29.4 OUTUBRO/DEZEMBRO 2014
REVISTA BRASILEIRA DE CIRURGIA CARDIOVASCULAR | BRAZILIAN JOURNAL OF CARDIOVASCULAR SURGERY
VOL. 29 Nº 4 OUTUBRO/DEZEMBRO 2014
Agende esta data e garanta sua presença no SBCCV 2015
Educação Médica
2
01
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
www.sbccv.org.br
www.facebook.com/SBCCV
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
4 TEMAS LIVRES
A programação, como de hábito, vai reunir especialistas de reconhecido mérito acadêmico, destacando presenças nacionais e internacionais.
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.
ORGANIZAÇÃO
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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 - Publicação online ISSN 0102-7638 - Publicação impressa RBCCV 44205
Fator de Impacto: 0,632
BRAZILIAN JOURNAL OF CARDIOVASCULAR SURGERY Rev Bras Cir Cardiovasc, (São José do Rio Preto, SP - Brasil) out/dez - 2014;29(4) 473-676
SUMÁRIO/CONTENTS 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 Normas para publicação na Revista Brasileira de Cirurgia Cardiovascular...............................................................................670 Meeting Calendar/ Calendário de Eventos......................................................................................................................................675
Impresso no Brasil Printed in Brazil
Projeto Gráfico e Diagramação: Heber Janes Ferreira Impressão e acabamento: Gráfica Pigma
Editorial
Adib Domingos Jatene (1929-2014) Adib Domingos Jatene (1929-2014)
Domingo M. Braile1 DOI: 10.5935/1678-9741.20140123
O
de Cardiologia, em Brasília, que a partir de 2015 a RBCCV/ BJCVS) será publicada exclusivamente em inglês, a língua franca das ciências nos tempos atuais. Este é um passo importante não apenas para a consolidação da nossa revista no cenário internacional, como também um incentivo para que os cirurgiões cardíacos e profissionais de áreas afins que submetem os manuscritos à RBCCV/BJCVS possam aprimorar-se no idioma inglês. Agradeço aos colegas e à Diretoria da SBCCV, pelo empenho para que esta mudança se tornasse realidade. Esta nova dinâmica também vai agilizar a disponibilização no Scielo e nas outras bases de dados, dando maior visibilidade e possibilitando que os artigos mais recentes possam ser lidos e, certamente, citados com reflexos positivos no Fator de Impacto, fato decisivo para evolução da nossa publicação no concerto das nações. Por uma questão de fluxo de trabalho, a Scielo disponibiliza a edição nos dois idiomas conjuntamente. Como a versão em português ficava pronta antes, em razão da edição impressa, ocorria um lapso de tempo grande até que as duas versões estivessem disponíveis. Embora no site próprio (www.rbccv.org.br) esse problema não ocorra, a Scielo é a responsável por distribuir os arquivos para o PubMed e essa demora acaba fazendo com que os artigos estivessem acessíveis naquela base de dados somente meses após a sua finalização, uma situação incompatível com a agilidade indispensável nestes dias de comunicação instantânea. Com relação aos manuscritos, para aqueles já enviados em português, após a aprovação para publicação, será solicitado que o autor envie a versão em inglês. Caso isso não ocorra, a versão será feita pela equipe de tradutores da RBCCV/BJCVS, com os custos sendo arcados pelos autores, conforme, já consta nas Normas aos Autores. Para que o processo possa ser ágil e a publicação ocorra em menos tempo, é fundamental que os manuscritos sejam submetidos em inglês, com qualidade compatível com os níveis internacionais da linguagem científica. Temos alguns pontos importantes a ponderar: a- Praticamente todas as revistas da nossa especialidade, mesmo as da Alemanha, França, Itália, Japão, China, Índia, Turquia etc. são publicadas em inglês. Nós não podemos ficar fora da competição, apresentando os artigos em inglês de má qualidade. b- A RBCCV/BJCVS é uma das raras revistas de acesso livre, que não cobra dos autores as altas somas praticadas pelas
Professor Adib Domingos Jatene, marco indelével de pioneirismo, honradez, sabedoria e técnica cirúrgica apurada, deixou esta vida no dia 14 de novembro. Entristeceu toda a nação brasileira, empobrecida, sem sua marcante e ilustre presença, sempre dedicada a curar os doentes do coração e as mazelas do nosso Brasil. Consternou especialmente, os cirurgiões cardiovasculares, que o têm como paradigma e mestre exemplar. Foi Presidente do Departamento de Cirurgia Cardiovascular da Sociedade Brasileira de Cardiologia; Sócio-fundador e Presidente da Sociedade Brasileira de Cirurgia Cardiovascular (SBCCV); um dos idealizadores e primeiro Editor-Chefe da Revista Brasileira de Cirurgia Cardiovascular/Brazilian Journal of Cardiovascular Surgery (RBCCV/BJCVS) nos idos de 1982, concretizando a criação da revista em 1986. Certamente, como Sócrates, o Professor Jatene não morreu! Continuará vivo em sua missão de grande médico, mestre dedicado, inventor, líder de classe, competente administrador nos mais altos cargos acadêmicos e de governo, além de cidadão exemplar. O legado deixado aos milhares de discípulos que formou, e aos amigos que tiveram o privilégio de com ele conviver ao longo dos 85 anos de sua profícua existência será eterno, pois, suas lições continuarão a ser propagadas ao longo dos tempos em um encadeamento de ideias e condutas dignas dos grandes formadores de opinião de âmbito nacional e internacional. Leia mais sobre a vida e o papel do Dr. Adib Jatene na cirurgia cardiovascular brasileira a partir da página 473. Dr. Raul Rabelo Também o Dr. Raul Correa Rabelo, de Belo Horizonte, MG, nos deixou no dia 12 de novembro, aos 68 anos. Foi uma das figuras mais marcantes da história da Cirurgia Cardiovascular Brasileira, deixando um grande legado, e um exemplo de dignidade e perseverança para todos aqueles que tiveram o privilégio de com ele conviver. Foi membro atuante do Conselho Deliberativo da Sociedade Brasileira de Cirurgia Cardiovascular nas gestões 1990-1992 e 1992-1994. RBCCV em inglês Em uma decisão histórica, os associados da SBCCV aprovaram, em assembleia realizada durante o Congresso Brasileiro
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congêneres para publicar os artigos, portanto, a colaboração dos colegas para que invistam em uma tradução de bom padrão será a garantia do sucesso da BJCVS e dos próprios pesquisadores. O Corpo Editorial manterá em seu staff de tradutores confiáveis para checarem a qualidade da linguagem. Caso seja indispensável, a tradução será rejeitada e o trabalho não será publicado, enquanto não estiver de acordo com as normas estabelecidas. Contamos com a compreensão de todos, para que o futuro do BJCVS seja de plena ascensão pela conquista de mais leitores, que divulguem nossos trabalhos em suas citações, para que não tenhamos a frustração que tivemos na última avaliação da Thomson Reuters em que nosso Fator de Impacto sofreu uma queda de 35%. c- Esperamos com estas medidas voltar a crescer acima dos níveis que já tivemos. O Corpo Editorial da RBCCV/BJCVS está à disposição para esclarecer eventuais dúvidas, por qualquer meio disponível. Não é nosso desejo prejudicar os colegas, e sim oferecer-lhes a oportunidade de contarem com um órgão de divulgação na altura da grandeza da nossa Sociedade e da Cirurgia Cardíaca brasileira.
menos conhecidas têm sido responsáveis pela publicação de artigos de grande impacto. Bohannon cita um estudo do Google Scholar (“Rise of the Rest: The Growing Impact of Non-Elite Journals”[2]), que mostra que em 1995 somente 27% das citações eram de artigos publicados em periódicos fora da “elite” (os dez periódicos mais citados). Em 2013, esta proporção subiu para 47%! Embora especialistas apontem algumas restrições ao estudo do Google Scholar, como não diferenciar os tipos de artigos, além de fatores como o crescimento do número de revistas e repositórios de acesso livre, não há como negar que esses números mostram uma tendência de mudança, que precisa ser observada. Estes fatos nos deixam muito esperançosos. Desde que assumi o cargo de Editor-Chefe da RBCCV/BJCVS, em 2002, tenho insistido na importância de ampliar os horizontes da revista. Publicando em inglês e com a tendência de descentralização do fluxo internacional dos artigos, poderemos atrair mais e melhores trabalhos, que darão a necessária visibilidade científica à nossa revista. PubMed Central A RBCCV/BJCVS superou mais uma etapa no processo de admissão ao PubMed Central. Fomos aprovados na avaliação técnica e aguardamos, agora, a análise dos documentos e do banner que enviamos para que, finalmente possamos ser aceitos nessa importante base de dados. Não há prazo para a divulgação do resultado, mas esperamos poder dar, em breve, mais uma boa notícia para nossos leitores.
Periodicidade bimestral Outra novidade é que a RBCCV vai passar de trimestral para bimestral (uma Edição a cada dois meses), mudança que tem por objetivo agilizar o fluxo dos artigos. Contando atualmente com um grande número de submissões, alguns manuscritos, após aprovados, ficam muito tempo à espera para serem publicados. Para minimizar este problema, evitando prejuízos aos autores e à própria revista, foi adotado, como em um grande número de concorrentes a publicação on-line “Ahead of Print”, disponibilizando o trabalho no nosso site (http://www. rbccv.org.br/publication-proofs) já com a atribuição do DOI que permite a prova da precedência do artigo, assim como sua citação. Mesmo assim, nosso interesse sempre foi o de publicar o maior número de trabalhos possível, o mais rápido possível. Infelizmente, as limitações de espaço e os altos custos da edição impressa (gráfica, postagem) impedem que essa ampliação ocorra, mantendo-se o número atual de edições por ano. Para termos um fluxo mais ágil, é importante que os autores e revisores cumpram rigorosamente os prazos estipulados.
CNPq Como temos feito todos os anos, solicitamos ao CNPq a concessão do Auxílio Editorial para 2015. Foi aprovada uma verba de R$ 35 mil, valor R$ 5 mil superior ao recebido em 2014. Apesar de a quantia ainda ser aquém das necessidades da revista, é importante para cobrir algumas despesas. EMC Os seguintes artigos estão disponíveis para os testes de Educação Médica Continuada (EMC) nesta edição: “Risk factors of atheromatous aorta in cardiovascular surgery” (pág. 487), “Very short cycles of postconditioning have no protective effect against reperfusion injury. Experimental study in rats” (pág. 521), “Carotid endarterectomy in awake patients: safety, tolerability and results” (pág. 574) e “Therapeutic options to minimize allogeneic blood transfusions and their adverse effects in cardiac surgery: A systematic review” (pág. 606). Lembro que o EMC, além de ser um instrumento útil para testar e atualizar os conhecimentos, vale 0,5 ponto linear na prova de Título da SBCCV, caso o candidato tenha respondido todas as questões dos testes disponíveis dos volumes 28.4 ao 29.3.
Pequenos, porém importantes O artigo “Uprising: Less prestigious journals publishing greater share of high-impact papers”, de John Bohannon[1], divulgado na Newsletter da Science, em outubro, trouxe à tona um tema pouco comentado, mas muito importante: publicações
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2015 Encerro este Editorial agradecendo aos patrocinadores, que acreditam na qualidade da revista, aos autores, aos revisores, ao Corpo Editorial e à SBCCV, que por meio de seus associados e Diretorias, sempre nos tem apoiado ao longo desses anos. A todos, Feliz Natal e um Excelente 2015! Recebam o abraço de sempre do,
REFERÊNCIAS 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-Chefe RBCCV/BJCVS 1
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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
O professor Adib Domingos Jatene, primeiro editor da Revista Brasileira de Cirurgia Cardiovascular/Brazilian Journal of Cardiovascular Surgery (RBCCV/BJCVS), marco indelével de pioneirismo, honradez, sabedoria e técnica cirúrgica apurada, deixou esta vida no dia 14 deste mês de novembro. Entristeceu toda a nação brasileira, empobrecida, sem sua marcante e ilustre presença, sempre dedicada a curar os doentes do coração e as mazelas do nosso Brasil. Certamente, como Sócrates, o Professor Jatene não morreu! Continuará vivo em sua missão de grande médico, mestre dedicado, inventor, líder de classe, competente administrador nos mais altos cargos acadêmicos e de governo, além de cidadão exemplar... O legado deixado aos milhares de discípulos que formou, e aos amigos que tiveram o privilégio de com ele conviver ao longo dos 85 anos de sua profícua existência será eterno, pois suas lições continuarão a ser propagadas no decorrer dos tempos em um encadeamento de ideias e condutas digna dos grandes formadores de opinião de âmbito nacional e internacional. Deve servir-nos de exemplo a trajetória deste profissional cujo lema foi ser útil ao próximo, sem que isto lhe custasse qualquer esforço, pois era de sua natureza o desejo de servir à nação, no melhor de sua grande capacidade realizadora. Nascido nos confins da Amazônia, no Estado do Acre, em Xapuri, ainda hoje uma fronteira da civilização no seio da intocada floresta. Fundada em 1902 por brasileiros, foi o foco da revolução da qual resultou a incorporação deste território boliviano ao Brasil. Adib era filho de imigrantes libaneses que, em busca do Eldorado, enfrentaram o desconhecido no início do Século XX, indo viver em plena selva. Seu pai, Domingos Jatene, era comerciante de borracha, o ouro branco (Látex) extraído das seringueiras nativas.
O Professor Adib Jatene operou pessoalmente mais de 20 mil pacientes.
Em uma de suas incursões pela espessa mata, voltou com febre alta e icterícia. Em poucos dias morreu! Adib tinha apenas dois anos. Lá viveu até os 10 anos, quando sua mãe, com os demais filhos, mudou-se para o Estado de Minas Gerais, na cidade de Uberlândia, onde a civilização já estava presente.
Editor-Chefe da Revista Brasileira de Cirurgia Cardiovascular E-mail: domingo@braile.com.br 2 Professor Titular de Cirurgia Cardíaca da Escola Paulista de Medicina Universidade Federal de São Paulo 1
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Esta vivência teve grande influência no caráter do jovem, marcando seu desejo de ajudar os mais necessitados. Em 1947, com o desejo de estudar engenharia ou medicina, muda-se para São Paulo a Capital do Estado. Em 1948, entra na Faculdade de Medicina da Universidade de São Paulo, que traçou sua carreira e seu destino. Era seu desejo especializar-se em Saúde Pública e voltar para a sua cidade natal no Acre. Em 1951, no quarto ano médico, começa a trabalhar no grupo do Professor Euryclides de Jesus Zerbini, um dos pioneiros da Cirurgia Cardíaca mundial. Atua como instrumentador na primeira operação para correção de Estenose Mitral digital fechada sem visão direta da lesão, apenas usando o tato, realizada pelo Professor Zerbini no Hospital das Clínicas da FMUSP. Encanta-se pela Cirurgia Cardíaca, abandona a ideia de especializar-se em Saúde Pública e voltar para o Acre! Forma-se médico em 1953, aos 23 anos. Faz especialização sob orientação de Zerbini em 1954. Casa-se com a nutricionista Aurice Biscegli Jatene. Muda-se para Uberaba em 1955, como Professor de Anatomia Topográfica e Cirurgião Cardiotorácico.
ciação naqueles anos. Era admirado por seus assistentes, entre eles o Professor E.J. Zerbini e o Professor Adib Jatene, seus substitutos na evolução de suas brilhantes carreiras. Com o apoio integral deste eminente Professor, Zerbini, com grande espirito cívico e ideias próprias a respeito de invenções e inovações, estimulava seus assistentes a criar equipamentos para a Cirurgia Cardíaca, aqui no Brasil. Com esta visão, criou-se no Hospital das Clínicas da Universidade de São Paulo uma Oficina para iniciar esta caminhada rumo ao futuro. Recebeu o nome pomposo de: “Oficina do Coração Artificial”. Mostrando seu pendor pela construção de equipamentos, o Professor Adib demonstrou toda sua capacidade desenvolvendo aperfeiçoadas Máquinas de CEC, oxigenadores, trocadores de calor, termômetros etc. suprindo as necessidades não só do Brasil, como também de nações da América do Sul. Alguns modelos foram enviados para a Europa, com grande aceitação. O Professor Adib Jatene foi fundamental na evolução do grupo de Cirurgia Cardíaca do Hospital das Clínicas entre 1957 e 1961, quando transferiu-se para o incipiente “Instituto de Cardiologia do Estado de São Paulo”, uma instituição governamental dirigida por um cardiologista avançado para o tempo: Professor Dante Pazzanese, pioneiro em variados campos da especialidade. Com muita justiça, hoje o Instituto leva seu nome. Na nova casa, Jatene desenvolveu toda sua criatividade e competência como exímio cirurgião, formador de discípulos brilhantes e criador de muitos insumos importantes para o desenvolvimento da Cirurgia Cardíaca, que avançava a largos passos para sua consolidação. Nesta época de grandes desafios, Jatene criou já em 1962 outra oficina para produzir equipamentos: Oficina Experimental, precursora da Fundação Adib Jatene (1984). Apenas como exemplo, citamos algumas das conquistas desta instituição: Válvulas Cardíacas artificiais, tipo Starr Edwards, apenas dois anos após a original ser desenvolvida. Foi usada por muitos anos, com desempenho até melhor que as importadas. Desfibriladores; Marca-Passos, que nos permitiram avançar neste campo sem qualquer atraso em relação aos países desenvolvidos. Máquinas de CEC, com incorporações tecnológicas importantes em relação às primitivas; Oxigenadores de Bolhas, concêntricos, compactos em aço inoxidável. Com o advento das membranas ocas, desenvolveu o primeiro oxigenador brasileiro de membrana, comercializado em todo o mundo por uma empresa nacional. Outros equipamentos foram somando-se a estes, alguns mais simples, como aspiradores de vários tipos e modelos, assim como instrumentos cirúrgicos não existentes no país. Desenvolveu uma válvula de disco basculante da qual resultou uma patente internacional. Desde os primórdios, o Professor Jatene investiu na pesquisa de corações mecânicos artificiais, implantáveis, ideia que nunca abandonou, até os últimos dias de sua vida, em
Dr. Adib Jatene e esposa Aurice, companheira de todas as horas por mais de meio século. Dotado de grande habilidade, frequenta uma oficina mecânica, impressionando os seus “mestres” pela facilidade com que, usando as ferramentas adequadas, fabricava produtos para a cirurgia. Foi assim que desenvolveu uma máquina de circulação extracorpórea e um oxigenador de discos, com os quais fazia cirurgias cardíacas experimentais em cães. Estava adiante de seu tempo! Em 1957, o Professor Zerbini, intuindo o potencial de Jatene, convida-o para voltar ao Hospital das Clínicas da FMUSP, agora como seu assistente. O ambiente era efervescente na 1ª Clínica Cirúrgica, cujo Catedrático era o emblemático Professor Alípio Corrêa Netto, humilde em sua grandeza, imune à inveja, foi criador de um grande número de especialidades, que iniciavam sua diferen-
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que trabalhava (sempre acompanhado dos melhores técnicos e engenheiros) no aperfeiçoamento de mais um modelo incorporando avanços técnicos apreciáveis. Os últimos modelos foram implantados em bezerros, mostrando performance adequada. Pode parecer que seja exagero salientar estas qualidades de um cirurgião do quilate do Professor Jatene, mas isto fez toda a diferença para o desenvolvimento da Cirurgia Cardíaca do Brasil, hoje com 200 centros e 100 mil operações por ano, cobrindo de norte a sul e de leste a oeste todo o território nacional. Não foi o que ocorreu na maior parte dos países em desenvolvimento, que preferiram importar os equipamentos. Isto fez toda a diferença, representando o embrião da indústria brasileira na área cardiovascular, que além de suprir o mercado nacional, exporta para muitos países, criando empregos de qualidade. A ligação do Professor Adib com a Universidade nunca deixou de existir. No ano de 1983, com a aposentadoria do seu mestre, o Professor Zerbini, Jatene vence memorável concurso e tornase Professor Titular de Cirurgia Cardiotorácica da venerável instituição de ensino, agora dotada em uma moderna unidade, o INCOR, com mais de 600 leitos e equipamentos de última geração, exclusivamente dedicada ao ensino, pesquisa e tratamento, clínico e cirúrgico de cardiopatas. Jatene, como sempre, destacou-se neste novo desafio, implementando sua maneira de trabalhar por resultados. Foi Diretor da Faculdade de Medicina no período de 1990 a 1994, cargo de alta relevância para um professor com tantos méritos. Aposentou-se do INCOR e da USP em 1999, como Professor Emérito, após ter-se dedicado à sua alma mater durante 16 anos! A aposentadoria pouco significou com relação à atividade cirúrgica de Jatene. Além de todos os afazeres em organizações governamentais públicas, o Professor Adib a convite da Associação do Sanatório Sírio, em 1986 assume o cargo de seu Diretor. Hoje, o HCor é um grande complexo hospitalar, com especial foco na Cirurgia Cardíaca. Jatene continuou atuando como Cirurgião neste Hospital, sem fins lucrativos, que permitiu-lhe manter-se em plena atividade até 2014, juntamente com seus filhos Cirurgiões Cardíacos como ele: Fábio Jatene, Professor Titular do Universidade de São Paulo (INCOR), Marcelo Jatene, Professor Associado, responsável pela Cirurgia Cardíaca Infantil, também na Universidade de São Paulo (INCOR) e sua filha Ieda Jatene, Cardiologista Pediátrica. Em sua profícua existência, o Professor Jatene operou pessoalmente mais de 20 mil pacientes e, sob sua liderança, as equipes que comandou operaram mais de 100 mil cardiopatas. É autor e coautor de cerca de 800 trabalhos científicos, publicados na literatura nacional e internacional. Na seara cirúrgica, Jatene teve contribuições impactantes: Em 1962, implantou a primeira válvula aórtica fabricada no Brasil.
Dr. Adib Jatene e seus filhos, cirurgiões cardíacos como ele, Fábio, Ieda e Marcelo. Em 1970, fez a primeira Revascularização do Miocárdio, tendo tido uma contribuição conspícua neste campo. Em 8 de maio de 1975, Jatene surpreendeu o mundo científico por ter operado o primeiro paciente com uma nova técnica por ele descrita: Correção Anatômica da Transposição das Grandes Artérias". Tornou-se conhecida como “Operação de Jatene”. Esta pioneira técnica foi responsável pelo advento de uma nova subespecialidade: A Cirurgia Cardíaca de Neonatos, com todo cabedal da sua complexidade durante o ato cirúrgico e do pós-operatório, propiciando maior desenvolvimento das Unidades Cirúrgicas de Cuidados Intensivos especializadas em neonatos. A subespecialidade cristalizou novos especialistas: Cirurgiões Cardíacos e Neonatologistas Infantis, com formação específica na área. Hoje, milhares de pacientes beneficiam-se desta operação e destas conquistas, que devolvem a anatomia cardíaca a neonatos gravemente enfermos. Em 1984, recebeu o prestigioso Título de "Honorary Member of American Association for Thoracic Surgery”. Em 1985 foi “Honorary Guest” da American Association for Thoracic Surgery. Nessa ocasião, apresentou o trabalho sobre reconstrução do Ventrículo Esquerdo em pacientes com Aneurisma Ventricular. Esta técnica foi inovadora neste campo e no conceito de reconstrução ventricular para o tratamento dos aneurismas e da Insuficiência Cardíaca. ATIVIDADE ASSOCIATIVA 1981 - Presidente do Departamento de Cirurgia Cardiovascular da Sociedade Brasileira de Cardiologia; 1984 - Sócio-fundador e primeiro Presidente da Sociedade Brasileira de Cirurgia Cardiovascular; 1985 - Presidente da Sociedade Brasileira de Cardiologia; 1986 - Presidente da “International Society for Cardiovascular Surgery”; 1986 - Primeiro Editor da Revista Brasileira de Cirurgia Cardiovascular/Brazilian Journal of Cardiovascular Surgery.
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PRÊMIOS E COMENDAS 1989 - Membro Titular da Academia Nacional de Medicina; 1998 - “Honorary Fellow” da American Surgical Association; 2002 “Honorary Felloswship” da European Association for Cardio- Thoracic Surgery; 2003 - "Golden Hippocrates International Prize for Excellency in Medicine", pelo Horev Medical Center (Haifa-Israel) 2003 - Prêmio "Talal El Zein" pela Mediterranean Association of Cardiology and Cardiac Surgery; 2006 - Prêmio "Fundação Conrado Wessel de Medicina 2005"; 2007 - "Seven Wise Men of the World in Cardiovascular Surgery”; 2008 Prêmio Medalha do Conhecimento, Categoria Gestores/Pesquisadores pelo Ministério do Desenvolvimento, Indústria Comércio Exterior; 2011 - "Bakulev Award for Cardiovascular Surgery” (Moscou); 2012 - “Comenda Sérgio Arouca” pelo desempenho ético e compromisso social com a Medicina. Membro de 32 Sociedades científicas de várias regiões do mundo. Recebeu 178 Títulos e Honrarias de vários países, dos quais citamos apenas os principais.
Dr. Adib Jatene e Aurice durante homenagem.
LIVROS PUBLICADOS - 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. VIDA PÚBLICA Acreditando no alcance da Saúde Pública, mesmo apolítico, assumiu Cargos de Governo. 1979-1982 - Secretário Estadual da Saúde do Estado de São Paulo, no Governo de Paulo Maluf. Projetou 490 Centros de Saúde e 40 Hospitais para a Grande São Paulo. 1992 - Ministro da Saúde na gestão Presidente Fernando Collor de Mello. 1996 a 1998 - Ministro da Saúde na gestão Presidente Fernando Henrique Cardoso.
Dr. Fábio Jatene e Aurice Biscegli Jatene: família unida.
Pela sua origem amazônica, trazia grande amor pela terra, gostava imensamente das fazendas que possuía, dedicando-se a culturas das mais variadas. Tinha maior predileção pela pecuária, sendo um criador de primeira grandeza, bastante premiado pelos seus rebanhos de gado Nelore, do qual era também um interessado conhecedor da progenie e das características fenotípicas.
ATIVIDADES PESSOAIS Quando jovem, Adib foi um bom esportista. Durante a faculdade era muito requisitado para as disputas da famosa Mac-Med, uma competição, agora centenária, entre o Mackenzie e a Medicina da USP. Destacava-se em vários esportes, especialmente no remo, em competições no Rio Tietê. Continuou a exercitar-se durante toda a vida. Tinha também sensibilidade artística, sendo apreciador principalmente dos artistas da Semana da Arte Moderna, como: Di Cavalcanti, Alfredo Volpi e Tarsila do Amaral, entre muitos outros que adornavam sua bem selecionada coleção.
ADIB JATENE PENSADOR FRASISTA ● "Eu sou contra essa história de dizer: - Eu não faço por que não me dão condições. Se você é capaz de fazer você cria as condições." ● "Eu nunca discuto problema, tem gente que se perde na discussão do problema. Eu só discuto solução."
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Braile DM & Buffolo E - Adib Jatene: June 4, 1929/November 14, 2014
● "O segredo é descobrir o jeito. E pesquisa é descobrir o jeito."
Marcelo, Ieda (médicos) e Iara (arquiteta), genros e noras, dez netos e quatro bisnetos.
● “O que mata não é o trabalho, e sim a raiva!” ● "Inveja, vaidade excessiva e nervosismo fazem mal ao coração" ● “Nunca me queixo. O presente é fantástico” ● “O papel do médico é amenizar o sofrimento e a aflição das pessoas. Nessa profissão, os valores universais, como fé, amor e solidariedade, devem estar acima dos interesses particulares.” ● “O maior problema do pobre é só conhecer pobres. Não tem ninguém por Eles!” Deixa uma família exemplar: Sua esposa Aurice (nutricionista), quatro filhos: Fábio,
Os filhos Ieda, Marcelo e Fábio (médicos) e Iara (arquiteta).
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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 do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo InCor-HCFMUSP, São Paulo, SP, Brasil. 2 Museu Anátomo Cirúrgico do Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo InCor-HCFMUSP, São Paulo, SP, Brasil. 3 Departamento de Patologia do Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo InCor-HCFMUSP, São Paulo, SP, Brasil.
Endereço para correspondência: 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, Brasil - CEP: 05403-000 E-mail: moise.dalva@gmail.com
Descriptors: Heart. Mitral Valve. Tricuspid Valve. Cardiomyopathy, Dilated.
1
Não houve suporte financeiro.
Trabalho realizado no Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo InCor-HCFMUSP, São Paulo, SP, Brasil.
Artigo recebido em 29 de dezembro de 2013 Artigo aprovado em 16 de março de 2014
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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.
Abreviações, acrônimos e símbolos AVD AVE CAPPesq CMD CMDId CMDIsq DistAV-AP DP FMUSP HC-FMUSP HE ICC INCOR ISFC MAGPs MMPs RFO SPSS SVOC USA WHO
Anel atrioventricular direito Anel atrioventricular esquerdo Comissão de Ética para Análise de Projetos de Pesquisa Cardiomiopatia dilatada Cardiomiopatia dilatada idiopática Cardiomiopatia dilatada isquêmica Distância do sulco atrioventricular até o ápice ventricular esquerdo Desvio padrão Faculdade de Medicina da Universidade de São Paulo Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo Hematoxilina-Eosina Insuficiência cardíaca congestiva Instituto do Coração International Society and Federation of Cardiology Microfibrilas associadas às glicoproteínas Metaloproteinases Resorcina-Fuccina de Weigert com oxidação prévia por oxona Statiscal package for the social sciences Serviço de verificação de óbitos da Capital United States of America 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.
INTRODUÇÃO
de capital importância[1], porém apesar deste fato relevante o mecanismo de dilatação anular ainda não está completamente esclarecido[2-4]. A presença de insuficiência valvar pode contribuir para aumento da morbidade em pacientes valvopatas[5] ou que possuam CMD das mais diversas etiologias[6]. Existe uma tendência em considerar os tecidos valvares como inertes, em virtude da sua estrutura histológica simples e população celular esparsa, porém, tal fato parece menos razoável à luz da enorme carga mecânica imposta a essas estruturas ao longo da vida e a consequente necessidade de manutenção de sua integridade tecidual a custa de equilíbrio entre a produção de colágeno e sua degradação[7]. Embora a presença de miócitos e a circulação coronária sejam capitais para o funcionamento do coração como bomba, os elementos que compõem a matriz extracelular (MEC), particularmente as fibras colágenas dos tipos I e III são reconhecidos como fundamentais para a manutenção do ciclo cardíaco[8]. Dentre suas inúmeras funções, as mais importantes são a de fornecer arcabouço estrutural para os miócitos e vasos, bem como prover o órgão de propriedades de resistência e resiliência, proporcionando tônus sistólico e diastólico, ajudando o coração a manter sua conformação[8-12].
A insuficiência cardíaca congestiva (ICC) é entidade causadora de grande impacto em termos de morbimortalidade, sendo sua principal etiologia as cardiomiopatias dilatadas (CMD), que em suas diversas etiologias, constituem-se em grave problema de saúde pública, com prevalência estimada de 4-8 casos por 100.000 pessoas por ano e com incidência estimada de 36,5 por 100.000 pessoas[1]. O aspecto fisiopatológico determinante de tais entidades é a grave disfunção sistólica causada pela perda da eficiência do coração em agir como bomba hidráulica. Embora o componente miocelular esteja presente de forma importante, outros mecanismos tais como o remodelamento ventricular e a ativação do sistema renina-angiotensina-aldosterona são fatores contribuintes para perpetuação do quadro[1]. O remodelamento ventricular caracterizado por alterações morfogeométricas tanto à direita quanto à esquerda, propicia ciclo vicioso de deterioração funcional, uma vez que o coração perde a conformação anatômica original, fundamental para sua eficiência. Neste contexto, a insuficiência valvar causada primariamente por dilatação dos anéis atrioventriculares é
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O desarranjo destas fibras pode eventualmente persistir mesmo após a remoção da doença de base em diversas situações. Em pacientes portadores de patologia da valva mitral com insuficiência tricúspide secundária, pode não haver normalização do fluxo regurgitativo tricúspide mesmo com a correção da patologia mitral[13]. Este fato suscita controvérsia na literatura sobre a real necessidade da realização de plastia do anel valvar tricúspide quando este está secundariamente dilatado[13], e em que medida a não normalização do refluxo pode estar associada à alterações histológicas irreversíveis no anel atrioventricular. Tal fato se reveste de capital importância, haja vista o fato de que cerca de metade dos pacientes portadores de doenças da valva mitral com indicação cirúrgica apresenta insuficiência tricúspide significativa[14]. Os autores que advogam a não realização da plastia insistem no fato que a correção da lesão mitral leva à normalização da pós-carga do ventrículo direito por diminuição da pressão do leito vascular pulmonar[15]. Em contraste, aqueles que advogam a realização de plastia do anel tricúspide sustentam o fato de que a dilatação do anel pode não ser naturalmente reversível em casos avançados, a despeito da correção total da valva mitral[16,17]. Tal fato poderia, eventualmente, ocorrer devido a alterações estruturais microscópicas do anel atrioventricular com ocorrência de colagenólise e substituição das fibras de colágeno por tecido de outra natureza, com comprometimento de sua integridade. O conceito anatômico de que o esqueleto fibroso do coração não se dilata foi refutado[2,3,18], sendo comprovado o seu alargamento nos casos de insuficiência cardíaca grave causada por cardiomiopatia dilatada de etiologia isquêmica (CMDIsq) ou idiopática (CMDId) não chagásica[2,3]; porém, não existe na literatura estudo histológico comparativo dos anéis atrioventriculares direito e esquerdo nos casos de CMDId à luz deste novo conceito. Ao mesmo tempo, o conhecimento disponível acerca do papel exercido pela MEC em termos de controle e regulação deste processo ainda é escasso, de modo que existe vasto campo de pesquisa a ser desenvolvido nesta área.
Material Foram estudados espécimes de corações normais e dilatados. Os normais foram provenientes do Serviço de Verificação de Óbitos da Capital (SVOC-USP), e os dilatados foram provenientes do Laboratório de Anatomia Patológica do Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (InCor-HCFMUSP). Foram selecionados 26 espécimes agrupados da seguinte forma: Grupo 1 – (CMDId) Composto de 13 corações portadores de CMDId Grupo 2 – (NORMAL) Composto de 13 corações provenientes de indivíduos isentos de cardiomiopatia e considerados normais Após sua obtenção, as peças foram fixadas em formol, com posterior retirada dos grandes vasos e dos átrios, permanecendo apenas os anéis atrioventriculares e a massa ventricular. Após as etapas de preparo e fixação das peças, foram realizadas secções transversais da massa ventricular, partindo-se do sulco atrioventricular em direção ao ápice do coração (DistAV-AP). As secções transversais foram realizadas em nível correspondente a 80% (basal), 50% (equatorial) e 20% (apical) desta distância, sendo a seguir fotografadas com câmera digital (Sony, modelo Cyber Shot DSC W 200) que foi fixada em uma mesa por meio de uma estativa distando 15 cm das peças. As imagens obtidas foram transferidas para um computador onde foram realizadas as mensurações com o software Image Tool, (Department of Dental Diagnostic Science of the University of Texas Health Science Center, San Antonio, USA). Todas as peças foram fotografadas ao lado de uma régua que serviu de referência para as mensurações. Após a realização das fotografias, os anéis atrioventriculares direito e esquerdo foram completamente dissecados, porém não foram separados, mantendo-os unidos pelo corpo fibroso central. Os anéis foram acomodados em caixetas e enviadas ao serviço de patologia, sendo a seguir parafinados e laminados, sendo realizados cortes histológicos de 5 micrometros de espessura e empregados os seguintes métodos de coloração: • Hematoxilina-Eosina (H.E.) – Coloração padrão nos serviços de anatomia patológica, sendo utilizada para identificação de artefatos técnicos e alterações histopatológicas que eventualmente pudessem comprometer análise pelos demais métodos. • Picrossírius - Coloração utilizada para estudo de fibras colágenas. • Resorcina-Fuccina de Weigert com oxidação prévia por oxona (RFO)- Coloração utilizada para estudo de fibras elásticas. A análise morfométrica quantitativa foi realizada por meio de análise digital de imagens com utilização de sistema composto por microscópio óptico Leyca DMR (Leyca Microsystems Wetzlar Gmb H, Alemanha) conectado a um computador por uma câmera de vídeo.
Objetivo Os objetivos do presente estudo são: 1-Avaliar comparativamente os perímetros dos ventrículos direito e esquerdo em diferentes segmentos e dos anéis atrioventriculares direito e esquerdo nos corações normais e portadores de CMDId. 2-Comparar a porcentagem por área de fibras colágenas e elásticas dos anéis atrioventriculares direito e esquerdo entre os corações normais e portadores de CMDId. MÉTODOS O projeto deste estudo foi inicialmente submetido e aprovado pela Comissão de Ética da Instituição.
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Os cortes histológicos dos anéis atrioventriculares direito e esquerdo foram fotografados em 15 pontos escolhidos aleatoriamente em um aumento de 100 vezes, e as imagens capturadas foram analisadas com a utilização do software Image Pro Plus versão 4.1 (Media Cybernetics – Silver Spring, MD, USA), que quantifica a área ocupada por fibras e depois quantifica a área total, sendo possível calcular a porcentagem de fibras colágenas e elásticas de cada ponto fotografado. Para cada anel, foi utilizada a média das porcentagens de fibras dos quinze pontos fotografados. Após obtenção dos dados macroscópicos, foram realizadas comparações das médias dos perímetros de cada segmento ventricular (Apical, Equatorial e Basal) entre os grupos CMDId e NORMAL dos ventrículos direito e esquerdo, bem como comparações das médias dos perímetros ventriculares entre cada segmento (Apical, Equatorial e Basal) dentro de cada grupo (CMDId e NORMAL). Os perímetros dos anéis atrioventriculares direito e esquerdo também foram comparados. Com relação aos dados microscópicos, foram realizadas comparações das médias das porcentagens por área das fibras colágenas e elásticas dos anéis atrioventriculares direito e esquerdo entre cada grupo (CMDId e NORMAL). Com relação à estatística, as análises descritivas foram realizadas, apresentado médias acompanhadas dos respectivos desvios padrão (±DP) e valores mínimos e máximos. Os pressupostos da distribuição normal em cada grupo e a homogeneidade das variâncias entre os grupos foram ava-
liados, respectivamente, com o teste de Shapiro-Wilk e com o teste de Levene. A análise inferencial para os perímetros ventriculares foi realizada utilizando-se a análise de variância (ANOVA) de medidas repetidas para comparação das médias de cada segmento entre os grupos (fator intergrupos). O teste t foi utilizado para avaliar os perímetros médios dos anéis atrioventriculares direitos e esquerdos e as porcentagens médias de fibras elásticas e colágenas dos anéis. As análises estatísticas descritivas e inferenciais foram executadas com o software SPSS versão 13 (SPSS 13.0 for Windows). RESULTADOS Um dos objetivos foi avaliar os perímetros dos ventrículos direito e esquerdo (segmento apical, equatorial e basal) para cada grupo (CMDId e NORMAL), porém, o ponto para secção do segmento apical (20%) não abrangeu a cavidade ventricular direita dos corações dos grupos CMDId e NORMAL na maioria dos casos. Assim, nos ventrículos direitos dos corações dos grupos CMDId e NORMAL, foram analisados apenas os perímetros dos segmentos equatorial e basal. Os resultados descritivos para as variáveis perímetros dos ventrículos direito (segmentos equatorial e basal) e esquerdo (segmentos apical, equatorial e basal) para cada grupo, estão apresentados nas Tabelas 1 e 2 e os resultados descritivos para as variáveis perímetros dos anéis atrioventriculares direito e esquerdo para cada grupo estão apresentados nas Tabelas 3 e 4.
Tabela 1. Medidas descritivas das variáveis perímetro equatorial e basal nos grupos CMDId e NORMAL (mm) ventrículo direito. Grupos CMDId
NORMAL
Segmento Equatorial
N 13
Média 170,812
Desvio Padrão 44,60938
Mínimo 84,36
Máximo 242,99
Basal
13
223,339
29,03743
190,58
287,34
Equatorial
13
112,66
20,58866
74,78
142,72
Basal
13
173,38
24,82283
123,59
216,54
CMDId=Cardiomiopatia dilatada idiopática
Tabela 2. Medidas descritivas das variáveis perímetro apical, equatorial e basal nos grupos CMDId e NORMAL (mm) ventrículo esquerdo. Grupos CMDId
NORMAL
Segmento Apical Equatorial Basal
N 13 13 13
Média 101,5862 191,3458 181,9777
Desvio Padrão 38,23844 30,37638 35,22137
Mínimo 56,34 146,81 140,39
Máximo 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
CMDId=Cardiomiopatia dilatada idiopática
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Os resultados descritivos para as variáveis porcentagens por área de fibras colágenas dos anéis atrioventriculares direito e esquerdo para cada grupo estão apresentados nas Tabelas 5 e 6, e os resultados descritivos para as variáveis porcentagens por área de fibras elásticas dos anéis atrioventriculares direito e esquerdo para cada grupo estão apresentados nas Tabelas 7 e 8. Na análise de comparação de médias dos perímetros ventriculares direitos dos segmentos equatorial e basal entre os grupos NORMAL e CMDId, foram encontradas diferenças estatisticamente significantes (P<0,05) em todos os segmentos estudados. Na análise de comparação de médias dos perímetros dos anéis atrioventriculares direitos entre os grupos CMDId e NORMAL, foi encontrada diferença estatisticamente significante (P<0,05). Na análise de comparação de médias dos perímetros ventriculares esquerdos dos segmentos apical, equatorial e basal entre os grupos CMDId e NORMAL, foram encontradas
diferenças estatisticamente significantes (P<0,05) em todos os segmentos. Os resultados do teste Post-Hoc com correção de Bonferroni para comparações múltiplas evidenciaram diferenças estatisticamente significantes para todas as comparações, exceto com relação à comparação entre perímetros ventriculares equatoriais e basais. Na análise de comparação de médias dos perímetros dos anéis atrioventriculares esquerdos entre os grupos CMDId e NORMAL, não foi encontrada diferença significativamente estatística (P>0,05). Na análise de comparação de médias das fibras colágenas dos anéis atrioventriculares direitos e esquerdos entre os grupos CMDId e NORMAL, foi encontrada diferença estatisticamente significante (P<0,05). Na análise de comparação de médias das fibras elásticas dos anéis atrioventriculares direitos e esquerdos entre os grupos CMDId e NORMAL, não foi encontrada diferença estatisticamente significante (P>0,05).
Tabela 3. Medidas descritivas da variável perímetro anel AVD nos grupos CMDId e Normal (mm). Grupos CMDId NORMAL
N 13 13
Média 120,1915 104,0046
Desvio Padrão 15,33305 13,88195
Mínimo 94,85 75,77
Máximo 141,78 128,89
AVD=Anel atrioventricular direito; CMDId=Cardiomiopatia dilatada idiopática Tabela 4. Medidas descritivas da variável perímetro anel AVE nos grupos CMDId e Normal (mm). Grupos CMDId NORMAL
N 12 13
Média 108,3233 97,2723
Desvio Padrão 13,76889 16,40091
Mínimo 87,35 69,02
Máximo 128,01 118,09
AVE=Anel atrioventricular esquerdo; CMDId=Cardiomiopatia dilatada idiopática Tabela 5. Medidas descritivas da variável fibras colágenas do AVD nos grupos CMDId e NORMAL (percentual). Grupos CMDId NORMAL
N 13 13
Média 19,2332 38,5756
Desvio Padrão 14,19502 21,51783
Mínimo 1,51 13,43
Máximo 60,73 88,89
AVD=Anel atrioventricular direito; CMDId=Cardiomiopatia dilatada idiopática Tabela 6. Medidas descritivas da variável fibras colágenas do AVE nos grupos CMDId e NORMAL (percentual). Grupos CMDId NORMAL
N 13 13
Média 22,0962 38,4603
Desvio Padrão 12,85746 14,75941
Mínimo 1,44 14,85
Máximo 59,55 59,55
AVE=Anel atrioventricular esquerdo; CMDId=Cardiomiopatia dilatada idiopática Tabela 7. Medidas descritivas da variável fibras elásticas do AVD nos grupos CMDId e NORMAL (percentual). Grupos CMDId NORMAL
N 13 13
Média 19,5032 17,5873
Desvio Padrão 11,33865 13,42513
AVD=Anel atrioventricular direito; CMDId=Cardiomiopatia dilatada idiopática
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Mínimo 8,12 0,29
Máximo 45,4 43,46
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Tabela 8. Medidas descritivas da variável fibras elásticas do AVE nos grupos CMDId e NORMAL (percentual). Grupos CMDId NORMAL
N 13 13
Média 21,0929 18,1184
Desvio Padrão 11,16968 13,63213
Mínimo 7,13 1,26
Máximo 43,78 50,78
AVE=Anel atrioventricular esquerdo; CMDId=Cardiomiopatia dilatada idiopática
DISCUSSÃO
Embora as alterações da MEC miocárdica já tenham sido investigadas nos casos de CMDId, dois fatores permanecem incógnitos, quais sejam a eventual alteração da composição histológica da MEC dos anéis atrioventriculares direito e esquerdo e o comportamento das fibras colágenas em termos de balanço entre sua produção, degradação e organização. Tais fatos motivaram a realização do presente estudo. Do ponto de vista macroscópico, notou-se que existe dilatação de ambos os ventrículos no grupo CMDId, embora com morfologia distinta, uma vez que a dilatação do AVD acompanha a dos segmentos ventriculares equatorial e basal, ao contrário do que acontece no AVE, que não apresentou dilatação significativa em relação ao grupo normal, apesar de ter havido dilatação dos segmentos equatorial e basal a esquerda. Em relação ao AVE, tais achados confirmam os resultados de Juliani[22] e de Hueb et al.[2,3], que afirmam não ser o grau de dilatação do ventrículo esquerdo que determina o grau de dilatação do anel mitral, pois eles ocorrem de maneira independente. Tal afirmação sempre foi motivo de controvérsias na literatura. Em estudo que analisou a medida do AVE em 102 corações, 78 dos quais possuíam dilatação ventricular esquerda, Bulkley & Roberts[23] concluem que a dilatação do ventrículo esquerdo isolada raramente causa insuficiência da valva atrioventricular esquerda. Citam que a afirmativa em contrário foi por muito tempo tida como verdade, como postulavam grandes nomes da cardiologia, como Flint e Osler em livros datados do final do século XIX. A associação de insuficiência da valva atrioventricular esquerda aumenta a morbimortalidade dos pacientes portadores de ICC causada por CMDId[1]. Embora frequentemente tida como secundária apenas ao remodelamento ventricular, sendo portanto classificada como “funcional”, estudos recentes indicam que possivelmente existam componentes intrínsecos a estrutura valvar como um todo que atuando de forma distinta podem ser os responsáveis pela insuficiência observada[4,6]. Os folhetos valvares, embora considerados como sendo apenas inertes, em virtude de aparentemente não estarem comprometidos nos casos de CMDId, ao contrário do que acontece em outras formas de regurgitação valvar, possuem características próprias que devem ser levadas em consideração, tais como inervação aferente e eferente, propriedades contráteis intrínsecas, e orientação espacial das fibras colagênicas que permite ótima distribuição da tensão mecânica, de forma que o remodelamento dos folhetos possivelmente exerce um papel intrínseco na gênese da insuficiência valvar, conforme demonstrado por Timek et al.[4], em estudo experimental rea-
O entendimento médico sobre a ICC evoluiu de forma notável desde os primeiros registros desta entidade, que podem ser rastreados em escritos atribuídos a Hipócrates, sendo possível identificar sua evolução histórica, que progrediu em simetria com o avanço do conhecimento científico[19]. Do ponto de vista funcional, ocorre perda da função de bombeamento com dissipação energética, fato derivado de mecanismos como aumento da massa cardíaca, dilatação dos ventrículos, presença de trombos nas câmaras cardíacas e dilatação dos anéis atrioventriculares[1]. A MEC teve seu papel revisado na gênese das CMDId. Inicialmente, seus componentes eram tidos como parte de suporte passivo no qual os miócitos se entrelaçam, porém estudos recentes apontam para o fato de que tais componentes exercem papel ativo em todas as fases do ciclo cardíaco normal, pois conferem ao coração propriedades fundamentais tais como resistência, resiliência e elasticidade, com consequente alteração destas características no ciclo cardíaco patológico, cuja principal característica é o remodelamento ventricular, que pode ser observado em nível macroscópico e microscópico[8,20]. O colágeno miocárdico normal é composto predominantemente pelos tipos I (que corresponde a cerca de 80% da massa colagênica total) e III, que formam uma rede estrutural tridimensional que inclui as valvas, cordas tendíneas e os componentes colagênicos perivascular e intersticial, o qual se organiza em feixes. Denominados epimísio (que cobre cada fibra, muscular individualmente), perimísio (que cobre grupos de miócitos) e endomísio (encontrado entre cada miócito)[8]. Com relação ao comportamento das fibras colágenas nas cardiomiopatias, os estudos mostram resultados conflitantes, podendo haver aumento[21] ou diminuição[20] do componente colagênico, bem como desarranjo de sua estrutura normal. Weber et al.[8], em estudo histológico que analisou três corações de pacientes que morreram devido à CMDId, relataram que houve diminuição do colágeno tipo I (mais resistente) e aumento do colágeno tipo III (menos resistente) em relação ao padrão normal, bem como perda da arquitetura funcional normal das fibras colagênicas. Postularam que o aumento do colágeno menos resistente é o provável responsável pelo mecanismo de remodelamento, com diminuição da eficiência contrátil. Tal discrepância de resultados parece estar relacionada em parte à metodologia utilizada e em parte devido ao fato de que o colágeno pode assumir formas distintas em se tratando do colágeno miocárdico normal ou de fibrose.
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lizado com ovelhas. Tal fato vem de encontro aos resultados observados em nosso estudo, uma vez que não foi observada dilatação estatisticamente significante do AVE, o que parece corroborar o fato de que não é apenas a possível dilatação do anel que causa a insuficiência O fato de ter havido dilatação estatisticamente significativa do AVD pode estar eventualmente associado à ausência de anel colagenoso completo em torno do orifício atrioventricular direito, ao contrário do que ocorre do lado esquerdo, onde tal orifício é efetivamente circundado por forte anel colagenoso, o que poderia diminuir a propensão para a dilatação anular. Segundo Juliani[22] ocorre dilatação transversal ventricular esquerda na CMDId, sendo esta majoritariamente causada por alterações nos segmentos basal e equatorial. O fato de não ocorrer dilatação do AVE pode ser componente significativo no processo de remodelamento ventricular, pois anatomicamente o anel é parte do ventrículo que o contêm, e em virtude de sua não dilatação poderia haver alteração na configuração anatômica ventricular, com afilamento de sua porção superior. Tal fato ocorre exclusivamente a esquerda, pois a direita ocorre dilatação dos segmentos basal, equatorial e do AVD, fato que enseja uma conformação ventricular diferente, com morfologia da parte superior mais alargada. Tais achados parecem corroborar os resultados de Hueb[3], que observou o fato de que a insuficiência da valva AVD acompanha a dilatação do anel direito, fato que não ocorre do lado esquerdo. A proporcionalidade entre os diferentes tipos de colágeno parece representar papel preponderante na manutenção da conformação geométrica normal do coração[8]. Embora a quantidade de colágeno total possa aumentar no miocárdio, em função principalmente da substituição de tais fibras por tecido de cicatrização, com consequente desarranjo funcional, parece haver evidências que apontam para o fato que a composição da MEC no miocárdio podem variar de acordo com a localização anatômica. Gunja-Smith et al.[24], em trabalho que comparou 8 corações com CMDId, extraídos de receptores de transplante cardíaco, com 12 corações normais, afirmam taxativamente que “trata-se de simplificação assumir que todo o coração tenha composição semelhante”. No presente estudo, analisou-se a MEC com relação aos seus componentes colagênicos e elásticos exclusivamente na região dos anéis atrioventriculares. Até onde saibamos, não existe na literatura trabalho semelhante, motivo que pode eventualmente explicar as discordâncias encontradas com relação à quantidade total de colágeno, pois neste estudo notou-se à análise inferencial microscópica, que a quantidade percentual de fibras colágenas totais foi substancialmente menor no grupo CMDId com relação ao grupo normal em ambos os anéis atrioventriculares.
termos macroscópicos como superior a 80%, não foi possível o cálculo em termos microscópicos, uma vez que não existem na literatura estudos específicos sobre a alteração na MEC dos anéis atrioventriculares na CMDId que servissem de embasamento à semelhante cálculo. A possibilidade de realização de estudo piloto não foi contemplada pela impossibilidade prática de obtenção de maior número de peças, uma vez que as únicas disponíveis foram efetivamente utilizadas no estudo. Tal limitação poderá eventualmente ser sobrepujada a partir da realização de estudos com modelos animais, uma vez que já existem modelos desenvolvidos para tal fim. A análise microscópica foi limitada por questões relativas aos métodos de coloração utilizados, principalmente em relação ao estudo das fibras elásticas. A coloração com o uso da resorcina-fuccina oxidada permite avaliar a totalidade das fibras elásticas presentes, porém não se presta adequadamente à diferenciação entre os três diferentes tipos de tais fibras (oxitalânicas, elauínicas e maduras). Estudos com utilização de colorações alternativas, tais como os métodos de Verhoeff para coloração exclusiva de fibras elásticas maduras e resorcina-fuccina de Weigert, que permite reconhecer as fibras maduras e elauínicas, podem auxiliar a elucidar o comportamento do sistema elástico de forma qualitativa e não apenas quantitativa. Com relação às fibras colágenas, a metodologia utilizada permitiu a quantificação do total de fibras presentes, porém, não permitiu a diferenciação dos diferentes tipos de fibras presentes, de modo que não foi possível avaliar quanto do colágeno estudado foi composto por material de cicatrização e fibrose. No presente estudo, não houve o propósito de investigar a variação da quantidade total de colágeno e de fibras elásticas em regiões anatômicas distintas do coração, o que poderia levar à confirmação da hipótese de que a estrutura da MEC varia de acordo com a região anatômica, apresentando padrão de aumento em algumas estruturas e diminuição em outras. Considerações finais A variação anatômica do anel atrioventricular em termos de presença de MEC já foi demonstrada. Angelini et al.[25] analisaram após necropsia a junção atrioventricular esquerda em 13 indivíduos, sendo 7 isentos de cardiopatia e 6 portadores de prolapso valvar mitral, tendo concluído que excetuando-se a distância intertrigonal, onde reside a continuidade mitro-aórtica existe grande variedade do arranjo de MEC, com presença de porções fibrosas de tamanho variável permeando áreas onde se encontram o miocárdio atrial e o miocárdio ventricular, tendo adicionalmente constatado que a quantidade de colágeno no anel variou de porções espessas e facilmente identificáveis até porções bastante finas. Esta mesma hipótese foi levantada por Juliani[22], que em estudo anatômico que analisou 43 corações humanos, sendo 18 deles oriundos de pacientes falecidos por CMDId, ao constatar a independência da dilatação do anel atrioventricular esquerdo
Limitações do estudo Com relação à seleção da amostra, embora tenha-se calculado o poder para explicar qualquer alteração encontrada em
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com relação à dilatação dos segmentos ventriculares, postulou que “Uma hipótese seria que os tecidos formadores do anel mitral são mais ricos em matriz fibrosa, em especial a região da menor distância intertrigonal, que o músculo ventricular e, portanto, mesmo sofrendo a “pressão” da dilatação ventricular, além de estarem sujeitos aos mesmos agentes etiológicos que determinam a dilatação do ventrículo esquerdo na CMDId e CMDIsq, seu ritmo de dilatação se dá de modo diferente”.
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. 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.
CONCLUSÃO Os resultados obtidos permitem concluir que: 1) Houve aumento dos perímetros ventriculares no grupo CMDId em relação ao grupo NORMAL tanto à direita quanto à esquerda nos diferentes segmentos avaliados. O perímetro do AVD foi maior no grupo CMDId em relação ao grupo NORMAL, não havendo diferença significativa em relação ao AVE entre os dois grupos. 2) Com relação ao percentual por área de fibras colágenas, os anéis atrioventriculares direito e esquerdo apresentaram percentagem de fibras menor no grupo CMDId em relação ao grupo normal. Com relação ao percentual por área de fibras elásticas, não houve diferença entre os grupos.
7. Henney AM, Parker DJ, Davies MJ. Collagen byosinthesis in normal and abnormal human heart valves. Cardiovasc Res. 1982;16(11):624-30. 8. Weber KT. Cardiac interstitium in health and disease: the fibrillar collagen network. J Am Coll Cardiol. 1989;13(7):1637-52. 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.
Papéis & responsabilidade dos autores MD
ATC
NFJ PHNS FBJ
Análise e/ou interpretação dos dados, análise estatística, aprovação final do manuscrito, concepção e desenho do estudo, realização das operações e/ou experimentos, redação do manuscrito ou revisão crítica de seu conteúdo Análise e/ou interpretação dos dados, análise estatística, aprovação final do manuscrito, concepção e desenho do estudo, realização das operações e/ou experimentos, redação do manuscrito ou revisão crítica de seu conteúdo Realização das operações e/ou experimentos Concepção e desenho do estudo, redação do manuscrito ou revisão crítica de seu conteúdo Análise e/ou interpretação dos dados, aprovação final do manuscrito, concepção e desenho do estudo, redação do manuscrito ou revisão crítica de seu conteúdo
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.
REFERÊNCIAS 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, Brasil.
Endereço para correspondência: Fernando Antibas Atik Instituto de Cardiologia do Distrito Federal Estrada Parque Contorno do Bosque s/n - Cruzeiro Novo – Brasília, DF, Brasil – CEP: 70658-700 E-mail: atikf@mac.com
1
Trabalho realizado no Instituto de Cardiologia do Distrito Federal (IC-DF), Brasília, DF, Brasil.
Artigo recebido em 3 de outubro de 2013 Artigo aprovado em 24 de março de 2014
Não houve suporte financeiro.
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isoladas em 561 (27,5%) e operações combinadas em 400 pacientes (19,6%), e outros procedimentos em 170 (8,3%). Outros procedimentos foram compostos de operações de doença congênita em adulto em 84 pacientes (4,1%), operações de aorta isolada 45 em pacientes (2,2%) e uma miscelânea de operações no restante. Dos pacientes em que foi identificada a ateromatose da aorta, 47 (69%) foram submetidos à revascularização do miocárdio isolada, 5 (7%) à operação valvar e o restante a operações combinadas (24%). A circulação extracorpórea não foi utilizada em 15 (32%) pacientes dos que foram submetidos a revascularização do miocárdio isolada. Por outro lado, foi utilizada em todos os submetidos a outras operações. A decisão em relação a condução da cirurgia a partir do diagnóstico da ateromatose ficou a critério do cirurgião. A aorta deixou de ser manipulada por completo em 16% dos pacientes. Mudanças no local de canulação ocorreram em 79% dos pacientes, mudança do local de pinçamento em 69% e mudança nas anastomoses proximais ou aortotomia em 59%. A substituição da aorta sob hipotermia profunda e parada circulatória total foi realizada em 16% dos pacientes.
Abreviações, acrônimos e símbolos AVC CE NYHA VE
Acidente vascular cerebral Coronária esquerda New York Heart Association Ventrículo esquerdo
INTRODUÇÃO A presença de ateromatose da aorta torácica é um conhecido fator complicador de pacientes submetidos à cirurgia cardiovascular, por determinar mudanças no planejamento intraoperatório, e incrementar o risco por maior morbidade e mortalidade[1]. As correlações entre aterosclerose nas artéria coronárias e em outros territórios arteriais foram extensivamente documentadas[2,3], em especial nas artérias carótidas[4]. Por sua vez, pacientes com aterosclerose das artérias carótidas também apresentam maior taxa de ateromatose da aorta torácica[5]. Já a ateromatose da aorta torácica é comum nos idosos, e estudos populacionais[6,7] verificaram que estes pacientes apresentam maior prevalência de eventos cardiovasculares e acidente vascular cerebral. Embora estas evidências demandem um acompanhamento mais cuidadoso em grupos de risco, não existem dados nacionais em relação ao tema. O conhecimento da prevalência e dos fatores de risco de ateromatose da aorta podem determinar maior previsibilidade de sua ocorrência e do prognóstico da mesma. Podem, ainda, levar a mudanças terapêuticas que visem minimizar o risco operatório. Os objetivos deste trabalho são determinar a prevalência e as características de ateromatose da aorta ascendente e/ou arco aórtico em pacientes submetidos à cirurgia cardiovascular num centro brasileiro, os fatores de risco de sua ocorrência e a implicação prognóstica imediata da mesma.
Análise estatística As variáveis categóricas foram expressas por meio de frequências e percentagens e as contínuas por meio de médias e desvio-padrão. As variáveis contínuas com distribuição heterogênea foram expressas por meio de medianas e intervalos de confiança referentes a um desvio padrão. Na comparação das características pré e intraoperatórias e dos eventos de morbidade e mortalidade entre os grupos, os testes qui-quadrado, exato de Fisher, T de Student e Wilcoxon foram utilizados, quando indicados. Regressão logística multivariada foi utilizada na determinação dos fatores de risco de ateromatose e na implicação prognóstica da mesma na ocorrência de óbito, acidente vascular cerebral e insuficiência renal aguda. Variáveis significativamente (P<0,05) relacionadas com cada um dos eventos por meio de análise univariada foram retidas. A seguir, regressão logística stepwise backward foi usada na construção dos modelos multivariados. A calibração e descriminação dos modelos foram determinadas pelo teste de Hosmer-Lemeshow e pela análise da curva ROC (receiver-operating characteristic), respectivamente.
MÉTODOS No período de janeiro de 2007 a junho de 2011, 2042 pacientes adultos consecutivos foram submetidos à cirurgia cardiovascular. A idade média foi de 57,4±15 anos (variação de 16 anos a 87 anos) e 1168 (57,2%) eram do sexo masculino. Todos os pacientes foram estudados, não havendo critério de exclusão. As características pré, intra e pós-operatórias dos pacientes foram colhidas prospectivamente e armazenadas em banco de dados eletrônico. O diagnóstico de ateromatose da aorta foi realizado pela palpação da mesma durante o ato operatório pelo cirurgião, sendo que a coleta dos dados levou em consideração o relato completo do cirurgião em relação às características da ateromatose. O estudo foi aprovado pela Comissão de Ética e Pesquisa com o número 069883/2013, de acordo com as normas de Helsinki. As operações realizadas foram revascularização do miocárdio isolada em 911 pacientes (44,6%), operações valvares
RESULTADOS Prevalência e descritivo da ateromatose A ateromatose da aorta ascendente e/ou arco aórtico foi diagnosticada pelo cirurgião no intraoperatório em 68 pacientes, o que corresponde a 3,3% do total. Os achados intraoperatórios foram placa calcificada isolada delimitada em 35%, placa calcificada extensa ou múltipla em 33% e aorta em porcelana em 32%. Diante desses acha-
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dos, vários tipos de repercussão adviram: impossibilidade de qualquer manipulação da aorta em 33,3%, impossibilidade de canulação em 9,7%, impossibilidade de pinçamento em 4,2% e impossibilidade de canulação e pinçamento em 2,8%. Na metade restante dos pacientes, houve possibilidade de instalação de circulação extracorpórea com mudanças nos locais de canulação, clampeamento e anastomoses proximais.
se ocorreram com maior frequência no grupo ateromatose, quando comparado ao controle. Além disso, houve maior frequência de acometimento de outros territórios arteriais no grupo ateromatose da aorta, como, por exemplo, doença arterial coronária, em especial quando associada à obstrução do tronco da coronária esquerda e doença vascular periférica. Houve tendência de associação entre a doença carotídea obstrutiva e a ateromatose da aorta. A análise multivariada identificou os fatores independentes de risco de ateromatose da aorta na população estudada (Tabela 2), como sendo a idade superior a 61 anos (OR=2,79; IC95% 2,43 – 3,15; P<0,0001), a presença de 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).
Fatores de risco de ateromatose A Tabela 1 verificou as diferenças entre o grupo ateromatose e o controle, pela análise univariada, no que se refere a dados demográficos, comorbidades e fatores de risco amplamente reconhecidos para cirurgia cardiovascular. Neste sentido, a idade mais avançada no grupo ateromatose foi particularmente expressiva (65,8±9,7 anos versus 54,3±15 anos, P<0,0001). Ainda, todos os fatores de risco de aterosclero-
Tabela 1. Características pré-operatórias de pacientes com e sem ateromatose da aorta submetidos à cirurgia cardiovascular.
Dados demográficos Idade (anos) Sexo masculino Peso (kg) Altura (cm) Cirurgia cardíaca prévia Classe funcional (NYHA) I II III IV Doença arterial coronária Síndrome coronária aguda Infarto do miocárdio<30d Lesão de tronco CE Número de vasos acometidos 1 2 3 Fração de ejeção do VE Hipertensão pulmonar Doença carotídea Fatores de risco Hipertensão arterial Diabetes mellitus Dislipidemia Tabagismo Comorbidades AVC prévio Fibrilação atrial Doença vascular periférica Endocardite Creatinina Hemoglobina sérica
Ateromatose (N=68)
Controle (N=1974)
P
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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Tabela 2. Análise multivariada de fatores de risco de ateromatose da aorta em pacientes submetidos à cirurgia cardiovascular. Variável Ateromatose† Intercept
Estimativa±SE
P
3,24±0,33
<0,0001
Idade > 61 anos
0,51±0,13
<0,0001
DAC
0,57±0,19
0,002
HAS
0,41±0,19
0,03
Doença vascular periférica
0,57±0,28
0,04
OR
IC 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
† Teste de Hosmer-Lemeshow, P=0,09; C-statistic 0,77; DAC=Doença arterial coronária; HAS=Hipertensão arterial sistêmica
Tabela 3. Dados de morbidade e mortalidade em pacientes com e sem ateromatose da aorta submetidos à cirurgia cardiovascular. Ateromatose (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)
Mortalidade hospitalar Acidente vascular cerebral Infarto do miocárdio Sepse Insuficiência renal aguda Ventilação mecânica prolongada Tempo de terapia intensiva (dias) Tempo de internação (dias)
Controle (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
Tabela 4. Análise multivariada da ocorrência de acidente vascular cerebral em pacientes submetidos à cirurgia cardiovascular. Estimativa±SE
P
Intercept
-0,31±0,65
0,64
Ateromatose
0,62±0,24
0,01
Fração de ejeção
2,84±0,99
0,004
Classe funcional IV
1,35±0,4
0,0007
Variável Ateromatose†
OR
IC 95%
3,46
3,18 – 3,76
9,42
1,98 – 42,6
3,86
1,93 – 5,35
† Teste de Hosmer-Lemeshow, P=0,9; C-statistic 0,7
Implicações prognósticas A Tabela 3 exibe o impacto da ateromatose da aorta na mortalidade hospitalar e nos principais desfechos de morbidade pela análise univariada. Observou-se maior mortalidade hospitalar e maior ocorrência de acidente vascular cerebral, sepse, infarto do miocárdio, insuficiência renal aguda, ventilação mecânica prolongada e maior tempo de internação no grupo de pacientes com ateromatose da aorta quando comparado ao controle. Quanto à análise multivariada, a presença de ateromatose da aorta foi preditor independente da ocorrência
de acidente vascular cerebral no pós-operatório (OR=3,47; IC95% 3,18 – 3,76; P=0,01), conforme documentado na Tabela 4. Não houve correlação, na análise de fatores de risco, entre a presença de ateromatose da aorta e a mortalidade hospitalar ou a insuficiência renal aguda no pós-operatório. Não se identificou maior risco de acidente vascular cerebral de acordo com o tipo de acometimento ateromatoso na aorta. Pacientes com aorta em porcelana tiveram o mesmo risco que outros com placas ateromatosas delimitadas (12,5% versus 9,5%, P=0,87). Ainda, evitar a manipulação
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da aorta não preveniu a ocorrência de complicação cerebral (9% versus 10,2%, P=0,91), assim como mudar o sítio de canulação (P=0,61), pinçamento (P=0,12) ou utilizar parada circulatória total (P=0,9).
rém, apresenta desvantagens em relação ao uso de radiação e seu uso rotineiro está associado a custo elevado para o sistema de saúde. Pode, entretanto, ser utilizada nos grupos de maior risco previamente a cirurgia[13]. No intraoperatório, tradicionalmente o cirurgião palpa a aorta a fim de diagnosticar a ateromatose da aorta. Todavia, Wareing et al.[10], estudando mais de 500 pacientes, verificaram a palpação ser imprecisa, tendo sido detectados somente 38% dos diagnósticos positivos à ultrassonografia. O melhor exame de imagem é a ultrassonografia epiaórtica[16,17] realizada no intraoperatório com transdutores de alta resolução que avaliam a parede e a luz da aorta nos diversos segmentos. As informações precisas em relação às características patológicas da aorta têm implicações no manejo da circulação extracorpórea, na proteção miocárdica e cerebral e no planejamento cirúrgico, no sentido de minimizar a indesejável embolia de micropartículas de ateroma, especialmente para o cérebro. O nosso estudo e outros[1,18] demonstraram que a presença de ateromatose na aorta é fator independente de risco do desenvolvimento de acidente vascular cerebral no pós-operatório, com risco absoluto por volta de 10%, risco este consistente em várias séries. Blauth et al.[12] revisaram os achados de necropsia de 221 pacientes submetidos a cirurgia cardíaca. Revelouse que a embolia cerebral ocorreu em 37% dos pacientes com aterosclerose da aorta, contra apenas 2% dos que não tinham. Van der Linden et al.[19] mostraram que o tipo de envolvimento da aorta tem riscos diferenciados de acidente vascular cerebral. Na nossa experiência, não pudemos corroborar os achados deste último estudo de maior risco relacionado ao tipo de acometimento, inclusive no que se refere a aorta em porcelana. Os mais diversos tipos de estratégia cirúrgica são possíveis de ser executados, como exemplificado na nossa experiência, não existindo consenso na literatura em relação à melhor estratégia. Podemos citar a revascularização com enxertos arteriais compostos em circulação extracorpórea sem pinçamento aórtico, as mudanças dos sítios de canulação, pinçamento e anastomoses proximais, até a substituição da aorta sob parada circulatória total em hipotermia profunda. Porém, nenhuma destas estratégias é capaz de impedir o risco de deslocamento de partículas de ateroma. É intuitivo afirmar que evitar qualquer tipo de manipulação da aorta seja aconselhável na presença de ateromatose. Entretanto, esta estratégia não é possível na totalidade dos casos, particularmente na necessidade de operações combinadas que envolvam as valvas cardíacas e aorta torácica. Existem, ainda, alguns dados de estudos observacionais[1,8,10-12,14] sugerindo que a mudança na tática operatória possa minimizar o risco de complicações, apesar de que os índices de morbidade permaneçam mais elevados que o habitual. Não pudemos verificar na nossa experiência superioridade de nenhuma abordagem na minimização do risco de
DISCUSSÃO Este estudo observacional procurou estudar a ateromatose da aorta ascendente e/ou arco aórtico em um grupo de pacientes adultos consecutivos submetidos à cirurgia cardiovascular. Apesar da prevalência encontrada ser relativamente baixa nesta população, ela é concordante com outras séries da literatura[8]. A prevalência poderia ser mais elevada se a nossa população fosse mais idosa, já que guardou-se relação direta entre idade e a presença de ateromatose. Davila-Roman et al.[9] encontraram ateromatose importante da aorta ascendente em aproximadamente um terço dos pacientes acima de 80 anos submetidos a cirurgia cardiovascular. O aumento da expectativa de vida da população brasileira certamente determinará maior ocorrência de pacientes com este problema sendo tratados por cirurgia cardiovascular. Além da idade, identificou-se que os principais fatores de risco de aterosclerose[5] são os mesmos relacionados à ateromatose da aorta pela análise univariada. Entretanto, somente a hipertensão arterial sistêmica foi considerada fator independente de risco pela análise multivariada. Além deste último, outros fatores encontrados na nossa série foram a doença arterial coronária e a doença vascular periférica, reforçando a coexistência de acometimento aterosclerótico em diversos territórios arteriais. A maioria dos estudos na literatura[10-12] considera como fatores de risco de ateromatose da aorta a doença carotídea obstrutiva, aneurisma de aorta abdominal, obstrução do tronco da coronária esquerda, diabetes mellitus e hipertensão arterial. A estenose aórtica calcificada e a insuficiência renal crônica são ainda outros fatores de risco implicados[13]. Analisando criticamente, as características pré-operatórias dos pacientes têm pouco valor preditivo, pois grande parte dos pacientes encaminhados à cirurgia cardiovascular apresenta tais características, o que requer, portanto, avaliações mais precisas. Na nossa experiência, tais avaliações são realizadas de forma infrequente e dependente do nível de suspeição do médico. A importância de complementar o diagnóstico a fim de permitir o melhor planejamento operatório possível. Os exames de imagem tradicionais que podem identificar a ateromatose da aorta são imprecisos, como a radiografia simples de tórax ou o cateterismo cardíaco. O ecocardiograma transesofágico[14] é melhor que os anteriores, porém, apresenta limitações de aquisição de imagem na aorta ascendente distal e arco aórtico proximal, locais frequentemente utilizados para canulação e pinçamento. A tomografia computadorizada[15] é um ótimo exame para detecção de ateromatose da aorta, po-
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complicações cerebrais. Tanto a cirurgia sem CEC sem manipulação da aorta apresentou as mesmas taxas de acidente vascular cerebral que os pacientes submetidos a cirurgia com CEC. As tentativas de mudar o sítio de canulação, de pinçamento e de realização de anastomoses proximais ou de aortotomia não reduziram este risco. Nem tão pouco a substituição da aorta sob parada circulatória total em hipotermia profunda obteve o mesmo benefício, apesar de não carregar risco adicional. A cirurgia cardíaca com manipulação da aorta guiada pela ultrassonografia epiaórtica tem valor clínico incerto. Estudos clínicos têm detectado menor embolização cerebral do Doppler transcraniano[20] e melhor desempenho neuropsicológico[21,22], mas não se demonstrou menores taxas de acidente vascular cerebral. Diante de um paciente com aorta em porcelana, portador de doença valvar ou na aorta que requeiram tratamento cirúrgico, a maioria dos cirurgiões hesitaria em realizar procedimentos cirúrgicos complicados envolvendo parada circulatória total e substituição da aorta num paciente idoso que já apresenta frequentemente outros fatores de risco operatórios, o que abre a possibilidade da troca da valva aórtica transapical quando indicada[23]. Por outro lado, se a operação proposta for a revascularização do miocárdio isolada, realizá-la sem circulação extracorpórea e sem manipulação da aorta parece ser estratégia mais adequada quando possível[24]. Deve-se ressaltar que a nossa experiência não corrobora tais condutas, nem tão pouco existem evidências fortes na literatura que as suportem até o momento.
Papéis & responsabilidade dos autores FAA IAS CRC
Coleta de dados, análise estatística, interpretação dos dados e redação do manuscrito Redação do manuscrito Revisão do manuscrito
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Limitações do estudo Trata-se de estudo observacional, com as limitações inerentes ao seu desenho. Utilizou-se a palpação da aorta como método de diagnóstico da ateromatose, o que certamente reduziu a prevalência. O uso de ultrassonografia epiaórtica deveria ser o padrão do nosso serviço. O número restrito de pacientes e as condutas muito variadas adotadas pelos cirurgiões na presença de ateromatose dificultaram a determinação do impacto da mudança de tática intraoperatória nos resultados de morbidade e mortalidade. Por este motivo, este não foi listado como objetivo deste trabalho. Um estudo multicêntrico com número mais robusto de pacientes voltado para esta finalidade seria interessante de ser desenvolvido.
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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.
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ascending aorta during cardiac operations. A strategy for detection and treatment. J Thorac Cardiovasc Surg. 1992;103(3):453-62.
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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.
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.
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. 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.
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.
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.
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.
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17. Davila-Roman VG, Barzilai B, Wareing TH, Murphy SF, Kouchoukos NT. Intraoperative ultrasonography evaluation of the
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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).
1
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 58±14 years; 65% male.
Statistical analysis Continuous variables with normal distribution were described using mean ± SD and compared using Student’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 didn´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 (“TASP”). 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 didn´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.
Authors’ roles & responsibilities MCS JDFF CA LDS AMR EAL PEL MRNP FAL
Author Coauthor Coauthor Coauthor Coauthor Coauthor Coauthor Coauthor Coauthor
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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
1
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 EDA EDV ESA ESV G1 G2 HR IM IP LADCA LVEF SD SHAM
Acute myocardial infarction End diastolic area End diastolic volume End systolic area End systolic volume Group 1 Group 2 Heart rate Intramuscular Intraperitoneal Left anterior descending coronary artery Left ventricular ejection fraction Standard deviation 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. 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 rat’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 surgeon’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.
Authors’ 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, Brasil.
Endereço para correspondência: 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 – CEP: 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
1
Trabalho realizado no Hospital de Base da Faculdade de Medicina de São José do Rio Preto (FAMERP), São José do Rio Preto, SP, Brasil. Não houve suporte financeiro.
Artigo recebido em 14 de fevereiro de 2014 Artigo aprovado em 25 de maio de 2014
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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.
Abreviações, acrônimos e símbolos AKIN BIA CEC CRM DAC FA FAMERP HB IC IMC OR P ROC SIRS STS SUS UTI
Acute Kidney Injury Network Balão intra-aórtico Circulação extracorpórea Cirurgia de revascularização do miocárdio Doença arterial coronária Fibrilação atrial Faculdade de Medicina de São José do Rio Preto Hospital de Base Intervalo de confiança Índice de massa corpórea Odds Ratio Nível de significância Receiver Operating Characteristics Síndrome de resposta inflamatória sistêmica Society of Thoracic Surgeons Sistema Único de Saúde Unidade de Terapia Intensiva
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.
INTRODUÇÃO
superior a de países como Estados Unidos (2,9%)[11] e Canadá (1,7%)[12], provavelmente devido à elevada prevalência de fatores de risco cardiovascular entre os brasileiros submetidos a CRM[13]. Atualmente, existe maior prevalência de condições cardíacas precárias e comorbidades associadas[14]. A taxa de mortalidade por CRM pode apresentar variação dependendo de diversos fatores relacionados aos períodos pré, per e pós-operatórios. Variáveis pós-operatórias como tempo de internação em terapia intensiva, fibrilação atrial, lesão renal aguda, lesão neurológica tipo I e diálise têm relação com o aumento da mortalidade pós-operatória[14-17]. Considerando a importância da CRM na correção da isquemia miocárdica consequente à obstrução das artérias coronárias, procurando-se o alívio dos sintomas, a melhora da qualidade de vida, o retorno do paciente ao trabalho, assim como o aumento da expectativa de vida, justifica-se a presente pesquisa, pois estudos a longo prazo sobre variáveis pré, intra e pós-operatórias que podem influenciar na mortalidade de pacientes submetidos a CRM com CEC são escassos. Além disso, é importante ressaltar que todas operações cardíacas foram realizadas pela mesma equipe e em hospital universitário, com programa de residência médica em cirurgia cardiovascular. O objetivo desta pesquisa foi estudar fatores de risco para mortalidade no período pós-operatório de pacientes submetidos à revascularização miocárdica com circulação extracorpórea (CEC), considerando-se variáveis pré, intra e pós-operatórias e sua influência na mortalidade.
Doenças cardiovasculares são as principais causas de morte na população, compreendendo as doenças cerebrovasculares, isquêmicas cardíacas, hipertensivas, aterosclerose, febre reumática e outros agravos do coração. Segundo dados da Organização Mundial de Saúde em 2008 ocorreram 17,3 milhões de óbitos no mundo[1], sendo que 7,3 milhões foram devido à doença arterial coronariana (DAC)[2]. No Brasil, em 2009 as internações por DAC totalizaram 209.029 pacientes, ocorrendo 12.619 óbitos com taxa de mortalidade de 6,04%[3]. O tratamento de DAC pode ser clínico/medicamentoso ou cirúrgico. Apesar dos avanços da terapêutica clínica e das intervenções percutâneas, a cirurgia de revascularização do miocárdio (CRM) é um procedimento seguro realizado em todo o mundo com taxas baixas de mortalidade e morbidade na população geral[4], sendo ainda excelente opção para tratamento de DAC obstrutiva[5], mesmo em pacientes diabéticos[6], idosos[7] e em pacientes com baixa fração de ejeção de ventrículo esquerdo[8]. Além disso, a CRM pode controlar a isquemia persistente e a progressão para o infarto agudo do miocárdio, podendo propiciar alívio sintomático e prevenir complicações isquêmicas[9]. A CRM é a cirurgia cardíaca mais praticada em nosso país, sendo a maior parte realizada pelo Sistema Único de Saúde (SUS) tanto em hospitais públicos como em filantrópicos ou privados[10]. No período de 2005 a 2007 foram realizadas 63.272 CRM no Brasil, sendo a taxa de mortalidade de 6,2%[10]
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MÉTODOS Foram estudados retrospectivamente e de forma consecutiva 1.674 pacientes submetidos à cirurgia cardíaca para revascularização do miocárdio com circulação extracorpórea (CEC), independente de sexo e raça, no Hospital de Base (HB) de São José do Rio Preto, SP, no período de dezembro/1999 a fevereiro/2012. Este estudo foi aprovado pelo comitê de ética, parecer 454.518 de 12/11/2013. Desse total, 46 (2,7%) foram excluídos por apresentar falha no registro de informações em seus prontuários. Os dados dos pacientes foram revisados prospectivamente por meio de coleta em sistema informatizado. Foram considerados como critérios de exclusão pacientes submetidos a CRM sem CEC ou associada com outras cirurgias cardíacas (orovalvares, aneurismas ventriculares, comunicações interventriculares adquiridas, cardiopatias congênitas) ou vasculares além da revascularização do miocárdio e, que faleceram no período intraoperatório. Os dados de cada paciente foram obtidos em fichas de perfusão do Serviço de Cirurgia Cardíaca do HB, incluindo variáveis demográficas ou não cardíacas como sexo, idade e índice de massa corpórea (IMC), enquanto as variáveis cardíacas incluíram tempo entre admissão hospitalar e procedimento cirúrgico, uso de balão intra-aórtico (BIA), tempo de circulação extracorpórea (CEC), número total de pontes, fibrilação atrial aguda, infecção respiratória, creatinina pico-admissão (mg/ dL), diálise, infecção de sítio cirúrgico profundo (mediastinite), lesão neurológica tipo I, tempo de permanência na unidade coronariana de até 30 dias e mortalidade em 30 dias. Foram definidos como variáveis do período pós-operatório: Creatinina pico-admissão (mg/dL): alteração na creatinina sérica definida como diferença entre creatinina de admissão na Unidade de Terapia Intensiva (UTI) e o mais alto valor obtido durante a permanência nessa unidade. Arritmias cardíacas: fibrilação atrial aguda com duração superior a 1 hora. Complicações pulmonares: reintubação traqueal por insuficiência respiratória devida a alterações mecânicas da ventilação ou infecção respiratória. Mediastinite: secreção mediastinal associada a sinais clínicos (febre, dor torácica) e laboratoriais (leucocitose) de infecção com ou sem instabilidade esternal e com cultura de secreções e hemocultura positiva. Lesão neurológica tipo I: déficit motor focal novo e persistente, coma, convulsão ou lesão encefálica. Óbitos: mortalidade por todas as causas no período de 30 dias.
Tabela 1. Estatística descritiva para variáveis pré, intra e pósoperatórias em pacientes submetidos à revascularização miocárdica no período de dezembro/1999 a fevereiro/2012 (n=1.628). Variáveis média dp mediana min max Idade (anos) 60,7 9,4 61 25 91 IMC (Kg/m2) 27 4,2 26,6 15,3 49,3 Tempo admissão-cirurgia (d) 6,2 5,8 4 0 38 Permanência Ucor até 30 4,1 5,2 2 0 30 dias (d) Creatinina pico - admissão 0,4 0,7 0,1 -0,2 7,5 (mg/dL) Total de pontes 2,7 0,7 3 1 5 Tempo de CEC (min) 94,4 25,5 92 24 218 IMC=índice de massa corporal; CEC=circulação extracorpórea Tabela 2. Distribuição percentual de variáveis pré e pós-operatórias em pacientes submetidos à revascularização miocárdica no período de dezembro/1999 a fevereiro/2012 (n=1.628). Variáveis N (%) N (%) M F Sexo 1125 (69,1) 503 (30,9) Presença Ausência BIA 114 (7) 1514 (93) FA aguda 141 (8,7) 1487 (91,3) CP 227 (14,4) 1351 (85,6) Diálise 40 (2,5) 1588 (97,5) Mediastinite 25 (1,5) 1603 (98,5) Lesão neurológica I 71 (4,4) 1557 (95,6) N =número de indivíduos; M =sexo masculino; F=sexo feminino; CP=complicações pulmonares; BIA=balão intra-aórtico; FA=fibrilação atrial
para dados categóricos. As variáveis numéricas foram submetidas à curva ROC para definição de ponto de corte de cada uma delas em relação a óbito no período pós-operatório. Regressão logística, Odds Ratio (OR) e IC95% foram utilizados para definição de fatores de risco para mortalidade no período pós-operatório. Para os demais testes, valor de P<0,05 foi considerado significante. Utilizou-se o programa de cálculos estatísticos GraphPad InStat versão 3.00 (GraphPad Software, San Diego, Califórnia, Estados Unidos). RESULTADOS Os resultados referentes a variáveis pré, intra e pós-operatórias encontradas em pacientes submetidos à CRM com CEC (n=1.628) encontram-se nas Tabelas 1 e 2. As mais frequentes incluíram sexo masculino (69,1%), complicações pulmonares (14,4%), fibrilação atrial aguda (8,7%) e uso de balão intraaórtico (7%).
Análise Estatística Os dados obtidos foram submetidos ao teste de normalidade de Kolmogorov-Smirnov e, subsequentemente, a análises paramétrica pelo teste t de Student não pareado ou não paramétrica pelo teste de Mann-Whitney e exato de Fisher
Análise de Variáveis em Pacientes que faleceram Do total de 1.628 pacientes submetidos à CRM com
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CEC, 141 (8,7%) morreram. Os resultados referentes a variáveis pré, intra e pós-operatórias encontradas nesses pacientes estão expressas nas Tabelas 3 e 4. As principais foram sexo masculino (67%), complicações pulmonares (40%), uso de balão intra-aórtico (21%) e lesão neurológica tipo I (19%).
Tabela 3. Estatística descritiva para variáveis pré, intra e pósoperatórias em pacientes submetidos à revascularização miocárdica que foram a óbito no período de dezembro/1999 a fevereiro/2012 (n=141). Variáveis média dp mediana min max Idade (anos) 65,89 8,96 66 35 91 IMC (Kg/m2) 26,46 4,89 26,22 15,27 40,35 Tempo admissão-cirurgia (d) 7,28 6,59 6 0 38 Permanência Ucor até 30 6,09 7,15 2 0 29 dias (d) Creatinina pico - admissão 1,07 1,28 0,6 0 6,3 (mg/dL) Total de pontes 2,80 0,74 3 1 4 Tempo de CEC (min) 108,58 33,01 101 24 191
Influência de Variáveis na Mortalidade Os resultados da curva ROC para idade, tempo entre admissão hospitalar e procedimento cirúrgico, creatinina pico-admissão e tempo de CEC estão na Figura 1. A idade (anos) apresentou valor de corte de 65,128, sensibilidade de 54%, especificidade de 69% e área sob a curva de 0,670 (IC95% 0,620 - 0,721). No tempo entre admissão hospitalar e procedimento cirúrgico (dias) o valor de corte foi 5,016, sensibilidade de 54%, especificidade de 59% e área sob a curva de 0,558 (IC95% 0,506 - 0,609). A alteração na creatinina pico-admissão (mg/dL) mostrou valor de corte de 0,400, sensibilidade de 57%, especificidade de 82% e área sob a curva de 0,682 (IC95% 0,631 - 0,732). O tempo de CEC (min) apresentou valor de corte de 115,18, sensibilidade de 38%, especificidade de 84% e área sob a curva de 0,640 (IC95% 0,589 - 0,691). Analisando fatores de risco para mortalidade em pacientes submetidos a CRM com CEC (Tabela 5), observou-se que a possibilidade relativa de pacientes que utilizaram BIA irem a óbito é 238% maior do que aqueles que não necessitaram desse tipo de dispositivo para assistência ventricular (OR=3,38; IC 95% 1,98-5,79; P<0,0001). Com relação à necessidade de diálise, a chance relativa de óbito nos pacientes com necessidade desse tratamento no pós-operatório é 661% maior do que aqueles não submetidos à diálise (OR=7,61; IC 95% 3,58-16,20; P<0,0001). Em pacientes com lesão neurológica tipo I, a possibilidade relativa de óbito é 342% maior em relação àqueles sem essa lesão (OR=4,42; IC 95% 2,48-7,81; P<0,0001). Considerando a idade dos pacientes, a chance relativa de indivíduos > 65 anos irem a óbito é 131% maior quando comparado aqueles < 65 anos (OR=2,31; IC 95% 1,553,44; P<0,0001). A análise do tempo entre admissão hospitalar e procedimento cirúrgico mostrou que a possibilidade relativa de óbito é 53% maior quando esse tempo foi > 5 dias (OR=1,53; IC 95% 1,03-2,27; P=0,0352). Com relação à alteração na creatinina sérica (pico-admissão), a chance relativa de óbito é 167% maior quando essa variação é ≥ 0,4 mg/dL (OR=2,67; IC 95% 1,794,00; P<0,001). Quanto ao tempo de CEC, a possibilidade relativa de óbito é 209% maior quando está acima de 115 minutos (OR=3,09; IC 95% 2,04-4,68; P<0,001).
dp=desvio padrão; min=valor mínimo; max=valor máximo; IMC=índice de massa corpórea; d=dias; UCor=unidade coronária; CEC=circulação extracorpórea
Tabela 4. Distribuição percentual de variáveis pré e pós-operatórias em pacientes submetidos à revascularização miocárdica que foram a óbito no período de dezembro/1999 a fevereiro/2012 (n=141). Variáveis N (%) N (%) M F Sexo 95 (67) 46 (33) Presença Ausência BIA 30 (21) 111 (79) FA aguda 23 (16) 118 (84) CP 56 (40) 85 (60) Diálise 23 (16) 118 (84) Mediastinite 6 (4) 135 (96) Lesão neurológica I 27 (19) 114 (81) N=número de indivíduos; M=sexo masculino; F=sexo feminino; BIA = balão intra-aórtico; FA=fibrilação atrial; CP=complicações pulmonares
Tabela 5. Resultados da regressão logística de fatores de risco para mortalidade em pacientes submetidos à revascularização miocárdica no período de dezembro/1999 a fevereiro/2012 (n=1.628). Fatores de risco OR IC 95% P BIA 3,38 1,98-5,79 <0,0001* Diálise 7,61 3,58-16,20 <0,0001* Lesão neurológica I 4,42 2,48-7,81 <0,0001* Diabetes 1,38 0,92-2,08 0,1168 Idade > 65 anos 2,31 1,55-3,44 <0,0001* IMC > 23,4 Kg/m2 0,67 0,43-1,05 0,0807 Tempo admissão-cirurgia 1,53 1,03-2,27 0,0352* > 5 dias Creatinina pico - admissão 2,67 1,79-4,00 <0,0001* > 0,4 mg/dL Tempo de CEC >115 min 3,09 2,04-4,68 <0,0001* OR=Odds ratio; IC=intervalo de confiança; N=número de indivíduos; M=sexo masculino; F=sexo feminino; BIA=balão intra-aórtico; FA=fibrilação atrial; IMC=índice de massa corpórea; UCor=Unidade Coronária; CEC=circulação extracorpórea; *estatisticamente significativo
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Fig. 1 - Curvas ROC (receiver operating characteristics) da idade, tempo entre admissão hospitalar e procedimento cirúrgico, tempo de circulação extracorpórea e da creatinina pico-admissão para óbito em até 30 dias.
DISCUSSÃO
ressaltar que a realização de cirurgia combinada incrementa o risco de mortalidade. Essas taxas de mortalidade são superiores a de países como Estados Unidos (2,9%)[11] e Canadá (1,7%)[12], possivelmente devido à elevada prevalência de fatores de risco cardiovascular entre os brasileiros submetidos a CRM[13]. Por outro lado, a comparação entre resultados cirúrgicos obtidos em centros nacionais em relação a centros europeus e norte-americanos é inadequada, pois tanto o registro da Society of Thoracic Surgeons (STS) como o UK Cardiac Surgical Register são voluntários, enquanto o DATASUS é administrativo. No presente estudo, a creatinina pico-admissão ≥ 0,4 mg/ dL foi considerada fator de risco para óbito. Esse achado foi próximo ao encontrado por Machado et al.[15] que, estudando 817 pacientes com lesão renal aguda (LRA), verificaram que a creatinina pico-admissão≥0,3 mg/dl foi preditora independente de óbito em 30 dias após CRM com CEC. Contudo, esses autores utilizaram o critério proposto pela classificação Acute Kidney Injury Network (AKIN), ou seja, aumento percentual (≥ 50%) ou absoluto (≥ 0,3 mg/dL) da creatinina sérica caracteriza LRA. Nesta pesquisa, o valor da creatinina
Este estudo identificou 7 fatores de risco para mortalidade de pacientes submetidos à revascularização miocárdica com circulação extracorpórea. Nos pacientes que foram a óbito, as variáveis mais frequentes incluíram sexo masculino, complicações pulmonares, uso de balão intra-aórtico e lesão neurológica tipo I. Após regressão logística, constituíram-se fatores de risco para mortalidade: diálise (OR=7,61), lesão neurológica tipo I (OR=4,42), uso de balão intra-aórtico (OR=3,38), tempo de circulação extracorpórea (OR=3,09), creatinina pico - admissão > 0,4 mg/dL (OR=2,67), idade > 65 anos (OR=2,31) e tempo entre admissão hospitalar e procedimento cirúrgico (OR=1,53). Nesta pesquisa, a taxa de mortalidade foi 8,7%, próxima à registrada pelo DATASUS para CRM, ou seja, 7%[18]. No período de 2005 a 2007, Piegas et al.[10] analisaram 63.272 CRM realizadas em 191 hospitais verificaram que a taxa de mortalidade foi 6,2%. Cadore et al.[14], investigando 2.809 pacientes submetidos a CRM isolada ou combinada com troca valvar, relataram que a taxa de mortalidade foi 10%. Vale
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pico-admissão ≥ 0,4 mg/dL foi definido como ponto de corte em relação a óbito por meio da curva ROC. A avaliação da função renal por meio da dosagem de creatinina sérica em pacientes submetidos a CRM com CEC é essencial, pois mesmo um aumento subclínico é considerado preditor independente de óbito em 30 dias após CRM em pacientes com função renal normal ou lesão renal pré-operatória[19]. Além disso, LRA após CRM é complicação frequente que aumenta o tempo de permanência hospitalar e na UTI, estando relacionada à taxa elevada de morbimortalidade[16,20], tendo importância prognóstica. Do total de 1.628 pacientes submetidos à CRM com CEC, 40 (2,5%) necessitaram de diálise no pós-operatório. A necessidade de terapia dialítica é observada em até 30,6% dos casos[16,20,21]. Yehia et al.[21], analisando 104 pacientes submetidos a CRM, constataram que 41,3% deles desenvolveram LRA após a cirurgia, com necessidade de diálise em até 9,6%, principalmente naqueles com lesão renal pré-operatória. Santos et al.[16] constataram que de 223 pacientes submetidos a CRM com CEC, a diálise foi necessária em 4,9% deles. Nesta casuística, dos 40 pacientes que necessitaram de diálise no pós-operatório, 23 (57,5%) foram a óbito, próximo a taxa de mortalidade registrada por Santos et al.[16] e Chertow et al.[20], 63,6% (n=223) e 63,7% (n=460), respectivamente. Apesar dessa proximidade, a comparação entre os trabalhos é complexa, pois está relacionada ao número e características dos hospitais envolvidos em cada estudo, perfil dos pacientes e tamanho da amostra. A chance relativa de óbito nos pacientes que necessitaram de tratamento dialítico no pós-operatório foi significativamente elevada (OR=7,61; IC 95% 3,58-16,20; P<0,0001). Esse achado é concordante com a literatura. Segundo Chertow et al.[20] a necessidade de diálise aumenta em 7,9 vezes o Odds Ratio de morte entre esses pacientes. Quando há lesão renal grave o suficiente para requerer a diálise ocorre aumento acentuado na mortalidade[20]. Portanto, a identificação de fatores de risco pré-operatórios associados à LRA pode contribuir para o uso de estratégias preventivas, visando minimizar os riscos e melhorar tratamento desta lesão. Nesta série, a idade > 65 anos foi considerada fator de risco para mortalidade. Esse achado foi similar ao encontrado por Rocha et al.[22] em pacientes com idade ≥ 70 anos. Naughton et al.[23] estudando 3.683 pacientes submetidos a CRM, verificaram que idade ≥ 75 anos foi considerada fator de risco independente para mortalidade no período de 30 dias. Entretanto, Aikawa et al.[4] investigando o impacto da CRM em 253 pacientes idosos, verificaram que idade ≥ 65 anos não foi associada a variável óbito. Considerando o aumento da prevalência de DAC com a idade[24], é possível que um número crescente de pacientes idosos seja candidato à CRM nos próximos anos. Portanto, uma avaliação criteriosa de variáveis cardíacas e não cardíacas nos períodos pré, intra e pós-operatório de pacientes com
mais de 65 anos é necessária, pois a idade pode estar associada a outras comorbidades impactantes como lesões renal e neurológica no pós-operatório. Neste estudo, o tempo de CEC foi identificado como fator de risco para mortalidade. O tempo médio nos pacientes submetidos a CRM foi 94,4 min. Na literatura esse tempo varia de 65,8 a 120 min[13,16,24]. Nos pacientes que faleceram, o tempo médio de CEC foi superior (118,58 min), confirmando os achados de Oliveira et al.[13]. A possibilidade relativa de óbito é 209% maior quando o tempo de CEC é superior a 115 minutos (OR=3,09; IC 95% 2,04-4,68; P<0,001). Uma das maiores preocupações relacionadas à circulação extracorpórea é a síndrome de resposta inflamatória sistêmica (SIRS), caracterizada por alterações clínicas na função ventricular, pulmonar e renal, distúrbios da coagulação, suscetibilidade a infecções, alteração da permeabilidade vascular e acúmulo de líquidos no interstício, leucocitose, vasoconstricção e hemólise[25]. Vale ressaltar que apesar dessas alterações, a capacidade do organismo reverter esse quadro, e o uso de corticoide, uma alternativa eficaz na diminuição dos efeitos sistêmicos causados pela liberação de citocinas durante e após CEC[26], podem reduzir a taxa de morbimortalidade. Por outro lado, a CEC substitui as funções cardiopulmonares, busca manter integridade celular, estrutura, função e metabolismo dos órgãos e sistemas do indivíduo, permitindo operações mais complexas e prolongadas[27] como a revascularização miocárdica. No presente estudo, do total de pacientes estudados (n=1.628) 4,4% apresentaram lesão neurológica tipo I. Esse achado foi condizente com as duas maiores séries na literatura, que avaliaram mais de 16.000 pacientes submetidos a CRM com incidências de 2 a 4,6%[28,29]. Em nosso país, Guaragna et al.[17], avaliando 1.760 pacientes submetidos a CRM com CEC, encontram essa lesão em 3% deles. Dentre os pacientes que faleceram (n=141), 19% apresentaram lesão neurológica tipo I. Esse resultado é concordante com estudos prévios que evidenciaram taxa elevada de mortalidade (13 a 41%) em pacientes que tiveram essa lesão após CRM[30]. A chance relativa de óbito nos pacientes com lesão neurológica tipo I no pós-operatório foi significativamente elevada (OR = 4,42; IC 95% 2,48-7,81; P<0,0001). Esse achado foi similar ao constatado por Guaragna et al.[17], sendo a chance relativa de óbito 4,6 vezes maior em pacientes com essa lesão. Considerando a gravidade desse tipo de lesão no pós-operatório de pacientes submetidos a CRM com CEC, algumas medidas preventivas podem ser adotadas como estratégia de manejo individualizado para pacientes com doença cerebrovascular prévia, incluindo manipulação mínima da artéria aorta e manutenção do gradiente pressórico mais elevado durante a CEC. Dentre os 141 pacientes submetidos a CRM com CEC que faleceram, 21% deles utilizaram balão intra-aórtico. Essa taxa
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foi condizente com a literatura. Em revisão de 27 anos de uso de BIA realizado pelo Massachusetts General Hospital, a mortalidade dos pacientes que receberam BIA variou de 13,6 a 35%[31]. Segundo Christenson et al.[32] o uso profilático pré-operatório do BIA tem grande valia para prevenção de complicações trans e pós-operatórias. Nesta casuística, a possibilidade relativa de pacientes que utilizaram esse tipo de dispositivo para assistência ventricular irem a óbito foi significativamente elevada. A utilização de BIA está relacionada à existência de baixa fração de ejeção do ventrículo esquerdo e ou lesão coronariana considerável, indicadores de condição cardíaca precária, que podem aumentar a taxa de morbimortalidade em pacientes submetidos a CRM com CEC. Nos pacientes que foram a óbito, a mediana do tempo entre admissão hospitalar e procedimento cirúrgico foi 6 dias. Oliveira et al.[13] verificaram que a mortalidade foi maior entre pacientes com tempo de permanência pré-operatória igual ou superior a 3 dias. É importante salientar que o tempo de internação hospitalar antes do procedimento cirúrgico pode estar relacionado à maior gravidade clínica do paciente, sugerindo grau avançado de comprometimento coronariano que poderá implicar em aumento da taxa de morbimortalidade no pós-operatório. Como limitações do trabalho, devemos referir que trata-se de estudo não randomizado. Além disso, a influência de variáveis pré, intra e pós-operatórias na mortalidade de pacientes submetidos à CRM com CEC necessita de mais pesquisas científicas a longo prazo. A importância clínica dos resultados aqui obtidos reforça o enfoque multidisciplinar do paciente submetido à revascularização miocárdica, especialmente no pós-operatório. A identificação de fatores de risco para mortalidade é fundamental, uma vez que esse conhecimento pode subsidiar intervenções visando ao planejamento e execução de novas estratégias preventivas, e minimizando as complicações associadas a essa cirurgia. Essas informações também poderão ser utilizadas como um importante indicador da qualidade do cuidado no período pós-operatório, neste caso prestado no âmbito do SUS.
Papéis & responsabilidade dos autores CAS
MABO ACB PHHB JCMB MAS MFG DMB
Análise e/ou interpretação dos dados, aprovação final do manuscrito, concepção e desenho do estudo, realização das operações e/ou experimentos, redação do manuscrito ou revisão crítica de seu conteúdo Análise e/ou interpretação dos dados, análise estatística, redação do manuscrito ou revisão crítica de seu conteúdo Realização das operações e/ou experimentos, redação do manuscrito ou revisão crítica de seu conteúdo Concepção e desenho do estudo, realização das operações e/ ou experimentos Análise e/ou interpretação dos dados, aprovação final do manuscrito Aprovação final do manuscrito, concepção e desenho do estudo, redação do manuscrito ou revisão crítica de seu conteúdo Análise e/ou interpretação dos dados, análise estatística, concepção e desenho do estudo Análise e/ou interpretação dos dados, aprovação final do manuscrito, redação do manuscrito ou revisão crítica de seu conteúdo
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CONCLUSÃO
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.
Nos pacientes submetidos à revascularização miocárdica com circulação extracorpórea que foram a óbito, as variáveis pré, intra e pós-operatórias mais frequentes foram sexo masculino, complicações pulmonares, uso de balão intra-aórtico e lesão neurológica tipo I. 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 identificados como fatores de risco para mortalidade no período pós-operatório.
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
1
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®). 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®), 50 mg/ ml, and Hydrochloride of Xylazine (Xilazin®) 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. 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.
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1. Parks DA, Granger DN. Contributions of ischemia and reperfusion to mucosal lesion formation. Am J Physiol. 1986;250(6 Pt 1):G749-53.
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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, L’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 therapeu-
tic success rates and re- interventions obtained demonstrate the necessity of thorough clinical follow-up of these patients in a long time.
Faculdade de Medicina da Universidade de São Paulo (FMUSP), SP, Brasil, Instituto Dante Pazzanese de Cardiologia (IDPC), São Paulo, SP, Brasil e Hospital Salvalus (HS), São Paulo, SP, Brasil. 2 Faculdade de Medicina da Universidade de São Paulo (FMUSP), SP, Brasil e Seção Médica de Cirurgia Vascular e Centro de Intervenções Endovasculares (CIEV) do Instituto Dante Pazzanese de Cardiologia (IDPC), São Paulo, SP, Brasil. 3 Seção Médica de Radiologia e Centro de Intervenções Endovascular (CIEV) do Instituto Dante Pazzanese de Cardiologia (IDPC), São Paulo, SP, Brasil. 4 Secretaria da Saúde do Estado de São Paulo, São Paulo, SP, Brasil e Departamento das Doenças da Aorta do Instituto Dante Pazzanese de Cardiologia (IDPC), São Paulo, SP, Brasil 5 Seção Médica de Cirurgia Vascular e do Centro de Intervenções do Instituto Dante Pazzanese de Cardiologia (IDPC), São Paulo, SP, Brasil. 6 Faculdade de Medicina da Universidade de São Paulo (FMUSP), SP, Brasil e Instituto Dante Pazzanese de Cardiologia (IDPC), São Paulo, SP, Brasil.
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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. 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%
Hospital Salvalus (HS), São Paulo, SP, Brasil. Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brasil e Instituto Dante Pazzanese de Cardiologia (IDPC), São Paulo, SP, Brasil.
1
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Trabalho realizado no Instituto Dante Pazzanese de Cardiologia (IDPC), São Paulo, SP, Brasil e Hospital Salvalus (HS), São Paulo, SP, Brasil. Não houve suporte financeiro. Endereço para correspondência: Patrick Bastos Metzger Rua Dr. Dante Pazzanese, 500 - Vila Mariana, São Paulo, SP, Brasil – CEP: 04012-909 E-mail: patrickvascular@gmail.com Artigo recebido em 27 de janeiro de 2014 Artigo aprovado em 3 de março de 2014
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e 83,3%, respectivamente. A mortalidade perioperatória foi de 11,1%. Não houve óbito durante o acompanhamento de 1 ano. A taxa de reintervenção 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 de-
monstrou 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.
INTRODUÇÃO
servacional, realizado em dois centros de referência para afecções cardiovasculares, no período de janeiro de 2010 a dezembro de 2012, num total de 18 pacientes submetidos ao reparo híbrido das doenças do arco aórtico.
O manejo dos pacientes com 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[1,2]. Tradicionalmente, o reparo cirúrgico total do arco aórtico demanda um período de hipotermia profunda e parada circulatória, podendo provocar altas taxas de morbimortalidade perioperatória[1-3]. A realização das derivações dos troncos supra-aórticos seguidas do reparo aórtico endovascular é uma alternativa menos invasiva para o tratamento dessa grave afecção, tendo sido relatado em diversos estudos clínicos, revisões sistemáticas e meta-análises recentes[3-5]. O reparo endovascular total do arco aórtico tem se mostrado nas últimas 2 décadas como um método promissor, entretanto, existe na literatura uma divergência de informações quanto à segurança desta técnica a curto e médio prazo, aos critérios de seleção dos pacientes, além do que, pouco se sabe a respeito da durabilidade do material e do método a longo prazo[5-8]. Os dados disponíveis na literatura dos diversos tipos de tratamento são resultados de pequenas séries de casos, com amostras heterogêneas e seguimento limitado[9]. Portanto, o método ideal para o tratamento das doenças do arco aórtico é ainda motivo de intenso debate. O objetivo deste estudo é analisar os resultados a curto e médio prazo de uma série consecutiva de pacientes submetidos ao tratamento híbrido das doenças do arco aórtico tendo como desfechos estudados o sucesso técnico e terapêutico, a morbimortalidade perioperatória e em 1 ano, os desfechos neurológicos em 30 dias, a taxa de vazamentos e de reintervenções durante o seguimento.
Critérios de inclusão e exclusão Foram incluídos no estudo pacientes de ambos os sexos, com ou sem sintomas torácicos, com indicação de correção aórtica por: 1. Aneurismas de aorta torácica com diâmetro maior que 60 mm ou dissecções agudas complicadas tipo B de Stanford (AAT), apresentando zonas de ancoragem proximal inadequadas (extensão < 2 cm e/ou presença de trombo ou placas calcificadas maiores que 50% da circunferência do colo proximal). 2. Pseudoaneurisma de arco aórtico. 3. Úlcera penetrante do arco aórtico ou de aorta torácica com mais de 2 cm de diâmetro e 1 cm de profundidade sem zonas de ancoragem proximal. 4. Aneurismas verdadeiros de arco aórtico (AArA). 5. Dissecção tipo A crônica. Foram excluídos do estudo pacientes com: colo aórtico de fixação proximal de extensão maior que 20 mm, diâmetro das artérias ilíacas externas menor que 7 mm, creatinina sérica maior 2,0 mg/dl ou clearence de creatinina menor 30 ml/min. Pacientes que foram submetidos à correção endovascular de aneurisma de aorta torácica e que não realizaram a revascularização dos trancos supra-aórticos foram excluídos do presente estudo. A avaliação do risco cardiológico e/ou anestésico não foi considerada na inclusão ou exclusão dos pacientes. A programação terapêutica foi realizada com angiotomografia em todos os casos, sendo a arteriografia pré-operatória método diagnóstico opcional. Todas as tomografias foram reconstruídas no software OSIRIX® MD em modo 3D (tridimensional) e em modo MPR (reconstrução multiplanar), sendo, então, obtidos os diâmetros, angulações e extensões do colo aórtico proximal (Figura 1).
MÉTODOS Tipo de estudo Trata-se de um estudo retrospectivo, longitudinal, ob-
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Fig. 1 - Angiotomografia com reconstrução multiplanar e tridimensional. A=Corte axial demonstrando a porta de entrada da dissecção ao nível de origem de artéria subclávia esquerda. B=Maior diâmetro da aorta. C=Corte sagital. D=Artéria mesentérica superior com origem na luz verdadeira. E=Acometimento da aorta abdominal. F=Dissecção ao nível de artéria ilíaca esquerda. G=Reconstrução tridimensional em oblíqua anterior esquerda. H=Reconstrução tridimensional em oblíqua anterior direita
Técnica cirúrgica A extensão da revascularização dos troncos supra-aórticos foi programada após a avaliação angiotomográfica das zonas de ancoragem proximais e estratificada utilizando a classificação de Ishimaru & Mitchell[10] (Figura 2): Zona 0: Revascularização de 3 ou 4 vasos supra-aórticos com a realização de esternotomia mediana (Figura 3A). Zona 1: Enxerto carotídeo-carotídeo com tunelização retrofaringeana ou anterior à traqueia associada à revascularização da artéria subclávia por transposição ou enxerto carotídeo-subclávio (Figura 3B). Zona 2: Revascularização da artéria subclávia por transposição ou enxerto carotídeo- subclávio (Figura 3C). Técnica endovascular Todos os procedimentos foram realizados no laboratório de Hemodinâmica do Centro de Intervenções Endovasculares (CIEV) do Instituto Dante Pazzanese de Cardiologia e do Hospital Salvalus, pelo mesmo grupo formado por cirurgiões vasculares, cardiovasculares e radiologistas intervencionistas. Os pacientes foram tratados sob anestesia geral inalatória. A profilaxia antimicrobiana foi realizada com 1,5 g de cefuroxima, no momento da indução anestésica. A abordagem foi preferencialmente realizada pela artéria femoral comum por dissecção cirúrgica aberta unilateral. Na impossibilidade dessa via de acesso, optou-se pela abordagem da artéria ilíaca externa por acesso retroperitoneal.
Fig. 2 - Zonas de ancoragem do aneurisma torácico segundo classificação de Ishimaru e Mitchell. Nas doenças que acometem as zonas 0 a 2, procedimentos de revascularização dos troncos supra-aórticos são necessários.
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Fig. 3 - Enxerto carotídeo- subclávia esquerdo com ancoramento da prótese em zona 2. A=Angiotomografia em corte axial demonstrando volumoso aneurisma torácico sem zona de ancoragem proximal. B=Reconstrução angiografia tridimensional pré-implante de endoprótese. C=Angiografia por subtração digital com ancoramento da prótese em zona 2 e enxerto carotídeo-suclávia patente. D=Reconstrução angiográfica tridimensional após implante de endoprótese sem vazamentos
O controle radiográfico foi feito com aparelho Siemens® Artis Flat Panel ou em sala híbrida com o aparelho Siemens® Artis zeego Hybrid. Foram utilizados os dispositivos: Valiant® (Medtronic Inc, Santa Rosa, Calif), Zenith TX2® (Cook, Bloomington, Ind), TAG® (W.L. Gore & Assoc, Flagstaff, Ariz), Relay® (Bolton Medical, Sunrise, Fla). Os diâmetros das endopróteses variaram em 10% a 20% de oversize a depender do tipo de doença aórtica a ser tratada. Nos casos de aneurismas verdadeiros foi utilizado um oversize de 20% e em casos de dissecção o utilizado foi 10% a 15%. A drenagem do líquido cérebro-espinhal foi realizada em casos selecionados a depender da extensão de cobertura da aorta ou da presença de cirurgias aórticas prévias. Nos pacientes onde as próteses foram implantadas na zona 0, taquicardia induzida por marca-passo temporário foi utilizada. Nos casos de implante em zona 1 e 2, hipotensão permissiva foi utilizada para a liberação precisa da endoprótese. A arteriografia intraoperatória foi realizada em todos os pacientes. O pós-operatório imediato foi feito em unidade de terapia intensiva em todos os casos.
2-Sucesso terapêutico: Quando a liberação da endoprótese ocorreu sem vazamentos tipo I e/ou III, ou outras intercorrências que repercutissem na evolução favorável da doença aórtica, preservando a patência dos troncos supra-aórticos revascularizados. 3-Mortalidade perioperatória: Número de óbitos registrados dentro dos primeiros 30 dias após o procedimento. 4-Morbidade neurológica nos primeiros 30 dias: acidente vascular encefálico isquêmico (AVE-i) e paraplegia secundária à isquemia medular. 5- Mortalidade durante o seguimento de 1 ano. RESULTADOS No período compreendido entre janeiro de 2010 a dezembro de 2012, foram realizadas 95 correções endovasculares de doenças da aorta torácica, dos quais 18 pacientes foram submetidos à correção híbrida dessas de forma consecutiva. As características demográficas, as comorbidades e indicações de tratamento estão descritas na Tabela 1. A idade média foi de 62,3±8,3 anos, com prevalência do sexo masculino. Os pacientes eram assintomáticos em 13 casos (72,2%), foram diagnosticados em achados de exames de rotina. A hipertensão esteve presente em todos os pacientes. Entre as comorbidades presentes, encontramos elevada incidência de doença pulmonar obstrutiva crônica (DPOC) (44,4%) e de cardiopatia isquêmica (27,8%). Observamos também que 2 pacientes foram submetidos à correção prévia de aneurisma de aorta ascendente (11,1%) e 1 foi submetido à correção endovascular de aneurisma de aorta abdominal previamente. (Tabela 1) A maior parte das indicações para o tratamento híbrido foram: aneurismas verdadeiros do arco aórtico e da aorta torácica descendente com colo de ancoragem < 2 cm ou desfavorável (Tabela 1). A maioria dos pacientes foi tratada de forma eletiva (72,2%), com o tratamento híbrido estagiado em dois tempos. Cinco pacientes que apresentaram dissecção tipo A ou B aguda complicada foram submetidos à cirurgia de urgência com tratamento cirúrgico e endovascular no mesmo tempo.
Acompanhamento pós-operatório Os pacientes foram acompanhados com avaliação ambulatorial aos 15, 30, 180, e 360 dias após a correção. Após o primeiro ano, as consultas foram realizadas anualmente. O controle com angiotomografia foi realizada no 30° e no 360° dias de seguimento ambulatorial. O ultrassom – Doppler (USG-D) foi realizado no 30o, 180o dias e anualmente com a finalidade de avaliar a patência dos enxertos supra-aórticos. Desfechos e definições Os desfechos primários analisados foram assim definidos: 1-Sucesso técnico: Quando a derivação dos troncos supra-aórticos foi realizada de maneira previamente planejada; e quando o objetivo de liberar a endoprótese na área acometida foi alcançado, mesmo na presença de vazamentos ou outras intercorrências que pudessem influenciar desfavoravelmente a evolução da doença aórtica.
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Anestesia geral inalatória foi utilizada em todos os casos, com drenagem liquórica seletiva. As técnicas usadas para a revascularização dos troncos supra-aórticos estão descritas na Tabela 2. Foram realizados 8 enxertos anatômicos (revascularização total do arco aórtico) e 10 enxertos extra- anatômicos (enxertos carotídeo direito-carotídeo esquerdo e/ou enxerto ou transposição carotídeo esquerdo-subclávia esquerda). Todos os enxertos anatômicos foram feitas com prótese de Dacron® bifurcado e/ou reto. Quanto às pontes extra-anatômicas, foram realizadas com o uso de PTFE anelado 6 ou 8, com tunelização retrofaringeana em 2 casos e em um caso por tunelização anterior à traqueia. Quanto às pontes carotídea esquerda–subclávia, foram confeccionadas 7 transposições de artéria subclávia e 3 enxertos carotídeo-subclávia. Um dos pacientes, que já possuía correção prévia da aorta ascendente, realizou enxerto aorta ascendente-tronco braquiocefálico associado a enxerto carotídeo-carotídeo e em segundo tempo um implante de plug vascular na origem do tronco braquiocefálico e correção aórtica endovascular com implante de endoprótese em zona 0. Neste caso, foi feita oclusão intencional da artéria subclávia esquerda, após confirmação da patência e dominância da artéria vertebral direita (Figura 3). Não foram observadas durante o período intra e pós-operatório lesões venosas, linfáticas ou neurológicas. Durante o seguimento de um ano, não ocorreram oclusões ou estenoses hemodinamicamente significativas nos enxertos anatômicos ou extra-anatômicos (Figuras 4 e 5). As revascularizações que necessitaram de troca do segmento da aorta ascendente foram realizadas com parada cardíaca total e circulação extracorpórea, enquanto nos casos em que apenas a revascularização supra-aórtica foi empregada a anastomose proximal foi realizada por meio de pinçamento parcial da aorta, sem interrupção do fluxo. As anastomoses cervicais foram demarcadas com material radiopaco com a finalidade de facilitar o implante da endoprótese. Todos os acessos aórticos foram realizados por esternotomia mediana convencional. Os acessos cervicais via incisão supraclavicular e/ou cervical anterior uni ou bilaterais, foram utilizadas a depender do tipo de revascularização supra-aórtica desejada. O sucesso técnico foi obtido em 94,5%, ou seja, em 17 pacientes foi possível realizar o enxerto supra-aórtico programado e liberar a endoprótese no local desejado. O sucesso terapêutico foi de 83,3%, ou seja, em 15 pacientes a prótese foi liberada sem vazamentos ou outras intercorrências que repercutissem na evolução favorável da intervenção. As causas de insucesso terapêutico foram o vazamento tipo I em 2 casos e um óbito ocorrido no intraoperatório durante uma correção de dissecção tipo A de Stanford, que evoluiu com dissecção retrógrada e ruptura aórtica com tamponamento cardíaco.
Tabela 1. Dados clínicos ( n=18). Valor ( %) Características da população Idade média (anos) Sexo masculino Doença Sintomática AAT verdadeiros Pseudoaneurismas AArA Dissecção Aórtica tipo B aguda Dissecção tipo A aguda Dissecção tipo A crônica Diabetes Mellitus Hipertensão Dislipidemia Tabagismo Insuficiência Renal crônica Cardiopatia Isquêmica Doença Pulmonar Obstrutiva Crônica Cirurgia Aórtica prévia Acidente Vascular Encefálico Insuficiência Cardíaca Congestiva
n=18 62,3±8,3 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%)
AAT=aneurismas da aorta torácico; AArA=aneurisma do arco aórtico Tipo A e B da classificação de Stanford
Tabela 2. Detalhes técnicos em 18 revascularizações dos troncos supra-aórticos. Detalhes técnicos
Número Descrição da de eventos (%) revascularização Procedimento estagiado 13 (72,2%) Zona 0 8 (44,4%) 2 pontes Ao-Ao + revascularização do Tbc + Cce + Sbc 5 pontes Ao-Tbc + Ao-Cce + Sbc 1 ponte Ao-Tbc (tronco aórtico unicarotídeo) + embolização proximal do Tbc Zona 1
4 (22,2%)
3 pontes Ccd-Cce + transposição de Sbc 1 transposição Sbc-Cce (tronco unicarotídeo)
Zona 2
6 (33,3%)
3 transposições Sbc-Cce 3 pontes Sub- Cce.
21
15 pacientes utilizaram uma endoprótese. 3 pacientes utilizaram duas endopróteses.
Número de endopróteses utilizadas.
Ao- Ao= aorto-aórtico; Tbc=Tronco braquio-cefálico; Cce=carótida comum esquerda; Sbc=Subclávia; Ccd=Carótida comum direita
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Fig. 4 - Enxerto carotídeo-carotídeo associado à transposição da artéria subclávia esquerda e implante da endoprótese em zona 1. A=angiotomografia em corte sargital com aneurisma torácico sem zona de ancoragem adequada em zona 2 devido à extrema proximidade entre a carótida esquerda e a subclávia esquerda. B=Angiotomografia em corte axial demonstrando volumoso aneurisma torácico. C=Angiotomografia com reconstrução volumétrica. D=Revascularização dos troncos supra- aórticos com enxerto carotídeo-carotídeo associado à transposição da artéria subclávia esquerda. E=Aortografia pré-implante de endoprótese com patência dos enxertos extra-anatômicos. F=Aortografia após implante de endoprótese demonstrando endoprótese aórtica em Zona 1, sem vazamentos e com perviedade dos troncos supra-aórticos
A taxa de complicação pós-operatória intra-hospitalar foi de 27,7%, sendo: duas lesões neurológicas isquêmicas (11,1%), dois casos de complicação pulmonar (11,1%) e um caso de insuficiência renal aguda (5,5%) (Tabela 3). A mortalidade perioperatória foi de 11,1%. Os dois óbitos ocorreram devido à dissecção A retrograda: um por ruptura e tamponamento cardíaco agudo durante o tratamento endovascular e outro por dissecção de tronco coronário esquerdo e infarto agudo do miocárdio no 8° dia pós-operatório (Tabela 4). Após o período de 30 dias de seguimento, não houve óbitos. A taxa de vazamento primário foi de 16,6%, ocorrendo o vazamento tipo I em 2 casos e tipo II em 1 caso. Não houve casos de vazamentos tipo III e de migração de endoprótese durante o seguimento dos pacientes. A taxa de reintervenção em um ano foi de 16,7% devido ao tratamento de vazamentos do tipo I e II de forma satisfatória (Tabela 4). A sobrevida anual, durante nosso acompanhamento, foi de 89,9%. Os dispositivos das endopróteses utilizadas foram: em 7 casos (38,9 %) a Zenith TX2® (Cook Medical; Bloomington, INC, EUA), 6 casos (33,3%) a TAG® (Gore Medical; Flagstaff, AZ, EUA), em 3 casos a (16,6%) Valiant® (Medtronic; Minneapolis,
MN, EUA), e em 2 casos (11,1%) Relay® (Bolton Medical, Sunrise, Fla). Foram utilizadas um total de 21 endopróteses. O tempo médio de procedimento endovascular foi de 65 min (variação de 48 minutos a 151 min), o tempo médio do procedimento de revascularização dos troncos supra-aórticos foi de 196 min e o tempo de internação médio foi de 9,7 dias, com variação de 10 dias. O tempo médio de seguimento pós operatório foi de 13 meses (5 a 22 meses). DISCUSSÃO O aprimoramento das técnicas endovasculares e a associação à revascularização cirúrgica dos troncos supra-aórticos permitiram sua aplicação nas doenças do arco aórtico, território em que o tratamento cirúrgico convencional pode trazer altas taxas de morbimortalidade[11]. Revisões sistemáticas e estudos clínicos recentes têm confirmado as vantagens do método endovascular sobre o tratamento cirúrgico convencional neste segmento aórtico[1-3,7,11-13]. Uma zona de ancoragem adequada, em que haja ao menos 2 cm de extensão de aorta sadia é necessária para um correto implante da endoprótese, prevenindo assim o endoleak tipo I e mantendo a durabilidade da prótese por um longo período[14].
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Fig. 5 - Enxerto aorta ascendente-tronco bráquiocefálico associado a enxerto carotídeo- carotídeo com colocação de plug vascular e implante de endoprótese aórtica em Zona 0. Oclusão intencional de artéria subclávia esquerda. A=Enxerto cirúrgico aorta ascendente-tronco braquiocefálico. B=Arteriografia pré-operatória demonstrando perviedade do enxerto aorta ascendente-tronco braquiocefálico e carotídeo-carotídeo direita-esquerda. C=Implante de endoprótese em zona 0 e arteriografia por subtração via subclávia direita demonstrando vazamento do tipo 2 oriundo do tronco braquiocefálico com enchimento da artéria sublávia esquerda. D=Implante de plug vascular de 22 mm no óstio do tronco braquiocefálico. E=Arteriografia de controle sem vazamentos do tipo 2. F: Aortografia torácica sem vazamentos e com desconexão dos troncos supra-aórticos nativos.
Tabela 3. Complicações intra e perioperatórias (n=18). Número de eventos (%) Desfechos Amostra n=18
Tabela 4. Dados dos vazamentos primários (n=18). Número de eventos (%) Amostra Tipos de Endoleak n=18
Complicações intraoperatórias Embolização periférica Lesão femoral Tamponamento cardíaco Complicações intra-hospitalares Paraplegia Complicação pulmonar AVE-i Insuficiência Renal Aguda Infarto agudo do miocárdio Óbito
Total Tipo Ia Tipo Ib Tipo II Tipo III Tipo IV Taxa de reintervenção
0 0 1 (5,5%) 1 (5,5%) 2 (11,1%) 1 (5,5%) 1 (5,5%) 1 (5,5%) 2 (11,1%)
AVE-i=Acidente vascular encefálico isquêmico
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3 (16,6%) 2 (11,1%) 0 1 (5,5%) 0 0 3 (16,6%)
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Para os pacientes com colo proximal desfavorável, a revascularização dos troncos supra-aórticos, seguida do avanço do dispositivo endovascular para zonas de aorta sadia, torna factível o tratamento dessa doença, evitando o procedimento cirúrgico convencional que demande parada circulatória e hipotermia profunda. A mortalidade do procedimento cirúrgico convencional sobre o arco aórtico, mesmo em centros com grande volume cirúrgico, varia entre 0,9 a 9,3%[3,15,16]. Entretanto, de acordo com os dados do National Inpatient Sample Database e do Medicare Provider Analysis and Reviewer, que refletem melhor a realidade mundial, as taxas de mortalidade variam entre 15 a 20%[17-20]. Apesar da invasibilidade da técnica híbrida, seu grau de morbidade pode ser minimizado utilizando-se menor tempo de pinçamento aórtico ou técnicas de pinçamento parcial da mesma quando se necessite avançar a prótese até a zona 0. Nos casos em que um colo de aterrissagem adequado possa ser obtido nas zonas 1 e 2, os procedimentos estagiados sem pinçamento aórtico com o uso de enxertos extra-anatômicos devem ser utilizados[2,3]. Obtivemos uma taxa de sucesso técnico de 94,5% e de terapêutico de 83,3%. A taxa de sucesso técnico foi influenciada pelo óbito intraoperatório, enquanto a taxa de sucesso terapêutico foi influenciada pela presença de vazamentos tipo Ia, gerando uma taxa de vazamento primário de 16,6%. Os dois vazamentos do tipo Ia foram tratados com o avanço de uma segunda endoprótese proximalmente de maior diâmetro com selamento completo do vazamento, enquanto que o vazamento do tipo II pela artéria subclávia foi tratada com embolização da mesma com o uso de mola, o que gerou uma taxa de reintervenção de 16,6%. Moulakakis et al.[1] relatam uma taxa de sucesso técnico de 92,8%, apresentando uma taxa de vazamentos similar de 16,6% cuja maioria era do tipo I. Os autores justificam este dado devido a presença de dissecção tipo A retrógrada em 4,5% de seus pacientes, com o avanço da endoprótese até zona 0[1]. Atualmente, os resultados tardios do tratamento híbrido do arco aórtico são pouco conhecidos, a maioria dos estudos apresentando acompanhamento de 15 a 18 meses[6,21]. Estes dados são extremamente escassos e heterogêneos quando especificamente se avaliam os endoleaks. Esta taxa varia na literatura de 0 a 15%, sendo que os dados de vazamentos a longo prazo são virtualmente ausentes[4,8,21]. Czerny et al.[4], em recente estudo com dados de registro transcontinental incluindo 66 pacientes com revascularização total do arco aórtico e um acompanhamento médio de 25 meses, encontraram apenas 1 endoleak tardio do tipo Ib e uma sobrevida em 5 anos de 96%[4]. Já Vallejo et al.[6] em uma série de 38 reparos híbridos do arco aórtico, com uma média de seguimento de 28 meses, obtiveram 4 endoleaks tipo I e dois endoleaks tipo II[6]. Bavaria et al.[8], em acompanhamento de 30 meses, não observaram a presença de vazamentos do tipo I ou III. Em nosso estudo, não observamos a presença de vazamentos tardios do tipo I, II e III durante o seguimento médio de 13 meses.
A população do nosso estudo apresentava alto risco para cirurgia convencional devido à elevada prevalência de doença pulmonar obstrutiva crônica (50%) e de cardiopatia isquêmica (38,9%), sendo que 5 desses pacientes foram tratados de forma emergencial devido à dissecção aguda tipo A ou tipo B complicada, por isso, nossa taxa de mortalidade no período de 30 dias foi de 11,1%. Um paciente veio a óbito durante o período intraoperatório devido à progressão retrógrada da dissecção tipo A com a ruptura aórtica e tamponamento cardíaco e outro paciente veio a óbito no 8° DPO devido também à progressão da dissecção tipo A retrógrada com acometimento do tronco da coronária esquerda e infarto agudo do miocárdio. Autores brasileiros relatam taxa de mortalidade de 16,7% no período perioperatório utilizando a mesma técnica[2]. Uma recente meta-análise publicada em 2013, com 956 pacientes analisados, obteve uma taxa de mortalidade perioperatória de 11,9%[1]. Entretanto, séries de menores de casos têm sido publicadas com mortalidade variando entre 3 a 6%[3,11]. As taxas de injúria neurológica na literatura as taxas variam de 4 a 12%[11]. Quando se separam AVE-i de isquemia da coluna espinhal com paraplegia definitiva observam-se taxas de 7,6% e 3,6%, respectivamente, no estudo meta-analítico publicado por Moulakakis et al.[1] Em nosso meio, observamos uma taxa de AVE-i de 5,5%. Este ocorreu durante o avanço da endoprótese até a zona 0. A ocorrência deste desfecho neurológico está relacionada diretamente com a qualidade da aorta nativa, tendo como características desfavoráveis a presença de placas e trombos neste segmento aórtico[22]. A baixa taxa de AVE-i encontrada por Shirakawa et al.[11], em seu estudo clínico com 40 pacientes e um acompanhamento de 15,5 meses, é justificada pelo autor devido à seleção pré-operatória criteriosa dos pacientes com angiotomografia, avaliando as condições de implante da endoprótese na aorta ascendente. Quando uma aorta sadia foi encontrada, o tratamento híbrido foi realizado[11]. Tivemos um caso de isquemia medular em paciente que apresentava previamente uma correção aberta da aorta ascendente e uma correção endovascular prévia de aneurisma de aorta abdominal infra-renal. Este paciente apresentou sinais de paraplegia no 3° DPO, sendo realizada drenagem liquórica imediata, porém, permaneceu com paraplegia definitiva como sequela. A isquemia medular está diretamente relacionada à área de cobertura aórtica e ao tempo de pinçamento aórtico[1,3,23], por isso, as taxas de isquemia medular nos procedimentos híbridos são menores quando comparadas às correções aórticas abertas, uma vez que nos procedimentos híbridos a área de cobertura aórtica é menor assim como o tempo de pinçamento. Neste paciente, a área de manipulação aórtica prévia ao procedimento híbrido favoreceu esta complicação. Quanto às complicações pós-operatórias, destaca-se a baixa incidência de complicação pulmonar (11,1%). Dois pacientes apresentaram desmame ventilatório prolongado e infecção
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pulmonar associada, sendo tratados em unidade de terapia intensiva por período prolongado, mas evoluindo satisfatoriamente. As principais morbidades clínicas no pós-operatório no tratamento aberto e híbrido das doenças da aorta torácica são as complicações pulmonares e cardiológicas. A taxas destas complicações foram de 19,7% e 6%, respectivamente, na meta-análise publicada em 2013[1]. Em nosso estudo, tivemos um óbito por infarto agudo do miocárdio provocado por dissecção retrógrada com acometimento de tronco de coronária esquerda. Apesar do grande número de pacientes com DPOC em nosso estudo, a baixa taxa de complicações pulmonares é explicada devido à rigorosa estratificação e preparo clínico pré-operatório, assim como cuidados intensivos dedicados à reabilitação cardiopulmonar adequada. A dissecção tipo A retrógrada é uma complicação descrita durante o reparo aberto e endovascular da aorta ascendente nativa[1,7,21]. Quando se avaliam os estudos clínicos quanto à presença desta complicação, observa-se que os dados são divulgados em relação a toda a casuística tratada, apresentando uma taxa absoluta de 3,8% na meta-análise mais recente publicada; porém, quando se observam apenas as aortas ascendentes nativas sobre risco, obtêm-se taxas mais elevadas desta complicação. No estudo publicado por Andersen et al.[7], uma incidência similar de 3,4% é relatada numa série de 87 pacientes com reparo híbrido do arco aórtico. Entretanto, os autores relatam que a verdadeira taxa deveria ser 11,1% (3 de 27 casos) quando são incluídos apenas os pacientes com aorta ascendente nativa que estão sob risco desta complicação[3,7]. Tivemos 2 casos de dissecção tipo A retrógrada em 16 aortas ascendentes nativas (12,5%). Novas técnicas com o manejo endovascular completo dos aneurismas do arco aórtico utilizando endopróteses ramificadas e fenestradas estão em desenvolvimento. O primeiro estudo clínico está sendo conduzido e, dessa forma, pouco se sabe sobre os resultado a médio e longo prazo desta técnica[24]. Procedimentos endovasculares utilizando as técnicas de Snorkel e Chaminé, apesar de viáveis, expõem o paciente ao endoleak tipo I e a dissecção tipo A retrógrada[25].
O acometimento da aorta ascendente por dissecção tipo A e a necessidade de implante na zona 0 apresentaram uma taxa maior de eventos neurológicos agudos e de dissecção tipo A retrógrada. As taxas de sucesso terapêutico e das reintervenções necessárias nos diversos segmentos do arco aórtico tratados demonstram a necessidade de seguimento clínico rigoroso desses pacientes a longo prazo. Papéis & responsabilidade dos autores PBM
FHR SMM MI NMI JJD DSN AMK
Análise e/ou interpretação dos dados, análise estatística, aprovação final do manuscrito, concepção e desenho do estudo, realização das operações e/ou experimentos, redação do manuscrito ou revisão crítica de seu conteúdo Aprovação final do manuscrito, realização das operações e/ou experimentos, redação do manuscrito ou revisão crítica de seu conteúdo Aprovação final do manuscrito, realização das operações e/ou experimentos Aprovação final do manuscrito, realização das operações e/ou experimentos Aprovação final do manuscrito, realização das operações e/ou experimentos Aprovação final do manuscrito, realização das operações e/ou experimentos Realização das operações e/ou experimentos Aprovação final do manuscrito, realização das operações e/ou experimentos, redação do manuscrito ou revisão crítica de seu conteúdo
REFERÊNCIAS 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. 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.
Limitações do estudo Devido ao pequeno número de casos, ao grupo heterogêneo de pacientes e de tipos de procedimentos realizados, assim como ao seguimento curto de acompanhamento, a comparação entre as técnicas e a relação com seus desfechos limitam os resultados de nosso estudo. Por fim, a acurácia dos resultados pode ser afetada pela análise retrospectiva dos dados.
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. 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.
CONCLUSÃO
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.
Em nosso estudo, o tratamento híbrido das doenças do arco aórtico demonstrou ser uma alternativa tecnicamente viável e com resultados satisfatórios ao curto e médio prazo.
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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
28 72
2 36 33 23
2.1 38.3 35.1 24.5
38 62
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
Death
48 36
46.2 34.6
12 8
11.5 7.7
25 59
24 56.7
9 11
8.7 10.6
56 26
57.7 26.8
11 4
11.3 4.1
1 83
1 79.8
2 18
1.9 17.3
37 47
35.6 45.2
13 7
12.5 6.7
20 60
20 60
8 12
8 12
35 41
37.2 43.6
3 15
3.2 16
55 23
56.7 23.7
9 10
9.3 10.3
65 15
65.7 15.2
12 7
12.1 7.1
29 51
29 51
9 11
9 11
50 33
48.5 32
15 5
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 45.35±17.8 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. Echocardiography’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.
Authors’ 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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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
1
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 patients’ 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 × 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.
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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)
1
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® 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.
Authors’ 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.
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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, Brasil.
Endereço para correspondência:
Trabalho realizado no Hospital Ana Nery (HAN), Salvador, BA, Brasil.
Felipe da Silva Pereira Rua Saldanha Marinho, S/N - Caixa d’Água - Salvador, BA Brasil - CEP: 40320-010 E-mail: fs.pereira@globomail.com
1
Não houve suporte financeiro.
Artigo recebido em 20 de agosto de 2013 Artigo aprovado em 11 de dezembro de 2013
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Existem poucos estudos avaliando a mortalidade em pacientes com cardiopatia valvar. O foco deste estudo é avaliar o impacto da escolha do tipo de prótese na taxa de mortalidade intra-hospitalar em pacientes com cardiopatia reumática e não-reumática que realizaram cirurgia para troca valvar.
Abreviações, acrônimos e símbolos DP DR MS SPSS
Desvio Padrão Doença Reumática Ministério da Saúde Statistical Package for the Social Sciences
MÉTODOS Estudo analítico de corte transversal, com amostra de conveniência de pacientes que realizaram cirurgia para troca de válvula, durante um período de três anos no Hospital Ana Nery, Salvador, Bahia, Brasil. Todos os dados foram obtidos de prontuários médicos. A análise dos dados foi realizada com base nas diretrizes para a notificação de mortalidade e morbidade após intervenções de válvulas cardíacas[9]. 35 pacientes foram excluídos do estudo por insuficiência de dados registrados; assim, a amostra total estudada foi 353. Os dados foram analisados utilizando o SPSS versão 17.0. As variáveis contínuas tiveram a sua normalidade testada com o teste de Kolmogorov-Smirnov. Para comparação de médias, o teste T foi utilizado para variáveis de distribuição normal. Para comparar as variáveis categóricas o teste do qui-quadrado foi utilizado. O valor de P adotado como estatisticamente significante foi de P≤0,05. O projeto foi aprovado pelo comitê de ética institucional do Hospital Ana Nery sob o protocolo 59/10.
INTRODUÇÃO A doença cardíaca valvar se constitui em um importante problema de saúde pública. Desde a década de 50, a prevalência da doença valvar nos países desenvolvidos tem variado da etiologia reumática para doença valvar degenerativa[1]. No começo do século XX, a doença reumática (DR) foi uma das principais causas de morbidade e mortalidade entre os jovens de países desenvolvidos e em desenvolvimento[2,3], acometendo-os de maneira similar. Este padrão mudou por diversos fatores, a exemplo de um diagnóstico precoce, um tratamento mais adequado da DR e também devido ao aumento da expectativa de vida populacional levando ao acometimento da doença valvar em indivíduos mais idosos. A doença reumática, ainda nos dias atuais, tem alta prevalência em países em desenvolvimento como o Brasil, sendo uma importante causa de doença cardiovascular e responsável por elevados custos para o sistema público de saúde. De acordo com dados fornecidos pelo MS, durante o ano de 2011, houve 5.512 admissões hospitalares devido à febre reumática aguda e 8.127 relacionadas à valvulopatia reumática[4]. A taxa de mortalidade intra-hospitalar pós-cirúrgica é muito variável, em sua maior parte devido à gravidade dos pacientes internados e ao grau de experiência da equipe cirúrgica. De acordo com outros estudos a taxa de mortalidade varia entre 1% e 15%[1,5-8]. Após 40 anos de experiência com cirurgia de troca de válvula em território nacional, a decisão pelo tipo de prótese valvar mais apropriada a ser implantada na cirurgia ainda é controversa e, por vezes, complicada, principalmente para pacientes advindos de zonas rurais ou de pequenos centros urbanos. Não existe um substituto ideal. Existe um baixo risco de eventos tromboembólicos e hemorragia na utilização de prótese biológica, mas a sua durabilidade é curta. Por outro lado, a prótese metálica pode oferecer uma duração maior, porém com maior risco de sofrer tais eventos[9]. Marchand et al.[10] e Mykén et al.[11] demonstraram evolução satisfatória na sobrevida de pacientes em 14 e 15 anos, respectivamente, livre de disfunção estrutural em biopróteses tanto de sitio atrioventricular quanto aórtica.
RESULTADOS A amostra total estudada foi de 353 pacientes submetidos à cirurgia de troca da valva sendo que 73 destes foram realizaram substituição valvar e valvoplastia. 49,6% (n=175) eram do sexo masculino e 50,4% (n=178) do sexo feminino. A idade da população estudada variou de 6 a 82 anos e a idade média foi de 41,87±17,9 anos de idade. Na população em estudo foi observada um maior número de indivíduos provenientes de cidades do interior ou de zonas rurais (n=216, 61,2%) em relação aos da capital (n=137, 38,8%) (dados demográficos - Tabela 1). Foi observado um total de 698 válvulas acometidas, sendo 282 (40,4%) mitral, 214 (30,7%) aórtica, 183 (26,2%) tricúspide e 19 (2,7%) da válvula pulmonar. Destes, 53 (7,6%) apresentaram estenose, 461 (66%) tinham insuficiência e 184 (26,4%) cursaram com dupla lesão. Os pacientes também foram divididos a partir de seu principal mecanismo de lesão valvar: 204 (57,8%) tiveram doença reumática como a principal causa para a doença da válvula e 134 (38%) tinham doenças valvares por outras causas, como prolapso, secundaria a isquemia ou doença degenerativa, e 15 (4,2%) não tiveram etiologia definida. Em relação ao tipo de prótese usada, 70% (n=247) foram substituídos por bioprótese e 30% (n=106) por prótese metálica. A preferência por prótese biológica foi observada em todas as faixas etárias (Figura 1).
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Tabela 1. Dados demográficos. Classificação Gênero Masculino Feminino Idade 0-20 anos 21-30 anos 31-40 anos 41-50 anos 51-60 anos > 60 anos Etiologia da doença valvar Doença reumática Doença não reumática Dados perdidos Prótese Biológica Metálica Valva acometida Mitral Aórtica Mitral e aórtica
N
%
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 - Distribuição das próteses valvares por faixa etária.
A mortalidade global foi de 11% (n=39), não sendo observado diferença entre o tipo de prótese sobre a mortalidade global. A mortalidade por prótese mecânica em comparação com prótese biológica foi de 30,7% (n=12) x 69,3% (n=27), respectivamente, P=0,915. Na análise apenas dos pacientes com doença reumática também não foi observada diferença estatisticamente significante na taxa de mortalidade entre prótese metálica x biológica, 33,3% (n=3) x 66,7%, (n=6), respectivamente, P=0,586. A idade média±DP para o grupo que morreu era 54,49±21,9 anos, contra 41,19±16,8 anos daqueles que receberam alta hospitalar, P=0,000 (Figura 2). Entre os pacientes que morreram, 33 realizaram substituição de apenas uma válvula. Portanto, não houve impacto da dupla troca valvar sobre a mortalidade. Em relação ao local da cirurgia de substituição da válvula, os resultados são mostrados na Figura 3.
Fig. 2 - Número de óbitos vs. faixa etária.
DISCUSSÃO Houve grande prevalência da valvulopatia reumática (58,5%), nesse estudo, e esses dados estão de acordo com dados anteriores sobre a doença reumática, sendo esta uma das principais causas de doença cardíaca em países em desenvolvimento[10]. Não houve influência sobre a mortalidade no tipo de prótese utilizada na cirurgia de troca valvar para esse grupo estudado.
Fig. 3 - Número de óbitos vs. sítio valvar.
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A taxa de mortalidade pós-operatória é muito variável, sendo influenciada por vários fatores, tais como, troca múltipla de válvula, local acometido, reoperação, presença de outros procedimentos associados. Este estudo demonstrou uma taxa de mortalidade 10,6%, o que está de acordo com os dados da literatura que variam de 1% a 15%[12,13]. A idade média dos pacientes que morreram foi de 54,4±21,5 anos, maior que amostra total do estudo (40,40±16,8 anos), P=0,001. Provavelmente, essa diferença se deve às valvas que se apresentam com lesões mais graves, associada ou não à maior presença de comorbidades na população mais velha, uma vez que não houve associação entre o tipo de prótese e mortalidade quando a idade foi levada em consideração. Pacientes que realizaram troca de válvula mitral tiveram uma mortalidade maior, independentemente do tipo de prótese utilizada. Esse dado é compatível com que está relatado na literatura[7,14,15]. O impacto da escolha da prótese valvar para pacientes que tem etiologia reumática não foi devidamente estabelecida. O uso de bioprótese nessa população influencia na mortalidade tardia, já que pode significar um novo procedimento após alguns anos, um estudo prévio demonstra mortalidade semelhante à primeira cirurgia (1% a 15%)[16]. No entanto, Cen et al.[17] publicaram em 2001 que a escolha do tipo de prótese implantada não interferiu estatisticamente na sobrevida dos pacientes submetidos à re-troca valvar em 10 anos. No nosso estudo, foi possível observar que as vítimas de sequela reumática foram adultos jovens, especialmente as mulheres, acarretando em repercussões socioeconômicas como o aumento dos custos na saúde pública e a redução da produção laboral. Este estudo destacou que a lesão mais frequente foi a regurgitação valvar (66,2%) seguido da dupla lesão (25,9%) e estenose (7,9%), em desacordo com a literatura onde é demonstrado um predomínio de lesões estenóticas. Contudo, essa é uma comparação difícil de realizar diante da escassez de dados sobre a prevalência de lesões específicas, principalmente na doença reumática[18]. Geralmente, é muito difícil avaliar estes pacientes devido à baixa adesão ao tratamento, uma vez que suas famílias precisam realizar longas viagens, lidar com custo de alimentação e estadia, num cenário de um orçamento familiar limitado. Infelizmente, esse é um marco negativo para o tratamento com impacto sobre a escolha da prótese e possíveis consequências para um prognóstico mais tardio[19]. A maior prevalência de bioprótese no presente estudo pode ser justificada pelo grande número de pacientes de cidades do interior sem os adequados serviços médicos especializados, fato que frequentemente leva à má adesão ao tratamento e impede a instituição de terapêutica anticoagulante. O tipo de prótese não teve influência na mortalidade intra-hospitalar na população estudada, contudo, pode ser considerado um importante fator prognóstico para mortalidade
tardia na população valvulopata, com alta prevalência de etiologia reumática. Portanto, estudos de coorte com populações semelhantes, especialmente em países em desenvolvimento, devem ser estimulados.
Papéis & responsabilidade dos autores AMSF FSP LSB AVPN GBB ARD RAJ INL
Autor principal Coleta de material, análise estatística Coautora Pesquisa de referências Levantamento de prontuário, coleta de material Pesquisa de referências Pesquisa de referências Pesquisa de referências
REFERÊNCIAS 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
1
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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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
1
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 BMI CABG CAD COPD CPB DM HT Htc ICU LDL LIMA LMCA MI
Aortic cross-clamping Levels, body mass index Coronary artery bypass graft Atherosclerotic coronary artery disease Chronic obstructive pulmonary disease Cardiopulmonary bypass Diabetes mellitus Hypertension Pre- and postoperative hematocrit Intensive care unit Low-density lipoprotein Left internal mammarian artery Left main coronary artery 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 +
1
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 ECG EEG MAP
Cerebrovascular accidents Electrocardiogram Electroencephalography 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
METHODS
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.
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 ≤ 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
1
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 CPB DVT ECG EuroSCORE ICU LMCA MI POAF
Atrial fibrillation Cardiopulmonary bypass Deep vein thrombosis Electrocardiogram (European) System For Cardiac Operative Risk Evaluation Score Intensive care unit Left main coronary artery Myocardial infarction 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%)
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. 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
Requirement for Inotropes 0.057 IABP 1.000 Ventilation time (hours) 0.794 ICU stay (days) 0.559 Surgical site infection 1.000 Re-exploration for bleeding 0.62 or tamponade Pleural effusion 0 (0%) 0.24 3 (3%) DVT 1 (1%) 1.000 1 (1%) Atrial Fibrillation 18 (18%) 0.718 20 (20%) Inotrope requirement in 18 (18%) 0.32 12 (12%) ICU Hospital Stay (days) 7.4 ± 2.2 0.388 7.1 ± 1.4 IABP=Intra-aortic Balloon Pump; ICU=Intensive Care Unit; DVT=Deep Vein Thrombosis
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
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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
1
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
P
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, Zünd 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, Zakliczyński 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 factor for thrombosis in the postoperative period. Patients using AAS tend to deposit material in the tube wall. The small sample
Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (InCor-HCFMUSP), São Paulo, SP, Brasil. 2 Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP, Brasil. 3 Hospital do Coração, ASS, São Paulo, SP, Brasil.
Endereço para correspondência: Cristiane Felix Ximenes Pessotti Instituto do Coração (InCor) do Hospital das Clínicas da Faculdade de Medicina da 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
1
Trabalho realizado no Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo InCor-HCFMUSP, São Paulo, SP, Brasil.
Artigo recebido em 5 de abril de 2014 Artigo aprovado em 23 de setembro de 2014
Não houve suporte financeiro.
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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.
Abreviações, acrônimos e símbolos AAS POI SHCE TEP
Ácido acetil salicílico Pós-operatório imediato Síndrome de Hipoplasia do Coração Esquerdo Tromboembolismo pulmonar
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), submetidos à derivação cavopulmonar total com tubo extracardíaco, entre
Descritores: Técnica de Fontan. Embolia e Trombose. Varfarina. Aspirina. Estudos Prospectivos.
INTRODUÇÃO
pós-operatória da operação cavopulmonar total pode chegar a 20%. Em metanálise publicada recentemente[3], a incidência de tromboembolismo encontrada variou de 3 a 20%, com diferenças relacionadas à técnica cirúrgica, população considerada e acurácia dos métodos de imagem. A manifestação pode se dar pela formação de trombo venoso, arterial ou intracardíaco, evoluindo para óbito em cerca de 25% dos pacientes, mesmo quando instituído tratamento específico imediato[4,5]. A etiologia de complicações trombóticas em pacientes submetidos a operação tipo Fontan é multifatorial. Relatos de literatura suportam a hipótese de que outros fatores, além de estase venosa e baixa velocidade de fluxo, contribuem para a formação do trombo. Entre eles, estaria alterações de fatores de coagulação, tais como: proteína S, proteína C, antitrombina III, fator VII e VIII. Baseados nos achados de desbalanço entre estes fatores pró e anticoagulantes, muitos estudos sugerem que estes pacientes mantenham um estado de resistência a anticoagulação, ou hipercoagulabilidade[3,6]. Não há, até o momento, um consenso na literatura mundial a respeito da melhor droga na prevenção da formação de trombo no paciente em pós-operatório da derivação cavopulmonar total com tubo extracardíaco, sendo as drogas habitualmente utilizadas, o ácido acetil salicílico (AAS) e a varfarina.
Os corações univentriculares correspondem a um grupo de cardiopatias congênitas com diferentes combinações anatômicas, que culminam em uma característica comum: um único ventrículo responde pela circulação sistêmica e pulmonar. Na maioria dos casos, é possível caracterizar a presença de dois ventrículos distintos - direito e esquerdo - sendo um deles hipoplásico e chamado rudimentar e o outro, bem formado, chamado câmara principal. Entre as formas anatômicas mais comuns está a Atresia Tricúspide, em suas diferentes apresentações, responsável por 0,3-5,3% das cardiopatias congênitas, presente em aproximadamente 0,6 de cada 10.000 nascidos vivos[1]. No que diz respeito ao ventrículo direito dominante, a principal representação anatômica fica por conta da Síndrome de Hipoplasia do Coração Esquerdo (SHCE), que representa cerca de 3,8% das cardiopatias congênitas, presente em aproximadamente 1,8 a 3,65 de cada 10.000 nascidos vivos [2]. A partir do diagnóstico no período neonatal, diferentes estratégias cirúrgicas podem ser adotadas, de acordo com o achado anatômico e fisiopatológico, de maneira que o ventriculo dominante fique exclusivamente responsável pela circulação sistêmica e o retorno venoso sistêmico seja direcionado diretamente para as artérias pulmonares. Para tanto, uma série de cirurgias paliativas é realizada de maneira estadiada, até o estágio final, a operação cavopulmonar total, atualmente realizada através de conexão extracardíaca com tubo interposto entre a veia cava inferior e a artéria pulmonar direita (APD). A ocorrência de fenômenos tromboembólicos na evolução
OBJETIVOS Objetivos primários 1. Comparar a eficácia do uso do anticoagulante oral (Varfarina), e do antiagregante plaquetário (AAS), na profilaxia
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de trombose e fenômenos tromboembólicos, no pós-operatório da operação cavopulmonar total com tubo extracardíaco. 2. Identificar eventuais alterações laboratoriais: hematócrito, função hepática e fatores de coagulação; nos períodos pré e pós-operatórios. 3. Identificar e comparar a viabilidade dos diferentes tratamentos, quanto a aspectos clínicos, adesão, segurança e implicações sociais.
ção, como por exemplo qualquer indicação de que o paciente usasse necessariamente uma das duas drogas avaliadas, ou contraindicação no uso de uma delas. 4. Recusa do responsável legal, em assinar o Termo de Consentimento Pós-Informação A idade no momento da operação não foi considerada como fator de indicação ou contraindicação, sendo operadas crianças de diferentes idades. As crianças foram, dentro do protocolo de rotina da instituição, submetidas a estudo hemodinâmico pré-operatório, com cateterismo cardíaco e medidas de pressão média de artéria pulmonar (PAPm). Fez parte da avaliação pré-operatória, o Ecocardiograma Bidimensional com Doppler Colorido, Eletrocardiograma e Cateterismo Cardíaco. Sendo elegível para a realização da derivação cavopulmonar total, e assinado o Termo de Consentimento pós-informação, o paciente era randomizado como Grupo I ou Grupo II, seguindo lista de randomização gerada por programa específico. A partir deste momento, a criança era submetida à avaliação das características demográficas e clínicas, constando de história e exame físico e, então, avaliada conforme previsto pelo protocolo de estudo. Os dados eram registrados em uma ficha de avaliação e seguimento. Dependendo do grupo alocado pela randomização, o paciente recebia o ACO Varfarina (Grupo I), na dose inicial de 0,1mg/kg/dia; ou o antiagregante plaquetário AAS (Grupo II), na dose de 10mg/kg/dia (dose máxima de 100mg/dia). Ambos eram iniciados no momento em que o paciente tinha condição de receber medicação oral, sendo que até então, ficava em uso de heparina de baixo peso molecular (Enoxaparina) subcutânea na dose de 1mg/kg/dia, uma vez ao dia. Nos casos randomizados para uso de ACO, os pacientes eram mantidos em uso de heparina subcutânea, até o INR entrar na faixa desejada de 2 a 3. Na avaliação pré-operatória (Momento 1), era realizado um ecocardiograma bidimensional com Doppler colorido, via transtorácica, eletrocardiograma, e estudo hemodinâmico por cateterismo cardíaco. Era, ainda, realizada avaliação laboratorial com dosagem de enzimas hepáticas, INR, hematócrito, e fatores de coagulação VII, VIII e Proteína C da coagulação. No pós-operatório imediato (Momento 2), considerado até o décimo dia de pós-operatório (PO), era registrada a técnica cirúrgica utilizada (realização ou não de fenestração e tamanho do tubo extracardíaco), evolução e intercorrências no período, era realizado um ecocardiograma transesofágico, eletrocardiograma e controle de INR. O seguimento ambulatorial, iniciava com 3 meses de PO (Momento 3), sendo avaliada evolução e intercorrências clinicas, eletrocardiograma, ecocardiograma transesofágico e analise laboratorial: INR, Hematócrito, enzimas hepáticas e fatores de coagulação: Proteína C da coagulação, Fator VII e Fator VIII. A avaliação de 6 meses (Momento 4) era semelhante ao momento 3, sendo agora realizada a angiotomogra-
Objetivos secundários 1. Identificar alterações de fluxo pelo tubo extracardíaco, em crianças em pós-operatório da derivação cavopulmonar total, avaliando a ocorrência de fluxo lento e/ou autocontraste, por meio de estudo ecocardiográfico seriado. 2. Identificar alterações na parede interna do tubo extracardíaco, por meio de exames seriados ecocardiográficos e angiotomográficos. 3. Identificar a ocorrência de tromboembolismo pulmonar (TEP) subclínico por meio da cintilografia ventilação/ perfusão pulmonar. MÉTODOS O Projeto foi aprovado pela Comissão de Ética em Pesquisa do Hospital do Coração – Associação do Sanatório Sírio, e teve a ciência da Comissão de Ética para Análise de Projetos de Pesquisa do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP) – CAPPesq. Trata-se de estudo prospectivo e randomizado, com seguimento pós-operatório de 2 anos, com inclusão de 30 pacientes submetidos a operação cavopulmonar total com tubo extracardíaco no período entre 2008 e 2011. O seguimento pós-operatório foi realizado no setor ambulatorial da mesma instituição, com consultas e avaliações realizadas pela investigadora, nos períodos pré determinados pelo protocolo de pesquisa. Foram critérios de inclusão: 1. Crianças portadoras de coração com morfologia univentricular, em programação estadiada, para a cirurgia de derivação cavopulmonar total. Foram critérios de exclusão: 1. Algum aspecto de caráter anatômico ou angiográfico, que contraindicasse a operação cavopulmonar, entre eles: a. Fração de ejeção do ventrículo principal inferior a 60%, ou disfunção importante da valva atrioventricular relacionada ao ventrículo predominante. b. Alteração anatômica grave, não tratável, do retorno venoso pulmonar c. Anatomia da árvore pulmonar gravemente desfavorável. 2. Impossibilidade de realizar o acompanhamento ambulatorial; 3. Qualquer condição clínica que impedisse a randomiza-
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fia de tórax. No momento 5 (um ano de pós operatório), era realizada avaliação idêntica ao momento 4, agora acrescida de cintilografia pulmonar de ventilação e perfusão. A última avaliação, de dois anos de pós operatório, momento 6, era idêntica ao momento 5. A coleta de amostra sanguínea foi realizada por punção periférica. A metodologia de avaliação da amostra consiste em Método Coagulométrico para dosagem de Fator VII, VIII e TP/AP/INR, Método Funcional para dosagem de Proteína C da coagulação e Método de Química Seca na dosagem de AST, ALT E GGT. O ecocardiograma pré-operatório foi realizado por via transtorácica, bidimensional, com doppler colorido e os exames pós-operatórios por via transesofágica, aparelho IE 33 Philips (Bathel-Andover), com sonda pediátrica em menores 20 Kg e sonda adulto em crianças com peso maior ou igual a 20 Kg, por examinador único. A avaliação do tubo foi realizada em corte longitudinal e transversal, com avaliação do fluxo por mapeamento de fluxo em cores, e ao Doppler, sendo o trombo avaliado pelo método bidimensional. A função sistólica ventricular foi realizada por análise subjetiva e função diastólica ventricular, por traçado de doppler da veia pulmonar. A angiotomografia foi realizada por dois examinadores médicos radiologistas. Foi aplicado contraste iodado endovenoso, na dose de 1,5 ml/kg de peso, e realizada única aquisição durante apneia; dois minutos após a injeção do contraste, sem sincronização com o eletrocardiograma. A cintilografia, ventilação/perfusão, foi realizada após um e dois anos de pós-operatório. Os exames foram realizados com câmara à cintilação com dois detectores, equipada com colimador de baixa energia, canais paralelos e alta resolução. Os exames de inalação pulmonar foram realizados com sistema de radioaerosol fechado, para evitar contaminação do ar ambiente, empregando-se DTPA-Tc99m. As imagens foram realizadas após 10 minutos de inalação contínua, quando se espera que 10% da dose inserida no sistema seja absorvida no espaço alveolar dos pulmões. As imagens planas foram realizadas com matriz 128 x 128, adquirindo-se 350.000 contagens por projeção. As projeções foram realizadas nas incidências anterior, posterior, oblíquas anteriores e posteriores e laterais de tórax. Os estudos de perfusão foram realizados com o mesmo equipamento, com administração intravenosa de macroagregado de albumina, marcado com Tc99m. As crianças realizaram manobra de expiração forçada (Valsalva). A dose foi de 2-3 mCi, com número de partículas não superior à 500.000. Em caso de sinal clínico de cianose, o número de partículas foi reduzida para o máximo de 100.000. As imagens foram adquiridas nas mesmas projeções do estudo inalatório, acumulando-se 1000k contagens por projeção. Os critérios de interpretação seguiram esquema de padronização conforme guidelines estabelecidas pelo PIODED. A dose de exposição para as crianças foi de aproximadamente 1 mSv por procedimento.
Os dados foram registrados em uma ficha de seguimento sendo computados e analisados periodicamente. Durante o acompanhamento, quando identificada a presença de trombo ou de fenômeno tromboembólico em pacientes em uso de AAS, estes foram submetidos a tratamento específico. Foi realizada heparinização endovenosa e posterior anticoagulação e consequente término de seu seguimento, dentro do protocolo de avaliação. Análise Estatística A análise estatística de todas as informações coletadas nesta pesquisa foi inicialmente feita de forma descritiva. Para as variáveis de natureza quantitativa (numérica) foram calculadas algumas medidas-resumo, como média, mediana, valores mínimo e máximo, desvio-padrão, e confeccionados gráficos do tipo diagrama de dispersão unidimensional. As variáveis de natureza qualitativa (categorizada) foram analisadas por meio do cálculo de frequências absoluta e relativa (porcentagem), além da construção de gráficos de barras. As análises inferenciais empregadas com o intuito de confirmar ou refutar evidências encontradas na análise descritiva foram: · Teste de Qui-quadrado de Pearson, teste Exato de Fisher ou sua extensão para o estudo da comparação dos perfis dos grupos de tratamento, segundo gênero, diagnóstico, primeira e segunda cirurgia, ocorrência prévia de trombo, hematócrito, função hepática, proteína C, fatores VII e VIII, disfunção ventricular, e técnica cirúrgica (com ou sem fenestração do tubo extracardíaco); · Teste t-Student para amostras independentes na comparação dos níveis médios da pressão pulmonar no pré-operatório entre os grupos de tratamento; · Teste de Mann-Whitney na comparação da idade dos grupos de tratamento; · Estimativa das curvas de sobrevivência (Kaplan-Meier) e teste de Log-rank na comparação do tempo (dias) livre de trombo, segundo grupo de tratamento, faixa etária, diagnóstico, pressão pulmonar no pré-operatório, técnica cirúrgica, história prévia de trombo, proteína C, fatores VII e VIII, disfunção ventricular em cada momento de tempo, alto contraste em cada momento pós-operatório, óbito e reintervenção. Em todas as conclusões obtidas por meio das análises inferenciais foi utilizado o nível de significância igual a 5%. Os dados foram digitados em planilhas do Excel 2010 for Windows para o adequado armazenamento das informações. As análises estatísticas foram realizadas com o software R versão 2.15.2. RESULTADOS Os aspectos clínicos e demográficos estão apresentados na Tabela 1.
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Tabela 1. Distribuição das características gerais das crianças dos grupos AAS e ACO. gênero feminino masculino idade (anos) média mediana mínimo máximo desvio-padrão diagnóstico VUE AT VUD SHCE pressão pulmonar (mmHg) média mediana mínimo máximo desvio-padrão
AAS (n=15)
ACO (n=15)
Total (n=30)
P
8 53,3% 7 46,7%
5 33,3% 10 66,7%
13 43,3% 17 56,7%
0,269a
4,8 3,7 2,0 15,6 3,3
5,8 4,1 2,7 15,6 3,8
5,3 4,0 2,0 15,6 3,5
0,330b
4 26,7% 8 53,3% 3 20,0% -
5 33,3% 1 6,7% 8 53,3% 1 6,7%
9 30,0% 9 30,0% 11 36,7% 1 3,3%
0,026c
14,9 15,0 11,0 19,0 2,3
16,7 16,0 9,0 23,0 3,6
15,8 15,5 9,0 23,0 3,1
0,102d
Qui-quadrado de Pearson, bMann-Whitney, cExato de Fisher ou sua extensão, dt-Student para amostras independentes
a
mação de trombo. Desses, cinco apresentaram trombo no tubo extracardíaco e um na veia cava inferior, diagnosticado ao ecocardiograma transesofágico, no pós-operatório imediato (dentro dos 10 primeiros dias de pós-operatório). Entre eles, quatro estavam em uso de AAS e dois em uso de ACO. Mediante a formação de trombo, o paciente era submetido a heparinização endovenosa em UTI e a seguir acompanhado conforme a necessidade clínica, e interrompido o seguimento pelo protocolo de estudo. Durante o seguimento, houve dois óbitos, ambos alocados no grupo do ACO, não relacionados a ocorrência de trombos. Um paciente teve óbito com cinco meses de pós-operatório, antes da alta, durante a cirurgia de takedown por falência do circuito de Fontan. A segunda criança, evoluiu com quadro de enteropatia perdedora de proteína, imunossupressão e complicações infecciosas, sendo optado por fenestrar o tubo, indo a óbito no pós-operatório do procedimento de fenestração, um ano após a derivação cavopulmonar total. A Tabela 3 resume a ocorrência de trombo desde o pré-operatório até o 24º mês do pós-operatório. Até o final do acompanhamento (24 meses pós-operatório), o grupo AAS apresentou 46,7% (7/15) de crianças com trombo. No grupo ACO, observamos 20,0% (3/15) crianças com trombo, apesar da diferença, esta não teve significância estatística P=0,121. A ocorrência de trombo para os demais momentos está descrito na Tabela 3.
Tabela 2. Procedimento cirúrgico realizado na anastomose cavopulmonar total. Procedimento Cirúrgico TEC isolado TEC Fenestrado TEC e Damus-Kaye-Stansel TEC e Anastomose de Glenn
Grupo ACO: n(%) 11 (73,33%) 1 (6,66%) 2 (13,33%) 1 (6,66%)
Grupo II: n (%) 12 (80%) 3 (20%) 0 0
TEC=Tubo Extracardíaco
Todos os procedimentos foram realizados com tubo extracardíaco de PTFE (politetrafluoroetileno expandido), variando de número 16 mm a 20 mm, e 19 (63,3%) pacientes foram operados com circulação extracorpórea (CEC). Nos casos em que foi necessário corrigir defeito intracardíaco ou atriosseptostomia, foi instalado circuito de CEC. O uso da fenestração entre o tubo extracardíaco e o átrio direito foi essencialmente uma decisão da equipe cirúrgica nos casos menos favoráveis, nos quais estivessem presentes leves alterações da árvore pulmonar ou pressão pulmonar limítrofe (16-18 mmHg). O tipo de procedimento cirúrgico associado a derivação cavopulmonar total com tubo extracardíaco, está ilustrado na Tabela 2. Seguimento Clínico Dos 30 pacientes acompanhados, seis apresentaram for-
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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
Tabela 3. Distribuição da ocorrência de trombo entre as crianças dos grupos AAS e ACO, segundo momento de tempo. Pré-operatório (antecedente de trombo) presente ausente Total
n 4 11 15
Pós-operatório imediato presente ausente Total
AAS
% 26,7% 73,3% 100,0%
N 2 13 15
4 11 15
26,7% 73,3% 100,0%
3 meses de pós-operatório presente ausente óbito Total
11 15
6 meses de pós-operatório presente ausente óbito Total
ACO
Total
% 13,3% 86,7% 100,0%
n 6 24 30
2 13 15
13,3% 86,7% 100,0%
6 24 30
20,0% 80,0% 100,0%
73,3% 100,0%
12 1 15
80,0% 6,7% 100,0%
23 1 30
76,7% 3,3% 100,0%
11 15
73,3% 100,0%
12 1 15
80,0% 6,7% 100,0%
23 1 30
76,7% 3,3% 100,0%
12 meses de pós-operatório presente ausente óbito Total
2 9 15
13,3% 60,0% 100,0%
1 10 2 15
6,7% 66,7% 13,3% 100,0%
3 19 2 30
10,0% 63,3% 6,7% 100,0%
24 meses de pós-operatório presente ausente óbito Total
1 8 15
6,7% 53,3% 100,0%
10 2 15
66,7% 13,3% 100,0%
1 18 2 30
3,3% 60,0% 6,7% 100,0%
Com o intuito de investigar os fatores que interferem sobre o tempo de sobrevida livre de trombo, entre eles a droga utilizada na profilaxia (ACO ou AAS), a idade da realização da derivação cavopulmonar total (arbitrariamente dividida em: menor do que cinco anos e maior do que cinco anos), a morfologia do ventrículo único (VUE ou VUD), a PAPm no pré-operatório (≥ a 18 mmHg), a presença de fenestração, a história prévia de trombo, bem como a disfunção ventricular em cada momento de avaliação; foram construídas curvas de sobrevida e posteriormente, foi aplicado o teste de Log-Rank. Os resultados desses testes confirmaram que o tempo livre de trombo não está relacionado ao fatores: · Uso de AAS ou ACO (P=0,156) – Figura 1 · Faixa etária (P=0,471); · Diagnóstico (P=0,960), · PAPm no pré-operatório (P=0,606), · Fenestração (P=0,477), · Disfunção ventricular nos momentos pré-operatório (P=0,224) no pós-operatório imediato (P=0,329), 3 meses
% 20,0% 80,0% 100,0%
de pós-operatório (P=0,967), 6 meses de pós-operatório (P=0,664), 12 meses de pós-operatório (P=0,458) e 24 meses de pós-operatório (P=0,409). Dentre todas as variáveis avaliadas, a principal que mostrou influenciar na ocorrência de trombo, na evolução pós-operatória, foi a presença de trombo prévio: o tempo livre de trombo das crianças sem história prévia de trombo é estatisticamente maior quando comparado às crianças com história prévia de trombo (P=0,035) - Figura 2. Com relação aos fatores de coagulação, é considerável o número de pacientes em cada grupo que já apresentam estes fatores alterados no momento pré-operatório, principalmente a proteína C da coagulação, importante fator anticoagulante. O nível sérico de proteína C foi baixo em 33% dos pacientes do grupo AAS e 40% do grupo ACO. No entanto, surpreendentemente, o número de pacientes que evoluiu livre de trombo, foi significativamente maior entre os indivíduos com déficit dessa proteína no pré-operatório (P=0,047) do que entre os que apresentavam níveis séricos normais deste fator anticoagulante, no mesmo momento de avaliação.
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Fig. 1 - Curva de sobrevida livre de trombo comparando o Grupo em uso de AAS ao Grupo em uso de ACO.
Fig. 2 - Curva de sobrevida livre de trombo comparando pacientes com história de ocorrência prévia de trombo e sem ocorrência prévia de trombo.
Já o nível sérico pré-operatório dos fatores VII e VIII não teve influência no tempo livre de trombo no pós-operatório dos pacientes avaliados com valores de P=0,550 e P=0,329, respectivamente. A comparação dos níveis séricos dos fatores de coagulação avaliados, no pós-operatório, não pode ser considerada por sofrerem forte influência da varfarina. Entre os pacientes em acompanhamento ambulatorial, cinco deles tiveram falta de aderência ao tratamento e falha no uso da medicação. A monitorização clínica foi possível, exclusivamente, por cobrança rígida da pesquisadora, com o auxílio do serviço de Assistência Social da Instituição. Os pais justificaram a falta de aderência com alguns argumentos, entre eles: a dificuldade financeira para custear o transporte, para comparecer às consultas e realizar exames. Outra justificativa foi a percepção do bom estado clínico da criança, levando-os a julgar dispensáveis as reavaliações ou o uso de qualquer medicação. Dentre esses cinco pacientes, quatro estavam em uso de ACO, e consequentemente, fora da faixa terapêutica quando da avaliação de retorno. Entre os pacientes em uso de varfarina, o valor de INR variava de 1 a 6,4. Entre os 15 pacientes que compunham esse grupo (ACO), 14 (93,3%) tiveram pelo menos uma medida de INR fora da faixa durante o seguimento, e dois (13,3%) tiveram INR superior a 4, o que implica em risco de sangramento. A ocorrência de fluxo lento pelo tubo, com presença de alto contraste em diferentes graus, foi achado relativamente comum no pós-operatório imediato: cinco pacientes em cada um dos grupos (33,33%). No entanto, a ocorrência de alto
contraste no tubo extracardíaco, avaliado pelo ecocardiograma transesofágico do pós-operatório imediato, não interferiu na evolução livre de trombo (P=0,148). Alterações na parede interna do tubo extracardíaco, aqui descritas como depósito de material hipoatenuante, visibilizado pela angiotomografia de tórax, foi achado comum em ambos os grupos desde a primeira avaliação angiotomográfica, e pode ser visibilizada nas imagens abaixo (Figura 3A e 3B).
Fig. 3A - Material depositado em Tubo Extracardíaco Angiotomografia de tórax em eixo curto realizado após 6 meses da derivação cavopulmonar total com tubo extracardíaco. Corte de eixo curto (seta)
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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
Fig. 4 - Tromboembolismo Pulmonar - Imagem de cintilografia de ventilação-perfusão de paciente em uso de AAS, realizada após dois anos da Derivação cavopulmonar Total com Tubo Extracardíaco, evidenciando tromboembolismo pulmonar no ápice do pulmão esquerdo (segmento 11)
o passar do tempo de pós-operatório, tal atapeteamento mostrou-se mais importante no grupo em uso do AAS no qual 35,7% tinham depósito de material com espessura maior que 2 mm, conforme a Tabela 5. Nenhum paciente no grupo em uso de ACO apresentava material que atingisse espessura desta dimensão, com P=0,08. A ocorrência de TEP subclínico foi baixa. Apenas dois pacientes, ambos em uso de antiagregante plaquetário, apresentaram cintilografia pulmonar ventilação-perfusão com padrão de TEP (Figura 4), sem manifestar qualquer alteração clínica típica da ocorrência do mesmo. Uma das crianças evoluiu com comprometimento hemodinâmico do circuito tipo Fontan e enteropatia perdedora de proteína, seguido do achado diagnóstico descrito. Comparando a ocorrência de TEP no grupo em uso de AAS com o grupo em uso de ACO, não houve diferença estatisticamente significante (P=0,483).
Fig. 3B - Material depositado no Tubo Extracardíaco - Imagem de angiotomografia de tórax em eixo longo realizada após 6 meses da derivação cavopulmonar total com tubo extracardíaco. Paciente estava em uso de AAS evoluiu com acotovelamento da parede do tubo com depósito de grande quantidade de material. Corte de eixo longo, com material depositado em local de dobra do tubo (seta)
A Tabela 4 descreve a ocorrência de material depositado na parede do tubo extracardiaco, visibilizado pela angiotomografia de tórax. A espessura da imagem hiperecogênica em questão variou de 0,9 mm a 3,5 mm, sendo esta última correlacionada a imagem de trombo ao ecocardiograma transesofágico. Com
Tabela 4. Distribuição dos resultados da tomografia das crianças dos grupos AAS e ACO. 6 meses de pós-operatório alterada não alterada Total
AAS
ACO
Total
P
11 3 14
78,6% 21,4% 100,0%
8 4 12
66,7% 33,3% 100,0%
19 7 26
73,1% 26,9% 100,0%
0,665c
12 meses de pós-operatório alterada 11 não alterada 3 Total 14
78,6% 21,4% 100,0%
10 2 12
83,3% 16,7% 100,0%
21 5 26
80,8% 19,2% 100,0%
>0,999c
24 meses de pós-operatório alterada 10 não alterada 2 Total 12
83,3% 16,7% 100,0%
6 3 9
66,7% 33,3% 100,0%
16 5 21
76,2% 23,8% 100,0%
0,611c
Exato de Fisher
c
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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
Tabela 5. Distribuição da espessura do material depositado dos pacientes dos grupos AAS e ACO, nos momentos 4, 5 e 6. AAS
ACO
Total
P
espessura no momento 4 maior ou igual a 2mm menor que 2 mm Total
3 10 13
23,1% 76,9% 100,0%
4 7 11
36,4% 63,6% 100,0%
7 17 24
29,2% 70,8% 100,0%
0,603a
espessura no momento 5 maior ou igual a 2 mm menor que 2 mm Total
3 10 13
23,1% 76,9% 100,0%
3 7 10
30,0% 70,0% 100,0%
6 17 23
26,1% 73,9% 100,0%
0,500a
espessura no momento 6 maior ou igual a 2 mm menor que 2 mm Total
5 9 14
35,7% 64,3% 100,0%
8 8
100,0% 100,0%
5 17 22
22,7% 77,3% 100,0%
0,082a
a
teste unilateral de comparação de proporções
DISCUSSÃO
ao ecocardiograma transesofágico. Dados condizentes com publicações recentes que também mostraram maior incidência de trombo nos primeiros dias de pós-operatório da derivação cavopulmonar total (sem unanimidade na técnica com tubo extracardíaco)[9]. Ao final de dois anos de seguimento, a ocorrência total de trombo foi de 46,7% dos pacientes em uso de AAS e 20% dos pacientes em uso de ACO. Fatores como: a idade da indicação; a PAPm no momento pré-operatório; o uso da fenestração; fluxo lento pelo tubo extracardíaco e disfunção sistólica do ventrículo único não tiveram interferência na ocorrência de trombo durante todo o seguimento. Apenas o histórico de trombo prévio mostrou interferir na formação de trombo no pós-operatório. Fato que está relacionado ao estado de hipercoagulabilidade da criança portadora de coração univentricular. Já entre os estágios pré-derivação cavopulmonar total, o trombo ocorre tanto por alteração na quantidade quanto na atividade de fatores de coagulação; por alterações hemodinâmicas e de oximetria da fisiologia univentricular; assunto este de importantes publicações ao longo dos últimos anos, e já discutido previamente neste texto[3,6, 8,10]. Em ambos os momentos acima citados, a diferença na ocorrência de trombo entre os dois grupos não teve significância estatística, provavelmente pelo número reduzido da amostra deste estudo. É difícil, no entanto, ignorar o fato do número de pacientes que evoluíram com trombo no grupo em uso de AAS, ser maior do que o dobro do número dos pacientes do grupo em uso de Varfarina. A proteína C da coagulação é um anticoagulante natural, sintetizado no fígado, como uma proteína dependente da vitamina K. Após ser ativada pela trombina, ela inibe os fatores de coagulação Va e VIIIa, estimulando a fibrinólise. Sendo assim, a deficiência desta proteína está associada a um estado trombogênico. Do mesmo modo que a deficiência de
Em 2011, Monagle et al.[7] publicaram estudo multicêntrico, prospectivo e randomizado, de 111 pacientes em pós-operatório da operação de Fontan modificada comparando as duas estratégias de profilaxia primária habitualmente utilizadas: AAS (57 pacientes) e Varfarina (54 pacientes), sendo realizado diagnóstico de trombo em 21% dos pacientes em uso da primeira droga e 24% da segunda. Os pacientes foram avaliados por ecocardiograma transtorácico e transesofágico aos 3 e 24 meses de pós-operatório, confirmando alta incidência de trombose, independente da estratégia utilizada. Em 2012, Manlhiot et al.[8] se preocuparam em estudar os aspectos das complicações tromboembólicas, e da tromboprofilaxia, nos três estágios de estadiamento cirúrgico do coração univentricular e mostraram que o uso de varfarina, como profilaxia, tem uma redução significante no risco de trombose, quando comparado ao uso de AAS ou ausência de profilaxia. A comparação da eficácia do uso do ACO e do antiagregante plaquetário é uma discussão bastante antiga, e a escolha de cada uma das drogas, bem como a associação das mesmas vem sendo realizada de acordo com a preferência e experiência de cada grupo. Uma meta-análise publicada em 2011[3] avaliou 20 estudos relacionados ao assunto, com amostras que variaram de 6 a 282 pacientes. Sendo que, sete dos trabalhos cuja a profilaxia fora realizada com AAS, outros três com o uso apenas do anticoagulante oral e, as dez publicações restantes, com a aplicação de ambos, com taxa de tromboembolismo variando de 0 a 16%, sendo semelhante entre pacientes em independente da estratégia utilizada. A ocorrência de trombo foi mais frequente na primeira avaliação pós-operatória, momento 2. Momento no qual 26,7% das crianças em uso de AAS e 13,3% das crianças em uso de Varfarina tiveram imagem de trombo diagnosticado
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tal fator de coagulação no pré-operatório da derivação cavopulmonar total, também no pós-operatório, vários estudos tem demonstrado tal deficiência[3,10] e que existe ainda uma redução gradual nessa deficiência com o aumento do tempo de seguimento[11]. Em nossa amostra, 33,3% dos pacientes tinham deficiência da proteína C da coagulação na avaliação pré-operatória. Dentre estes pacientes, cerca de 90% cursaram livres de trombo, mostrando que a proteína C da coagulação, no pré-operatório, não foi fator de proteção contra a ocorrência de trombo. No entanto, não é possível avaliar o comportamento deste fator de coagulação em todos os pacientes desta amostra no pós-operatório, uma vez que os pacientes em uso de varfarina teriam os resultados comprometidos. A segurança em usar a varfarina na faixa etária pediátrica é uma preocupação de todos nós que lidamos com esse tipo de paciente. Em 1999, uma ampla avaliação de 319 crianças entre 1 mês a 18 anos de vida em uso de Varfarina por diferentes motivos, acompanhados em um centro de anticoagulação, encontrou dados importantes aplicáveis a população por nós aqui estudada[12]: • Crianças com circuito do tipo Fontan necessitam de maior dose de varfarina para atingir o RNI esperado • Existe dificuldade no manejo da anticoagulação em crianças com idade inferior a 6 anos, com necessidade de maiores doses da Varfarina; • O longo tempo de necessidade de sobreposição da varfarina com a heparina para que o INR esteja na faixa desejada; necessidade de tempo prolongado até dosagens mais frequentes de INR e necessidade de ajustes mais frequentes de dose. Em nossa amostra, cinco pacientes (16,6%) tiveram falta de aderência ao seguimento, sendo a manutenção deste só possível por constante insistência dos pesquisadores e com o apoio da equipe de assistência social do Hospital, estando quatro (80%) em uso de varfarina, e, consequentemente, o INR oscilava fora da faixa, com valores entre 1 e 6,4. Além disso, de maneira geral, no grupo em uso da varfarina 93,3% apresentou, pelo menos, um INR abaixo da faixa desejada, o que aumenta significativamente o risco de trombose, como mostra estudo prospectivo multicêntrico já citado anteriormente, no qual, o grupo em uso de varfarina, durante avaliação do INR, tinha menos do que 30% com RNI superior a 2[7]. Alterações na parede interna do tubo extracardíaco utilizado na derivação cavopulmonar total ainda vem sendo pobremente estudada, com dados escassos a este respeito. Em nossa casuística, aos dois anos de pós-operatório, tanto o número de crianças com material depositado na parede do tubo era maior no grupo do AAS (83,3%), quanto a espessura do material (que variou em toda a avaliação de 0,9 a 3,5 mm) era maior (superior a 2 mm). Imagem superior a 2 mm não foi visualizada nas crianças em uso de varfarina neste momento, com P=0,082; mostrando assim uma tendência em se
afirmar que o depósito de material, com aumento do tempo de seguimento, é maior no grupo em uso de AAS. O material aqui descrito como atapeteamento, em estudo publicado recentemente[13], foi chamado de trombo de base larga, aderido à parede interna do tubo extracardíaco em 3 de 10 pacientes. A abordagem e interpretação do material encontrado traz à tona uma importante discussão, tanto no que diz respeito ao tamanho quanto ao aspecto, podendo ser a tomografia uma importante ferramenta no diagnóstico precoce do trombo, evitando o tromboembolismo pulmonar. A ocorrência do TEP subclínico, com liberação de pequenos êmbolos para a circulação pulmonar, é um importante problema na fisiologia do tipo Fontan pela queda na saturação de oxigênio e aumento da resistência vascular pulmonar. A cintilografia pulmonar não é realizada rotineiramente em pacientes submetidos a derivação cavopulmonar total, o que torna difícil a comparação. No entanto, foi diagnosticado TEP em dois pacientes, ambos em uso de AAS, após um e dois anos de pós-operatório. Pela importância do comprometimento hemodinâmico do circuito de Fontan na vigência do tromboembolismo pulmonar, estratégias devem ser traçadas em busca de um diagnóstico prático e seguro desta alteração, sendo a princípio, a tomografia uma opção possível[13]. A baixa incidência do coração com fisiologia univentricular entre as cardiopatias congênitas, somado à mortalidade no período interestágio, limita significativamente o número de pacientes a ser incluídos em um estudo, prospectivo e randomizado, do pós-operatório da derivação cavopulmonar total. O fenômeno tromboembólico no pós-operatório deste procedimento é muito importante, tanto no que diz respeito a alta incidência, quanto ao comprometimento na morbimortalidade. Entre os achados desta amostra, há sugestão de que o grupo em uso de AAS tenha sido mais comprometido em todas as frentes de investigação de ocorrência de trombo. Entretanto, devido à pequena amostragem, faz-se mandatório um esforço cooperado em se conseguir uma amostra com poder estatístico maior para comprovação final dessa teoria. Possivelmente de maneira multicêntrica e com a colaboração conjunta de cardiopediatras e cirurgiões cardíacos pediátricos para vencer esse desafio que muda o curso prognóstico de tantas crianças. CONCLUSÃO 1 - A ocorrência de trombo foi nitidamente maior no grupo submetido ao uso de AAS, no entanto, esta diferença não teve diferença estatística. a - quando avaliamos cada um dos fatores estudados na interferência da sobrevida livre de trombo, notamos que os únicos fatores que realmente interferem são a ocorrência prévia de trombo (P=0,035) e deficiência da concentração de proteína C da coagulação no pré-operatório (P=0,047). 2 - Função Hepática e de fatores de coagulação:
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a - com exceção da proteína C da coagulação, os fatores de coagulação e enzimas hepáticas não mostraram interferência na evolução livre de trombo. 3 - Quanto à viabilidade da profilaxia habitual para tromboembolismo, nenhuma das duas drogas avaliadas levou a efeitos colaterais importantes, bem como sangramentos. Nenhuma das crianças teve a droga suspensa por intolerância. 4 - A velocidade de fluxo é reduzida pelo tubo extracardíaco e a ocorrência de trombo foi mais frequente em pacientes com fluxo lento, sem significância estatística. 5 - No grupo em uso de AAS, encontramos uma tendência a maior ocorrência de atapeteamento com espessura maior (superior a 2 mm), quando comparado ao grupo em uso de ACO (P=0,082). 6 - Tromboembolismo pulmonar subclínico ocorreu em dois pacientes, sem significância estatística. Pacientes com história prévia de trombose, e que serão submetidos à derivação cavopulmonar total tipo Fontan, deverão ser mantidos no pós-operatório em uso de Varfarina. É necessário ampliar o número da amostra deste estudo para darmos força estatística ao fato de que o dobro de crianças em uso de AAS evolui com fenômeno tromboembólico; pacientes em uso de AAS têm maior quantidade de material aderido à parede do tubo, atingindo espessura superior a 2 mm, e têm maior chance de tromboembolismo pulmonar comprometendo o circuito tipo Fontan, e, com isso, poderemos preconizar que estes pacientes, sempre que sua condição social permitir, sejam anticoagulados com uso de Varfarina no pós-operatório da derivação cavopulmonar total.
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. 4. Monagle P, Cochrane A, McCrindle B, Benson L, Williams W, Andrew M. Thromboembolic complications after Fontan 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. 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.
Papéis & responsabilidade dos autores CFXP MBJ IBJ PMO FMPS VMM RWL SRFFP
Desenho do estudo, coleta de dados, pesquisa de referências Desenho do estudo Desenho do estudo Coleta de dados Coleta de dados Coleta de dados Coleta de dados Coleta de dados
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. 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.
REFERÊNCIAS 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.
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.
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.
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.
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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, Brasil.
Endereço para correspondência: Antônio Alceu dos Santos Rua Maestro Cardim, 769, Bloco I, 2º andar, Sala 202 – Bela Vista – São Paulo, SP, Brasil – CEP: 01323-900 E-mail: antonioalceu@cardiol.br
Descriptors: Blood Transfusion. Bloodless Medical and Surgical Procedures. Blood Preservation. Operative Blood Salvage. Cardiac Surgical Procedures.
1
Trabalho realizado no Real e Benemérita Associação Portuguesa de Beneficência de São Paulo, São Paulo, Brasil.
Artigo recebido em 22 de maio de 2014 Artigo aprovado em 30 de setembro de 2014
Não houve suporte financeiro.
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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.
Abreviações, acrônimos e símbolos AVC CCP CEC CH CRM DDAVP EuroSCORE FA HNA IC IM IR LILACS MEDLINE MeSH r-FVIIa r-Hu-EPO r-Hu-TPO SciELO
Acidente vascular cerebral Concentrado de complexo protrombínico Circulação extracorpórea Concentrado de hemácias Cirurgia de revascularização miocárdica 1-deamino-8-D-arginine vasopressin European System for Cardiac Operative Risk Evaluation Fibrilação atrial Hemodiluição normovolêmica aguda Insuficiência cardíaca Infarto do miocárdio Insuficiência renal Literatura Latino-Americana em Ciências da Saúde Medical Literature Analysis and Retrieval System Online Medical Subject Headings Fator VII recombinante ativado Eritropoietina humana recombinante Trombopoietina humana recombinante 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.
INTRODUÇÃO
Por mais de meio século, a prática transfusional não foi questionada, visto não existirem evidências de efeitos adversos significativos. Porém, a partir da década de 80, vários estudos vêm avaliando segurança e eficácia das transfusões de sangue. Inicialmente, verificou-se a correlação entre a transfusão de hemocomponentes em CRM e complicações clínicas como insuficiência renal (IR), processos infecciosos, tempo de ventilação prolongado, danos neurológicos[5]. Mais recentemente, ficou evidente que a transfusão de sangue alogênico em cirurgia cardíaca é uma terapia com outros graves efeitos adversos tais como fibrilação atrial (FA), acidente vascular cerebral (AVC), infecções respiratórias, sepse, infarto do miocárdio (IM)[6,7], incluindo risco de morte[8-10]. Mesmo após correção para idade, sexo, peso, altura e várias doenças, como diabetes mellitus, hipertensão, doença pulmonar obstrutiva crônica, doença vascular periférica, insuficiência cardíaca (IC), doença vascular cerebral, as he-
Desde o século XIX, o sangue alogênico tem sido utilizado em frequência e intensidade crescente em todo mundo. A taxa de transfusão de hemocomponentes em cirurgia de revascularização miocárdica (CRM) chega a 92,8% para glóbulos vermelhos, 97,5% para plasma fresco congelado e 90,4% para infusão de plaquetas[1]. Atualmente, verifica-se uma redução mundial das doações de sangue, resultando em bancos de sangue com estoques reduzidos[2]. Em nosso meio, esta situação é real e a tendência é piorar, pois a demanda de sangue no país não é proporcional as doações, indicando assim a possibilidade no futuro próximo da falta deste recurso terapêutico para se realizar e/ou finalizar cirurgias[3]. Assim, desde 2008, já existe uma preocupação médica sobre o que fazer se o paciente estiver sangrando e não existir sangue disponível para transfundir[4].
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motransfusões podem resultar em aumento de até 70% na mortalidade pós-operatória de cirurgia cardíaca[8]. Em nossa pesquisa, também ficou demonstrado que a transfusão de glóbulos vermelhos foi um fator preditor independente de morte após CRM em uma população de 1.888 pacientes. Mesmo em um subgrupo de pacientes de baixo risco (idade < 60 anos e com EuroSCORE ≤ 2%), houve significativamente mais óbitos no grupo hemotransfundidos[9]. Outros estudos evidenciaram que esta mortalidade é diretamente proporcional ao número de unidades de concentrado de hemácias (CH) transfundidas. Cada unidade de CH administrada pode aumentar em 77% o risco de mortalidade após CRM[5]. Santos et al.[10] também observaram que o risco de mortalidade é dose-dependente do número de unidades de CH alogênicas transfundidas após avaliar 3.010 pacientes submetidos a CRM. Quanto mais unidades de hemácias transfundidas, maior foi o risco de mortalidade no pós-operatório. Além das questões relacionadas aos riscos transfusionais, o custo também é um fator que precisa ser considerado. Embora varie entre países, o preço estimado de uma bolsa de sangue, em 2010, nos Estados Unidos da América (EUA) chegava a US$1200, quando consideradas todas as atividades envolvidas na transfusão de sangue[11]. A transfusão de CH também foi associada a uma maior permanência hospitalar, resultando em aumento dos custos hospitalares[6,7]. Diante destas evidências de aumento na incidência de infecções, sepse, AVC, FA, IR, IC, IM, maior risco de morte[5-10], maiores custos[6,7] e escassez de hemocomponentes[2,3], torna-se necessário outras opções de tratamento não-transfusional. Tem-se proposto várias alternativas[4,12-16], a fim de diminuir o consumo de sangue alogênico em cirurgias cardíacas, porém devido à praticidade da terapia transfusional ainda são pouco conhecidas e raramente utilizadas. O objetivo desta revisão é reunir e descrever de maneira estruturada, objetiva e prática todas as estratégias clínicas e cirúrgicas, como opções terapêuticas que possam contribuir para o cirurgião, anestesiologista, clínico e/ou médico de terapia intensiva, reduzir ou evitar transfusões sanguíneas alogênicas em cirurgias cardíacas e, consequentemente, seus efeitos adversos.
critores pelo MeSH, foram incluídos os termos “Blood management” e “Cardiac surgery”, devido a sua grande utilização como palavra-chaves e sua importância quanto ao tema abordado. O cruzamento dos termos “Blood management” e “Cardiac surgery”, “Blood management” e “Blood transfusion” e, finalmente, “Blood transfusion” e “Cardiac surgery” resultou em 9.018, 11.299 e 5.998 artigos, respectivamente. Critérios de inclusão Presença de uma ou mais alternativas às transfusões de sangue no artigo. Para reunir todas as possibilidades terapêuticas com evidências em reduzir o consumo de sangue alogênico foram selecionados os artigos mais recentes de revisão sistemática e meta-análise, estudos randomizados multicêntricos coorte prospectivos, estudos de coorte retrospectivos, série de casos e outros, sem restrição do número mínimo de pacientes para cada estudo, em todos os idiomas de 1 de janeiro de 1980 a 31 de janeiro de 2014. Critérios de exclusão Não foram selecionados: estudos com títulos não relacionados diretamente ao tema da pesquisa; estudos que não continham nos resumos dados relevantes relacionados à pesquisa; estudos mais antigos que relataram estratégias repetidas (recuperação sanguínea intraoperatória, hemodiluição normovolêmica aguda, uso de agentes estimuladores da eritropoiese, uso dos diversos agentes hemostáticos sistêmicos e tópicos, estratégias restritiva de transfusão de sangue e outras). Seleção dos estudos Por meio de uma triagem individual dos artigos encontrados após a busca na base de dados com o uso dos descritores utilizados, foram extraídos dos textos dados com as principais e mais frequentes alternativas ao uso de hemocomponentes em cirurgia cardíaca. A Figura 1 mostra um organograma da metodologia para a obtenção dos 76 artigos selecionados para esta revisão. Inicialmente, foi feita uma análise de todos os títulos encontrados pelo cruzamento de busca dos termos descritos. Os títulos diretamente relacionados à pesquisa, com ênfase em estratégias para minimizar transfusões sanguíneas e seus efeitos adversos em cirurgia cardíaca, passaram nesta triagem inicial. Em seguida, excluímos aqueles títulos com temas repetidos, selecionando os mais atualizados para leitura dos seus respectivos resumos. Caso o resumo não apresentasse estratégias relacionadas à cirurgia cardíaca, ou apresentasse estratégias que não pudessem ser aplicadas à cirurgia cardiovascular, também não era selecionado para a leitura completa do artigo. A seleção final dos artigos favoráveis ao tema estudado foi feita por meio de buscas individuais com cruzamento das informações por dois autores e supervisão de um terceiro.
MÉTODOS Estratégia de busca Para esta revisão, foi efetuada uma pesquisa bibliográfica no mês de Fevereiro de 2014 nos bancos de dados on line PUBMED/MEDLINE, LILACS, biblioteca COCHRANE e SciELO para artigos publicados entre 1 de janeiro de 1980 e 31 de janeiro de 2014. A busca restringiu-se ao descritor “Blood transfusion” na versão inglesa MeSH (Medical Subject Headings) e aos termos “Cardiac surgery” e “Blood management”. Mesmo não sendo des-
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Fig. 1- Organograma da metodologia sobre as diferentes etapas de busca. MeSH - Medical Subject Headings
RESULTADOS
A Figura 2 mostra um fluxograma de importantes ações em cada pilar para um novo comportamento não-transfusional no pré, intra e pós-operatório.
De acordo com este estudo de revisão, foram obtidas um grande número de ações com impacto na redução do consumo de sangue alogênico. Para facilitar a ação do profissional médico, as principais estratégias selecionadas para evitar ou reduzir a prática transfusional foram separadas em três pilares importantes: I - otimizar a massa eritrocitária e o estado de coagulação; II - minimizar a perda de sangue e III - tolerância à anemia. De maneira estruturada colocamos outras informações úteis obtidas nesta pesquisa em cada um destes pilares para atingir o objetivo desta revisão.
I - Otimizar a massa eritrocitária e o estado de coagulação Para reduzir ou evitar transfusão de sangue alogênico é necessário fazer uma avaliação pré-operatória que inclua a detecção e tratamento da anemia e plaquetopenia. A Tabela 1 evidencia as principais ações para otimizar a massa eritrocitária e o estado de coagulação. Resumidamente, descrevemos cada uma delas: 1 - Histórico de anemia e sangramento anormal Avaliar distúrbios hemorrágicos congênitos ou adquiridos.
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Fig. 2 - Fluxograma de ações para evitar ou reduzir transfusões de sangue alogênico. CCP= Concentrado de complexo protrombínico; CFH= Concentrado de fibrinogênio humano; EACA= Ácido épsilon aminocapróico; Fator VIIa= Fator VII recombinante ativado; IV= Intravenosa; PAM= Pressão arterial média; PAS= Pressão arterial sistólica; r-Hu-EPO= Eritropoietina humana recombinante; r-Hu-TPO= Trombopoietina recombinante humana
2 - Identificar medicamentos em uso que podem ter efeitos adversos sobre a anemia, trombocitopenia e coagulopatia[17] Ácido acetil salicílico (AAS), anti-inflamatórios não hormonais, anticoagulantes, inibidores de agregação plaquetária, antibióticos beta-lactâmicos (como as penicilinas,
ticarcilina), betabloqueadores, bloqueadores de canais de cálcio, bloqueadores-H2, furosemida, diuréticos tiazídicos, alfa-metildopa, quinidina, anticonvulsivantes, fármacos mielossupressores, suplementos dietéticos ou fitoterápicos podem afetar a coagulação ou a função plaquetária.
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Tabela 1. Principais ações para otimizar a massa eritrocitária e o estado de coagulação. Estudo Drews[17] Goodnough[18] Weltert et al.[20] Corwin et al.[21] Silverberg et al.[24] Bussel et al.[29] Wang et al.[30]
Principais ações para otimizar a massa eritrocitária e estado de coagulação Identificar anemia, trombocitopenia e coagulopatia Tratar as deficiências de ferro r-Hu-EPO no pré-operatório para pacientes anêmicos Dose de 40.000 UI/semana reduz transfusão de sangue Terapia androgênica anabólica pode potencializar respostas a r-Hu-EPO Eltrombopag estimula a trombocitpoiese e reduz transfusão de plaquetas r-Hu-TPO estimula a trombocitopoiese e reduz transfusão de plaquetas
r-Hu-EPO= Eritropoietina humana recombinante, r-Hu-TPO= Trombopoietina humana recombinante
3 - Exame físico Procurar manifestações de doenças conhecidas como associadas à disfunção hemostática (hepatomegalia, esplenomegalia, petéquias, púrpura, equimoses, hemartrose, evidência de defeitos colágeno-vasculares, telangiectasia).
d) Dosagem e Via de administração r-Hu-EPO A reação a r-Hu-EPO depende da dosagem e varia de paciente para paciente. Excetuando-se insuficiência renal crônica, relataram-se dosagens de r-Hu-EPO variando de 150 a mais de 600 UI/kg/semana, com vários esquemas de intervalos entre doses, para acelerar a recuperação de anemia aguda[20]. Em pacientes criticamente doentes em terapia intensiva, a administração subcutânea de 40.000 UI por semana de r-Hu-EPO resultou em aumento significativo no nível de hemoglobina e, consequentemente, redução de 19% na necessidade de transfusão de sangue[21]. Alguns pacientes requerem dosagens maiores de r-HuEPO para alcançar uma resposta adequada. Há evidências sugerindo que dosagens de r-Hu-EPO em intervalos de 24-72 horas (150300 UI/kg) podem ser mais eficazes do que doses únicas semanais (600 UI/kg). Se a causa da ineficácia ao tratamento com r-Hu-EPO não pode ser identificada ou corrigida, considere o uso de dosagens mais altas[22]. Em anemia grave, o uso concomitante de ferro IV pode potencializar a resposta aos agentes eritropoiéticos[18]. A terapia agressiva para anemia não deve ser retardada até o nível de hemoglobina cair a níveis críticos. Eritropoietina de até 200 UI/kg/dia (1.400 UI/kg/semana em doses divididas) tem se mostrado segura e bem tolerada em crianças[23]. Concomitante terapia androgênica anabólica pode potencializar a resposta a agentes eritropoiéticos por aumentar a sensibilidade das células eritroides progenitoras[24]. A via intravenosa atinge concentrações mais altas de eritropoietina no plasma. Para anemia aguda grave, doenças críticas, deficiente absorção subcutânea (devido a edema ou alterações no fluxo sanguíneo) considerar administração IV inicial de r-Hu-EPO seguida de doses subcutâneas[25]. e) Outras considerações sobre r-Hu-EPO A terapia com r-Hu-EPO pode produzir um moderado e passageiro aumento dose-dependente na reatividade das plaquetas[26]. Uma pobre resposta à terapia estimulante da eritropoiese inclui, além da deficiência de ferro, processos infecciosos, inflamatórios ou malignos, perda oculta de sangue, hiperparatiroidismo e doenças hematológicas[27]. Os agentes eritropoiéticos têm sido associados com aumento dos níveis da pressão arterial em pacientes com insuficiência renal crônica ou com hipertensão prévia. Daí a ne-
4 - Avaliação laboratorial seletiva Hemograma completo, reticulócitos, ferritina, vitamina B12, folato, coagulograma completo, testes de função e agregação plaquetária, concentração de fibrinogênio, testes de funções hepática, renal e tireoide. Se a investigação laboratorial pré-operatória for anormal, o ideal é adiar a cirurgia até que as anormalidades tenham sido corrigidas ou após realizar um estudo preliminar mais detalhado. Nestes casos, recomenda-se avaliação do hematologista. Para cirurgias de urgências, normalizar a coagulação com agentes apropriados, conforme ações bem definidas ainda neste artigo. 5 - Tratamento de anemia a) Identificar e tratar as deficiências hematínicas A causa mais frequente e tratável de anemia é a deficiência de ferro[18]. A administração profilática de hematínicos (ferro, ácido fólico, vitamina B12) sempre deve ser considerada. b) Tratamento das deficiências de ferro Ferro intravenoso (IV), por infusão salina, como exemplo, o sacarato de hidróxido férrico (dose de 3 a 5 mg/kg/dia e máximo de 200 mg/dia) ou a carboximaltose (dose 15 mg/kg e máximo de 1.000 mg em infusão única) pode repor as reservas de ferro mais rápida. Pode-se aumentar a biodisponibilidade do ferro oral por meio de concomitante administração de ácido ascórbico. O uso simultâneo de produtos lácteos, gema de ovo, café, chá, antiácidos, ou fibra reduz a absorção do ferro oral. Recomenda-se uso de ferro parenteral em pacientes com intolerância ao ferro oral, absorção inadequada, ou perda de sangue crônica ou severa, ou nos casos de pacientes que não respondam ao tratamento[19]. c) Terapia com eritropoietina humana recombinante (r-Hu-EPO) É recomendada para aumentar a massa eritrocitária no préoperatório em pacientes anêmicos ou que recusam o uso de hemocomponentes ou naqueles propensos a ter anemia pós-operatória[16,20]. Antes do início e/ou durante a terapia com r-Hu-EPO corrigir as deficiências de ferro, ácido fólico e vitamina B12.
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cessidade de monitorar e controlar os níveis pressóricos. Em pacientes com anemia e neoplasia maligna, deve-se avaliar o risco-benefício da terapia com r-Hu-EPO devido ao aumento de eventos tromboembólicos, progressão do tumor e risco de mortalidade aumentada nesta população de pacientes[28]. A darbepoietina (dose 0,45 µg/kg/semana) e o CERA (continuous erythropoietin receptor activator - dose 0,60 µg/kg a cada duas semanas) são outros agentes estimuladores da eritropoiese com maior estabilidade metabólica e meia-vida mais longa, no momento ainda não disponível em vários países. 6 - Tratamento da plaquetopenia A maioria dos casos de plaquetopenia se resolve suspendendo ou evitando agentes causais (drogas citotóxicas, circulação extracorpórea (CEC), hemodiluição excessiva), tratando doenças que afetam a medula óssea (infecções graves, púrpura trombocitopênica trombótica ou imune), esplenectomia (hiperesplenismo). Independentemente da etiologia, as seguintes drogas podem ser usadas separadamente para estimular a trombocitopoiese: a) Eltrombopag: dose 50-100 mg/dia; b) Interleucina-11 humana recombinante (oprelvecina): dose 50 µg/kg/dia; c) Trombopoietina humana recombinante (r-Hu-TPO): dose 300 IU/kg/dia; d) Imunoglobulina humana: dose 200-400 mg/kg/dia. A literatura evidencia eficácia do eltrombopag[29] e da r-Hu-TPO[30] para estimular a trombocitopoiese e, consequentemente, redução de transfusão plaquetas. 7 - Nutrição Alimentação enteral precoce, conforme tolerada. Nutrição parenteral intravenosa em pacientes que não podem ser
alimentados através do aparelho digestivo. Suplementação proteica para apoiar a eritropoiese. 8 - Planejamento pré-operatório adicional Se a perda sanguínea esperada no pós-operatório for elevada, podendo resultar em um quadro de grave anemia, seria necessário considerar um enfoque cirúrgico diferenciado, ou combinações apropriadas de estratégias pré-operatórias para otimizar o nível perioperatório de hemoglobina, os fatores de coagulação e a condição do paciente. Combinações de métodos de conservação sanguínea no intra e pós-operatório também poderão ser considerados. A doação de sangue autóloga pré-operatória ainda não está bem definida em relação ao seu real benefício e custo-efetividade. Seu uso em cirurgia cardíaca é bastante discutível. II - Minimizar a perda de sangue A cirurgia cardíaca está frequentemente associada a sangramento. Quanto maior for esta perda sanguínea, mais será indicado o uso de múltiplas modalidades de preservação sanguínea. O uso de combinações apropriadas de técnicas tem um efeito sinérgico na redução do sangramento cirúrgico e não cirúrgico (causado por coagulopatia). A perda de sangue excessiva está relacionada com efeitos adversos[31]. A Tabela 2 evidencia as principais ações para minimizar perdas de sangue em cirurgias. Resumidamente, descrevemos cada uma delas:
Tabela 2. Principais ações para minimizar a perda de sangue. Estudo 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]
Principais ações para minimizar a perda de sangue To eliminate daily multiple routine phlebotomies Minimizar o volume de sangue retirado para diagnóstico (usar tubos pequenos) Evitar ou reduzir ao máximo o tempo de CEC Sistema e minicircuitos em CEC reduz hemotransfusões Ultrafiltração reduz hemorragia e transfusões de sangue Hipotermia moderada (temperatura durante a CEC entre 30 e 32ºC) Pressão Arterial no menor nível possível que mantenha a perfusão tecidual (PAM de 50-65 mmHg) Hemostasia meticulosa (controle rápido e extremamente cuidadoso de hemorragias) Agentes hemostáticos tópicos para controlar sangramento local Hemostasia farmacológica com ácido tranexâmico ou ácido épsilon animocaproico Desmopressina aumenta a adesão plaquetária e melhora hemostasia r-FVIIa para controlar hemorragias em situações de trombocitopenia, desordens da função plaquetária e coagulopatias pré-existentes ou induzidas por drogas CCP para restaurar de forma rápida os fatores de coagulação e controlar sangramento maior Concentrado de fibrinogênio humano para repor fibrinogênio e controlar sangramento maior Fator XIII recombinante humano para controlar sangramentos maior, quando outros hemostáticos não produziram resultados satisfatórios Hemodiluição normovolêmica aguda é segura e custo-efetivo em reduzir transfusão de sangue alogênico em cirurgias Recuperação sanguínea intraoperatória (cell saver) em cirurgias para conservação do sangue autólogo
CCP=Concentrado de complexo protrombínico; CEC=Circulação extracorpórea; PAM=Pressão arterial média; r-FVIIa=Fator VII recombinante ativado
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1 - Reduzir flebotomias para fins diagnósticos Realizar somente os testes essenciais. Eliminar múltiplas flebotomias rotineiras diárias[32]. Solicitar somente testes ou procedimentos com probabilidade de alterar o tratamento. 2 - Minimizar o volume de sangue retirado para diagnóstico Utilizar tubos pediátricos (de volume pequeno) para retiradas de sangue em adultos[33]. Realizar microcoletas de sangue. Monitoramento não invasivo (oximetria de pulso, oximetria transcutânea). Uso restritivo de sondas de demora. 3 - Reduzir a perda de sangue em procedimentos médicos invasivos Minimizar inserção de cateteres arteriais ou venosos centrais, hemofiltragem, diálise, cateterização cardíaca. Aplicação criteriosa de procedimentos invasivos em pacientes recebendo anticoagulantes ou inibidores da agregação plaquetária. 4 - Preservação sanguínea intraoperatória e manejo do sangue autólogo a) Técnicas cirúrgicas para minimizar a perda sanguínea Hemostasia meticulosa. Controle rápido e extremamente cuidadoso de hemorragias[34]. Enfoque cirúrgico menos traumático (cirurgia minimamente invasiva e/ou considerar um enfoque que evite operar através de aderências conhecidas ou suspeitas). Oclusão mecânica (ligaduras, clipes vasculares, grampos, suturas). Reduzir a duração da cirurgia, principalmente o uso de CEC. Em estudo multicêntrico, demonstrou-se que a cirurgia sem CEC reduziu significativamente a necessidade de transfusão e de reoperação por sangramento[35]. Em uma meta-análise de estudos randomizados, verificou-se que o emprego do sistema de minicircuitos em CEC foi eficaz em reduzir o número de hemotransfusões[36]. Se possível, adaptar o circuito da CEC para acomodar um prime pequeno, de cerca de 750 a 1.200 ml de cristaloides. O uso da ultrafiltração em cirurgia cardíaca, avaliada em outra meta-análise, resultou em redução de hemorragia e, consequentemente, significativa redução das transfusões de sangue[37]. O emprego do prime autólogo retrógado durante a CEC é seguro e efetivo em reduzir o grau de hemodiluição e, assim, proporcionar um adequado transporte de oxigênio, minimizando o consumo de sangue alogênico[38]. Hipotermia moderada. A manutenção da temperatura durante a CEC entre 30 e 32ºC está relacionada com redução do sangramento no intra e pós-operatório[39]. Reinfundir todo o sangue do circuito de CEC, e se possível o sangue coletado pela drenagem do mediastino nas primeiras seis horas de pós-operatório. Verificar, durante e imediatamente após a CEC, o tempo de coagulação ativado (TCA) para evitar a hiperheparinemia. Corrigir com sulfato de protamina (1mg de protamina é capaz de inativar em média 100 UI de heparina sódica). Dividir em etapas os procedimentos complexos. b) Embolização angiográfica pré-operatória profilática Se há suspeita de sangramento mas não se sabe ao certo
qual a causa, empregue o uso precoce de angiografia seletiva e embolização para parada rápida da perda de sangue. c) Permitir hipotensão moderada durante o sangramento Em sangramentos não controlados, a normalização da pressão arterial pode ser prejudicial. Em pacientes com hemorragias agudas de risco, sugere-se tolerar hipotensão de leve à moderada, isto é, pressão arterial no menor nível possível que mantenha a perfusão tecidual (pressão arterial média de 50-65 mmHg)[40]. d) Manuseio da pressão arterial Lento e gradual retorno à pressão normal após o controle do sangramento. Moderada hipotensão pós-operatória (pressão sanguínea sistólica de 80-90 mmHg no paciente normotenso) é suficiente para manter a perfusão dos órgãos vitais e evitar picos pressóricos com risco de desencadear hemorragias posteriores[40]. e) Instrumentos cirúrgicos hemostáticos: eletrocautério/ eletrocirurgia; coagulador com raio de argônio; pinça bipolar; ablação térmica por radiofrequência; laser. f) Hemostasia farmacológica: agentes hemostáticos sistêmicos As diretrizes de cirurgia cardíaca[16] recomendam inicialmente: ácido tranexâmico: dose 25 mg/kg de peso. A dose máxima não pode ultrapassar 50-100 mg/kg, devido à neurotoxicidade; ácido épsilon aminocaproico: dose de ataque de 150 mg/kg de peso. A administração deve ser continuada pela infusão de 10 mg/kg/hora, durante quatro ou cinco horas, sendo a dose máxima em 24 g (um grama por hora). Em caso de sangramento excessivo, pode-se associar outros agentes hemostáticos: vasopressina: dose 0,2-0,4 U/min, até parar o sangramento, e manutenção de 12 horas; estrogênios conjugados: dose de 20 mg por via IV, preferencialmente. Se necessário repetir a administração após 6 a 12 horas. Deve-se ter cautela em pacientes portador de cardiopatia grave, renal ou hepática[41]. g) Hemostasia farmacológica: agentes que aumentam a atividade dos fatores de coagulação Acetato de desmopressina (DDAVP) Dose 0,3 µg/ kg de peso. Como profilaxia de sangramento em CRM, em particular para os pacientes em uso de AAS ou nos casos de tempo de CEC prolongado[16]. A desmopressina pode aumentar a adesão plaquetária e os níveis de fatores de coagulação VIII e von Willebrand no plasma[42]. Em uma meta-análise de 38 estudos randomizados, placebo-controlados verificou-se que a desmopressina reduz significativamente o sangramento intraoperatório e transfusão de componentes do sangue, sem aumentar os riscos de complicações tromboembólicas[43]. A desmopressina pode ser usada com os ácidos épsilon aminocaproico e tranexâmico sem efeitos adversos. Devido ao risco de hipotensão, sugere monitorização do paciente. Vitamina K (fitomenadiona) Dose em adultos: 10-20 mg IV lenta (máximo de 50 mg/
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dia) e 100 mg via oral. Em hemorragia, pode-se considerar administração parenteral de vitamina K no pós-operatório[44]. Fator VII recombinante ativado (r-FVIIa) Dosagem 40-90 µg/kg de peso corpóreo. Esta dose pode ser repetida a cada 2 horas de acordo com o tipo e gravidade da hemorragia. Pode ser utilizada uma dose única de 270 µg/kg em casos de hemorragias moderadas. O uso do r-FVIIa podem ser considerado em situações clínicas em que a abordagem convencional de hemostasia cirúrgica e farmacológica falharam e uma hemorragia incontrolável coloca um elevado risco de desfechos graves e com risco de morte[16]. O r-FVIIa tem sido relacionado à redução de perda sanguínea em pacientes não-hemofílicos em várias situações clínicas incluindo sangramento pós operatório, trombocitopenia, desordens congênitas ou adquiridas da função plaquetária e tendências adquiridas de sangramento e coagulopatias pré-existente ou induzidas por drogas[45]. Terapia de reposição de fator VIII de coagulação (concentrado) O fator VIII (25 UI/kg de peso) está disponível como produto recombinante e uso específico. Concentrado de complexo protrombínico (CCP) Dosagem 20-40 UI/kg de peso. O CCP atua nos estágios de iniciação e amplificação da coagulação. Restauram de forma rápida os níveis normais dos fatores de coagulação. Permitem a progressão da via da protrombina[46]. A literatura demonstra eficácia do CCP comparável à transfusão de plasma fresco congelado em controlar sangramento maior e evitar mortalidade após trauma[47]. Concentrado de fibrinogênio humano Dosagem 25-50 mg/kg de peso. Recomenda-se o uso de 1-2 g para sangramento pequeno e 4-8 g para um sangramento excessivo. É eficaz para controlar sangramento maior durante cirurgia e, com isso, evitar ou minimizar o uso de transfusão de plasma e/ou plaquetas[48]. Recomenda-se uma concentração de fibrinogênio mínima de 1,5-2,0 g/L em pacientes cirúrgicos. Condições associadas à hipofibrinogenemia: perda maciça de sangue, transfusão maciça, diluição do sangue com substitutos do plasma, lesão tecidual extensa, coagulação intravascular disseminada, hemodiálise, cirurgia ou lesão de órgãos com potencial pró-fibrinolítico, insuficiência hepática, terapia fibrinolítica. Fator XIII recombinante humano Dosagem 20-35 UI/kg/dia até cessar o sangramento. É recomendado para estabilizar coágulos em pacientes com sangramentos excessivo pós-cirurgia cardíaca, quando outros hemostáticos não produziram resultados satisfatórios[49]. h) Hemostasia farmacológica: agentes hemostáticos tópicos Eficazes em controlar o sangramento local, principalmente quando a hemostasia cirúrgica não foi efetiva[49,50]: hemostato de celulose oxidada para compressão da ferida; adesivos para tecidos/cola de fibrina/selantes; gel de fibrina ou de plaquetas; colágeno hemostático; espuma/esponjas de gelatina; tamponamento tópico de trombina ou embebido com trombina; polissacarídeos de origem vegetal; alginato de cálcio.
5 - Hemodiluição Normovolêmica Aguda (HNA) A hemodiluição, além de ser uma estratégia de baixo custo, pode produzir efeitos benéficos, como por exemplo, menos insuficiências de órgãos em resultado do aumento da liberação de oxigênio ao nível microcirculatório e menos complicações trombóticas como consequência de menor agregação plaquetária. Além das técnicas convencionais de preservação do miocárdio, a HNA pré-operatória promove maior proteção cardíaca em pacientes submetidos a CRM[51]. A quantidade de sangue a ser removido durante a hemodiluição é determinada pela fórmula de Gross[52]: V = EBV x (Hcti- Hctf) / Hctav onde V = volume de sangue retirado, EBV é o volume sanguíneo estimado, Hcti é o hematócrito inicial ideal, Hctf é o hematócrito mínimo e Hctav é o hematócrito médio [(Hcti + Hctf)/2]). Regra prática: para cada bolsa de sangue retirada (450 ml), infundir lentamente (para evitar hipervolemia) 1.000 ml de cristaloides. A HNA talvez seja mais eficaz quando se consegue retirar pelo menos 1.000 ml de sangue no início da cirurgia. A HNA, além de ser custo-efetivo, tem sido usada com segurança em evitar ou reduzir transfusões de sangue homólogo em cirurgia cardíaca de adultos[16,53] e crianças[54]. A Figura 3 mostra uma representação esquemática de uma HNA. 6 - Recuperação sanguínea intraoperatória/Autotransfusão A recuperação intraoperatória de sangue é uma das estratégias mais importantes em cirurgias cardiotorácicas capaz de reduzir a perda de sangue total e a necessidade de transfusão de sangue homólogo e é recomendado pelas diretrizes de conservação de sangue autólogo[16,49,55]. Por ser uma estratégia facilmente aplicável, alguns autores defendem seu uso em todos os pacientes submetidos à cirurgia cardíaca com CEC, independentemente da perda esperada de sangue relacionada à cirurgia[55]. Trata-se de uma importante estratégia para cirurgia cardíaca pediátrica complexa e grave[54]. No caso de paciente oncológico e cirurgia cardíaca, com necessidade de recuperação sanguínea, considerar uso de filtros de remoção de leucócitos sozinhos ou em combinação com irradiação. Em recente revisão sistemática realizada pela Cochrane Database of Systematic Reviews[56], os autores concluíram que a recuperação sanguínea intraoperatória é eficaz na redução da necessidade de transfusão de sangue alogênico em cirurgia cardíaca. A Figura 4 mostra uma representação esquemática de uma recuperação sanguínea intraoperatória. 7 - Estratégias adicionais Uma outra estratégia para reduzir sangramento em cirurgia consiste na infusão contínua de noradrenalina e uma hidratação restritiva. O risco absoluto de transfusão de sangue durante a internação reduziu em 28%. Os autores concluíram ainda que este procedimento é fácil de realizar, barato e seguro[57].
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Fig. 3 - Representação esquemática da hemodiluição normovolêmica aguda - (A) Bolsas de sangue sendo retiradas imediatamente antes do início da cirurgia, juntamente com a infusão de expansor para manter a normovolemia. (B) Bolsas de sangue sendo reinfundidas durante e/ou imediatamente após o término da cirurgia.
Fig. 4 - Representação esquemática da recuperação sanguínea intraoperatória - O sangue coletado é misturado com anticoagulante, filtrado, lavado, concentrado e devolvido ao paciente.
III - Tolerância à anemia A tolerância individual de cada paciente à anemia é um dos fatores mais importantes no momento de decidir sobre transfundir ou não. Na literatura não temos estudos demonstrando um gatilho mínimo de hemoglobina para se recomendar uma hemotransfusão segura. No entanto, temos vários ensaios clínicos, randomizados demonstrando que uma estratégia restritiva de transfusão de sangue é segura e eficaz em reduzir o uso de sangue alogênico, e não aumenta o risco de complicações ou morte em cirurgias cardíacas em adultos[12] e crianças[58].
Através de uma meta-análise e revisão sistemática recente da literatura ficou comprovado que uma maior tolerância à anemia, uma conduta mais restritiva para transfundir, é realmente benéfica para pacientes criticamente doentes[59]. Senay et al.[14] verificaram que um hematócrito até 17% durante a CRM, é bem tolerado e não tem impacto adverso no resultado. O conhecimento deste fato resultaria em evitar muitas transfusões alogênicas desnecessárias, visto que, na maioria das vezes, não é o paciente, e sim, o médico que não tolera a anemia. Frequentemente, transfusões são indicadas
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mediante valores laboratoriais de hemoglobina e/ou hematócrito. Essa prática não é recomendada por Murphy et al.[60] ao considerarem as indicações de transfusão de sangue em cirurgias cardíacas, por ter evidência de que o hematócrito não é um indicador ideal da oferta de oxigênio aos tecidos. A literatura evidencia que o ser humano é capaz de tolerar níveis extremamente baixos de hemoglobina. Graffeo et al.[61] relataram um caso que, após um quadro de hemorragia grave e coagulação intravascular disseminada, chegou a um nadir mínimo de 1,9 g/dL de hemoglobina. Em outro relato, após cirurgia de grande escoliose toraco-lombar, a paciente também sobreviveu sem uso de transfusão de sangue, mesmo após atingir nível crítico de 1,4 g/dL de hemoglobina[62]. Nestes dois casos, a tolerância à anemia foi uma opção terapêutica que resultou em economia de hemocomponentes para os bancos de sangue. A Tabela 3 evidencia as principais ações para melhorar a tolerância à anemia. Esta estratégia envolve pelo menos duas terapias fundamentais:
ou na frequência cardíaca. Deverá ser individualizada com base em parâmetros fisiológicos que incluem uma contínua reavaliação da perfusão tecidual e da oxigenação, bem como da função hemodinâmica. Se existir dúvida sobre o estado volêmico ou o débito cardíaco do paciente anêmico, faça uma avaliação apropriada do quadro clínico, por exemplo: prova de volume, ecoDopplercardiograma, etc. Variações tanto na pressão arterial sistólica como na pressão de pulso com o ciclo ventilatório podem indicar depleção de volume no paciente em ventilação mecânica. Mesmo durante hipotensão relativa, o fluxo e a oxigenação do sangue microcirculatório nem sempre dependem da pressão arterial[64]. Expansores de volume sem sangue Cristaloides: a infusão deve ser de três mililitros de cristaloides para cada um mililitro de sangue perdido com uma velocidade de infusão de 60-80 ml/kg/hora (preferencialmente lactato de Ringer). O Advanced Trauma Life Support (ATLS) recomenda que no paciente traumatizado, se houve uma perda de 700 ml, o paciente receba 2.100 ml de cristaloides. Podem ser utilizadas: 1) solução salina normal, 2) soluções eletrolíticas balanceadas ou 3) solução salina hipertônica Coloides (soluções de amido e gelatinas): dose de um mililitro de coloide para cada um mililitro de sangue perdido, sendo a dose máxima recomendada de 1.500 a 2.000 ml por dia. Criteriosa reposição de fluidos. No paciente hipovolêmico, a estratégia de reposição de volume (tempo, ritmo de administração e a quantidade) pode ser mais importante do que a escolha do fluido. Existe o risco de se provocar mais sangramento por elevação excessiva da pressão arterial e hemodiluição em excesso. Administração criteriosa do volume com níveis baixos de hemoglobina pode otimizar o fluxo e a oxigenação microvascular, bem como aumentar a tolerância à anemia[65]. Em quantidades moderadas, cristaloides não estão associados com efeitos colaterais significativos, particularmente em hemostasia. A infusão de cristaloide (lactato de Ringer) resultou em menor perda de sangue que os coloides (Hydroxyethyl Starch) em investigação recente[66].
1 - Otimização da entrega de oxigênio a) Avaliar perfusão e oxigenação tecidual Índices de perfusão global: os marcadores de hipoperfusão incluem oligúria, diminuição do sensório, acidose lática, déficit ou excesso de bases e taquicardia. Índices de perfusão regional: avaliar os marcadores de funções orgânicas: isquemia miocárdica (anormalidades do segmento ST), disfunção renal (decréscimo no débito urinário e/ou aumento dos níveis de ureia/creatinina) e disfunção do sistema nervoso central (estado mental alterado). Observar as evidências em combinação com os índices de perfusão/hipóxia tecidual[63]. b) Aumentar o débito cardíaco Otimizar o volume circulante Conhecer a capacidade cardíaca do paciente. A pressão arterial média, ritmo cardíaco, padrão respiratório, débito urinário e balanço hídrico devem ser avaliados. A reposição de fluidos não deve ser baseada apenas na pressão arterial
Tabela 3. Principais ações para melhorar tolerância à anemia. Estudo 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]
Principais ações para melhorar tolerância à anemia Paciente tolera anemia no perioperatório Paciente tolera anemia no pós-operatório Conduta restritiva para transfusão sanguínea Avaliar índices de perfusão/hipóxia tecidual Hematócrito não é um indicador ideal da oferta de oxigênio aos tecidos Criteriosa reposição de volume para otimizar o fluxo e a oxigenação microvascular em anemia grave A infusão de cristaloide (lactato de Ringer) resulta em menor perda de sangue que os coloides Corrigir hipovolemia com cristaloide, ao invés das soluções de amido, resulta em menor risco de mortalidade Ventilação mecânica (hiperóxica) assegura a oxigenação dos tecidos na vigência de anemia aguda grave Manter a normotermia em doentes graves (aquecer pacientes hipotérmicos e resfriar pacientes febris)
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Corrigir hipovolemia, se possível, sempre com cristaloide. Em uma revisão sistemática realizada pela Cochrane Database of Systematic Reviews[67], os autores verificaram maior risco de mortalidade com as soluções de amido. c) Oxigenoterapia precoce/Oxigênio suplementar A tolerância à anemia pode ser aumentada ao ventilar o paciente com uma alta fração inspirada de oxigênio (FiO2). Enquanto é mantida a normovolemia, a ventilação hiperóxica (100% de oxigênio) pode ser considerada uma terapia de salvamento na vigência de hemorragia importante associada à anemia aguda grave com risco de morte[62,68]. Ventilar com 100 % de oxigênio resulta em aumento rápido do conteúdo arterial de oxigênio, assegura a oxigenação dos tecidos mesmo com uma hemoglobina muito baixa e mostra ser uma estratégia importante em reduzir transfusão alogênica[69]. Para pacientes com resposta insuficiente a outras medidas para a melhoria da oxigenação (exemplo: correção do volume em circulação, agentes vasoativos, inotrópicos), sugere-se empregar sedação e suporte ventilatório (pressão positiva contínua nas vias aéreas [CPAP], pressão positiva intermitente [BIPAP]). Quanto mais rápido for detectada e corrigida a deficiência de oxigênio nos tecidos, tanto maiores serão as probabilidades de melhores resultados. Uma vez que a hipoxemia apresenta riscos imediatos maiores do que a toxicidade do oxigênio ou a hipercapnia, pode valer a pena correr os riscos envolvidos em frações supranormais de oxigênio inspirado para sustentar a vida do paciente com anemia grave[70]. O uso de terapia com oxigênio hiperbárico para alcançar uma alta tensão arterial (PaO2) têm o potencial de salvar a vida do paciente com anemia grave[71]. d) Compostos carreadores de oxigênio e soluções de hemoglobina polimerizada O perfluorocarbono e MP4OX (oxygenated polyethylene glycol-modified hemoglobin) ainda necessitam de evidências garantindo segurança e eficácia, além de custo-efetividade. 2 - Minimização do consumo de oxigênio a) Analgesia apropriada b) Sedação e relaxantes musculares Sugere-se administrar a menor dose efetiva para a menor duração de analgesia e sedação. Considerar bloqueio neuromuscular. Diminuir o consumo de oxigênio mediante a redução da taxa metabólica e prevenção de calafrios, agitação e ansiedade. c) Ventilação mecânica Pode ser recomendada em caso de anemia grave, para melhorar a oferta e reduzir o consumo de oxigênio pelos tecidos. d) Controle da temperatura Manter a normotermia (aquecer ativamente pacientes hipotérmicos e resfriar pacientes febris)[72]. O uso de resfriamento terapêutico em pacientes com anemia grave em terapia intensiva pode reduzir a necessidade de oxigenação dos tecidos, diminuir a taxa metabólica e oferecer proteção cerebral em subgrupos de pacientes[73].
DISCUSSÃO A transfusão de sangue é na sua essência um transplante de células alogênicas, que consiste na infusão de grandes quantidades de antígenos estranhos na circulação do receptor, resultando em múltiplas reações inflamatórias e imunológicas[74]. Esta é uma das principais explicações dos resultados adversos desta prática médica. Centros em todo mundo buscam instituir protocolos para se racionar o uso do sangue e isso tornou-se um critério de qualidade hospitalar perseguido pelas agências certificadoras de qualidade, como por exemplo, a Joint Commission International[75]. Vários caminhos podem ser utilizados como parte destes protocolos de conservação de sangue. É importante tornar conhecido as principais possibilidades terapêuticas às transfusões para economizar hemocomponentes, que já se encontram escassos nos bancos de sangue. Quando se tem o propósito e o envolvimento multiprofissional para gerenciar e conservar o sangue autólogo é possível realizar cirurgias cardíacas complexas, como um retransplante cardíaco, sem o uso de sangue alogênico[54]. Mediante aplicação de uma ou mais estratégias, conforme expressas nas Tabelas 1, 2 e 3 é possível diminuir o consumo de sangue alogênico. Uma medida simples, mas de fundamental importância é o diagnóstico e tratamento de anemia com reposição de ferro, ácido fólico, vitamina B12 e, quando necessário, r-Hu-EPO. As principais ações para minimizar a perda de sangue envolvem eliminar múltiplas flebotomias rotineiras diárias, evitar ou reduzir o tempo de CEC, hemostasia meticulosa, hemostasia farmacológica com ácido tranexâmico ou ácido épsilon aminocapróico, uso de medicamentos que aumentam a atividade dos fatores de coagulação (desmopressina, r-FVIIa, CCP, Fator XIII), além da HNA e recuperação sanguínea intraoperatória (cell saver). Outra medida importante para racionar sangue é adotar uma conduta restritiva de transfusão, com ações para melhorar a oxigenação tecidual do paciente anêmico. Estas e outras estratégias estão descritas na Figura 2. Quanto mais terapias alternativas forem aplicadas, maior é a possibilidade de tratar um paciente sem a necessidade de transfusão[76]. Os benefícios não estão restritos à esfera econômica, mas também à incidência e à gravidade das complicações, em particular a mortalidade, relacionadas às hemotransfusões alogênicas. Esta revisão da literatura reúne múltiplas opções terapêuticas para reduzir o número de doentes transfundidos e a quantidade de sangue e seus componentes administrados a cada doente. Mas, antes de implantar tais medidas, é fundamental um desejo de mudar o comportamento transfusional, principalmente em relação à tolerância à anemia. Algumas medidas são simples e seguras e podem ser facilmente implementadas, outras requerem um processo bem orquestrado. Estas estratégias não são mutuamente exclusivas e a realidade de cada serviço pode guiar quais ações são melhores e mais
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factíveis. Um centro médico que estabelece um processo de conservação de sangue autólogo pode reduzir em até 70% tanto no número de unidades de hemocomponentes infundidos, como o número de pacientes hemotransfundidos[76]. Estimulamos este novo conceito na medicina transfusional que, com o menor uso de sangue alogênico em cirurgias cardíacas, poderá resultar em redução na morbimortalidade total dos pacientes, bem como amenizar a demanda nos bancos de sangue. Sugere-se novos estudos para avaliar segurança e eficácia das transfusões de sangue alogênico. Uma das principais limitações para utilização de algumas destas opções às transfusões de sangue diz respeito ao custo e disponibilidade de determinada estratégia, como por exemplo, a máquina de recuperação sanguínea intraoperatória, certos medicamentos (r-Hu-TPO, eltrombopag, Fator VIIa, Fator XIII, CCP, CFH) e curva de aprendizado de técnicas cirúrgicas mais apuradas para evitar sangramentos. A técnica do prime autólogo retrógado também é uma opção limitada, devido a potenciais complicações de instabilidade hemodinâmica, resultante da hipovolemia. Outra limitação para o emprego de algumas destas estratégias ocorrerá em cirurgias de emergências. Um fator importante a ser considerado em relação à prática transfusional e não transfusional é a avaliação do binômio risco/benefício. Quando decisões médicas são tomadas por equipes multidisciplinares há uma redução no potencial de causar dano pelo tratamento, quer para determinados subgrupos de pacientes ou mesmo para a população em geral.
coagulação, minimizar a perda de sangue e melhorar tolerância à anemia. 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. Estes recursos terapêuticos deveriam ser incorporados à prática médica mundial, visando diminuir o consumo de hemocomponentes, reduzir a morbimortalidade e custos hospitalares.
Papéis & responsabilidade dos autores AAS JPS LFS AGS
CONCLUSÃO
RFP
Existem múltiplas estratégias clínicas e cirúrgicas com evidências em otimizar a massa eritrocitária e o estado de
JFB
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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.
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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.
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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.
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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
1
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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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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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
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CONCLUSION
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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.
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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.
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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
1
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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Yuan SM - S100 and S100ß: biomarkers of cerebral damage in cardiac surgery with or without the use of cardiopulmonary bypass
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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Rev Bras Cir Cardiovasc 2014;29(4):630-41
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.
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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.
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
CASE PRESENTATION 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
1
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
Authors’ 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 Mendonça 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
1
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-
1
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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Canale LS & Bonatti J - How to perform a coronary artery anastomosis in complete endoscopic fashion with robotic assistance
We here describe our technique of choice for robotic LIMA-LAD anastomosis. Pictures and video further illustrates the procedure. Authors’ 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.
1
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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Aazami MH, et al. - Right-sided reverse T composite arterial grafting to complete revascularization of the right coronary artery
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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Rev Bras Cir Cardiovasc 2014;29(4):657-62
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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Conception and study design, performed procedures and/or experiments, writing of the manuscript or review of its content Final approval of manuscript Final approval of manuscript conception and design of the study analysis and/or interpretation of data, carrying out of operations and/or experiments, writing of the manuscript or review of its content
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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.
1
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 – A) Preoperative transesophageal echocardiography. Fig. 1 – 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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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.
Authors’ 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
Revisores RBCCV/BJCVS 29.4 A Revista Brasileira de Cirurgia Cardiovascular/Brazilian Journal of Cardiovascular Surgery (RBCCV/BJCVS) agradece o trabalho dedicado dos revisores que colaboram nesta edição, cujas sugestões e observações são fundamentais para manter o nível científico da nossa revista.
Domingo Braile Editor-Chefe 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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NORMAS DA RBCCV Revista Brasileira de Cirurgia Cardiovascular/BRAZILIAN JOURNAL OF CARDIOVASCULAR SURGERY Editor Prof. Dr. Domingo M. Braile Av. Juscelino Kubitschek de Oliveira, 1.505 – Jardim Tarraf I 15091-450 – São José do Rio Preto – SP - Brasil E-mail: revista@sbccv.org.br
Submissão Eletrônica Os manuscritos devem ser, obrigatoriamente, submetidos eletronicamente no site http://www.rbccv.org.br/sgp/ Quando entrar nesse link, o sistema irá pedir seu nome de usuário e senha, caso já esteja cadastrado. Caso contrário, clique no botão “Quero me cadastrar” e faça seu cadastro. Ou ainda, caso tenha esquecido sua senha, use o mecanismo para lembrar sua senha, que gerará um e-mail contendo sua senha.
A Revista Brasileira de Cirurgia Cardiovascular/ Brazilian Journal of Cardiovascular Surgery (RBCCV/BJCVS) é o órgão oficial de divulgação da Sociedade Brasileira de Cirurgia Cardiovascular (SBCCV), trata-se de uma publicação trimestral, com circulação regular desde 1986. A RBCCV/ BJCVS está indexada na base de dados Thomson Scientific (ISI), Medline/PubMed, SCOPUS, SciELO, LILACS, SCIRUS e SCImago. A RBCCV/BJCVS tem como objetivo registrar a produção científica em cirurgia cardiovascular, fomentar o estudo, aperfeiçoamento e atualização dos profissionais da especialidade. Os trabalhos enviados para publicação na RBCCV/ BJCVS devem versar sobre temas relacionados à cirurgia cardiovascular e áreas afins. A revista publica as seguintes categorias de artigos: artigo original, editorial, artigo de revisão, artigo especial, relato de caso, como-eu-faço”, comunicações breves, notas prévias, correlação clínicocirúrgica, trabalho experimental, multimídia e carta ao editor. A aceitação será feita baseada na originalidade, significância e contribuição científica. Artigos com objetivos meramente propagandísticos ou comerciais não serão aceitos. Os autores são responsáveis pelo conteúdo e informações contidas em seus manuscritos. A RBCCV/BJCVS repudia veementemente o plágio e o autoplágio. A revista será publicada na íntegra no site da revista (www. rbccv.org.br/www.bjcvs.org) e da SciELO (www.scielo.br/ rbbcv), com links específicos no site da SBCCV (www.sbccv. org.br) e da CTSNET (www.ctsnet.org).
O sistema de submissão é autoexplicativo e inclui 8 passos: • 1º Passo: classificação do artigo • 2º Passo: inclusão de título e palavras-chave • 3º Passo: cadastro de autores • 4º Passo: inclusão de Resumo e Abstract • 5º Passo: inclusão do manuscrito propriamento dito com referências • 6º Passo: envio das imagens • 7º Passo: geração das declarações de transferência de direitos autorais (copyright), conflito de interesses e cópia do Parecer do Comitê de Ética em Pesquisa da Instituição • 8º Passo: aprovação do autor/ finalização da submissão Os textos devem ser editados em word e as figuras e tabelas devem estar em arquivos separados. Mantenha seu cadastro atualizado, pois a comunicação com os autores é exclusivamente por e-mail. Ao terminar a submissão de seu trabalho, será gerado um e-mail informando se a submissão foi efetuada corretamente, outro e-mail será gerado após conferir se o mesmo está dentro dos padrões. Caso o artigo esteja “Fora de padrão”, o autor será avisado por e-mail e poderá corrigí-lo entrando no SGP/RBCCV em www.rbccv.org.br/sgp. Os autores poderão acompanhar a tramitação de seu trabalho a qualquer momento pelo SGP/RBCCV, por meio do código de fluxo gerado automaticamente pelo SGP, ou ainda pelo título de seu trabalho.
POLÍTICA EDITORIAL Norma A RBCCV/BJCVS adota as Normas de Vancouver - Uniform Requirements for Manuscripts Submitted to Biomedical Journals, organizadas pelo International Committee of Medical Journal Editors, disponíveis em: www.icmje.org Política de Submissão e Publicação Só serão considerados para revisão os manuscritos cujos dados não estejam sendo avaliados por outros periódicos e/ou que não tenham sido previamente publicados. Os manuscritos aprovados só poderão ser reproduzidos, no todo ou em parte, com o consentimento expresso do editor da RBCCV/BJCVS.
Avaliação pelos Pares (peer review) Todas as contribuições científicas são revisadas pelo Editor, Editores Associados, Membros do Conselho Editorial e/ou Revisores Convidados. Os revisores respondem a um
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questionário no qual fazem a classificação do manuscrito, sua apreciação rigorosa em todos os itens que devem compor um trabalho científico, atribuindo uma nota para cada um dos itens do questionário. Ao final são realizados comentários gerais sobre o trabalho e sugestão se o mesmo deve ser publicado, corrigido segundo as recomendações ou rejeitado definitivamente. De posse desses dados, o Editor tomará a decisão. Em caso de discrepâncias entre os avaliadores, poderá ser solicitada uma nova opinião para melhor julgamento. Quando forem sugeridas modificações, as mesmas serão encaminhadas ao autor principal e, em seguida, aos revisores, para estes verificarem se as exigências foram satisfeitas. Os autores têm o prazo de 30 dias para proceder às modificações solicitadas pelos revisores e ressubmeter o artigo. Na resposta aos comentários/sugestões dos revisores, os autores deverão destacar no texto as alterações realizadas. A não-observância desse prazo implicará a retirada do artigo do processo de revisão. Quando o artigo for aprovado, o autor será comunicado pelo e-mail cadastrado no site e deve encaminhar um resumo de até 60 palavras, em português e inglês, do artigo. Eles serão inseridos no mailing eletrônico enviado a todos os sócios quando a RBCCV/BJCVS estiver disponível on-line. Uma vez aceito para publicação, uma prova do artigo editorado (formato PDF) será enviada ao autor correspondente para sua avaliação e aprovação definitiva.
Os estudos randomizados devem seguir as diretrizes CONSORT (disponível em: www.consort-statement.org/ consort-statement). A RBCCV/BJCVS apóia as políticas para registro de ensaios clínicos da Organização Mundial de Saúde (OMS) e do International Committee of Medical Journal Editors (ICMJE), reconhecendo a importância dessas iniciativas para o registro e divulgação internacional de informação sobre estudos clínicos, em acesso aberto. Sendo assim, somente serão aceitos para publicação, os artigos de pesquisas clínicas que tenham recebido um número de identificação em um dos Registros de Ensaios Clínicos validados pelos critérios estabelecidos pela OMS e ICMJE, cujos endereços estão disponíveis no site do ICMJE (http://www.icmje.org/). O número de identificação deverá ser registrado ao final do resumo. A declaração de aprovação do estudo na Comissão de Ética e/ou Científica institucional deverá ser encaminhada no momento da submissão do manuscrito. Transferência de Direitos Autorais e Declaração de Conflito de Interesses Os autores dos manuscritos deverão encaminhar, no momento da submissão, a declaração de transferência de direitos autorais (copyright) assinada por todos os autores. Todos os manuscritos publicados tornam-se propriedade permanente da Revista Brasileira de Cirurgia Cardiovascular e não podem ser publicados sem o consentimento por escrito de seu editor. Da mesma forma, para efetivação da submissão do manuscrito deverá ser encaminhada uma declaração de conflito de interesses, assinada por todos os autores. Ambos os documentos, declaração de transferência de direitos autorais e declaração de conflitos de interesse, são padronizados e gerados pelo SGP no momento da submissão do manuscrito.
Idioma Os artigos devem ser redigidos em português ou inglês, empregando linguagem fácil e precisa e evitando-se a informalidade da linguagem coloquial. Para os trabalhos que não possuírem versão em inglês ou que essa seja julgada inadequada pelo conselho editorial, a revista providenciará a tradução e custos deverão ser assumidos pelos autores. A RBCCV/BJCVS priorizará a publicação de trabalhos submetidos em inglês.
Critérios de Autoria & Contribuição Individual para a Pesquisa Sugerimos que sejam adotados os critérios de autoria dos artigos segundo as recomendações do International Committee of Medical Journal Editors. Assim, apenas aquelas pessoas que contribuíram diretamente para o conteúdo intelectual do trabalho devem ser listadas como autores.
Pesquisa com Seres Humanos e Animais Investigação em seres humanos deve ser submetida ao Comitê de Ética da instituição, cumprindo a Declaração de Helsinque de 1975, revisada em 2008 (World Medical Association, disponível em: http://www.wma.net/ en/30publications/ 10policies/b3/17c.pdf), e a Resolução 196/96 do Conselho Nacional de Saúde (disponível em: http:// conselho.saude. gov.br/resolucoes/reso_96.htm). Nos trabalhos experimentais envolvendo animais, devem ser respeitadas as normas estabelecidas no Guide for the Care and Use of Laboratory Animals (Institute of Laboratory Animal Resources, National Academy of Sciences, Washington, D.C., Estados Unidos), de 1996, e em Princípios Éticos na Experimentação Animal (Colégio Brasileiro de Experimentação Animal – COBEA, disponível em: www. cobea.org.br), de 1991.
Os autores devem satisfazer a todos os seguintes critérios, de forma a poderem ter responsabilidade pública pelo conteúdo do trabalho: 1. ter concebido e planejado as atividades que levaram ao trabalho ou interpretado os resultados a que ele chegou, ou ambos; 2. ter escrito o trabalho ou revisado as versões sucessivas e tomado parte no processo de revisão; 3. ter aprovado a versão final.
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Pessoas que não preencham os requisitos acima e que tiveram participação puramente técnica ou de apoio geral, podem ser citadas na seção Agradecimentos.
ou nos respectivos links disponíveis no sistema de submissão da revista. Corpo do manuscrito. Os Artigos Originais e Trabalhos Experimentais devem ser divididos nas seguintes seções: Introdução, Método, Resultados, Discussão, Conclusão e Agradecimentos (opcional). Os Relatos de Caso devem ser estruturados nas seções: Introdução, Relato do Caso e Discussão; e as Correlações clínico-cirúrgicas em Dados Clínicos, Eletrocardiograma, Radiograma, Ecocardiograma, Diagnóstico e Operação. A seção Multímidia devem apresentar as seguintes seções: Caracterização do Paciente e Descrição da Técnica Empregada. Os Artigos de Revisão e Artigos Especiais podem ser estruturados em seções a critério do autor. As Cartas ao Editor, em princípio, deve comentar, discutir ou criticar artigos publicados na RBCCV/BJCVS, mas também pode versar sobre outros temas de interesse geral. Recomendase tamanho máximo de 1000 palavras, incluindo referências, que não devem exceder a cinco, podendo ou não incluir título. Sempre que cabível e possível, uma resposta dos autores do artigo em discussão será publicada junto com a carta.
No momento da submissão, deve ser explicitado o tipo de contribuição de cada autor na execução do estudo e preparação do manuscrito, nas seguintes áreas: 1. Desenho do estudo 2. Coleta, análise e interpretação dos dados 3. Redação do manuscrito Abreviações e Terminologia O uso de abreviaturas deve ser mínimo. Quando expressões extensas precisam ser repetidas, recomenda-se que suas iniciais em maiúsculas as substituam após a primeira menção. Esta deve ser seguida das iniciais entre parênteses. Todas as abreviações em tabelas e figuras devem ser definidas nas respectivas legendas. Deve ser evitado o emprego de abreviaturas no Resumo e Abstract. Apenas o nome genérico do medicamento utilizado deve ser citado no trabalho, sendo desaconselhado o emprego de nomes comerciais. RBCCV/BJCVS adota a Terminologia Anatômica Oficial Universal, aprovada pela Federação Internacional de Associações de Anatomistas (FIAA).
Referências As referências dos documentos impressos e eletrônicos devem ser normalizadas de acordo com o estilo Vancouver, elaborado pelo International Committee of Medical Journal Editors (ICMJE, disponível em: http://www.icmje.org). As referências devem ser identificadas, no corpo do texto, com algarismos arábicos sobrescritos, entre colchetes, obedecendo à ordem de citação no texto. A acurácia das referências é de responsabilidade do autor. Se forem citadas mais de duas referências em sequência, apenas a primeira e a última devem ser digitadas, sendo separadas por um traço (Exemplo: [6-9]). Em caso de citação alternada, todas as referências devem ser digitadas, separadas por vírgula (Exemplo: [6,7,9]). Publicações com até 6 autores, devem ser citados todos os autores; publicações com mais de 6 autores, citam-se os 6 primeiros seguidos da expressão latina “et al.”. Títulos de periódicos devem ser abreviados de acordo com o List of Journals Indexed for MEDLINE (disponível em: http://www.nlm.gov/tsd/serials/lji.html).
PREPARAÇÃO DO MANUSCRITO Seções do Manuscrito Título e Autores. O título do trabalho, em português e inglês, deve ser conciso e informativo. Devem ser fornecidos os nomes completos dos autores, titulação e vinculação institucional de cada um deles. Resumo e Abstract. O resumo deve ser estruturado em quatro seções: Objetivo, Métodos, Resultados e Conclusão. O Abstract (versão literal, em inglês, do Resumo em português) deve seguir a mesma estrutura do Resumo, em quatro seções: Objective, Methods, Results e Conclusion. Devem ser evitadas abreviações. O número máximo de palavras deve seguir as recomendações da tabela. Nos artigos tipo Relatos de Casos e Como-eu-Faço, o resumo e o abstract não devem ser estruturados (informativo ou livre). As Correlações clínico-cirurgicas e seções Multimídia dispensam resumo e abstract.
Modelos de Referências Artigo de Revista Issa M, Avezum A, Dantas DC, Almeida AFS, Souza LCB, Sousa AGMR. Fatores de risco pré, intra e pós-operatórios para mortalidade hospitalar em pacientes submetidos à cirurgia de aorta. Rev Bras Cir Cardiovasc. 2013;28(1):10-21.
Descritores e Descriptors: Também devem ser incluídos de três a cinco descritores (palavras-chave), assim como a respectiva tradução para os descriptors. Os descritores podem ser consultados no endereço eletrônico http://decs. bvs.br/, que contém termos em português, espanhol e inglês ou www.nlm.nih.gov/mesh, para termos somente em inglês,
Organização como Autor Diabetes Prevention Program Research Group. Hypertension, insulin, and proinsulin in participants with impaired glucose tolerance. Hypertension. 2002;40(5):679-86.
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Sem indicação de autoria 21st century heart solution may have a sting in the tail. BMJ. 2002;325(7357):184.
As figuras somente serão publicadas em cores se o autor concordar em arcar com os custos de impressão das páginas coloridas. Só serão aceitas imagens nos formatos TIFF ou JPEG, com resolução mínima de acordo com o tipo de imagem, tanto para imagens em preto e branco como para imagens em cores, conforme exemplos abaixo.
Artigo publicado eletronicamente antes da versão impressa (“ahead of print”) Atluri P, Goldstone AB, Fairman AS, Macarthur JW, Shudo Y, Cohen JE, et al. Predicting right ventricular failure in the modern, continuous flow left ventricular assist device era. Ann Thorac Surg. 2013 Jun 21. [Epub ahead of print]
Regras de formatos de imagens:
Artigo de periódico na Internet Machado MN, Nakazone MA, Murad-Junior JA, Maia LN. Surgical treatment for infective endocarditis and hospital mortality in a Brazilian single-center. Rev Bras Cir Cardiovasc [online]. 2013[cited 2013 Jun 25];28(1):29-35. Available from: <http://www.scielo.br/scielo.php?script=sci_ arttext&pid=S0102-76382013000100006&lng=en&nrm=iso> Capítulo de Livro Chai PJ. Intraoperative myocardial protection. In: Mavroudis C, Backer C, eds. Pediatric cardiac surgery. 4th ed. Chichester: Wiley-Blackwell; 2013. p.214-24. Livro Cohn LH. Cardiac surgery in the adult. 4th ed. New York: McGraw-Hill;2012. p.1472. Tese Dalva M. Estudo do remodelamento ventricular e dos anéis valvares na cardiomiopatia dilatada: avaliação anátomopatológica [Tese de doutorado]. São Paulo: Universidade de São Paulo, 2011. 101p. Legislação Conselho Nacional de Saúde. Resolução n. 196, de 10 de outubro de 1996. Dispõe sobre diretrizes e normas regulamentadoras de pesquisas envolvendo seres humanos. Bioética. 1996;4(2 Supl):15-25.
Exemplo de figura
Outros exemplos de referências podem ser consultados no site: http://www.nlm.nih.gov/bsd/uniform_requirements.html Tabelas e Figuras As Tabelas e Figuras devem ser numeradas de acordo com a ordem de aparecimento no texto, conter um título e estar em arquivos separados. As tabelas não devem conter dados redundantes já citados no texto. Devem ser abertas nos lados e com fundo totalmente branco. As abreviaturas utilizadas nas tabelas devem ser mencionadas em ordem alfabética, no rodapé, com as respectivas formas por extenso. Da mesma forma, as abreviaaturas empregadas nas figuras devem ser explicitadas nas legendas.
Fig. 1 - Histogram showing effects of transdermal 17ß-estradiol on left internal mammary artery (LIMA) graft cross-sectional area. It increased by 30% (3.45 ± 1. 2 mm2 versus 4.24 ± 1 mm2; P = 0.039).
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Exemplo de tabela
A RBCCV/BJCVS solicita que os autores arquivem em seu poder as imagens originais, pois caso as imagens submetidas on-line apresentem algum impedimento para impressão, entraremos em contato para que nos envie estes originais.
Table 1. Lung Cancer Invading the Airway: Site of the Tumor and Number of Treatments Patients
Treatments
Trachea
36 (13%)
43
Carina
28 (10%)
38
Main bronchi
154 (56%)
195
Bronchus intermedius 29 (11%)
38
Distal airway
26 (10%)
37
Total
273
351
Limites por Tipo de Artigo Visando racionalizar o espaço da revista e permitir maior número de artigos por edição, devem ser observados os critérios abaixo delineados por tipo de publicação. A contagem eletrônica de palavras deve incluir a página inicial, resumo, texto, referências e legenda de figuras. Os títulos têm limite de 100 caracteres (contando-se os espaços) para Artigos Originais, Artigos de Revisão e Atualização e Trabalho Experimental e de 80 caracteres (contando-se os espaços) para as demais categorias.
Artigo Original
Editorial
Artigo de Revisão/ Atualização
Relato de Caso
“Como eu faço”
Comunicação Breve/Nota Prévia
Carta ao Editor
Trabalho Experimental
Correlação ClínicoCirúrgica
Multimidia
Nº máximo de autores
8
4
8
4
4
8
4
6
4
4
Resumo Nº máximo de palavras
250
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100
100
Nº máximo de palavras
5.000
1.000
6.500
1.500
1.500
2.000
400
5.000
800
800
Nº máximo de referências
25
10
75
6
6
6
6
25
10
10
Nº máximo de tabelas + figuras
8
2
8
2
4
2
1
8
2
1
250 ---
A versão em inglês das Normas aos Autores da Revista Brasileira de Cirurgia Cardiovascular/Brazilian Journal of Cardiovascular Surgery está disponível nos sites: http://www.scielo.br/revistas/rbccv/iinstruc.htm ou http://www.rbccv.org.br/page/6
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Rev Bras Cir Cardiovasc | Braz J Cardiovasc Surg
Meetings Calendar/Calendário de Eventos
Rev Bras Cir Cardiovasc 2014;29(4):675-6
MEETINGS CALENDAR /CALENDÁRIO DE EVENTOS - 2015
Janeiro
25 e 26 - 7th Leeds Advanced VATS Course Leeds, Reino Unido Informação: Richard Milton Fone: +44 113 2068760 Fax: +44 113 2068824 E-mail: richard.milton@leedsth.nhs.uk Site: www.vatscourse.com
9 e 10 - International Workshop on Aortic Diseases-Arch & Thoracoabdominal Hybrid & Open Repair Chennai, Índia Informação: PROF V V BASHI E-mail: vaijyanath3@gmail.com Site: www.miothospitals.com
25 e 26 - Transcatheter Aortic Valve Implantation Windsor, Reino Unido Informação: EACTS Fone: +44 (0)1753 832 166 Fax: +44 (0)1753 620407 E-mail: info@eacts.co.uk Site: http://www.eacts.org/academy/2015-programme/
10 - NYSTS 2015 Oral Board Preparation Bronx, Estados Unidos Informação: Samuel Weinstein, MD Fone: 17189207745 E-mail: sweinste@montefiore.org Site: www.nysts.org
25 a 27 - Hands-on Cardiac Morphology (Spring Edition) Londres, Reino Unido Informação: Professor Yen Ho Fone: 44 207 3518751 Fax: 44 207 351 8230 E-mail: morphology@rbht.nhs.uk Site: www.rbht.nhs.uk/cardiacMorphology
18 a 23 - 33rd Annual Sympoium: Clinical Update in Anesthesiology, Surgery and Perioperative Medicine Saint Kitts, Índias Ocidentais Informação: George Silvay, M.D., Ph.D. Fone: 212 241 8346 Fax: 212 876 3906 E-mail: george.silvay@mountsinai.org Site: http://icahn.mssm.edu/
25 e 26 - Transcatheter Aortic Valve Implantation Windsor, Reino Unido Informação: EACTS Fone: +44 (0)1753 832 166 Fax: +44 (0)1753 620407 E-mail: info@eacts.co.uk Site: http://www.eacts.org/academy/2015-programme/
Fevereiro 2 a 6 - Fundamentals in Cardiac Surgery: Part I Windsor, Reino Unido Informação: EACTS Fone: +44 (0)1753 832166 Fax: +44 (0)1753 620407 E-mail: info@eacts.co.uk Site: http://www.eacts.org/academy/2015-programme/
Março 1 a 6 - Interventional Cardiology 2015: 30th Annual International Symposium Snowmass Village, Estados Unidos Informação: Promedica International CME Fone: 760-720-2263 E-mail: rlaw@promedicacme.com Site: http://www.promedicacme.com/meeting/InterventionalCardiology-2015-30th-Annual-106.html
8 a 11 - German Society for Thoracic and Cardiovascular Surgery 44th Annual Meeting Braunschweig, Alemanha Informação: PD Dr. Wolfgang Harringer, Cardiac Surgery, Braunschweig Site: http://www.dgthg-jahrestagung.de/ 11 a 15 - CREF 2015 35th Annual Cardiothoracic Surgery Symposium San Diego, CA, Estados Unidos Informação: CREF Fone: 805-534-0300 E-mail: info@crefmeeting.com Site: http://www.crefmeeting.com
1 a 4 - APACVS 34th Winter Educational Meeting Las Vegas, Estados Unidos Informação: Lisa Weber Fone: 978-927-8330 Site: http://apacvs.org/conferences/Winter-Educational/ 5 a 7 - The Houston Aortic Symposium: Frontiers in Cardiovascular Disease, the Eighth in the Series Houston, Estados Unidos Informação: Promedica International CME Fone: 760-720-2263 Fax: 760-720-6263 E-mail: rlaw@promedicacme.com
20 e 21 - Functional Mitral and Tricuspid Regurgitation Windsor, Reino Unido Informação: EACTS Fone: +44 (0)1753 832 166 Fax: +44 (0)1753 620407 E-mail: info@eacts.co.uk Site: //www.eacts.org/academy/2015-programme/
675
Rev Bras Cir Cardiovasc | Braz J Cardiovasc Surg
Meetings Calendar/Calendário de Eventos
Rev Bras Cir Cardiovasc 2014;29(4):675-6
8 a 15 - 33rd Cardiovascular Surgical Symposium Arlberg, Áustria Informação: Karl Landsteiner, Institute of Cardiovascular Surgical Research E-mail: congress@surgery-zurs.at
E-mail: sctsadmin@scts.org Site: www.scts.org 26 a 28 – 42th Congress of the Brazilian Society of Cardiovascular Surgery Curitiba, Brasil Informação: Ab Eventos Fone: +55 51 3061-2959 E-mail: recepcao@abev.com.br Site: http://sbccv.org.br/42Congresso/
12 a 15 - General Thoracic Surgical Club 28th Annual Meeting Naples, Estados Unidos Informação: Bonnie Lemmerman Fone: 507-696-4665 E-mail: gtscmail@gmail.com Site: www.gtsc.org
26 a 28 - Ventricular Assist Device Coordinator Educational Course Windsor, Reino Unido Informação: EACTS Fone: +44 (0)1753 832166 Fax: +44 (0)1753 620407 E-mail: info@eacts.co.uk Site: http://www.eacts.org/academy/2015-programme/
17 a 20 - Advanced Module: Open and Endovascular Aortic Therapy Windsor, Reino Unido Informação: EACTS Fone: +44 (0)1753 832166 Fax: +44 (0)1753 620407 E-mail: info@eacts.co.uk Site: http://www.eacts.org/academy/2015-programme/
26 a 29 - 64th International Congress of the European Society for Cardiovascular and Endovascular Surgery Istambul, Turquia Informação: Bengu Tokatlioglu Fone: +90 212 292 88 08 Fax: +90 212 292 88 07 E-mail: info@escvs2015.org Site: http://escvs2015.org/
25 a 27 - ACTA/SCTS Joint Annual Meeting & Cardiothoracic Forum Manchester, Reino Unido Informação: Isabelle Ferner Fone: +44 (0)20 7869 6893 Fax: +44 (0)20 7869 6890
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RBCCV em números 28 anos de circulação ininterrupta Fator de Impacto 0,632
www.rbccv.org.br www.scielo.br/rbccv www.bjcvs.org
Consultada por leitores de mais de 110 países 1.307.934 acessos no site próprio (www.rbccv.org.br) em 2013 625.235 acessos no site da SciELO (www.scielo.br/rbccv) em 2013 5.305 visitantes diariamente, em média 578,47 gigabytes (GB) transferidos, média de 1,58 GB por dia 55.020.119 impressões de páginas em 2013 (requisição do navegador de um visitante para uma página web que possa ser exibida), média diária de 150.740,11. Presente em nas bases de dados EBSCO, Lilacs, Scielo, Latindex, Index Copernicus, Scopus, PubMed, Thomson Scientific (ISI), Google Scholar
Fig.1 – Número de acessos ao site da RBCCV em 2013
Fig. 2 – Transferência de bytes no site da RBCCV durante 2013
Fig. 3 – Número de impressões de páginas da RBCCV em 2013