. Site of pleural drain insertion and early postoperative pulmonary function following coronary artery bypass grafting with internal mammary artery. Chest. 1999;115(3):757-61.

18. Jakob H, Kamler M, Hagl S. Doubly angled pleural drain circumventing the transcostal route relieves pain after cardiac surgery. Thorac Cardiovasc Surg. 1997;45(5):263-4.

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Pessotti CFX,ORIGINAL et al. - Comparative trial of the use of antiplatelet and oral ARTICLE anticoagulant in thrombosis prophylaxis in patients undergoing total cavopulmonary operation with extracardiac conduit: echocardiographic, tomographic, scintigraphic, clinical and laboratory analysis

Comparative trial of the use of antiplatelet and oral anticoagulant in thrombosis prophylaxis in patients undergoing total cavopulmonary operation with extracardiac conduit: echocardiographic, tomographic, scintigraphic, clinical and laboratory analysis Estudo comparativo entre o uso do antiagregante plaquetário e do anticoagulante oral na profilaxia de trombose em pacientes submetidos à operação cavopulmonar total com tubo extracardíaco: análise ecocardiográfica, angiotomográfica, cintilográfica, laboratorial e clínica

Cristiane Felix Ximenes Pessotti1, MD, PhD; Marcelo Biscegli Jatene2, MD, PhD; Ieda Biscegli Jatene2, MD, PhD; Patrícia Marques Oliveira3, MD; Fabiana Moreira Passos Succi3, MD; Valeria de Melo Moreira3, MD; Rafael Willain Lopes2, MD, PhD; Simone Rolim Fernandes Fontes Pedra2, MD, PhD

DOI 10.5935/1678-9741.20140111

RBCCV 44205-1595

Abstract Objective: To compare the efficacy of aspirin and warfarin for prophylaxis of thrombosis in patients undergoing total cavopulmonary anastomosis. Evaluate whether coagulation factors (VII, VIII and protein C), clinical data, fenestration or hemodynamic factors, interfere with postoperative thrombosis. Methods: A prospective, randomized study of 30 patients, randomized into Group I (Warfarin) and Group II (AAS), underwent total cavopulmonary shunt with extracardiac conduit, between 2008 and 2011, with follow-up by clinical visits to evaluate side effects and adhesion. Performed transesophageal echocardiography in post operatory time, 3, 6,12 and 24 months;

angiotomography at 6, 12 and 24 months to evaluate changes in the internal tube wall or thrombi and pulmonary scintigraphy to evaluate possible PTE. Results: Two deaths in group I; 33.3% of patients had thrombus (46.7% in Group II). The previous occurrence of thrombus and low levels of coagulation protein C were the only factors that influenced the time free of thrombus (P=0.035 and 0.047). Angiotomographic evaluation: 35.7% in group II presented material accumulation greater than 2 mm (P=0.082). Scintigraphy: two patients had PTE in group II. Five patients had difficulty to comply with the treatment, 4 in group I with INR ranging from 1 to 6.4. Conclusion: The previous occurrence of thrombus is a risk

Instituto do Coração of Hospital das Clínicas da Faculdade de Medicina of Universidade de São Paulo (InCor-HCFMUSP), São Paulo, SP, Brazil. 2 Faculdade de Medicina of Universidade de São Paulo (FMUSP), São Paulo, SP, Brazil. 3 Hospital do Coração, ASS, São Paulo, SP, Brazil.

Correspondence address: Cristiane Felix Ximenes Pessotti Instituto do Coração (InCor) of Hospital das Clínicas of Faculdade de Medicina of Universidade de São Paulo Av. Dr. Enéas Carvalho de Aguiar, 44 - Cerqueira César, São Paulo, SP, Brasil – CEP: 05403-000 E-mail: crisximenes08@gmail.com

This study was carried out at Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo InCor-HCFMUSP, São Paulo, SP, Brazil.

Article received on April 5th, 2014 Article accepted on September 23rd, 2014

No financial support.

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Pessotti CFX, et al. - Comparative trial of the use of antiplatelet and oral anticoagulant in thrombosis prophylaxis in patients undergoing total cavopulmonary operation with extracardiac conduit: echocardiographic, tomographic, scintigraphic, clinical and laboratory analysis

dos à derivação cavopulmonar total com tubo extracardíaco, entre 2008 e 2011, com seguimento de dois anos. Foram realizadas consultas clínicas que avaliavam efeitos colaterais e aderência. Realizado ecocardiograma transesofágico no pós-operatório imediato, 3, 6,12 e 24 meses; angiotomografia aos 6, 12 e 24 meses de pós-operatório para avaliação de alterações na parede interna do tubo ou trombos e cintilografia pulmonar, para avaliar possível TEP. Resultados: Dois óbitos no grupo I; 33,3% dos pacientes apresentaram trombo (46,7% no Grupo II). A ocorrência prévia de trombo e baixos níveis de proteína C da coagulação foram os únicos fatores que influenciaram no tempo livre de trombo (P=0,035 e 0,047). Avaliação angiotomográfica: 35,7% dos pacientes do grupo II tinham atapeteamento maior que 2 mm (P=0,082). Cintilografia: dois pacientes apresentaram TEP no grupo II. Cinco pacientes tiveram dificuldade de aderência, 4 no grupo I com INR variando de 1 a 6,4. Conclusão: A ocorrência prévia de trombo é um fator de risco para trombose no pós-operatório. Pacientes em uso de AAS tendem a depósito de material na parede do tubo. O número reduzido da amostra não permitiu concluir qual a droga mais eficaz na prevenção da trombose na população estudada.

Abbreviations, acronyms and symbols ASA HLHS IPO PTE

Acetylsalicylic acid Hypoplastic Left Heart Syndrome Immediate postoperative Pulmonary thromboembolism

factor for thrombosis in the postoperative period. Patients using AAS tend to deposit material in the tube wall. The small sample size did not allow to conclude which is the most effective drug in the prevention of thrombosis in this population. Descriptors: Fontan Procedure. Thrombosis. Warfarin. Aspirin. Prospective Studies. Resumo Objetivo: Comparar a eficácia do AAS e da Varfarina na profilaxia da trombose em pacientes submetidos a operação cavopulmonar total. Avaliar se fatores de coagulação (VII, VIII e Proteína C), dados clínicos, fenestração ou fatores hemodinâmicos, interferem na trombose no pós-operatório. Métodos: Estudo prospectivo e randomizado de 30 pacientes, randomizados em Grupo I (Varfarina) e Grupo II (AAS), submeti-

Descritores: Técnica de Fontan. Embolia e Trombose. Varfarina. Aspirina. Estudos Prospectivos.

INTRODUCTION

becomes solely responsible for the systemic circulation and the systemic venous return is delivered directly to the pulmonary arteries. A series of palliative surgery is performed in a staged manner until the final stage, the total cavopulmonary operation, which is currently performed by the extracardiac conduit interposed between the inferior vena cava and the right pulmonary artery (RPA). The occurrence of thromboembolic events in the postoperative evolution of the total cavopulmonary operation can reach 20%. In a meta-analysis recently published[3], the incidence of thromboembolism found ranged from 3 to 20%, with differences related to surgical technique, population considered and accuracy of imaging methods. The demonstration can be given by the formation of venous, arterial or intracardiac thrombosis, leading to death in about 25% of patients, even when they received specific and immediate treatment[4,5]. The etiology of thrombotic complications in patients undergoing the Fontan operation is multifactorial. Literature reports support the hypothesis that other factors, in addition to venous stasis and low flow velocity contributes to thrombus formation. Among them, we could note the presence

The univentricular hearts correspond to a group of congenital heart disease with different anatomical combinations, which culminate in a common feature: a single ventricle is responsible for the systemic and pulmonary circulation. In most cases it is possible to characterize the presence of two distinct ventricles - right and left – when one of them is hypoplastic and called rudimentary and the other, well-formed, called main camera. Among the most common anatomical forms is Tricuspid Atresia, in its different presentations, responsible for 0.3 to 5.3% of the congenital heart diseases, present in approximately 0.6 of every 10,000 live births[1]. With regard to the dominant right ventricle, the main anatomical representation is the hypoplastic left heart syndrome (HLHS), which represents about 3.8% of the congenital heart diseases, present in approximately 1.8 to 3.65 of 10,000 live births[2]. From the diagnosis in the neonatal period, different surgical approaches can be adopted, according to the anatomical and pathophysiological findings, so that the dominant ventricle

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of change in coagulations factors such as Protein S, protein C, antithrombin III, factor VII and VIII. Based on the findings of imbalance between the pro and anticoagulant factors, many studies suggest that these patients maintain resistant to an anticoagulation or hypercoagulable state[3,6]. There is still not a consensus in the literature about the best drug in the prevention of thrombus formation in patients in the postoperative period of total cavopulmonary connection with extracardiac conduit, and the commonly used drugs are acetylsalicylic acid (ASA) and warfarin.

Exclusion criteria were: 1. Some aspect of anatomical or angiographic features that contraindicated the cavopulmonary operation, including: a. Main ventricular ejection fraction less than 60%, or significant impairment of atrioventricular valve related to the predominant ventricle. b. Serious anatomical alteration of the pulmonary venous return (untreatable) c. Anatomy of severely unfavorable pulmonary tree. 2. Inability to perform outpatient treatment; 3. Any medical condition that prevented the randomization, for example, any indication that the patient used necessarily one of the two drugs evaluated, or contraindication to the use of them. 4. Refusal of legal guardian to sign the Post-information Consent The age during operation was not considered as indication or contraindication factors, being operated children of different ages. The children, within the routine protocol of the institution, underwent preoperative hemodynamic studies with cardiac catheterization and mean pulmonary artery pressure measurements (mPAP). The preoperative evaluation was consisted of two-dimensional color Doppler echocardiogram, electrocardiogram and cardiac catheterization. Once they were eligible for total cavopulmonary connection, and signed the informed consent form, patients were randomized to Group I or Group II, following randomization list generated by specific program. From this point forward, the child was subjected to evaluation of demographic and clinical characteristics, consisting of history and physical examination, and then evaluated according to the study protocol. Data were recorded on a follow-up and evaluation form. Depending on the group allocated by randomization, the patient received warfarin (Group I), at an initial dose of 0.1 mg/kg/day; or antiplatelet drug ASA (Group II), at a dose of 10 mg/kg/ day (maximum dose of 100 mg/day). Both were started at the time when the patient was receiving oral medication, and until then, was to use low molecular weight heparin (Enoxaparin) subcutaneously at a dose of 1mg/kg/day, once a day. In the randomized cases appropriate for the use of warfarin, patients were kept in use of subcutaneous heparin until the INR values reached 2-3. In the preoperative evaluation (Phase 1), a two-dimensional color Doppler echocardiography, transthoracically, electrocardiogram, and hemodynamic study by cardiac catheterization were performed, as well as lab tests with dosage of liver enzymes, INR, hematocrit, and factors coagulation VII, VIII, protein C. In the immediate postoperative period (Phase 2), until the tenth postoperative day (PO) the surgical technique used was recorded (whether or not fenestration and size of the extracardiac conduit), evolution and occurrences during the

Objectives Primary objectives 1. To compare the efficacy of oral anticoagulants (warfarin) and antiplatelet (ASA) for prophylaxis of thrombosis and thromboembolic events in the postoperative period of total cavopulmonary operation with extracardiac conduit. 2. To identify laboratory findings: hematocrit, liver function and coagulation factors in the preoperative and postoperative periods. 3. To identify and compare the viability of different treatments, as the clinical features, adhesion, safety and social implications. Secondary objectives 1. To identify flow changes by the extracardiac conduit in children in the postoperative period of total cavopulmonary connection, assessing the occurrence of slow flow and/or auto-contrast, through echocardiographic study series. 2. To identify changes in the internal wall of the extracardiac conduit by echocardiographic and angiotomographic serial examinations. 3. To identify the occurrence of subclinical pulmonary embolism (PE) by scintigraphy ventilation/pulmonary perfusion. METHODS The project was approved by the Coração Hospital Research Ethics Committee - Syrian Sanatorium Association, and Research Ethics Committe of the University of São Paulo Medical School (HCFMUSP) - CAPPesq. This is a prospective randomized study, with a 2-year follow-up, with the inclusion of 30 patients who underwent total cavopulmonary operation with extracardiac conduit in the period between 2008 and 2011. The follow-up was performed in the outpatient sector of the same institution, with consultations and assessments carried out by the researcher in the predetermined periods according to the study protocol. Inclusion criteria were: 1. Children with heart with univentricular morphology in staged programming, for total cavopulmonary shunt operation.

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period, transesophageal echocardiogram, electrocardiogram and INR control would be performed. The outpatient follow-up began in the 3rd month of the postoperative period (Phase 3), assessing progress and clinical complications, electrocardiogram, transesophageal echocardiogram and laboratory analysis: INR, hematocrit, liver enzymes and coagulation factors: Protein C, Factor VII and Factor VIII. The evaluation in the 6th month (Phase 4) was similar to the one in Phase 3, however, angiography of the chest was performed in this moment. In Phase 5 (one year after surgery) we performed an evaluation similar to that in Phase 4, adding ventilation/perfusion pulmonary scintigraphy. The last evaluaiton, two years after surgery, in Phase 6, was identical to that one in Phase 5. The collection of blood sample was performed by peripheral puncture. The sample assessment methodology consists of coagulometric method for dosing Factor VII, VIII and PT/ PR/INR, Functional Method for Protein C and dry chemical method for dosing AST, ALT and GGT. The preoperative echocardiogram was performed by transthoracic two-dimensional color doppler and postoperative examinations by transesophageal routes, Philips IE 33 device (Bathel-Andover), with pediatric probe in children weighing less than 20kg and adult probe in children with weighing greater than or equal to 20 kg, by a single examiner. The evaluation of the conduit was performed in longitudinal and cross-sectional cut, evaluating the flow by color flow mapping, and Doppler, with the thrombus evaluated by two-dimensional method. The ventricular systolic function was performed by subjective analysis and ventricular diastolic function by plotting the pulmonary vein Doppler. Angiotomography was performed by two radiologists examiners. Iodinated contrast material was applied at a dose of 1.5 ml/kg, and only one acquisition was made during apnea; two minutes after contrast injection, without synchronization with the electrocardiogram. The ventilation/perfusion scintigraphy was performed after one and two years after surgery. The examinations were performed with the camera flicker with two detectors, equipped with a low energy collimator, parallel channels and high resolution. Pulmonary inhalation tests were performed with radioaerosol closed system to prevent ambient air contamination, using Tc99m-DTPA. The pictures were taken after 10 minutes of continuous inhalation when it is expected that 10% of the dose inserted into the system to be absorbed into the alveolar space in the lungs. Planar images were acquired with 128 x 128 matrix, with 350.000 counts per projection. The projections were carried out in the anterior, posterior, anterior and posterior oblique and lateral chest incidences. Perfusion studies were performed with the same equipment, with intravenous administration of albumin macroaggregates, labeled with Tc99m. The children performed forced expiratory

maneuver (Valsalva). The dose was 2-3 mCi, with the number of particles not exceeding 500.000. In case of clinical signs of cyanosis, the number of particles was reduced to a maximum of 100.000. Images were acquired in the same projections of the inhaled study, accumulating 1000k counts per projection. The interpretation criteria followed standardization scheme as guidelines established by PIODED. The exposure dose for children was about 1 mSv per procedure. Data were recorded on a follow-up chart being stored and analyzed periodically. During the follow-up period, when identified the presence of thrombus or thromboembolic events in patients using ASA, these patients were subjected to specific treatment. Intravenous heparinization and subsequent anticoagulation were performed, and its consequent end of the follow-up period was within the assessment protocol. Statistical Analysis Statistical analysis of all information collected in this research was initially carried out in a descriptive manner. For quantitative variables (numerical) some summary measures were calculated, such as mean, median, minimum and maximum values, standard deviation, and one-dimensional scatter plot graph was drawn. The qualitative variables (categorized) were analyzed by calculating the absolute and relative frequencies (percentages), besides the construction of bar graphs. The inferential analyzes used in order to confirm or refute evidence found in the descriptive analysis were: • Pearson’s chi-square test, Fisher’s exact test or its extension to the study comparing the profiles of the treatment groups, according to gender, diagnosis, first and second surgery, pre-occurence of thrombus, hematocrit, liver function, protein C , factors VII and VIII, ventricular dysfunction, and surgical technique (with or without fenestration of the extracardiac conduit); • Student’s t test for independent samples comparing average levels of pulmonary pressure in the preoperative period between treatment groups; • Mann-Whitney test when comparing the age of the treatment groups; • Estimation of the survival curves (Kaplan-Meier) and log-rank test comparing the time (days) free of thrombus, according to treatment group, age, diagnosis, pulmonary pressure before surgery, surgical technique, history of thrombus, protein C, factor VII and VIII, ventricular dysfunction in every phase, high contrast in every phase after surgery, death and reintervention. In all the conclusions obtained by means of inferential analyzes, we used a 5% significance level. Data were entered in Excel 2010 spreadsheets for Windows for proper storage of information. Statistical analyzes were performed using the R 2.15.2 software.

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Table 1. Distribution of the general characteristics of children of ASA and OAC groups. gender female male age (years) mean median minimum maximum standard deviation diagnosis VUE AT VUD SHCE pulmonary pressure (mmHg) mean median minimum maximum standard deviation

ASa (n=15) 8 53.3% 7 46.7% 4.8 3.7 2.0 15.6 3.3 4 26.7% 8 53.3% 3 20.0% 14.9 15.0 11.0 19.0 2.3

OAC (n=15) 5 33.3% 10 66.7% 5.8 4.1 2.7 15.6 3.8 5 33.3% 1 6.7% 8 53.3% 1 6.7% 16.7 16.0 9.0 23.0 3.6

Total (n=30)

13 43.3% 17 56.7%

0.269a

5.3 4.0 2.0 15.6 3.5

0.330b

30.0% 30.0% 36.7% 3.3%

0.026c

15.8 15.5 9.0 23.0 3.1

0.102d

9 9 11 1

Chi-square test, bMann-Whitney test, cFisherâ&#x20AC;&#x2122;s Exact test or its extension, Studentâ&#x20AC;&#x2122;s dt-test for independent samples a

pulmonary connection the with extracardiac conduit is shown in Table 2.

Table 2. Surgical procedure performed on total cavopulmonary anastomosis. Surgical Procedure Isolated ECC Fenestrated ECC ECC and Damus-Kaye-Stansel ECC and Glenn Anastomosis ECC=Extracardiac conduit

OAC Group: n(%) 11 (73.33%) 1 (6.66%) 2 (13.33%) 1 (6.66%)

Grupo II: n (%) 12 (80%) 3 (20%) 0 0

Clinical follow-up Among the thirty patients treated, six had thrombus formation. Five of these patients had thrombus in the extracardiac conduit and one of them in the inferior vena cava, diagnosed by transesophageal echocardiography in the immediate postoperative period (within the first 10 days after surgery). Among them, four were using ASA and two using OAC. Due to the formation of thrombus, the patient underwent intravenous heparin in ICU and then watched according to the clinical need, the follow-up was then interrupted by the study protocol. During the follow-up period, there were two deaths, both allocated to the OAC group, not related to the occurrence of thrombus. One patient had died five months after surgery, before hospital discharge, during the takedown surgery due to Fontan circuit failure. The second child evolved with protein-losing enteropathy, immunosuppression and infectious complications, and opted for fenestrating the conduit, dying in the postoperative period of the fenestration procedure, one year after total cavopulmonary connection. Table 3 summarizes the occurrence of thrombus from the preoperative period to the 24th month after surgery. By the end of the follow-up period (24 months postoperatively), ASA group had 46.7% (7/15) of children with thrombus. In OAC group, we observed 20.0% (3/15) children with thrombus, despite

RESULTS The clinical and demographic characteristics are presented in Table 1. All procedures were performed with extracardiac PTFE (polytetrafluoroethylene) conduit, varying from 16mm to 20mm, and 19 (63.3%) patients underwent surgery with cardiopulmonary bypass (CPB). In cases where it was necessary to correct intracardiac defect or atrioseptostomy, a CPB circuit was installed. The use of fenestration between the extracardiac conduit and the right atrium was essentially a decision of the surgical team for the worst cases, in which we could note the presence of light changes of the pulmonary tree or borderline pulmonary pressure (16-18 mmHg). The type of surgical procedure associated with total cavo-

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Table 3. Distribution of the occurrence of thrombosis in children of ASA and ACO groups, second phase. Preoperative period (history of thrombus) present absent Total Immediate postoperative period present absent Total 3 months after surgery present absent death Total 6 months after surgery present absent death Total 12 months after surgery present absent death Total 24 months after surgery present absent death Total

ASA n % 4 26.7% 11 73.3% 15 100.0% 4 26.7% 11 73.3% 15 100.0% - 11 73.3% - 15 100.0% - 11 73.3% - 15 100.0% 2 13.3% 9 60.0% - 15 100.0% 1 6.7% 8 53.3% - 15 100.0%

the difference, it was not statistically significant P=0.121. The occurrence of thrombus for the other phases are described in Table 3. In order to investigate the factors that interfere in thrombusis-free-survival time, including the drug used in the prophylaxis (OAC or ASA), the age of total cavopulmonary connection (arbitrarily divided into: less than five years and greater than five years), the morphology of single ventricle (VUE or SUVs), the mPAP in the preoperative period (≥ to 18 mmHg), the presence of fenestration, history of thrombus and ventricular dysfunction in every phases during the evaluation; survival curves were constructed, and then, the log-rank test was used. The results of these tests confirmed that the thrombus free time is not related to the following factors: • Use of aspirin or OAC (P=0.156) - Figure 1 • Age group (P=0.471); • Diagnosis (P=0.960), • mPAP in the preoperative period (P=0.606),

OAC N % 2 13.3% 13 86.7% 15 100.0% 2 13.3% 13 86.7% 15 100.0% - 12 80.0% 1 6.7% 15 100.0% - 12 80.0% 1 6.7% 15 100.0% 1 6.7% 10 66.7% 2 13.3% 15 100.0% - 10 66.7% 2 13.3% 15 100.0%

Total n % 6 20.0% 24 80.0% 30 100.0% 6 20.0% 24 80.0% 30 100.0% - 23 76.7% 1 3.3% 30 100.0% - 23 76.7% 1 3.3% 30 100.0% 3 10.0% 19 63.3% 2 6.7% 30 100.0% 1 3.3% 18 60.0% 2 6.7% 30 100.0%

• Fenestration (P=0.477), • Ventricular dysfunction during preoperative period (P= 0.224) in the immediate postoperative period (P=0.329), three months after surgery (P=0.967), 6 months after surgery (P=0.664), 12-month postoperative period (P=0.458) and 24 months after surgery (P=0.409). Among all variables analzed, the one that showed main influence on the occurrence of thrombus in the postoperative course, was the presence of thrombus prior: thrombus free time in children with no history of thrombosis is statistically higher when compared to children with a history of thrombus (P=0.035) Figure 2. Concerning the coagulation factors, there is a considerable number of patients in each group who already have these changed factors in the preoperative period, mainly Protein C, which is an important anticoagulation factor. Serum Protein C was low in 33% of patients in the ASA group and 40% of the OAC group. However, surprisingly, the number of patients who developed free of thrombus was significantly higher

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Fig.1 - Thrombus-free survival curve comparing the ASA group to the OAC group.

Fig.2 - Thrombus-free survival curve comparing patients with history of prior occurrence of thrombus and without occurrence of thrombus.

among individuals with a deficit of this protein in the preoperative period (P=0.047) than those with normal levels of this anticoagulant factor, at the same moment of the evaluation. On the other hand, serum factors VII and VIII levels had no influence on thrombus free time in the postoperative period in patients evaluated with values of P=0.550 and P=0.329, respectively. The comparison of serum levels of coagulation factors evaluated in the postoperative period can not be considered, as they were under strong influence of warfarin. Among patients undergoing outpatient follow-up, five of them had lack of adherence to treatment and did not use the medication properly. Clinical monitoring was possible exclusively due to the researcherâ&#x20AC;&#x2122;s urgent demand, with the aid of the Institution social assistance service. Parents justified the lack of adherence by giving some resons, including: financial difficulty to pay for transport to attend appointments and check ups. Another reason was the perception of good clinical condition of the child, leading them to judge that the use of medication or any revaluations were not necessary. Among these five patients, four were using OAC, and consequently, outside the therapeutic range during the follow-up evaluation. Among patients on warfarin, the INR value ranged from 1 to 6.4. Among the 15 patients who made up this group (OAC) 14 (93.3%) had at least one INR measure out of range during the follow-up period, and two (13.3%) had INR greater than 4, which implies bleeding risk.

The occurrence of slow flow through the conduit, with the presence of high contrast in varying degrees, was a relatively common finding in the immediate postoperative period, five patients in each group (33.33%). However, the occurrence of high contrast in extracardiac conduit, assessed by transesophageal echocardiography in the immediate postoperative period, did not interfere in the free development of thrombus (P=0.148).

Fig.3A - Material deposited in the extracardiac conduit - Chest angiotomography image (short axis) performed 6 months after total cavopulmonary connection with extracardiac conduit. Short axis cuts (arrow)

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Fig. 4 - Pulmonary thromboembolism - Ventilation/perfusion scintigraphy in patient using ASA, performed two years after total cavopulmonary connection with extracardiac conduit, showing pulmonary thromboembolism at the apex of the left lung (segment 11).

Table 4 describes the occurrence of material deposited on the wall of the extracardiac conduit, visualized by chest angiotomography. The thickness of the hyperechoic image in question ranged from 0.9 mm to 3.5 mm, with the latter correlating thrombus image to transesophageal echocardiography. Over the postoperative period, this characteristic was more important in ASA group in which 35.7% had deposited material with thickness greater than 2 mm, as shown in Table 5. None of the patients in the group using OAC presented material thickness that reached this size, with P=0.08. The occurrence of subclinical PTE was low. Only two patients, both in use of antiplatelet agents had ventilation/perfusion pulmonary scintigraphy with PTE pattern (Figure 4), without showing any clinical alteration typical of its occurrence. One of the children has evolved with hemodynamic compromise,

Fig. 3B - Material deposited in the extracardiac conduit - Chest angiotomography image (long axis) performed 6 months after total cavopulmonary connection with extracardiac conduit. Patient who was using ASA developed with conduit kinking with deposit of large amount of material. Long axis cuts with material deposited in the conduit bending site (arrow)

Changes in the inner wall of the extracardiac conduit, described as a deposit of low attenuating material visualized by chest angiotomography, has been found to be common to both groups since the first angiotomographic evaluation, and can be visualized on the pictures below (Figure 3A and 3B).

Table 4. Distribution of the results of tomography in children of ASA and ACO groups. 6 months after surgery altered non-altered Total 12 months after surgery altered non-altered Total 24 months after surgery altered non-altered Total

ASA 11 78.6% 3 21.4% 14 100.0% 11 78.6% 3 21.4% 14 100.0% 10 83.3% 2 16.7% 12 100.0%

OAC 8 66.7% 4 33.3% 12 100.0% 10 83.3% 2 16.7% 12 100.0% 6 66.7% 3 33.3% 9 100.0%

Fisherâ&#x20AC;&#x2122;s Exact test

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Total 19 73.1% 7 26.9% 26 100.0% 21 80.8% 5 19.2% 26 100.0% 16 76.2% 5 23.8% 21 100.0%

P 0.665c

>0.999c

0.611c

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Table 5. Distribution of the thickness of the deposited material of patients in ASA and OAC groups in phases 4, 5 and 6. thickness (phase 4) greater or equal to a 2mm less than 2 mm Total thickness (phase 5) greater or equal to 2 mm less than 2 mm Total thickness (phase 6) greater or equal to 2 mm less than 2 mm Total a

ASA 3 23.1% 10 76.9% 13 100.0% 3 23.1% 10 76.9% 13 100.0% 5 35.7% 9 64.3% 14 100.0%

OAC 4 36.4% 7 63.6% 11 100.0% 3 30.0% 7 70.0% 10 100.0% - 8 100.0% 8 100.0%

Total 7 29.2% 17 70.8% 24 100.0% 6 26.1% 17 73.9% 23 100.0% 5 22.7% 17 77.3% 22 100.0%

P 0.603a

0.500a

0.082a

aunilateral test comparing proportions

the Fontan circuit and protein-losing enteropathy, followed by the described diagnostic finding. Comparing the occurrence of PTE in the group using ASA with the group using OAC, there was no statistically significant difference (P=0.483).

first postoperative evaluation, phase 2. It was when 26.7% of children using ASA and 13.3% of children using warfarin use had the thrombus image diagnosed by transesophageal echocardiography. Data consistent with recent publications have also shown a higher incidence of thrombus in early postoperative period of total cavopulmonary connection (no unanimity about the technique with the extracardiac conduit)[9]. After a 2-year-follow-up period, the total occurrence of thrombosis was 46.7% of patients using ASA and 20% of patients using OAC. Factors such as the age; the mPAP in the preoperative period; the use of fenestration; slow flow by extracardiac conduit and single ventricle systolic dysfunction, had no interference in the occurrence of thrombus during the whole follow-up period. Only the prior history of thrombus showed interference with thrombus formation in the postoperative period. This fact is related to the hypercoagulable state of the children with univentricular heart. Among the pre-stages of total cavopulmonary connection, the thrombus occurs either by changing the number, as in the activity of coagulationg factors; by hemodynamic changes and oximetry of the univentricular physiology; which is a relevant subject of important publications over the past few years, and previously discussed in this article[3,6, 8,10]. In both instances mentioned above, the difference in the occurrence of thrombus between the two groups was not statistically significant, probably due to the small sample size of this study. It is difficult, however, to ignore the fact that the number of patients who developed thrombi in the group using ASA, is greater than twice the number of patients in the warfarin group. Protein C is a natural anticoagulant synthesized in the liver as a vitamin K-dependent protein. Once activated by thrombin, it inhibits the coagulation factors Va and VIIIa, stimulating fibrinolysis. Thus, the deficiency of this protein is associated with

DISCUSSION In 2011, Monagle et al.[7] published a multicenter, prospective, and randomized study, with 111 patients in the postoperative period of modified Fontan operation comparing the two primary prophylaxis strategies commonly used: ASA (57 patients) and warfarin (54 patients), with diagnosis of thrombus in 21% of patients using the former and 24% the latter. The patients were assessed by transthoracic and transesophageal echocardiography in the 3rd and 24th months after surgery, confirming a high incidence of thrombosis, regardless of the strategy used. In 2012, Manlhiot et al.[8] studied the aspects of thromboembolic complications, and thromboprophylaxis in the three stages of surgical staging of univentricular heart and showed that the use of warfarin, as a prophylaxis, has a significant reduction in thrombosis risk when compared to the use of ASA or absence of prophylaxis. Comparison of the efficacy of the OAC and the antiplatelet agent is an old discussion, and the choice of each drug, as well as their association, have been performed according to the preference and experience of each group. A meta-analysis published in 2011[3] evaluated 20 studies related to the subject, with samples ranging from 6 to 282 patients. Seven of this researches whose prophylaxis were performed with ASA, three using only the oral anticoagulant, and the remaining ten publications with the application of both, with thromboembolism rate ranging from 0 to 16%, which was similar among patients regardless of the strategy used. The occurrence of thrombosis was more frequent in the

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a thrombogenic condition. Just as the deficiency of this coagulation factor in the preoperative period of total cavopulmonary connection, also in the postoperative period, several studies have shown such deficiency[3,10] and that there is a gradual reduction in this deficiency with increasing follow-up time[11]. In our sample, 33.3% of patients had protein C in the preoperative evaluation. Among these patients, about 90% were free of thrombus, showing that the Protein C was not a protective factor against the occurrence of thrombus in the preoperative period. However, it is not possible to evaluate the behavior of the coagulation factor in all patients in this sample after surgery, since the patients using warfarin have compromised results. The safety of using warfarin in pediatric patients is a concern for all of us who deal with this type of patient. In 1999, a comprehensive evaluation of 319 children aged 1 month to 18 years of life using warfarin for different reasons, followed up in a anticoagulation center, found important data applicable to the population that we studied[12]: • Children undergoing Fontan circuit surgery require higher dose of warfarin to achieve an expected INR value; • There is difficulty in the management of anticoagulation in children younger than 6 years of age, requiring higher doses of warfarin; • The long time of warfarin necessity overlapping with heparin, thus the INR is within the desired range; need for prolonged periods; more frequent dosing and need for more frequent dose adjustments. In our sample, five patients (16.6%) had lack of adherence during the follow-up period, and its maintenance was possible only due to the researchers’ insistence and with the aid of the support staff, with four (80%) using warfarin, and consequently, the INR oscillated out of range, with values between 1 and 6.4. Furthermore, in general, in the group using warfarin, 93.3% had at least an INR value below the desired range, which significantly increases the risk of thrombosis, as shown in a multicenter prospective study already mentioned, in which, the group taking warfarin during the INR evaluation, had less than 30% with INR greater than 2[7]. Changes in the inner wall of the extracardiac conduit used in total cavopulmonary connection is still being poorly studied, with sparse data in this regard. In our study, during the 2-year-follow-up period, both the number of children with material deposited in the conduit wall was higher in the ASA group (83.3%) and the thickness of the material (which varied throughout the evaluation from 0.9 to 3.5 mm) was higher (more than 2 mm). Images larger than 2 mm were not seen in children using warfarin at this time, with P=0.082; thus, showing a tendency to affirm that the deposit of materials, with increasing follow-up time, is higher in the ASA group. The material described as material accumulation in a recently published study[13] was called large thrombus base, adhered to the inner wall of the extracardiac conduit in 3 of 10 patients.

The approach and interpretation of the found material, brings up inmportant aspects for discussion, both as regards the size and appearance, thus, tomography may be an important tool in the early diagnosis of the thrombus preventing pulmonary thromboembolism. The occurrence of subclinical PTE, releasing small emboli to the pulmonary circulation, is a major problem in Fontan physiology, due to the decrease in oxygen saturation and increased pulmonary vascular resistance. The pulmonary scintigraphy is not routinely performed in patients undergoing total cavopulmonary connection, which makes it difficult to compare. However, PTE was diagnosed in two patients, both using ASA, after one and two years after surgery. Due to the importance of hemodynamic compromise of the Fontan circuit in the presence of pulmonary thromboembolism, strategies must be drawn in search of a practical and reliable diagnosis of this alteration, and tomography would be a possible option[13]. The low incidence of heart with univentricular physiology among congenital heart diseases, coupled with mortality in the interstage period, significantly limits the number of patients to be added to a prospective and randomized study in the postoperative period of total cavopulmonary connection. The thromboembolic phenomenon in the postoperative period of this procedure is very important, both with regard to a high incidence and mortality. CONCLUSION 1 - The occurrence of thrombosis was significantly higher in the ASA group, however, this difference was not statistically different. a - when we evaluated all the factors studied in the thrombosis-free-survival, we noted that the only factors that really affect are the previous occurrence of thrombus (P=0.035) and deficiency of Protein C in the preoperative period (P=0.047). 2 - Hepatic function and coagulation factors: A - with the exception of Protein C, coagulation factors and liver enzymes showed no interference in the free development of thrombus. 3 - Regarding the viability of the usual prophylaxis for thromboembolism, neither drug led to significant side effects and bleeding. None of the children had the drug suspended due to intolerance. 4 - The flow rate is reduced by the extracardiac conduit and the occurrence of thrombus was more frequent in patients with slow flow, without statistical significance. 5 - In the group using ASA, we found a tendency to a higher incidence of thicker material accumulation (greater than 2 mm) compared to the group using OAC (P=0.082). 6 - Subclinical pulmonary thromboembolism occurred in two patients, without any statistically significance. Patients with history of thrombosis, which will be submit-

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ted to total cavopulmonary connection (Fontan type), should be maintained in the postoperative period, with the use of warfarin. It is necessary to expand the sample numbers of this study to give statistical power to the fact that twice as many children using ASA evolves with thromboembolic phenomena, patients using ASA has more material adhered to the wall of the conduit, reaching a thickness exceeding 2 mm, and are more likely to pulmonary thromboembolism compromising the Fontan circuit, therefore, we suggest that these patients, when they can afford this treatment, should be anticoagulated with the use of warfarin in the postoperative period of total cavopulmonary connection.

procedure: the role of prophylactic anticoagulation. J Thorac Cardiovasc Surg. 1998;115(3):493-8. 5. Rosenthal DN, Friedman AH, Kleinman CS, Kopf GS, Rosenfeld LE, Hellenbrand WE. Thromboembolic complications after Fontan operations. Circulation. 1995;92(9 Suppl):II287-93. 6. Coon PD, Rychik J, Novello RT, Ro PS, Gaynor JW, Spray TL. Thrombus formation after the Fontan operation. Ann Thorac Surg. 2001;71(6):1990-4. 7. Monagle P, Cochrane A, Roberts R, Manlhiot C, Weintraub R, Szechtman B, et al. A multicenter, randomized trial comparing heparin/warfarin and acetylsalicylic acid as primary thromboprophylaxis for 2 years after the Fontan procedure in children. J Am Coll Cardiol. 2011;58(6):645-51. 8. Manlhiot C, Brandão LR, Kwok J, Kegel S, Menjak IB, Carew CL, et al. Thrombotic complications and thromboprophylaxis across all three stages of single ventricle heart palliation. J Pediatr. 2012;161(3):513-9.

Authors' roles & responsibilites CFXP MBJ IBJ PMO FMPS VMM RWL SRFFP

Study design, data collection, reference search Study design Data collection Data collection Data collection Data collection Data collection Data collection

9. McCrindle BW, Manlhiot C, Cochrane A, Roberts R, Hughes M, Szechtman B, et al. Factors associated with thrombotic complications after the Fontan procedure: a secondary analysis of a multicenter, randomized trial of primary thromboprophylaxis for 2 years after the Fontan procedure. J Am Coll Cardiol. 2013;61(3):346-53. 10. Odegard KC, Zurakowski D, DiNardo JA, Castro RA, McGowan FX Jr, Neufeld EJ, et al. Prospective longitudinal study of coagulation profiles in children with hypoplastic left heart syndrome from stage I through Fontan completion. J Thoracic Cardiovasc Surg. 2009;137(4):934-41.

REFERENCES 1. Cavalcanti CV, Ikari NM, Hazin SMV. Atresia tricúspide. In: Croti UA, Mattos SS, Pinto Jr VC, Aiello VD, eds. Cardiologia e cirurgia cardiovascular Pediátrica. São Paulo: Roca; 2008. p.522-34.

11. van Nieuwenhuizen RC, Peters M, Lubbers LJ, Trip MD, Tijssen JG, Mulder BJ. Abnormalities in liver function and coagulation profile following the Fontan procedure. Heart. 1999;82(1):40-6.

2. Taussig HB, Blalock A. The tetralogy of Fallot; diagnosis and indications for operation; the surgical treatment of the tetralogy of Fallot. Surgery. 1947;21(1):145.

12. Streif W, Andrew M, Marzinotto V, Massicotte P, Chan AK, Julian JA, et al. Analysis of warfarin therapy in pediatric patients: a prospective cohort study of 319 patients. Blood. 1999;94(9):3007-14.

3. Marrone C, Galasso G, Piccolo R, de Leva F, Paladini R, Piscione F, et al. Antiplatelet versus anticoagulation therapy after extracardiac conduit Fontan: a systematic review and metaanalysis. Pediatr Cardiol. 2011;32(1):32-9.

13. Grewal J, Al Hussein M, Feldstein J, Kiess M, Ellis J, Human D, et al. Evaluation of silent thrombus after the Fontan operation. Congenit Heart Dis. 2013;8(1):40-7.

4. Monagle P, Cochrane A, McCrindle B, Benson L, Williams W, Andrew M. Thromboembolic complications after Fontan

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Santos AA, etREVIEW al. - Therapeutic options to minimize allogeneic blood ARTICLE transfusions and their adverse effects in cardiac surgery: A systematic review

Therapeutic options to minimize allogeneic blood transfusions and their adverse effects in cardiac surgery: A systematic review Opções terapêuticas para minimizar transfusões de sangue alogênico e seus efeitos adversos em cirurgia cardíaca: Revisão sistemática

Antônio Alceu dos Santos1, MD; José Pedro da Silva1, MD, PhD; Luciana da Fonseca da Silva1, MD, PhD; Alexandre Gonçalves de Sousa1, MD; Raquel Ferrari Piotto1, MD, PhD; José Francisco Baumgratz1, MD

DOI: 10.5935/1678-9741.20140114

RBCCV 44205-1596

Abstract Introduction: Allogeneic blood is an exhaustible therapeutic resource. New evidence indicates that blood consumption is excessive and that donations have decreased, resulting in reduced blood supplies worldwide. Blood transfusions are associated with increased morbidity and mortality, as well as higher hospital costs. This makes it necessary to seek out new treatment options. Such options exist but are still virtually unknown and are rarely utilized. Objective: To gather and describe in a systematic, objective, and practical way all clinical and surgical strategies as effective therapeutic options to minimize or avoid allogeneic blood transfusions and their adverse effects in surgical cardiac patients. Methods: A bibliographic search was conducted using the MeSH term “Blood Transfusion” and the terms “Cardiac Surgery” and “Blood Management.” Studies with titles not directly related to this research or that did not contain information related to it in their abstracts as well as older studies reporting on the same strategies were not included.

Results: Treating anemia and thrombocytopenia, suspending anticoagulants and antiplatelet agents, reducing routine phlebotomies, utilizing less traumatic surgical techniques with moderate hypothermia and hypotension, meticulous hemostasis, use of topical and systemic hemostatic agents, acute normovolemic hemodilution, cell salvage, anemia tolerance (supplementary oxygen and normothermia), as well as various other therapeutic options have proved to be effective strategies for reducing allogeneic blood transfusions. Conclusion: There are a number of clinical and surgical strategies that can be used to optimize erythrocyte mass and coagulation status, minimize blood loss, and improve anemia tolerance. In order to decrease the consumption of blood components, diminish morbidity and mortality, and reduce hospital costs, these treatment strategies should be incorporated into medical practice worldwide.

Real e Benemérita Associação Portuguesa de Beneficência de São Paulo, São Paulo, SP, Brazil.

Correspondence address: Antônio Alceu dos Santos Rua Maestro Cardim, 769, Bloco I, 2º andar, Sala 202 – Bela Vista – São Paulo, SP, Brazil – Zip Code: 01323-900 E-mail: antonioalceu@cardiol.br

Descriptors: Blood Transfusion. Bloodless Medical and Surgical Procedures. Blood Preservation. Operative Blood Salvage. Cardiac Surgical Procedures.

This study was carried out at Real e Benemérita Associação Portuguesa de Beneficência de São Paulo, São Paulo, SP, Brazil.

Article received on May 22nd, 2014 Article accepted on September 30th, 2014

No financial support.

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outras opções de tratamento. Estas alternativas existem, porém são pouco conhecidas e raramente utilizadas. Objetivo: Reunir e descrever de maneira sistemática, objetiva e prática todas as estratégias clínicas e cirúrgicas, como opções terapêuticas eficazes para minimizar ou evitar transfusões de sangue alogênico e seus efeitos adversos nos pacientes submetidos à cirurgia cardíaca. Métodos: Foi efetuada uma pesquisa bibliográfica com busca ao descritor “Blood transfusion” (MeSH) e aos termos “Cardiac surgery” e “Blood management”. Estudos com títulos não relacionados diretamente ao tema da pesquisa, estudos que não continham nos resumos dados relacionados à pesquisa, estudos mais antigos que relataram estratégias repetidas foram excluídos. Resultados: Tratar anemia e plaquetopenia, suspender anticoagulantes e antiplaquetários, reduzir flebotomias rotineiras, técnica cirúrgica menos traumática com hipotermia e hipotensão moderada, hemostasia meticulosa, uso de agentes hemostáticos sistêmicos e tópicos, hemodiluição normovolêmica aguda, recuperação sanguínea intraoperatória, tolerância à anemia (oxigênio suplementar e normotermia), bem como várias outras opções terapêuticas mostram ser estratégias eficazes em reduzir transfusões de sangue alogênico. Conclusão: Existem múltiplas estratégias clínicas e cirúrgicas para otimizar a massa eritrocitária e o estado de coagulação, minimizar a perda de sangue e melhorar tolerância à anemia. Estes recursos terapêuticos deveriam ser incorporados à prática médica mundial, visando diminuir o consumo de hemocomponentes, reduzir a morbimortalidade e custos hospitalares.

Abbreviations, acronyms and symbols AF ANH ASA CABG CPB DDAVP EuroSCORE HF KF LILACS MEDLINE MeSH MI PCC PRBC r-FVIIa r-Hu-EPO r-Hu-TPO SciELO

Atrial fibrillation Acute normovolemic hemodilution Acetylsalicylic acid Coronary artery bypass graft Cardiopulmonary bypass 1-deamino-8-D-arginine vasopressin European System for Cardiac Operative Risk Evaluation Heart failure Kidney failure Literatura Latino-Americana em Ciências da Saúde Medical Literature Analysis and Retrieval System Online Medical Subject Headings Myocardial infarction Prothrombin complex concentrate Packed red blood cell Recombinant activated factor VII Recombinant human erythropoietin Recombinant human thrombopoietin Scientific Electronic Library Online

Resumo Introdução: O sangue alogênico é um recurso terapêutico esgotável. Novas evidências demonstram um consumo excessivo de sangue e uma diminuição das doações, resultando em estoques de sangue reduzidos em todo o mundo. As transfusões de sangue estão relacionadas a aumento na morbimortalidade e maiores custos hospitalares. Deste modo, torna-se necessário procurar

Descritores: Transfusão de Sangue. Procedimentos Médicos e Cirúrgicos de Sangue. Preservação de Sangue. Recuperação de Sangue Operatório. Procedimentos Cirúrgicos Cardíacos.

INTRODUCTION

existed. However, since the 1980´s, numerous studies have been analyzing the safety and efficacy of blood transfusions. Initially, a correlation has been found between transfusion of blood components in CABG and clinical complications, such as kidney failure (KF), infectious processes, prolonged ventilation, and neurological damages[5]. Most recently, it became evident that allogeneic blood transfusion in cardiac surgery is a therapy with other serious adverse effects such as atrial fibrillation (AF), stroke, respiratory infections, sepsis, myocardial infarction (MI)[6,7], including the risk of death[8-10]. Even after taking into account factors such as age, gender, weight, height, as well as various diseases such as diabetes mellitus, hypertension, chronic obstructive pulmonary disease, peripheral vascular disease, heart failure (HF), cerebrovascular disease, the use of blood transfusions can lead to an increase up to 70% in the mortality rate of cardiac surgery postoperatively[8]. In our research, we have found that transfusion of red cells was an independent predictor factor of death after

Since the 19th century, allogeneic blood has been frequently utilized in increased numbers worldwide. The percentage of transfusions of hemocomponents in coronary artery bypass graft (CABG) has reached 92.8% for red cells, 97.5% for fresh frozen plasma, and 90.4% for platelet infusion[1]. Currently, reduction in blood donations worldwide has resulted in a shortage of blood supply in blood banks[2]. This situation is a real problem among us and it will likely get worse, as the blood demand in the country is not proportional to the donations, indicating a possibility in the near future a shortage of this therapeutic resource to be used to perform and/or complete surgical procedures[3]. Therefore, since 2008, medical professionals have been concerned over what to do with a patient who is bleeding and no blood is available for transfusion[4]. For over half a century, transfusion therapy had not been questioned since no significant evidence of adverse effects

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CABG in a population of 1,888 patients. Even in a subgroup of low-risk patients (age < 60 years and EuroSCORE ≤ 2%), there was a significant higher mortality rate in the group who had received blood transfusions[9]. Other studies have showed the mortality rate to be directly proportional to the number of packed red blood cell (PRBC) units transfused. Each unit of PRBC transfused can increase the mortality risk to 77% post CABG[5]. After analyzing 3,010 patients who had undergone CABG, Santos et al.[10] have also observed that the mortality risk is dose-dependent on the number of units of allogeneic PRBCs transfused. The higher the units of red blood cells transfused, the higher the mortality risk postoperatively. In addition to the risks related to blood transfusions, the cost is also a factor that needs to be considered. Although it varies in other countries, when all activity-based costs of blood transfusion was taken into account, in 2010 the estimated cost for one unit of blood in the United States of America (USA) was about 1,200 dollars[11]. Transfusion of PRBC has also been associated with increased length of hospital stay resulting in higher hospital costs[6,7]. Given the evidence of increased incidence of infections, sepsis, stroke, AF, KF, HF, MI, increased risk of death[5-10], higher costs[6,7] and shortage of blood components[2,3], other nontransfusional treatment options are necessary. In the attempt to decrease allogeneic blood consumption during cardiac surgeries, numerous alternative treatment options have been proposed[4,12-16], however, due to the practicality of transfusional therapy, these options are virtually unknown and are rarely used. The aim of this review is to gather and describe in a systematic, objective, and practical way all clinical and surgical strategies as therapeutic treatment options that could assist the surgeon, anesthesiologist, clinical and/or critical care physician, as well as other critical care professionals, to reduce or avoid allogeneic blood transfusions in cardiac surgeries, and consequently, their adverse effects.

“Blood management” and “Blood transfusion”, and finally, “Blood transfusion” and “Cardiac surgery” resulted in 9,018; 11,299 and 5,998 articles, respectively. Inclusion Criteria Presence of one or more alternative treatment options for blood transfusion in the article. In order to assemble all possible therapeutic options with evidence of reducing allogeneic blood consumption, recent articles were selected containing a systematic review process and meta-analysis, prospective multicenter randomized cohort studies, retrospective cohort studies, case studies and others, without restriction on the minimum number of participants for each study, in all languages from January 1, 1980 to January 31, 2014. Exclusion Criteria Studies excluded from this review were: studies with titles not directly related to this research; studies that did not contain in their abstract data relevant to this research; older studies reporting on the same strategies (intraoperative blood salvage, acute normovolemic hemodilution, use of erythropoiesis-stimulating agents, use of various systemic and topical hemostatic agents, strategies to restrict the use of blood transfusion and others). Selection of Studies By means of an individual triage of the articles found after the database search was performed using specific terms, data containing the main and most frequent treatment alternatives to the use of blood components in cardiac surgery was extracted from the articles. Figure 1 shows an organogram of the methodology used for obtaining the 76 articles selected for this review. Initially, an analysis was performed of all the tittles found during the search combination of the specific terms used. Titles directly related to the study, with emphasis on strategies to minimize blood transfusions and their adverse effects during cardiac surgery, passed during this initial triage process. Then, we excluded similar repetitive titles, selecting the most up-todate ones to read their respective abstracts. Abstracts that did not present strategies related to cardiac surgery or presented strategies that could not be applied to cardiovascular surgery, were also not selected for a complete analysis of the article. The final selection of the articles relevant to this research was performed through individual searches with data crossing done by two authors and supervised by a third.

METHODS Search Strategy For this review, a bibliographic search was performed in the month of February, 2014 using the online databases PUBMED/ MEDLINE, LILACS, COCHRANE library and SciELO for articles published between January 1, 1980 and January 31, 2014. The search was limited to the MeSH (Medical Subject Headings) term “Blood transfusion” and the terms “Cardiac surgery” and “Blood management”. Despite not being MeSH terms, “Blood management” and “Cardiac surgery” were included in the search because they are important keywords highly relevant to the subject being discussed. The combination of the terms “Blood management” and “Cardiac surgery”,

RESULTS According to this study review, numerous strategies have shown to have impact on reducing allogeneic blood consumption. To facilitate the medical practitioner´s course of action, the main strategies selected to avoid or reduce the transfu-

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Fig. 1 - Organogram of the methodology about the different search steps. MeSH=Medical Subject Headings

sional practice were separated into three important pillars: I – optimize the erythrocyte mass and the coagulation status; II – minimize blood loss, and III – anemia tolerance. To reach the aim of this review, additional helpful information obtained from this study has been structurally included in each of these pillars. Figure 2 shows a flowchart containing important strategies in each pillar for a new nontransfusional approach during the pre, intra, and postoperative care.

a detection and treatment of anemia and thrombocytopenia. Table 1 shows the main strategies to optimize the erythrocyte mass and the coagulation status. We briefly described each one of them below: 1 – History of anemia and abnormal bleeding Assessment of congenital or acquired hemorrhagic disturbances. 2 – Identify the use of medications that could have adverse effects on anemia, thrombocytopenia and coagulopathy[17] Acetylsalicylic acid (ASA), nonsteroidal anti-inflammatory drugs, anticoagulants, platelet aggregation inhibitors, beta-lac-

I – Optimize the erythrocyte mass and the coagulation status To reduce or avoid allogeneic blood transfusion is necessary to perform a preoperative assessment that includes

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Fig. 2 - Flowchart with strategies to minimize allogeneic blood transfusions and their adverse effects. CBC - Complete blood count; EACA - epsilon aminocaproic acid; Factor VIIa - Recombinant activated factor VII; HFC - Human fibrinogen concentrate; IV - Intravenous; MAP - Mean arterial pressure; PCC - Prothrombin complex concentrate; r-Hu-EPO - Recombinant human erythropoietin; r-Hu-TPO - Recombinant human thrombopoietin; SBP - Systolic blood pressure

3 â&#x20AC;&#x201C; Physical exam Search for manifestations of illnesses known to be associated with hemostatic dysfunction (hepatomegaly, splenomegaly, petechiae, purpura, ecchymosis, hemarthrosis, evidence of collagen vascular disorders, telangiectasia).

tam antibiotics (such as penicillins, ticarcillin), beta blockers, calcium channel blockers, H2 blockers, furosemide, thiazide diuretics, alpha-methyldopa, quinidine, anticonvulsants, myelosuppressive agents, diet and herbal supplements can affect the coagulation or the platelet function.

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Table 1. Main estrategies to optimize the erythrocyte mass and coagulation status. Research study Drews[17] Goodnough[18] Weltert et al.[20] Corwin et al.[21] Silverberg et al.[24] Bussel et al.[29] Wang et al.[30]

Main estrategies to optimize the erythrocyte mass and coagulation To identify anemia, thrombocytopenia and coagulopathy To treat iron deficiencies r-Hu-EPO in the preoperative period for anemic patients Dose of 40,000 UI/week reduces blood transfusions Anabolic androgenic therapy can optimize the responses to r-Hu-EPO Eltrombopag stimulates trombocytopoiesis and reduces platelets transfusion r-Hu-TPO stimulates trombocytopoiesis and reduces platelets transfusion

r-Hu-EPO=Recombinant human erythropoietin, r-Hu-TPO=Recombinant human thrombopoietin

4 â&#x20AC;&#x201C;Selective laboratory evaluation Complete blood count with differentiation, reticulocytes, ferritin, vitamin B12, folate, complete coagulogram, platelet function and aggregation tests, fibrinogen concentration, hepatic, renal and thyroid function tests. If the preoperative laboratorial results are abnormal, then ideally the surgery should be postponed until the abnormalities are corrected or until more detailed preliminary studies can be obtained. In such cases, a hematologist evaluation is recommended. In the event of urgent surgeries, normalize the coagulation status with appropriate agents, as courses of actions well defined later in this article.

varies from patient to patient. Excluding chronic renal insufficiency, r-Hu-EPO dosages varying from 150 to more than 600 IU/kg/week with various dosing intervals and schedules have been reported to accelerate the recovery of acute anemia[20]. In critically ill patients in intensive care, the subcutaneous administration of r-Hu-EPO 40,000 IU per week resulted in a significant increase in hemoglobin levels and consequently in a reduction of 19% of blood transfusion needs[21]. Some patients require higher dosages of r-Hu-EPO to reach an adequate response. Some evidences suggest that r-Hu-EPO dosages in intervals of 24-72 hours (150-300 IU/kg) can be more effective than weekly single doses (600 IU/kg). If unable to determine or correct the cause r-Hu-EPO treatment resistance or hyporesponsiveness, consider the use of higher dosages[22]. In severe anemia, the concomitant use of IV iron can optimize the response to erythropoietic agents[18]. Aggressive anemia therapy must not be delayed until the hemoglobin levels fall and reach critically low levels. Erythropoietin of up to 200 IU/kg/day (1,400 IU/kg/week in divided dosages) has been shown to be safe and well tolerated by children[23]. Concomitant anabolic androgenic therapy can optimize the response to erythropoietic agents by increasing the sensibility of the progenitor erythroid cells[24]. The intravenous route allows for higher levels of erythropoietin concentration in the plasma. For severe acute anemia, critical illnesses, deficiency in subcutaneous absorption (due to edema or blood flow alterations) consider initial IV administration of r-Hu-EPO followed by subcutaneous dosages[25].

5 â&#x20AC;&#x201C; Anemia treatment a) Identify and treat hematinic deficiencies Iron deficiency is the most treatable and frequent cause of anemia[18]. Prophylactic administration of hematinics (iron, folic acid, vitamin B12) should always be considered. b) Treatment of iron deficiencies Intravenous (IV) iron by saline infusion, for example, iron hydroxide saccharate (dosage of 3 to 5 mg/kg/day and the maximum of 200 mg/day) or carboxymaltose (dosage 15 mg/kg and the maximum of 1,000 mg in single infusion) can rapidly replenish iron reserves. Oral iron bioavailability can be increased by a concomitant administration of ascorbic acid. The simultaneous use of dairy products, egg yolks, coffee, tea, antacids, or fiber reduces the absorption of oral iron. Parenteral administration of iron is recommended in patients with oral iron intolerance, inadequate absorption, chronic or severe blood loss, or nonresponsiveness to treatment[19].

e) Other considerations about r-Hu-EPO The treatment with r-Hu-EPO can produce a moderate and temporary dose-dependent increase on platelet reactivity[26]. A poor response to erythropoiesis-stimulating therapy includes iron deficiency as well as infectious, inflammatory or malignant processes, occult blood loss, hyperparathyroidism and hematologic diseases[27]. Erythropoietic agents have been associated with increased blood pressure levels in patients with chronic renal insufficiency or previous hypertension. Monitoring and controlling blood pressure levels are necessary. In patients with anemia and malignant neoplasm, the risks and benefits of r-Hu-EPO treatment should be assessed due to increased thromboembolic events, tumor progression and mortality risk with this patient population[28].

c) Recombinant human erythropoietin (r-Hu-EPO) therapy This therapy is recommended preoperatively to increase the erythrocyte mass in patients who are anemic or who refuse the use of blood components or in patients with risk of anemia postoperatively[16,20]. Before the initiation and/or during treatment with r-Hu-EPO, correct deficiencies in iron, folic acid and vitamin B12. d) Dosage and administration route r-Hu-EPO The responsiveness to r-Hu-EPO depends on the dosage and

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Darbepoetin (dose 0.45 µg/kg/week) and CERA (continuous erythropoietin receptor activator - dose 0.60 µg/kg every two weeks) are other erythropoiesis-stimulating agents with higher metabolic stability and longer half-life, currently not yet available in many countries.

nutrition in patients who cannot be fed through the digestive system. Protein supplementation to support erythropoiesis. 8 – Additional preoperative planning If high blood loss is expected postoperatively, potentially causing a severe case of anemia, consider a differential surgical approach or appropriate combinations of preoperative strategies to optimize perioperative hemoglobin levels, coagulation factors, and patient´s condition. Combination of blood conservation methods during the intra and postoperative care can also be considered. Preoperative autologous blood donation has not yet been well defined in relation to its real benefit and cost-effectiveness. Its use in cardiac surgery is very disputable.

6 – Thrombocytopenia treatment The majority of thrombocytopenia cases resolves by suspending or avoiding the causative agents (cytotoxic drugs, cardiopulmonary bypass (CPB), excessive hemodilution), treating disorders that affect the bone marrow (severe infections, idiopathic or thrombotic thrombocytopenic purpura), splenectomy (hypersplenism). Regardless of the etiology, the following drugs can be separately used to stimulate thrombocytopoiesis: a) Eltrombopag: dose 50-100 mg/day; b) Recombinant human interleukin-11(oprelvekin): dose 50 µg/kg/day; c) Recombinant human thrombopoietin (r-Hu-TPO): dose 300 IU/kg/day; d) Human immunoglobulin: dose 200-400 mg/kg/day. The literature shows that eltrombopag[29] and r-Hu-TPO[30] are effective in stimulating thrombocytopoiesis and consequently reducing platelet transfusions.

II – Minimize blood loss Cardiac surgery has been frequently associated with bleeding. The higher the blood loss, the greater the indication will be to use multiple modalities of blood preservation. The use of appropriate combinations of techniques has a synergistic effect in reducing surgical and nonsurgical bleeding (caused by coagulopathy). Excessive blood loss is linked to adverse effects[31]. Table 2 shows the main strategies to minimize surgical blood loss. We briefly described each one of them below:

7 - Nutrition Early enteral feeding as tolerated. Intravenous parenteral

Table 2. Main strategies to minimize surgical blood loss. Research study Chu et al.[32] Dech et al.[33] Lamy et al.[35] Zangrillo et al.[36] Boodhwani et al.[37] Van der Linden et al.[39] Degoute[40] Milas et al.[34] Abrishami et al.[50] Menkis et al.[16] Carless et al.[42] Lin et al.[45] Nienaber et al.[47] Rahe-Meyer et al.[48] Ferraris et al.[49] Davies et al.[53] Carless et al.[56]

Main strategies to minimize surgical blood loss To eliminate daily routine phlebotomies To minimize blood volumes withdrawn for diagnostic test (use small tubes) To avoid or reduce as much as possible the time of CPB Mini-circuit systems in CPB reduce blood transfusions Ultrafiltration reduces hemorrhage and blood transfusions Moderate hypotermia (temperature during CPB between 30 and 32ºC) Arterial blood pressure at the lowest possible level that mantains tissue perfusion (MAP of 50-65 mmHg) Meticulous hemostasis (fast and extremaly careful control of hemorrhages) Topics hemostatics agents to control local bleeding Pharmacological hemostasis with tranexamic acid or epsilon animocaproic acid Desmopressin increases platelet adhesion and improves hemostasis r-FVIIa to control hemorrhages associated with thrombocytopenia, disorders of platelet function and preexistent or drug-induced coagulopaties PCC to rapidly restore the clotting factors and to control major bleeding Human fibrogen concentrate to replace fibrinogen and to control major bleeding Human recombinant factor XIII to control major bleedings, when others hemostatic agents have not produced satisfactory results Acut normovolemic hemodilution is safe and cost-effective in reducing allogenic blood transfusion in surgeriess Intraoperative blood recovery (cell saver) in surgeries for autologous blood conservation

CPB=Cardiopulmonary bypass, MAP=Mean arterial pressure, PCC=Prothrombin complex concentrate, r-FVIIa=Recombinant activated factor VII

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1 - Reducing diagnostic phlebotomies Perform only essential tests. Eliminate daily multiple routine phlebotomies[32]. Only order tests or procedures that would probably alter the treatment.

the use of early selective angiography and embolization to quickly stop the blood loss. c) Allow for moderate hypotension during bleeding In uncontrolled bleedings, normalizing blood pressure could be harmful. In patients with dangerous acute hemorrhages, tolerating light to moderate hypotension is suggested, that is, arterial blood pressure at the lowest level possible to maintain tissue perfusion (mean arterial pressure of 50-65 mmHg)[40].

2 - Minimizing blood volumes withdrawn for tests Utilize pediatric tubes (small volume) to draw blood in adults[33]. Perform blood microsampling. Noninvasive monitoring (pulse oximetry, transcutaneous oximetry). Restrictive use of indwelling catheters. 3 – Reducing blood loss during invasive medical procedures Minimize placements of central arterial or venous catheters, hemofiltration, dialysis, cardiac catheterization. Use caution with invasive procedures in patients receiving anticoagulants or platelet aggregation inhibitors.

d) Blood pressure management Slow and gradual return to normal pressure after the bleeding has been controlled. Postoperative moderate hypotension (systolic blood pressure of 80-90 mmHg in normotensive patient) is sufficient to maintain perfusion of vital organs and to avoid pressure peaks that could potentially cause late hemorrhaging[40].

4 – Intraoperative blood preservation and autologous blood management a) Surgical techniques to minimize blood loss Meticulous hemostasis. Fast and very careful control of bleeding[34]. Less traumatic surgical approach (minimally invasive surgery and/or consider an approach that avoids operating through known or suspected adhesions). Mechanical occlusion (ligature, vascular clips, staples, sutures). Reducing surgical duration, especially the use of CPB. A multicenter study has shown evidence of significant reduction of blood transfusion needs and reoperation for bleeding in surgeries without CPB[35]. In a meta-analysis of randomized studies, the data shows that the use of mini-circuit systems in CPB has been effective in reducing the number of blood transfusions[36]. If possible, adapt the CPB circuit to accommodate a small prime of about 750 to 1,200 ml of crystalloids. The use of ultrafiltration in cardiac surgery, assessed in another meta-analysis, resulted in reduction of hemorrhage and consequently in significant reduction in blood transfusions[37]. The use of retrograde autologous priming during the CPB is safe and effective in reducing the degree of hemodilution, therefore, providing adequate oxygen delivery minimizing allogeneic blood consumption[38]. Moderate hypothermia. Temperature maintained between 30 and 32ºC during the CPB is associated with reduction of bleeding during the intra and postoperative period[39]. Re-infuse all the blood of the CPB circuit and if possible the blood collected from the drainage of the mediastinum during the first six hours postoperatively. Verify, during and immediately after the CPB, the activated clotting time (ACT) to avoid hyperheparinemia. Correct it with protamine sulfate (1 mg of protamine is able to inactivate in average 100 IU of sodium heparin). Divide complex procedures into stages.

e) Hemostatic surgical instruments: electrocautery/electrosurgery; argon beam coagulator; bipolar forceps; radiofrequency thermal ablation; laser. f) Pharmacological hemostasis: systemic hemostatic agents The surgical cardiac guidelines[16] recommend initially: tranexamic acid: dose 25 mg/kg of body weight. The maximum dose cannot exceed 50-100 mg/kg, due to its neurotoxicity effects; epsilon aminocaproic acid: loading dose of 150 mg/ kg. The administration should be continued with an infusion of 10 mg/kg/hour, for four to five hours, with a maximum dose of 24 g (one gram per hour). In case of excessive bleeding, other hemostatic agents can also be used: vasopressin: dose 0.2-0.4 U/min, until the bleeding is stopped, maintenance dose of 12 hours; conjugated estrogens: dose of 20 mg via IV, preferably. If necessary repeat the administration after 6 to 12 hours. Caution should be used with renal, hepatic and severe cardiomyopathy patients[41]. g) Pharmacological hemostasis: agents that increase the coagulation factors activity Desmopressin acetate (DDAVP) Dose 0.3 µg/kg of body weight. Used prophylactically for bleeding with CABG, particularly with patients using ASA or in cases with prolonged CPB time[16]. Desmopressin can increase the platelet adhesion and the levels of coagulation factors VIII and von Willebrand in the plasma[42]. In a meta-analysis of 38 randomized placebo-controlled studies, desmopressin was shown to significantly reduce intraoperative bleeding and transfusion of blood components without increasing the risks of thromboembolic complications[43]. Desmopressin can be used with epsilon aminocaproic and tranexamic acids without adverse effects. Due to risk of hypotension, monitoring patient is suggested.

b) Prophylactic preoperative angiographic embolization If bleeding is suspected but the cause is unknown, employ

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Vitamin K (phytomenadione) Dose in adults: 10-20 mg IV slow (maximum 50 mg/ day) and 100 mg by mouth. Postoperative administration of parenteral vitamin K can be considered with hemorrhages[44]. Recombinant activated factor VII (r-FVIIa) Dose 40-90 μg/kg of body weight. This dose can be repeated every 2 hours according to the type and severity of the hemorrhage. A single dose of 270 μg/kg can be used in cases of moderate hemorrhages. The use of r-FVIIa can be considered in clinical situations where the conventional approach to surgical and pharmacological hemostasis has failed and an uncontrolled hemorrhaging has increased the risk of serious outcomes and the risk of death[16]. The r-FVIIa has been associated with blood loss reduction in nonhemophiliac patients in numerous clinical situations including postoperative bleeding, thrombocytopenia, congenital or acquired disorders of platelet function, acquired bleeding predisposition and pre-existent or drug induced coagulopathies[45]. Replacement therapy of clotting factor VIII (concentrate) Factor VIII (25 IU/kg of body weight) is available as a recombinant product and specific use. Prothrombin complex concentrate (PCC) Dose 20-40 IU/kg of body weight. PCC acts in the phases of initiation and amplification of coagulation. Rapidly restoring normal levels of clotting factors. Allows for progression of the prothrombin pathway[46]. The literature shows the efficacy of PCC is similar to the transfusion of fresh frozen plasma in controlling major bleeding and avoiding post trauma mortality[47]. Human fibrinogen concentrate (HFC) Dose 25-50 mg/kg of body weight. The use of 1-2 g for small bleeding and 4-8 g for excessive bleeding is recommended. It is effective in controlling major bleeding during surgery, hence, avoiding or minimizing the use of plasma and/or platelet transfusions[48]. It is recommended a minimum fibrinogen concentration of 1.5-2.0 g/L in surgical patients. Conditions associated with hypofibrinogenemia: massive blood loss, massive transfusion, blood dilution with plasma substitutes, extensive tissue injury, disseminated intravascular coagulation, hemodialysis, surgery or injury of organs with pro-fibrinolytic potential, hepatic insufficiency and fibrinolytic therapy. Human recombinant factor XIII Dose 20-35 IU/kg/day until bleeding is stopped. Recommended for clot stabilization in post-surgical cardiac patients with excessive bleeding, when other hemostatic agents have not produced satisfactory results[49].

gelatin sponge/foam; thrombin-soaked or topical thrombin tamponade; plant based polysaccharides; calcium alginate. 5 – Acute Normovolemic Hemodilution (ANH) Hemodilution, besides being a low-cost strategy, can produce beneficial effects, such as less organ insufficiencies due to the increased release of oxygen in the microcirculatory level and less thrombolytic complications resulted from decreased platelet aggregation. In addition to conventional techniques of myocardial preservation, preoperative ANH promotes greater cardiac protection in patients undergoing CABG[51]. The amount of blood to be removed during hemodilution is determined by Gross´s formula[52]: V = EBV x (Hcti - Hctf)/ Hctav where V = volume of blood withdrawn, EBV is the estimated blood volume, Hcti is the ideal initial hematocrit, Hctf is the minimum hematocrit and Hctav is the average hematocrit [(Hcti + Hctf)/2]). General practical rule: for each unit of blood removed (450 ml), slowly infuse (to avoid hypervolemia) 1,000 ml of crystalloids. The ANH might be more effective if able to remove at least 1,000 ml of blood in the beginning of surgery. The ANH, besides being cost-effective, has been safely used in avoiding or reducing homologous blood transfusions in adult[16,53] and pediatric[54] cardiac surgeries. Figure 3 shows a schematic representation of an ANH.

h) Pharmacological hemostasis: topical hemostatic agents Efficient in controlling local bleeding, especially when surgical hemostasis has not been effective[49,50]: oxidized cellulose hemostat for wound compression; tissues adhesives/ fibrin glue/sealants; fibrin or platelet gel; hemostatic collagen;

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6 – Intraoperative blood recovery (cell saver)/Autotransfusion Intraoperative blood recovery is one of the most important strategies in cardiothoracic surgeries with the ability to reduce the total blood loss and homologous blood transfusion needs and it is recommended by the autologous blood conservation guidelines[16,49,55]. Since this strategy is easy to be applied, some authors defend its use in all patients undergoing cardiac surgery with CPB, regardless of the expected surgical blood loss[55]. This is an important strategy for serious and complex pediatric cardiac surgery[54]. In surgical cardiac and cancer patients with blood recovery needs, consider the use of leukocyte removal filters alone or in combination with irradiation. In a recent systemic revision conducted by Cochrane Database of Systematic Reviews[56] the authors concluded that intraoperative blood recovery is efficient in reducing allogeneic blood transfusion needs in cardiac surgery. Figure 4 shows a schematic representation of an intraoperative blood recovery. 7 – Additional Strategies Another strategy to reduce surgical bleeding consists of continuous infusion of noradrenaline and restrictive hydration. The absolute risk of blood transfusions during hospitalizations had a 28% reduction. The authors also concluded that this procedure is safe, inexpensive and easy to accomplish[57].

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Fig. 3 - Schematic representation of acute normovolemic hemodilution. (A) Bags of blood being removed immediately before the initiation of surgery, along with the infusion of volume expanders to maintain normovolemia. (B) Bags of blood being re-infused during and/or immediately after the surgery is completed.

Fig. 4 - Schematic representation of intraoperative blood recovery. The collected blood is mixed with anticoagulant, filtered, washed, concentrated and returned to the patient.

III â&#x20AC;&#x201C; Anemia tolerance Individual patient anemia tolerance is one of the most important factors in deciding whether to transfuse or not. We do not have in the literature studies demonstrating a minimum hemoglobin trigger to recommend a safe blood transfusion. However, we have numerous randomized clinical trials demonstrating that a restrictive strategy of blood transfusion is safe and efficient in reducing allogeneic blood and does not increase the risk of complications or death in cardiac surgeries in adults[12] and children[58]. Through a recent meta-analysis

and systematic review of the literature it was confirmed that a greater tolerance of anemia, a more restrictive approach to transfusion, is actually beneficial to critically ill patients[59]. Senay et al.[14] observed that a hematocrit of 17% during CABG is well tolerated and does not have an adverse impact on the outcome. Knowledge of this evidence would prevent many unnecessary allogeneic transfusions, since in most cases it is not the patient but the doctor who does not tolerate anemia. Frequently, transfusions are indicated based on laboratory results of hemoglobin and/or hematocrit. This practice is not

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recommended by Murphy et al.[60] when indications for blood transfusions for cardiac surgeries were considered due to the evidence that hematocrit is not the ideal clinical indicator of tissue oxygen delivery. The literature shows that the human being is capable of tolerating extremely low levels of hemoglobin. Graffeo et al.[61] reports a case that, after a severe hemorrhagic event and disseminated intravascular coagulation, reached its nadir minimum hemoglobin level of 1.9 g/dL. In another case, after surgery of severe thoracic-lumbar scoliosis, a patient had also survived without the use of blood transfusion even after reaching a critical hemoglobin level of 1.4 g/dL[62]. In these two cases, anemia tolerance was a therapeutic option that resulted in economy of blood components for blood banks. Table 3 shows the main strategies to improve anemia tolerance. They involve at least two fundamental therapies:

continuous reevaluation of tissue perfusion and oxygenation as well as hemodynamic function. If unsure on the volume status or cardiac output of the anemic patient, perform an appropriate assessment of the patient´s clinical condition, for example: evidence of volume, echodopplercardiogram, etc. Variations both in the systolic arterial pressure and in the pulse pressure with the ventilatory cycle can indicate volume depletion in the patient on mechanical ventilation. Even during relative hypotension, the microcirculatory blood flow and oxygenation do not always depend on the arterial blood pressure[64]. Volume expanders without blood Crystalloids: the infusion should be three milliliters of crystalloids for each one milliliter of blood lost with an infusion rate of 60-80 ml/kg/hour (preferably Ringer´s lactate). The Advanced Trauma Life Support (ATLS) recommends in the case of trauma patient with a 700 ml of blood loss, the patient should receive 2,100 ml of crystalloids. Other solutions may be used: 1) normal saline solution, 2) balanced electrolyte solutions or 3) hypertonic saline solution. Colloids (starch and gelatin solutions): dose of one milliliter of colloid for each one milliliter of blood lost, with the maximum recommended dose of 1,500 to 2,000 ml per day. Careful and adequate fluid replacement. In the hypovolemic patient, the strategy for volume replacement (duration, rate of administration and the amount) can be more important than the choice of the solution. There is risk of causing more bleeding with excessive hemodilution and by increasing the blood pressure excessively. Careful administration of the volume, with low levels of hemoglobin, can optimize the microvascular flow and oxygenation, as well as increase anemia tolerance[65]. In moderate amounts, crystalloids are not associated with significant side effects, particularly in hemostasis. Crystalloid infusion (Ringer´s lactate) has resulted in less blood loss than colloids (Hydroxyethyl Starch) in recent investigation[66].

1 – Optimization of oxygen delivery a) Assess tissue perfusion and oxygenation Indices of global perfusion: markers of hypoperfusion include oliguria, decreased sensorium, lactic acidosis, base excess or deficit, and tachycardia. Indices of regional perfusion: assess the markers of organic functions: myocardial ischemia (abnormalities of ST segment), renal dysfunction (decreased urine output and/or increased levels of urea/creatinine) and central nervous system dysfunction (altered mental status). Observe the evidence in combination with the indices of tissue perfusion/hypoxia[63]. b) Increase the cardiac output Optimize the circulating volume Know the patient´s cardiac capacity. The mean arterial pressure, cardiac rhythm, respiratory pattern, urinary output and fluid balance should be assessed. Fluid replacement should not be based only on blood pressure or heart rate. It should be individualized, based on physiological parameters that include

Table 3. Main strategies to improve anemia tolerance. Research study Senay et al.[14] Graffeo et al.[61] Salpeter et al.[59] Demetriades et al.[63] Murphy & Angelini[60] Wettstein et al.[65] Rasmussen et al.[66] Perel et al.[67] Araújo Azi et al.[62] Marik[72]

Main strategies to improve anemia tolerance Patient tolerates anemia in the perioperative period Patient tolerates anemia in the postoperative period Restrictive conduct towards blood transfusion To evaluate indexes of tissue perfusion/hypoxia Hematocrit is not the ideal indicator of tissue oxygen delivery Careful and adequate fluid replacement to optimize the microvascular flow and oxygenation in severe anemia The infusion of crystalloid (Ringer's lactate) results in less blood loss than colloids Correcting hipovolemia with crystalloids, instead of starch solutions, results in lower mortality risk Mechanical ventilation (hyperoxic) assures tissue oxigenation in the presence of severe acute anemia Mantain normothermia in critically ill patients (warm hipothermic patients and cool down febrile patients)

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Correct hypovolemia, if possible, always with crystalloid. In a systematic revision conducted by Cochrane Database of Systematic Reviews[67] the authors have observed evidence of greater mortality risk with the starch solutions.

cooling in patients with severe anemia in intensive therapy can reduce the need of tissue oxygenation, decrease the metabolic rate and offer cerebral protection in subgroups of patients[73]. DISCUSSION

c) Early oxygenotherapy/Oxygen supplementation Anemia tolerance can be increased ventilating the patient with a high fraction of inspired oxygen (FiO2). While normovolemia is being maintained, hyperoxic ventilation (100% of oxygen) can be considered a lifesaving therapy in the presence of gross hemorrhage associated with severe acute anemia with the risk of death[62,68]. Ventilation with 100% oxygen results in rapid increase of the arterial oxygen content, assures tissue oxygenation even with very low hemoglobin and shows to be an important strategy in reducing allogeneic transfusion[69]. For patients with insufficient response to other strategies to improve oxygenation (for example: correction of volume in circulation, vasoactive agents, inotropes), the recommendation is to use sedation and ventilatory support (continuous positive airway pressure [CPAP], intermittent positive pressure [BIPAP]). The faster the tissue oxygen deficiency is detected and corrected, the more probability of better results. Once hypoxemia presents greater immediate risks than oxygen toxicity or hypercapnia, it might be worth the risks involved in supranormal fractions of inspired oxygen to sustain the life of the patient with severe anemia[70]. The use of hyperbaric oxygen therapy to reach a high arterial tension (PaO2) has the potential to save the life of the patient with severe anemia[71].

Blood transfusion is in essence a transplant of allogeneic cells, consisting of the infusion of foreign antigens in great quantities in the recipientÂ´s circulation, resulting in multiple inflammatory and immunological reactions[74]. This is one of the main explanations to the adverse outcomes of this medical practice. Centers worldwide are seeking to institute protocols to limit the use of blood and this has become a criterion for high-quality hospital care surveyed by certifying agencies of quality assurance, such as the Joint Commission International[75]. Numerous pathways can be utilized as part of these blood conservation protocols. It is important to raise awareness of the main therapeutic possibilities to transfusions in order to economize the already scarce hemocomponent supply of blood banks. When there is multiprofessional purpose and involvement in managing and conserving autologous blood, complex cardiac surgeries such as cardiac retransplantation can be performed without the use of allogeneic blood[54]. By applying one or more strategies as described in Tables 1, 2 and 3, allogeneic blood consumption can be decreased. A simple course of action, but fundamentally important, is the diagnosis and treatment of anemia with iron, folic acid and vitamin B12 replacement and, when necessary, r-Hu-EPO. The principal strategies to minimize blood loss involve eliminating multiple daily routine phlebotomies, avoiding or reducing the time of the CPB, meticulous hemostasis, pharmacological hemostasis with tranexamic acid or epsilon aminocaproic acid, use of medications that increase the activity of coagulation factors (desmopressin, r-FVIIa, PCC, Factor XIII), in addition to ANH and intraoperative blood recovery (cell saver). Another important strategy to limit blood consumption is to adopt a restrictive transfusion practice, with a plan of action to improve tissue oxygenation of the anemic patient. These and other strategies are described in Figure 2. The more alternative therapies used, the higher the possibility to treat a patient without the need of transfusions[76]. The benefits are not restricted to the economic sphere, but also to the gravity and incidence of complications, in particular to mortality, related to allogeneic blood transfusions. This literature review compiles multiple therapeutic options to reduce the number of transfused patients as well as the amount of blood and its components administered to each patient. Nonetheless, before implementing these methods, it is fundamental to have a desire to change the transfusional attitude, especially in relation to anemia tolerance. Some of the methods are simple and safe and can be easily implemented;

d) Artificial oxygen carriers and polymerized hemoglobin solutions Perfluorocarbon and MP4OX (oxygenated polyethylene glycol-modified hemoglobin) still need evidences guaranteeing safety and efficiency, as well as cost-effectiveness. 2 â&#x20AC;&#x201C; Minimization of oxygen consumption a) Appropriate analgesia b) Sedation and muscle relaxants It is recommended to administer the lowest effective dose for the lowest duration of analgesia and sedation. Consider neuromuscular blockade. Decrease oxygen consumption by reducing the metabolic rate and preventing shivering, agitation and anxiety. c) Mechanical ventilation It can be recommended in severe anemia cases to improve the supply and to reduce the consumption of oxygen by the tissues. d) Temperature Control Maintain normothermia (actively warm hypothermic patients and cool down febrile patients)[72]. The use of therapeutic

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others require a carefully orchestrated process. These strategies are not mutually exclusive and the reality of each procedure can guide which plan of action is better and more feasible. A medical center that establishes an autologous blood conservation process can reduce in up to 70% of the number of blood component units infused as well as the number of hemotransfused patients[76]. We encourage a new concept in the transfusional medicine in that, with the least amount of allogeneic blood use in cardiac surgeries, can result in a reduction of the total morbimortality of patients, as well as easing the demand on blood banks. New studies are recommended to evaluate the safety and efficacy of allogeneic blood transfusions. One of the main limitations of utilizing some of these options as alternatives to blood transfusions are related to the cost and availability of a determined strategy, such as the intraoperative cell salvage machine, certain medications (r-Hu-TPO, eltrombopag, Factor VIIa, Factor XIII, PCC, HFC) and the learning curve of more refined surgical techniques to avoid bleeding. The retrograde autologous priming technique is also a limited option, due to potential complications of hemodynamic instability resulted from hypovolemia. Another limitation in applying some of these strategies will occur with emergency surgeries. The assessment of the risk-benefit binomial is an important factor to consider in relation to the transfusional and nontransfusional practice. When medical decisions are made by multidisciplinary teams, the treatment potential damage is reduced whether for certain patient subgroups or even for the general population.

phlebotomies, utilizing less traumatic surgical techniques with moderate hypothermia and hypotension, meticulous hemostasis, use of topical and systemic hemostatic agents, acute normovolemic hemodilution, intraoperative blood recovery, anemia tolerance (supplemental oxygen and normothermia), as well as numerous other therapeutic options have proved to be effective strategies in reducing allogeneic blood transfusions. In order to decrease the consumption of blood components, diminish morbidity and mortality, and reduce hospital costs, these treatment strategies should be incorporated into medical practice worldwide.

Authors’ roles & responsibilities AAS JPS LFS

CONCLUSION

AGS

There are multiple clinical and surgical strategies with evidence of optimizing the erythrocyte mass and the coagulation status, minimizing blood loss and improving anemia tolerance. Treating anemia and thrombocytopenia, suspending anticoagulants and antiplatelet agents, reducing routine

RFP JFB

REFERENCES

Conception and design of the study, analysis and/or interpretation of data, writing of the manuscript or critical review of its content, final approval of the manuscript Writing of the manuscript or critical review of its content, analysis and/or interpretation of data, final approval of the manuscript Writing of the manuscript or critical review of its content, final approval of the manuscript Writing of the manuscript or critical review of its content, analysis and/or interpretation of data, final approval of the manuscript Writing of the manuscript or critical review of its content, analysis and/or interpretation of data, final approval of the manuscript Final approval of the manuscript

but the patient is bleeding? South Afr J Anaesth Analg. 2008;14(1):39-43.

1. Bennett-Guerrero E, Zhao Y, O’Brien SM, Ferguson TB Jr, Peterson ED, Gammie JS, et al. Variation in use of blood transfusion in coronary artery bypass graft surgery. JAMA. 2010;304(14):1568-75.

5. Koch CG, Li L, Duncan AI, Mihaljevic T, Cosgrove DM, Loop FD, et al. Morbidity and mortality risk associated with red blood cell and blood-component transfusion in isolated coronary artery bypass grafting. Crit Care Med. 2006;34(6):1608-16.

2. Sojka BN, Sojka P. The blood donation experience: selfreported motives and obstacles for donating blood. Vox Sang. 2008;94(1):56-63.

6. Murphy GJ, Reeves BC, Rogers CA, Rizvi SI, Culliford L, Angelini GD. Increased mortality, postoperative morbidity, and cost after red blood cell transfusion in patients having cardiac surgery. Circulation. 2007;116(22):2544-52.

3. Novaretti MCZ. Importância dos carreadores de oxigênio livre de células. Rev Bras Hematol Hemoterapia. 2007;29(4):394-405.

7. Dorneles CC, Bodanese LC, Guaragna JCVC, Macagnan FE, Coelho JC, Borges AP, et al. O impacto da hemotransfusão na

4. Mackenzie CF, Shander A. What to do if no blood is available

618

Rev Bras Cir Cardiovasc | Braz J Cardiovasc Surg

Santos AA, et al. - Therapeutic options to minimize allogeneic blood transfusions and their adverse effects in cardiac surgery: A systematic review

Rev Bras Cir Cardiovasc 2014;29(4):606-21

morbimortalidade pós-operatória de cirurgias cardíacas. Rev Bras Cir Cardiovasc. 2011;26(2):222-9.

19. Swain RA, Kaplan B, Montgomery E. Iron deficiency anemia. When is parenteral therapy warranted? Postgrad Med. 1996;100(5):181-2.

8. Engoren MC, Habib RH, Zacharias A, Schwann TA, Riordan CJ, Durham SJ. Effect of blood transfusion on long-term survival after cardiac operation. Ann Thorac Surg. 2002;74(4):1180-6.

20. Weltert L, D’Alessandro S, Nardella S, Girola F, Bellisario A, Maselli D, et al. Preoperative very short-term, high-dose erythropoietin administration diminishes blood transfusion rate in off-pump coronary artery bypass: a randomized blind controlled study. J Thorac Cardiovasc Surg. 2010;139(3):621-6.

9. Santos AA, Sousa AG, Thomé HO, Machado RL, Piotto RF. Impact on early and late mortality after blood transfusion in coronary artery bypass graft surgery. Rev Bras Cir Cardiovasc. 2013;28(1):1-9.

21. Corwin HL, Gettinger A, Pearl RG, Fink MP, Levy MM, Shapiro MJ, et al; EPO Critical Care Trials Group. Efficacy of recombinant human erythropoietin in critically ill patients: a randomized controlled trial. JAMA. 2002;288(22):2827-35.

10. Santos AA, Sousa AG, Piotto RF, Pedroso JC. Mortality risk is dose-dependent on the number of packed red blood cell transfused after coronary artery bypass graft. Rev Bras Cir Cardiovasc. 2013;28(4):509-17.

22. Eckardt KU. Anaemia of critical illness: implications for understanding and treating rHuEPO resistance. Nephrol Dial Transplant. 2002;17(Suppl 5):48-55.

11. Shander A, Hofmann A, Ozawa S, Theusinger OM, Gombotz H, Spahn DR. Activity-based costs of blood transfusions in surgical patients at four hospitals. Transfusion. 2010;50(4):753-65.

23. Ohls RK, Harcum J, Schibler KR, Christensen RD. The effect of erythropoietin on the transfusion requirements of preterm infants weighing 750 grams or less: a randomized, double-blind, placebo-controlled study. J Pediatr. 1997;131(5):661-5.

12. Hajjar LA, Vincent JL, Galas FR, Nakamura RE, Silva CM, Santos MH, et al. Transfusion requirements after cardiac surgery: the TRACS randomized controlled trial. JAMA. 2010;304(14):1559-67.

24. Silverberg D, Wexler D, Blum M, Schwartz D, Iaina A. The use of androgens in anaemia resistant to erythropoietin and i.v. iron in patients with heart and renal failure. Nephrol Dial Transplant. 2004;19(4):1021.

13. Souza DD, Braile DM. Avaliação de nova técnica de hemoconcentração e da necessidade de transfusão de hemoderivados em pacientes submetidos à cirurgia cardíaca com circulação extracorpórea. Rev Bras Cir Cardiovasc. 2004;19(3):287-94.

25. Kaufman JS, Reda DJ, Fye CL, Goldfarb DS, Henderson WG, Kleinman JG, et al. Subcutaneous compared with intravenous epoetin in patients receiving hemodialysis. Department of Veterans Affairs Cooperative Study Group on Erythropoietin in Hemodialysis Patients. N Engl J Med. 1998;339(9):578-83.

14. Senay S, Toraman F, Karabulut H, Alhan C. Is it the patient or the physician who cannot tolerate anemia? A prospective analysis in 1854 non-transfused coronary artery surgery patients. Perfusion. 2009;24(6):373-80.

26. Stohlawetz PJ, Dzirlo L, Hergovich N, Lackner E, Mensik C, Eichler HG, et al. Effects of erythropoietin on platelet reactivity and thrombopoiesis in humans. Blood. 2000;95(9):2983-9.

15. Society of Thoracic Surgeons Blood Conservation Guideline Task Force, Ferraris VA, Ferraris SP, Saha SP, Hessel EA 2nd, Haan CK, Royston BD, et al; Society of Cardiovascular Anesthesiologists Special Task Force on Blood Transfusion. Perioperative blood transfusion and blood conservation in cardiac surgery: the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists clinical practice guidelines. Ann Thorac Surg. 2007;83(5 Suppl):S27-86.

27. Drüeke T. Hyporesponsiveness to recombinant human erythropoietin. Nephrol Dial Transplant. 2001;16(Suppl 7):25-8. 28. Bohlius J, Wilson J, Seidenfeld J, Piper M, Schwarzer G, Sandercock J, et al. Recombinant human erythropoietins and cancer patients: updated meta-analysis of 57 studies including 9353 patients. J Natl Cancer Inst. 2006;98(10):708-14.

16. Menkis AH, Martin J, Cheng DC, Fitzgerald DC, Freedman JJ, Gao C, et al. Drug, devices, technologies, and techniques for blood management in minimally invasive and conventional cardiothoracic surgery: a consensus statement from the International Society for Minimally Invasive Cardiothoracic Surgery (ISMICS) 2011. Innovations (Phila). 2012;7(4):229-41.

29. Bussel JB, Provan D, Shamsi T, Cheng G, Psaila B, Kovaleva L, et al. Effect of eltrombopag on platelet counts and bleeding during treatment of chronic idiopathic thrombocytopenic purpura: a randomised, double-blind, placebo-controlled trial. Lancet. 2009;373(9664):641-8.

17. Drews RE. Critical issues in hematology: anemia, thrombocytopenia, coagulopathy, and blood product transfusions in critically ill patients. Clin Chest Med. 2003;24(4):607-22.

30. Wang Y, Wang Z, Wu L, Zhang J, Wang J, Yan L. Recombinant human thrombopoietin is an effective treatment for thrombocytopenia in hemophagocytic lymphohistiocytosis. Ann Hematol. 2013;92(12):1695-9.

18. Goodnough LT. Iron deficiency syndromes and iron-restricted erythropoiesis (CME). Transfusion. 2012;52(7):1584-92.

31. Whitlock R, Crowther MA, Ng HJ. Bleeding in cardiac surgery:

619

Rev Bras Cir Cardiovasc | Braz J Cardiovasc Surg

Santos AA, et al. - Therapeutic options to minimize allogeneic blood transfusions and their adverse effects in cardiac surgery: A systematic review

Rev Bras Cir Cardiovasc 2014;29(4):606-21

its prevention and treatment--an evidence-based review. Crit Care Clin. 2005;21(3):589-610.

44. Prasad GV, Abidi SM, McCauley J, Johnston JR. Vitamin K deficiency with hemorrhage after kidney and combined kidneypancreas transplantation. Am J Kidney Dis. 1999;33(5):963-5.

32. Chu UB, Clevenger FW, Imami ER, Lampard SD, Frykberg ER, Tepas JJ 3rd. The impact of selective laboratory evaluation on utilization of laboratory resources and patient care in a level-I trauma center. Am J Surg. 1996;172(5):558-62.

45. Lin Y, Stanworth S, Birchall J, Doree C, Hyde C. Recombinant factor VIIa for the prevention and treatment of bleeding in patients without haemophilia. Cochrane Database Syst Rev. 2011;(2):CD005011.

33. Dech ZF, Szaflarski NL. Nursing strategies to minimize blood loss associated with phlebotomy. AACN Clin Issues. 1996;7(2):277-87.

46. Monroe DM, Hoffman M. What does it take to make the perfect clot? Arterioscler Thromb Vasc Biol. 2006;26(1):41-8.

34. Milas BL, Jobes DR, Gorman RC. Management of bleeding and coagulopathy after heart surgery. Semin Thorac Cardiovasc Surg. 2000;12(4):326-36.

47. Nienaber U, Innerhofer P, Westermann I, Schöchl H, Attal R, Breitkopf R, et al. The impact of fresh frozen plasma vs coagulation factor concentrates on morbidity and mortality in trauma-associated haemorrhage and massive transfusion. Injury. 2011;42(7):697-701.

35. Lamy A, Devereaux PJ, Prabhakaran D, Taggart DP, Hu S, Paolasso E, et al; CORONARY Investigators. Off-pump or onpump coronary-artery bypass grafting at 30 days. N Engl J Med. 2012;366(16):1489-97.

48. Rahe-Meyer N, Hanke A, Schmidt DS, Hagl C, Pichlmaier M. Fibrinogen concentrate reduces intraoperative bleeding when used as first-line hemostatic therapy during major aortic replacement surgery: results from a randomized, placebo-controlled trial. J Thorac Cardiovasc Surg. 2013;145(3 Suppl):S178-85.

36. Zangrillo A, Garozzo FA, Biondi-Zoccai G, Pappalardo F, Monaco F, et al. Miniaturized cardiopulmonary bypass improves short-term outcome in cardiac surgery: a meta-analysis of randomized controlled studies. J Thorac Cardiovasc Surg. 2010;139(5):1162-9.

49. Society of Thoracic Surgeons Blood Conservation Guideline Task Force, Ferraris VA, Brown JR, Despotis GJ, Hammon JW, Reece TB, Saha SP, et al; Society of Cardiovascular Anesthesiologists Special Task Force on Blood Transfusion, International Consortium for Evidence Based Perfusion. 2011 update to the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists blood conservation clinical practice guidelines. Ann Thorac Surg. 2011;91(3):944-82.

37. Boodhwani M, Williams K, Babaev A, Gill G, Saleem N, Rubens FD. Ultrafiltration reduces blood transfusions following cardiac surgery: a meta-analysis. Eur J Cardiothorac Surg. 2006;30(6):892-7. 38. Rosengart TK, DeBois W, O’Hara M, Helm R, Gomez M, Lang SJ, et al. Retrograde autologous priming for cardiopulmonary bypass: a safe and effective means of decreasing hemodilution and transfusion requirements. J Thorac Cardiovasc Surg. 1998;115(2):426-38.

50. Abrishami A, Chung F, Wong J. Topical application of antifibrinolytic drugs for on-pump cardiac surgery: a systematic review and meta-analysis. Can J Anaesth. 2009;56(3):202-12. 51. Licker M, Ellenberger C, Sierra J, Kalangos A, Diaper J, Morel D. Cardioprotective effects of acute normovolemic hemodilution in patients undergoing coronary artery bypass surgery. Chest. 2005;128(2):838-47.

39. Van der Linden P, De Hert S, Daper A, Trenchant A, Jacobs D, De Boelpaepe C, et al. A standardized multidisciplinary approach reduces the use of allogeneic blood products in patients undergoing cardiac surgery. Can J Anesth. 2001;48(9):894-901.

52. Gross JB. Estimating allowable blood loss: corrected for dilution. Anesthesiology. 1983;58(3):277-80.

40. Degoute CS. Controlled hypotension: a guide to drug choice. Drugs. 2007;67(7):1053-76. 41. Frenette L, Cox J, McArdle P, Eckhoff D, Bynon S. Conjugated estrogen reduces transfusion and coagulation factor requirements in orthotopic liver transplantation. Anesth Analg. 1998;86(6):1183-6.

53. Davies L, Brown TJ, Haynes S, Payne K, Elliott RA, McCollum C. Cost-effectiveness of cell salvage and alternative methods of minimizing perioperative allogeneic blood transfusion: a systematic review and economic model. Health Tech Assess. 2006;10(44):iii-iv, ix-x, 1-210.

42. Carless PA, Stokes BJ, Moxey AJ, Henry DA. Desmopressin use for minimizing perioperative allogeneic blood transfusion. Cochrane Database Syst Rev. 2008;(1):CD001884.

54. Santos AA, Silva JP, Fonseca L, Baumgratz JF. Retransplante cardíaco em criança sem o uso de hemoderivados. Rev Bras Cir Cardiovasc. 2012;27(2):327-30.

43. Crescenzi G, Landoni G, Biondi-Zoccai G, Pappalardo F, Nuzzi M, Bignami E, et al. Desmopressin reduces transfusion needs after surgery: a meta-analysis of randomized clinical trials. Anesthesiology. 2008;109(6):1063-76.

55. Dunning J, Versteegh M, Fabbri A, Pavie A, Kolh P, Lockowandt U, et al; EACTS Audit and Guidelines Committee. Guideline on antiplatelet and anticoagulation management in cardiac surgery. Eur J Cardiothorac Surg. 2008;34(1):73-92.

620

Rev Bras Cir Cardiovasc | Braz J Cardiovasc Surg

Santos AA, et al. - Therapeutic options to minimize allogeneic blood transfusions and their adverse effects in cardiac surgery: A systematic review

Rev Bras Cir Cardiovasc 2014;29(4):606-21

56. Carless PA, Henry DA, Moxey AJ, O’Connell D, Brown T, Fergusson DA. Cell salvage for minimising perioperative allogeneic blood transfusion. Cochrane Database Syst Rev. 2010;(4):CD001888.

metabolic disorder in experimental hemorrhagic shock. Shock. 2004;21(3):235-40. 66. Rasmussen KC, Johansson PI, Højskov M, Kridina K, Kistorp T, Thind P, et al. Hydroxyethyl starch reduces coagulation competence and increases blood loss during major surgery: results from a randomized controlled trial. Ann Surg. 2014;259(2):249-54.

57. Wuethrich PY, Studer UE, Thalmann GN, Burkhard FC. Intraoperative continuous norepinephrine infusion combined with restrictive deferred hydration significantly reduces the need for blood transfusion in patients undergoing open radical cystectomy: results of a prospective randomised trial. Eur Urol. 2014;66(2):352-60.

67. Perel P, Roberts I, Ker K. Colloids versus crystalloids for fluid resuscitation in critically ill patients. Cochrane Database Syst Rev. 2013;2:CD000567.

58. Lacroix J, Hebert PC, Hutchison JS, Hume HA, Tucci M, Ducruet T, et al.; TRIPICU Investigators; Canadian Critical Care Trials Group; Pediatric Acute Lung Injury and Sepsis Investigators Network. Transfusion strategies for patients in pediatric intensive care units. N Engl J Med. 2007;356(16):1609-19.

68. Meier J, Kemming GI, Kisch-Wedel H, Wölkhammer S, Habler OP. Hyperoxic ventilation reduces 6-hour mortality at the critical hemoglobin concentration. Anesthesiology. 2004;100(1):70-6.

59. Salpeter SR, Buckley JS, Chatterjee S. Impact of more restrictive blood transfusion strategies on clinical outcomes: a meta-analysis and systematic review. Am J Med. 2014;127(2):124-131.

70. Neff TA, Stocker R, Wight E, Spahn DR. Extreme intraoperative blood loss and hemodilution in a Jehovah’s Witness: new aspects in postoperative management. Anesthesiology. 1999;91(6):1949-51.

69. Habler O, Kleen M, Kemming G, Zwissler B. Hyperoxia in extreme hemodilution. Eur Surg Res. 2002;34(1-2):181-7.

60. Murphy GJ, Angelini GD. Indications for blood transfusion in cardiac surgery. Ann Thorac Surg. 2006;82(6):2323-34.

71. Van Meter KW. A systematic review of the application of hyperbaric oxygen in the treatment of severe anemia: an evidencebased approach. Undersea Hyperb Med. 2005;32(1):61-83.

61. Graffeo C, Dishong W. Severe blood loss anemia in a Jehovah’s Witness treated with adjunctive hyperbaric oxygen therapy. Am J Emerg Med. 2013;31(4):756.

72. Marik PE. Fever in the ICU. Chest. 2000;117(3):855-69.

62. Araújo Azi LM, Lopes FM, Garcia LV. Postoperative management of severe acute anemia in a Jehovah’s Witness. Transfusion. 2014;54(4):1153-7.

73. Akingbola OA, Custer JR, Bunchman TE, Sedman AB. Management of severe anemia without transfusion in a pediatric Jehovah’s Witness patient. Crit Care Med. 1994;22(3):524-8.

63. Demetriades D, Chan LS, Bhasin P, Berne TV, Ramicone E, Huicochea F, et al. Relative bradycardia in patients with traumatic hypotension. J Trauma. 1998;45(3):534-9.

74. Flohé S, Kobbe P, Nast-Kolb D. Immunological reactions secondary to blood transfusion. Injury. 2007;38(12):1405-8. 75. Kumar A. Perioperative management of anemia: limits of blood transfusion and alternatives to it. Cleve Clin J Med. 2009;76(Suppl 4):S112-8.

64. LeDoux D, Astiz ME, Carpati CM, Rackow EC. Effects of perfusion pressure on tissue perfusion in septic shock. Crit Care Med. 2000;28(8):2729-32.

76. Tinmouth A, Macdougall L, Fergusson D, Amin M, Graham ID, Hebert PC, et al. Reducing the amount of blood transfused: a systematic review of behavioral interventions to change physicians’ transfusion practices. Arch Intern Med. 2005;165(8):845-52.

65. Wettstein R, Tsai AG, Erni D, Lukyanov AN, Torchilin VP, Intaglietta M, et al. Improving microcirculation is more effective than substitution of red blood cells to correct

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Yuan SM - Anomalous of coronary artery: taxonomy and clinical REVIEWorigin ARTICLE implication

Anomalous origin of coronary artery: taxonomy and clinical implication Origem anômala da artéria coronária: taxonomia e implicação clínica

Shi-Min Yuan1, MMed, PhD RBCCV 44205-1597

DOI: 10.5935/1678-9741.20140109 Abstract Objective: Anomalous origin of coronary artery is uncommon. The taxonomies of anomalous origin of coronary artery are inconsistent and complex. Conceptual and therapeutic debates remain. The aim of the present study is to reappraise the concept of anomalous origin of coronary artery and to discuss the potential hazards and treatment rationale of this anomaly on basis of literature review. Methods: A comprehensive literature review was made in terms of the taxonomies including “simple”, “multiple” and “complex” types of anomalous origin of coronary artery. Results: Anomalous origin of coronary artery can be simply categorized according to the ectopically originated coronary artery. There are a couple of complex anatomical variants: “multiple” type, involving more than one coronary artery or branch, which can be subdivided into 2 subtypes, A) more than one coronary arteries or branches arising from one place; and B) two coronary arteries/branches arising from separate ectopic sites; and “complex” type, associated with acquired heart disease, or congenital heart defects. Conclusion: Sudden cardiac death in anomalous origin of coronary artery is associated with the anatomical features including abnormal coursing, acute angle take-off and ostial abnormalities. Atherosclerosis is prone to be in the right-sided ectopic and retroaortic coursing coronary artery. Surgical treatment is a definitive therapy. Simple coronary artery bypass grafting is not recommended due to the potential hazards of coronary steal phenomenon and poor patency of mammary arterial grafts, and modified maneuvers such as coronary ostial reimplantation, impinged coronary segment unroofing and coronary stent deployment are advocated instead.

Resumo Objetivo: A origem anômala da artéria coronária é incomum. As taxonomias de origem anômala da artéria coronária são inconsistentes e complexas. Os debates conceituais e terapêuticos permanecem. O objetivo do presente estudo é reavaliar o conceito de origem anômala da artéria coronária e discutir os riscos potenciais e fundamentos para o tratamento desta anomalia, com base em revisão de literatura. Métodos: A revisão da literatura foi feita com termos das taxonomias, incluindo origem anômala da artéria coronária “simples”, “múltipla” e “complexa”. Resultados: A origem anômala da artéria coronária pode ser simplesmente classificada de acordo com a origem ectópica da artéria coronária. Há um par de variações anatômicas complexas: “múltipla”, envolvendo mais de uma artéria coronária ou ramo, que podem ser subdivididos em dois subtipos: A) mais de uma das artérias coronárias ou ramos decorrentes de um lugar; e B) duas artérias coronárias/ramos decorrentes de sítios ectópicos separados; e tipo “complexo”, associado à doença cardíaca adquirida ou defeitos cardíacos congênitos. Conclusão: A morte súbita cardíaca de origem anômala da artéria coronária está associada com as características anatômicas incluindo curso anormal, descolamento de ângulo agudo e anormalidades ostiais. A aterosclerose é propensa a ocorrer na artéria coronária ectópica e retroaórtica, do lado direito. O tratamento cirúrgico é uma terapia definitiva. Revascularização do miocárdio simples não é recomendada devido aos riscos potenciais do fenômeno de “roubo” do fluxo coronário e patência ruim dos enxertos com a artéria torácica interna. Manobras modificadas como reimplante ostial coronário, destelhamento do segmento coronário impingido e implantação de stent coronário são defendidas em seu lugar.

Descriptors: Classification. Coronary Artery Disease. Coronary Vessels. Death, Sudden, Cardiac.

Descritores: Classificação. Doença da Artéria Coronariana. Vasos Coronários. Morte Súbita Cardíaca.

The First Hospital of Putian, Teaching Hospital, Fujian Medical University, Putian, Fujian Province, People’s Republic of China.

Correspondence address: Shi-Min Yuan Longdejing Street, 389 - Chengxian District, Putian, Fujian Province, People’s Republic of China E-mail: shi_min_yuan@yahoo.com

This study was carried out at First Hospital of Putian, Teaching Hospital, Fujian Medical University, Putian, Fujian Province, People’s Republic of China.

Article received on July 14th, 2014 Article accepted on September 14th, 2014

No financial support.

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Yuan SM - Anomalous origin of coronary artery: taxonomy and clinical implication

unusual morphologic finding >1%, and anomaly is a morphologic finding <1% of the general population[11]. Both LAD and LCx separately originating from the left coronary cusp with an absence of a left main coronary artery (LM) and the conal branch arising from the right coronary cusp are regarded as normal variants[3]. However, a septal branch arising from the aorta is an anomaly[12]. Based on these definitions, some classifications of anomalous origin of coronary artery that involving absence of the left main stem are wrong[13].

Abbreviations, acronyms & symbols LAD LCA LCx LM LVOT RCA

Left anterior descending artery Left coronary artery Left circumflex artery Left main coronary artery Left ventricular outflow tract Right coronary artery

INTRODUCTION

Taxonomies There have been many ways of taxonomies of anomalous origin of coronary artery. Firstly, it can be simply categorized according to the ectopically originated coronary artery. Based on large patient population studies, it has been recognized that the LCx is the most common to be ectopically originated followed by single coronary artery, and ectopic LCA, LAD and RCA accounting for 58.3%, 12.5%, 10.4%, 10.4% and 8.5%, respectively[14]. In a total of 23,300 coronary angiograms, the incidence of the anomalous coronary arteries was 0.4%: LCx (46, 47%), RCA (25, 25.5%), LM (10, 10.2%), LAD (3, 3.1%), single coronary arteries (3, 6.1%) and other anomalies (8, 8.2%)[15]. In another series with 24,959 patients with coronary angiograms, 73 (0.3%) had major coronary artery anomalies: 70 (95.9%) had one coronary anomaly and 3 (4.1%) had two coronary anomalies. The most common anomaly involved the LCx (60%), 69% of which arose from a separate ostium in the right coronary sinus and 31% as a branch of the RCA[16]. The most frequent categorical method is that of the ectopic origin site, which involves ectopic origin of coronary artery from, 1) the aorta, either from a wrong sinus or beyond the sinuses; 2) the pulmonary artery; 3) as a branch of another coronary artery; 4) other arteries; and 5) the ventricular chamber (Table 1). Ectopic aortic origin is the most common type, of which an anomalous origin from a wrong sinus of Valsalva predominates (Figures 1-3)[17,18]. There are a couple of complex anatomical variants with regard to the categories of the ectopic origin of coronary artery: “multiple” type, involving more than one coronary artery or branch, which can be subdivided into 2 subtypes: A) more than one coronary artery or branch arising from one place; and B) two coronary arteries/branches arising from separate ectopic sites[19]; and “complex” type, associated with acquired heart disease (coronary artery disease or valve disorder), or congenital heart defects (common or uncommon).

Coronary artery anomalies are uncommon but potentially lethal with an incidence of about 1% in patients for coronary angiography[1]. Anomalous origin of coronary artery is a common type of congenital coronary artery anomaly. However, the taxonomies of anomalous origin of coronary artery are inconsistent and complex without any homogeneity in terms of the conceptual extensions. Different classifications of anomalous origin of coronary artery have been proposed by different authors, including single coronary artery, split coronary ostium, absent left main coronary artery, hypoplastic coronary artery, anomalous location of coronary ostia and anomalies of intrinsic coronary arterial anatomy[2]. In addition, distinctions between anomalous origin and normal variant of coronary artery have not been well described[3]. A taxonomy, which elaborates the anomalous origin of coronary artery in detail, is scanty. Moreover, the anomalous origin of coronary artery has significant clinical implications due to its association with myocardial ischemia[4,5], lethal arrhythmia[6] and even sudden cardiac death[7]. In some patients, atherosclerotic coronary artery disease or valvular heart disease can be associated with anomalous origin of coronary artery[8]. Accordingly, this lesion is often called a “malignant” coronary artery anomaly[9]. The clinical implications of anomalous origin of coronary artery in relation to the anatomic features remain to be elaborated. Detailed knowledge of the anatomies of the coronary artery variations would be necessary for the diagnosis and treatment of the underlying heart diseases[10]. The aim of the present study is to reappraise the concept of anomalous origin of coronary artery and to discuss the potential hazards and treatment rationale of this anomaly on basis of literature review. DEFINITIONS The right coronary artery (RCA), left coronary artery (LCA), left anterior descending (LAD) and left circumflex (LCx) arteries are defined as “arteries”, while the more distal coronary vessels are defined as “branches”[3]. Moreover, before talking about anomaly, it is necessary to make clear the concepts of “normal” and “normal variants”. Normal is defined as a morphologic finding >1%, normal variant is an

Clinical Implications The most frequent indication for coronary angiography is angina (43.9%)[15]. As a branch of another coronary artery, anomalous origin of LCA from the proximal RCA may cause severe angina even at rest, which can be an indication for coronary artery bypass grafting[20].

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Origin of coronary artery arising from the innominate artery can be the cause of syncope[21] or chest pain in adults[22,23]. Origin of the right coronary artery from the descending thoracic aorta may be associated with atypical and striking elastotic changes and wall thickening of the coronary artery as the underlying pathogenesis of severe consequences[24]. The circulatory symptoms may also derived from ectopic coronary arterial course between the pulmonary trunk and aorta in spite of the lack of the atherosclerotic plaques in the coronary artery[25]. Anomalous origin of coronary artery can be associated with common congenital heart defect[26], or with rare congenital heart defect like cervical aortic arch[27]. Robiseck[28] reported such a case in a 4-year-old boy associated with tetralogy of Fallot which was successfully repaired without any postoperative complications. Anomalous origin of coronary artery from other arteries other than coronary is often associated with more complex congenital heart defects and the treatment is more challenging and the prognosis is poorer[29]. Total anomalous origin of coronary arteries from the pulmonary artery can be isolated or combined with other congenital heart defects. It is often considered a cause of neonatal and infantile death with congenital coronary anomalies as a result of hypoxia due to the insufficient flow to the myocardium under lower pressure. Hoganson et al.[30] reported a neonatal death due to a single coronary artery arising from the pulmonary artery died at 10 day of life. Bharati et al.[31] reported an infant with total anomalous origin of coronary artery from the pulmonary artery associated with hypoplastic left heart syndrome died of congestive heart failure on hospital day 3 in spite of prostaglandin administration. Lloyd et al.[32] reported total anomalous origin of coronary artery from the pulmonary artery was found during the operation for ventricular septal defect and aorticopulmonary septal defect in a 7-week old baby. Finally the baby was failed to be resuscitated from the operation and died. Davis and Lie[33] reported a case of the origin of a single coronary artery arising from the innominate artery (brachiocephalic trunk). Associated cardiovascular malformations were truncus arteriosus and a single ventricle and died 12 hours after birth. Heart failure

Table 1. Categories of the ectopic origin of coronary artery. Ectopic origin site From the aorta

• Left main coronary artery arising from the right anterior sinus • Right coronary artery originating from the left coronary sinus • Left circumflex or left anterior descending coronary artery arising from the right coronary sinus • A single coronary artery arising from the right, left and/or non-coronary sinus • Ascending aorta (high aortic origin) • Descending aorta

From the pulmonary artery

• Left coronary artery arising from the pulmonary artery (Bland-White-Garland syndrome) • Right coronary artery arising from the pulmonary artery • Left anterior descending coronary artery arising from the pulmonary artery • Both left and right coronary arteries arising from the pulmonary artery

As a branch of another coronary artery

• Left coronary artery from the proximal right coronary artery • Left circumflex coronary artery from a right coronary artery • Right coronary artery as a branch of the left circumflex coronary artery • Right coronary artery arising from the left anterior descending artery

From other arteries

• Innominate artery • Branchiocephalic trunk • Left mammary artery • Left subclavian artery • Carotid artery • Bronchial artery

From the left ventricle

Fig. 1 - Right coronary artery arising from the left coronary sinus[10]: (A) from a separate ostia with the left coronary artery; (B) from the left main stem coursing between the aorta and pulmonary artery; and (C) from the left main stem with a retroaortic course.

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Yuan SM - Anomalous origin of coronary artery: taxonomy and clinical implication

Fig. 2 - Left coronary artery arising from the right coronary sinus[12,13]: (A) from a separate ostia with the right coronary artery; (B) sharing a same ostia with the right coronary artery coursing between the aorta and pulmonary artery; (C) sharing a same ostia with the right coronary artery with a retroaortic course; (D) coursing via the right ventricular outflow tract; and (E) with an anterior course of the left anterior descending coronary artery and a retroaortic course of the left circumflex artery.

Fig. 3 - Coronary artery arising from the noncoronary sinus: (A) left coronary artery arising from the noncoronary sinus; and (B) both left and right coronary arteries arising from the noncoronary sinus.

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evidenced by severe pulmonary and hepatic congestion was the probable cause of death. However, when associated with a lesion that may enhance the oxygen content or right heart pressure, a longer survival can be expected. Anomalous origin of coronary artery can sometimes be associated with acquired heart disease including coronary artery disease or heart valve disorders. Acute myocardial infarction has been reported in a patient with anomalous origin of coronary artery with diffuse coronary stenotic lesions[18]. Kalyani et al.[34] discovered well-formed atherosclerotic plaques in both the aorta and coronary artery by autopsy in a young male with anomalous origin of RCA as a branch of the LCx. Anomalous origin of RCA as a branch of LAD was reported in a 54-year-old male patient presenting with acute myocardial infarction in the LAD and RCA territories[35]. Concurrent severe stenosis, occlusion and ectasia of coronary artery may present[36]. A 48-year-old man presented with acute myocardial infarction. On aortography, the LAD, LCx and RCA were seen to arise separately from the right coronary sinus and there was a diffuse stenotic lesion in the distal LCx. He was successfully treated with coronary stenting[18]. Coronary artery disease of the RCA in the normal location with two consecutive 95% stenosis in the proximal section was once reported in a patient with anomalous origin of LM from the innominate artery[37]. Modi et al.[38] reported a 62-year-old male patient with RCA originating from the LAD and LCx and severe mitral regurgitation. The patient underwent surgery for reimplantation of the anomalous RCA to an anterior aortic sinus and mitral valve repair by ring annuloplasty with no complications.

In an anomaly as such, the blood supply to the first portion of the septum is usually provided by the descending septal branches originating from the right sinus of Valsalva or from the proximal RCA[41]. Anomalous origin of LCx from the aorta is generally viewed as a benign coronary arterial anomaly[42]. However, two patients had myocardial infarction in the distribution of the aberrant vessel[42]. The atherosclerotic predilection is evident only in anomalous coronary artery arising from the right side and pursuing a retroaortic course, and the anomalous artery is likely to be responsible for myocardial infarction in patients 60 years or older[43]. Sudden death (28/49, 57%) and exercise-related death (18/28, 64%) are most common with anomalous origin of LM from the right coronary sinus. Anomalous origin of RCA from the left coronary sinus is also frequently associated with exercise-related sudden death (6/13, 46%). The high risk anatomies responsible for the sudden death are coronary artery segment coursing between the pulmonary artery and aorta[44], acute angle take-off of the left coronary artery[45] and ostial abnormalities including ostial valve-like ridge[46], slit-like orifice[47] and flutebeak-shaped ostium[48]. The anomalous origin of coronary artery may have various degree of left-to-right shunting, which may lead to steal phenomenon worsening myocardial hypoxia and predispose cardiac sudden death[17]. Other predisposing risk factors leading to sudden death are intramural course, interarterial course, vessel spasm and intussusception of the anomalous artery[3]. A 3-6 folds higher sudden cardiac death rate was noted in military and athletes with increased physical activities with anomalous origin of coronary artery than in general population with the lesion[49].

PREDISPOSING RISK FACTORS

DIAGNOSIS

Approximately 5% of the patients with acute myocardial infarction do not have atherosclerotic coronary artery disease but have other causes for their luminal narrowing. The nonatherosclerotic narrowing coronary arteries focus on congenital coronary artery anomalies, coronary fistula and high take-off position of coronary ostia[39]. The risk of ischemia is probably exacerbated by the associated anatomical factors, A) flap closure of the slit-like deformation of the coronary ostium; B) acute (non-orthogonal) angle of take-off and kinking of the coronary artery as it exits from the aorta; and C) hypoplasia and/or stenosis of the intramural segment, particularly at the level of the valvar commissure. In addition, cumulative episodes of myocardial ischemia may lead to patchy myocardial necrosis and fibrosis responsible for ventricular arrhythmias[40]. The blood supply to the first portion of the ventricular septum is provided by 1 or 2 descending septal branches from the anomalous LM when it courses between the aorta and pulmonary trunk. When the anomalous LM courses posteriorly to the aorta, it does not provide any septal branches.

The diagnosis of anomalous origin of coronary artery from other arteries can be challenging. Most of the coronary anomalies are asymptomatic and benign but may cause myocardial ischemia and sudden death[50]. Anomalous origin of coronary artery is often associated with a pathophysiologic state of inadequate tissue perfusion and subsequent hypoxia[51]. Transthoracic echocardiography may offer indirect diagnostic signs like abnormal biphasic flows in the left ventricular outflow tract (LVOT), i.e., systolic flow from the LVOT and diastolic flow toward the LVOT. The origin of the RCA in the LVOT may be visualized by computed tomographic angiography and by transthoracic echocardiography[52]. Combined coronary angiography and computed tomographic angiography are reliable for the diagnosis of origin of RCA from the left ventricle[53]. Anomalous origin of left coronary artery from the pulmonary artery is a rare congenital anomaly and one of the causes of myocardial ischemia. Due to atypical signs and symptoms in childhood, it can be misdiagnosed

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as dilated cardiomyopathy[54]. The definitive diagnosis can be reached by multislice computed tomography and coronary angiography[55]. Conventional angiography and magnetic resonance imaging depict the origin and proximal courses of these arteries[56]. Kim et al.[57] reported during the coronary angiography the LCA could not be catheterized and was thus unable to be demonstrated on right coronary angiography or root aortography in a patient who was eventually diagnosed with anomalous origin of LCA from the innominate artery.

tion, impinged coronary segment unroofing and coronary stent deployment are advocated instead.

Authors’ roles & responsibilities SMY

Management Policies The management of anomalous origin of coronary artery remains debating. Surgical treatment is a definitive therapy that is recommended even for asymptomatic patients. Only a few patients were treated medically with no follow-up available. Simple ligation of the coronary system is less traumatic and is the simplest alternative, but the risk of a single ostium coronary system still persists. Some authors suggested a simple coronary artery bypass grafting. However, others objected due to the potential hazards of coronary steal phenomenon and poor patency of internal mammary arterial bypasses, and modified maneuvers such as coronary ostial reimplantation, impinged coronary segment unroofing and coronary stent deployment were advocated[58]. It was therefore concluded that internal mammary arterial bypass is not an appropriate approach for this lesion[59]. In some cases, reimplantation was tried initially but could not be performed due to the fragility of the anomalous coronary artery. As a result, the patients required ligation of the anomalous coronary artery. Heart valve repair or replacement is recommended at the time of coronary surgery for those who are associated with an acquired heart valve disorder. Although successful reimplantation of the anomalous coronary artery to the aorta, persistent symptoms and myocardial ischemia may still be present in some patients. Due to the debates of outcomes and limited information of long-term follow-up, large series of patients for the evaluations of their ventricular function and the patency of the reimplanted vessel are necessary.

Main Author

REFERENCES 1. Yamanaka O, Hobbs RE. Coronary artery anomalies in 126,595 patients undergoing coronary angiography. Cathet Cardiovasc Diagn. 1990;21(1):28-40. 2. Radswiki. Congenital coronary artery anomalies [citado em 1 de dezembro de 2014]. Disponível em: http://radiopaedia.org/ articles/congenital-coronary-artery-anomalies 3. Angelini P. Normal and anomalous coronary arteries: definitions and classification. Am Heart J. 1989;117(2):418-34. 4. Aydin M, Ozeren A, Peksoy I, Cabuk M, Bilge M, Dursun A, et al. Myocardial ischemia caused by a coronary anomaly: left circumflex coronary artery arising from right sinus of valsalva. Tex Heart Inst J. 2004;31(3):273-5. 5. Dogan SM, Gursurer M, Aydin M, Gocer H, Cabuk M, Dursun A. Myocardial ischemia caused by a coronary anomaly left anterior descending coronary artery arising from right sinus of Valsalva. Int J Cardiol. 2006;112(3):e57-9. 6. Cheitlin MD, De Castro CM, McAllister HA. Sudden death as a complication of anomalous left coronary origin from the anterior sinus of Valsalva: a not-so-minor congenital anomaly. Circulation. 1974;50(4):780-7. 7. Greet B, Quinones A, Srichai M, Bangalore S, Roswell RO. Anomalous right coronary artery and sudden cardiac death. Circ Arrhythm Electrophysiol. 2012;5(6):e111-2.

CONCLUSION

8. Kimbiris D, Iskandrian AS, Segal BL, Bemis CE. Anomalous aortic origin of coronary arteries. Circulation. 1978;58(4):606-15.

Sudden cardiac death in anomalous origin of coronary artery is associated with the anatomical features including abnormal coursing, acute angle take-off and ostial abnormalities. Atherosclerosis is prone to be in the right-sided ectopic and retroaortic coursing coronary artery. Surgical treatment is a definitive therapy. Simple coronary artery bypass grafting is not recommended due to the potential hazards of coronary steal phenomenon and poor patency of the internal mammary arterial grafts, and modified maneuvers such as coronary ostial reimplanta-

9. Golubickas D, Motiejūnaitė J, Jankauskas A, Slapikas R, Basevičius A. Incidentally diagnosed malignant coronary artery anomaly: a clinical case. Medicina (Kaunas). 2013;49(10):462-5. 10. Ortale JR, Meciano Filho J, Paccola AM, Leal JG, Scaranari CA. Anatomia dos ramos lateral, diagonal e ântero-superior no ventrículo esquerdo do coração humano. Rev Bras Cir Cardiovasc. 2005;20(2):149-58.

627

Rev Bras Cir Cardiovasc | Braz J Cardiovasc Surg

Yuan SM - Anomalous origin of coronary artery: taxonomy and clinical implication

Rev Bras Cir Cardiovasc 2014;29(4):622-9

11. Pursnani A, Jacobs JE, Saremi F, Levisman J, Makaryus AN, Capuñay C, et al. Coronary CTA assessment of coronary anomalies. J Cardiovasc Comput Tomogr. 2012;6(1):48-59.

of the right coronary artery from the descending thoracic aorta: angiographic diagnosis and unique coronary artery anatomy at autopsy. Cathet Cardiovasc Diagn. 1987;13(5):321-4.

12. Palomo AR, Schrager BR, Chahine RA. Anomalous separate origin of the septal perforator coronary artery from the left sinus of Valsalva. Cathet Cardiovasc Diagn. 1984;10(4):385-8.

25. Mahajan D, Agnihotri G, Brar R. Anomalous origin of right coronary artery: an anatomico-clinical perspective of 2 cases. Acta Inform Med. 2012;20(1):56-7.

13. Li JM, Zhu L. Advances of research of anomalous origin of coronary artery. Chin J Clin. 2013;7(3):1205-8.

26. McMahon CJ, DiBardino DJ, Undar A, Fraser CD Jr. Anomalous origin of left coronary artery from the right pulmonary artery in association with type III aortopulmonary window and interrupted aortic arch. Ann Thorac Surg. 2002;74(3):919-21.

14. Yüksel S, Meriç M, Soylu K, Gülel O, Zengin H, Demircan S, et al. The coronary angiographic analysis of 16573 patients for coronary artery origination and course anomalies [Cited 2014 Dec 1]. Available at: http://spo.escardio.org/eslides/view. aspx?eevtid=48&fp=P4221

27. Charrot F, Tarmiz A, Glock Y, Léobon B. Diagnosis and surgical treatment of an aneurysm on a cervical aortic arch associated with an anomalous origin of the left main coronary artery. Interact Cardiovasc Thorac Surg. 2010;10(2):346-7.

15. Barriales-Villa R, Morís C, Sanmartín JC, Fernández E, Pajín F, Ruiz Nodar JM. Anomalous coronary arteries originating in the contralateral sinus of Valsalva: registry of thirteen Spanish hospitals (RACES). Rev Esp Cardiol. 2006;59(6):620-3.

28. Robicsek F. Origin of the left anterior descending coronary artery from the left mammary artery. Am Heart J. 1984;108(5):1377-8. 29. Liu F, Huang G, Zhang J. Anomalous origin of a coronary artery from the right branchiocephalic trunk associated with complex congenital heart disease. Pediatr Cardiol. 2010;31(1):163-5.

16. Click RL, Holmes DR Jr, Vlietstra RE, Kosinski AS, Kronmal RA. Anomalous coronary arteries: location, degree of atherosclerosis and effect on survival: a report from the Coronary Artery Surgery Study. J Am Coll Cardiol. 1989;13(3):531-7.

30. Hoganson G, McPherson E, Piper P, Gilbert EF. Single coronary artery arising anomalously from the pulmonary trunk. Arch Pathol Lab Med. 1983;107(4):199-201.

17. Byard RW. Vascular condition. In: Byard RW, ed. Sudden death in the young. 3rd ed. Cambridge: University Press; 2010. p.273-343.

31. Bharati S, Szarnicki RJ, Popper R, Fryer A, Lev M. Origin of both coronary arteries from the pulmonary trunk associated with hypoplasia of the aortic tract complex: a new entity. J Am Coll Cardiol. 1984;3(2 Pt 1):437-41.

18. Cho HO, Cho KH, Jeong YS, Ahn SG, Choi SJ, Yoo JY, et al. Anomalous origin of the left coronary artery from the right sinus of Valsalva, which presented as acute myocardial infarction. Korean Circ J. 2006;36(12):817-9.

32. Lloyd TR, Marvin WJ Jr, Lee J. Total anomalous origin of the coronary arteries from the pulmonary artery in an infant with aorticopulmonary septal defect. Pediatr Cardiol. 1987;8(2):153-4.

19. Chaitman BR, Bourassa MG, Lespérance J, Dominguez JL, Saltiel J. Aberrant course of the left anterior descending coronary artery associated with anomalous left circumflex origin from the pulmonary artery. Circulation. 1975;52(5):955-8.

33. Davis JS, Lie JT. Anomalous origin of a single coronary artery from the innominate artery. Angiology. 1977;28(11):775-8.

20. Liberthson RR, Zaman L, Weyman A, Kiger R, Dinsmore RE, Leinbach RC, et al. Aberrant origin of the left coronary artery from the proximal right coronary artery: diagnostic features and pre- and postoperative course. Clin Cardiol. 1982;5(6):377-81.

34. K a l y a n i R , T h e j M J , P r a b h a k a r K , K i r a n J . R i g h t coronary artery originating from left circumflex artery: an unusual coronary anomaly at autopsy. J Clin Biomed Sci. 2011;1(2):77-80.

21. Santucci PA, Bredikis AJ, Kavinsky CJ, Klein LW. Congenital origin of the left main coronary artery from the innominate artery in a 37-year-old man with syncope and right ventricular dysplasia. Catheter Cardiovasc Interv. 2001;52(3):378-81.

35. Sreenivas Kumar ML, Rajasekhar D, Vanajakshamma V, Shashanka C. Anomalous right coronary artery arising from left anterior descending artery. J Clin Sci Res. 2012;3:144-7.

22. Duran NE, Duran I, Aykan AC. Congenital anomalous origin of the left main coronary artery from the innominate artery in a 73-year-old woman. Can J Cardiol. 2008;24(12):e108.

36. Li CB, Bi YW, Sun WY, Li RJ, Li GS, You BA, et al. Images in cardiology. Aberrant origin of circumflex coronary artery from left subclavian artery. J Am Coll Cardiol. 2011;57(1):e1.

23. Kim YM, Choi RK, Lee CK. Anomalous origin of left coronary artery from innominate artery. J Am Coll Cardiol. 2009;54(2):176.

37. Santucci PA, Bredikis AJ, Kavinsky CJ, Klein LW. Congenital origin of the left main coronary artery from the innominate artery in a 37-year-old man with syncope and right ventricular dysplasia. Catheter Cardiovasc Interv. 2001;52(3):378-81.

24. Cheatham JP, Ruyle NA, McManus BM, Gammel GE. Origin

628

Rev Bras Cir Cardiovasc | Braz J Cardiovasc Surg

Yuan SM - Anomalous origin of coronary artery: taxonomy and clinical implication

Rev Bras Cir Cardiovasc 2014;29(4):622-9

38. Modi H, Ariyachaipanich A, Dia M. Anomalous origin of right coronary artery from pulmonary artery and severe mitral regurgitation due to myxomatous mitral valve disease: a case report and literature review. J Invasive Cardiol. 2010;22(4):E49-55.

49. Corrado D, Basso C, Pavei A, Michieli P, Schiavon M, Thiene G. Trends in sudden cardiovascular death in young competitive athletes after implementation of a preparticipation screening program. JAMA. 2006;296(13):1593-601. 50. Bayat P, Masoud F, Ghanbari A, Gannnnji-Harsini S. Anomalous origin of the circumflex branch from the right coronary artery. Int J Morphol. 2013;31(1):169-71.

39. Waller BF, Fry ET, Hermiller JB, Peters T, Slack JD. Nonatherosclerotic causes of coronary artery narrowing: Part I. Clin Cardiol. 1996;19(6):509-12.

51. Lin Y, Cornish S, Lim R. A case of an anomalous origin of left main coronary artery from right sinus of Valsalva leading to sudden death. UWOMJ. 2012;81(1):41-2.

40. Gaudin R, Raisky O, Vouhé PR. Anomalous aortic origin of coronary arteries: 'anatomical' surgical repair. Multimed Man Cardiothorac Surg. 2014;2014:mmt022. 41. Kimbiris D. Anomalous origin of the left main coronary artery from the right sinus of Valsalva. Am J Cardiol. 1985;55(6):765-9.

52. Ciarka A, Lens V, Beissel J, Wagner DR. Right coronary artery originating in the left ventricle. J Am Coll Cardiol. 2010;56(16):1351.

42. Silverman KJ, Bulkley BH, Hutchins GM. Anomalous left circumflex coronary artery: "normal" variant of uncertain clinical and pathologic significance. Am J Cardiol. 1978;41(7):1311-4.

53. Kang N, Tan SY, Ding ZP, Chua YL. Abnormal origin of right coronary artery from left ventricle with bicuspid aortic stenosis. Ann Thorac Surg. 2013;96(2):e43-5.

43. Samarendra P, Kumari S, Hafeez M, Vasavada BC, Sacchi TJ. Anomalous circumflex coronary artery: benign or predisposed to selective atherosclerosis. Angiology. 2001;52(8):521-6.

54. Bakiler AR, Eliaçık K, Köse S, Atay Y. Anomalous origin of the left coronary artery from the pulmonary artery presenting as dilated cardiomyopathy. Turk Kardiyol Dern Ars. 2013;41(5):448-50.

44. Taylor AJ, Rogan KM, Virmani R. Sudden cardiac death associated with isolated congenital coronary artery anomalies. J Am Coll Cardiol. 1992;20(3):640-7.

55. Gribaa R, Slim M, Ben Salem H, Neffati E, Boughzela E. Anomalous origin of the left coronary artery from the pulmonary artery presenting as dilated cardiomyopathy: a case report. J Med Case Rep. 2014;8:170.

45. Catanzaro JN, Makaryus AN, Catanese C. Sudden cardiac death associated with an extremely rare coronary anomaly of the left and right coronary arteries arising exclusively from the posterior (noncoronary) sinus of Valsalva. Clin Cardiol. 2005;28(11):542-4.

56. Patel KB, Gupta H, Nath H, Aqel RA, Zoghbi GJ, Soto B, et al. Origin of all three major coronary arteries from the right sinus of Valsalva: clinical, angiographic, and magnetic resonance imaging findings and incidence in a select referral population. Catheter Cardiovasc Interv. 2007;69(5):711-8.

46. Virmani R, Chun PK, Goldstein RE, Robinowitz M, McAllister HA. Acute takeoffs of the coronary arteries along the aortic wall and congenital coronary ostial valve-like ridges: association with sudden death. J Am Coll Cardiol. 1984;3(3):766-71.

57. Kim YM, Choi RK, Lee CK. Anomalous origin of left coronary artery from innominate artery. J Am Coll Cardiol. 2009;54(2):176.

47. Kron IL. The best approach to repair anomalous origin of the right coronary artery. Eur J Cardiothorac Surg. 2012;41(2):290.

58. Elhmidi Y, Nöbauer C, Hörer J, Schreiber C, Lange R. Surgical unroofing of an anomalous right coronary artery arising from the posterior left sinus of Valsalva. World J Pediatr Congenit Heart Surg. 2013;4(4):433-5.

48. Maresi EA, Argo AM, Spanò GP, Novo GM, Cabibi DR, Procaccianti PG. Images in cardiovascular medicine. Anomalous origin and course of the right coronary artery. Circulation. 2006;114(22):e609-11.

59. Kron IL. The best approach to repair anomalous origin of the right coronary artery. Eur J Cardiothorac Surg. 2012;41(2):290.

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Yuan SM - S100REVIEW and S100ß:ARTICLE biomarkers of cerebral damage in cardiac surgery with or without the use of cardiopulmonary bypass

S100 and S100ß: biomarkers of cerebral damage in cardiac surgery with or without the use of cardiopulmonary bypass S100 e S100ß: biomarcadores de dano cerebral em cirurgia cardíaca com ou sem o uso de circulação extracorpórea

Shi-Min Yuan1, MMed, PhD DOI 10.5935/1678-9741.20140084

RBCCV 44205-1598

Abstract Objective: The present study is to describe the clinical impact of S100 and S100ß for the evaluation of cerebral damage in cardiac surgery with or without the use of cardiopulmonary bypass (CPB). Methods: Quantitative results of S100 and S100ß reported in the literature of the year range 1990-2014 were collected, screened and analyzed. Results: Cerebrospinal fluid and serum S100 levels showed a same trend reaching a peak at the end of CPB. The cerebrospinal fluid/serum S100 ratio decreased during CPB, reached a nadir at 6 h after CPB and then increased and kept high untill 24 h after CPB. Serum S100 at the end of CPB was much higher in infant than in adults, and in on-pump than in off-pump coronary artery bypass patients. ΔS100 increased with age and CPB time but lack of statistical significances. Patients receiving an aorta replacement had a much higher ΔS100 than those receiving a congenital heart defect repair. Serum S100ß reached a peak at the end of CPB, whereas cerebrospinal fluid S100 continued to increase and reached a peak at 6 h after CPB. The cerebrospinal fluid/serum S100ß ratio decreased during CPB, increased at the end of CPB, peaked 1 h after CPB, and then decreased abruptly. The increase of serum S100ß at the end of CPB was associated with type of operation, younger age, lower core temperature and cerebral damages. ΔS100ß displayed a decreasing trend with age, type of operation, shortening of CPB duration, increasing core temperature, lessening severity of cerebral damage and the application of intervenes. Linear correlation analysis revealed that serum S100ß concentration at the end of CPB correlated closely with CPB duration.

Conclusion: S100 and S100ß in cerebrospinal fluid can be more accurate than in the serum for the evaluations of cerebral damage in cardiac surgery. However, cerebrospinal fluid biopsies are limited. But serum S100ß and ΔS100ß seem to be more sensitive than serum S100 and ΔS100. The cerebral damage in cardiac surgery might be associated with younger age, lower core temperature and longer CPB duration during the operation. Effective intervenes with modified CPB circuit filters or oxygenators and supplemented anesthetic agents or priming components may alleviate the cerebral damage.

The First Hospital of Putian, Teaching Hospital, Fujian Medical University

Correspondence address: Shi-Min Yuan Longdejing Street, 389 - Chengxian District, Putian, Fujian Province, People’s Republic of China E-mail:shi_min_yuan@yahoo.com Article received on April 25th, 2014 Article accepted on June 22th, 2014

Descriptors: Cardiopulmonary Bypass. Cerebrospinal Fluid. Circulatory Arrest, Deep Hypothermia Induced. S100 Proteins. Resumo Objetivo: O presente estudo descreve o impacto clínico de S100 e S100ß para a avaliação do dano cerebral em cirurgia cardíaca com ou sem o uso de circulação extracorpórea (CEC). Métodos: Os resultados quantitativos de S100 e S100ß relatados na literatura entre os anos 1990 e 2014 foram recolhidos, rastreados e analisados. Resultados: Os níveis do fluido cerebroespinal e níveis séricos S100 mostram uma mesma tendência, atingindo um pico no final da CEC. A relação de fluido cerebroespinal e soro S100 diminuiu durante a CEC, chegando a um nadir 6 h após a CEC, aumentando e mantendo alta até 24 h após a CEC. O soro S100 no final da CEC foi muito maior no infantil do que em adultos, e em pacientes de revascularização miocárdica com

Work carried out at First Hospital of Putian, Teaching Hospital, Fujian Medical University, Putian, Fujian Province, People’s Republic of China. No financial support.

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idade, menor temperatura do coração e danos cerebrais. ΔS100ß exibiu tendência decrescente com a idade, tipo de operação, encurtamento da duração da CEC, o aumento da temperatura do coração, diminuindo a gravidade do dano cerebral e da aplicação de intervenções. Análise de correlação linear revelou que a concentração sérica de S100ß no final da CEC está intimamente relacionada com a duração do procedimento. Conclusão: Níveis de S100 e S100ß no líquido cefalorraquidiano podem ser mais precisos do que no soro para as avaliações de dano cerebral em cirurgia cardíaca. No entanto, as biópsias liquóricas são limitadas. Mas S100ß e ΔS100ß do soro parecem ser mais sensíveis do que o soro S100 e ΔS100. O dano cerebral em cirurgia cardíaca pode estar associado com a idade mais jovem, menor temperatura do núcleo e maior duração da CEC durante a operação. Intervenções eficazes com filtros modificados no circuito de CEC ou oxigenadores complementadas com agentes anestésicos ou componentes iniciadores podem aliviar o dano cerebral.

Abbreviations, acronyms & symbols CABG CPB CSF OPCAB POD

Coronary artery bypass grafting Cardiopulmonary bypass Cerebrospinal fluid Off-pump coronary artery bypass Postoperative day

CEC do que em pacientes sem CEC. ΔS100 aumentou com a idade e tempo de CEC, mas sem significância estatística. Os pacientes que receberam substituição da aorta tinham um ΔS100 muito maior do que aqueles que fizeram reparo dos defeitos cardíacos congênitos. Soro S100ß atingiu um pico no final da CEC, enquanto líquido cefalorraquidiano S100 continuou a aumentar e atingir um pico 6 h após a CEC. A proporção entre soro S100ß e líquido cefalorraquidiano diminuiu durante a CEC, aumentando no final da CEC, com pico 1 h após a CEC, em seguida, diminuiu abruptamente. O aumento de soro S100ß no final da CEC foi associado com o tipo de operação, menor

Descritores: Ponte Cardiopulmonar. Líquido Cefalorraquidiano. Parada Circulatória Induzida por Hipotermia Profunda. Proteínas S100.

INTRODUCTION

Blood-brain barrier dysfunction secondary to cerebral damages may expedite the release of these cerebral specific proteins from the astroglial or Schwann cells into cerebrospinal fluid (CSF) and blood circulation[4,5]. During cardiac operations, neurological disorders may occur and are believed to be the results of thromboembolism (embolism is not always caused by a thrombus, but can be air embolism, calcium embolism or detachment of atheromatous plaques from the aorta at the time of cannulation or decannulation) and systemic inflammatory reactions[6]. S100 and S100ß have been reliable serum markers of cerebral damage due to breakdown of the blood-brain barrier caused by head trauma, anoxia, ischemia, neoplasm and cardiac surgery[7]. Both hypo- and hypertension may also cause cerebral damage by impairment of cerebral autoregulation[8]. S100 and S100ß proteins leak from structurally damaged neurocytes into CSF and then across the blood-brain barrier. S100ß protein increases 50~100-fold after cardiac operation with cardiopulmonary bypass (CPB), supporting links between CPB, microembolization and cerebral damage[9] and indicating postoperative adverse neurologic outcomes[10]. However, debates remain with regard to the accuracy of the results during and early after the operation as well as the correlations between the expression of the proteins and the surgical conditions. In order to highlight these aspects, a comprehensive review is made based on quantitative data reported in the literature.

S100 protein family members with a molecular mass of 10-12 kDa are acidic proteins characterized by their calcium-dependent biological effects[1]. It is expressed in different tissues, but shows brain tissue specific, and therefore implicated in cerebral damage. They may form into homodimers, heterodimers and even oligomers based on a calcium-dependent conformational change[1]. Most S100 proteins have a low binding affinity for calcium, which increase dramatically to control a cellular activity in the presence of a target[2]. This protein family represents the largest subgroup within the superfamily of EF-hand Ca2+ binding proteins. Ca2+ binding to the first EF-hand (helix I, loop and helix II) is weaker than binding to the second EF-hand (helices III and IV)[3]. S100ß, a 10.7 kDa protein, is a member of S100 protein family. It is highly expressed in astrocytes and is one of the most abundant soluble proteins in human brain, constituting 0.5% of them. S100ß functions as both an intracellular Ca2+ receptor and an extracellular neuropeptide by way of the receptor for advanced glycation end-products, a main transducer of extracellular functions of this protein[1]. S100ß is displayed as a homodimer with a high binding affinity under all biological circumstances while the monomers are absent[1].

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METHODS

and linear correlations were assessed between independent and dependent variables. P<0.05 was considered statistically significant.

Literature Retrieval A literature search for English articles published from 1990 to 2012 concerning S100 and S100ß in relation to cardiovascular surgery in PubMed, Highwire Press and Google search engine yielded totally 69 publications[8-73]. The search terms included “S100”, “S100ß(B)”, “cardiopulmonary bypass” “off-pump coronary artery bypass”, “circulatory arrest, induced”, “profound hypothermic circulatory arrest”, “cardiac surgery”, “congenital heart defects”, “heart valves”, “coronary artery bypass grafting”, “aortic surgery” and “cardiac surgical procedures”. Quantitative data of S100 and S100ß measured in the unit of µg/L were screened, collected and analyzed. Articles or patient cohorts reported in articles with no quantitative data were excluded from this study.

RESULTS Patient information The 69 articles reported the quantitative results of S100(ß) of 4439 patients: 20 (29.0%) on serum S100[8-30], 45 (65.2%) on serum S100ß[31-73], 2 (2.9%) on serum and CSF S100[74,75], 1 (1.4%) on serum and CSF S100ß[76] and 1 (1.4%) on CSF S100ß[77]. The 2 articles reporting CSF S100 comprised 22 patients with 15 males and 6 females with a median age of 63 years. All received a thoracic aorta operation with postoperative spinal cord injury in 2 (9.1%) patients; and the 2 articles reporting CSF S100ß included 49 patients with 28 males and 23 females (gender of 8 patients was unidentified) with a median age of 64 years. All received a thoracic aorta operation with postoperative spinal cord injury in 10 (20.4%) patients. The demographics of the patients with serum S100(ß) detections were listed in Table 1.

Sampling Sampling times were before operation (baseline) (T0), during CPB (T1), at the end of CPB (T2), 1, 4, 6, 12, 24, 48, and 72 h after operation (T3-9). Indicators The indicators of evaluating the cerebral damage included dynamics of CSF and serum S100(ß), ΔS100(ß), i.e., the difference between peak and baseline S100(ß)[14] and CSF/ serum S100(ß) ratios.

Assays Immunoradiometry, immunoluminometry and immunofluorometry were the 3 main assays used for the detection of the biomarkers (Table 1).

Subgroups 1) Age: There were 4 age subgroups: neonate, infant, child and adult; 2) Operation: The operations were classified as aorta, valve, congenital heart defect, coronary artery bypass grafting (CABG) and off-pump coronary artery bypass (OPCAB); 3) CPB duration: There were 2 subgroups based on whether the CPB duration was >100 minutes; 4) Core temperature: There were 3 subgroups according to core temperatures during CPB: deep hypothermia, mild and moderate hypothermia and normothermia; 5) Cerebral damage: The patients with cerebral damage were divided into either functional (confusion, agitation, disorientation, or epileptic seizures) or organic (stroke, stupor, or coma) subgroups. Those without cerebral damage were defined as control; and, 6) Intervene: Patients with utilizations of modified CPB circuit and oxygenators[25,26,60,72], cell saving reservoir[33], anesthetic agents and priming components (propofol[53], isoflurane[64], hydroxyethyl[46] and starch[42]) during the operation aiming at lessening the cerebral damage were defined as the Intervene Subgroup. Those without intervenes were defined as control.

Biomarkers CSF and serum S100 levels showed a same trend during the early observational stage before T5, increased at T1, reaching a peak at T2 and then gradually decreased. After T5, CSF S100-serum S100 separation phenomenon was seen. The CSF/ serum S100 ratio decreased from T1, reached a nadir at T5 and then increased and kept high till T7 (Figure 1).

Statistical analysis Data were expressed as mean±standard deviation. Comparisons between groups were conducted with unpaired t-test,

Fig. 1 - Dynamics of CSF S100, serum S100 and CSF/serum S100 ratio. CSF=Cerebrospinal fluid

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Table 1. Demographics of patients with serum S100 and serum S100ß detections. Variable Report number Patient number Gender (male/female) Age

S100 20 1741 1217/352 51.8±26.1 (range, 3 days-77 years; median, 68 years)

S100ß 45 2682 829/451 47.7±27.8 (range, 8.6 days81 years; median, 62 years)

98.1±36.5 (range, 48-217; median, 90.3) Crossclamp time (min) 63.8± 31.5 (range, 29-175; median, 56) Hypothemic circulatory arrest time (min) 43.1±24.2 (range, 26-60.2; median, 43.1) Core temperature (℃) 30.1±4.4 (range, 18-34.5; median, 31.5)

116.5±55.0 (range, 49-308; median, 103.2) 64.9±29.9 (range, 28-164; median, 60) 31.6±9.1 (range, 20-45; median, 32) 29.46±6.5 (range, 10.5-37; median, 32)

Operative conditions CPB (min)

Age group, n (%) Neonate Infant Child Adult

25 (1.4) 17 (1.0) 21 (1.2) 1678 (96.4)

173 (6.5) 69 (2.6) 18 (0.7) 2422 (90.3)

Core temperature, n (%) Deep hypothermia Mild-moderate hypothermia Normothermia

44 (2.6) 1576 (93.9) 58 (3.5)

278 (10.4) 2250 (83.9) 154 (5.7)

Operation, n (%) Aorta replacement Valve replacement Congenital heart defect repair CABG OPCAB Not given

31 (1.8) 14 (0.8) 64 (3.7) 1335 (76.7) 229 (13.2) 68 (3.9)

192 (7.1)* 156 (5.8) 270 (10.0) 1941 (72.2) 129 (4.8)

Cerebral damage, n (%) Organic cerebral damage Stroke Transient ischemic attack Spinal cord injury Subclinical cerebral damage Functional cerebral damage Intervene (with modified filter, oxygenator or anesthetic agents)

23 (1.3) 23 (100) 3 (13.0) 1 (4.3) 3 (13.0) 16 (69.6) 0 (0) 259 (14.9)

121 (4.5) 65 (53.7) 58 (89.2) 0 (0) 2 (3.1) 5 (7.7) 56 (46.3) 330 (12.3)

Assay, n (%) Immunoradiometry 891 (33.2) 985 (56.6) Enzyme linked immunosorbent assay 235 (8.8) 163 (9.4) Immunoluminometry 668 (24.9) 161 (9.2) Immunofluorometry 500 (18.6) Luminometry 128 (4.8) Immunoassay 72 (2.7) Electrochemoluminescence immunoassay 21 (0.8) Not given 167 (6.2) 432 (24.8) *at least 5 patients had concurrent procedures. CABG=coronary artery bypass grafting; CPB=Cardiopulmonary bypass; OPCAB=off-pump coronary artery bypass

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Fig. 2 - An inter-subgroup comparison of serum S100 at T2 and T7. CABG=Coronary artery bypass; CHD=Congenital heart defect; DHCA=Deep hypothermia circulatory arrest; FCD=Functional cerebral damage; MMH=Mild-moderate hypothermia; NM=Normothermia; OCD=Organic cerebral damage; OPCAB=Offpump coronary artery bypass; T2=At the end of cardiopulmonary bypass; T7=24 hours after cardiopulmonary bypass

Fig. 3 - An inter-subgroup comparison of serum ΔS100 at T2 and T7. CABG=Coronary artery bypass; CHD=Congenital heart defect; DHCA= Deep hypothermia circulatory arrest; FCD=Functional cerebral damage; MMH=Mild-moderate hypothermia; NM=Normothermia; OCD=Organic cerebral damage; OPCAB=Offpump coronary artery bypass

Serum S100 at T3 was much higher in infant than in adults (2.4±1.2 µg/L vs. 0.9±1.0 µg/L, P=0.034) and in CABG patients than in OPCAB patients (2.8±2.4 µg/L vs. 0.8±0.6 µg/L, P=0.010). Patients with a CPB time >100 min had a higher serum S100 level at T2 than those with a CPB time <100 min, but lack of a statistical significance, however, significant reductions were noted at T7 in comparison to T2 in both subgroups (CPB >100 min: 3.3±2.3 µg/L vs. 0.6±0.6 µg/L, P=0.005; CPB duration <100 min: 2.1±2.3 µg/L vs. 0.3±0.2 µg/L, P=0.016). Deep hypothermia circulatory arrest was associated with much higher serum S100 at T2 than mild-moderate hypothermia and normothermia patients, and mild-moderate hypothermia with higher serum S100 than normothermia. No difference in the serum S100 levels was noted between patients with cerebral damage in particular stroke and those without. Intervenes with CPB filter, oxygenator, or anesthetic agents led to significant decreased serum S100 at T2 and T7 (Figure 2). ΔS100 could be calculated in 25 series of patients in whom at least a baseline and a peak value were reported. The peaks were at T1 in 5 (20%), T2 in 16 (64%) and T3 in 4 (16%) patient

cohorts, respectively (χ2=7.5, P=0.023). ΔS100 increased with age and CPB time but lack of statistical significances. Patients receiving an aorta replacement had a much higher ΔS100 than those receiving a congenital heart defect repair, in line with the increasing trend with age. No difference was found in ΔS100 between deep hypothermia and mild-moderate hypothermia patients or between the organic cerebral damage and control patients. Intervenes led to a decrease of ΔS100 in comparison to non-intervene patients but no significance was found (Figure 3). CSF and serum S100ß levels started to increase at T1, but separation was noted since T2. Serum S100ß reached a peak at T2, whereas CSF S100ß continued to increase and reach a peak at T5. Both recovered to normal at T7. The CSF/serum S100ß ratio decreased at T1, increased at T2, peaked at T3 and then decreased abruptly (Figure 4). Serum S100ß at T2 showed a successive decrease in the operation subgroups in a sequence of aorta, valve, congenital, CABG and OPCAB operations. Patients with organic and functional cerebral damages showed higher S100ß levels at T2 than those without. Infant showed a little bit higher serum S100ß than adults, patients with CPB duration >100 min

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showed higher serum S100ß than those with CPB duration <100 min, deep hypothermia and mild-moderate hypothermia were associated with higher serum S100ß than normothermia, and intervene led to reduced serum S100ß other than non-intervene, but no significances were found (Figure 5).

Fig. 4 - Dynamics of CSF S100ß, serum S100ß and CSF/serum S100ß ratio. CSF=Cerebrospinal fluid Fig. 6 - An inter-subgroup comparison of serum ΔS100ß at T2 and T7. CABG=Coronary artery bypass; CHD=Congenital heart defect; DHCA=Deep hypothermia circulatory arrest; FCD=Functional cerebral damage; MMH=Mild-moderate hypothermia; NM=Normothermia; OCD=Organic cerebral damage; OPCAB=Offpump coronary artery bypass

Fig. 7 - Linear correlation analysis between serum S100 concentration at T2 and cardiopulmonary bypass, crossclamp time and core temperature.

Fig. 5 - An inter-subgroup comparison of serum S100ß at T2 and T7. CABG=Coronary artery bypass; CHD=Congenital heart defect; DHCA=Deep hypothermia circulatory arrest; FCD=Functional cerebral damage; MMH=Mild-moderate hypothermia; NM=Normothermia; OCD=Organic cerebral damage; OPCAB=Offpump coronary artery bypass; T2=At the end of cardiopulmonary bypass; T7=24 hours after cardiopulmonary bypass

ΔS100ß could be calculated in 51 series of patients. The peak values were present at T1 in 5 (9.8%), T2 in 36 (70.6%) and T3 in 10 (19.6%) patient cohorts, respectively (χ2=48.9, P=0.000):

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ΔS100ß displayed a decreasing trend with age, surgical operations (from aorta, valve, congenital, CABG to OPCAB), shortening of CPB duration, increasing core temperature, lessening severity of cerebral damage and the application of intervenes. Significant differences were present in age, surgical operation, core temperature and cerebral damage subgroups (Figure 6). Linear correlation analysis did not reveal any significant correlation between serum S100 concentration at T2 and CPB, crossclamp time and core temperature (Figure 7). However, serum S100ß concentration at T2 correlated closely with CPB duration (Figure 8).

The release of S100ß from adipose tissue with surgery would be more extensive with more complex and longer operations. These patients are at a higher risk of cerebral damage and this confounding effect may explain the correlations between early rise in S100ß and neurological injury. In stroke, an elevation of S100ß correlates with the amount of the damaged brain tissue. Poor neurological outcome is related to S100ß levels. The peak levels of S100ß occur on day 3 following the stroke[83]. S100ß as an indicator of cerebral injury, however, is uncertain how autotransfusion of S100ß from extracerebral sources is like. There is good evidence to show that autologous blood recorery through cardiotomy suckers results in significantly higher serum levels of S100ß[84]. Some authors have determined that shed mediastinal blood collected during surgery by cardiotomy suction contained high levels of S100ß as well as chest tube blood used for autotransfusion after surgery. Therefore, early elevated serum S100ß levels immediately after cardiac operations may have been contaminated by extracerebral sources of S100ß[33]. Comparing the patients with retrograde cerebral perfusion with non-retrograde cerebral perfusion groups, the mean serum S100ß levels are 0.09 and 0.09 mg/L, preoperatively, 3.8 and 4.2 mg/L 30 minutes after CPB, and 0.82 and 0.53 mg/L on POD 1[52]. S100ß levels early after CPB are increased because of release from adipose tissue or thymus into cardiotomy suction. This masks neurally released S100ß. High levels of S100ß have been found in pleural drainage following thoracotomy, and in surgical wounds, mediastinal fat and skeletal muscle[85]. Neonates and infants had reduced S100ß at 24 h after surgery than before surgery. However, this finding may reflect dilution of the protein in serum from postoperative blood, colloid and crystalloid infusions in small babies[36]. The increases of S100ß in the early phase after cardiac surgery are not due to release of S100ß from brain alone but also from tissue outside the brain[86]. Therefore, S100ß protein is a nonspecific marker of tissue injury as glial fibrillary acidic protein might serve as a specific marker of cerebral damage after cardiac surgery[86]. Cerebral damage following cardiac surgery cannot be differentiated from cardiac or other tissue damage by measurement of S100ß levels until the initial elevation of S100ß due to non-brain tissue damage has declined, which does not occur for at least 24 h after surgery[86]. It has been reported that S100 correlated significantly with age, body surface area, nasopharyngeal temperature and PaCO2 in infants and children[14]. However, it could be the result of dilution of the protein in serum from infusions of fluid and blood products[36]. Both older age and prolonged CPB duration correlated with levels of S100 protein at T0, but the correlation was weak for both variables[19]. Serum S100 values at the end of CPB and POD 1 significantly correlated with CPB time[11]. The duration of absent cerebral perfusion time (duration of circulatory arrest minus retrograde cerebral perfusion) correlated well with S100 on POD 1[11].

Fig. 8 - Linear correlation analysis showed serum S100ß concentration at T2 correlated closely with cardiopulmonary bypass duration.

DISCUSSION Detectable concentrations of S100 were found 20 min after CPB[13]. On the operative day, CSF S100 levels increased with time for patients with spinal cord injury; whereas there was a non-specific increase of serum S100. In patients with spinal cord injury, CSF S100 was increased at 6 h after crossclamp removal[74]. Serum S100 reached the peak values at the end of CPB and decreased on postoperative day (POD) 1[11]. At the end of the operation, S100 decreased rapidly and progressively but remained significantly higher on POD 2[12]. S100 peaked 20 min after the start of CPB, being significantly higher than the baseline value[12] . Serum S100ß increased during CPB, peaked at the late phase of CPB[78], recovered to normal at 36 h after the operation[8] untill POD 6[32]. S100ß significantly increased 24 h after total circulatory arrest[79]. In studies showing a correlation between neurological deficit and elevated S100ß protein level after ischemic cerebral infarction, the blood level of S100ß protein consistently peaked on day 2 to 3 after the clinical event[80-82].

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In adults, S100 on POD 1 correlated with duration of circulatory arrest[11], and peak S100ß correlated with CPB time[32]. S100ß on POD 1 correlated with duration of absent cerebral perfusion time[11]. S100ß concentration at 5 h and 24 h correlated significantly with the duration of total circulatory arrest[35] and S100ß at 5 h negatively correlated with core temperature[35]. S100ß also correlated with the total embolus count at the arterial line[78], CPB time[57] and intubation duration[30]. In roller pump group, peak S100ß correlated with crossclamp time[34]. Ashraf et al.[34] reported S100ß did not correlate with duration of CPB time. Johnsson[87] reported no relationship between serum S100ß at 24 h after surgery and CPB duration, crossclamp time, or use of hypothermic circulatory arrest, and it did not correlate with 30-day surgical mortality. Pulsatile flow lowers cerebral destruction than laminar flow[50]. S100 was nonsignificantly higher in cold than in warm CPB patients[63].The S100ß rise was significantly less in patients administered sevoflurane in comparison to total intravenous anesthesia[64]. CPB with covalent bonded heparin attached to the CPB circuit in combination with a reduced systemic heparin dose seemed to reduce the operative stroke[88]. The S100 level was elevated at the end of operation but returned toward normal at 5 h. A secondary increase in S100 protein level coincided with the clinical presentation of stroke on the day after the operation[27]. The peak values of S100ß were higher in died patients than in the survived[10]. Taggart et al.[27] reported 21 of 43 patients had an elevated serum S100ß value 4 h after the operation and none of the patients had neurological symptoms, and S100ß reached a peak value on PODs 2-3 in stroke patients[10]. Patient with cerebral infarction showed slightly increased S100ß during operation but decreased to normal concentration on POD 1. In patients with temporary left-side hemiplegia lasting 24 h after the operation, S100ß protein increased and reached its peak after aortic crossclamp removal, but decreased to a normal concentration on POD 1 while still hemiplegic. In patients with a conscious disturbance lasting 24 h, S100ß level was indistinguishable from the patients without neurological complications. There was a weak but significant correlation between peak concentrations of S100ß protein and aortic crossclamp time in the CPB group[47]. The patient with the highest S100 values at the end of CPB and on POD 1 presented postoperative stroke[11]. Permanent cerebral damage was associated with much higher serum S100 than transient[89]. However, the appropriate time to measure S100ß after CABG for prognostic value has not been established but is probably 5 h after surgery[24]. In the hypothermic circulatory arrest group, CPB time correlated with peak S100. Peak S100ß levels occurred in both the CABG and hypothermia circulatory arrest groups at the end of CPB. After 24 h, the S100ß levels returned to normal in the CABG patients but were still elevated in all cases in the hypothermia circulatory arrest group. CPB patients may face major treatment-related cognitive performance decline. Persistently high levels of neuron-specific enolase might be

a useful biomarker to identify patients with cognitive performance deficits at discharge; while no significant correlation between S100ß levels and impaired cognitive function have been found[90]. High-dose propofol triggered short-term neuroprotection and long-term neurodegeneration in neuronal cultures from rat embryos[91]. A high dose of propofol (with plasma concentrations of 3.2 mg/mL) may offer advantages over a low dose of propofol (with plasma concentrations of 1.8 mg/mL) for brain protection during CPB[53]. Previous studies have shown that OPCAB is better than conventional CABG by decreasing the release of S100ß protein. Consequently, the pattern of S100ß release at different stages of OPCAB procedures has become a valuable indicator of the early detection of neuronal clinical and subclinical injury[36,92]. The present study revealed that CSF and serum S100 and S100ß began to increase during CPB, peaked at the end of CPB for each indicator. However, CSF 100 showed a second peak at T7, and CSF S100ß continued to be high until T4 and then gradually reduced. The results may indicate that S100 and S100ß concentrations in the CSF are more sensitive than in the serum for indicating cerebral damage during cardiac surgery. CSF/serum S100 and S100ß ratios may reflect the cerebral damage more accurately with a CSF-serum separation showing a sustained S100(ß) release from the damaged brain tissues. The separation trends displayed from T5 for S100, and between T2 and T7 for S100ß, respectively. This may hint that physiological and hemodynamic properties of the two proteins can be different and therefore showing distinct metabolic features after cardiac surgery. Intra-subgroup comparisons of serum S100(ß) at T3 and T7 showed younger age, OPCAB, normothermia and positive intervene and even shorter CPB duration may reduce significantly the release of S100 and S100ß. Serum ΔS100 and ΔS100ß may also illustrate the severity of the cerebral damage during the operation. ΔS100, the difference between peak S100 and baseline S100, was reported to be 0.88 (0.48-3.23) in overall, 0.29 (0.18-0.44) in neonates and 1.1 (0.48-3.23) in infants[14]. In line with the results of serum S100(ß) at T3 and T7, the study showed discrepancy of ΔS100 between aorta and congenital heart defect operations as well as extensive discrepancies of ΔS100ß within age, operation, core temperature and cerebral damage subgroups. Despite the possible influence by the blood recovery transfusion, the indicators may still reflect the cerebral damage during cardiac surgery. In general, the release of S100 and S100ß may correlate with age, operative method, CPB duration, core temperature and the application of intervenes during the operation. CSF S100(ß) may be more reliable than serum S100(ß), however, too aggressive drainage of CSF carries the risk of cerebral hernia and subdural hemorrhage[93]. CONCLUSION S100 and S100ß in CSF can be more accurate than in the serum for the evaluations of cerebral damage in cardiac surgery.

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However, CSF biopsies are limited. But serum S100ß and ΔS100ß seems to be more sensitive than serum S100 and ΔS100. The cerebral damage in cardiac surgery might be associated with younger age, lower core temperature and longer CPB duration during the operation. Effective intervenes with modified CPB circuit filters or oxygenators and supplemented anesthetic agents or priming components may alleviate the cerebral damage.

Börner A, Lindner A, et al. Predictive value of S-100beta and neuron-specific enolase serum levels for adverse neurologic outcome after cardiac surgery. J Thorac Cardiovasc Surg. 2000;119(1):138-47. 11. Astudillo R, Van der Linden J, Radegran K, Hansson LO, Aberg B. Elevated serum levels of S-100 after deep hypothermic arrest correlate with duration of circulatory arrest. Eur J Cardiothorac Surg. 1996;10(12):1107-12. 12. Basile AM, Fusi C, Conti AA, Paniccia R, Trefoloni G, Pracucci G, et al. S-100 protein and neuron-specific enolase as markers of subclinical cerebral damage after cardiac surgery: preliminary observation of a 6-month follow-up study. Eur Neurol 2001;45(3):151-9.

Authors’ roles & responsibilities SMY

Main Author

13. Blomquist S, Johnsson P, Lührs C, Malmkvist G, Solem JO, Alling C, et al. The appearance of S-100 protein in serum during and immediately after cardiopulmonary bypass surgery: a possible marker for cerebral injury. J Cardiothorac Vasc Anesth. 1997;11(6):699-703.

REFERENCES 1. Carvalho SB. Structural and conformational effects of metal binding to the S100B cytokine. Tese orientada por Doutor Cláudio M. Gomes (ITQB-UNL) e Doutora Ana A. Coutinho (FC-UL) Mestrado em Bioquímica. 2011. Available from: http://repositorio. ul.pt/bitstream/10451/8475/1/ulfc103891_tm_Sofia_Carvalho.pdf

14. Camci E, Tuğrul M, Korkut K, Tireli E. Blood S-100 protein concentration in children undergoing cardiac surgery. J Cardiothorac Vasc Anesth. 2001;15(1):29-34. 15. Chaney MA, Nikolov MP, Blakeman BP, Bakhos M. Attempting to maintain normoglycemia during cardiopulmonary bypass with insulin may initiate postoperative hypoglycemia. Anesth Analg. 1999;89(5):1091-5.

2. Liriano MA. Structure, dynamics and function of S100B and S100A5 complexes. ProQuest® Dissertations & Theses. Available from: http://gradworks.umi.com/35/26/3526916.html

16. Dar MI, Gillott T, Ciulli F, Cooper GJ. Single aortic cross-clamp technique reduces S-100 release after coronary artery surgery. Ann Thorac Surg. 2001;71(3):794-6.

3. Rezvanpour A, Shaw GS. Unique S100 target protein interactions. Gen Physiol Biophys. 2009;28 Spec No Focus:F39-46. 4. Raabe A, Seifert V. Fatal secondary increase in serum S-100B protein after severe head injury. Report of three cases. J Neurosurg. 1999;91(5):875-7.

17. Gao F, Harris DN, Sapsed-Byrne S. Time course of neuronespecific enolase and S-100 protein release during and after coronary artery bypass grafting. Br J Anaesth. 1999;82(2):266-7.

5. Cata JP, Abdelmalak B, Farag E. Neurological biomarkers in the perioperative period. Br J Anaesth. 2011;107(6):844-58.

18. Jensen E, Sandström K, Andréasson S, Nilsson K, Berggren H, Larsson LE. Increased levels of S-100 protein after cardiac surgery with cardiopulmonary bypass and general surgery in children. Paediatr Anaesth. 2000;10(3):297-302.

6. Murkin JM. Etiology and incidence of brain dysfunction after cardiac surgery. J Cardiothorac Vasc Anesth. 1999;13(4 Suppl 1):12-7. 7. Einav S, Shoshan Y, Ovadia H, Matot I, Hersch M, Itshayek E. Early postoperative serum S100 beta levels predict ongoing brain damage after meningioma surgery: a prospective observational study. Crit Care. 2006;10(5):R141.

19. Johnsson P, Lundqvist C, Lindgren A, Ferencz I, Alling C, Ståhl E. Cerebral complications after cardiac surgery assessed by S-100 and NSE levels in blood. J Cardiothorac Vasc Anesth. 1995;9(6):694-9. 20. Jönsson H, Johnsson P, Alling C, Westaby S, Blomquist S. Significance of serum S100 release after coronary artery bypass grafting. Ann Thorac Surg. 1998;65(6):1639-44.

8. Schmidt M, Scheunert T, Steinbach G, Schirmer U, Marx T, Freitag N, et al. Hypertension as a risk factor for cerebral injury during cardiopulmonary bypass. Protein S100B and transcranial Doppler findings. Anaesthesia. 2001;56(8):733-8.

21. Lloyd CT, Ascione R, Underwood MJ, Gardner F, Black A, Angelini GD. Serum S-100 protein release and neuropsychologic outcome during coronary revascularization on the beating heart: a prospective randomized study. J Thorac Cardiovasc Surg. 2000;119(1):148-54.

9. Bonacchi M, Prifti E, Maiani M, Bartolozzi F, Di Eusanio M, Leacche M. Does off-pump coronary revascularization reduce the release of the cerebral markers, S-100beta and NSE? Heart Lung Circ. 2006;15(5):314-9.

22. Matheis G, Abdel-Rahman U, Braun S, Wimmer-Greinecker G, Esmaili A, Seitz U, et al. Uncontrolled reoxygenation by initiating

10. Georgiadis D, Berger A, Kowatschev E, Lautenschläger C,

638

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Yuan SM - S100 and S100ß: biomarkers of cerebral damage in cardiac surgery with or without the use of cardiopulmonary bypass

Rev Bras Cir Cardiovasc 2014;29(4):630-41

cardiopulmonary bypass is associated with higher protein S100 in cyanotic versus acyanotic patients. Thorac Cardiovasc Surg. 2000;48(5):263-8.

34. Ashraf S, Bhattacharya K, Zacharias S, Kaul P, Kay PH, Watterson KG. Serum S100beta release after coronary artery bypass grafting: roller versus centrifugal pump. Ann Thorac Surg. 1998;66(6):1958-62.

23. Mazzei V, Nasso G, Salamone G, Castorino F, Tommasini A, Anselmi A. Prospective randomized comparison of coronary bypass grafting with minimal extracorporeal circulation system (MECC) versus offpump coronary surgery. Circulation. 2007;116(16):1761-7.

35. Bhattacharya K, Westaby S, Pillai R, Standing SJ, Johnsson P, Taggart DP. Serum S100B and hypothermic circulatory arrest in adults. Ann Thorac Surg. 1999;68(4):1225-9.

24. Rasmussen LS, Christiansen M, Hansen PB, Moller JT. Do blood levels of neuron-specific enolase and S-100 protein reflect cognitive dysfunction after coronary artery bypass? Acta Anaesthesiol Scand. 1999;43(5):495-500.

36. Bokesch PM, Appachi E, Cavaglia M, Mossad E, Mee RB. A glialderived protein, S100B, in neonates and infants with congenital heart disease: evidence for preexisting neurologic injury. Anesth Analg. 2002;95(4):889-92.

25. Svenmarker S, Sandström E, Karlsson T, Häggmark S, Jansson E, Appelblad M, et al. Neurological and general outcome in low-risk coronary artery bypass patients using heparin coated circuits. Eur J Cardiothorac Surg. 2001;19(1):47-53.

37. Carrier M, Denault A, Lavoie J, Perrault LP. Randomized controlled trial of pericardial blood processing with a cell-saving device on neurologic markers in elderly patients undergoing coronary artery bypass graft surgery. Ann Thorac Surg. 2006;82(1):51-5.

26. Svenmarker S, Sandström E, Karlsson T, Jansson E, Häggmark S, Lindholm R, et al. Clinical effects of the heparin coated surface in cardiopulmonary bypass. Eur J Cardiothorac Surg. 1997;11(5):957-64.

38. de Baar M, Diephuis JC, Moons KG, Holtkamp J, Hijman R, Kalkman CJ. The effect of zero-balanced ultrafiltration during cardiopulmonary bypass on S100b release and cognitive function. Perfusion. 2003;18(1):9-14.

27. Taggart DP, Mazel JW, Bhattacharya K, Meston N, Standing SJ, Kay JD, et al. Comparison of serum S-100beta levels during CABG and intracardiac operations. Ann Thorac Surg. 1997;63(2):492-6.

39. Diegeler A, Hirsch R, Schneider F, Schilling LO, Falk V, Rauch T, et al. Neuromonitoring and neurocognitive outcome in off-pump versus conventional coronary bypass operation. Ann Thorac Surg. 2000;69(4):1162-6.

28. Wandschneider W, Thalmann M, Trampitsch E, Ziervogel G, Kobinia G. Off-pump coronary bypass operations significantly reduce S100 release: an indicator for less cerebral damage? Ann Thorac Surg. 2000;70(5):1577-9.

40. Dworschak M, Franz M, Czerny M, Gorlitzer M, Blaschek M, Grubhofer G, et al. Release of neuron-specific enolase and S100 after implantation of cardioverters/defibrillators. Crit Care Med. 2003;31(8):2085-9.

29. Westaby S, Johnsson P, Parry AJ, Blomqvist S, Solem JO, Alling C, et al. Serum S100 protein: a potential marker for cerebral events during cardiopulmonary bypass. Ann Thorac Surg. 1996;61(1):88-92.

41. Flom-Halvorsen HI, Ovrum E, Brosstad F, Tangen G, Ringdal M, Oystese R. Effects of two differently heparin-coated extracorporeal circuits on markers for brain and myocardial dysfunction. Perfusion. 2002;17(5):339-45.

30. Westaby S, Saatvedt K, White S, Katsumata T, van Oeveren W, Bhatnagar NK, et al. Is there a relationship between serum S-100beta protein and neuropsychologic dysfunction after cardiopulmonary bypass? J Thorac Cardiovasc Surg. 2000;119(1):132-7.

42. Gazzolo D, Masetti P, Kornacka M, Abella R, Bruschettini P, Michetti F. Phentolamine administration increases blood S100B protein levels in pediatric open-heart surgery patients. Acta Paediatr. 2003;92(12):1427-32.

31. Abdul-Khaliq H, Schubert S, Fischer T, Böttcher W, Harke C, Alexi-Meskishvili V, et al. The effect of continuous treatment with sodium nitroprusside on the serum kinetics of the brain marker protein S-100beta in neonates undergoing corrective cardiac surgery by means of hypothermic cardiopulmonary bypass. Clin Chem Lab Med. 2000;38(11):1173-5.

43. Grocott HP, Croughwell ND, Amory DW, White WD, Kirchner JL, Newman MF. Cerebral emboli and serum S100 beta during cardiac operations. Ann Thorac Surg. 1998;65(6):1645-9.

32. Anderson RE, Hansson LO, Vaage J. Release of S100B during coronary artery bypass grafting is reduced by off-pump surgery. Ann Thorac Surg. 1999;67(6):1721-5.

44. Groom RC, Quinn RD, Lennon P, Welch J, Kramer RS, Ross CS, et al; Northern New England Cardiovascular Disease Study Group. Microemboli from cardiopulmonary bypass are associated with a serum marker of brain injury. J Extra Corpor Technol. 2010;42(1):40-4.

33. Anderson RE, Hansson LO, Liska J, Settergren G, Vaage J. The effect of cardiotomy suction on the brain injury marker S100beta after cardiopulmonary bypass. Ann Thorac Surg. 2000;69(3):847-50.

45. Ilcol YO, Basagan-Mogol E, Cengiz M, Ulus IH. Elevation of serum cerebral injury markers correlates with serum choline decline after coronary artery bypass grafting surgery. Clin Chem Lab Med. 2006;44(4):471-8.

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Rev Bras Cir Cardiovasc | Braz J Cardiovasc Surg

Yuan SM - S100 and S100ß: biomarkers of cerebral damage in cardiac surgery with or without the use of cardiopulmonary bypass

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46. Iriz E, Kolbakir F, Akar H, Adam B, Keceligil HT. Comparison of hydroxyethyl starch and ringer lactate as a prime solution regarding S-100 beta protein levels and informative cognitive tests in cerebral injury. Ann Thorac Surg. 2005;79(2):666-71.

serum marker evidence of brain injury during transcatheter aortic valve implantation. Acta Anaesthesiol Scand. 2012;56(2):240-7. 59. Robson MJ, Alston RP, Deary IJ, Andrews PJ, Souter MJ. Jugular bulb oxyhemoglobin desaturation, S100 beta, and neurologic and cognitive outcomes after coronary artery surgery. Anesth Analg. 2001;93(4):839-45.

47. Ishida K, Gohara T, Kawata R, Ohtake K, Morimoto Y, Sakabe T. Are serum S100 beta proteins and neuron-specific enolase predictors of cerebral damage in cardiovascular surgery? J Cardiothorac Vasc Anesth. 2003;17(1):4-9.

60. Schoenburg M, Kraus B, Muehling A, Taborski U, Hofmann H, Erhardt G, et al. The dynamic air bubble trap reduces cerebral microembolism during cardiopulmonary bypass. J Thorac Cardiovasc Surg. 2003;126(5):1455-60.

48. Jönsson H, Johnsson P, Birch-Iensen M, Alling C, Westaby S, Blomquist S. S100B as a predictor of size and outcome of stroke after cardiac surgery. Ann Thorac Surg. 2001;71(5):1433-7.

61. Scholz M, Wimmer-Greinecker G, Kleine P, Dzemali O, Martens S, Moritz A, et al. Cariporide (HOE642) limits S-100B release during cardiac surgery. J Cardiovasc Pharmacol. 2003;41(3):468-73.

49. Krnjak L, Trunk P, Gersak B, Osredkar J. Correlation of serum S100B concentration with hospital stay in patients undergoing CABG. Acta Clin Croat. 2008;47(4):221-6. 50. Kusch B, Vogt S, Sirat AS, Helwig-Rohlig A, Kasseckert S, Moosdorf R. Serum S-100 beta protein release in coronary artery bypass grafting: laminar versus pulsatile flow. Thorac Cardiovasc Surg. 2001;49(3):179-83.

62. Shaaban-Ali M, Harmer M, Vaughan RS, Dunne JA, Latto IP, Haaverstad R, et al. Changes in serum S100 beta protein and Mini-Mental State Examination after cold (28 degrees C) and warm (34 degrees C) cardiopulmonary bypass using different blood gas strategies (alpha-stat and pH-stat). Acta Anaesthesiol Scand. 2002;46(1):10-6.

51. Lardner D, Davidson A, McKenzie I, Cochrane A. Delayed rises in serum S100B levels and adverse neurological outcome in infants and children undergoing cardiopulmonary bypass. Paediatr Anaesth. 2004;14(6):495-500.

63. Shaaban Ali M, Harmer M, Elliott M, Thomas AL, Kirkham F. A pilot study of evaluation of cerebral function by S100 beta protein and near-infrared spectroscopy during cold and warm cardiopulmonary bypass in infants and children undergoing open-heart surgery. Anaesthesia. 2004;59(1):20-6.

52. LeMaire SA, Bhama JK, Schmittling ZC, Oberwalder PJ, Köksoy C, Raskin SA, et al. S100 beta correlates with neurologic complications after aortic operation using circulatory arrest. Ann Thorac Surg. 2001;71(6):1913-8.

64. Singh SP, Kapoor PM, Chowdhury U, Kiran U. Comparison of S100ß levels, and their correlation with hemodynamic indices in patients undergoing coronary artery bypass grafting with three different anesthetic techniques. Ann Card Anaesth. 2011;14(3):197-202.

53. Ma G, Chen J, Meng X, Deng L, Gao Y, Meng J. High-dose propofol reduces S-100ß protein and neuron-specific enolase levels in patients undergoing cardiac surgery. J Cardiothorac Vasc Anesth. 2013;27(3):510-5.

65. Janigro D. A response to ‘Cerebral and extracerebral release of protein S100B in cardiac surgical patients’, Snyder-Ramos SA, Gruhlke T, Bauer H, Bauer M, Luntz AP, Motsch J, Martin E, Vahl CF, Missler U, Wiesmann M and Bottiger BW, Anaesthesia. 2004;59:344-9. Anaesthesia. 2004;59(11):1149-50.

54. Snyder-Ramos SA, Gruhlke T, Bauer H, Bauer M, Luntz AP, Motsch J, et al. Cerebral and extracerebral release of protein S100B in cardiac surgical patients. Anaesthesia. 2004;59(4):344-9. 55. Motallebzadeh R, Kanagasabay R, Bland M, Kaski JC, Jahangiri M. S100 protein and its relation to cerebral microemboli in on-pump and off-pump coronary artery bypass surgery. Eur J Cardiothorac Surg. 2004;25(3):409-14.

66. Svenmarker S, Engström KG, Karlsson T, Jansson E, Lindholm R, Aberg T. Influence of pericardial suction blood retransfusion on memory function and release of protein S100B. Perfusion. 2004;19(6):337-43. 67. Svenmarker S, Sandström E, Karlsson T, Aberg T. Is there an association between release of protein S100B during cardiopulmonary bypass and memory disturbances? Scand Cardiovasc J. 2002;36(2):117-22.

56. Rasmussen LS, Christiansen M, Eliasen K, Sander-Jensen K, Moller JT. Biochemical markers for brain damage after cardiac surgery: time profile and correlation with cognitive dysfunction. Acta Anaesthesiol Scand. 2002;46(5):547-51.

68. Takayama H, Soltow LO, Chandler WL, Vocelka CR, Aldea GS. Does the type of surgery effect systemic response following cardiopulmonary bypass? J Card Surg. 2007;22(4):307-13.

57. Rasmussen LS, Sztuk F, Christiansen M, Elliott MJ. Normothermic versus hypothermic cardiopulmonary bypass during repair of congenital heart disease. J Cardiothorac Vasc Anesth. 2001;15(5):563-6.

69. Tamura A, Imamaki M, Shimura H, Niitsuma Y, Miyazaki M. Release of serum S-100 beta protein and neuron-specific enolase after off-pump coronary artery bypass grafting with and without

58. Reinsfelt B, Westerlind A, Ioanes D, Zetterberg H, Fredén-Lindqvist J, Ricksten SE. Transcranial Doppler microembolic signals and

640

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Yuan SM - S100 and S100ß: biomarkers of cerebral damage in cardiac surgery with or without the use of cardiopulmonary bypass

Rev Bras Cir Cardiovasc 2014;29(4):630-41

intracranial and cervical artery stenosis. Ann Thorac Cardiovasc Surg. 2011;17(1):33-8.

neuron-specific enolase concentrations in blood as indicators of infarction volume and prognosis in acute ischemic stroke. Stroke. 1997;28(10):1956-60.

70. Ueno T, Iguro Y, Yamamoto H, Sakata R, Kakihana Y, Nakamura K. Serial measurement of serum S-100B protein as a marker of cerebral damage after cardiac surgery. Ann Thorac Surg. 2003;75(6):1892-7.

82. Ali MS, Harmer M, Vaughan R. Serum S100 protein as a marker of cerebral damage during cardiac surgery. Br J Anaesth. 2000;85(2):287-98.

71. Wimmer-Greinecker G, Matheis G, Brieden M, Dietrich M, Oremek G, Westphal K, et al. Neuropsychological changes after cardiopulmonary bypass for coronary artery bypass grafting. Thorac Cardiovasc Surg. 1998;46(4):207-12.

83. Motallebzadeh R, Jahangiri M. The effect of the dynamic air bubble trap on cerebral microemboli and S100 beta. J Thorac Cardiovasc Surg. 2004;128(1):154. 84. Vaage J, Anderson R. Biochemical markers of neurologic injury in cardiac surgery: the rise and fall of S100 beta. J Thorac Cardiovasc Surg. 2001;122(5):853-5.

72. Wimmer-Greinecker G, Matheis G, Martens S, Oremek G, AbdelRahman U, Moritz A. Synthetic protein treated versus heparin coated cardiopulmonary bypass surfaces: similar clinical results and minor biochemical differences. Eur J Cardiothorac Surg. 1999;16(2):211-7.

85. Missler U, Orlowski N, Nötzold A, Dibbelt L, Steinmeier E, Wiesmann M. Early elevation of S-100B protein in blood after cardiac surgery is not a predictor of ischemic cerebral injury. Clin Chim Acta. 2002;321(1-2):29-33.

73. Wong CH, Rooney SJ, Bonser RS. S-100 beta release in hypothermic circulatory arrest and coronary artery surgery. Ann Thorac Surg. 1999;67(6):1911-4.

86. Babin-Ebell J, Misoph M, Müllges W, Neukam K, Reese J, Elert O. Intraoperative embolus formation during cardiopulmonary bypass affects the release of S100B. Thorac Cardiovasc Surg. 1999;47(3):166-9.

74. Khaladj N, Teebken OE, Hagl C, Wilhelmi MH, Tschan C, Weissenborn K, et al. The role of cerebrospinal fluid S100 and lactate to predict clinically evident spinal cord ischaemia in thoraco-abdominal aortic surgery. Eur J Vasc Endovasc Surg. 2008;36(1):11-9.

87. Johnsson P. S100-B in blood: a marker of brain damage or simply a covariate? Scand Cardiovasc J. 2000;34(6):548-9.

75. van Dongen EP, Ter Beek HT, Boezeman EH, Schepens MA, Langemeijer HJ, Aarts LP. Normal serum concentrations of S-100 protein and changes in cerebrospinal fluid concentrations of S-100 protein during and after thoracoabdominal aortic aneurysm surgery: is S-100 protein a biochemical marker of clinical value in detecting spinal cord ischemia? J Vasc Surg. 1998;27(2):344-6.

88. Svenmarker S, Sandström E, Karlsson T, Jansson E, Häggmark S, Lindholm R, et al. Clinical effects of the heparin coated surface in cardiopulmonary bypass. Eur J Cardiothorac Surg. 1997;11(5):957-64. 89. Oki A, Ohtake H, Okada Y, Kawada T, Takaba T. Simultaneous monitoring of somatosensory evoked potentials and regional cerebral oxygen saturation combined with serial measurement of plasma levels of cerebral specific proteins for the early diagnosis of postoperative brain damage in cardiovascular surgery. J Artif Organs. 2004;7(1):13-8.

76. Kunihara T, Shiiya N, Yasuda K. Changes in S100beta protein levels in cerebrospinal fluid after thoracoabdominal aortic operations. J Thorac Cardiovasc Surg. 2001;122(5):1019-20. 77. Shiiya N, Kunihara T, Miyatake T, Matsuzaki K, Yasuda K. Tau protein in the cerebrospinal fluid is a marker of brain injury after aortic surgery. Ann Thorac Surg. 2004;77(6):2034-8.

90. Baranyi A, Rothenhäusler HB. The impact of S100b and persistent high levels of neuron-specific enolase on cognitive performance in elderly patients after cardiopulmonary bypass. Brain Int. 2013;27(4):417-24.

78. Ashraf S, Bhattacharya K, Tian Y, Watterson K. Cytokine and S100B levels in paediatric patients undergoing corrective cardiac surgery with or without total circulatory arrest. Eur J Cardiothorac Surg. 1999;16(1):32-7.

91. Berns M, Seeberg L, Schmidt M, Kerner T. High-dose propofol triggers short-term neuroprotection and long-term neurodegeneration in primary neuronal cultures from rat embryos. J Int Med Res. 2009;37(3):680-8.

79. Büttner T, Weyers S, Postert T, Sprengelmeyer R, Kuhn W. S-100 protein: serum marker of focal brain damage after ischemic territorial MCA infarction. Stroke. 1997;28(10):1961-5.

92. Wang KJ, Wu HH, Fang SY, Yang YR, Tseng AC. Serum S-100 beta protein during coronary artery bypass graft surgery with or without cardiopulmonary bypass. Ann Thorac Surg. 2005;80(4):1371-4.

80. Fassbender K, Schmidt R, Schreiner A, Fatar M, Mühlhauser F, Daffertshofer M, et al. Leakage of brain-originated proteins in peripheral blood: temporal profile and diagnostic value in early ischemic stroke. J Neurol Sci. 1997;148(1):101-5.

93. Weaver KD, Wiseman DB, Farber M, Ewend MG, Marston W, Keagy BA. Complications of lumbar drainage after thoracoabdominal aortic aneurysm repair. J Vasc Surg. 2001;34(4):623-7.

81. Missler U, Wiesmann M, Friedrich C, Kaps M. S-100 protein and

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Ozyuksel BRIEF A, et al. COMMUNICATION - Saccular aneurysm formation of the descending aorta associated with aortic coarctation in an infant

Saccular aneurysm formation of the descending aorta associated with aortic coarctation in an infant Formação de aneurismas saculares da aorta descendente associados com coarctação aórtica em criança

Arda Ozyuksel1, MD; Emir Canturk1, MD; Aygun Dindar2, MD; Atif Akcevin1, MD

DOI 10.5935/1678-9741.20140041

RBCCV 44205-1599

Abstract Aneurysm of the descending aorta associated with CoA is an extremely rare congenital abnormality. In this report, we present a 16 months old female patient in whom cardiac catheterization had been performed which had revealed a segment of coarctation and saccular aneurysm in the descending aorta. The patient was operated and a 3x2 centimeters aneurysm which embraces the coarcted segment in descending aorta was resected. In summary, we present a case of saccular aortic aneurysm distal to aortic coarctation in an infant without any history of intervention or vascular inflammatory disease. Our case report seems to be the youngest patient in literature with this pathology.

Resumo Aneurisma da aorta descendente associada à coarctação aórtica é uma anomalia congênita extremamente rara. Neste relato, apresentamos uma paciente de 16 meses de idade, nos quais o cateterismo cardíaco foi realizado, que havia revelado um segmento de coarctação e aneurisma sacular na aorta descendente. A paciente foi operada e um aneurisma de 3x2 centímetros, englobando o segmento coarctada na aorta descendente foi ressecado. Em resumo, apresentamos um caso de aneurisma sacular distal à coarctação da aorta em uma criança sem histórico de intervenção ou doença inflamatória vascular. Nosso caso parece ser o do paciente mais jovem na literatura com esta afecção.

Descriptors: Aortic Aneurysm, Thoracic. Aortic Coarctation. Infant.

Descritores: Aneurisma da Aorta Torácica. Coarctação Aórtica. Lactente

INTRODUCTION

this report, we present the youngest patient per our literature search with CoA and saccular descending aortic aneurysm. CASE PRESENTATION

Coarctation of the aorta (CoA) is defined as the hemodynamically significant narrowing of the descending thoracic aorta, usually just distal to the left subclavian artery where the ligamentum arteriosum originates[1]. CoA accounts for 6.5% of all congenital heart defects[2]. CoA is usually classified into three categories: I.Isolated CoA, II. CoA with ventricular septal defect (VSD) and III. CoA with complex cardiac anomalies[3]. Aneurysm of the descending aorta associated with CoA is an extremely rare congenital abnormality. In

A 16 months old female patient was admitted to our clinic with diagnosis of aortic coarctation and descending aortic aneurysm. She presented with poor feeding and failure to thrive (body weight: 8 kg). The prenatal and postnatal history was unremarkable; any umbilical vascular catheterization was not performed. Physical examination revealed

Istanbul Medipol University (Medipol UNV) and Department of Cardiovascular Surgery, Istanbul, Turkey. 2 Istanbul University and Department of Pediatric Cardiology, Istanbul, Turkey.

Correspondence address: Arda Ozyuksel Medipol University, Department of Cardiovascular Surgery TEM Otoyolu, Göztepe cikisi, No:1 Bagcilar, Istanbul, Turkey 34212 E-mail: ozyukselarda@yahoo.com

This study was carried out at Istanbul Medipol University (Medipol UNV) and Department of Cardiovascular Surgery, Istanbul, Turkey.

Article received on August 26th, 2013 Article accepted on February 23th, 2014

No financial support.

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segments of both coarctation and aneurysm formation. Basophilic degeneration and vacuole formation were remarkable (Figure 2). The postoperative period was uneventful and the patient was discharged at the sixth postoperative day without any complication. At the sixth postoperative month, a second intervention was performed because of recoarctation. The MR angiography revealed a recoarctation at the descending aorta, in which balloon dilatation was performed with a residual gradient of 25 mmHg (Figure 3). The patient is followed up by echocardiographic evaluations with regular intervals.

Abbreviations, acronyms & symbols CoA VSD

Coarctation of the aorta Ventricular septal defect

80 mmHg systolic pressure difference between upper and lower extremities. Femoral pulses were weak but palpable. There was a systolic murmur (3/6) at the left sternal border which was also heard at the interscapular area. The leukocyte count, C-reactive protein level and erythrocyte sedimentation rate were all within normal limits. The patient had been admitted to another clinic a few months ago and transthoracic echocardiography had demonstrated aortic coarctation with 60mmHg peak systolic gradient. Any intracardiac pathology had not been encountered. Cardiac catheterization had been performed in order to confirm the diagnosis and perform a balloon angioplasty if possible; however the catheterization had revealed a segment of coarctation and saccular aneurysm in the descending aorta (Figure 1). Therefore, the patient was referred to our clinic for surgical repair. The patient was operated under general anesthesia and a left posterolateral thoracotomy was performed at the 4th intercostal space. A 3x2 cm aneurysm which embraces the coarcted segment in descending aorta was encountered (Figure 1). Descending aorta was mobilized, resection and end-to-end anastomosis was performed with 6/0 polyprolene suture. The sutures were continuous at the posterior wall, whereas they were interrupted at the anterior wall of the anastomosis, in order to provide potential for growth. Residual gradient was less than 5 mmHg. The resected specimen was examined by the pathology department. Gross and microscopic cross sectional examination of the coarctation area revealed the

Fig. 2 - Gross cross sectional examination of the area of coarctation and aneurysm formation (left side) (black arrows indicate the area of coarctation and white arrow heads indicate the area of aneurysm formation). Hematoxylin eosin stained section revealing the zone of transition between the area of coarctation and aneurysm (right side) (x40 magnification) (black arrow indicates the area of coarctation and white arrow head indicates the area of aneurysm formation. Basophilic degeneration and vacuole formation were remarkable indicated with white arrow).

Fig. 1 - Coarctation and saccular aneurysm formation in the descending aorta in cardiac catheterization (left side - arrow). Saccular aneurysm embracing the segment of coarctation in the descending aorta, operative view (right side - arrow).

Fig. 3 - MR angiography revealing the recoarctation at the descending aorta (left) which was dilated with percutaneous intervention (right).

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DISCUSSION

Authorsâ&#x20AC;&#x2122; roles & responsibilities

Surgical repair of CoA mostly depends on the accompanying cardiac anomalies in the patient. The main treatment target is providing a non stenotic aortic continuity with efforts to enhance the growth potential of the native vascular tissues, with or without the repositioning of the left subclavian artery[4]. Although rarely seen, aortic wall pathology such as aneurysm formation, aortic dissection and rupture are mainly the presenting symptoms of adult CoA. When pediatric age group is concerned, the saccular aortic aneurysms distal to coarcted segment are very rare and data about these patients are only confined to limited case reports[5]. Our case report seems to be the youngest patient in literature with this pathology. In such cases, recoarctation may be encountered in the follow up which may be managed by percutaneous balloon dilatation as presented in our case. Extensive mobilization of the aorta and its branches with a meticulous surgical technique is mandatory in order to reduce the tension at the anastomosis site. In summary, we present a case of saccular aortic aneurysm distal to aortic coarctation in an infant without any history of intervention or vascular inflammatory disease. We speculate that localized weakness of the aortic wall may be responsible for aneurysm formation, since basophilic degeneration and vacuole formation were remarkable at the transition zone between the coarcted and aneurysmatic segments under microscope.

AO EC AD AA

Included in surgical team, preparation of the manuscript Included in surgical team, preparation of the manuscript Preoperative diagnostic workup of the patient, preparation and final control of the paper Head of surgical team, preparation and final control of the paper

REFERENCES 1. Backer CL, Mavroudis C. Congenital Heart Surgery Nomenclature and Database Project: patent ductus arteriosus, coarctation of the aorta, interrupted aortic arch. Ann Thorac Surg. 2000;69(4 Suppl):S298-307. 2. Flyer DC. Report of the New England Regional Infant Cardiac Program. Pediatrics. 1980;64:432-36. 3. Backer CL, Paape K, Zales VR, Weigel TJ, Mavroudis C. Coarctation of the aorta. Repair with polytetrafluoroethylene patch aortoplasty. Circulation. 1995;92(9 Suppl):II132-6. 4. Croti UA, Braile DM, Marchi CH, Beani L. Aortic coarctation: aortoplasty with interposition of the left subclavian artery (the Teles MendonĂ§a technique). Rev Bras Cir Cardiovasc. 2007;22(2):255-6. 5. Celik T, Iyisoy A, Kursaklioglu H, Unlu M, Kose S, Ozmen N, et al. A large calcified saccular aneurysm in a patient with aortic coarctation. Int J Cardiovasc Imaging. 2006;22(1):93-5.

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Evora PRB, et al. COMMUNICATION - A variant technique for the surgical treatment of left BRIEF ventricular aneurysms

A variant technique for the surgical treatment of left ventricular aneurysms Variante técnica para o tratamento cirúrgico de aneurismas do ventrículo esquerdo

Paulo Roberto Barbosa Evora1, MD, PhD; Paulo Victor Alves Tubino1, MD; Luis Gustavo Gali2, MD; Lafaiete Alves Junior1, MD; Cesar Augusto Ferreira1, MD, PhD; Solange Bassetto1, MD, Antônio Carlos Menardi1, MD, PhD; Alfredo José Rodrigues1, MD, PhD; Walter Vilella de Andrade Vicente1, MD, PhD

DOI 10.5935/1678-9741.20140110

RBCCV 44205-1600

Abstract Objective: To present a surgical variant technique to repair left ventricular aneurysms. Methods: After anesthesia, cardiopulmonary bypass, and myocardial protection with hyperkalemic tepic blood cardioplegia: 1) The left ventricle is opened through the infarct and an endocardial encircling suture is placed at the transitional zone between the scarred and normal tissue; 2) Next, the scar tissue is circumferentially plicated with deep stitches using the same suture thread, taking care to eliminate the entire septal scar; 3) Then, a second encircling suture is placed, completing the occlusion of the aneurysm, and; 4) Finally, the remaining scar tissue is oversewn with an invaginating suture, to ensure hemostasis. Myocardium revascularization is performed after correction of the left ventricle aneurysm. The same surgeon performed all the operations. Results: Regarding the post-surgical outcome 4 patients (40%) had surgery 8 eight years ago, 2 patients (20%) were operated on over 6 years ago, and 1 patient (10%) was operated on

more than 5 years ago. Three patients (30%) were in functional class I, class II in 2 patients (20%) and 2 patients (20%) with severe comorbidities remains in class III of the NYHA. There were three deaths (at four days, 15 days and eight months) in septuagenarians with acute myocardial infarction, diabetes and pulmonary emphysema. Conclusion: The technique is easy to perform, safe and it can be an option for the correction of left ventricle aneurysms.

Department of Surgery and Anatomy, Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (FMRP-USP), Ribeirão Preto, SP, Brazil. 2 Department of Medical Clinic Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (FMRP-USP), Ribeirão Preto, SP, Brazil.

Correspondence address: Paulo Roberto Barbosa Evora Rua Rui Barbosa, 367, apt. 15 - Centro, Ribeirão Preto, SP, Brazil Zip code: 14015-120 E-mail: prbevora@fmrp.usp.br

Descriptors: Left ventricle aneurysm. Left ventricle aneurysmectomy. Ischemic heart disease. Thoracic surgery. Resumo Objetivo: Apresentar uma variante técnica para correção de aneurismas do ventrículo. Métodos: Após anestesia geral, circulação extracorpórea e proteção miocárdica com cardioplegia sanguínea tépida hiperpotassêmica: 1) O ventrículo esquerdo é aberto através da área

This study was carried out at Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (FMRP-USP), Ribeirão Preto, São Paulo, Brazil. Financial support: CNPq, FAEPA, HCFMRP-USP

Article received on June 8th, 2014 Article accepted on September 30th, 2014

No conflict of interest.

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revascularização do miocárdio. Todos os pacientes foram operados pelo mesmo cirurgião. Resultados: Em relação ao tempo de evolução pós-cirúrgica 4 pacientes (40%) superaram o tempo de 8 anos, 2 pacientes (20%) foram operados há mais de 6 anos e 1 paciente (10%) foi operado há mais de 5 anos. Três pacientes estão em classe funcional I (30%), 2 pacientes em classe II (20%) e 2 em classe III (20%) da NYHA. Ocorreram 3 óbitos (30%) em curto prazo (4 dias, 15 dias e 8 meses) em pacientes septuagenários, infarto agudo do miocárdio menos de 30 dias, diabetes e enfisema pulmonar. Conclusão: A técnica é segura, tecnicamente fácil, e pode ser uma opção para a correção de aneurismas do ventrículo esquerdo.

Abbreviations, acronyms & symbols CCS LV NYHA SVR

Canadian Cardiovascular Society Left ventricular New York Heart Association Surgical ventricular reconstruction

de infarto e procede-se a uma cerclagem do endocárdio (polipropileno 2-0) em torno da zona de transição entre a cicatriz e tecido normal; 2) No passo seguinte, o tecido cicatricial é circularmente plicado com pontos grosseiros e profundos, utilizando o mesmo fio de sutura, tomando cuidado para eliminar toda a cicatriz septal; 3) A seguir, uma segunda cerclagem completa a oclusão do aneurisma, e; 4) Finalmente, o tecido cicatricial restante é submetido a uma sutura invaginante para garantir a hemostasia. Terminada a correção do aneurisma, realiza-se a

Descritores: Aneurisma do ventrículo esquerdo. Aneurismectomia do ventrículo esquerdo. Doença isquêmica do coração. Cirurgia torácica.

INTRODUCTION

patients were male (50%), and five were female (50%). The follow-up period was completed in 2014 by means of office visits. Follow-up consisted of obtaining information about the functional class of congestive heart failure (New York Heart Association [NYHA]), angina (Canadian Cardiovascular Society [CCS]), and nonroutine control echocardiograms. All patients were clinically treated and free of angina and presented severe congestive heart failure (Class IV/NYHA). The surgeries were performed under cardiopulmonary bypass, aortic cross-clamping and anterograde hyperkalemic tepid blood cardioplegia.

According Donst in a paper published in Heart Failure Review Surgical, "Reconstruction of physiological shape and size of a postischemically remodeled left ventricle has been advocated to improve ventricular function and improve patient long-term outcome. What initially started as linear aneurysm resection surgery developed over the years into the endoventricular repair techniques that have also been applied in patients with postischemically dilated ventricles and mainly anterior akinesia"[1]. In 1985, while describing the circular endoventricular suture, in the transition zone between the scared tissue and the viable myocardium, Jatene [2] introduced the concept of “anatomical reconstruction of the left ventricle”. Dor et al.[3] described the use of the endoventricular suture to rebuild a failing ventricle with an endoventricular patch after extended endocardectomy for ventricular tachycardia. The concept of excluding all the diseased tissue from the cavity, especially the septum, is the basis of the good results[4]. Afterwards, in 2001, Caldeira & McCarthy described a technique for a “no-patch” repair of left anterior descending aneurysms[5]. The aim of this paper is to present an option of “no-patch” variant technique to treat left ventricular aneurysms, without arguing whether there is a significant difference from others’ techniques or that it is measurably better. The proposed variant technique was previously published[6], emphasizing that Gomes et al.[7,8] reported a variant technique that eliminates the use of synthetic materials for left ventricle reconstruction.

Technique After general balanced anesthesia, cardiopulmonary bypass and blood cardioplegia: 1) The left ventricle is opened through the infarcted area, and an endocardial encircling suture is placed at the transitional zone between the scarred and normal tissue (Figure 1A); 2) In the next step, the scar tissue is circumferentially plicated with deep stitches using the same suture thread (Figure 1B); 3) Then, a second encircling suture is placed, completing occlusion of the the aneurysm, taking care to eliminate the entire septal scar (Figure 1C), and; 4) Finally, the remaining scar tissue is oversewn with an invaginating suture, to ensure hemostasis (Figure 1D). Myocardial revascularizations were performed after the left ventricle reconstruction. The same surgeon carried out all operations. RESULTS

METHODS

In seven patients (70%), thrombi were found in the cavities of ventricular aneurysms. Besides the left ventricular aneurysmectomy, nine patients (90%) underwent coronary artery

From July 2005 to March 2014, 10 consecutive patients (65.2±8.2 years-old) with ischemic heart disease underwent the aneurysmectomy surgery described herein. Five

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Regarding the post-surgical outcome, four patients (40%) had surgery over eight years ago, two patients (20%) were operated on over six years ago, and one patient (10%) was operated on more than five years ago. Three patients (30%) were in functional class I, class II in 2 patients (20%) and 2 patients (20%) with severe comorbidities remains in class III of the NYHA. There were three deaths (at our days, 15 days and eight months) in septuagenarians with, acute myocardial infarction, diabetes and pulmonary emphysema (Table 1). Just for illustration purposes, echocardiographic data of five patients operated on more than five years ago is shown (Table 2), in addiction to echocardiogram imaging showing the preserved shape of the left ventricle (Figure 1). These data correspond to two years after the reconstruction. DISCUSSION Dor was the first surgeon to demonstrate that the endoventricular patch plasty repair could be applied not only to left ventricular (LV) aneurysm, but also to a dilated akinetic ischemic LV. He emphasized the concept of reducing the LV size and reconstructing a more elliptical cavity, treating the dilatation in all its components (anterior, apical and septal). The concept of excluding all the diseased tissue from the cavity, especially the septum, is the basis of the good results[4]. The present surgical technique is quite similar to that which was described by the Caldeira & McCarthy[5] technical report (no patch and two encircling sutures), retaining the Jatene “geometric preservation” principle and the “endoventricular suture and scar tissue exclusion” Dor principle. The technique details include: a) The entire operation is performed using a single suture tied after the two encircling stitches adjustments and at the final external suture; b) Before the second encircling “purse-string”, circular plication of the scar tissue is carried out, and; c) The final closure is completed by an invaginating suture that ensures improved hemostasis. Finally, it is emphasized that the no-patch surgi-

Fig. 1 – A) First endocardial encircling suture around the transitional zone between the scarred and normal tissue; B) Scar tissue plication using the same suture thread (this surgical maneuver keeps the aneurysm neck occluded, preserving the pyriform left ventricle shape); C) Second encircling suture is tightened, completing the aneurysm occlusion; D) The remaining scar tissue is oversewn with a running “out-out” suture, to ensure hemostasis.

bypass grafting, and one patient (10%) underwent coronary artery bypass grafting as well as mitral valve replacement (Table 1). In nine patients, (90%) mechanical circulatory support with intra-aortic balloon pump was used in the first 12 hours postoperatively.

Table 1. Patient metadata of the ten operated patients. Patient 1. CFC 2. MSM 3. HM 4. AL 5. TGSS 6. EZ 7. JT 8. MDE 9. DQ 10. STZ

Age 69 73 58 56 49 75 62 69 67 74

Gender Female Female Male Male Female Male Male Female Female Male

Thrombi Myoc. Revasc. Yes S-DP,M-LCX Yes No S-RCA, R-LCX, M-LDA Yes S-DP, S-DIAG, M-LDA No S-RCA, M-LDA No S-DP, M-LDA Yes S-DP, M-LDA Yes Mitral Prost., S-DP, S-LDA Yes S-LDA Yes S-DP, S-LCX, M-LDA

IABP Yes Yes No No Yes No No Yes No No

Outcome 4 days 7 months 8 years 8 years 8 years 8 years 6 years 15 days 5 years 5 years

Funcional Class Death Death II II III III I Death I I

S=Saphenous vein, M =Mammary artery; Prost=Prosthesis; Myoc. Revasc.=Myocardium Revascularization; LDA= Left descending artery; LCX=Left circumflex, Diag=diagonalis; DP=descending posterior; IABP=Intra-aortic balloon pump

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Table 2. Echocardiography data of five patients two years after surgery. Patient 1) STZ 2) DQ 3) HM 4) EZ 5) T

Dimension LA (pre) mm 50 46 50 42 53

Dimension LA (post) mm 52 45 47 42 46

FLVDD (pre) mm 62 45 64 48 63

FLVDD (post) mm 52 47 62 42 63

LVMI (pre) mg/m2 103 118 147 96 185

LVMI (post) mg/m2 87 83 158 88 154

LVEF (pre) % 30 25 42 44 17

LVEF (post) % 34 50 47 42 25

LA=Left atrium; FLVDD=Final left ventricle diastólic diameter; LVMI=Left ventricle mass index; LVEF=Left ventricle injection fraction

cal strategy has the indirect advantage of saving time since the stitches are performed in a continuous manner. The surgical technique can also be considered a variant of the one proposed by Gomes et al.[7,8] that also reported the unnecessary use of synthetic materials. This technique, with the elimination of prosthetic materials, virtually eliminates left ventricle akinetic areas and potentially attenuates chronic inflammatory reaction. Based on superbly written opinion, Doenst[1] theorized that left surgical ventricular reconstruction (SVR) approaches are “a matter of perspective”. According to the German author, the STICH trial (Surgical Treatment for IsChemic Heart failure) presented rather sobering information with its Hypothesis 2 outcome by demonstrating identical 5-year survival rates between SVR plus bypass grafting (CABG) and CABG alone. SVR also did not improve quality of life. This neutral finding spawned a series of critical responses with respect to trial design and conduct accompanied by appropriate responses by the trial’s leadership. At the end of this dispute, it appears that SVR has been accepted as not very useful for most patients and is less and less performed in daily practice. However, though SVR may be of low value for patients with dilated and massively remodeled ventricles, the surgery still bears therapeutic potential for some patients, for different reasons, so that the surgeon’s ability to perform this operation should not bet lost[1]. It is relevant to mention that there are, beside experiences around the world, convincing Brazilian experiences for ventricular reconstruction: 1) Direct suture[9]; 2) Modification of the Cooley technique with patch suture[10]; 3) Dor patch plasty with septal exclusion[11-13]; 4) Jatene geometric reconstruction with semi-rigid bovine pericardial prosthesis[14-17]; and 5) Attempts to compare different techniques without definitive proof of superiority among them[18,19]. However, from the point of view of safety and reduction of surgical time, the “no patch” surgical variants techniques would be useful for the decision whether to operate left ventricular aneurysm or akinesia.

Fig. 2 - Echocardiogram. A) Presence of a large aneurysm of the left ventricular apex; B) Mild dilatation of the left atrium with other cardiac chambers of normal size. Note the postoperative elliptical shape of the left ventricle (2 years after surgery).

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CONCLUSION

7. Gomes WJ, Jaramillo JI, Asanuma F, Alves FA. Physiologic left ventricular reconstruction: the concept of maximum ventricular reduction and minimum inflammatory reaction. Rev Bras Cir Cardiovasc. 2004;19(4):353-7.

In conclusion, it is important to keep in mind that the data of this small number of patients who underwent the “no patch” left ventricle reconstruction variant was presented only to attest that the surgical technique is viable and safe. However, even considering these reasonable results, it remains hard to argue that this is a significant difference from other techniques. Moreover, one must take into account that surgical repair of aneurysms of the left ventricle is not the same for all patients since there are aneurysms with and without contractile lap, or even without lap, both accompanied by mitral regurgitation due to remodeling, consequent to the formation of ventricular aneurysm after acute myocardial infarction.

8. Gomes WJ, Saavedra RE, Garanhão DM, Carvalho AR, Alves FA. The renewed concept of the Batista operation for ischemic cardiomyopathy: maximum ventricular reduction. Rev Bras Cir Cardiovasc. 2011;26(4):544-51. 9. Kalil RK, Prates PR, Lucchese FA, Bertoletti VE, Nesralla IA. Resection of chronic aneurysms of the left ventricle postmyocardial infarct. Arq Bras Cardiol. 1977;30(1):37-42. 10. Prates PR, Vitola D, Sant’Anna JR, Lucchese FA, Kalil RA, Nesralla IA, et al. Modified Cooley technique for surgical repair of left ventricular aneurysms. Arq Bras Cardiol. 1991;56(3):219-22. 11. Almeida RMS, Lima Jr JD, Bastos LC, Carvalho CT, Loures DR. Remodelamento do ventrículo esquerdo pela técnica da endoventriculoplastia com exclusão septal: experiência inicial. Rev Bras Cir Cardiovasc. 2000;15(4):302-7.

Authors’ roles & responsibilities PRBE PVAT LGG LAJ CAF SB ACM AJR WVAV

Paper review, data, and writing Paper review and data Paper review and data Paper review Paper review Paper review Paper review Paper review and data Paper review and data

12. Prates PR, Homsi Neto A, Lovato LM, Teiseira GF, Sant’Anna JR, Yordi LM, et al. Late results of endoventricular patch plasty repair in akinetic and dyskinetic areas after acute myocardial infarction. Arq Bras Cardiol. 2002;79(2):107-16. 13. Almeida RM. Surgical reverse remodelling of the left ventricle: 111 months of follow-up. Rev Bras Cir Cardiovasc. 2009;24(4):470-7. 14. Braile DM, Mustafá RM, Santos JLV, Ardito RV, Zaiantchick M, Coelho WMC, et al. Correção da geometria do ventrículo esquerdo com prótese semi-rígida de pericárdio bovino. Rev Bras Cir Cardiovasc. 1991;6(2):109-15.

REFERENCES 1. Doenst T. Surgical approaches to left ventricular reconstruction: a matter of perspective. Heart Fail Rev. 2013;18(1):15-25.

15. Branco JN, Buffolo E, Andrade JC, Succi JE, Leão LE, Biscegli JF, et al. Aneurysmectomy of the left ventricle. Geometric reconstruction using a semi-rigid teflon prosthesis. Arq Bras Cardiol. 1982;39(4):241-5.

2. Jatene AD. Left ventricular aneurysmectomy. Resection or reconstruction. J Thorac Cardiovasc Surg. 1985;89(3):321-31. 3. Dor V, Kreitmann P, Jourdan J. Interest of physiological closure (circumferential plasty on contractile areas) of left ventricle after resection and endocardectomy for aneurysm or akinetic zone. Comparison with classical technique about a series of 209 left ventricular resections. J Cardiovasc Surg 1985; 26:73 [abstract].

16. Silveira WL, Leite AF, Soares EC, Nery MW, Carneiro AF, Oliveira VG. Short-term follow-up of patients after aneurysmectomy of the left ventricle. Arq Bras Cardiol. 2000;75(5):401-4.

4. Dor V, Saab M, Coste P, Kornaszewska M, Montiglio F. Left ventricular aneurysm: a new surgical approach. J Thorac Cardiovasc Surg. 1989;37(1):11-9.

17. Silveira Filho LM, Petrucci O, Vilarinho KAS, Baker RS, Garcia F, Oliveira PPM, et al. A bovine pericardium rigid prosthesis for left ventricle restoration: 12 years of follow-up. Rev Bras Cir Cardiovasc. 2011;26(2):164-72.

5. Caldeira C, McCarthy PM. A simple method of left ventricular reconstruction without patch for ischemic cardiomyopathy. Ann Thorac Surg. 2001;72(6):2148-9.

18. Borzellino DA, Puig LB, Martins SN, de Borzellino MR, Macruz H, de Oliveira SA, et al. Evaluation of the surgical treatment of left ventricular aneurysms. Arq Bras Cardiol. 1984;43(4):245-9.

6. Evora PR, Bassetto S, Junior LA. A variant “no-patch” technique for surgery of left ventricular aneurysms. Asian Cardiovasc Thorac Ann. 2014;22(2):242-4.

19. Dancini JL, Rodrigues JJ, Santos J, Pinto RFA, Burgos FJC, Conforti CA. Aneurismectomia do ventrículo esquerdo: avaliação tardia. Rev Bras Cir Cardiovasc. 1996;11(1):23-9.

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Leal JCF, et al. - Implantation of transcatheter aortic valve prosthesis through HOW TO DO IT the ascending aorta concomitant with coronary artery bypass grafting without cardiopulmonary bypass

Implantation of transcatheter aortic valve prosthesis through the ascending aorta concomitant with coronary artery bypass grafting without cardiopulmonary bypass Implante de prótese valvar aórtica transcateter através da aorta ascendente concomitante com revascularização do miocárdio sem circulação extracorpórea

João Carlos Ferreira Leal1, MD, PhD; Luis Ernesto Avanci2, MD; Achilles Abelaira Filho3, MD; Thiago Faria Almeida3, MD; Domingo Marcolino Braile4, MD, PhD

DOI: 10.5935/1678-9741.20140117

RBCCV 44205-1601

Abstract Introduction: The transcatheter aortic valve implantation in the treatment of high-risk symptomatic aortic stenosis has increased the number of implants every year. The learning curve for transcatheter aortic valve implantation has improved since the last 12 years, allowing access alternatives. Objective: The aim of this study is to approach the implantation of transcatheter aortic valve through transaortic via associated with off-pump cardiopulmonary bypass surgery in a 67-year-old man, with chronic obstructive pulmonary disease, arterial hypertension and kidney transplant. Methods: Off-pump coronary artery bypass surgery was performed and the valve in the aortic position was released successfully. Results: There were no complications in the intraoperative and postoperative period. Gradient reduction, effective orifice in-

creasing of the prosthesis and absence of valvular regurgitation after implantation were observed by transesophageal echocardiography. Conclusion: Procedural success demonstrates that implantation of transcatheter aortic valve through the ascending aorta associated with coronary artery bypass surgery without CPB is a new option for these patients.

Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil; Faculdade de Medicina de São José do Rio Preto (FAMERP), São José do Rio Preto, SP, Brazil and Hospital Beneficência Portuguesa de São José do Rio Preto, São José do Rio Preto, SP, Brazil. 2 Associação de Medicina Intensiva Brasileira (AMIB), São Paulo, SP, Brazil and Hospital Beneficência Portuguesa de São José do Rio Preto, São José do Rio Preto, SP, Brazil. 3 Hospital Beneficência Portuguesa de São José do Rio Preto, São José do Rio Preto, SP, Brazil. 4 Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil and Faculdade de Medicina de São José do Rio Preto (FAMERP), São José do Rio Preto, SP, Brazil.

No financial support.

Descriptors: Thoracic Aorta. Aortic valve stenosis. Valve Prosthesis Implantation. Cardiopulmonary bypass, Coronary artery bypass grafting, Systemic inflammatory response syndrome. Resumo Introdução: O implante de prótese aórtica transcateter no tratamento da estenose aórtica sintomática de alto risco vem aumentando de número a cada ano no mundo. A curva de apren-

Correspondence address: João Carlos Ferreira Leal Hospital Beneficência Portuguesa de São José do Rio Preto Rua Carlos Rodrigues Nogueira, 825 – Vila Redentora – São José do Rio Preto, SP, Brazil - Zip code: 15015-750 E-mail: joaocarlos@braile.com.br

This work was carried out in Hospital Beneficência Portuguesa de São José do Rio Preto, SP, Brazil.

Article received on July 17th, 2014 Article accepted on October 17th, 2014

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com doença pulmonar obstrutiva crônica, hipertensão arterial sistêmica e transplante de rim. Métodos: A revascularização miocárdica e o implante da prótese aórtica transcateter foram realizados com sucesso sem o auxílio da circulação extracorpórea. Resultados: No intra e pós-operatório não houve complicações, a redução do gradiente transvalvar, o aumento do orifício efetivo e ausência de regurgitação paravalvar foram observados pelo ecocardiograma transesofágico. Conclusão: O implante da prótese aórtica transcateter pela aorta ascendente associado com revascularização do miocárdio sem circulação extracorpórea é uma nova alternativa para pacientes de alto rico.

Abbreviations, acronyms & symbols CABG CCS COPD CPB LVEDD NYHA TEE

Coronary Artery Bypass Grafting 3 Canadian Cardiovascular Society Angina Classification Chronic obstructive pulmonary disease Cardiopulmonary by-pass Left ventricular end diastolic diameter New York Heart Association Transesophageal echocardiography

dizado para implante da prótese aórtica transcateter melhorou os resultados ao longo dos últimos 12 anos, o que permitiu o surgimento de outras vias de acesso como alternativas. Objetivo: Este trabalho refere-se ao implante de prótese aórtica transcateter pela via transaórtica associada à revascularização do miocárdio sem em paciente do sexo masculino de 67 anos

Descritores: Aorta torácica. Estenose da valva aórtica. Implante de Prótese de Valva. Circulação extracorpórea. Revascularização do miocárdio. Síndrome da resposta inflamatória sistêmica.

INTRODUCTION

mmHg aortic valve, ejection fraction of 80%, left ventricular end diastolic diameter (LVEDD) of 51 mm, left atrium and aorta of 46 mm and 31 mm, respectively. The creatinine was 2.8 mg/dl and creatinine clearance of 58 ml plasma/min/m2. Other comorbidities included left carotid disease with significant asymptomatic atherosclerotic plaque. The EuroSCORE II was 14.86%. CABG and implantation of transcatheter aortic prosthesis for ascending aorta without the use of CPB (Figures 1 and 2) were performed. Both internal thoracic arteries were dissected and a segment of the magna right saphenous vein was removed. The CPB circuit was installed by the vein and femoral artery in case of any complication during the procedure.

The learning curve for transcatheter aortic prosthesis implantation over the last 12 years has improved the results and allowed the emergence of other approach vias as implant alternatives. Access through the ascending aorta is a possibility for cases in which the transfemoral and transapical vias are contraindicated, mainly in combined procedures of aortic valve replacement and coronary artery bypass grafting. This study describes the implantation of a transcatheter aortic prosthesis through the ascending aorta concomitant with coronary artery bypass grafting without cardiopulmonary bypass in high risk patients. METHODS Operative sequence 67-years-old male patient, white, with chronic obstructive pulmonary disease (COPD), hypertension and right kidney transplanted seven years ago, was admitted to our hospital with angina pectoris, CCS 3 (Canadian Cardiovascular Society Angina Classification) and dyspnea at minimum effort, NYHA Class IV (New York Heart Association). Arterial blood pressure of 150x90 mmHg, heart rate 98 bpm, cardiac auscultation with presence of an ejection murmur in the aortic area, presence of Gallavardin phenomenon[1] and B1 hypophonetic sound. Coronary angiography showed critical obstructive lesions of 80% in the distal third of the right coronary anterior descending artery with 70% in the proximal third, 99% diagonalis in the proximal third and 80% in the first marginal branch ostium. A transthoracic echocardiogram (TTE) showed a double aortic valve lesion with predominant severe and calcified stenosis. The flow rate was 4.44 m/s, mean gradient of 48

Fig. 1 – Image of the procedure.

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without the need for inotropic support or temporary pacemaker. Postoperative TEE showed reduced transvalvular gradient, effective increased orifice, and absence of paravalvular regurgitation. The patient was asymptomatic and returned to professional activity after three months follow-up. DISCUSSION The implantation of transcatheter aortic prosthesis represents a paradigm shift in the treatment of aortic stenosis in symptomatic or high risk patients considered inoperable. The first implantation of transcatheter aortic prosthesis in humans was published in 2002[4], and the first randomized study to determine safety and effectiveness of transcatheter prosthesis in the aortic position demonstrated the noninferiority of the method compared with conventional surgery[5]. The global sample exceeded 100 thousand cases of transcatheter prostheses implantation over the last twelve years. In Brazil, three types of transcatheter prostheses are used, including a Brazilian prosthesis with good results through transapical access[6] and as an alternative it was implemented by femoral access with success[7]. Transapical and transfemoral approaches are the most used for the transcatheter treatment of symptomatic calcified aortic stenosis. However, in patients with peripheral arterial disease, deformed chest and fragile left ventricular apical segment, other approaches can be used. The transaortic approach through the ascending aorta and ministernotomy is an attractive therapeutic option[8]. However, there are few reports in the literature on thoracotomy through a median sternotomy involving implantation of transcatheter aortic prosthesis concomitant to off-pump coronary artery bypass grafting. The study by Mohammad et al.[9] in 2011 on the transcatheter aortic prosthesis implantation through the ascending aorta and coronary artery bypass grafting showed reproducible results with success. Our study concerns a patient who had severe aortic stenosis and associated coronary artery disease, and the “Heart Team” opted for transaortic via in the ascending portion with full median sternotomy due to the need for CABG; two mammary arteries and one great saphenous vein segment were used. The aid of 3D TEE allowed the release of INOVARE® transcatheter aortic prosthesis at the desired location without complication. Full off-pump CABG was performed, and the right coronary artery was not revascularized because it presented an obstructive lesion in the distal third. The CPB system was on standby, allowing to perform the procedure safely if there were any complications. However, there were some difficulties during the procedure, the largest of which was to establish the optimal length of the introducer and release device of the transcatheter valve between puncture in the aortic wall up to the aortic valve annulus. Leaving the guidewire until the tip of the left ventricle

Fig. 2 – Intraoperative 3D Transesophageal Echocardiogram.

The procedure was performed in a hybrid operating room with C-shaped arch Philips BV Pulsera and transesophageal echocardiography (TEE) GE Vivid E9 3D. The response curve dose of systemic heparin, described by Bull and colleagues in 1975 was used[2]. The right internal thoracic artery was anastomosed to the left internal thoracic artery, making a Y-shaped branch. Thus, the left internal thoracic artery was grafted to the descending artery and the right internal thoracic artery to the diagonal branch, and the saphenous vein segment to the first marginal branch. CPB was not used at any stage of the procedure. During the anastomoses of coronary grafts we used stabilizer and intracoronary shunts of 1.5 for diagonal and 1.75 for anterior descending and first marginal branch. In the anastomosis of the saphenous marginal branch there was a hemodynamic instability due to the presence of cardiac dislocation and severe aortic stenosis, by releasing the heart to hemodynamic stability, then resumed the anastomoses without instability. The implantation of transcatheter aortic valve prosthesis was performed through the ascending aorta in the anterior, superior and lateral wall, locations with lower prevalence of calcification[3]. To prevent bleeding a purse was performed using 4.0 prolene wires and bovine pericardial pledges. The prosthesis used was No. 24 and the 28 balloon catheter, the implantation in the aortic valve annulus without pre-dilatation guided the previously introduced guidewire into the left ventricle. Heart rate was increased to 160 bpm using a temporary pacing electrode in the right ventricle, this maneuver was used to decrease blood flow in the aorta during the release of the prosthesis and the total time of the aortic procedure lasted 28 minutes. There was no intraoperative and postoperative complication, the patient was extubated eight hours after the procedure

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and determine the exact point of release of the prosthesis are important maneuvers to the aforementioned procedure. The hybrid operative treatment with transcatheter aortic prosthesis implantation through the ascending aorta and CABG is an alternative therapy that justifies the indication for symptomatic calcified aortic stenosis associated with coronary artery disease in high-risk patients.

aortic valve implantation and its relevance to the transaortic approach. JACC Cardiovasc Interv. 2012;5(5):470-6. 4. Cribier A, Eltchaninoff H, Bash A, Boronstein N, Tron C, Bauer F, et al. Percutaneous trancatheter implantation of an aortic valve prosthesis for calcific aortic stenosis: first human case description. Circulation. 2002;106(24);3006-8. 5. Leon MB, Smith CR, Mack M, Miller C, Moses JW, Svensson LG, et al; PARTNER Trial Investigators. Transcatheter aortic valve implantation for aortic stenoses in patients who cannot undergo surgery. N Engl J Med. 2010;363(17):1597-607.

Authors’ roles & responsibilities JCFL LEA AAF TFA DMB

Analysis and/or interpretation of data, conception and design of the study, performing surgeries and/or experiments Performing surgeries and/or experiments Performing surgeries and/or experiments Performing surgeries and/or experiments, writing of the study or critical analysis of its content Writing of the study or critical analysis of its content

6. Gaia DF, Palma JH, Ferreira CBND, Souza JAM, Agreli G, Guilhen JCS, et al. Implante transapical de valva aórtica: resultados de uma nova prótese brasileira. Rev Bras Cir Cardiovasc. 2010;25(3):293-302. 7. Pontes JCDV, Duarte JJ, Silva AD, Gardenal N, Dias AMAS, Benfatti RA, et al. Experiência inicial e pioneira do implante de valva aórtica transcateter (Inovare) por via femoral ou ilíaca. Rev Bras Cir Cardiovasc. 2013;28(2):208-16.

REFERENCES

1. Gallavardin L, Ravault P. The murmur of aortic stenosis undergoes a change in timbre becoming musical when radiating to the apex. Lyon Med. 1925;135:523-9.

8. Bapat V, Khawaja MZ, Attia R, Narayana A, Wilson K, Macgillivray K, et al. Transaortic Transcatheter Aortic valve implantation using Edwards Sapien valve: a novel approach. Catheter Cardiovasc Interv. 2012;79(5):733-40.

2. Bull BS, Huse WM, Brauer FS, Korpman RA. Heparin therapy during extracorporeal circulation, II. The use of a dose-response curve to individualize heparin and protamine dosage. J Thorac Cardiovasc Surg. 1975;69(5):685-9.

9. Mandegar MH, Nazeri I, Abdi S, Roshanali F. Successful transcatheter aortic valve implantation through ascending aorta and total revascularization using Edwards SAPIEN Transcatheter Heart Valve System. Ann Thorac Surg. 2011;92(6):2262-3.

3. Bapat VN, Attia RQ, Thomas M. Distribution of calcium in the ascending aorta in patients undergoing transcatheter

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Canale LS & Bonatti How to IT perform a coronary artery anastomosis in HOWJ -TO DO complete endoscopic fashion with robotic assistance

How to perform a coronary artery anastomosis in complete endoscopic fashion with robotic assistance Como realizar anastomose coronariana totalmente endoscópica com assistência robótica

Leonardo Secchin Canale1, MD; Johannes Bonatti2, MD

DOI 10.5935/1678-9741.20140079

RBCCV 44205-1602

Abstract Current technology in robotic surgery allows us to perform myocardial revascularization procedures in a totally endoscopic fashion. We will describe the technique of choice for left internal mammary artery to left anterior descendent artery anastomosis with the use of cardiopulmonary bypass machine. The method is efficient and there is long term follow-up showing similar patency of the graft when compared to conventional methods (when performed through sternotomy).

Resumo A tecnologia atual em cirurgia robótica permite realizar-se procedimento de revascularização do miocárdio de modo totalmente endoscópico. Descreveremos aqui a técnica de escolha para anastomose de artéria mamaria interna esquerda em artéria coronariana descendente anterior com uso de circulação extracorpórea. O método e eficaz e já existe acompanhamento a longo prazo mostrando patência do enxerto semelhante ao método convencional por esternotomia.

Descriptors: Myocardial Revascularization. Surgical Procedures, Minimally Invasive. Thoracoscopy.

Descritores: Revascularização Miocárdica. Procedimentos Cirúrgicos Minimamente Invasivos. Toracoscopia.

Totally endoscopic coronary artery bypass surgery with robotic assistance has become a feasible, safe and effective method for surgical coronary revascularization in selected patients[1]. Either as an isolated therapy or as part of a hybrid approach the most common and main part of the procedure is the left internal mammary artery (LIMA) to left anterior descending artery (LAD) anastomosis. Different methods of endoscopic anastomosis have been described: running suture, use of nitinol clips and use of anastomotic connector device. Here we describe our technique of choice of running suture with Pronova 7-0. The general conduct of operation has been extensively described elsewhere[2] but can be summarized as follow. A dual lumen endotracheal tube is used to allow single right

lung ventilation. The patient cart of the robotic system approaches the patient from the right. The ports are placed on the left hemithorax with a deflated left lung: the camera port is inserted in the left fifth intercostal space in the anterior axillary line, the two robotic arm ports are inserted in the third and seven intercostal spaces, 3 cm anteriorly to the camera port. Lastly the myocardial stabilizer is inserted through a left subcostal port in the midclavicular line. The mammary takedown is performed with fine deBakey robotic forceps and a robotic electrocautery spatula using low energy (15W). A full description can be found elsewhere[3]. While one surgeon is performing the LIMA harvesting, another one is preparing the left groin vessels for cardiopulmonary bypass (CPB) cannulation and insertion of an

Watch the video acessing the link below: http://www.rbccv.org.br/video/2307/Como-realizar-anastomose-coronariana-totalmente-endoscopica-com-assistencia-robotica 1 2

Cleveland Clinic Foundation, Cleveland, Ohio, USA. Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates.

Correspondence address: Leonardo Secchin Canale Cleveland Clinic Foundation 9500 Euclid Avenue, J4-133, Cleveland, Ohio, USA - Zip code: 44195 E-mail: leonardo.canale@gmail.com

This study was carried out at Cleveland Clinic Foundation, Cleveland, Ohio, USA.

Article received on March 10th, 2014 Article accepted on June 8th, 2014

No financial support.

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Canale LS & Bonatti J - How to perform a coronary artery anastomosis in complete endoscopic fashion with robotic assistance

travelling proximally. The mammary artery is then brought down. The suture continues proximally with the needle being handled in a right hand fashion. Adjustment of the line of suture is possible using the needle. When the heel is reached, extra care should be taken to avoid suturing the posterior wall, which would lead to obstruction of the anastomosis. The Black Diamond forceps can be used to kindly test for patency. When the heel is passed, the running suture continues, but the needle is handled in a left hand fashion (Figure 3). This continues up to the middle of the front wall. At this point this needle is parked and the first one is taken again. The suture then comes from distal to proximal, including the toe of the anastomosis (Figure 4). Again, this can be tested for patency with the fine Black Diamond forceps. When the two sutures meet in the middle of the anterior wall, the needles are removed by breaking the stitch and they are used to put tension on the whole suture line. This is an important step since this procedure is performed in a solo fashion, without an assistant keeping tension on the suture during its confection.

Abbreviations, acronyms & symbols CPB LAD LIMA

Cardiopulmonary bypass Left anterior descending artery Left internal mammary artery

intra-aortic occlusive device. After the LIMA harvesting is complete, CPB is initiated, the pericardium is opened and the LAD target is identified. The intra-aortic occlusion device is inflated, and cardioplegia is delivered thorough its tip. Our cardioplegia solution of choice is Modified Buckberg. This is infused every 15 min, or earlier if there is electrical activity. When cardiac arrest is achieved our attention turns to the anastomosis confection. The coronary stabilizer is brought in and placed over the area of interest. A proper spot for the anastomosis is chosen in the LAD based on quality of the artery wall and size of the vessel. The LIMA is checked for adequate flow and clamped with a bulldog device. An endoscopic clip is placed in the adventitia of the mammary securing it to pericardial fat allowing it to be still. The mammary end is prepared by cutting it in a beveled fashion with endoscopic Pott scissors. The LAD is opened with an endoscopic scalpel (Figure 1) and the arteriotomy is increased with Pott scissors to a size of 4 mm. If considerable backflow from the perforators compromise view, proximal and distal snare of the artery are possible with vessel loops. The mammary artery is positioned close to the opened coronary artery. For the anastomosis confection two delicate Black Diamonds forceps are used. The stitch used is a 7-0 Pronova, 7 cm long with small needle. The first stitch goes from inside to the outside of the coronary close to the toe of the anastomosis, in the back wall. The needle is pulled and parked in the myocardial fat. The other needle takes a bite inside-out in the mammary artery at the distal back wall (Figure 2). The next three stitches will enter the coronary artery from the outside and the mammary artery in a parachute mode,

Fig. 2 - First stitch in the mammary artery.

Fig. 1 - Opening of coronary artery (LAD) with endoscopic scalpel.

Fig. 3 - LIMA-LAD anastomosis half way through.

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We here describe our technique of choice for robotic LIMA-LAD anastomosis. Pictures and video further illustrates the procedure. Authorsâ&#x20AC;&#x2122; roles & responsibilities LSC JB

Fig. 4 - Last stitch in LIMA-LAD anastomosis.

Final approval of the manuscript conception and study design, performed procedures, and/or experiments, writing of the manuscript or review of its content Final approval of manuscript conception and study design, performed procedures, and/or experiments, writing of the manuscript or review of its content

REFERENCES 1. Bonaros N, Schachner T, Lehr E, Kofler M, Wiedemann D, Hong P, et al. Five hundred cases of robotic totally endoscopic coronary artery bypass grafting: predictors of success and safety. Ann Thorac Surg. 2013;95(3):803-12.

The suture is then tied down with several knots. The mammary artery is opened to test for any bleeding and repair stitches are placed as necessary (Video 1). After the anastomosis is complete, the endo-ballon is deflated and the heart starts to beat. An ultrasound probe is brought into the cavity through the left subcostal port and applied to the mammary artery to access for flow. Further hemostasis of the anastomosis and mammary artery bed are performed. The patency of robotic totally endoscopic LIMA-LAD anastomosis has been found to be similar to conventional open procedures[1,4,5]. Angiographic and coronary CT studies have found this patency to be between 92%[4] and 98%[5] on the long term. The average time to perform the anastomosis has been reported in several studies to be between 18 and 35 minutes[6]. In many situations the revascularization approach follows a hybrid philosophy. In this case one or two IMAs are anastomosed to arteries of the left ventricle with robotic assistance and percutaneous intervention with stents are performed to the remaining vessels. The order of the procedures can vary and depends on clinical status, risk of bleeding and severity of coronary lesions.

2. Canale LS, Mick S, Mihaljevic T, Nair R, Bonatti J. Robotically assisted totally endoscopic coronary artery bypass surgery. J Thorac Dis. 2013;5(Suppl 6):S641-9. 3. Canale LS, Bonatti J. Mammary artery harvesting with the Da Vinci Si robotic system. Rev Bras Cir Cardiovasc. 2014;29(1):107-9. 4. Folliguet TA, Dibie A, Philippe F, Larrazet F, Slama MS, Laborde F. Robotically-assisted coronary artery bypass grafting. Cardiol Res Pract. 2010;2010:175450. 5. Srivastava S, Gadasalli S, Agusala M, Kolluru R, Barrera R, Quismundo S, et al. Beating heart totally endoscopic coronary artery bypass. Ann Thorac Surg. 2010;89(6):1873-9. 6. Bonatti J, Schachner T, Bonaros N, Lehr EJ, Zimrin D, Griffith B. Robotically assisted totally endoscopic coronary bypass surgery. Circulation. 2011;124(2):236-44.

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Aazami MH, et HOW al. - Right-sided TO DO ITreverse T composite arterial grafting to complete revascularization of the right coronary artery

Right-sided reverse T composite arterial grafting to complete revascularization of the right coronary artery Enxerto arterial composto reverso T do lado direito para completar a revascularização da artéria coronária direita

Mathias H. Aazami1, MD; Mohammad Abbasi-Teshnizi2, MD; Shahram Amini3, MD; Nasim Sadat Lotfinejad4, MD

DOI 10.5935/1678-9741.20140069

RBCCV 44205-1603

Abstract Complete arterial revascularization for the right coronary artery is underused mainly due to technical issues. Herein we report on a new approach for complete arterial revascularization of arterial revascularization for the right coronary artery branches. Complete arterial revascularization for the right coronary artery revascularization was performed in 8 patients using a reverse T composite arterial graft. None of the patients suffered perioperative myocardial infarction. All patients underwent noninvasive coronary imaging, displaying an early patency rate of 100%. Complete arterial arterial revascularization for the right coronary artery revascularization using a reverse T graft offers a new paradigm with enhanced technical flexibility in performing all arterial myocardial complete revascularizations in selected patients.

Resumo Revascularização arterial completa para a artéria coronária direita é subutilizada, principalmente devido a problemas técnicos. Nós relatamos uma nova abordagem para a revascularização arterial completa para os ramos da artéria coronária direita. Revascularização arterial completa da artéria coronária direita foi realizada em 8 pacientes usando um enxerto T arterial composto inverso. Nenhum dos pacientes sofreu infarto do miocárdio perioperatório. Todos os pacientes foram submetidos a exame de imagem não invasivo coronária não invasiva, exibindo taxa de patência precoce de 100%. Revascularização arterial completa da artéria coronária direita com enxerto inversa T oferece um novo paradigma com maior flexibilidade técnica na execução todas as revascularizações arteriais completas do miocárdio em pacientes selecionados.

Descriptors: Coronary Artery Bypass. Coronary Circulation. Internal Mammary-Coronary Artery Anastomosis. Tomography Scanners, X-Ray Computed. Radial Artery.

Descritores: Ponte de Artéria Coronária. Circulação Coronária. Anastomose de Artéria Torácica Interna-Coronária. Tomógrafos Computadorizados. Artéria Radial.

Cardiac Surgery Department, Cardiac Anesthesia Research Center ad Cardiothoracic Surgery and Transplantation Research Center of Imam Reza Hospitalthe Mashhad University of Medical Sciences, Mashad, Iran. 2 Cardiac Surgery Department of Imam Reza Hospital the Mashad University of Medical Sciences, Mashhad, Iran. 3 Cardiac Surgery Department and Cardiac Anesthesia Research Center of Imam Reza Hospitalthe Mashhad University of Medical Sciences, Mashhad, Iran. 4 Mashhad University of Medical Sciences, Mashhad, Iran.

No financial support.

Correspondence address: Nasim Sadat Lotfinejad Faculty of Medicine, Azadi Square, Pardis Campus, Mashhad-Iran E-mail: nasim.lotfinezhad@gmail.com

This study was carried out at Cardiac Surgery Department of Imam Reza Hospital, The Mashhad University of Medical Sciences, Mashhad, Iran.

Article received on February 28th, 2014 Article accepted on May 3nd, 2014

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1) In-situ reverse T grafting (IRTG) using RITA (Figure 2A). 2) Coronaro-coronary reverse T grafting (CRTG) (Figures 2B and 2C). Eight patients with a mean age of 57.13 9.7 years old (female 25%; mean logistic Euroscore: 5.2±5.6%; elective: 75%; mean preoperative left ventricle ejection fraction (LVEF): 45.71±9.32%; diabetes mellitus: 75%) underwent CRR as a part of complete arterial revascularization. 75% of patients had a three vessel or left main disease and had a history of recent myocardial infarction (MI). Two patients underwent previous PTCA with intracoronary stenting (mean stent per patient: 4). An occluded LAD and RCA were noticed in 50% of patients, and RCA was dominant in 6 patients.

Abbreviations, acronyms & symbols RCA MDR CCR CBF CRTG ICB IRTG ITA IVS LAD LITA MI RA RITA

Right coronary artery Multisite diseased right coronary artery Complete RCA revascularisation Coronary blood flow Coronaro-coronary reverse T grafting Intracoronary bridge In situ reverse T grafting Internal thoracic artery Interventricular septum Left anterior descending artery Left internal thoracic artery Myocardial infarction Radial artery Right internal thoracic artery

RESULTS The mean number of total arterial anastomoses (distal/ composite/ proximal coronary-coronary) was 7±1.5 per patient. The mean numbers of distal and CRR anastomoses were 4.88± 1.26 and 2.25±0.463 per patient respectively. Double internal thoracic arteries (ITAs) and RA were used in 75 and 62.5% of the patients. Six patients had right- and left-sided double composite arterial grafting. CRR was performed as IRTG in 5 and as CRTG in the remaining patients. An ICB was constructed using a segment of RA in 5 patients or ITA in the rest. An anterolateral or acute marginal branch was revascularized in 6 patients directly or via their supporting RCA segment (4 patients). Fifty percent of patients required extensive LAD reconstruction (endarterctomy, arterial roofing, and On-Lay anastomosis). Two patients needed concomitant releasing of a muscle bridge on LAD (>3 cm). The mean pump and ischemic times were 257±47.7 and 180±47.3 minutes respectively. None of the patients suffered perioperative MI, nor required mechanical/inotropic cardiocirculatory support. 87.5% of patients were extubated within the first 24 hours postoperatively and the mean time of ICU stay was 3.1±1.5 days. None of the patients suffered major cardiocerebral adverse events except one with resolving postoperative neurocognitive dysfunction (preoperative strokes with carotid stenting). The mean LVEF at discharge was 45.71±3.45%. All patients underwent noninvasive coronary imaging within the first four months postoperatively displaying an early patency rate of 100% for the grafts and distal anastomoses.

INTRODUCTION The right coronary artery (RCA) is an important provider of collateral flow to the left coronary system and interventricular septum (IVS)[1,2]. In the setting of a multisite diseased right coronary artery (MDR), surgical revascularization is generally confined to its inferoposterior branches. We report on a new approach, attempted at complete arterial revascularization of RCA (CRR) in selected patients. These techniques enable us to achieve double inflow all arterial revascularizations using two arterial composite grafts at their utmost technical aspect. METHODS This study was approved by our institutional ethics committee, and written informed consent was obtained from each patient. This approach is based on constructing a reverse T composite arterial graft placed between the RCA targets along with complete left-sided arterial revascularization. Arterial revascularization is performed using left internal thoracic artery (LITA); right internal thoracic artery (RITA), or radial artery (RA). Bicaval venous cannulation in view of optimal integrated myocardial protection, cold blood intermittent anteroretrograde cardioplegia, mild systemic hypothermia, and peri- and postoperative tight glycemia control were used systematically. An intracoronary bridge (ICB) is constructed between the RCA targets using a segment of free arterial graft (Figure 1A-D). Preprocedural measuring of the grafts’ length and ICB on a fully beating heart avoids pitfalls in its final layout; thereby preventing kinking/angulation. An anterolateral or acute marginal branch can be bypassed directly (diameter > 1 mm) or indirectly through RCA segments giving them takeoff (Figure 1C). Then ICB is connected to an arterial inflow according to two distinct modes, the choice of which depends on final layouts for left- and right-sided revascularizations in line with availability of the arterial grafts:

DISCUSSION A double inflow feature of coronary arterial system confers RCA the role of a main provider for collateral flow with regards to the left coronary system and IVS; thereby, federating a salient backup in regulations of coronary blood flow (CBF)[1,2].

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Fig. 1 - The examples of a right-sided intracoronary bridge. A-I: severe three vessel CAD with an occluded LAD. A-II: Diffuse MDR involving an anterolateral branch (the dashed arrow). A-III: ICB placed between the anterolateral branch and distal RCA. [ICB: radial artery; Inflow mode: IRTG with in situ RITA, see Fig. 2A]. B-I: Left coronary branches with diffuse LAD disease. B-II: a MDR. The dashed arrows show a second anterolateral and acute marginal branches arising from the RCA segment between the two stenoses. B-III: ICB placed between mid and distal RCA. [ICB: radial artery; Inflow mode: ITRG with in situ RITA]. C-I: LAD is nearly occluded; the distal segment of a dominant RCA is filled retrogradely (arrow). C-II: an occluded MDR, a second anterolateral and acute marginal branches are detected (dashed arrows). C-3: ICB providing 3 distal anastomoses. The distal anastomoses for second anterolateral and acute marginal branches are placed on the corresponding RCA segments. [ICB: radial artery; Inflow mode: IRTG with in situ RITA]. D-I: the arrow shows the left posterolateral branch; LAD is occluded. D-II: arrow shows an intrastent stenosis placed in mid RCA.D-III: ICB placed between PDA and left posterolateral branch [ICB: free-LITA; inflow mode: CRTG with free RITA; see Fig. 2B]

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Fig. 2 - The arterial Inflow modes by in situ RITA (IRTG) and coronaro-coronary grafting (CRTG). A-I: operative view of an ITRG with in situ RITA. A-II: postoperative CT angiography showing the arterial inflow (arrow) and ICB (dashed arrow). A-III: the postoperative CT-angiography of the left-sided composite arterial graft (endarterctomized LAD with extensive arterial roofing). B-I: operative view of CRTG: arrows and dashed arrows show the arterial inflow and ICB respectively. BII: postoperative CT angiography of CRTG. The head of arrow shows the native RCA with in-stent stenosis. The arrow displays the arterial inflow and ICB at the level of their composite anastomosis. B-III: operative view and postoperative control of the left-sided composite arterial graft. C-I: preoperative coronary angiography displaying an occluded RCA and LAD in a patient with three vessel disease. The arrows show an acute marginal branch and distal RCA. C-II: the post-operative CT angiography showing the patent CRTG (arrow: arterial inflow; dashed arrow: ICB). [ICB: free LITA; Inflow mode: CRTG using radial artery].

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Restoring the collateral pathways and functional features of coronary circulation should render the aim of complete revascularization more attainable. Reaching a coronary reserve closer to the normal does support a better myocardial protection and enhances the ability of myocardium to meet an increased demand in CBF. Despite a myriad of all arterial bypassing techniques being successfully reported; yet, controversy exists regarding their functional capacity to restore an aortocoronary reserve close to that of a normal double inflow coronary system. A single inflow feature and increased vulnerability of the arterial grafts facing native competitive flow are still matters of debate[3-5]. In the setting of coronary artery disease with MDR referred to surgical revascularization, bypassing the right coronary system is generally confined to its inferoposterior territory. An inadequate length of arterial grafts, a more complex layout required for sequential bypassing, a small size of an anterolateral or acute marginal branch to host for a distal anastomosis, and severe calcifications are technically the main limiting factors that could compromise graft’s patency. In addition, the existence of a differential profile along RCA for native competitive flow (adversely affecting patency of the arterial grafts especially for coronary stenosis less than 90%) arouses the current reluctance for arterial CRR[2-5]. From a technical point of view, using an ICB overcomes the aforementioned technical issues: ICB reduces the number of sequential bypassing, enhances technical flexibility in fashioning sequential anastomoses with proper angulations if required, and remedies the limiting length of arterial grafts. Performing the distal anastomosis on an intermediate segment of RCA supporting an anterolateral or acute marginal branch is an alternative in a case of unsuitable anatomy (Figure 1C). It may be preferable to establish the final layout of ICB operatively, as the preoperative coronary angiography could lead to over- or underestimation of the total number of targets amenable to revascularization (Figure 1). Patients with compromising revascularization of LAD or distal RCA (poor runoff, extensive endarterectomy, and arterial reconstruction) incur an exceptionally high risk for perioperative myocardial infarction, therefore restoring some amount of the coronary collateral pathways as a “backup” sounds crucial. Diffuse coronary artery disease severely affects the epicardial arterial network that is in charge of optimizing the diastolic phase of CBF. The latter can be partly compensated for by using an arterial ICB, creating a new functional epicardial arterial network. Our results show a 100 % early patency rate for ICBs placed between different RCA branches with various degrees of stenosis, suggesting a better aptitude of ICB to face the native competitive flow. It can be speculated that ICB acts

as a systolic redistributing circuit between the targets, thereby reducing the amount of systolic reversed flow in its arterial inflow. Right-sided reverse T grafting should only be performed on carefully selected patients. If any doubts remain about the suitability of target sites for hosting a distal anastomosis, difficulty in dissection for RCA or its branches, and quality of arterial grafts, the patient should not be put on the risk side of the benefit/ risk ratio. It is definitively inadvisable to proceed with such a procedure using the unsuitable distal rest of arterial conduits. Being technically more demanding with an increased ischemic time can be reproached. The increased ischemic time is related to a greater number of large arterial anastomoses that should be fashioned meticulously. In addition, 50% of patients in the current series needed extensive coronary arterial reconstruction. A safer pump run, meticulous cardioprotection encompassing a protocol for tight glycemic control, and the expected benefits of a double inflow complete revascularization do outweigh the foreseeable and inevitable reluctances[1,2]. Bicaval cannulations with right atrial isolation were used in this series as part of integrative myocardial protection. By the time of heart displacement, kinking of vena cava increases venous pressures; therefore, selective drainage of vena cava provides additional organ protection, specially reducing the rate of neurologic and neurocognitive disorders. As the appropriate lengths of all grafts and ICB are measured pre-procedurally on loaded heart, its subsequent unloading with bicaval drainage does not induce errors in estimation. The absence of in-hospital mortality and occurrence of major adverse cardiocerebral events supports the aforementioned perioperative majors and the current techniques, recalling that best myocardial protection is provided by integrated revascularization. So far, further functional investigations, a larger scale clinical series, and longer-term results are mandatory to support the advocated benefits of CRR using a composite arterial reverse T graft.

Authors’ roles & responsibilities MHA MAT SA NSL

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Aazami MH, et al. - Right-sided reverse T composite arterial grafting to complete revascularization of the right coronary artery

REFERENCES

results of the radial artery graft patency according to the degree of native coronary stenosis. Eur J Cardiothorac Surg. 2008;33(3):341-8.

1. Osswald BR, Blackstone EH, Tochtermann U, Schweiger P, Thomas G, Vahl CF, et al. Does the completeness of revascularization affect early survival after coronary artery bypass grafting in elderly patients? Eur J Cardiothorac Surg. 2001;20(1):120-5.

4. Nakajima H, Kobayashi J, Tagusari O, Bando K, Niwaya K, Kitamura S. Competitive flow in arterial composite grafts and effect of graft arrangement in off-pump coronary revascularization. Ann Thorac Surg. 2004;78(2):481-6.

2. Gaudino M, Alessandrini F, Glieca F, Luciani N, Cellini C, Pragliola C, et al. Effect of surgical revascularization of a right coronary artery tributary of an infarcted nonischemic territory on the outcome of patients with three-vessel disease: a prospective randomized trial. J Thorac Cardiovasc Surg. 2004;127(2):435-9.

5. Gaudino M, Alessandrini F, Pragliola C, Cellini C, Glieca F, Luciani N, et al. Effect of target artery location and severity of stenosis on mid-term patency of aorta-anastomosed vs. internal thoracic artery-anastomosed radial artery grafts. Eur J Cardiothorac Surg. 2004;25(3):424-8.

3. Yie K, Na CY, Oh SS, Kim JH, Shinn SH, Seo HJ. Angiographic

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Schaitza GA, et al. - Surgical treatment HOW TO DO IT of a giant left ventricular aneurysmA case report

Surgical treatment of a giant left ventricular aneurysm- A case report Tratamento cirúrgico do aneurisma gigante de ventrículo esquerdo - Relato de caso

Gustavo Alves Schaitza1, MD; José Rocha Faria Neto2, MD, PhD; Julio Cesar Francisco2, PhD; Cristiana Pellegrino Baena2, MD, PhD; Helcio Giffhorn3, MD, MsC; Bruna Olandoski4; Leanderson Franco de Meira2, Me; Luiz César Guarita-Souza5, MD, MsC, PhD

DOI 10.5935/1678-9741.20140107

RBCCV 44205-1604

Abstract An aneurysm of the left ventricle is a complication of acute myocardial infarction. We report a case of a giant aneurysm of the left ventricle after myocardial infarction in a 59 year-old male patient. The surgery to correct the aneurysm was performed with the use of cardiopulmonary bypass under normothermia. A bovine pericardial patch was used for the geometric reconstruction of the ventricular wall affected by the aneurysm. After the procedure, echocardiography and magnetic resonance imaging revealed improvement in left ventricular ejection fraction and volume reduction.

Resumo O aneurisma de ventrículo esquerdo é uma complicação do infarto agudo do miocárdio. Relatamos um caso de um aneurisma gigante de ventrículo esquerdo pós-infarto de miocárdio em um paciente de 59 anos do sexo masculino. A cirurgia para correção do aneurisma foi realizada com uso de circulação extracorpórea sob normotermia. Utilizou-se uma placa de pericárdio bovino para a reconstrução geométrica da parede ventricular acometida pelo aneurisma. Após o procedimento, ecocardiografia e ressonância magnética revelaram melhora da fração de ejeção com redução do volume ventricular esquerdo. Descritores: Aneurisma. Aneurisma cardíaco. Infarto do Miocárdio.

Descriptors: Aneurysm. Heart Aneurysm. Myocardial Infarction.

INTRODUCTION

tion with coronary angioplasty performed in the acute phase of the event. The condition can be classified as a true aneurysm when the aneurysm forms at the damaged wall of the myocardium and as a pseudoaneurysm when the cardiac rupture is contained by adherent pericardium or scar tissue[1,2].

Although a left ventricular aneurysm is a common complication following a myocardial infarction, its incidence has declined, primarily due to the treatment of a myocardial infarc-

Watch the videos acessing the link below: http://www.rbccv.org.br/article/2306/Tratamento-cirurgico-do-aneurisma-gigante-de-ventriculo-esquerdo---Relato-de-caso Universidade Federal do Paraná (UFPR), Curitiba, PR, Brazil and Hospital de Clínicas da Universidade Federal do Paraná (HC/UFPR), Curitiba, PR, Brazil. 2 Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, PR, Brazil. 3 Hospital Nossa Senhora do Pilar (HP), Curitiba, PR, Brazil. 4 Faculdade Evangélica do Paraná (FEPAR), Curitiba, PR, Brazil. 5 InCor-Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo(HCFMUSP), São Paulo, SP, Brazil, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, PR, Brazil and Universidade Federal do Paraná (UFPR), Curitiba, PR, Brazil.

No financial support.

Correspondence address: Luiz César Guarita-Souza Pontifícia Universidade Católica do Paraná – PUCPR Rua Imaculada Conceição, 1155 – Prado Velho, Curitiba, PR, Brazil Zip code: 80215-901 E-mail: guaritasouzalc@hotmail.com

This study was carried out at Hospital Nossa Senhora do Pilar (HP), Curitiba, PR, Brazil, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, PR, Brazil and Universidade Federal do Paraná (UFPR), Curitiba, PR, Brazil.

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Article received on May 7th, 2014 Article accepted on September 2nd, 2014

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Schaitza GA, et al. - Surgical treatment of a giant left ventricular aneurysmA case report

Abbreviations, acronyms & symbols CPB MRI NYHA TEE

Cardiopulmonary bypass Magnetic resonance imaging New York Heart Association Transesophageal echocardiography

The main complications of a left ventricular aneurysm are heart failure, ventricular arrhythmias, systemic embolization, cerebrovascular accident, and ventricular rupture. The main surgical indications occurring in patients with a true aneurysm, intractable ventricular arrhythmias and heart failure unresponsive to drug treatment. Other possible indications include refractory angina and systemic embolization in patients who cannot take oral anticoagulants. In cases of pseudoaneurysm, surgical treatment is the best option, given its high probability of symptom dissolution[2,3]. Surgical techniques currently in use for correction of a left ventricular aneurysm are based on reconstruction of the left ventricle or a reduction of its volume with the goal of restoring normal cardiac geometry[4,5]. The present article reports a case of a giant ventricular aneurysm post-myocardial infarction in a 59 year-old male patient and shows an example of a positive outcome of surgical correction with the ventricular remodeling technique. The case report contains full imaging documentation with cardiac magnetic resonance imaging and transesophageal echocardiography images. CASE REPORT A 59 year-old male patient suffered from hypertension and dyslipidemia. He was a smoker and had a positive family history for coronary artery disease. Following an acute myocardial infarction in February 2013, he underwent a circumflex coronary stent implantation. Twenty-five days after stent implantation, the patient presented with acute coronary symptoms, which were found to be due to stent occlusion; however, another angioplasty proved to be impossible due to technical difficulties. In August 2013, the patient suffered heart failure, functional class III (NYHA). A giant aneurysm of the left ventricle was present. Transesophageal echocardiography (TEE) and cardiac magnetic resonance imaging (MRI) were performed (ejection fraction: 19% [Simpson]; leftend diastolic volume: 402.7 cm3; left-end systolic volume: 324 cm3; ejection fraction: 19%; left-end diastolic volume: 490 ml; left-end systolic volume: 398 ml). Left ventricle weight was 144 gm2. The aneurysm was 7.3 x 6.4 x 7.5 cm with tapered walls towards the base of the left ventricle; a thrombus was present (Figures 1A and 1B).

Fig. 1 â&#x20AC;&#x201C; A) Preoperative transesophageal echocardiography. Fig. 1 â&#x20AC;&#x201C; B) Preoperative cardiac magnetic resonance imaging.

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Fig. 2 – A) Giant aneurysm of the left ventricle after the establishment of cardiopulmonary bypass. Fig. 2 – B) Aneurismectomy performed with removal of thrombus and identification of the transition zone between the healthy myocardium and fibrotic area. Fig. 2 – C) Pericardial patch implanted in the transition zone between healthy myocardium and fibrotic area.

The patient underwent repair surgery of the left ventricle with geometric correction through a median sternotomy (video 1). Cardiopulmonary bypass (CPB) from the aorta to the right atrium was established under normothermia (Figure 2A). Myocardial protection was held with anterograde and retrograde cardioplegia under continuous normothermic esmolol, potassium, and magnesium. After incising the aneurysm (video 2) and extracting a large thrombus (video 3) measuring 8 x 3 cm (Figure 2B), a 7 x 5 cm bovine pericardial patch was placed and anchored with Teflon wires (videos 4 and 5). A transition zone was established between the healthy myocardium and an area of fibrosis (video 6) using 2.0 ethibond thereby excluding the infarcted region and a geometric correction was performed (Figure 2C). The mitral valve was competent. Cardiopulmonary bypass time was 56 minutes and the aorta was clamped for 48 minutes. The patient was weaned from the CPB with a low dose of intravenous dobutamine, which was maintained until closure of the incision. A new transesophageal echocardiography was performed and revealed a 30% (Simpson) ejection fraction; left-end diastolic volume of 138.6 cm3, and left-end systolic volume of 96.87 cm3 (Figure 3A). The patient was extubated in the operating room and transferred to the intensive care unit where he remained for 36 hours. Intraoperative blood loss was 450 ml. He was discharged 72 hours later with prescriptions for carvedilol 12.5 mg daily and acetylsalicylic acid 100 mg daily. At the one month follow-up examination, the patient was at functional class I (NYHA). He underwent an MRI that identified: ejection fraction of 41%, leftend diastolic volume of 198 ml, left ventricular systolic volume of 115 ml, and left ventricular weight of 144 gm2 (Figure 3B). DISCUSSION Although left ventricular aneurysm is a common complication following myocardial infarction, its incidence has de-

Fig. 3 – A) Postoperative transesophageal echocardiography. Fig. 3 – B) Postoperative cardiac magnetic resonance imaging.

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Schaitza GA, et al. - Surgical treatment of a giant left ventricular aneurysmA case report

clined, primarily due to the treatment of myocardial infarction with coronary angioplasty performed in the acute phase of the event. The condition can be classified as a true aneurysm when the aneurysm forms at the damaged wall of the myocardium and as a pseudoaneurysm when the cardiac rupture is contained by adherent pericardium or scar tissue[1,2]. The main complications of a left ventricular aneurysm are heart failure, ventricular arrhythmias, systemic embolization, cerebrovascular accident, and ventricular rupture. The main surgical indications occur in patients with a true aneurysm; include intractable ventricular arrhythmias and heart failure not responsive to drug treatment. Other possible indications are refractory angina and systemic embolization in patients who cannot take oral anticoagulants. In cases of pseudoaneurysm, surgical treatment is the best option, given its high probability of symptom dissolution[2,3]. Surgical techniques currently in use for correction of a left ventricular aneurysm are based on reconstruction of the left ventricle or a reduction of its volume with the goal of restoring the normal cardiac geometry[4-6]. This case exemplifies a positive outcome of surgical correction with the ventricular remodeling technique. When appropriate indications are present, the procedure can result in improved ejection fraction of the left ventricle and ventricular volume reduction.

Authorsâ&#x20AC;&#x2122; roles & responsibilities GAS JRFN JCF CPB HG BO LFM LCGS

Conception and study design, performing the procedures and/ or experiments, writing of the manuscript or review of its content Conception and study design, performing the procedures and/ or experiments Drafting of the manuscript or review of its content Drafting of the manuscript or review of its content Performing the procedures and/or experiments Performing the procedures and/or experiments Final approval of the manuscript, performing the procedures and/or experiments Final approval of the manuscript, performing the procedures and/or experiments

REFERENCES 1. Vijayvergiya R, Pattam J, Rana SS, Singh JD, Puri GD, Singhal M. Giant left ventricular pseudoaneurysm presenting with hemoptysis. World J Cardiol. 2012;4(6):218-20. 2. Inan MB, Yazicioglu L, Acikgoz B, Tasoz R, Ozyurda, U. Giant posterolateral left ventricular aneurysm diagnosed 6 weeks after incomplete surgical revascularization. Ann Thoracic Surg. 2012;93(3):980-2. 3. Antman EM, Anbe DT, Armstrong PW, Bates ER, Green LA, Hand M, et al.; American College of Cardiology; American Heart Association Task Force on Practice Guidelines; Canadian Cardiovascular Society. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction). Circulation. 2004;110(9):e82-292.

Video 1 - Giant left ventricular aneurysm before the establishment of the cardiopulmonary bypass. The aneurysm is clearly delimited by the surgeon fingers. Video 2 - The aneurysm wall is opened revealing its extension. Video 3 - A large thrombus measuring 8 x 3 cm is removed from the aneurysm wall. Video 4 - After the thrombus removal, the bovine pericardial patch was placed and anchored with Teflon wires in order to reconstruct the geometry of the ventricular wall impaired by the aneurysm formation.

4. Jatene AD. Left ventricular aneurysmectomy: resection or reconstruction. J Thorac Cardiovasc Surg. 1985;89(3):321-31. 5. Dor V, Saab M, Coste P, Kornaszewska M, Montiglio F. Left ventricular aneurysm: a new surgical approach. Thorac Cardiovasc Surg. 1989;37(1):11-9.

Video 5 - Bovine pericardial patch fully anchored to the wall.

6. Silveira Filho LM, Petrucci O, Vilarinho KA, Baker RS, Garcia F, Oliveira PP, et al. A bovine pericardium rigid prosthesis for left ventricle restoration: 12 years of follow-up. Rev Bras Cir Cardiovasc. 2011;26(2):164-72.

Video 6 - A transition zone was established with 2.0 Ethibond between the healthy myocardium and an area of fibrosis, excluding the infarcted region.

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Letters to the Editor/Cartas ao Editor

Letters to the Editor/Cartas ao Editor DOI: 10.5935/1678-9741.20140120

RBCCV 44205-1605

Comments on “Impact of type of procedure and surgeon on EuroSCORE operative risk validation”

In general, Atik and coauthors confirm with their study, as the literature reported, ES I limitations. However, it seems that the cardiac surgical community put a lot of unfulfillable expectations in the use of scoring models. We should keep in mind, that those models evaluate only the risk and not the quality of care, meaning that a surgeon should not decide about an indication for surgery based on the scoring. In addition a scoring system should be adjusted on the specific institutional needs and features in order to achieve best possible calibration and discrimination. Nevertheless the individual clinical judgment of the patient based on clinical entities and symptoms, which potentially may affect the outcome, remains the cornerstone in decision making and cannot be totally replaced by a scoring model.

Dear Editor, We read with great interest the article by Atik et al.: “Impact of type of procedure and surgeon on EuroSCORE operative risk validation”, published recently in the Brazilian Journal of Cardiovascular Surgery[1]. The issue is very relevant especially in the current era of continuous quality improvement and increasing societal demand for consistent performance assessment and monitoring. We would like to take the chance to add some thoughts about the use of risk stratification models for the prediction of hospital mortality after adult cardiac surgery. The EuroSCORE in its original version (ES I) firstly introduced in 1999[2] was a simple and easily applicable risk assessment tool adopted by many surgical units and cardiothoracic surgery societies worldwide. The system performance was highly successful for a decade, but it became less well calibrated, due to the evolution in the field of cardiac surgery, despite a constant adequate discriminatory power with an area under curve (AUC) of 0.75–0.80. To overcome this problem an updated model-version the EuroSCORE II (ES II) was presented in 2011[3]. This system resulted from a refinement and modification of some of the established risk factors and the way the model evaluates them. The series of Atik et al.[1] consists of 2,320 consecutive patients operated on between January 2006 and June 2011. Despite the fact that the study population seems to differ widely, as presented in Table 1, in crucial characteristics such as age, proportion of female patients, incidence of comorbidities, and spectrum of performed surgical procedures, from the EuroSCORE reference population, there is a certain amount of cases operated in a time period contemporary to the ES II development. However this last variable, namely the impact of the institutional cardiac surgical evolution on the EuroSCORE (including ES II), was not evaluated by the authors. In our eyes this specific study-collective structure justifies a validation of the ES II, as long as firstly there exist up to now only a few external model validation studies outside of Europe[4], and secondly the published European series partly posed concern about the predictive power of the new ES II version especially in high risk- or combined procedures patients[5].

Kyriakos Spiliopoulos, MD1; Oliver Deutsch, MD2;Walter Eichinger, MD2; Brigitte Gansera, MD2 REFERENCES 1. Atik FA, Cunha CR. Impact of type of procedure and surgeon on EuroSCORE operative risk validation. Rev Bras Cir Cardiovasc 2014;29(2):131-9. 2. Nashef SA, Roques F, Michel P, Gauducheau E, Lemeshow S, Salamon R. European system for cardiac operative risk evaluation (EuroSCORE). Eur J Cardiothorac Surg. 1999;16(1):9-13. 3. Nashef SA, Roques F, Sharples LD, Nilsson J, Smith C, Goldstone AR, et al. EuroSCORE II. Eur J Cardiothorac Surg. 2012;41(4):734-45. 4. Lisboa LA, Mejia OA, Moreira LF, Dallan LA, Pomerantzeff PM, Dallan LR, et al. EuroSCORE II and the importance of a local model, InsCor and the future SP-SCORE. Rev Bras Cir Cardiovasc 2014;29(1):1-8 5. Spiliopoulos K, Bagiatis V, Deutsch O, Kemkes BM, Antonopoulos N, Karangelis D, et al. Performance of EuroSCORE II compared to EuroSCORE I in predicting operative and mid-term mortality of patients from a single center after combined coronary artery bypass grafting and aortic valve replacement. Gen Thorac Cardiovasc Surg. 2014;62(2):103-11. Department of Cardiovascular Surgery, Klinikum München Bogenhausen GmbH, Munich, Germany Department of Thoracic and Cardiovascular Surgery. University of Thessaly (Lecturer). 2Department of Cardiovascular Surgery, Klinikum München Bogenhausen GmbH, Munich, Germany 1

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Letters to the Editor/Cartas ao Editor

DOI: 10.5935/1678-9741.20140121

RBCCV 44205-1606

the patient population is different, hospital protocols may vary among different centers, diverse surgeon’s background may influence patient’s management, regardless of strict protocols. We proved that there is significant variability in outcomes in the same hospital, using a standardized patient care, adjusting to patient’s severity. Since it is impossible to control all the issues of concern, all risk models tend to be imprecise, subject to error and less than perfect. We then totally agree with Spiliopoulos and colleagues that we, as clinicians, should be extremely careful on interpreting a patient’s condition based on a scoring model that will never replace the good individual clinical judgment, which is the foundation of our profession.

Reply to the editor on “Impact of type of procedure and surgeon on EuroSCORE operative risk validation” Dear Mr. Editor: We appreciated the thoughtful comments by Spiliopoulos et al. regarding the article entitled “Impact of type of procedure and surgeon on EuroSCORE operative risk validation”, recently published in the Brazilian Journal of Cardiovascular Surgery[1]. We agree with their comments on the relevance of this issue due to the public scrutiny and demand for increasingly better quality of care. Moreover, risk stratification models in cardiac surgery are important to adjust outcomes to certain clinical profiles, being therefore useful in patient consent, quality assurance programs, as well as being used in patient selection for controlled randomized trials. We recognized that an outdated risk model (EuroSCORE I) was used to assess hospital mortality in our study, because that was the most accepted and worldwide used system available at the time for most of the patients studied. As you stated in your letter, our study confirmed some of the limitations that have been previously shown. However, that was not our primary purpose to validate the EuroSCORE I in a Brazilian single cardiovascular surgery center, since other Brazilian cardiac surgery groups[2,3] had already done so. Certainly, we will commit to validate our results to the new EuroSCORE II system in the nearest future, in order to determine its performance on a non European population. On the other hand, the primary objective of our study was to demonstrate that, regardless of the risk stratification model used, there are unmeasured factors that significantly influence its validation and performance. Besides the fact that

Fernando A. Atik, MD; Claudio Ribeiro da Cunha, MD Instituto de Cardiologia do Distrito Federal, Brasília, DF, Brazil REFERENCES 1. Atik FA, Cunha CR. Impact of type of procedure and surgeon on EuroSCORE operative risk validation. Rev Bras Cir Cardiovasc 2014;29(2):131-9. 2. Andrade ING, Moraes Neto FR, Oliveira JPS, Silva ITC, Andrade TG, Moraes CRR. Avaliação do EuroSCORE como preditor de mortalidade em cirurgia cardíaca valvar no Instituto do Coração de Pernambuco. Rev Bras Cir Cardiovasc 2010;25(1):11-8. 3. Mejia OAV, Lisboa LAF, Puig LB, Dias RR, Dallan LA, Pomerantzeff PM, et al. Os escores 2000 Bernstein-Parsonnet e EuroSCORE são similares na predição da mortalidade no Instituto do Coração-USP. Rev Bras Cir Cardiovasc 2011;26(1):1-6.

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REVIEWERS

Reviewers RBCCV/BJCVS 29.4 Brazilian Journal of Cardiovascular Surgery/Revista Brasileira de Cirurgia Cardiovascular (BJCVS/RBCCV) is grateful for the dedicated work of the reviewers who collaborate in this edition, whose suggestions and observations are critical to maintaining the scientific level of our journal.

Domingo Braile Editor-in-Chief BJCVS/RBCCV Alexandre C. Hueb Alfredo Inácio Fiorelli Ana Paula Marques de Lima Oliveira Anderson Benício

Karlos Alexandre de Sousa Vilarinho Leonardo Andrade Mulinari Lindemberg da Mota Silveira Filho Luciano Cabral Albuquerque Luís Aberto Oliveira Dallan Luiz César Guarita Souza

Bruno da Costa Rocha Carla Tanamati

Magaly Arrais dos Santos Marcelo Matos Cascudo Marcos Aurélio Barboza de Oliveira Marden Leonardi Lopes Melchior Luiz Lima Michel Pereira Cadore Moise Dalva

Edmo Atique Gabriel Fabio Antonio Gaiotto Fabio P. Taniguchi Fernando Ribeiro Moraes Neto Frederico José Di Giovanni Gibran Roder Feguri Giovanni Dal Pogetto Molinari Guilherme Agreli

Orlando Petrucci Otoni Moreira Gomes

Hélcio Giffhorn Henrique Murad

Renato A. K. Kalil Renato Tambellini Arnoni Ricardo Ribeiro Dias Roberto Gomes de Carvalho Rodrigo Milani

Isabella Martins de Albuquerque Jarbas J. Dinkhuysen João de Deus e Brito José Glauco Lobo Filho José Maria Pereira de Godoy José Wanderley Neto

Valéria Braile Sternieri Walter José Gomes

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