Francesco Maisano and Julien Dreyfus discuss innovations in interventional cardiology
Reinfection Following Cardiovascular Implantable Electronic Device Editor's Pick:
Editorial Board 07 Welcome
Foreword
Congress Review
10 Review of the European Association of Percutaneous Cardiovascular Interventions (EuroPCR) 2024, 14th-17th May 2024
Congress Features
17 Transcatheter Aortic Valve Implantation in Challenging Anatomies
Laith Gergi
21 Innovative Strategies for Chronic Total Occlusions
Katrina Thornber
Abstract Reviews
24 Comparison of Proximal Optimisation with Kissing Inflation Technique with Kissing Balloon Inflation for Treatment of Coronary Bifurcations
Vassilev et al.
26 Lesion and Procedural Characteristics on Infrapopliteal Endovascular Procedures in Latin America: Insights from SOLACI Peripheral Registry
Ramón et al.
28 Peri-procedural Use of Topical Medications to Reduce Radial Artery Spasm Among Patients Undergoing Coronary Angiography: A Meta-analysis of Current Evidence
Borovac et al.
30 Aortic Distensibility Measured by CT as a Marker of Obstructive Coronary Artery Disease
71 Should Coronary Artery Fistula Be Treated? A Review Throughout a Case Series
Buitrago-Gomez et al.
78 An Incidental Finding of Asymptomatic Quadricuspid Pulmonary Valve at Autopsy: A Case Report and Comprehensive Literature Review
Mattu et al.
87 Role of Coronary Physiology in the Modern Catheterisation Lab
Occhipinti and Brugaletta
93 Percutaneous Coronary Intervention For Treatment of Unusual Origin of the Left Main Artery: A Case Report
Elkhayat et al.
"Awardees demonstrated extraordinary dedication to improving patient outcomes and advancing medical innovation globally"
Editorial Board
Editor-in-Chief
Dr Pablo Sepúlveda
Catholic University of Chile, Santiago, Chile
Dr Pablo Sepúlved specialised in interventional cardiology at Clinique Saint Jean in Belgium. With over 20 years’ experience in the field, Sepúlveda's research focuses on pulmonary arterial hypertension, heart failure, and acute coronary syndromes.
European Prevention Center joint with Medical Center Düsseldorf (Grand Arc), Germany
Dr Sanjog Kalra
University of Toronto, USA
Dr Aaron Kugelmass
Baystate Health System, USA
Prof Eduard Margetic Clinical Hospital Center Zagreb, Croatia
Dr Gregory Pavlides
University of Nebraska Medical Center, USA
Prof Dr Rainer Wessely
Center for Cardiovascular and Lung Medicine, Im Mediapark, Cologne, Germany
Aims and Scope
EMJ Interventional Cardiology is an open access, peerreviewed ejournal committed to helping elevate the quality of practices in interventional cardiology globally by informing healthcare professionals on the latest research in the field.
The journal is published annually, six weeks after the European Association for Percutaneous Cardiovascular Interventions (EuroPCR) Event, and features highlights from this event, alongside interviews with experts in the field, reviews of abstracts presented at EuroPCR, as well as in-depth features on sessions from this event. The journal also covers advances within the clinical and pharmaceutical arenas by publishing sponsored content from congress symposia, which is of high educational value for healthcare professionals. This undergoes rigorous quality control checks by independent experts and the in-house editorial team.
EMJ Interventional Cardiology also publishes peer-reviewed research papers, review articles, and case reports in the field. In addition, the journal welcomes the submission of features and opinion pieces intended to create a discussion around key topics in the field and broaden readers’ professional interests. The journal is managed by a dedicated editorial team that adheres to a rigorous double-blind peer-review process, maintains high standards of copy editing, and ensures timely publication.
EMJ Interventional Cardiology endeavours to increase knowledge, stimulate discussion, and contribute to a better understanding of practices in the field. Our focus is on research that is relevant to all healthcare professionals in this area. We do not publish veterinary science papers or laboratory studies not linked to patient outcomes. We have a particular interest in topical studies that advance knowledge and inform of coming trends affecting clinical practice in interventional cardiology.
Further details on coverage can be found here: www.emjreviews.com
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EMJ is supported by various levels of expertise:
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On submission, all articles are assessed by the editorial team to determine their suitability for the journal and appropriateness for peer review.
Editorial staff, following consultation with either a member of the Editorial Board or the author(s) if necessary, identify three appropriate reviewers, who are selected based on their specialist knowledge in the relevant area.
All peer review is double blind. Following review, papers are either accepted without modification, returned to the author(s) to incorporate required changes, or rejected.
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All information obtained by EMJ and each of the contributions from various sources is as current and accurate as possible. However, due to human or mechanical errors, EMJ and the contributors cannot guarantee the accuracy, adequacy, or completeness of any information, and cannot be held responsible for any errors or omissions. EMJ is completely independent of the review event (EuroPCR 2024) and the use of the organisations does not constitute endorsement or media partnership in any form whatsoever. The cover photo is of Paris, France, the location of EuroPCR 2024.
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Welcome
Dear Readers,
Welcome to the 2024 issue of EMJ Interventional Cardiology! This edition brings you the latest updates from the course of the European Association of Percutaneous Cardiovascular Interventions (EuroPCR) that took place in Paris, France. We are excited to present key highlights including the exciting results from the NOTION-2 and the LANDMARK trials.
Do not miss our in-depth coverage of the sessions on transcatheter aortic valve implantation (TAVI) in challenging anatomies and innovative strategies for chronic total occlusions. These sessions gave a taste of cutting-edge approaches that are shaping the future of the field. Our exclusive expert interviews provide key takeaways from this year’s EuroPCR, with leading professionals discussing advancements in the field of interventional cardiology.
Our selection of peer-reviewed articles include our Editor’s Pick on cardiovascular implantable electronic device infections and the diagnostic challenges they present. In another compelling article, the authors present a case series of percutaneous closure of symptomatic coronary artery fistula for which closure was decided. Read on to find out more about the decision-making process for this condition.
I would like to close by thanking our contributors, interviewees, reviewers, and Editorial Board for their invaluable input and for helping bring together this great issue. We welcome your feedback on this content on our page and look forward to your contributions for our next publication.
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Evgenia Koutsouki
Foreword
Dear Colleagues,
I am delighted to present the 12th issue of EMJ Interventional Cardiology. This edition is packed with a wealth of content designed to engage and inform, from in-depth interviews with leading experts to visually captivating infographics. We strive to provide a comprehensive resource for our readers, and this issue is no exception.
Inside, you will find extensive coverage of the 2024 European Association of Percutaneous Cardiovascular Interventions (EuroPCR) Congress, which took place this year in Paris, France, from 13th–16th May. EuroPCR served as an epicentre for experts to share the latest breakthroughs from clinical trials, present abstracts, and discuss current challenges in the field. Our coverage includes two feature articles on the key topics of transcatheter aortic valve implantation and chronic total occlusion percutaneous coronary intervention, along with four abstract reviews that highlight cutting-edge research presented for the first time at EuroPCR.
The level of expertise from this year’s interviewees was exceptional. Our noncongress interviews feature insights from Damien Kenny, Stephen Hoole, and Alessia Callegari, while our congress interviews include conversations with Julien Dreyfus
and EuroPCR board member Francesco Maisano. I extend special thanks to each guest for their insightful commentaries on the field, and for sharing a snippet of their personal backstory with our readers.
The level of expertise from this year’s interviewees was exceptional
I am pleased to say that EMJ Interventional Cardiology 12.1 includes a diverse array of case reports, research articles, and review articles, covering topics from coronary artery fistulas to percutaneous intervention. Also featured is our very own infographic, titled ‘Catheter-Based Renal Denervation’, which explores the mechanism behind resistant hypertension and the potential benefits renal denervation may provide in treating it.
I hope you all enjoy the variety of content offered as much as we did curating it! I would like to extend my thanks to all the authors, peer reviewers, and interviewees for their participation in this issue, and to the Editorial Board and team at EMJ for their constant commitment to delivering an exceptionally high standard of content.
Pablo Sepúlveda
Catholic University of Chile, Santiago, Chile
EuroPCR 2024
From late-breaking clinical trials to abstract presentations, to simulation-based learning sessions, EuroPCR 2024 had it all
Congress Review
Review of the European Association of Percutaneous Cardiovascular Interventions (EuroPCR) 2024
Location: Paris, France
Date: May 14th–17th, 2024
Citation: EMJ Int Cardiol. 2024;12[1]:10-16. https://doi.org/10.33590/emjintcardiol/BJGP8023.
THIS year’s Annual Congress of the European Association of Percutaneous Cardiovascular Interventions (EuroPCR) took place once again in the dazzling city of Paris, France. Inside the walls of the Palais des Congrès, over 11,000 participants from across the globe gathered to discuss the latest advancements in the field of interventional cardiology.
This 4-day course, tailored for interventional cardiologists, nurses, cardiac surgeons, imaging specialists, radiologists, and other practitioners, featured a spectacle of sessions: from late-breaking clinical trials to abstract presentations, to simulation-based learning sessions, EuroPCR 2024 had it all.
The 2024 meeting also witnessed a record-breaking 3,100+ submissions of abstracts
From the Main Arena of the Palais des Congrès, the opening ceremony commenced, featuring Course Directors Thomas Cuisset, Nicolas Dumonteil, and Nieves Gonzalo; EuroPCR Co-Chairman Jean Fajadet; and PCR Chairman William Wijins. There was a noticeable buzz of excitement as colleagues looked forward to the next 4 days of cutting-edge sessions. The highly anticipated ‘Major Late-Breaking Trials’ session, for instance, revealed three prominent clinical trials believed to make a significant difference to clinical
practice. These included ‘First TAVI versus SAVR randomised trial in younger low-risk patients with severe tricuspid orbicuspid aortic valve stenosis - results from NOTION-2’, by De Backer et al.,1 ‘One-month DAPT followed by 5-month Ticagrelor monotherapy in ACS with DCB’ by Ling et al.,2 and ‘Early outcomes of a randomised non-inferiority trial comparing TAVI devices: the LANDMARK trial’ by Serruys et al.3
EuroPCR 2024 additionally featured 29 simulation-based learning sessions, providing practical hands-on guidance for procedures such as mitral transcatheter edge-to-edge repair, transseptal puncture, commissural alignment for transcatheter aortic valve implantation, and more. The 2024 meeting also witnessed a recordbreaking 3,100+ submissions of abstracts, resulting in over 1,500 presentations in Paris. Twelve live educational cases were also conducted, covering topics such as calcified lesions, transcatheter aortic valve implantation, left main stenosis, and mitral transcatheter edge-to-edge repair. These sessions were broadcasted from eight live centres worldwide, including Netcare
Sunninghill Hospital in Johannesburg, South Africa; Heart Center in Leipzig, Germany; and Hospital Clínico San Carlos in Madrid, Spain.
The prestigious Andreas Grüntzig Ethica Award was presented to two eminent cardiologists: Ottavio Alfieri, IRCCS Ospedale San Raffaele, Milan, Italy; and Frederick St Goar, El Camino Health, Mountain View, California, USA, in recognition of their exceptional contributions to the cardiovascular field. Ottavio Alfieri, renowned for pioneering valve surgery techniques such as the edge-to-edge mitral valve repair and the clover technique, also continues to advance cardiac treatment through the Alfieri Heart Foundation, which he founded. Frederick St Goar, celebrated for his role in developing intravascular ultrasound and the MitraClip device (Evalve, Inc., Menlo Park, California,
USA), also makes significant strides in maternal and infant health with the JADA® System (Organon, Jersey City, New Jersey, USA). Both awardees demonstrated extraordinary dedication to improving patient outcomes and advancing medical innovation globally.
References
1. Oler De Backer et al. First TAVI vs. SAVR randomised trial in younger low-risk patients with severe tricuspid or bicuspid aortic valve stenosisresults from NOTION-2 trial. EuroPCR 2024, 14-17 May, 2024.
2. Ling Tao et al. Stepwise dual antiplatelet therapy de-escalation in acute coronary syndrome patients after drug-coated balloon angioplasty. EuroPCR 2024, 14-17 May, 2024.
3. Patrick Serruys et al. Early outcomes of a randomised non-inferiority trial comparing TAVI devices: the LANDMARK trial. EuroPCR 2024, 14-17 May, 2024.
300
in-person delegates
400 attendees from around the world joining online to address the complex challenges faced by people living with rare diseases
29
simulation-based learning sessions
12
Live Educational Cases were also conducted
Novel Anti-Platelet Approach for Patients Treated with
Paclitaxel-Coated Balloons
A NOVEL anti-platelet approach for patients with acute coronary syndrome (ACS) treated with paclitaxel-coated balloons (PCB) may represent a viable alternative treatment for low-risk patients with ACS.
Drug-coated balloon treatment as a percutaneous coronary intervention (PCI) is an advantageous management option for coronary atherosclerotic heart disease, as it reduces the duration of anti-platelet medication. The administration of antiplatelet medication following drug-coated balloon treatment lowers the risk of ischaemic events in patients with ACS but is a contributor to major bleeding events, increasing the risk of mortality. Dual antiplatelet therapy (DAPT) utilising aspirin and ticagrelor for 12 months is the standard treatment in patients with ACS undergoing PCI. The REC-CAGEFREE II trial is a firstof-its-kind study investigating alternative anti-platelet therapy strategies specifically for PCB-treated PCI in patients with ACS, comparing stepwise de-escalation DAPT versus conventional DAPT.
The REC-CAGEFREE II trial was an openlabel, investigator-initiated, non-inferiority, multicentre randomised study comprised of 1,948 patients randomised to stepwise DAPT de-escalation (n=975) or standard DAPT (n=973). Patients in the stepwise DAPT de-escalation group received aspirin plus ticagrelor for 1 month, followed by 5 months of ticagrelor monotherapy, finishing with 6 months of aspirin monotherapy. Patients receiving standard DAPT therapy had 12 months of aspirin and ticagrelor. The primary objective of the study was an efficacy evaluation of net adverse clinical events after 1 year, including death, stroke, myocardial infarction, revascularisation, and major bleeding, within 1 year.
Non-inferiority of stepwise DAPT deescalation compared to standard 12-month DAPT was established, with 9.0% deescalation versus 8.7% standard of patients with ACS experiencing adverse events (P non-inferiority=0.01). Lower rates of Bleeding Academic Research Consortium (BARC) Type 3 or 5 were recorded in the de-escalation group (0.4%) versus the standard group (1.7%) (difference: -1.24%; 95% CI: -2.14− -0.33). However, the composite of all-cause death rates was similar between both groups (8.8% in de-escalation versus 7.6% in standard) (difference: 1.03%; 95 CI: -1.40–3.47).
The REC-CAGEFREE II study provided the first randomised evidence indicating the value of de-escalation therapy with ticagrelor compared to standard treatment. However, several limitations constrain the applicability of the results. Notably, only 40% of subjects could be considered high-risk patients undergoing PCI for STelevation myocardial infarction or non-STelevation myocardial infarction, while 60% had unstable angina. Furthermore, only 9% of all eligible patients from the multiple centres were enrolled, indicating a highly selected population. Therefore, the results support using stepwise DAPT de-escalation for PCB in low-risk populations, such as individuals with unstable angina with single small vessel disease.
The REC-CAGEFREE II study provided the first randomised evidence indicating the value of de-escalation therapy with ticagrelor compared to standard treatment
Comparing Treatments for Low-Risk Patients with Aortic Stenosis
THE LATEST research presented at EuroPCR 2024 has led to a recommendation from the European Society of Cardiology (ESC) Clinical Practice Guideline that transcatheter aortic valve implantation (TAVI) is indicated as the primary treatment option in patients >75 years who are anatomically suitable for the procedure.
A team based in Denmark compared the use of TAVI and surgical aortic valve replacement (SAVR) in low-risk patients with aortic stenosis (AS) in the NOTION-2 study.
Researchers randomised a group of patients ≤75 years of age (mean age:71.1 years) to TAVI or SAVR, including those with bicuspid valve anatomy. The primary endpoint at 1 year included all-cause mortality, stroke, and rehospitalisation (related to procedure, or valve or heart failure).
Further research is needed, but the NOTION-2 trial provided important short-term data
The team found that TAVI and SAVR showed similar rates of the primary endpoint at 1 year (TAVI 10.2%; SAVR 7.1%; P=0.3). Among the secondary endpoints, TAVI resulted in a lower incidence of new onset atrial fibrillation and major bleeding; however, it did demonstrate a higher incidence of non-disabling stroke, paravalvular leak, and
pacemaker implantation. A post hoc analysis demonstrated comparable results between TAVI and SAVR for tricuspid aortic valves (73% of all cases). However, the team did find that, in a non-prespecified analysis of the limited number of patients with bicuspid valves, outcomes were less favourable after TAVI (including the primary endpoint and the incidence of stroke).
These results showed that expanding TAVI indications to young patients with AS and longer life expectancy presents several challenges. Due to the strong indication of less favourable results with TAVI in this cohort, future dedicated and larger randomised studies comparing TAVI and SAVR should be carried out, as this study was done on a relatively small sample size. The longer life expectancy of this group also increased the likelihood of a second TAVI procedure being needed. Further research is needed, but the NOTION-2 trial provided important short-term data concerning the 1-year outcome of younger patients with AS with tricuspid valve anatomy treated with TAVI compared to SAVR.
Early Success for Myval Transcatheter Heart Valve in Landmark Trial
NON-INFERIORITY of the Myval transcatheter heart valve (THV; Meril Life Sciences, Gujarat, India) has been validated by the recent LANDMARK trial, marking a significant milestone in transcatheter aortic valve implantation (TAVI) device comparisons.
The Edwards SAPIEN balloon-expandable valve (BEV; Edwards Lifesciences, Irvine, California, USA) and Evolut™ supra-annular self-expanding valve (SEV; Medtronic, Dublin, Ireland) are the two most frequently used contemporary THVs, and other new THVs have demonstrated inferior safety and efficacy when put up against them in previous comparisons.
The Myval THV, a novel BEV, offers a unique wider range of prosthesis sizes (1.5 mm increments versus the 3 mm standard), allowing precise anatomical matching of the THV to the patient's specific anatomy. The LANDMARK trial was a randomised controlled trial investigating the noninferiority of this THV. The primary endpoint at 30-day follow-up was the composite of all-cause death, stroke, life-threatening or disabling bleeding, acute kidney injury, major vascular complications, paravalvular leak, and new permanent pacemaker implantation. Patients included were those clinically and anatomically suitable for a transfemoral TAVI procedure, including those with bicuspid aortic valve phenotypes and varying levels of surgical risk.
A total of 768 patients (mean age: 80 years) at low surgical risk were randomised
1:1 to receive either the Myval THV or an alternative contemporary TAVI device (BEV or SEV). At 30 days, the primary composite endpoint occurred in 24.7% of the Myval group and 27.6% of the control group, demonstrating non-inferiority of the Myval THV (risk difference: -2.7%; onesided upper 95% CI: 3.6%; P<0.0001 for non-inferiority). No significant differences were found in any individual components of the primary endpoint or in technical and device success. Secondary endpoints, including pacemaker implantation rates and haemodynamic parameters, were also similar between groups.
These findings validated the noninferiority of the Myval THV compared to established BEVs and SEVs. Importantly, the trial also included patients reflecting contemporary clinical practice, with varying surgical risks, and a percentage having bicuspid aortic valves. While short-term outcomes are promising, long-term data on haemodynamic performance and structural valve durability are necessary. A follow-up extending to 10 years is planned to address these questions.
At 30 days, the primary composite endpoint occurred in
24.7% of the Myval group and
27.6% of the control group
Radial Artery Occlusion: Distal Versus Conventional Transradial Access
TRANSRADIAL access (TRA) is the preferred strategy for coronary procedures due to the decreased risk of radial artery occlusion (RAO), which can affect future procedures and treatments.
600 patients who underwent coronary angiography via 6-F radial access
According to research presented at EuroPCR 2024, distal TRA (dTRA) does not reduce RAO risk more than conventional TRA (cTRA) during diagnostic coronary angiography, despite previous suggestions in this field of research.
The authors conducted a randomised, single-centre, open-label trial termed the RAPID trial. The trial consisted of 600 patients who underwent coronary angiography via 6-F radial access. Subjects were randomly allocated to receive dTRA or cTRA, and allocation was further stratified by periprocedural heparin use and pre-existing oral anticoagulation. The primary analysis consisted of patients with diagnostic coronary angiography only, excluding those undergoing percutaneous coronary intervention, with a final total of 222 patients in the dTRA group and 217 in the cTRA group.
The researchers discovered that dTRA resulted in significantly more puncture attempts (2.4±2.1 versus 1.5±1.1; P<0.001) and significantly more instances of access
site crossover due to failed punctures (11.3% versus 4.1%; P=0.005). Consequently, the total procedural time for dTRA was significantly longer than for cTRA (25 min versus 20 min; P=0.001), with no significant difference in fluoroscopy time, dose area product, or contrast volume. The researchers used vascular ultrasound and frequency of puncture-site bleeding events to examine the incidence of RAO in both groups. The team discovered that there were similar rates of RAO (20.3% dTRA versus 21.2% cTRA; P=0.810) and similar rates of puncture-site related bleedings (4.1% dTRA versus 6.9% cTRA; P=0.188) between the dTRA and cTRA groups. These findings were consistent across subgroups stratified by heparin use and pre-existing anticoagulation.
Therefore, the authors concluded that dTRA did not reduce the risk of RAO and puncture-site bleeding. Furthermore, dTRA had longer procedure times than cTRA due to a higher number of puncture attempts and access site crossovers.
Transcatheter Aortic Valve Implantation in Challenging Anatomies
Author: Laith Gergi, EMJ, London, UK
Citation: EMJ Int Cardiol. 2024;12[1]:17-20. https://doi.org/10.33590/emjintcardiol/JUFA1071.
TANJA Rudolph, Heart and Diabetes Center North Rhine-Westphalia, Germany; and Carla Romina Agatiello, Hospital Italiano de Buenos Aires, Argentina, chaired a captivating session exploring the challenges associated with transcatheter aortic valve implantation (TAVI) in patients with complex aortic stenosis. The European Association of Percutaneous Cardiovascular Interventions (EAPCI) hosted the session during the 35th Annual EuroPCR Global Course held in Paris, France, between the 14th–17th of May. The primary objectives of the session were to evaluate and emphasise the importance of detailed CT imaging and pre-procedural planning in TAVI. Moreover, the session focused on how the selected valve and implant techniques in aortic stenosis can be tailored to individual patient anatomy.
THE ERA OF TRANSCATHETER AORTIC VALVE IMPLANTATION
TAVI is a minimally invasive procedure employed in the treatment of patients with symptomatic severe aortic stenosis. Initially, TAVI was an alternative to surgical aortic valve replacement for patients with aortic stenosis identified as inoperable, and for higher-risk patients. However, since the first TAVI procedure more than two decades ago, its application has evolved and expanded across risk groups, encompassing low- and intermediate-risk patients, and becoming the most frequently performed structural technique in interventional cardiology. Nevertheless, a significant challenge for interventional cardiologists is the complex anatomical features that many patients referred for TAVI present with. Therefore, understanding the anatomical obstacles to successful TAVI, and optimising patient selection and device implantation, is crucial in improving prognosis.
LOW CORONARY ARTERY
Low coronary artery, where the distance between the aortic annulus and coronary
ostia is short, is a significant challenge in TAVI as it elevates the risk of coronary artery obstruction (CAO), and can impact future coronary access. Lisabeth Rosseel from Algemeen Stedelijk Ziekenhuis in Aalst, Belgium, presented the complexities and strategies in TAVI for patients with highly calcified tricuspid aortic stenosis and low coronary arteries. Rosseel emphasised the critical role of pre-procedural planning, including the precise selection of balloon size and the decision between balloonexpandable valves and self-expanding valves. These choices are essential to avoid complications such as CAO, particularly in patients with low coronary arteries. Though infrequent, CAO is a significant concern due to its severe outcomes. The incidence of CAO in native valves is 0.6%, with a 30-day mortality rate between 8–41%.1 In valvein-valve (ViV) procedures, the incidence increases to 2–3% with a 30-day mortality rate of up to 51%.1 The incidence of CAO in native aortic stenosis is higher than in ViV TAVI as it is more frequently performed, but the risk of obstruction is higher in ViV.1
Rosseel explained that CAO mechanisms include leaflet calcification, displacement of calcified leaflets, and obstruction by the
transcatheter heart valve (THV) skirt or commissure of the TAVI valve. The diseased native or bioprosthetic leaflets displace towards the coronary artery ostia or the sinotubular junction; otherwise, the skirt of the THV can directly obstruct the coronary artery. Anatomical risk factors in native valve procedures include low coronary height (<10–12 mm), small Sinus of Valsalva (<28–30 mm), and a Vent-to-Coronary distance <4 mm. Rosseel noted a CAO risk in ViV TAVI cases where prior stenting by prosthesis occurred, where the leaflet was mounted on the outside of the prosthesis.
Since the first TAVI procedure more than two decades ago, its application has evolved and expanded across risk groups
CORONARY ARTERY OBSTRUCTION PREDICTION
Rosseel discussed a recent study where researchers developed a novel computed tomography-based multivariate prediction model for CAO from TAVI in native aortic stenosis.1 This study comprised 60 patients with angiographically confirmed CAO and 1,381 without obstruction, evaluating the relationship between various anatomical artery measurements and CAO. Khan et al.1 identified that annular area and perimeter,
coronary height, sinus width, and STJ height were significantly smaller in patients with CAO, and that CAO was most commonly located in the left coronary artery ostium. The model demonstrated that when the cusp height is higher than the coronary height, with a virtual valve-to-coronary distance ≤4 mm or a culprit leaflet calcium volume >600 mm3, the patient can be considered high-risk for CAO, and likely requires protection.1
TECHNIQUES TO PREVENT AND MANAGE CORONARY ARTERY OBSTRUCTION
To address CAO risks, Rosseel discussed preventive measures in TAVI, including reconsidering surgical aortic valve replacement (SAVR), using retrievable valves, which allow repositioning if CAO risk is identified, avoiding THV oversizing, and deeper valve implantation. More advanced techniques mainly consist of chimney stenting and bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary artery obstruction during TAVR (BASILICA). The BASILICA technique involves splitting the leaflet via electrocauterisation to maintain coronary flow, and has emerged as a practical protective step.2 Khan et al.2 demonstrated that BASILICA is a safe method to avoid CAO, maintaining coronary patency up to 1 year post-procedure, particularly in VIV procedures. Rosseel also covered chimney
The incidence of CAO in native aortic stenosis is higher than in ViV TAVI as it is more frequently performed, but the risk of obstruction is higher in ViV
stenting, where a protective wire is placed in the coronary artery to deploy a stent if necessary. Pre-emptive coronary protection significantly improves survival rates, according to data from the chimney registry.
Rosseel’s presentation underscored the importance of individualised approaches and advanced procedural techniques in managing TAVI for patients with low coronary arteries. She expanded by explaining that, in the past, it has been the status quo to protect the coronary artery whenever a risk of CAO is suspected. However, there are new multivariate prediction models that allow interventional cardiologists to detect patients in real risk of CAO who need either protection or alternative strategy. Finally, she stressed the importance of ensuring commissure alignment, detailed pre-procedural planning using CT imaging and simulations to select appropriate methods and devices, and pre-emptive measures, such as BASILICA or chimney stenting for high-risk patients.
Matti Adam, University Hospital Cologne, Germany, presented an insightful session on ViV TAVI. The session focused on the intricacies and challenges of managing structural valve degeneration in patients with previous SAVR. ViV-TAVI has emerged as a vital option for managing deteriorating surgical bioprosthetic valves. However, it is not universally applicable due to potential complications such as patient-prosthesis mismatch (PPM), particularly in patients with small aortic roots or undersized original prostheses. Adam highlighted the 2022 EuroIntervention guidelines, which underline that, while ViV is an established treatment option, it is not feasible in all patients due
to the increased likelihood of PPM and thus, CAO, necessitating careful patient selection in ViV-TAVI.
Adam emphasised the diversity of surgical valves; stented, stentless, with internal or external leaflets, and rapid deployment or sutureless designs. These variations necessitate detailed pre-procedural planning to address interactions between the existing surgical valve, native anatomy, and the new TAVI valve.
Effective planning involves a thorough understanding and measurement of the existing surgical valve. Clinicians must know the valve’s inner diameter, height, true internal diameter, and left ventricular outflow tract diameter. Accurate patient anatomy assessment is also crucial, focusing on left and right coronary artery height, STJ height, and width. Adam stressed the importance of specific measurements such as the valve-tocoronary and valve-to-STJ distance. These parameters are vital to evaluate the risk of CAO. A valve-to-coronary distance of 4 mm and a valve-to-STJ distance >3.5 mm are considered safe thresholds, while intermediate values (2.5–3.5 mm) necessitate caution.
VALVE CRACKING
High gradients, indicative of PPM, are a significant concern in ViV TAVI, especially with SAVR valves labelled ≤21 mm.3
Research indicates worse 1-year mortality for patients with SAVR inner diameters <21 mm.3 Bioprosthetic valve fracture (BVF) is a technique that can alleviate high gradients, enhancing haemodynamic outcomes. This technique involved fracturing the sewing ring of the SAV with high-pressure, noncompliant balloon inflation. Adam presented a publication by Brinkman et al.4 which demonstrated that THV device success
ViV-TAVI has emerged as a vital option for managing deteriorating surgical bioprosthetic valves
was higher in patients BVF ViV-TAVI at 93%, compared to 68.4% in patients with ViVTAVI without BVF. However, a publication by Chhatriwalla et al.5 showed that mortality increased if BVF was deployed before ViVTAVI in patients with BVF. Mortality was 4.9% in patients with BVF versus 1.7% in patients without BVF (P=0.02; odds ratio: 2.9; 95% confidence interval: 1.2–2.9).
Nevertheless, the study also revealed that patients with post-implant BVF had an unchanged mortality, but a decreased aortic valve gradient and increased aortic valve area, which had remained unchanged in pre-implant BVF.5 Therefore, post-implant BVF is likely to yield better results for patients.
References
1. Khan JM et al. Coronary obstruction from TAVR in native aortic stenosis: development and validation of multivariate prediction model. Cardiovasc Interv. 2023;16(4):415-25.
2. Khan JM et al. Preventing coronary obstruction during transcatheter
Adam’s session underscored that ViV-TAVI is a robust treatment for failing surgical valves but requires meticulous planning to address PPM and coronary obstruction. BVF can significantly improve outcomes, and procedural success hinges on comprehensive pre-procedural assessment and strategic planning.
CONCLUSION
The talks by Rosseel and Adam presented at the symposium and highlighted in this feature demonstrate the critical importance of detailed CT imaging and personalised pre-procedural planning in TAVI to navigate the anatomical complexities of aortic stenosis. Advanced techniques and individualised approaches, such as the BASILICA procedure and BVF, are essential for mitigating risks like PPM and CAO, and ensuring optimal outcomes for patients with challenging anatomies.
aortic valve replacement: results from the multicenter international BASILICA registry. Cardiovasc Interv. 2021;14(9):941-8.
3. Bleiziffer S et al. Long-term outcomes after transcatheter aortic valve implantation in failed bioprosthetic valves. Eur Heart J. 2020;41(29): 2731-42.
4. Brinkmann C et al. Outcome of VIV-TAVI with and without BVF. EuroIntervention. 2021;17(10):848.
5. Chhatriwalla AK et al. Outcomes of bioprosthetic valve fracture in patients undergoing valve-in-valve TAVR. Cardiovasc Interv. 2023;16(5):530-9.
Innovative Strategies for Chronic Total Occlusions
Author: Katrina Thornber, EMJ, London, UK
Citation: EMJ Int Cardiol. 2024;12[1]:21-23. https://doi.org/10.33590/emjintcardiol/VVSE9757.
CHRONIC total occlusion percutaneous coronary intervention (CTO PCI) strategies were thoroughly discussed at the EuroPCR 2024 Annual Global Course in Paris, France. Experts in the field gathered to discuss the advantages and limitations of various approaches, including the use of intravascular ultrasound (IVUS) when locating ambiguous proximal caps. Experts discussed several techniques in the context of success rate and patient safety, with a focus on what changes can be made to current guidelines to ultimately improve patient outcomes in high-risk cases.
THE PARALLEL WIRE TECHNIQUE
Omer Goktekin, Memorial Bahçelievler Hospital, Istanbul, Türkiye, started by discussing the use of parallel wire technique (PWT) in cases where antegrade strategies fail. With PWT, a second guidewire is introduced whilst the first wire acts as a reference point and provides stability. Goktekin explained that the second wire should have better torque ability and may require a different tip shape according to the behaviour of the first wire; for example, a wire with a higher tip load may be necessary. While PWT is a well-known technique, it has been used less frequently in recent years due to the introduction of new, innovative wires, such as Gaia wires (Asahi Intecc USA, Irvine, California, USA). However, Goktekin emphasised that PWT should not be forgotten amid these newer strategies. “Parallel wiring is still a valid and quick option and tackles CTOs by utilising two wires simultaneously,” he said. In particular, PWT is a favourable option when the primary wire is in the subintima and has a good distal landing zone.
Goktekin also noted that, with PWT, the second wire manipulation can be augmented by a dual-lumen catheter on the first wire. In discussing the different uses of dual lumen catheters (when used during PWT, or as a device for achieving distal re-
entry [ADR]), panel members explained that when the wire is located before the distal cap, then you are performing a PWT; but when the wire is below the distal cap, you can transform your parallel wire technique to perform ADR, with the assistance of a ReCross device (IMDS, Roden, The Netherlands). Maksymilian Opolski, Institute of Cardiology, Warsaw, Poland, expanded on the differences between PWT and ADR, explaining that whilst PWT is safer and more time-effective, ADR has more technical success. Opolski also noted that PWT is cheaper and is still common in various countries, emphasising the point made by Goktekin, that “PWT is a classic but not an old-fashioned technique.” However, Goktekin did highlight that in cases where there is a large subintimal haematoma (for instance due to aggressive wire manipulation), or if there is a poor distal landing zone, then PWT is not the preferred choice.
AMBIGUOUS PROXIMAL CAPS: OPTIMISING THE USE OF IVUS AND CT
Evald Christiansen, Cardiology Department of Aarhus University Hospital, Denmark, narrowed the topic of discussion to focus on approaches used to target ambiguous proximal caps. He explained that IVUS
The implementation of an investment strategy will increase the accessibility and provision of CTO PCI
can be used to identify the presence of calcium in the cap, which can implicate wire choice. Currently, the Global Chronic Total Occlusion Crossing Algorithm acts as a guideline for strategy options when there is proximal ambiguity. The guideline states that if a proximal cap is ambiguous and there is the presence of a side branch, then you can conduct IVUS to identify the location of the proximal cap, and subsequently decide if there is a feasible retrograde option. Christiansen began his presentation by describing a case report in which both an antegrade puncture with a double lumen catheter and a retrograde puncture retrogradely with the support of a microcatheter failed during a procedure. A subsequent CT scan revealed that the proximal cap was not in the circumflex artery, as they had originally thought, but in the left anterior descending artery. Christiansen described how they subsequently used IVUS to confirm luminal entry and to verify the safety of the circumflex artery after stenting.
Importantly, the use of CT in this case report led to a discussion by the panel on the use of CT scans in current guidelines. Christiansen suggested that in all cases of failed puncture attempts, a CT scan should
be carried out. He informed the audience that the guidelines in Denmark state that a CT scan is the first course of action when a patient has stable symptoms. He proposed that all cardiologists should learn how to use and interpret CT scans in the context of complex CTO, and that CT should be incorporated into the Global Chronic Total Occlusion Crossing Algorithm. Opolski pointed out that sometimes IVUS can cause an artefact due to the large amount of calcium, particularly in patients that are post coronary artery bypass grafting; and therefore, CT is a better option in these cases. Gabriele Gasparini, Humanitas Research Hospital, Milan, Italy, argued that perhaps CT scans should be implemented in the pre-assessment stage, which is prior to the Global Chronic Total Occlusion Crossing Algorithm.
Roberto Diletti, Thoraxcenter, Erasmus MC, Rotterdam, the Netherlands, wrapped up the discussion by explaining that whether the procedure involves an IVUS-guided puncture, or if different software is utilised, it is essential to use IVUS afterwards to confirm that the puncture is in the correct location. Diletti concluded that “the final IVUS is the most important.”
INVESTMENT PROCEDURES AS STANDARD PRACTICE
The session was completed with an insightful talk by Margaret Mcentegart, Columbia University Irving Medical Center, New York, USA, whose presentation focused on her proposal to conduct an investment procedure for every high-risk patient.
In all cases of failed puncture attempts, a CT scan should be carried out
Mcentegart began by explaining that, while dedicated CTO registries of expert, high-volume operators report success rates with contemporary CTO PCI of up to 90%, in real-world databases, success rates are only about 60%. Additionally, the complications associated with CTO PCIs are higher than non-CTO PCIs, which further highlights the need to improve success rates and safety for patients who undergo CTO PCI procedures. To improve success rates and reduce complications, Mcentegart suggested that an investment procedure should be incorporated into the Global Chronic Total Occlusion Crossing Algorithm. She explained that this is different to a modification procedure (where the proximal cap and CTO body are modified after an unsuccessful CTO PCI), as an investment procedure is a planned, initial procedure to modify the proximal cap, occlusive segment, and distal cap before the subsequent completion procedure. Whilst modification procedures can improve safety and success rates, they occur after a failed attempt, which is something that physicians should try to avoid.
Mcentegart corroborated her argument by providing evidence from case reports of successful CTO PCIs after investment procedures. The two cases presented by Mcentegart are part of a prospective CTO study involving the assessment of investment procedures in 200 patients who are categorised as high-risk CTOs,
with a Japanese chronic total occlusion (J-CTO) score of at least 3 with highrisk retrograde options. Mcentegart and colleagues hypothesised that in higher-risk CTOs, a planned investment procedure will be associated with improved cumulative procedural success and safety and will facilitate an increased proportion of cases being completed antegrade. They also hypothesised that the implementation of an investment strategy will increase the accessibility and provision of CTO PCI, adding that it will make CTO PCI more palatable for the wider cardiology community.
Circling back to the use of IVUS when identifying ambiguous proximal caps, Mcentegart revealed that data from their prospective study have highlighted discrepancies between angiography and IVUS in imaging the location of the proximal cap. She explained that often, the distal cap location detected on IVUS is more proximal than it appears on an angiogram. Mcentegart suggested that the results of the study will provide insights into the morphology of CTOs and the difference between IVUS and angiograms.
In her closing remarks, Mcentegart emphasised that, unless there is a concern of perforation, which is unlikely with the implementation of the investment strategy, they advise not to take a final picture at the end of the procedure, as this can cause hydraulic injury. However, Mcentegart concluded that ultimately, patient safety is the main concern, and if there is suspicion of perforation, then physicians may deem this necessary.
Overall, the session underscored the need for continuous innovation and reassessment of strategies in CTO PCI. The discussions and proposals, such as the use of PWT and investment procedures, aim to refine techniques and improve patient outcomes. Future research might validate these strategies and lead to changes in global guidelines, ultimately enhancing the standard of care for high-risk patients.
Abstract Reviews
Sharing insights presented at the European Association of Percutaneous Cardiovascular Interventions (EuroPCR) 2024 Annual Meeting, the following abstract reviews spotlight exciting new developments in the field.
Comparison of Proximal Optimisation with Kissing Inflation Technique with Kissing Balloon Inflation for Treatment of Coronary Bifurcations
1. Specialized Hospital for Active Cardiology Treatment (SHATC) Medica Cor, Ruse, Bulgaria 2. Department of Cardiology, Pulmonology and Endocrinology, Medical Faculty, Medical University of Pleven, Bulgaria *Correspondence to nmileva91@gmail.com
Disclosure: The authors have declared no conflicts of interest.
Citation: EMJ Int Cardiol. 2024;12[1]:2425. https://doi.org/10.33590/emjintcardiol/ CZEA8428.
BACKGROUND
Percutaneous interventions of bifurcation stenoses represent a technical challenge and pose a high risk of complications.1 Various optimisation techniques such as the proximal optimisation technique (POT) and kissing balloon inflation (KBI) are applied after bifurcation stenting to achieve better post-procedural results.2 However, these methods could still result in incomplete strut apposition to the lateral wall of the side branch (SB).3 The proximal optimisation with KBI technique (POKI) was demonstrated as an alternative to KBI with or without POT, with the potential of shortening the procedure time, and resulting in better final SB ostial stenosis.4
The aim of this analysis is to compare angiographic and clinical outcomes at 12 months between the two groups.
METHODS AND RESULTS
A total of 93 patients with the POKI technique (simultaneous inflation of a balloon in POT fashion with SB balloon) and 295 patients with KBI, with complete 12-month follow-up, were included. Patients with ST-elevation myocardial infarction were excluded. There were no differences in POKI versus KBI groups regarding age (68±9 years versus 66±10 years), sex (67% versus 72% male), hypertension (100% versus 98%), diabetes (38% versus 43%), dyslipidaemia (97% versus 94%), previous myocardial infarction (29% versus 30%), previous percutaneous coronary intervention (48% versus 54%), estimated glomerular filtration rate <60 mL/min/kg (33% versus 31%). Patients in the POKI group had lower left ventricular ejection fraction (50%±7% versus 54%±9%; p=0.030) and higher SYNTAX score (19±7 versus 13±7; p<0.001). The most frequent target vessel in KBI was left anterior descending (66% versus 40% in the POKI group; p=0.027). The procedural time (92±28 min versus 100±38 min; p=0.064), fluoroscopic time (22.8±10.6 min versus 25.8±11.2 min; p=0.083), and total contrast volume (286±85 mL versus 340±121mL; p=0.039) were all lower in
POKI versus KBI. The final diameter stenosis in the main branch was not statistically different (15%±8% POKI versus 11%±5% KBI; p=0.067), but significantly lower in the SB (9%±13% POKI versus 13%±23% KBI; p=0.044; Figure 1). The 1-year all-cause mortality was 2.2% for POKI versus 7.8% for KBI (log-rank p=0.089), and cardiovascular mortality was 2.2% for POKI versus 5.7% for KBI (log-rank p=0.221).
CONCLUSION
The POKI technique demonstrated similar (even better in the SB) angiographic results in the treatment of coronary bifurcation lesions in comparison with standard KBI, shortening the procedure and fluoroscopic time, and reducing contrast volume. The survival rates at 1 year were numerically lower in POKI patients.
Figure 1: Comparison of angiographic results between patients in the proximal optimisation and kissing inflation technique, and kissing balloon inflation technique groups.
References
1. Louvard YLT, Morice MC, "Bifurcation lesions," In: Eekhout E, Serruys PW, Wijns W, Vahanian A, van Sambeek M, de Palma R (eds.), Percutaneous interventional cardiovascular medicine: the PCREAPCI textbook, Europa Edition, Toulouse (2012), pp.283-320.
2. Burzotta F et al. Percutaneous coronary intervention for bifurcation coronary lesions: the 15th consensus document from the European Bifurcation Club. EuroIntervention. 2021;16(16):1307-17.
3. Finet G et al. Comparative analysis of sequential proximal optimizing technique versus technique in provisional bifurcation stenting: fractal coronary
Lesion and Procedural Characteristics on Infrapopliteal Endovascular Procedures in Latin America: Insights from SOLACI Peripheral Registry
Authors: *Virgen-Carrillo Luis Ramón,1
Lugo-Gavidia Leslie Marisol,2 Díaz Larry,3
Rossi Maximiliano,4 Pedernera Gustavo Omar,5
Duarte Ernesto Ramon,6 Pascua Julio Andrés,7
Lamelas Pablo8
1. Virgen Cardiovascular Research, Universidad Autonóma de Guadalajara, Mexico
2. Mexican Academic Consortium for Clinical Data Acquisition, Mexico
3. Ascension Borgess Hospital, Kalamazoo, Michigan, USA
4. Instituto Cardiovascular Rosario, Argentina
5. ICBA Instituto Cardiovascular, Buenos Aires, Argentina
6. Hospital Escuela de Agudos Dr Madariaga, Posadas, Argentina
7. Hospital Italiano La Plata, Buenos Aires, Argentina
8. Instituto de Cardiologia y Cirugia Cardiovascular Hospital Universitario Fundacion Favaloro, Buenos Aires, Argentina
*Correspondence to drvirgen@cardiovascular.mx
Disclosure: The authors have declared no conflicts of interest.
Keywords: Infrapopliteal, Latin America, peripheral artery disease.
Citation: EMJ Int Cardiol. 2024;12[1]:26-28. https://doi.org/10.33590/emjintcardiol/XIVR8781.
BACKGROUND AND AIMS
Infrapopliteal lesions in patients with peripheral artery disease are becoming more common due to the global increase of risk factors such as diabetes, renal, and metabolic disease.1 Angioplasty has recently been shown to be superior to surgery for treating arterial disease below the knee.2 However, these patients commonly present multilevel disease, small calibre, and long lesions with high calcium burden, making endovascular interventions for the infrapopliteal region extremely challenging.1
A wide spectrum of revascularisation strategies and technologies have been developed to address the therapeutic needs in the infrapopliteal space of this region, including support catheters, retrograde access, specialised balloons, and atherectomy for calcified vessels.1, 3-5 The use of stents in this region is currently under investigation. The recent LIFE-BTK study showed better efficacy for adverse limb outcomes with reabsorbable scaffolds placement compared to angioplasty.6 However, the trial included a highly selected population, and the use of stents in infrapopliteal lessions is still uncommon (and not widely available) in world-wide 'real' clinical practice.
The aim of this current study is to describe the lesion characteristics, and procedural and technical aspects of infrapopliteal endovascular procedures in Latin America.
MATERIALS AND METHODS
The cohort included patients derived from the Latin American Society of Interventional Cardiology (SOLACI) peripheral registry. SOLACI peripheral is a prospective, multi-centre, observational, and hospital-based registry of patients with lower-limb peripheral arterial disease, who were treated with endovascular interventions across 10 Latin American countries.7 A total of 1,120 procedures were included in the SOLACI peripheral registry between January 2017–May 2023. The current analysis focuses on infrapopliteal interventions, performed as part of a single or multilevel revascularisation strategies (N=554 procedures).
• 10.4% Disease in other vascular beds (e.g., carotid, aorta)
• 9.6% Heart failure
• 6.7% Dialysis
Procedure Details
• 37.4% Use of drug-eluting balloon
• 8.5% Stenting
- 3.9% Rescue stenting/bailout
- Coronary DES used in 74.4%
• 19.1% Indirect revascularisation
• 1.3% Use of atherectomy
• 8.7% Used retrograde access to achieve success
Hospitalisation Major Adverse Events
• 15.9% Same day discharge
• 1.8% Overall death
- 0.9% Cardiovascular death
• 0.5% Myocardial infraction
• 0.2% Stroke
CABG: coronary artery bypass surgery; DES: drug-eluting stents; ICP: intracardiac microaxial pump; SOLACI: Latin American Society of Interventional Cardiology; TIA: transient ischaemic attack.
RESULTS
Overall, there was a high prevalence of cardiovascular risk factors and concomitant comorbidities, including hypertension (82.5%), dyslipidaemia (63.4%), diabetes (79.4%), myocardial infarction (15.7%), and stroke (9.0%). Most patients had chronic limb-threatening ischaemia (CLTI; 81.9%), while 17.7% presented with advanced intermittent claudication. From the entire cohort, 27 lesions had a previous endovascular treatment. More than one territory was treated in 250 procedures (45.1%). The target infrapopliteal lesions had a length of 144±88.4 mm and a diameter of 2.82±0.7 mm. Moderate calcification was present in 51.3% and 28.2% presented
severe calcification. Atherectomy was used in 1.3%. Stenting was used in 8.5% (47 interventions), of which 22 (3.9%) were performed as rescue stenting or bail-out. Lesions treated with stents were wider (mean diameter 3.20±0.70 mm versus 2.79±0.70 mm) and shorter (mean length 111±101 mm versus 147.0±86.6 mm) compared to lesions treated with balloon angioplasty alone. Most of the procedures using stents required a single device, and only 10 patients required two or more stents. Coronary drug eluting stents were the most commonly used (74.4%).
Successful revascularisation was achieved in 533 procedures (96.2%), with 19.1% of the procedures using indirect revascularisation. The most frequent intraprocedural
Figure 1: Lesion and Procedural Features of Infrapopliteal Endovascular Procedures from SOLACI Peripheral.
complication was thrombosis; 4.3% among patients with stents and 1.8% in patients without stents. Other main complications included embolism (1.3%), and access site haematoma (1.1%). Major adverse events during hospitalisation included death (1.8%), cardiovascular death (0.9%), myocardial infarction (0.5%), and stroke (0.2%).
CONCLUSION
This study illustrates the real-world LatinAmerican experience, and demonstrates the complexity of infrapopliteal procedures (high-risk factors, comorbidities burden, and complex lesions). Even though some procedures required specialised strategies (e.g., indirect revascularisation, retrograde access), there was a high rate of successful revascularisation with low use of additional dedicated devices such as atherectomy or stents. These strategies can help to reduce costs, amputations, and complications.
References
1. Beckman JA et al. Advances in revascularisation for peripheral artery disease: revascularisation in PAD. Circ Res. 2021;128(12):1885-912.
2. Bradbury AW et al. A vein bypass first versus a best endovascular treatment first revascularisation strategy for patients with chronic limb threatening ischaemia who required an infra-popliteal, with or without an additional more proximal infra-inguinal revascularisation procedure to restore limb perfusion (BASIL-2): an open-label, randomised, multicentre, phase 3 trial. Lancet. 2023;401(10390):1798-809.
3. Ambler GK et al. Atherectomy for peripheral arterial disease. Cochrane Database Syst Rev. 2014;17(3):CD006680.
4. Schmidt A et al. Retrograde tibioperoneal access for complex infrainguinal occlusions: shortand long-term outcomes of 554 endovascular interventions. JACC Cardiovasc Interv. 2019;12(17):1714-26.
5. Giannopoulos S et al. Three-year outcomes from the LIBERTY 360 study of endovascular interventions for peripheral artery disease stratified by Rutherford category. J Endovasc Ther. 2021;28(2):262-74.
6. Varcoe RL et al. Drug-eluting resorbable scaffold versus angioplasty for infrapopliteal artery disease. N Engl J Med. 2024;390(1):9-19.
7. Virgen-Carrillo LR et al. Rationale and design of the Latin-American registry of peripheral interventions: insights from SOLACI peripheral. JSCAI. 2024;DOI:10.1016/j.jscai.2024.101931.
Peri-procedural Use of Topical Medications to Reduce Radial Artery Spasm Among Patients Undergoing Coronary Angiography: A Meta-analysis of Current Evidence
Authors: *Josip Andelo Borovac,1 Lisa Fylling,2
Mislav Lozo,1 Dino Miric,1 Anteo Bradaric Slujo,1
Jaksa Zanchi,1 Frane Runjic1
1. Division of Interventional Cardiology, Cardiovascular Diseases Department, University Hospital of Split, Croatia
2. University of Split, School of Medicine, Croatia
*Correspondence to josip.borovac@me.com
Disclosure: The authors have declared no conflicts of interest.
Citation: EMJ Int Cardiol. 2024;12[1]:28-29. https://doi.org/10.33590/emjintcardiol/ BPKU9915.
BACKGROUND AND AIMS
Radial artery (RA) access is the gold standard for vascular access in modern interventional cardiology. For some patients undergoing transradial angiography (TRA), cannulating the radial artery can be painful and may lead to significant
vasoconstriction, thus precipitating radial artery spasm (RAS). Risk factors for RAS include female sex, smaller radial artery diameter, multiple puncture attempts, RA anomalies, moderate-to-severe pain during cannulation, and several other factors.1-4 This phenomenon is clinically relevant since the onset of significant RAS can result in a delay or prolongation of the index procedure, radial artery occlusion, inability to advance the catheter and coronary equipment, crossover to the femoral approach, and ultimately procedural failure. On the other hand, topical solutions such as nitroglycerine and lidocaine can effectively induce local radial artery vasodilation without altering systemic blood pressure and patient haemodynamics.5 Previous studies suggested the relevant effect of topical solutions on RAS decrease; however, results were inconclusive due to the low number of studies, limited sample size, and large heterogeneity across studies.6 This meta-analysis aimed to investigate whether applying topical premedication before RA puncture reduces the occurrence of RAS in patients undergoing TRA for suspected or established stable coronary artery disease (CAD), compared to the standard practice of subcutaneous lidocaine infiltration.
MATERIALS AND METHODS
A cumulative meta-analysis was conducted, including six randomised controlled or prospective non-randomised placebo-controlled trials identified in the literature, focusing on patients with stable or suspected CAD. All patients underwent TRA to identify and characterise their coronary anatomy and disease burden. The primary outcome was the odds ratio (OR) of radial artery spasms occurring during, or shortly after, RA cannulation. The effect measurement for RA spasm was determined using ORs with 95% confidence interval, and a fixed-effects statistical algorithm. The analysis utilised Cochrane’s Review Manager software (RevMan, version 5.4, The Cochrane Collaboration, 2020, London, UK).
RESULTS
A total of 1,365 patients were included in the six studies, with 687 patients in the experimental group and 678 in the control group. RAS occurred in 5.8% of cases in the experimental group (use of topical medications), compared to 9.7% in the control group. This demonstrated a significant reduction in the likelihood of RAS with the use of topical premedication compared to standard lidocaine infiltration alone (OR: 0.55; 95% CI: 0.36–0.84; P=0.005). The data indicated very low statistical heterogeneity among the included studies (χ2: 5.15; Higgins I2: 3%; P=0.403).
CONCLUSION
The current meta-analysis revealed that preprocedural applications of topical medications significantly reduces the odds of radial artery spasm by 45% compared to standard lidocaine infiltration alone. Thus, this approach may be a feasible, safe, and effective method for preventing radial artery spasms in patients with stable or suspected CAD undergoing TRA, thereby enhancing procedural success.
References
1. Roczniak J et al. Radial artery spasmsangiographic morphology, risk factors and management. Postepy Kardiol Interwencyjnej. 2024;20(1):53-61.
2. Ho HH et al. Radial artery spasm during transradial cardiac catheterization and percutaneous coronary intervention: incidence, predisposing factors, prevention, and management. Cardiovasc Revasc Med. 2012;13(3):193-5.
3. Ruiz-Salmerón RJ et al. Espasmo radial en el cateterismo cardíaco transradial. Análisis de los factores asociados con su aparición y de sus consecuencias tras el procedimiento. Rev Esp Cardiol. 2005;58(5):504-11.
4. Curtis E et al. Clinical predictors and management for radial artery spasm: an Australian crosssectional study. BMC Cardiovasc Disord. 2023;23(1):33. Erratum in: BMC Cardiovasc Disord. 2023;23(1):90.
5. Majure DT et al. Topical nitroglycerin and lidocaine locally vasodilate the radial artery without affecting systemic blood pressure: a dose-finding phase I study. J Crit Care. 2012;27(5):532.e9-13.
6. Curtis E et al. The effect of topical medications on radial artery spasm in patients undergoing transradial coronary procedures: a systematic review. JBI Database System Rev Implement Rep. 2018;16(3):738-51.
Aortic Distensibility Measured by CT as a Marker of Obstructive Coronary Artery Disease
Authors: *Niya Mileva,1 Panayot Panayotov,1,2
Dobrin Vassilev1
1. Specialized Hospital for Active Cardiology Treatment (SHATC) Medica Cor, Ruse, Bulgaria
2. Department of Cardiology, Pulmonology, and Endocrinology, Medical Faculty, Medical University of Pleven, Bulgaria
*Correspondence to nmileva91@gmail.com
Disclosure: The authors have declared no conflicts of interest.
Citation: EMJ Int Cardiol. 2024;12[1]:30-31. https://doi.org/10.33590/emj/WTYE9816.
BACKGROUND
Elastic arteries contain a high number of collagen and elastin filaments in their medial layer, providing the ability to stretch in response to ventricular contractions.1 The largest artery in the human body, the aorta acts as an elastic buffering chamber storing almost half of the left ventricular (LV) stroke volume during systole. In diastole, the elastic forces of the aortic wall release this residual volume to the peripheral circulation, thus creating a nearly continuous peripheral blood flow.2 With ageing, the elastic capacity of the aorta and the large arteries decreases, which leads to an increased cardiovascular risk.3 Therefore, the assessment of aortic elastic properties stands at the intersection of cardiovascular research, diagnosis, and risk stratification.4 CT has emerged as a valuable and reproducible method for the assessment of aortic elastic properties for risk stratification. The team aimed to compare the aortic
elastic properties acquired by coronary CT angiography (CTCA) in patients with obstructive and non-obstructive coronary artery disease (CAD), and evaluate the association between aortic distensibility and obstructive CAD.
METHODS AND RESULTS
In this observational prospective study, consecutive patients undergoing CTCA for suspected CAD with low-to-moderate risk between September 2022–June 2023 were considered eligible. Image acquisition was performed through CCTA using an ECG-gated CT scanner (SOMATOM go.Top, Siemens Healthineers, Erlangen, Germany) according to the protocol recommended by the Society of Cardiovascular Computed Tomography (SCCT). Vessel analysis software (syngo.via, Siemens Healthineers) was used to quantify the area of ascending and descending aorta through the cardiac cycle. Aortic distensibility in the segment of ascending and descending aorta was calculated using the following formula: AD=ΔA/(Ad*ΔP), (AD, ×10-3 mmHg-1), where ΔA is the difference between the maximal luminal measured area and the minimal luminal measured area, and ΔP is the difference between systolic pressure and diastolic pressure. Patients were divided into two groups based on the severity of the CAD: obstructive CAD when a stenosis ≥50% was noted, and non-obstructive CAD when a stenosis <50% or none was found. Of all 201 patients enrolled in the study, 115 subjects (57%) had ≥50% coronary stenosis, and the remaining 84 (43%) patients had non-obstructive or no coronary disease. Patients with obstructive
CAD were found to be significantly older (60.8±11.1 years versus 53±12 years; p=0.009); more often males (60.5% versus 53%; p=0.021); had a higher prevalence of diabetes (21.1% versus 15.2%; p=0.014); atrial fibrillation (12% versus 6%; p=0.018); and lower ascending aortic distensibility (1.45±0.94 10-3 mmHg-1 versus 2.03±0.88 10-3 mmHg-1; p=0.019). Univariate regression analysis including patient demographic and clinical characteristics, as well as aortic elastic properties obtained, was performed to search for independent predictors of significant CAD. Factors that showed significant predictive value were included in multivariate regression analysis. The results showed that ascending aortic distensibility assessed by CT had significant predictive value for the presence of coronary disease (hazard ratio [HR]: 1.92; 95% CI: 1.14–3.23; p=0.001), along with patient age (HR: 1.03; 95% CI: 1.00–1.05; p=0.029) and the presence of diabetes (HR: 1.11; 95% CI: 1.04–1.26; p=0.009) (Figure 1).
CONCLUSIONS
Evaluation of aortic elastic properties in patients referred for CTCA is feasible. Patients with obstructive CAD had lower distensibility of the ascending aorta. Furthermore, ascending aortic distensibility assessed by CT had significant predictive value for the presence of obstructive CAD.
References
1. Kassab GS. Biomechanics of the cardiovascular system: the aorta as an illustratory example. J R Soc Interface. 2006;3(11):719-40.
2. Belz GG. Elastic properties and Windkessel function of the human aorta. Cardiovasc Drugs Ther. 1995;9(1):73-83.
3. Mileva N et al. Aortic elasticity and cardiovascular risk stratification: a narrative review on the current understanding. J Vasc Dis. 2024;3(1):88-101.
4. Cheng K-S et al. Arterial elastic properties and cardiovascular risk/event. Eur J Vasc Endovasc Surg. 2002;24(5):38-97.
1 2 3
Figure 1: Predictive value of aortic distensibility for obstructive coronary artery disease.
disease.
Congress Interviews
Two experts in interventional cardiology discuss advancements in the field and their motivations for research. Conversations are centred around current topics: transcatheter edge-to-edge repair, tricuspid regurgitation interventions, and improving patient survival rates.
Francesco Maisano
Cardiac Surgeon, IRCCS Ospedale San Raffaele, Milan, Italy
I realised the immense value that less invasive procedures bring to patients
Citation: EMJ Int Cardiol. 2024;12[1]:32-34. https://doi.org/10.33590/emjintcardiol/DKBJ6606.
Q1
What initially led you to pursue a career in interventional cardiology, and what continues to motivate you at present?
I decided on cardiac surgery as a profession after being inspired by an encounter with Ottavio Alfieri, Professor of Cardiac Surgery and Chief of Department of Cardiac Surgery, San Raffaele University Hospital, Milan, Italy, who took care of my father while I was in the medical school. I was around during the era of surgery as the gold standard solution for structural heart disease, and I have been dedicating my career to valve disease, and specifically to mitral and tricuspid valve repair. As part of Alfieri’s team, I envisioned the evolution of edgeto-edge repair from a surgical to an endovascular procedure. This pushed me towards cross-training in interventional cardiology under Antonio Colombo, Humanitas Research Hospital, Milan, Italy, and I had the opportunity to connect with several leaders in the early 2000s, including Alain Cribier, Hospital-Charles Nicolle, University of Rouen, France; John Webb, University of British Columbia, Vancouver, Canada; Martin B Leon, Columbia University, Irving Medical Center,
New York, USA; Alec Vahanian, University of Paris, France; Karl Heinz Kuck, University Heart Center, Lübeck, Germany; and many others. Through this, I realised the immense value that less invasive procedures bring to patients, and have thus continued to practice both surgery and interventional procedures to deliver the best tailored treatment to my valve patients. My main motivation is to drive our community globally in the direction of achieving effective teamwork, building multidisciplinary teams that work for patients, and abolish the current siloes.
Q2
As a board member for the European Association of Percutaneous Cardiovascular Interventions annual conference (EuroPCR), what does your role entail, and what changes have you brought into effect whilst serving this position?
I feel honoured to be a part of this group. I bring my own perspective to it as a surgeon involved in the interventional community, and I think this reflects the open mind of the EuroPCR family, and the willingness to serve the cardiovascular community as a whole.
PCRonline is a gateway to education in the field of interventional cardiology, through creating courses across Europe. My main commitment in this role is to develop simulationbased certification programmes in collaboration with academic institutions around Europe, to raise the quality of care, and to bring EuroPCR education quality into academic programmes.
Q3
How much of an impact do you believe the EuroPCR has, both directly on interventional cardiologists and indirectly on patients?
EuroPCR is designed by, and for, the interventional cardiology community, with patient benefit at the centre of our scope. We care about our patients, and we try to learn from each other to improve our practice. EuroPCR events are designed around this objective: to learn from global community knowledge that can be transferred into clinical practice from the first day after the meeting. I am
currently running two certification programmes in the University Vita Salute of Milano, Italy, in co-operation with EuroPCR, on transseptal puncture and on transcatheter edge-to-edge repair.
Q4
Your area of interest lies in structural heart disease and implementing innovative therapies in clinical practice. Could you share some examples of innovative therapies you have been involved with, and the impact they have had on patient care?
I have been involved in aortic mitral and tricuspid innovation, and have performed the first mitral and tricuspid annuloplasty procedures using the Cardioband tricuspid system (Edwards Lifesciences, Irvine, California, USA). I have also explored different technologies, and I have been highly involved in the development of transcatheter edge-to-edge repair from the very beginning.
Q5 You recently published a paper entitled ‘Transcatheter treatment of the tricuspid valve: current status and perspectives’. Please provide the main takeaways from this research, and the impact it could have on clinical practice.
Tricuspid valve disease is highly prevalent in the community, and has relevant prognostic implications. In the last 10 years, thanks to the introduction of tricuspid interventions, there has been a great focus on it, with a lot of new knowledge developed and shared. New interventions, therefore, have not only brought new hope for patients, but also ignited new energy in exploring the right heart physiology and research in the field of tricuspid regurgitation (TR). TR is in the crossroad of several patient pathways, and these patients require a multidisciplinary approach to tackle the complex environment of multimorbid disease. Due to this effort, there are now multiple therapeutical
Only the combination of knowledge and tools from the different specialties will allow us to improve outcomes in our patients
choices, with many transcatheter solutions on top of surgical techniques, which are also evolving. The main effort of the EuroPCR tricuspid focus group is to define the ideal sweet spot for each therapy, and to encourage a multidisciplinary approach in the lifetime management of the patients. In the paper, which is written for a non-specialist community, all physicians involved in the care of patients with TR will find some inspiration to improve the outcomes of these patients.
Q6
With over 20 patents filed, and multiple start-up companies founded in cardiovascular medicine, what drives your passion for innovation in this field? Could you discuss some of the challenges you have faced in translating innovative ideas into successful products or treatments?
Being an innovator is a great challenge. You have to challenge the so-called standard of care, and fight against the ‘mainstream’. Innovation starts from the
identification of an unmet need. This is already a great challenge. To be an innovator, you need to be not only creative, but also honestly driven by curiosity, and a sense of unsatisfaction with the state of the current options.
Finding the areas that deserve optimisation is a key element of innovation. The technical solution is obviously the centre of any new device, but finding the right unmet need is key. This is why I am proud to have been one of the first to found a start-up on tricuspid interventions back in 2009, when tricuspid was not yet considered a hot topic, as we were in the hype of transcatheter aortic valve implantation.
Q7 Finally, what do you see as the most pressing challenges in the field of cardiovascular medicine today? How do you plan to address them in your role as a board member for EuroPCR?
The main challenge is to break down barriers among different professionals. EuroPCR, being
an educational entity, allows us to reach experts from different scientific societies, and build bridges for a better care. In my 30-year career, I have had the unique opportunity to grow in a multidisciplinary environment. I am member of European Association of Percutaneous Cardiovascular Interventions (EAPCI), the European Association of Cardiovascular Imaging (EACVI), the European Society of Cardiology’s Heart Failure Association (ESC-HFA), and the European Association for CardioThoracic Surgery (EACTS). I also participate in several scientific activities as a board member of EuroPCR, and bring this message of joining forces for an holistic approach to patients. Only the combination of knowledge and tools from the different specialties will allow us to improve outcomes in our patients. EuroPCR is, and will be, the voice of a wide community that is open to change, open to listening to all shareholders, and to patients above all.
Julien Dreyfus
Cardiologist, Centre Cardiologique du Nord, Saint-Denis, France
Citation: EMJ Int Cardiol. 2024;12[1]:35-38. https://doi.org/10.33590/emjintcardiol/YERQ9028.
Q1
What initially sparked your interest in cardiology, and what continues to motivate you in this field to this day?
I began my residency in cardiology at Bichat Hospital in Paris, France. At that time, it was one of the leading institutions for valvular heart disease, under the supervision of Alec Vahanian, who was also heading the European Guidelines for Valvular Heart Disease. The team included many brilliant colleagues, such as Bertrand Cormier, who developed a dedicated classification to predict procedural results after percutaneous mitral valve commissurotomy in patients with mitral stenosis, Bernard Lung, and David Messika-Zeitoun, who is now working in Ottawa, Canada, and has become my mentor. I was privileged to meet these people, discover this institution, and learn a lot from them. Working with passionate individuals, their enthusiasm becomes contagious, and it probably started for me at that time. I consider myself truly lucky.
Q2
Could you elaborate on the latest advancements in the diagnosis and treatment of tricuspid valve diseases, and how your research has contributed to these developments?
to compare measurements of the tricuspid annulus diameter using transthoracic and transoesophageal echography, and surgery to define the best method and appropriate cut-off values. This work followed Gilles Dreyfus' findings on the prognostic impact of tricuspid annulus dilatation, which led to the recommendation for concomitant tricuspid valve annuloplasty at the time of mitral valve surgery for patients with a dilated tricuspid annulus, which was included in the 2007 European Guidelines on Valvular Heart Disease. I performed approximately 200 transthoracic and transoesophageal echocardiographies at a time when few were focused on the tricuspid valve, often referred to as the ‘forgotten valve’. Today, the situation has changed significantly. The tricuspid valve is no longer overlooked, thanks to increased awareness and advancements in treating tricuspid valve disease, primarily due to the development of transcatheter therapies.
Q3
In 2023, you partook in a roundtable discussion, with Lenard Conradi and Philipp Lurz, at PCR Valves 2023, regarding the latest developments in tricuspid regurgitation treatment. Could you summarise the main takeaways of this session for our readers?
I had the privilege of discussing tricuspid valve treatment with two brilliant colleagues, Philipp Lurz, an interventional cardiologist, and Lenard Conradi, a cardiac surgeon, both from Germany. Our discussion was particularly enriching as it brought together three key specialists: an interventional cardiologist, a cardiac surgeon, In
Fifteen years ago, there was significant interest in aortic valve disease due to the advent of transcatheter interventions for aortic valve stenosis and later for mitral valve regurgitation. However, the tricuspid valve received little attention. My mentor, David, asked if I wanted to work on this underexplored area, and I agreed. My first project as a resident was
and a clinician focused on echocardiography. We agreed that early patient referral is crucial to improving outcomes and reducing in-hospital mortality, particularly after isolated tricuspid valve surgery. Additionally, we believe that the evolving transcatheter therapies for tricuspid valve repair and replacement will significantly change patient treatment. Our current goal is to identify patients who would benefit from curative treatment, whether surgical or transcatheter, and set objectives for optimal care. This task requires close collaboration between physicians and companies. We are just at the beginning of this journey, and the landscape will continue to evolve in the coming years.
Q4
During the discussion, you compared transcatheter tricuspid replacement and edge-toedge repair. From your perspective, what are the main factors that influence the choice between these two treatment options, and how do you foresee these interventions evolving in the future to improve patient outcomes?
This is a very important question, which is why we need to define our goals and identify which patients would benefit from a curative intervention. Once we establish these criteria, we can determine for each patient whether repair or replacement is more appropriate. Interestingly, current registries show that approximately 60% of patients who undergo isolated tricuspid valve
surgery receive a replacement, while 40% undergo a repair.
The choice between these options should be based on the valve's anatomy and the right ventricle's remodelling, aiming to achieve the lowest possible tricuspid regurgitation grade. If a repair cannot meet this goal, a replacement may be necessary. Additionally, the availability of devices varies by country, as most are only accessible through studies without reimbursement in many regions, often dictating our choices.
Replacement procedures are quick and reproducible, addressing conditions like huge gaps, multiple scallops, pacemaker leads, or concomitant stenosis. However, they carry higher risks, including vascular complications, need for transfusion, migration, and mortality. Repair, while often yielding poorer immediate results, rarely causes fatal complications, and may be preferrable when achieving optimal tricuspid regurgitation grades is possible.
In the future, long-term followup may reveal other issues such as thrombogenicity or durability for bioprostheses. Therefore, we must continue to define the best treatment strategies and work collaboratively to achieve these goals, as advancements in research and technology will continue to refine our approach and potentially offer more effective solutions.
Q5From your experience, in what ways has EuroPCR added to the field of interventional cardiology?
I think EuroPCR Congress is an amazing event, primarily created for interventional cardiologists; yet, it attracts a wide range of specialists, including clinicians and imaging specialists like myself, surgeons, and heart failure specialists. One of its main strengths is its ability to gather physicians from all over the world, fostering a multidisciplinary environment. Over 10,000 participants attend, including physicians, companies, and the press.
EuroPCR is highly educational, encouraging interactive discussions rather than passive listening. Initially focused on coronary artery disease, it has expanded to include valvular heart diseases, reflected in events like PCR London Valves, which is specifically dedicated to valvular heart disease. The creation of the PCR Tricuspid Focus Group, which I am part of, highlights PCR's commitment to advancing tricuspid valve disease management. This group, consisting of dedicated colleagues and companies, aims to improve patient care through collaborative efforts, regular meetings, and publications. This multidisciplinary, multicentric approach exemplifies how PCR fosters collaboration and innovation in interventional cardiology.
Please summarise the TRI-SCOREs trial for our readers. What motivated you to develop this trial, initially?
I began at Bichat Hospital with my mentor, David. Initially, we focused on the tricuspid annulus, but then we shifted to investigating inhospital mortality after isolated tricuspid valve surgery. Existing publications indicated a high mortality rate, around 8–10%, but lacked detailed explanations.
Frustrated by this lack of information, we collaborated with 12 tertiary French hospitals to collect baseline characteristics for patients undergoing isolated tricuspid valve surgery over 11 years. Despite being a highrisk surgery, we gathered data from 466 patients. Our analysis revealed that clinical presentation at the time of surgery, rather than the mechanism of tricuspid regurgitation, was the key predictor of in-hospital mortality. Factors such as age, right-sided heart failure signs, diuretic dosage, and kidney or liver dysfunction were critical.
To address the need for a dedicated risk assessment tool, we developed the TRI-SCORE, the first score specifically designed to predict in-hospital mortality for isolated tricuspid valve surgery. This score includes eight easily ascertainable parameters: age ≥70 years, NYHA Class III–IV, right-sided heart failure signs, diuretic dosage, kidney and liver dysfunction, and right and left ventricular dysfunction. The score ranges from 0–12 points, correlating with in-hospital mortality rates from 1–65%.
The TRI-SCORE has been validated in various countries, including Asia, proving effective in predicting outcomes. This tool guides individual clinical decisions and emphasises early intervention to improve patient survival. Our ongoing work, particularly with the TRIGISTRY registry, aims to refine treatment strategies and improve patient management across more than 30 centres in 10 countries.
Last year, we demonstrated that the TRI-SCORE could predict 2-year survival. Patients with a
low TRI-SCORE (≤3) who were referred for surgery had better outcomes, with improved survival compared to those receiving medical therapy. However, there was no benefit for patients with intermediate and higher TRISCORE (≥4), suggesting that early correction of the disease improves survival. We have also shown that transcatheter interventions improved 2-year survival compared to medical therapy in low- and intermediate-risk patients (TRI-SCORE ≤5) when procedural success is achieved, defined as mild-to-moderate or lower tricuspid regurgitation grade at discharge, but not in high-risk patients (TRI-SCORE ≥6).
Our research underscores the importance of early intervention based on TRI-SCORE to improve survival, highlighting the need to treat the right patient at the right time. To facilitate its use in daily practice, a free online TRI-SCORE calculator is available (www.triscore.com), and an app will be launched soon.
For aspiring cardiologists, remember that medicine, especially cardiology, is fundamentally about the patient
Q7 Are there any innovations on the horizon within interventional cardiology, that are of particular interest to you? What advice do you have for any aspiring cardiologists?
Innovations? There are indeed many, driven by the large number of patients and substantial financial investments. Fifteen years ago, companies overlooked the tricuspid valve, but now, witnessing the advancements with aortic stenosis, they realise its potential. I believe that within 15 years, the tricuspid valve will see similar breakthroughs. Companies understand this, and we are now collaborating closely, accelerating progress. New devices frequently emerge, although not all succeed. This is an exciting time with a lot of work and enthusiasm from everyone involved. While some innovations are remarkable and others less so, there is a genuine awareness of the disease. Many
people, including cardiologists, surgeons, and companies, are working together. For example, the PCR Tricuspid Focus Group has significantly impacted the field, and I am thrilled to be part of it.
For aspiring cardiologists, remember that medicine, especially cardiology, is fundamentally about the patient. If you choose this path, your focus should always be on patient care. You will spend a lot of time with patients and face frustrations, especially when treatments are not straightforward. Innovation often comes from these challenges. Even if you have great ideas, you cannot achieve everything alone. Collaboration with colleagues and companies to develop new devices and treatments is essential. It is a demanding field, and you must be prepared to work hard. Dedication and patience are key. If you are passionate and willing to put in the effort, you can make a significant impact and become a great doctor.
Interviews
This year we have had the pleasure of interviewing leading experts in the field of interventional cardiology: Stephen Hoole, Alessia Callegari, and Damien Kenny. Each share compelling insights on their background, career endeavours, and research focuses for the future. Discussions range from current interventions, such as coronary artery stenting and balloon pulmonary angioplasty, to current challenges facing adult congenital care.
Featuring: Stephen Hoole, Alessia Callegari, and Damien Kenny
Stephen Hoole
Consultant Cardiologist, Royal Papworth Hospital, Cambridge, UK; Affiliated Associate Professor, University of Cambridge, UK
Citation: EMJ Int Cardiol. 2024;12[1]:39-44. https://doi.org/10.33590/emjintcardiol/11000009.
Q1What led you to pursue a career in interventional cardiology?
I was always fascinated by general medicine during my training as a medical student and house officer at the John Radcliffe Hospital in Oxford, UK. I particularly liked the immediacy of surgical treatments, with the prospect of ridding a patient of their symptoms, and sometimes curing them with the flash of a scalpel!
I was drawn to cardiology as a junior doctor because, as a medical specialty, it really led the field of evidence-based practice, with large randomised controlled trials that enabled clinicians to know what was best for their patients. The diagnostic tools, with 2D and 3D echo, CT coronary angiography, cardiac MRI, invasive angiography, imaging, and physiology, were also second to none, and together this made clinical decision-making comparatively simple, which was appealing.
Interventional cardiology was an exciting and growing field at the time of my training. With the emergence of drug-eluting stents, and the prospect of transcatheter valve intervention, a physician could do surgery, which appeared to me to be the best of both worlds. I began my interventional training at Papworth Hospital in Cambridge, UK, and completed a doctorate studying cardioprotection during percutaneous coronary intervention (PCI), which led to an ongoing research interest in this field. This was facilitated by a Clinical Lecturer position, also in Cambridge. Following a yearlong interventional fellowship in Vancouver General Hospital, Canada, I was appointed as a National Health Service (NHS) Consultant in interventional cardiology at Papworth Hospital in 2011, with highly coveted, NHSfunded, dedicated research time.
Q2Coronary artery stenting is an area of your expertise. What are the unique challenges associated with this
surgical practice, and how do you improve stent safety and outcomes?
PCI has evolved in the four decades it has been available as a treatment. On the surface, the concept seems to be a simple one: a balloon, and sometimes a balloon-mounted stent, opens a blocked vessel and restores blood flow to heart muscle. But the safety and durability of the PCI result are its Achilles heel, and if not done optimally, results can be disappointing. Refinements in technique have addressed some of these issues. The preference for radial artery access has reduced bleeding complications, and is now mainstream; and the judicious use of intracoronary diagnostic physiology and imaging to guide lesion selection, adjunctive lesion modification before stenting, and post-stent optimisation in increasingly complex and calcified coronary artery disease, ensures the best long-term outcomes.
I was drawn to cardiology as a junior doctor because, as a medical specialty, it really led the field of evidence-based practice
However, good technique addresses only part of the challenge. PCI-related myocardial infarction (MI) and reperfusion injury may be inadvertently caused by stent deployment, and is deleterious. Furthermore, following successful stenting, chest pain may persist due, in part, to coronary microcirculatory dysfunction. We have evaluated several cardioprotective strategies to improve myocardial resistance to ischaemia at the time of PCI,
maintain microvascular integrity, and limit reperfusion injury, with mixed results. We recently successfully completed a pivotal safety trial, administering the anti-CD20 monoclonal antibody rituximab to reduce B-cells, which contribute to adverse remodelling, in patients with ST-elevation MI. This has led to an ongoing large, multinational, multicentre, randomised controlled trial, to hopefully establish the efficacy of this immunomodulatory strategy, to salvage myocardium in patients presenting with anterior STelevation MI.
Q3
The Royal Papworth is the only hospital in the UK that performs balloon pulmonary angioplasty (BPA). You are also the national interventional lead for the UK BPA service. Can you tell us more about this pioneering procedure, and its benefits for patients?
Chronic thromboembolic pulmonary hypertension (CTEPH) occurs when pulmonary emboli fail to spontaneously resorb after a period of anticoagulation, and instead form mesh-like narrowings, called ‘webs’, in the pulmonary arteries, leading to pulmonary hypertension and persistent breathlessness and fatigue. This may be treated by pulmonary endarterectomy (PEA), but 40% of patients with CTEPH are inoperable, due to either inaccessible subsegmental disease, or comorbidities that preclude surgery. Up until recently, these patients were only offered symptomatic relief with pulmonary vasodilator therapy, and their outlook was comparatively worse than those who had PEA. BPA offers a further treatment option for patients with inoperable CTEPH. The procedure leverages the techniques
employed in PCI: a balloon is delivered over a guidewire and dilates a channel through the web, relieving the obstruction, and enabling improved pulmonary perfusion and gas exchange. The patients are awake during the procedure, and typically have three to four treatment sessions to achieve the best results.
We are currently the only UK centre offering this pioneering treatment, and we have comparable results with other leading international centres. Our patients demonstrably improve their pulmonary haemodynamic status, with reduced echocardiographic and biomarker evidence of right heart strain, improved functional status and quality of life, and prolonged survival, comparable to that of patients treated by PEA. Importantly, our BPA service has been extremely safe, with no major procedural-related complications or deaths since we started our service over 8 years
ago. This attests to the skill of the whole team involved in the care of these complex patients.
Q4You recently coauthored the paper ‘The Index of Microcirculatory Resistance After Primary Percutaneous Coronary Intervention: A Pooled Analysis of Individual Patient Data’. What were the key learning points from this article, and how do these findings contribute to the existing literature on microvascular dysfunction after PCI?
This was a collaborative paper, led by a team at Stanford University, California, USA, which pooled pressure-wire data assessing microcirculatory dysfunction at the time of primary PCI, from several international centres. We had initially collected our dataset to confirm that manual thrombectomy, the removal of a clot from an occluded coronary artery during an ST-elevation MI before stent deployment,
contributed to, rather than prevented, procedure-related microembolic injury. The subsequent randomised controlled trials, demonstrating that routine manual thrombectomy did not improve clinical outcomes, were therefore somewhat expected.
The key take-home message of this paper, other than emphasising that we can achieve more by working together collaboratively, was to confirm, in a large cohort of patients with ST-elevation MI, that microcirculatory dysfunction measured at the time of primary PCI was an independent predictor of cardiac death at 5-year followup. Therefore, if we assess the index of microcirculatory resistance at the end of primary PCI, we can identify the highestrisk group of patients, who may benefit from additional cardioprotective therapies and monitoring. In addition, the trial justifies using the index of microcirculatory resistance as a surrogate endpoint for future
PCI has evolved in the four decades it has been available as a treatment
cardioprotective trials, which are still needed to improve the outcome of patients with STelevation MI.
Q5 With over 150 peerreviewed manuscripts to your name for your research in interventional cardiology, what do you believe to be the current gaps in the literature, and which topics merit greater attention?
Focusing on my own area of interest of coronary intervention, we still need to conquer reperfusion injury and microvascular dysfunction at the time of MI revascularisation. Both often limit the PCI therapeutic effect. It is astounding that almost half of the final infarct size is attributed to reperfusion injury caused by stenting the infarctrelated artery. Interventional cardiologists will be only too aware of the phenomenon of technical success: an open artery, but ultimately a disappointing therapeutic failure, when a large, completed MI occurs despite our efforts.
To date, the randomised trials that have assessed treatments targeting reperfusion injury have been disappointingly negative, despite promising initial data, and have not been endorsed or adopted clinically. This may be due, in part, to trial design, and the difficulties of translational research in this field. But we must persevere to achieve reperfusion quality, to further reduce infarct size and improve the outcomes of patients presenting with acute
MI. Furthermore, although we can quantitatively measure coronary microcirculatory dysfunction (CMD) invasively with pressure wire at the time of MI, and in stable coronary syndromes, and we know that CMD is widely prevalent in patients with chest pain, we lack specific therapies for CMD. Further trials are necessary to bridge this ‘therapeutic chasm’.
Finally, the iterative development of drug-eluting stents has probably reached its zenith, but despite this, there remains a small but significant yearon-year risk of coronary stent failure, even in those stents that have been implanted optimally. The concept of ‘leaving nothing behind’ remains an attractive one to many interventionists, including myself. Although the first foray into bioresorbable scaffolds ultimately led to failure, drug-eluting balloons and novel dissolvable stent platforms are still worth pursuing.
Q6
You are also a specialist and expert adviser to the Medicines and Healthcare products Regulatory Agency (MHRA), National Institute for Health and Care Excellence (NICE), and National Institute for Health and Care Research Health Technology Assessment (NIHR HTA) interventional device programmes. What is your main focus in these roles?
I act as an independent advisor to the MHRA and NIHR HTA, providing clinical assessments of new devices and technologies, and, in particular, reviewing the
design of new device trials. I have an interest in innovation, and with the help of others, I have developed two new devices: one in clinical use, and another undergoing clinical trials. I have found the regulatory experience from ‘the other side’ illuminating. Regulatory diligence is vital, in order for the public to have confidence that it is safe and worthwhile to participate in a new device trial in the UK, and for the findings to ultimately be meaningful. I hope I have helped to ensure that only well-designed new device trials are funded and approved, so that promising new devices are robustly assessed, and those that work may be rapidly made available for clinical use.
I have also sat on two guideline committees as an expert and Chair for NICE. Both were a rich and rewarding experience, allowing time for a detailed review of a subject with constructive discussion between a broad range of experts, and formulating guidance that will have real impact, not only to the care of patients within the UK, but internationally, too.
Q7How has the advent of new technologies impacted the field of interventional cardiology in recent years? Are there any innovations on the horizon that you think are particularly noteworthy?
Undoubtably, the big success story for the field of interventional cardiology has been the evolution of percutaneous valvular replacement and repair, and in particular, transcutaneous aortic valve implantation (TAVI). TAVI has been a revolutionary treatment for patients with aortic valve stenosis, with rapid recovery times, and good longterm outcomes enabling more patients to be treated. However, despite the hype of transcatheter edge-to-edge repair for mitral incompetence, this remains a palliative procedure in my view. The surgical Alfieri stitch repair, on which it is based, has all but disappeared from surgical practice, and innovative new solutions that deliver a functionally perfect percutaneous valve repair to the more complex mitral, and tricuspid, valves are a fertile ground for innovation.
In the coronary space, the old foe of coronary calcification has been dealt several blows with the iterative evolution of rotational atherectomy, as well as the development of orbital atherectomy, excimer laser coronary atherectomy, and intravascular lithotripsy. The latter, in particular, is the big success story due to its simplicity; any innovation that makes life easier for the operator, as well as improving outcomes for the patient, will achieve high market penetrance. The value of intracoronary imaging to guide calcium modification has also had a resurgence with the development of these tools, and improved user interface, which again makes life simpler, has been an important development.
There is still more to be done in the intracoronary diagnostic space to understand in vivo plaque biology, with new advances in automated vulnerable plaque detection software, and catheters that can detect trans-coronary biomarker gradients. In concert, these tools may soon provide further understanding to predict which coronary plaques are at risk
of causing future clinical events. Then, the question will be: what do we have in the interventional toolbox to deal with such plaques? This will inevitably lead to yet more innovative solutions, and, as frequently occurs with innovation, perhaps the return of old treatments like resorbable stents. Similarly, another area of unmet need is coronary microvascular dysfunction, where we have the diagnostic capability, but lack specific treatments; this area is ripe for growth. Innovations, like coronary sinus reducer, are an exciting development, that may be of help here.
Finally, it would be remiss of me not to mention a complication of acute MI that I think we have not made any meaningful progress in addressing in the last two decades: cardiogenic shock. Despite developments in mechanical circulatory support, the outlook for patients with cardiogenic shock remains bleak. Perhaps prevention, with better myocardial salvage at the time of initial acute MI presentation, will prove to be better than, and obviate the need for, a cure. Hopefully, effective adjunctive therapies to minimise reperfusion injury, associated microcirculatory
dysfunction, and adverse remodelling are on the horizon, and will make cardiogenic shock a rarity in the future.
Q8
Since your appointment to Consultant
Interventional Cardiologist at Royal Papworth, what has been your proudest achievement?
It is always gratifying to see interventional trainees and fellows, who I have mentored and taught, achieve success in their careers. I have been the interventional cardiology fellowship programme director in Cambridge for more than 10 years, and over that time, we have had over a dozen UK and international fellows join us for 12 months, which has brought mutual benefits. I have also been lucky to collaboratively supervise over 10 talented research fellows studying for a doctorate, who have immersed themselves in research projects from my group, and presented and published their work to acclaim; we recently had one fellow presented with a Young Investigator Award at the European Society of Cardiology (ESC) meeting, which was a particularly proud moment. I still get a buzz from presenting
and publishing new data, and contributing to the growth in knowledge of the field of cardiology, and I don’t see that ever changing.
I also get immense satisfaction from developing - new services in Cambridge to improve the outlook of patients that we serve. New services and innovation enable cutting-edge, highquality care delivery, and both are often a direct spin-off from research. This link advocates why we need more NHS clinicians participating in research. I have been lucky enough to see and take opportunities to successfully initiate or develop, and lead five local interventional services during my career so far: chronic total occlusion in 2013, BPA in 2015, TAVI in 2017, coronary sinus reducers in 2021, and excimer laser coronary atherectomy in 2023. Bringing these services online has acted as a series of career milestones that have kept me motivated, interested, and engaged clinically. Coronary reactivity testing is on the horizon for 2024, with acute pulmonary embolism and possibly stroke intervention to follow, if turf wars can be resolved amicably!
Alessia Callegari
Congenital Cardiology Fellow, Centre de Référence Malformations Cardiaques Congénitales Complexes-M3C, Hôpital Universitaire Necker-Enfants Malades, Assistance PubliqueHôpitaux de Paris (AP-HP), France; University Children’s Hospital of Zürich, Switzerland
Citation: EMJ Int Cardiol. 2024;12[1]:45-50. https://doi.org/10.33590/emjintcardiol/10304951.
Q1
What initially sparked your interest in paediatric cardiology?
My venture into paediatric cardiology began during my medical studies at the University of Padua, Italy. During my clinical rotation in paediatrics, I discovered the remarkable fact that children could survive with only one ventricle. Their treatment, or rather palliation, had been discovered only four decades earlier, leaving many questions open to debate, especially on the long-term management of these patients. I was incredulous at first, and decided to shadow a paediatric cardiologist examining a patient with a rare cardiac disease. To my amazement, upon entering the room, I found a teenager riding a bike to perform a functional test, who looked just like every other teenager. She wanted to be done with the examination, and go home to prepare for her planned ski weekend. Since nobody could tell her how many times she would be able to ski before being hospitalised again, she wanted to enjoy every second of her quality time. I was sincerely impressed from her disenchanted view on her reality, combined with genuine research for normality.
my first research project on the exercise capacity of patients with a single ventricle, and played a pivotal role in shaping my passion for paediatric cardiology. This mentorship added depth to my understanding of, and commitment to, evidence-based practice and research, combined with individualised patient-centred care.
As I progressed through my training in paediatrics at the University Children’s Hospital of Zürich, Switzerland, I solidified my commitment to this subspeciality, and completed my training last summer. While I explored the complexities of congenital heart challenges, and continued to perform medical research on patients with a single ventricle, I was driven by a sincere desire to contribute meaningfully to their wellbeing.
Q2You are primarily interested in paediatric interventional cardiology. What initially sparked your interest in this area?
I was stimulated to be part of the change, and inspire further females towards a similar path
Since my very first day of preschool, I was resolute in my decision to become a paediatrician and, as stubborn as I am, I did not back up from that plan. This experience sparked an additional profound interest for the subspecialty of paediatric cardiology within me. At that point, I met my supervisor Ornella Milanesi, who guided
I embarked on my journey into paediatric interventional cardiology during my training in Zürich, where I first witnessed the world of minimally invasive procedures for congenital heart defects in the cardiac laboratory, led by Oliver Kretschmar. The dynamic nature of paediatric interventional cardiology awakened my interest in this specialised field. In fact, I soon realised that many of these interventions do not depend on standardised techniques with dedicated material. Beside performing non-invasive
procedures, the role of the interventionalist is also to adapt the material to the patient; to rethink the intervention according to the specific anatomy; and to understand when the intervention should be stopped, and the patient referred to surgery.
The integration of cuttingedge techniques and evolving technologies, with a certain level of personal inventive and manual work, was very appealing to me. Moreover, the possibility of completing the diagnosis of a congenital cardiac defect, and performing firsthand the intervention that resolves that defect, was similarly engaging. Lastly, I felt that the team in my institution had a similar mindset to mine, and I enjoyed working there, which is also very important when work takes up most of your day.
My dedication to advancing paediatric interventional cardiology extended to an advanced fellowship at the Hôpital Universitaire Necker-Enfants Malades in Paris, France. This experience in a high-volume
centre is broadening my technical expertise, but also deepening my appreciation for the transformative potential of minimally invasive interventions in paediatric cardiac care.
Q3What do you think are the critical points of pursuing a career as a paediatric interventional cardiologist?
In the realm of academic meetings and discussions, there is often a predominant focus on success stories, creating an environment that tends to overshadow the inevitable challenges and setbacks that are integral parts of any professional journey. Acknowledging this reality, I approach my professional journey with a pragmatic perspective. The acknowledgment that success is not guaranteed, and that challenges are inherent in any ambitious pursuit, underscores my commitment to a realistic and grounded approach. The field of paediatric interventional cardiology is no exception, and while accomplishments are celebrated, it is equally important
to navigate the hurdles that come with the territory. While I cannot predict the trajectory of my career, I am earnestly working towards my goals, fully aware that difficulties are part of the journey. In this context, I have had the opportunity to meet other young paediatric cardiologists in a similar position, and learn how a community of practice can become the most relevant rescue net.
A further critical point remains that, in the context of interventional cardiology, females suffer a major underrepresentation. In fact, statistics from the adult interventional cardiologist show that only 4.5% of operators performing interventional procedures are female. The most ‘classic’ reason behind this relevant difference is the fact that such highrisk interventions in a highly competitive environment have historically been performed by our male colleagues. I was stimulated to be part of the change, and inspire further females towards a similar path, similarly to how
Only
Guiti Milani, the chief of the catheterisation lab at the Hôpital Universitaire Necker-Enfants Malades, has been an inspiring figure for me in this regard. Being part of this transformative journey is not only about advancing paediatric interventional cardiology, but also about contributing to a more diverse and inclusive future in the field.
Q4
In recent years, you have published several research studies. What would you say the key findings were?
Over the past year, our research has delved into various aspects of single ventricle patients' health. In fact, while surgical advancements have significantly improved shortterm survival, long-term morbidity and complications persist as challenges. The focus of our research was on emphasising the importance of considering non-cardiac factors in enhancing the long-term outcome of these patients. The importance of factors such as preserved respiratory function, welldeveloped pulmonary vascular bed, and peripheral musculature development, are highlighted in our publications.
diaphragmatic paralysis, scoliosis, a higher number of interventions, and lower BMI. We assessed respiratory function and volumes in a further cohort of patients with a single ventricle, and raised concerns regarding potential compression effects on the left main bronchus, originating from implanted stents in the pulmonary branches. In fact, patients with stents displayed a larger right-toleft ratio for the main bronchus area, suggesting a certain degree of bronchial compression. These findings underscore the need for further investigation into the respiratory parameters of this patient group.
One first multicentre, retrospective study examined the ventilatory function in patients with a single ventricle, revealing a high frequency of restrictive ventilatory pattern. This pattern, observed in 60% of patients, was associated with lower exercise capacity, and compromised quality of life. The study identified risk factors for ventilatory dysfunction, such as
The abnormal development of pulmonary vascular bed in patients with a single ventricle significantly impacts long-term outcomes. Insufficient crosssectional area of the pulmonary vasculature hampers the single ventricle circulation, and even minimal changes in pulmonary vascular resistance can cause significant alterations in cardiac output. Aggressive treatment of stenotic or hypoplastic areas, including percutaneous stenting, is deemed essential. A further study underscored the feasibility and safety of pulmonary stent implantation in cases of pulmonary stenosis, challenging potential reservations about adopting this approach. The growth patterns of pulmonary artery diameters post-stent implantation, especially the symmetric but limited growth with the contralateral side, offer valuable insights into the long-term effects of these interventions. Importantly, the results suggest that pulmonary artery stents should not be withheld when clinically indicated.
Peripheral muscular function also plays a crucial role in the context of a passive pulmonary flow, that
also relies on a properly functioning muscular pump. Patients with a single ventricle often experience decreased exercise capacity, due to clinical deconditioning and reduced muscle mass. Guidelines recommend physical activity, but patients frequently fall short. Training programmes positively influence exercise capacity and quality of life. Our study uncovered a surprising disparity between traditional indicators of heart function or exercise capacity, and the daily physical activity levels of patients with a single ventricle. Despite the complexities of their condition, only 18% of these patients met the recommended daily threshold for moderate-tovigorous physical activity. This finding is particularly intriguing due to the lack of correlation with conventional measures, emphasising the importance of considering broader aspects, such as quality of life and sleep quality, in understanding and promoting physical activity in this patient population.
In summary, our research results have brought forth a wealth of knowledge, spanning various non-strictly cardiological dimensions of single ventricle patients' health. These findings collectively contribute to a more comprehensive understanding of the challenges in managing these patients, while ongoing research remains crucial for guiding decisions on optimal timing, and considerations for interventions in this population.
Q5 Are there any developments that you have seen in your research that you are particularly excited about seeing translated into practice?
I am particularly enthusiastic about the advancements of our
investigation into predicting complications in the pulmonary arteries of patients with a single ventricle after surgery. Using a large patient database, we were able to create an algorithm to calculate a predictive score for anticipating complications in the pulmonary arteries after surgery (Glenn and Fontan surgeries). The independent risk factors that we observed were a larger ascending aorta, and a smaller left pulmonary artery.
The prospect of applying these findings to develop a preoperative risk-stratification is intriguing, and has the potential to improve how we approach single ventricle patients undergoing such surgeries. This project aligns with our overarching goal of contributing to the evidence base for optimising the care of children with complex congenital heart conditions. I am enthusiastic about integrating these research insights into clinical practice, and test the relevance of our predicting score in other institutions.
Q6
How have you seen the advent of new technologies, such as artificial intelligence (AI), significantly impact the field of interventional cardiology in recent years?
In paediatric cardiology practice, we have not seen any clinical changes deriving from AI, and our daily work activity has remained unchanged, as of yet. Even the answers of this interview were formulated by me, and not generated by an AI assistant.
Nevertheless, the integration of AI into adult interventional cardiology has brought about notable transformations, significantly enhancing various aspects of patient care, and
The focus of our research was on emphasising the importance of considering noncardiac factors
clinical workflows. For example, AI has been implemented in the analysis and interpretation of cardiac imaging in adults. Machine learning algorithms have demonstrated their proficiency in swiftly and accurately interpreting complex imaging data, such as angiograms and echocardiograms. Moreover, algorithms can assist in the precise measurement of anatomical features, and the identification of optimal routes for catheter navigation. This can not only expedite the diagnostic process, but also empower physicians to make more informed decisions during interventions.
However, it is important to note that when dealing with paediatric cardiology, this application of AI can be more challenging. The complexity and rarity of diseases in children pose unique obstacles. While the principles remain applicable, adapting AI technologies to the specific nuances of paediatric cases
requires careful consideration and ongoing research.
The move towards precision medicine has been another noteworthy impact in adult cardiology. AI's ability to analyse extensive datasets allows for the identification of patterns, and the prediction of individual patient responses to specific treatments. This facilitates a more personalised approach to interventions, optimising outcomes and risk assessment for each adult patient. This application of AI, if ethical consent is provided from all participants, could be of the highest value in our context of high-risk interventions, but only if used on a multicentre scale. In fact, a single institution rarely has enough patients for similar assessments.
In conclusion, AI has made remarkable strides in adult interventional cardiology, revolutionising diagnostics,
treatment planning, and risk assessment. As for paediatric cardiology, although more challenging, ongoing research and adaptation are essential to fully unlock the potential of AI, in addressing the unique complexities of paediatric cardiovascular diseases.
Q7
In terms of research, where can we expect to see your focus lie in the coming years?
In the coming years, my research focus will continue to revolve around advancing the care and outcomes for patients with a single ventricle. One of the pivotal projects I am currently involved in explores a novel approach to optimise haemodynamic and clinical outcomes during the first stage of palliation for patients with hypoplastic left heart syndrome.
This project aims to evaluate the technical feasibility, the role
The complexity and rarity of diseases in children pose unique obstacles
of multimodal imaging, and the clinical outcomes of a totally percutaneous transcatheter technique, replacing traditional surgical procedures. The outcome study, that also involves computational fluid analysis and simulation, is being conducted at Hôpital Universitaire NeckerEnfants Malades.
These projects align with my overarching goal of contributing to the evidence base for optimising the care of children with complex congenital heart conditions. As I transition back to the University Children's Hospital of Zürich after my fellowship in Paris, I anticipate further collaborative efforts, in addition to our multicentric ongoing research initiative aimed at understanding and improving the coagulation profile of these patients.
Q8What are some points of emphasis you incorporate into practice, to be the best interventional cardiologist you can be?
I think it would be more correct to say, you ‘try’ to incorporate, especially since this is a list that describes the best clinical practice that I can imagine for a paediatric interventional cardiologist.
Patient-centred care should form the foundation of our approach. Understanding the details of the medical history, needs, and difficulties of each case, to tailor our medical approach to the patient’s specific circumstances, is of the highest relevance.
Recognising the complexity of congenital heart conditions when working closely with a diverse team of specialists, including other healthcare professionals, is necessary to enable a comprehensive and wellrounded approach to patient care. Furthermore, it is fundamental to recognise the limits of our techniques, to refer a patient to surgery without insisting on a percutaneous approach.
Continuous learning is also a cornerstone of this discipline. In the rapidly evolving field of interventional cardiology, we should commit to ongoing education and professional development, staying at the forefront of new techniques, technologies, and research findings. In this context, contributing to research that can improve patient outcomes and redefine standards of care should be pursued.
Having benefitted from valuable mentorship in my career, I am passionate about paying that back going forward. Engaging in mentorship activities, I wish to share knowledge and skills with the next generation of medical professionals, fostering a culture of continuous learning.
Quality improvement is another area of active involvement. Regularly reviewing outcomes, and seeking opportunities for enhancement in practice, allowing for adjustments and improvements in the delivery of care, are fundamental.
Upholding the highest ethical standards is non-negotiable. I believe that maintaining the trust and confidence of my patients and colleagues is essential for the integrity of my practice. Finally, compassionate communication should be promoted, since it ensures that patients and families feel heard, understood, and supported throughout their medical journey.
Through the integration of these principles into my daily practice, I aim to provide the highest standard of care, fostering positive outcomes, and an improved quality of life for my patients.
Damien Kenny
Consultant Congenital Cardiologist, Children’s Health Ireland at Crumlin, and Mater Hospital, Dublin, Ireland
Citation: EMJ Int Cardiol. 2024;12[1]:51-59. https://doi.org/10.33590/emjintcardiol/GEOM4810.
Q1
What initially led you to pursue a career in interventional cardiology?
I was doing general paediatrics for a while, and was just not motivated by it. I found the physiology around cardiology fascinating; congenital heart disease is so varied, so constantly challenging in relation to understanding the physiology, and I think working with children is very rewarding. The nice aspect of an interventional subspecialty is that it allows you to be able to fix stuff, and I like the concept of providing alternative therapies to surgery. I think the fact that we can do things without the trauma of opening somebody’s chest, and stopping their heart, was very attractive to me. In a field that is quite wide and varied, it provided that extra piece for me to be able to care for these kids, and to be able to provide a definitive therapy for them.
Then once you start, you get hooked because of the evolution and the growth in this field, and the people that work in it
I think it is an evolving specialty as well; it is growing all the time. There is a general push towards trying to do things less invasively, so patients recover more quickly. Particularly for kids, let’s say you are doing an atrial septal defect (ASD) closure, and they have their procedure, they wake up afterwards, they are back up in the ward, home that evening or the next day, and back to their
normal activities without too much stress or trauma. I think that was one of the really attractive aspects of it. Then once you start, you get hooked because of the evolution and the growth in this field, and the people that work in it. It is a really nice group of people internationally to be involved with. We have common goals, we work well together; there is a real commitment from industry and academic institutions to try and collaborate, and to try and achieve the goals. So, for all those reasons, I think it is a great specialty to work in, and I have been very lucky to partake in it.
Q2
Please elaborate on your recent collaboration with the University of Bristol, UK, and Rush University Medical Centre, Chicago, Illinois, USA, developing a tissue-engineered valve mounted on a bioresorbable scaffold? What are the key takeaway messages from this research?
I went to the USA in 2010, and we had an animal facility there, so it gave me the opportunity to work in a preclinical lab, which was exciting. My mentor that I worked with in Chicago was very supportive of us getting involved in some cutting-edge work. We had a surgeon, Massimo Caputo, who came to join us from Bristol, and we developed a collaboration in that setting. Massimo was interested in providing a more definitive therapeutic solution for kids who needed valve surgery; because if you are 2 years old and need a valve, then by the time you are 10, you have probably grown out of the valve. Whereas,
if we could develop a valve to implant minimally invasively into a child, that would integrate or grow with the child, we would have really solved a significant problem that we face in congenital heart disease. So, we created this collaboration between the academic institutions. We had a very visionary charity, called A Giving Heart Foundation, that helped us and supported the work through charitable funds. It was all of these things, and a healthy collaboration between myself and Massimo, that facilitated conceptually the design of a valve, and how we would bring it forward.
We used a polydioxanone scaffold made by a company called ELLACS (Hradec Králové, Czechia), designed for oesophageal strictures. They were happy enough to work with us to develop a polyurethane covering for the scaffold. Then we looked at several different tissue platforms to create the valve leaflets, which we then placed into a porcine model through a subxiphoid approach. That is how it evolved. We then looked at follow-up out to 3 months, and looked at tissue pathology at sacrifice. We found a
lot of inflammation precipitated by the bioresorbable scaffolds, and by the leaflets; so, although the leaflets were somewhat functional, they precipitated a quite profound inflammatory response. I think this is one of the challenges we face: how do you mitigate the inflammatory response? This is before we get to the tissueengineered part of the valve, and looking at what cell subtypes are going to be more appropriate for these valve platforms, going from myocardium onto valve, and then onto an endovascular surface. These are the sort of challenges that we were facing, from three different sorts of tissue planes on one of these valve platforms.
What we have learned is that it is very valid work, and it is not easy, but we need to continue to pursue it. I suppose there is not as much interest from the large valve companies to do this for transcatheter aortic valve implantation, or for aortic valve replacement, because those patients are older, and maybe one or two valves will last them for the rest of their life, as they are fully grown. It is unique to younger patients and children, and I think
there are three parts to it. There is the bioresorbable scaffold; there is the optimum tissue substrate to use; and then the third part is, what is the optimum tissueengineered cell type, or cell types, to be able to seed appropriately onto the tissue platform that you have used, so that it will integrate appropriately into that child, and grow with that patient? Probably what we learned was that it is certainly not as simple as it looks on the slide, but it is valid and worthwhile to pursue.
Q3
In 2018, you issued a warning about the need for further funding and resources at the Mater Hospital Adult Congenital Unit in Dublin, Ireland. Do you feel there are any unmet needs in awareness and service provisions for adult congenital care, and if so, how do you feel we can bridge this gap?
This is a great question, and probably one of the things I am most passionate about; and most frustrated by. Our services on the paediatric side are well supported and developed, although that has taken time to come to fruition. What we had not realised is that, by doing such a good job
We need to provide the least invasive interventions that have the lowest long-term footprint on the heart
on the paediatric side, most of these children are now surviving to adulthood, and they become adults with their own challenges, and needs that really are not adequately addressed by the paediatric service. The service in the Mater (Adult) Hospital has evolved haphazardly. Having said that, I still think we provide a good service, but the service is chronically underfunded. There is a tsunami of patients; we have 300–400 patients graduating from the paediatric service every year into the adult congenital service, with no funding to support those patients coming through. Apart from the numbers, the pathologies are becoming more and more complex. I feel often quite sad by the fact that these terribly brave individuals have faced adversity to a level we will never understand through their childhood, and then they get catapulted out into an adult service that is just not in any way developed, or supported enough, to meet their needs.
A lot of these patients have psychological issues, because if they are born with a single ventricle physiology, they realise that their lifespan may be limited in relation to some of their friends. They are being treated somewhat differently; they have multiple admissions into hospital, whilst their friends are going to parties. We do not have the support services to help address their needs, predominately their psychological needs. It is a very sad situation, and we have made multiple attempts to try and highlight this. Unfortunately, the
healthcare system where I work is predominantly driven by crisis management. Unless you are able to amplify the appropriate message, with the appropriate number of people, at the appropriate time, it is very unlikely, while you have many other services shouting about their deficiencies, that you are going to get heard. I am not saying that we are more important than any other groups of patients, but I do think it is tragic, and it really saddens me that this group of patients does not get the resources that they need.
Most of the services in the UK have four full-time equivalent consultant cardiologists to deliver care in similar sized units. Meanwhile, we have somewhere between 1.3–1.7 full-time equivalent consultant staff, dealing with a significant population that is growing, and no plans to change that. I think often, in the adult hospital, we are seen as a group that are an annoyance, rather than a group that are contributing, because we are seen as an appendage of a paediatric service that is placed in the adult hospital; but a 25-year-old who has a serious congenital heart defect is really a valid patient in that service. Again, I just think that is not right. If you gave me one thing, on a wish list, it would be a psychologist to help these patients understand their condition, and help them develop techniques to deal with the challenges they face; because I am not qualified to do that. We just do not have the resources
to be able to help these young adults.
Q4Having published over 140 peer reviewed articles, and co-authored 20 chapters in international textbooks, what topics in interventional cardiology do you feel merit greater research attention?
One of the things that I am very conscious of is the footprint we leave on the heart. Surgery leaves scar on the heart, which will have implications for the future. It is a very successful process, but we may only see potentially negative consequences in later life. So, we think by doing things less invasively, the footprint we leave is less than surgery; but when we put big metal devices in the heart, they also stay forever. Now, they are effective, but what implications will they have for 50-, 60-, and 70-year-olds? We need to provide the least invasive interventions that have the lowest long-term footprint on the heart; because ultimately, interventions at a young age probably have implications in the future, be that an arrhythmia, be that scar, or be that scar and arrhythmia. Even with the simple things, like closing off a hole between the top collecting chambers of the heart, we may need to try and get back into the left side of the heart when that patient is older. To do this we will need to cross the wall we have ‘fixed’, which is now complicated by having a large metal device there.
We are therefore pushing for the development of bioresorbable devices, the development of tissue-engineered solutions, and aspiring to provide more precise and personalised therapies for kids, so that the anatomical
variances that exist are not just homogenously treated with a single device. We should consider potentially 3D printing a bespoke model, stent, or device for a patient, so that they get a personalised, precise therapy for their defect; but there are huge regulatory issues around that. I think there are challenges with funding, because there simply are not the same number of patients, and probably not the same financial recompense for industry, for our group as there would be with large-volume interventions, such as coronary artery stenting, or a transcatheter aortic valve replacement in adults. So, these are the challenges we are going to face.
We should consider potentially 3D printing a bespoke model, stent, or device for a patient
I do think these goals are achievable. We have a very motivated group of people working in the field, and there are several people out there in industry who are inspired by the work we do, who realise that the innovative nature of our work has often provided a platform for the development of other devices that have had a wider and broader remit. This means that there is a potential to recoup some of the costs that maybe go into the original devices. For example, the first transcatheter valve implant, which has now been done many millions of times around the world, was performed in a 12-year-old patient in the pulmonary side by a congenital cardiologist in September 2000. This was 2 years before the first transcatheter aortic valve implantation was
done, which is now a multibillion dollar industry. So, there is value in the innovative nature of the challenges we face, and the skills learned are transferrable beyond the actual specialty.
Q5As Director of the Paediatric and Adult Interventional Cardiac Symposium (PICS/AICS), what has been your proudest achievement in this role to date?
I am very fortunate; as my mentor Ziyad Hijazi was the one who established this, I got involved in 2010, when I went to work with him. He is very generous, and let me get involved in a more meaningful way. PICS/AICS is the largest symposium dedicated purely to the interventional therapy of congenital heart defects, and we normally have up to 1,000 delegates attend each year, from over 60 countries. We do live cases, from usually nine or 10 sites, for each meeting, and I think it has provided different benefits. Firstly, it has provided a good educational platform for people to learn, not only
through didactic means, but also by seeing these cases live. The live cases are challenging to put together, and there is a huge onus to make sure that these are carried out appropriately and safely, that what we are showing is relevant to the audience, and that the operators are comfortable with what they are doing in a stressful environment, with people watching. We work closely with the U.S. Food and Drug Administration (FDA) in this regard.
There is also the networking aspect of the meeting, which has provided a platform for us to share ideas about different complex diagnostic or therapeutic issues that exist. I think one of the tragedies of the COVID-19 pandemic is that, although we had an online or hybrid meeting, it took away that ability to sit in a room with somebody and just problem-solve.
The third piece is allowing us to interact with industry. As much as we may not like to admit it, we cannot survive without
the support and input of our colleagues from industry; and so, the meeting has provided us the opportunity to have discussions about what we need, and how we can make devices better, and for that group of people to listen to us. That has been a fascinating part for me, the opportunity to travel all over the world, meet different people, and learn from them. I think the more you see, the more you travel, the more you learn, you will ultimately be better at what you do. Due to the success of the Symposium, we have now established a society, called the PICS Society, to provide a home for congenital interventional cardiologists all over the world. With this we can advocate for our patient group, develop guidelines and educational platforms, and have a number of different subcommittees that will actually look at the needs of our members and the patients we treat.
This has been going for several years now, and we have had a couple of guideline documents either published or being
developed. We have a Congenital Heart Academy, starting soon, where we’re taking 25 young interventional cardiologists in our field through a 2-year training module to expose them to all the technical, psychological, and emotional challenges of dealing with our specialty; and I think that is very exciting as well. There are many new challenges and opportunities that have evolved out of having the PICS Symposium, which have now extended beyond just a meeting or educational platform. I think this has been great for our specialty.
Q6Could you please elaborate on the Congenital Heart Academy? For the upcoming Symposium, can you also give us an insight into any research, or initiatives, that you are planning to implement?
The Academy is just about to start. We had over 100 applicants for 25 spots. I suppose it does not sound like a lot, but we are a small field, and so sometimes the success of the society provides its own challenges. How do we decide which 25 are
more worthy of the first tranche of places for the 2-year cycle? When we were doing it, we were keen to not just focus on how to close an ASD, but on how to deal with the complications of an ASD, how to run a team, how to focus on delivering care in difficult situations, and how to discuss some of the emotional challenges that exist with conflict. So, we have tried to expand it beyond just the technical sides of the specialty. One of the other things that we have established is an online communication platform, through a company called DocMatter, San Francisco, California, USA, which allows us to share clinical problems across over 500 members of the society. Members can post a clinical problem in a very secure format, share images of a particular lesion, and ask opinions from interventionalists and colleagues from all over the world. I think that has been a huge addition.
In relation to the Symposium, we had a meeting in Istanbul, Türkiye, in April of this year. It was the second time we have run this, because we were conscious that
we were USA-based and, as a society, we want to have a more international reach. I think some interventionalists, particularly from Asia and the Middle East, cannot travel to the USA, so we wanted to provide a regional PICS experience. So, that meeting, as I said, ran its second iteration this April, with live cases from several different local and regional sites. We looked at some of the challenges that are specific to that part of the world, and how can we learn from people in low- and middle-income countries who are performing these interventions on a shoestring budget; and how can we contribute to helping them evolve and improve. This brings learning to both sides.
And then, in relation to the Symposium in San Diego this September, again, we have live cases, and a number of different topics that we are looking at. For instance, how is advanced imaging helping us to make better decisions on delivering better care? How are alternative platforms like interventional cardiac MRI helping us avoid radiation exposure, and how are
newer devices allowing us to intervene on smaller and younger patients, premature babies that historically were deemed too small for interventions? How can we evolve collectively to allow us to overcome ongoing challenges, and provide a platform for us to have discussions with our colleagues from industry, to see how we can work together to face future challenges?
How are newer devices allowing us to intervene on smaller and younger patients
Q7What motivated you to co-found the Congenital Heart Intervention and Mission Support (CHIMS), an organisation committed to centralising and redistributing donated catheterisation equipment to developing countries? What changes have you seen implemented because of CHIMS since its formation?
When I was in the USA, one of the things that became evident was that there was a resource and a need, and they were not aligning. We also realised that there were several catheter laboratories across North America that were throwing out expired equipment that could be valuable to other areas of the world. The concept of trying to bring those all together into a central repository, providing an online platform for people who are going on charity missions to request specific pieces of equipment, and then for us to ship that equipment to them, was an unmet clinical need. That was where it started from.
We initially partnered with the International Children’s Heart Foundation in Memphis, Tennessee, USA, and had good success. One of the things that I would like to do is bring in the PICS society as we evolve and grow. Having an international central repository, with online support, can allow people doing interventions in countries without the resources they need, to get online and request what they need from someone who has it. I think we need to broaden our thought processes around how achievable this is, and, in this small global world that we have, that is really where we would like to get with it. We have supported several missions, but I do not think it has taken off to the extent that I would like to have seen as yet. I am very committed to trying to, because when you look back on your career, and you think “I’ve closed ‘x’ amount of holes,” or “I’ve done this,” it is ultimately the infrastructure you leave behind, and the people you train, that are the most important things that you’ll achieve throughout your career. So, that is something that I would like to see through to the end.
Q8
For the next few years, what are the specific targets you have for CHIMS?
I would like to see a dedicated funded repository in at least North America and Europe. I would also like to see a welldeveloped online platform, through the PICS Society, to allow people to request online for specific pieces of equipment that may be present in a repository. Then, I would like to have a seamless process, whereby that piece of equipment could be shipped free of charge, to that particular institution, to be able
to deliver that therapy. And then finally, collect information around how effective the service was in meeting the needs, so that have a feedback loop in relation to the service itself.
Some of that is going to require some degree of funding, and we have had several volunteers. Kathleen Nolan, who is one of my nursing colleagues in the USA, has been amazing in supporting and keeping this afloat in the USA, and we will continue to need people who commit to that. Because of the nature of the work we do, I think there is great commitment and understanding of those less fortunate; to the point that most of us would have done charity missions somewhere in the world, despite busy clinical schedules in our own environments. Therefore, it is just about having better organisational skills to put it all together, so that it runs seamlessly. It just needs a bit more time, and funding, to be able to get to that point; but I do not see it as insurmountable because there is good will, and I think it is worthy and valid. It is doable.
Q9You recently coauthored the paper ‘Current status of transcatheter intervention for complex right ventricular outflow tract abnormalities.’ What were the key learning points from this article, and how do these findings contribute to the existing literature of valve therapy?
The right side of the heart is often seen as more relevant to congenital heart disease, whereas the left side of the heart is often seen as an acquired or structural problem. I do not think that is necessarily true; but we have an interest in the right ventricular outflow tract disease, because we see a lot of it in patients with
congenital heart disease, and I think adult cardiologists who are dealing with acquired structural heart disease do not see that much of it.
Because I have a practice that goes from very young patients to very old patients through the adult congenital services, it is understanding the downstream effect on patients as they get older, and having that 360 degree view of the lifetime management of right ventricular outflow tract disease is important. Yes, we can deal with obstructions to outflow in young babies now by putting stents in, but what implications does that have for the following surgery that may be inevitable, or the next transcatheter intervention that may be available, if that stent does not grow with the patient? And now we have a problem that we have created rather than solved. Even if they have surgery, what can we do, surgically, to promote longevity for that patient, in relation to their right ventricular outflow tract? How can we facilitate a less invasive therapy for that right ventricular outflow tract when it ultimately becomes dysfunctional? How can we join up our thinking in relation to the intervention, and hear how that impacts upon the next intervention? And how do we, as surgeons, interventionists, cardiologists, come together to say: “How do we map out this patient’s therapies over the course of their life? How do we make a decision that is going to be good, not only at this point in time, but also as they get older, so that we give them the best personalised, precise therapy for their particular type of condition, with the best physiological and anatomical outcome?” This then provides the best long-term survival for them, with the least amount of interventions.
We started off looking after babies and young children, and did not think: “What is this going to mean when they are 30-, 40-, and 50 years old?” We were thinking to just get on with the intervention. We are now seeing that what we have created here are implications for when they are older. So, we may need to modify our therapy, so that they get better long-term outcomes. I think that is really going to be a challenge for us, and the reason this hasn’t been part of our psyche to date is that we are only learning now that these patients are surviving longer into adulthood, and hoping for a normal life expectancy and quality of life. Therefore, our initial interventions should not only provide immediate, effective results, but longer-term sustained benefits as well.
Q10 Are there any notable innovations on the horizon of the field of interventional cardiology that are of particular interest to you?
Again, the most exciting prospect is personalised medicine through 3D-printed bespoke devices for a specific anatomical lesion, optimising lifetime management, and ensuring that we have a broader viewpoint on the therapies that we deliver. I think that feeds into some of the first three points that I have previously mentioned. I think greater collaboration between surgeons and interventionists that does not become ego-driven is key; it is all about the job we do collectively, to deliver the
best outcomes that we can. You have to invest in bringing people together, you have to get them to communicate and share problems; if we are only ever talking to each other, we are only going to be limited in the solutions that we come up with. When we run the PICS Symposium, we always invite surgeons to our meeting, giving a counter argument to our confirmation bias. It is very refreshing, because in a clinical setting, when we sit around to try and figure out solutions for patients, there is always a wide spectrum of disciplines within the room: surgery, non-invasive and invasive cardiology, and so on. Ultimately, when we are sitting in meetings, we should be trying to mimic that as much as we can.
The last piece is getting good data; data is so important. Historically, we have struggled, because we have a heterogeneous group of patients, and a heterogeneous group of lesions. It is hard to get large datasets on small numbers of disease entities like adult cardiology. That is why international registries are so vital, and dealing with General Data Protection Regulation (GDPR), particularly when you have different rules in North America and Europe, can be challenging, but again, not insurmountable. I think we will only learn by collecting data, reviewing that data, and saying: “Okay, maybe there’s a different way we should be looking at this.”
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Reinfection Rates Following Cardiovascular Implantable Electronic Device Reimplementation Post-device Primary
Infection
Editor's Pick
My Editor’s Pick for this year’s edition of EMJ Interventional Cardiology is a compelling reviewon cardiovascular implantable electronic device infections. The authors, Onyekachi Emmanuel Anyagwa et al., examine the diagnostic challenges of these infections, which affect 1 in 20 patients within 3 years of device implementation. The study provides valuable insights into prevention, diagnosis, and management of cardiovascular implantable electronic device infections in an ageing, medically complex patient population.
Dr Pablo Sepúlveda
Interventional Cardiologist, Division of Cardiovascular Diseases, Pontificia Universidad Católica de Chile, Santiago, Chile
Authors: Onyekachi Emmanuel Anyagwa,1 *Fatema Aliasger Rampurawala,2 Lama Alchaar,1 Taymaa Gharib,1 Miyukta Ravuri,1 Kulsum Fatima,3 Namrata Mishra,1 Rutvi Bhatt,4 Maha Prathiksha Arul Essakkiraj,1 Rajeeka Singh Tak,1 Maha Kassem1
1. New Vision University, Tbilisi, Georgia
2. David Tvildiani Medical University, Tbilisi, Georgia
3. Tbilisi State Medical University, Georgia
4. Caucasus International University, Tbilisi, Georgia *Correspondence to fatemaaliasger0786@gmail.com
Disclosure: The authors have declared no conflicts of interest.
Acknowledgements: The Georgian International Medical Students Society (GIMSOC) has provided this opportunity by giving their guidance and assistance throughout the research. The authors extend their gratitude to this organisation and its co-founders, Anyagwa, Singh Tak, and research director Kassem for the unwavering support throughout.
Citation: EMJ Int Cardiol. 2024;12[1]:62-70. https://doi.org/10.33590/emjintcardiol/11000027.
Abstract
Cardiovascular implantable electronic device (CIED) infections have become an increasing problem around the world, affecting one in 20 patients within 3 years of device implementation. Prevention of reinfection following CIED reimplantation is a prominent challenge. One of the most difficult aspects of managing CIED infections
is the complexities of their diagnosis: with the complexities of many infections, timely and correct diagnosis becomes complicated, frequently causing delays in commencing proper therapy, and worsening disease severity. As patients receiving CIED therapy are now older, and possess significant comorbidities, they are at a higher risk of infection. The American Heart Association (AHA) has issued a statement to educate clinicians about CIED infections, and the required care for those with suspected or diagnosed infections. To prevent an infection from spreading, it is important to isolate the causative pathogen and perform testing for susceptibility, which is required for crucial choices, including routes and duration of antimicrobial therapy. This review aims to serve as a valuable resource for healthcare professionals, by synthesising current knowledge and best practices; and providing insights into preventive measures, diagnostic challenges, therapeutic strategies, and evidence-based approaches to diagnose and improve the management of CIED infections in an ageing and medically complex patient population.
Key Points
1. With the growing challenges that arise among CIED recipients, especially within the ageing and medically complex patient population, understanding the reinfections that occur in at least one in 20 patients has become pivotal.
2. This review aims to serve as a valuable resource for healthcare professionals, by synthesising current knowledge and best practices, and providing insights into preventive measures, diagnostic challenges, therapeutic strategies, and evidence-based approaches to diagnose and improve the management of cardiovascular implantable electronic device (CIED) infections.
3. Reimplantation after more than 72 hours may increase the chance of reinfection, underscoring the significance of prompt action. The issues that must be addressed to manage CIED reinfections include reimplantation timing, patient comorbidities, and the interaction of systemic and surgical factors. To ensure effective management, continuous efforts must be made to improve infection prevention and treatment procedures.
INTRODUCTION
Cardiovascular implantable electronic devices (CIED) are a group of high-end medical hardware, used to monitor and regulate the activity of the heart. These include pacemakers, implantable cardiac defibrillators, and cardiac resynchronised therapy devices.1 These devices are placed into the patient’s body, usually in the chest region, and are connected to the heart via tiny cables called leads. Myriads of heart conditions with deranged electrical impulse activity are treated with placement of CIEDs.2 CIEDs are used for heart failure, bradycardia, and tachyarrhythmias, such as ventricular tachycardia and ventricular fibrillation, as a choice of management. To examine the need for devices, a thorough examination by cardiologists and electrophysiologists is necessary, together with information about the patient’s overall health.3
The use of CIEDs has proven to be beneficial, and increase patient longevity.4
There are a number of potential threats with CIEDs, some of which may require removal of the device, and reimplantation. This is considered in case of power unit failure, or device life that has reached its end, device malfunction, and infection at the site of implantation.5 Implantation site infection has significant mortality rates.6 CIED infections can occur by two major mechanisms, the most frequent one involving contamination of the pulse generators or leads during implantation or manipulation. The second mechanism is a direct bloodstream infection, and can also be a direct lead seeding.7,8
Approximately one in 20 patients develops an infection within 3 years of implantation of CIED. In such cases, the CIED and all of its components should be removed due to post-device primary infection, and reimplantation of the device should be performed, following guidelines by the American Heart Association (AHA), European Heart Rhythm Association (EHRA), and European Society of Cardiology (ESC).9
Although many studies have examined the rate of infection after implantation of CIEDs, the study of reinfection rates after CIED reimplantation post-device primary infection remains unclear. This is the driving force and the objective of this narrative review.10
METHODOLOGY
This review aimed to investigate reinfection rates following CIED reimplantation postprimary device infection. To achieve this, a thorough literature search was conducted from the specified databases, including PubMed, Scopus, Google Scholar, Cochrane Library, Medline, and Embase, using a combination of medical subject headings and keywords such as "CIED", "postdevice reinfection", and "reimplantation". All articles chosen as references were published between 2017–2023, and addressed reinfection rates and related factors. This methodological approach ensured a thorough examination of the current literature on CIED reimplantationassociated reinfection rates, facilitating a comprehensive understanding of this critical aspect of cardiac device management.
BACKGROUND
CIEDs represent cardiac rhythm management tools aimed at enhancing patient quality of life, and increasing patient survival. These devices come in three major categories: pacemakers, implantable cardioverter defibrillators, and cardiac resynchronisation therapy (CRT) devices (CRT pacers or CRT defibrillators).3 The incidence of CIED infections ranges from 0.5–2.2%, and this variation is influenced by a variety of factors, including patient demographics, device type, time since implantation, sex, chronic corticosteroid usage, presence of chronic obstructive pulmonary disease, diabetes, heart failure, and malignancy.11
In one of the largest contemporary prospective cohort studies, it was discovered that patients who had a reimplanted device faced a 1.8% risk of repeat reinfection.12 In February 2018,
out of the 280 studies screened, the incidence rate of CIED reinfection was determined to be 0.45% per year. Furthermore, the studies indicated that delaying the time to reimplantation was associated with an increased likelihood of reinfection.13
EPIDEMIOLOGY
In the USA, more than half a million different subtypes of CIEDs are inserted each year, with more than 4 million inserted between 1993–2008. For the first implantation, risk of infection ranges from 0.5–1.0%. For device removal, reimplantation, or upgrade, risk ranges from 1–5%. Early infections typically result from the implantation procedure itself, whereas late infections typically happen in patients who are already ill, or as a result of a process that eventually crosses a threshold of clinical significance. Infective endocarditis occurs as a result of procedures affecting the cardiac blood vessels, generator pocket, or cardiac tissues. The timing of CIED infection appears to be bimodal in distribution.14-16
The most frequently reported aetiology of CIED infection is coagulase-negative staphylococcus (range: 40–70%), followed by Staphylococcus aureus (range: 9–30%), and Gram-negative bacilli (range: 11–20%). The incident rate of reinfection following initial management of CIED infection is not insignificant. Findings from a systematic review and meta-analysis suggest that time to reimplantation affects rates of reinfection, when device reimplantation occurs at ≤72 hours, compared with >72 hours.14,15,17
PATHOGENESIS
Pathogenesis of repeated infection postreimplantation involves a complex interplay between the device, microbe, and host. Various risk factors related to the patient, device, and microbial virulence factors influence CIED infection development. Biofilm formation is a critical virulence factor that hinders the immune response, limits antibiotic effectiveness, and renders bacteria less susceptible to treatment.18,19
There are two basic mechanisms of infection development: bacterial contamination during implantation, and hematogenous seeding from a distant infection source.18,19 Bacterial contamination can occur during surgery, or perioperatively, either from handling the device, or through airborne exposure in the operating theatre. Hematogenous seeding is less common, and involves pathogens travelling through the bloodstream to the device.18,19
Infections often begin with contamination during implantation, emphasising the importance of surgical site prophylaxis. However, hematogenous seeding can also lead to device infections, with S. aureus posing the highest risk in this scenario. While there is a conceptual separation between local device pocket infection, and infection involving leads and bacteremia, it can be challenging to distinguish between the two in practice. Bacteria can migrate from the generator pocket along leads, reaching intracardiac structures.18,19
The MEDIC study, involving 434 patients with CIED infections at institutions in the USA, Spain, and Germany, from 2009–2012, aimed to assess the risk of repeat infections after CIED reimplantation, and evaluate reimplantation strategies. Participants underwent various tests upon admission. Device removal was attempted in most cases, and the timing varied. Bacteriology analysis and antibiotic therapy followed. Within 6 months, only four out of 11 patients who relapsed had initial device removal and reimplantation, resulting in a low repeat infection rate (1.8%). Patients who did not have device removal had worse outcomes, with higher mortality, repeat infections, and chronic antibiotic use. Those with device removal had better outcomes, with a high proportion remaining infectionfree.10 Limitations included the short followup period, potential missed infections after the study, and no differentiation between relapse and reinfection. There was also a referral bias, as all institutions were tertiary referral centres.20
Microbial virulence factors, which contribute to the formation of CIED
infections, pose a significant challenge for the management of CIED infections, due to the ability of staphylococci to adhere to devices; formation of biofilms that are antibiotic-resistant; and the presence of small-colony variants with reduced susceptibility to antibiotics, and increased pathogenic traits. The ability of staphylococci to form a multilayered biofilm becomes a major limitation, as it traps bacteria, making them dormant and less susceptible to antibiotics. This microbial persistence leads to high relapse rates, and increased mortality if the infected device is not removed. Additionally, the difficulty in isolating and culturing pathogens embedded in biofilms poses challenges for accurate diagnosis and treatment.18,19
DIAGNOSIS
It is important to perform a diagnostic workup for suspected CIED infection. During reoperation, a complete blood count, erythrocyte sedimentation rate, and levels of C-reactive protein and procalcitonin must be obtained. Two sets of blood samples should be obtained before antibiotic therapy. The routine blood samples are sent for culture, for recovery of both aerobic and anaerobic bacteria. For culturenegative CIED infections, especially in the case of central venous catheters and immunocompromised hosts, special fungal mycobacterial blood cultures can help isolate the causative pathogen. Device infection can occur from generator contamination or leads during the CIED system implantation/replacement. This depends on the causative organism type, and the onset timing of bacteremia from the date of implantation of the device.20
Patients with CIED infection have the four following scenarios: pocket erythema, swelling, discomfort, drainage, erosion, and local pain, which are the most common signs; fever and no local changes at the generator pocket site; bacteremia and no local changes at the generator pocket site; and lead thrombus or vegetation on echocardiography.20
Diagnosis is typically confirmed using an echocardiogram, which showslead vegetations. Transoesophageal echocardiogram has a better sensitivity compared to transthoracic echocardiogram in detecting CIED infections. Serial echocardiograms can be warranted, as some lead masses are asymptomatic, and up to 13% of patients have this. In these cases, the masses usually represent fibrin sheath, and do not increase the risk of infection.21
MICROBIOLOGIC DIAGNOSIS
Coagulase-negative staphylococci and S. aureus are the major pathogens in 60–80% of reported CIED infections, followed by Gram-negative bacilli, fungi, polymicrobial and other gram-positive coccus infections, and culture-negative cases. All patients with suspected CIED infection should gain a thorough physical examination and laboratory evaluation.21 The new 2019 International CIED Infection Criteria created by the EHRA show erythema, pocket swelling, warmth, pain, purulent discharge/sinus formation or pocket deformation, threatened adherence and erosion, or exposed generator or proximal leads, as diagnostics of definite CIED infection. Intracardiac echocardiography is used for vegetation detection, and PET and CT scans can show abnormal activity inside the pocket, or along the leads, which suggests presence of CIED infection. Lead or pocket culture may be sufficient for microbiological minor criteria.22
MANAGEMENT
Device reimplantation at a remote anatomic site will increase the risk for operative mortality, or recurrent infection. Initial antibiotic therapy is required, for instance consisting of ampicillin plus gentamicin.23
In case of high probability of CIED infection, it is important to carry out blood counts, blood cultures, and a transoesophageal echocardiogram. Simultaneously, a pacemaker dependency assessment is required. If confirmed, temporary pacing can be performed, and this can be followed
by complete hardware removal and culture of pocket tissue and material.24
Additionally, enterococci can be resistant to the killing effects of cell wall active agents (penicillin, ampicillin, and vancomycin), and are impermeable to aminoglycosides. The combination of the two agents, a cell wallactive agent with a synergistically active aminoglycoside, is required to cure many invasive infections, such as body substance isolation, and infective endocarditis. Combination of ampicillin and gentamicin is normally the preferred choice. However, there have been more combinations tested, such as ampicillin and ceftriaxone, which are useful, and saturate low-molecular-weight penicillin-binding proteins. This combination is found to be less nephrotoxic, so it is useful for aged patients. It can also be useful for Enterococcus faecalis infective endocarditis.25
For successful treatment of definite CIED infection, complete removal is required. Antibiotic therapy can increase 30-day mortality several times. To treat isolated pocket infection, antibiotics are given for 14 days for bacteremia prior to new implantation. However, in the case of endocarditis, this requires 4–6 weeks of antibiotics.26 The antibiotic of choice is vancomycin in the case of antistaphylococcal resistance and oxacillin resistance. Alternatives can be nafcillin and cefazolin, found in oxacillinsusceptible staphylococcal strains.27
DISCUSSION
A number of multivariate studies and meta-analyses have been conducted on reinfection rates following CIED reimplantation. A study conducted by Chew et al.13 showed that, following the first treatment for CIED infection, the combined reinfection rate was approximately 0.5% per person per year. The significant heterogeneity seen within the pooled examination recommends the nearness of a few factors that can influence the rate of reinfection. Components may incorporate the nearness of bacteremia, reaction to treatment, or persistent components, such as the nearness of immunosuppression.28
Since the risk of infection was examined based on the time of reimplantation, a time of >72 hours was associated with a fourfold higher incidence, compared with reimplantation at ≤72 hours. Using a cut-off time of 1 week, no difference in reinfection rate was observed between the time required for device reimplantation. The greater frequency of comorbid diseases in the respective research populations, or the high percentage of systemic infections necessitating additional time to cleanse the bloodstream of bacteremia, may be the cause of the higher reinfection rate correlated with a time to reimplantation >72 hours. The proportions of reported endocarditis, lead vegetations, or bacteremia, compared with localised pocket infection, were significant factors that the authors were unable to account for at the meta-regression level.28
The MEDIC study prospectively enrolled subjects at multiple institutions in the USA and abroad with CIED infections. Boyle et al.10 stated that the timing of device reimplantation did not appear to alter reinfection rates, despite the considerable variation in medical practice that was discovered by this investigation. The authors hypothesised that a variety of other risk variables may play a larger influence on assessing infection relapse rates than decisions regarding the time of reimplantation, with the constraint of a relatively small sample size and restricted follow-up.10
In a multivariate study of left ventricular assist devices (LVAD), Narui et al.29 showed age as a predictor of repeat infection, where younger age was a significant predictor of recurrent infection. The mechanism is not immediately evident, and has not been documented before. The fact that younger patients were more likely to have an implantable cardiac defibrillator may be a confusing factor. Despite not being a statistically significant predictor of repeat infection, this component did have a tendency in that direction. Another aspect revealed by this study indicated that CIED reimplantation on the same side as the initial site, particularly beyond a 3-month post-extraction period, was identified as
an independent predictor for recurring infections. Individuals undergoing a second CIED implantation on the original side exhibited an increased likelihood of infection during the follow-up period. The majority of these reimplantations occurred more than 3 months after the extraction procedure, and a minority involved pocket infections as the recurrent issue. This highlights a significant risk associated with reimplantation on the same side, even with a substantial time gap after CIED removal.29
In a study by Riaz et al.,30 individuals with CIED infections were examined while using an LVAD. Three of the patients only had pocket infections, and the other three developed CIED endocarditis after contracting an LVAD infection. Although the three patients with CIED endocarditis continued to take long-term suppressive antibiotics, five out of six patients were still alive after a median follow-up of 15 months. The LVAD driveline provides a channel from the exterior environment to the inside area, which is probably why these patients appear to have a bad prognosis. In one prospective research study, the median period from LVAD implantation to infection was 68 days, and the percentage of LVAD infection was 22%. Therefore, LVAD provides both source and reservoir of infection, and CIED removal does not fully address either of these factors.30
A study by Yu et al.31 showed that there are still worries about an elevated probability of recurrent infection in patients who have already had a device infection, despite the existence of evidence-based support for the effectiveness of using resterilised CIEDs.
In this study, the authors examined the incidence of infection relapse in patients who had previously had CIED infections, debrided their devices, and then had a new or resterilised CIED implanted. The authors discovered that there was not a significant difference in the rate of spreading infection with either device, and that either new or resterilised CIEDs had low relapse rates. This study is the first that the authors are aware of that specifically addresses the use of resterilised CIEDs in patients who have a history of device infection.
Additionally, the authors used a subpectoral muscular implantation method that puts the device deep within the ipsilateral pectoral muscle.31
PREVENTION
Contamination during implantation, frequently from the patient’s skin flora or airborne particles in the operating theatre, is the primary source of CIED infections. This contamination causes an internal infection, which spreads along the device’s leads, and may result in bloodstream infections that could eventually advance to systemic infection, and endocarditis.32
PRE-PROCEDURAL ACTIONS
Site Preparations
According to the Centers for Disease Control and Prevention (CDC), a surgical site infection in a clean incision typically occurs at a rate of ≤1%.33 Surgery site preparation must be given top priority if this objective is to be reached. This involves using antiseptic cleaning techniques involving chlorhexidine and alcohol, choosing electronic hair trimming over shaving, and making sure to wear the proper gowns and masks.34
To reduce the chance of infection, the timing and prescription for a given device should be carefully considered. Instead of ignoring an elevated risk for a disease that could have been prevented, delaying implantation, and allowing time for preventive measures, is preferable.35
Medications and Comorbidities
The treatment of concomitant disorders can help lower the risk of device-related infection problems because a significant percentage of patients getting CIEDs are older, and have a heavy comorbidity burden.
The rate of infection is not related just to diseases, but also to the drugs taken by the patient, especially corticosteroids and antithrombotic medications, which may increase the risk of infection.35
Prophylactic Antibiotics
According to systematic reviews and meta-analyses, prophylactic intravenous antibiotic therapy, such as intravenous cefazolin use before surgery, is the gold standard of care for preventing CIED infection, and reduces the relative risk of device-related infections by 70%.36
During the entire period that the incision is open and susceptible to bacterial contamination, optimal prophylaxis ensures that adequate concentrations of a suitable antibiotic are available in the blood, tissue, and wound. The antimicrobial agent should be effective against micro-organisms that are expected to be present during surgery. The patient’s normal bacterial flora, and the hospital’s microbiological ecology, should be least negatively impacted by the choice and timing of antibiotic prophylaxis.29
Intraoperative Procedures
As preventive measures, factors such as a proper ventilation system, air quality improvement, limited number of people, and temperature management during the operation, should all be taken into account. Furthermore, glove changing before dealing with the generator, and when handling the patient, may lower the risk of infection.36
Haematoma Prevention
Proper surgical procedures should be used to prevent haemorrhages. Avoiding pocket haemostasis should obtain special attention, especially in individuals who have a higher risk of bleeding,37 which could be ensured by using electrocautery pressure dressings, and preventing heparin-containing products.
Local Intraoperative Antibiotics
Other than the administration of preoperative antibiotics, clinicians should consider using a mesh envelope impregnated with minocycline and rifampin in high-risk patients, as major CIED infections were shown to be 40% less common when an antibacterial envelope was used in addition to standard of care infection-prevention methods. Patients who received the envelope did not experience
any more system- or procedure-related problems than patients who did not.38
Postoperative Procedures
The use of prophylactic antibiotics prior to surgery has been advised by the AHA and Heart Rhythm Society (HRS) because it has been linked to a decreased incidence of CIED infections.19,39 The PADIT trial, which investigated the clinical efficacy of using additional antibiotics to lower device infection rates, found that there was no benefit to incremental postoperative antibiotic use.40 Operating rooms and electrophysiology/catheterisation laboratories must adhere to sterile procedural standards, as for other surgeries associated with implants.41
CONCLUSION
This comprehensive review has clarified the critical concern surrounding reinfection rates after the reimplantation of CIEDs following primary device infections. The information presented here highlights the difficulty in treating CIED infections, which present a significant challenge to modern healthcare.
The likelihood of reinfection is significantly influenced by the date of device reimplantation, and several risk factors, including patient comorbidities. Reimplantation after >72 hours may increase the chance of reinfection, according to studies, underscoring the significance of prompt action. Reimplantation timing, patient comorbidities, and the interaction of systemic and surgical factors are only a few of the complicated issues that must be addressed to manage infections from CIEDs. In order to manage CIEDs effectively, continuous
References
1. Physiopedia. Cardiac implantable electronic devices (CIEDs). Available at: https://www.physio-pedia.com/ Cardiac_Implantable_Electronic_ Devices_(CIEDs). Last accessed: 17 January 2024.
2. Baher A, Valderrabano M. Management of ventricular tachycardia in heart
efforts must be made to improve infection prevention and treatment procedures, informed by ongoing research, while taking into account the practical challenges that come with their implementation.
This review further highlights the complex nature of CIED infections, where systemic and surgical variables both affect the total risk. In order to reduce the likelihood of CIED infections, prevention techniques such as suitable site preparation, prophylactic antibiotics, and local intraoperative antibiotics have been proposed. Nevertheless, obstacles including patient variability, resistance to antibiotics, and sensitivities in the surgical setting make it difficult to effectively apply preventive measures. Given the inherent constraints, a nuanced strategy is necessary.
To stop the spread of CIED infections, the causal pathogen must be isolated, and extensive susceptibility testing must be performed. This crucial phase is essential for making educated judgments about the type, route, and duration of antimicrobial therapy. The importance of evidence-based approaches cannot be overstated in helping doctors through the complexities of CIED infections, and ensuring optimal patient outcomes.
This review offers helpful insights for clinicians, researchers, and policymakers working to improve patient outcomes and lessen the burden of CIED-related complications in cardiovascular medicine, by thoroughly analysing the existing research, and investigating various aspects of CIED infections. In order to address this ongoing issue in cardiac care, more study and ongoing efforts in infection prevention and treatment are required.
failure. Methodist DeBakey Cardiovasc J. 2013;9(1):20-5.
3. Abi-Samra FM. Cardiac implantable electrical devices: bioethics and management issues near the end of life. Ochsner J. 2011;11(4):342-7.
4. Richardson CJ et al. Surgical techniques, complications, and long-term health effects of cardiac
5. Cleveland Clinic. Cardiac implantable electronic device replacement. Available at: https://my.clevelandclinic. org/health/treatments/16837-cardiacimplantable-electronic-devicereplacement. Last accessed: 5 September 2023.
6. Imberti JF et al. Low occurrence of infections and death in a real-world cohort of patients with cardiac implantable electronic devices. J Clin Med. 2023;12(7):2599.
7. Da Costa A et al. Role of the preaxillary flora in pacemaker infections: a prospective study. Circulation. 1998;97(18):1791-5.
8. Blomström-Lundqvist C et al. European Heart Rhythm Association (EHRA) international consensus document on how to prevent, diagnose, and treat cardiac implantable electronic device infections—endorsed by the Heart Rhythm Society (HRS), the Asia Pacific Heart Rhythm Society (APHRS), the Latin American Heart Rhythm Society (LAHRS), International Society for Cardiovascular Infectious Diseases (ISCVID) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Europace. 2020;22(4):515-49.
9. Heart.org. National CIED infection initiative [Internet]. Available at: https://www.heart.org/en/professional/ quality-improvement/national-ciedinfection-initiative. Last accessed: 5 September 2023.
10. Boyle TA et al. Reimplantation and repeat infection after cardiacimplantable electronic device infections: experience from the MEDIC (Multicenter Electrophysiologic Device Infection Cohort) database. Circ Arrhythm Electrophysiol. 2017;10(3):e004822.
11. Toriello F et al. Cardiac implantable electronic devices infection assessment, diagnosis and management: a review of the literature J Clin Med. 2022;11(19):5898
12. Rezar R et al. Infective endocarditis – a review of current therapy and future challenges. Hell J Cardiol. 2021;62(3):190–200.
13. Chew D et al. Timing of device reimplantation and reinfection rates following cardiac implantable electronic device infection: a systematic review and meta-analysis. BMJ Open. 2019;9(9):e029537.
15. Rodrigues CF et al. Early, delayed and late cardiac implantable electronic device infections: do the timing of onset and pathogens matter? J Clin Med. 2022;11(14):3929.
16. Cardiac Rhythm News. Low risk of repeat infection in reimplanted cardiac devices. Available at: https://
cardiacrhythmnews.com/low-riskof-repeat-infection-in-reimplantedcardiac-devices/. Last accessed: 17 January 2024.
17. Han H-C et al. Epidemiology of cardiac implantable electronic device infections: incidence and risk factors. Europace. 2021;23(Suppl 4):iv3-10.
18. Baddour LM et al. Update on cardiovascular implantable electronic device infections and their management. Circulation. 2010;121:458-77.
19. Ul Hag I et al. Etiology, pathology, and host-impaired immunity in medical implant-associated infections. J Infect Public Health. 2024;17(2):189-203.
20. DeSimone DC, Sohail MR. Approach to diagnosis of cardiovascular implantable-electronic-device infection. J Clin Microbiol. 2018;56(7):e01683-17.
21. Aguilera J et al. Imaging of cardiac device related information. Front Cardiovasc Med. 2021;DOI:https://doi. org/10.3389/fcvm.2021.729786.
22. American College of Cardiology; Chung EH. European consensus document on cardiac implantable electronic device infections. Available at: https://www.acc.org/ Latest-in-Cardiology/ten-pointsto-remember/2020/03/02/13/54/ European-Heart-Rhythm-AssociationEHRA. Last accessed: 1 January 2024.
23. Gavaldà J et al. Efficacy of ampicillin plus ceftriaxone in treatment of experimental endocarditis due to Enterococcus faecalis strains highly resistant to aminoglycosides. Antimicrob Agents Chemother. 1999;43(3):639-46.
24. Suarez K, Banchs JE. A review of temporary permanent pacemakers and a comparison with conventional temporary pacemakers. J Innov Card Rhythm Manag. 2019;10(5):3652-61.
25. Fernández-Hidalgo N et al. Ampicillin plus ceftriaxone is as effective as ampicillin plus gentamicin for treating enterococcus faecalis infective endocarditis. Clin Infect D. 2013;56(9):1261-8.
28. Polyzos KA et al. Risk factors for cardiac implantable electronic device infection: a systematic review and meta-analysis. Europace. 2015;17(5):767-77.
29. Narui R et al. Risk factors for repeat
infection and mortality after extraction of infected cardiovascular implantable electronic devices. JACC: Clinical Electrophysiol. 2021;7(9):1182-92.
30. Riaz T et al. Cardiovascular implantable electronic device infections in left ventricular assist device recipients. Pacing and clinical electrophysiology. 2014;37(2):225-30.
31. Yu C-M et al. Safety and efficacy of submuscular implantation with resterilized cardiac implantable electronic device in patients with device infection: a retrospective observational study in Taiwan. Open Forum Infect Dis. 2022;9(5):ofac100.
32. Palmisano P et al. Rate, causes, and impact on patient outcome of implantable device complications requiring surgical revision: large population survey from two centres in Italy. Europace. 2013;15(4):531-40.
33. Mangram AJ et al. Guideline for prevention of surgical site infection, 1999. Hospital Infection Control Practices Advisory Committee. Infect Control Hosp Epidemiol [Internet]. 1999;20(4):250-78.
34. Barbar T et al. Strategies to prevent cardiac implantable electronic device infection. J Innov Card Rhythm Manag. 2020;11(1):3949-56.
35. Blomstrom-Lundqvist C, Ostrowska B. Prevention of cardiac implantable electronic device infections: guidelines and conventional prophylaxis. Europace. 2021;23(Suppl 4):iv11-9.
36. Da Costa A et al. Antibiotic prophylaxis for permanent pacemaker implantation: a meta-analysis. Circulation. 1998;97(18):1796-801.
37. Masiero S et al.; SIMPLE Investigators. Wound haematoma following defibrillator implantation: incidence and predictors in the Shockless Implant Evaluation (SIMPLE) trial. Europace. 2017;19(6):1002-6.
38. Tarakji KG et al.; WRAP-IT Investigators. Antibacterial envelope to prevent cardiac implantable device infection. N Engl J Med. 2019;380(20):1895-905.
39. Kusumoto FM et al. 2017 HRS expert consensus statement on cardiovascular implantable electronic device lead management and extraction. Heart Rhythm. 2017;14(12):e503-51.
40. Krahn AD et al. Prevention of arrhythmia device infection trial. J Am Coll Cardiol. 2018;72(24):3098-109.
41. Haines DE et al. Heart rhythm society expert consensus statement on electrophysiology laboratory standards: process, protocols, equipment, personnel, and safety. Heart Rhythm. 2014;11(8):e9-51.
Should Coronary Artery Fistula Be Treated? A Review Throughout a Case Series
Authors: Mario Buitrago-Gomez,1 *Carlos H. Salazar,2
Natalia Sarmiento,3 Yefferson Salinas,3 Natalia Moscoso,3 Juan Quiros,3 Melquisedec Galvis,3 Javier Beltran3
1. Universidad Autónoma de Bucaramanga, Santander, Colombia
2. Universidad de Santander, Bucaramanga, Santander, Colombia
3. Los Comuneros Hospital Universitario and IDIME, Bucaramanga, Santander, Colombia
*Correspondence to chsalazart@gmail.com
Disclosure: The authors have declared no conflicts of interest. No funds were received to elaborate the present manuscript. Written, informed consent has been obtained from each patient, in line with the policy of the author’s institution for a case series. The author(s) confirm that written consent for submission and publication of this case report, including image(s) and associated text, has been obtained from the patient in line with COPE guidance.
Received: 18.10.23
Accepted: 04.01.24
Keywords: EMJ Int Cardiol. 2024;12[1]:71-77. https://doi.org/10.33590/emjintcardiol/11000007.
Background: Coronary artery disease (CAD) includes a wide spectrum of entities beyond the atherosclerotic disease. Coronary artery fistulas (CAF) represent an uncommon vascular abnormality that may cause several cardiovascular complications and symptoms, due to the coronary steal phenomena. Surgical or percutaneous closure should always be considered. The authors present a case series of patients with CAFs who developed cardiovascular manifestations, and underwent percutaneous closure safely and feasibly, with good clinical results.
Case Summary: Five patients with CAFs were treated from 2021–2023; three were male (60%), the mean age was 59 years, the most common symptom was chest pain, and two patients presented in the context of unstable angina. The authors documented pulmonary hypertension in three patients, none of them with haemodynamic compromise of right ventricle. Two of the patients had documented ischaemia or haemodynamic significance due to the CAF. Finally, in two cases, no CAD was noted in coronary angiography. Percutaneous closure was done using a 6 Fr or 7 Fr sheath; guiding catheter 6 or 7 Fr through a workhorse guidewire, a microcatheter was placed in the coronary origin of the fistula, closure was done using a liquid embolisation system or delivering coils into the defect. The number and length of coils may vary depending on the fistula’s size.
Discussion: The authors present five successful cases of percutaneous closure of symptomatic CAF, who presented with angina or dyspnoea as main symptoms. Once the diagnosis was made and further studies performed, the closure was decided based on the pulmonary hypertension or coronary steal phenomena.
Key Points
1. Coronary artery fistulas (CAF) are abnormalities that may lead to several cardiovascular complications depending on the size, flow, and anatomy of the defect.
2. The closure of the CAF can be performed percutaneously or surgically, with the latter being indicated if there is another condition requiring it.
3. The percutaneous closure of CAF is a safe intervention, and should be considered based on the size and symptoms associated with the defect.
INTRODUCTION
Coronary artery fistulas (CAF) are communications between a coronary artery and a major vessel or a cardiac chamber.1 More than 90% of CAFs have a congenital or sporadic presentation; nevertheless, coronary stent placement, heart surgery, chest irradiation, or coronary vessel diseases may lead to an acquired CAF.2 The prevalence is estimated in over 0.3% of congenital heart diseases.3 CAFs in adults are mostly asymptomatic, but the symptoms may vary depending on the size and haemodynamic compromise of the defect, varying from asymptomatic forms to dyspnoea and angina.4
In adults, closure is recommended in CAFs larger than two times the size of the normal vessel, regardless of symptoms; and medium or small when the patient develops symptoms like pulmonary hypertension, myocardial ischaemia, ventricular dysfunction, infective endocarditis, or cardiac arrythmias.4,5 Procedural devices vary from vascular plugs, duct occluders, detachable balloons, coils, covered stents, and chemicals, and the choice depends on the size of the defect, the clinical experience, and the delivery approach.6
Due to the lack of evidence, decision to treat may be difficult. Also, it is debatable whether the therapeutic approach should be surgical or percutaneous. Today, surgical closure is preferable in patients with other surgical intervention needed (valve replacement, coronary artery bypass grafting, tortuous or large defects).
Percutaneous closure is associated not only with less surgical complications (bleeding, infections, ischaemia, etc.), but also with fewer recurrence rates.5
This report included five patients who reported different cardiovascular symptoms and underwent coronary diagnostic angiogram. CAF was incidentally diagnosed (patient characteristics can be seen in Table 1). Closure decision was made by the cardiology team, depending on the symptoms and haemodynamic compromise of each defect, documented through diagnostic methods from transthoracic echocardiogram, non-invasive coronary stratification, or invasive fractional flow reserve measurement. Coronary anatomy before and after the procedure are illustrated in Figure 1 and Figure 2.
TIMELINE
1. Patients present to the hospital with symptoms and clinical findings that may suggest CAD.
2. Diagnostic coronary angiogram is performed with minimal use of contrast to obtain adequate images of coronary artery anatomy and diagnosing CAF.
3. Decision to treat is made within the cardiology team, based on the compromise of the defect.
4. Percutaneous CAF closure is performed to embolise the fistulas. Techniques and supplies may vary, depending on the size and placement of the defect.
Indication of closure Ischaemia with fractional flow
0.6
CAF origin LAD Intermediate ramus artery, LAD LAD
AF: atrial fibrillation; CAD: coronary artery disease; CAF: coronary artery fistula; LAD: left anterior descending artery; LES: liquid embolic system; LM: left main trunk; LVEF: left ventricle ejection fraction; min: minutes; MPA: main pulmonary artery; N/A: not applicable; SPAP: systolic pulmonary artery pressure.
CASE PRESENTATIONS
Case 1: Multimodal Invasive Diagnosis and Coronary Artery Fistulas
A 62-year-old male with a previous psychiatric disorder, arterial hypertension, and CAD presented with chest pain and shortness of breath. Transthoracic echocardiogram documented an ejection fraction (EF) of 45%, with no other significant findings. Coronary angiography documented a CAF from left anterior descending artery (LAD) to main pulmonary artery (MPA) and previously implanted stent in LAD. Intravascular ultrasound showed a mild stenosis in left main trunk with minimal lumen area in 10 mm2; no stent restenosis or disease progression was documented.
Giving the clinical manifestations, and despite the absence of progression of atherosclerotic disease evaluated by intracoronary imaging technique, the authors decided to assess the haemodynamic compromise of the CAF, and thus define the need of intervention at this level. Therefore, they advanced a pressure wire to LAD and performed fractional flow reserve distal and proximal to CAF, revealing haemodynamic significance due (0.69). Procedure was done using a 7 Fr sheath and a 7 Fr guiding catheter; through a workhorse guidewire, a microcatheter was placed in the origin of the CAF, then four coils were delivered to perform the successful closure (coil sizes: 2 mm x 8 cm, 2 mm x 4 cm, 3 mm x 8 cm, and 4 mm x 12 cm).
Table 1: Main clinical characteristics of the patients.
In further follow-up, the patient referred symptom improvement. No further reintervention was required, and no longer coronary percutaneous interventions have been needed to date yet.
Case 2: Comprehension of the Coronary Anatomy and its Implications
A 68-year-old male with history of sinus node dysfunction, arterial hypertension, and CAD came into the emergency department, presenting with an unstable angina. Transthoracic echocardiogram documented a preserved EF (58%), with no wall motion defects or severe valve diseases. Coronary angiography evidenced two CAFs, whose coronary origin were intermediate ramus and left anterior descending arteries to bronchial artery. It was decided to perform a percutaneous closure of the CAF to avoid coronary steal phenomena. Closure was performed using a 6 Fr sheath, 6 Fr guiding catheter, a workhorse guidewire, and a microcatheter was placed in the bronchial artery’s origin. The authors delivered a liquid embolic system with successful closure of the CAF, remaining distal flow to the bronchial artery. To date, the patient remains asymptomatic, without another reintervention.
Case 3: Non-invasive Diagnosis Essential to Guide Treatment
A 48-year-old female with history of arterial hypertension was referred to the hospital due to chest pain and bradycardia. A myocardial perfusion study revealed severe ischaemia of the anterior wall. Transthoracic echocardiogram evidenced a preserved EF (67%), and systolic pulmonary artery pressure (SPAP) of 35 mmHg without haemodynamic compromise of right heart chambers. The patient underwent coronary angiography with no evidence of CAD, but a CAF from LAD to MPA. Given the results of the non-invasive study, it was determined that the CAF was generating coronary steal to the anterior wall, and it was considered that it should be treated. Percutaneous closure was performed using a 6 Fr sheath, 6 Fr guiding catheter, and a workhorse guidewire; a microcatheter was placed into the coronary
origin of the CAF and then, two coils were delivered (4 mm x 15 cm, and 7 mm x 30 cm) to embolise the fistula. At follow-up, the patient remained asymptomatic, with a quality of life improvement, and no further interventions required.
Case 4: Coronary Artery Fistulas and Chagas
A 48-year-old female with history of Chagasic cardiomyopathy with an implantable cardioverter defibrillator presented to the emergency department with shortness of breath and syncope. Echocardiogram showed a preserved EF (70%), SPAP was 54 mmHg, and no valve disease or apical aneurysm was noted. No coronary atherosclerotic artery disease was documented in coronary arteriography, but there was a CAF from left main trunk to MPA. Despite pharmacological management and rehabilitation, the patient persisted symptomatic with New York Heart Association (NYHA) Stage III/IV. It was decided to perform percutaneous closure of the CAF. The authors performed percutaneous CAF embolisation using a 7 Fr sheath, 7 Fr guiding catheter, and a workhorse guidewire. They placed a microcatheter into the coronary origin of the CAF, and delivered four coils there (1.5 mm x 3.0 cm; 1 mm x 3 cm; 2 mm x 4 cm, and 1 mm x 4 cm). After discharge, she remained asymptomatic with NYHA I/IV.
Case 5: Reduced Ejection Fraction and Coronary Artery Fistulas
A 69-year-old male with previous CAD and atrial fibrillation presented to the hospital due to an unstable angina. Echocardiogram documented a moderated reduced EF (40%), SPAP of 35 mmHg, and a severe functional mitral insufficiency. During stress-echocardiography, inferior wall ischaemia was documented. Coronary angiography documented CAD in PDA, and a CAF from LAD to MPA. Given the context of the patient, with compromised systolic function added to the CAF in the LAD, and severe coronary disease in a PDA, the cardiology team defined percutaneous intervention of the CAD and CAF closure.
The authors performed the intervention with a 6 Fr sheath, 6 Fr guiding left and right catheter, and, with a workhorse guidewire, placed a drug-eluting stent in PDA. They then advanced the guidewire to LAD, and placed a microcatheter in the CAF, delivering a single 3 mm x 10 cm coil with successful closure. At follow-up, the patient was cardiovascular asymptomatic, without coronary reintervention or hospitalisation.
1: Angiographic characterisation of the CAF and the recommended therapeutic strategy.
A) Coronary angiogram of a CAF whose coronary origins are intermediate ramus and left anterior descending artery, and ends in bronchial artery. B–D) CAF from patients from LAD to MPA. E) Diagram of a CAF from LAD to MPA.
F) Flowchart of decision to treat, according to Al-Hijji et al.4
CAF: coronary artery fistula; LAD: left anterior descending; LM: left main.
Figure
Figure 2: Successful percutaneous embolisation of CAF using coils and liquid embolic system.
Case 2: comprehension the coronary anatomy and its implications
Case 3: non-invastive diagnosis essential to guide treatment
Case 4: CAF and Chagas
Case 5: reduced ejection fraction and CAF
A) CAF from intermediate ramus and LAD to bronchial artery closure procedure with LES. B) Preserved flow to bronchial artery after closure of the CAF (TIMI 3 flow). C) Preserved flow to coronary artery after closure of the CAF (TIMI 3 flow). D) CAF embolisation from LAD to MPA using two coils with sizes 4 mm x 15 cm and 7 mm x 30 cm. E) Successful closure of the CAF and preserved flow to the coronary artery (TIMI 3 flow). F) CAF embolisation from LM to MPA using four coils with sizes 1.5 mm x 3.0 cm, 1 mm x 3 cm, 2 mm x 4 cm, and 1 mm x 4 cm. G) Successful closure of the CAF and preserved flow to the coronary artery (TIMI 3 flow). H) CAF embolisation from LAD to MPA using a single 3 mm x 10 cm coil. I) Successful closure of the CAF and preserved flow to the coronary artery (TIMI 3 flow).
CAF: coronary artery fistula; LAD: left anterior descending; LES: liquid embolic system; LM: left main; MPA: main pulmonary artery.
DISCUSSION
CAFs are rare congenital or acquired abnormalities, associated to a wide spectrum of cardiovascular diseases. CAFs are classified depending on the anatomy of the defect, its origin and termination, its morphology and size, and its physiologic abnormalities. The most common CAF is coronary-pulmonary artery fistula. Other less common terminations are pulmonary veins, venae cavae, coronary sinus, bronchial vessels, or even coronary cameral fistulas.7
CAFs remain asymptomatic most of the time. However, they may lead to several unspecific symptoms, such as pulmonary hypertension, endarteritis, or myocardial ischaemia, whether due to early atherosclerotic CAD or coronary steal phenomena in the absence of CAD.1 As seen in previous cases, the haemodynamic compromise generated by the CAF has been corroborated with both invasive and non-invasive studies.
As the majority of CAFs remain asymptomatic, closure decision is controverted. Current evidence suggests closure should be considered when the CAF becomes symptomatic (documented ischaemia, ventricular dysfunction, cardiac arrythmia, or endarteritis), and its size is at least 1–2 times bigger than the normal size of the origin vessel; or when vessel aneurysm or rupture risk is present.4 Coronary-pulmonary artery fistula is indicated when a left-right shunt is documented.8 In the authors’ cases, the patients reported cardiovascular symptoms, and haemodynamic compromise was documented by invasive and non-
References
1. Kamal MM et al. Coronary artery to pulmonary artery fistula: catheter or scalpel? A case report. Int J Surg Case Rep. 2022;97:107416.
2. Mangukia CV. Coronary artery fistula. Ann Thorac Surg. 2012;93(6):2084-92.
3. Yun G et al. Coronary artery fistulas: pathophysiology, imaging findings, and management. Radiographics. 2018;38(3):688-703.
invasive studies, with LVEF reduction and pulmonary hypertension, with clear clinical improvement without reintervention after the therapeutic intervention.
Transcatheter closure is the most suitable choice in most of the cases, due to its minimal invasive techniques. Surgical closure should be only reserved for those patients who are meant to go into a concomitant cardiac surgical intervention, and estimate mortality risk is lower than 10%.7 Several percutaneous closure techniques have been described, depending on the access choice. The required equipment list includes 0.014 and 0.035 hydrophilic intracoronary wires, multipurpose catheters, microcatheters, and more.3 The authors’ percutaneous strategy, according to the anatomical characteristics, was performed by femoral access with 6 to 7 Fr according to the desired support. The usual workhorse guidewire and microcatheter were used to release the device or closure liquid. The authors’ experience, as well as experience in previously published literature, demonstrate that the use of a microcatheter through a 6 Fr or 7 Fr sheath, and the use of a coronary guidewire, may be sufficient to perform a successful percutaneous coil closure.9,10
As a case series manuscript, there are some limitations to declare. The first is due to the low incidence of the disease, which means that no large, randomised studies with statistic power are feasible. Also, confusion bias may be caused due to previous or concomitant cardiac diseases, such as CAD, sinus node dysfunction, atrial fibrillation, or Chagas disease.
4. Al-Hijji M et al. Coronary artery fistulas: indications, techniques, outcomes, and complications of transcatheter fistula closure. JACC Cardiovasc Interv. 2021;14(13):1393-406.
5. Buccheri D et al. Coronary artery fistulae: anatomy, diagnosis and management strategies. Heart Lung Circ. 2018;27(8):940-51.
6. Oto MA et al. Percutaneous approaches to closure of coronary artery fistulas. J Interv Cardiol. 2011;3(1)79-89.
7. Reddy G et al. Coronary artery fistulae. Circ Cardiovasc Interv. 2015;8(11):e003062.
8. Rubimbura V et al. Case report: coronary-pulmonary fistula closure by percutaneous approach: learning from mistakes. Front Cardiovasc Med. 2021;8:779716.
9. Akhtar A et al. Percutaneous coil embolization of coronary artery fistula complicated by refractory ventricular fibrillation and cardiogenic shock. JACC Case Rep. 2022;4(12):715-8.
10. Verdini D et al. Coronary-pulmonary artery fistulas. J Thorac Imaging. 2016;31(6):380-90.
An Incidental Finding of Asymptomatic Quadricuspid Pulmonary Valve at Autopsy: A Case Report and Comprehensive Literature Review
Authors: *Pushwant S. Mattu,1 Jamie Chen Yu Lee,2 Collin Pryma,2 Spencer D. Martin,2 Eric C. Belanger1
1. Department of Pathology and Laboratory Medicine, Vancouver General Hospital, Canada
2. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
*Correspondence to pushwant.mattu@phsa.ca
Disclosure: The authors have declared no conflicts of interest.
Citation: EMJ Int Cardiol. 2024;12[1]:78-86. https://doi.org/10.33590/emjintcardiol/CUPA6320.
Abstract
A quadricuspid pulmonary valve (QPV) is a rare congenital cardiac anomaly, mostly identified incidentally during autopsy or imaging examination. The authors report on an autopsy case report describing a case of a QPV recognised incidentally during the autopsy of a 91-year-old male with bilateral pneumonia. All four cusps of the pulmonary valve exhibited approximately equal sizes and showed no degenerative changes, while the remaining heart valves displayed no structural anomalies. There was no clinical or pathological evidence of stenosis or regurgitation. In this report, the authors discuss the clinical presentation, review the existing literature, investigate the diagnostic and clinical implications of QPV, and highlight the key factors involved in QPV embryogenesis.
Key Points
1. Quadricuspid pulmonary valve is a rare congenital cardiac anomaly, typically clinically quiescent and asymptomatic, mostly identified incidentally during autopsy or imaging examinations.
2. The identification of quadricuspid pulmonary valve in living patients is infrequent and often overlooked due to limitations in transthoracic echocardiography imaging. Diagnosis relies on imaging studies, with transoesophageal echocardiogram, cardiac CT, and cardiac MRI being the most sensitive methods, providing superior visualisation of the pulmonary valve.
3. Identifying anatomical variants can significantly impact clinical outcomes by reducing diagnostic delays.
INTRODUCTION
Quadricuspid pulmonary valve (QPV) is a rare congenital cardiac anomaly in which the pulmonary valve has four cusps, typically of various sizes, rather than three symmetrical cusps. QPV is usually an asymptomatic, isolated malformation that is difficult to detect clinically using routine strategies such as transthoracic echocardiography (TTE), and is thus underdiagnosed. Historically, most cases have been discovered incidentally during postmortem examination, but recent advances in cardiac imaging technologies and frequent health examinations have resulted in more incidental diagnoses of QPV. The precise embryology of QPV is unknown, but may result from a developmental anomaly during embryonic cardiac outflow tract septation and valvulogenesis.
CASE PRESENTATION
A 91-year-old male, fully recovered from multiple surgeries following various cancer diagnoses, was admitted for hypoxemic respiratory failure with a low-grade fever and tachycardia. Imaging revealed consolidation in the lower left lung and small bowel obstruction. The patient also had sinus tachycardia with occasional ventricular tachycardia, Escherichia coli infection, and low white blood cell counts. Despite antibiotic treatment and respiratory support, the patient’s blood pressure, heart rate, and respiratory rate fluctuated over the next 24 hours, and he passed away the following day. The autopsy confirmed extensive bilateral pneumonia as the cause of death.
The authors examined the heart thoroughly and identified certain abnormalities. The heart was slightly enlarged, weighing 456 grams. There was evidence of moderate coronary artery disease, with up to 25% stenosis of the left anterior descending and right coronary arteries, and 50% stenosis of the left main coronary artery. The heart showed mild left ventricular hypertrophy. No evidence of acute or chronic myocardial infarction, endocarditis, valvular stenosis, or regurgitation was identified. When examining the valves, the team identified a
QPV consisting of four approximately equalsized cusps, none with significant degenerative changes (Figure 1). The adjacent pulmonary wall was unremarkable, with normal diameter and thickness. The thickness of each valve was 2 mm, with no fenestrations, calcifications, or fibrosis. Additionally, the aortic valve displayed mild nodular calcifications and fibrous thickening, predominantly affecting the lower-tomid cusps. Given the lack of associated clinicopathologic findings with the QPV, it was felt to be an incidental finding.
DISCUSSION
QPV is a rare congenital cardiac malformation with an incidence from 0.1–0.2% at autopsy, and 0.2% in a European study of donor hearts.1,2 It is more frequent in males, with a male-tofemale ratio of 2:1.1 Advancements in cardiac imaging techniques, regular health screenings, and cardiac surgery have led to an increased number of incidentally discovered QPV.3,4 However, it is challenging to determine the true incidence of QPV given the retrospective nature of these autopsy studies, and in addition, QPV may be frequently overlooked given its clinically silent nature.5
The classification of QPV can be done using the Hurwitz and Roberts system, which categorises the valves based on the relative size of the supernumerary cusp in relation to the remaining cusps.1 Type B, the most common variant, accounts for 60% of cases, and features three cusps of equal size with a smaller fourth cusp. Type A represents 12% of cases and is characterised by four cusps of similar size, such as seen in the present case. Type C represents 15% of cases and exhibits two larger cusps with two smaller cusps. The remaining cases belong to Types D–G, which features four cusps of different sizes.1 An exploration of embryology is helpful for understanding the basis of these variants.
The semilunar valves develop from endocardial cushions located at the atrioventricular junction and in the cardiac outflow tract (OFT) during the 5th week
1: Autopsy heart with opened right ventricle and root of pulmonary artery.
A quadricuspid pulmonary valve with no gross pathologic change is present (arrow).
of gestation.6 The septation of the OFT plays an integral role in the development of semilunar valves. Initially, the embryonic cardiac OFT consists of a simple tubular structure connecting the primitive ventricle to the aortic sac, lined by two major cushions: the parietal and septal outflow endocardial cushions. These OFT cushions are arranged in a spiralling pattern, reflecting the course of the aortic and pulmonary flows in the adult. These cushions, initially composed of extracellular matrix (ECM) called cardiac jelly, are populated by mesenchymal cells through endocardial-to-mesenchymal transition, regulated by Notch, bone morphogenetic protein, and TGF-β signalling. These OFT cushions also receive neural crest-derived cells in addition to endocardium-derived mesenchymal cells.6 The migration of neural crest cells into the heart is regulated by Rho-kinases, Wnt, bone morphogenetic protein, fibroblast growth factor, and semaphorin signalling.7 These cushions
expand into the lumen and meet, initially fusing together. Subsequently, they merge with the aorticopulmonary septum, which is a protrusion formed by migratory cardiac neural crest cells from the dorsal wall of the aortic sac. Fusion of these components spirally grows into the OFT lumen, ultimately dividing the OFT into the aorta and pulmonary trunk in the 7th week of development (Figure 2A–2E).6
In addition to the major cushion involved in OFT septation, two minor intercalated ridges also form in the atrioventricular junction and OFT, and they receive extracardiac contributions from cardiac neural crest cells. After OFT septation, semilunar valves develop from mesenchymal outgrowths from proliferation of the OFT cushions and intercalated ridges. These outgrowths undergo apoptosis to form cusps, then mature through matrix remodelling to create aortic and pulmonic valve primordia (Figure
Figure
Figure 2: Embryology for an understanding of cardiac outflow tract septation development.
Aorticopulmonary Septum
Parietal OFT Cushion
Migratory Cardiac Neural crest cells
Aortic Sac
Cardiac Outflow Tract
Atrium
Ventricle
Myocardium
Endocardium
Aorticopulmonary Septum
Septal OFT Cushion
Parietal OFT Cushion
Septal OFT Cushion
A) Formation of endocardial cushions and aorticopulmonary septum: the coronal section of the cardiac outflow tract shows endocardial cushion, known as parietal and septal OFT cushions, composed of extracellular matrix, which are populated by mesenchymal cells through the endocardial-to-mesenchymal transition and infiltration of cardiac neural crest-derived cell. Additionally, the section shows aorticopulmonary septum, originating from the dorsal wall of the aorta and composed of migratory cardiac neural crest cells. The zoomed-in circle view details the development of parietal and septal endocardial cushions and the aorticopulmonary septum. B) Formation of septation: OFT cushions lay in spiralling fashion and initially fuse together, subsequently merging with the aorticopulmonary septum. C) Spiral septation: the spiralling of aorticopulmonary septum results into the aorta and pulmonary trunk. The spiral aorticopulmonary septum separates the systemic arterial flow (red line) from the pulmonary arterial flow (blue line). The arrows indicate the levels of the sections shown in Figure 2D. D) Separation of the aorta and pulmonary trunk is complete. Sections through the newly formed aorta and pulmonary trunk, showing the position of aorticopulmonary septum and the relationship between pulmonary trunk and aorta, differ in the lower, middle, and upper tracts. E) The final position of the ascending aorta and pulmonary trunk in the 7th week of development, spiralling around as they depart from the heart, maintains their spiral relationship post-septation.
OFT: outflow tract.
3A–3C). These primordia subsequently develop by thinning, reshaping, and elongation, forming mature valve cusps with organised ECM layers of collagen rich fibrosa, glycosaminoglycan rich spongiosa, and elastin-filled ventricularis. Cardiac neural crest cells are found at the tip of the cusps, contributing to remodelling and maturation. Each type of endocardial cushions and intercalated ridges contribute to specific valve formations. Semilunar valve leaflets attached to the facing walls of the aorta and pulmonary trunk originate from major OFT cushions, while those attached to non-facing walls originate from left and right intercalated ridges. The parietal OFT cushion forms the right aortic and pulmonary valves, whereas septal OFT cushion forms the left aortic and pulmonary valves. Left and right intercalated ridge cushions form the anterior pulmonary and posterior aortic valves, respectively (Figure 4A–4C).6
Genetic, transcriptional, and signalling disruptions can potentially lead to valve abnormalities, although the exact mechanisms of QPV formation remain unclear.6 Abnormal cusp formation appears to result from the atypical proliferation of mesenchymal cushions in
the cardiac OFT and aberrant fusion of the aorticopulmonary septum.1 One study suggests that QPV may arise from the splitting of a valve cushion during early valvulogenesis in an animal model.8 Another study indicates that disrupted signalling Rho-associated protein kinase pathways in cardiac neural crest cells can lead to abnormal aggregation, potentially resulting in extra cushions and the formation of a quadricuspid valve in an animal model.9
Although QPV often occurs as an isolated finding, such as in the case described above, some autopsy studies show an association of QPV with other congenital cardiac abnormalities such as patent ductus arteriosus, atrioventricular defects, atrial septal defects, and ventricular septal defects.5 Other case reports have described an association of QPV with significant pulmonary regurgitation, bicuspid aortic valve, stenosis and severe regurgitation, pulmonary artery aneurysm, and even sudden death.10-14 Although the authors’ case demonstrates an asymptomatic QPV, their understanding of how QPV contributes to cardiac pathology continues to evolve, and currently, its potential role in clinically detectable disease may be underestimated.
A) The initial formation of the parietal and septal OFT cushions in the cardiac outflow tract. B) Formation of right and left intercalated ridges during early septation. C) Completion of septation and separation process, leading to the formation of semilunar valves. The parietal OFT cushion gives rise to the right aortic and pulmonary valve, the septal OFT cushion to the left aortic and pulmonary valve, and the left and right intercalated ridge cushions to the anterior pulmonary and posterior aortic valves, respectively. OFT: outflow tract.
Figure 3: Development of semilunar valve in outflow tract of the heart.
4: Development of semilunar valvular cusps.
A B C
With the rise of radiology and its expanded application in assessing cardiac anatomy and function in adults, identification of QPV in living patients remains rare and often goes undetected due to limitations in TTE imaging (Table 1). The first possible explanation is that QPV is rarely associated with other cardiac anomalies, and is clinically quiescent. In such cases, there would be no clinical reason for obtaining cardiac imaging if QPV is the only defect during presentation without any symptoms.24 The second explanation is a technical challenge associated with TTE. Due to the anatomical disposition of the valve in relation to the thoracic wall, it is challenging to visualise its short axis accurately.16 The third explanation is that the innervation of the pulmonary valve remains relatively unaffected by ageing, while the innervation of the aortic valve is age-dependent and decreases in density with age.25 This may explain why the QPV is rarely linked to symptoms or significant abnormal valvular
A) Valve development begins with endocardial cushion formation, which becomes populated by mesenchymal cells through the endocardial-to-mesenchymal transition and infiltration of cardiac neural crest-derived cells. B) These cushions grow into primordial valves, undergoing excavation, thinning, and elongation, which leads to extracellular matrix (ECM) remodelling for reorganising ECM components in valve tissue. C) It concludes with the maturation of the semilunar valve, characterised by organised ECM layers of fibrosa, spongiosa, and ventricularis.
function. The fourth explanation is that, as in the case described above, the presence of four equal valve cusps results in equal stress distribution, complete valve coaptation with symmetrical overlap, and no flow disturbance. In contrast, patients with a small additional accessory cusp or varying size cusp could experience uneven stress distribution and abnormal cusp coaptation, potentially leading to progressive regurgitation. In one study, it was found that quadricuspid aortic valves with four equal sized leaflets are less prone to develop fibrous thickening and significant aortic regurgitation, while presence of an additional cusp smaller than the other, may lead to uneven stress distribution, fibrosis, and abnormal coaptation, potentially resulting in significant regurgitation.26
Diagnosing QPV relies on imaging studies, with TEE, cardiac CT, and cardiac MRI being the most sensitive methods, offering enhanced visualisation of the pulmonary
Figure
Table 1: A summary of past case reports and clinical impact on diagnosis of quadricuspid pulmonary valve.
Author and Year
Akerem Khan SK et al., 201215
Iosifescu AG et al., 20124
Jung SY, 201516
Olivares‐Reyes A et al., 201217
Czekajska-Chehab E et al., 200918
Kwon SH et al., 201219
Manuel AM et al., 201920
Ansari‐G ilani K et al., 201921
Clinical Impact
Cardiac CT offered better imaging of a QPV compared to TTE, which faced limitations in obtaining a short axis view of the pulmonary valve.
The incidental diagnosis of QPV during surgery underscores the pre-operative limitation of echocardiography.
The diagnosis of QPV was achieved through CT due to TTE limitations, showcasing CT's superiority in this context.
Inconclusive TTE imaging necessitated QPV diagnosis through TEE, later confirmed by CT angiography.
Multiple TTEs could not detect the QPV, whereas cardiac CT enabled an accurate diagnosis of QPV.
QPV was incidentally detected on cardiac CT imaging despite normal TTE findings.
Echocardiography was unable to detect QPV, while cardiac CT provided precise identification of QPV.
CT angiography incidentally diagnosed QPV, providing valuable functional and anatomical insights that TTE was unable to provide.
Henriques de Gouveia RHAM et al., 201914 This article emphasises the contribution of QPV to sudden and unexpected cardiac lethality in an asymptomatic individual.
Nollen GJ et al., 201322
Dunay SA et al., 20153
Shimizu T et al., 201823
QPV and a left pulmonary artery aneurysm were detected in an asymptomatic patient through cardiac MRI, despite normal TTE findings.
Cardiac CT successfully detected QPV, demonstrating its superior diagnostic capability in in an asymptomatic individual with normal TTE results.
Cardiac CT effectively identified the QPV, which was undetected by TTE, highlighting its superior ability to diagnose valve abnormalities.
valve.3 These imaging techniques not only enable the observation of morphological characteristics of the valve, but also reveal associated structural deformities, whereas echocardiography mostly evaluates the functional abnormalities of the pulmonary valve. Cardiac CT and cardiac MRI are fast emerging as the most preferred imaging modalities for pulmonary valve diseases in adults, likely to result in QPV being identified in living persons much more frequently as these technologies are more universally adopted.27
QPV is often clinically silent, but it can be associated with congenital aortic valve anomalies due to shared morphogenesis of aortic and pulmonary valves, potentially requiring surgical intervention. The Ross procedure is widely acknowledged as
effective in treating congenital aortic valve malformations by replacing the diseased aortic valve with patient’s own tricuspid pulmonary valve, followed by replacement of the pulmonary valve with a pulmonary homograft. This approach has been found to be effective in cases of congenital aortic valve malformations when a normal and functional tricuspid pulmonary valve is used. However, a QPV is not an ideal candidate for the Ross procedure due to its poorly understood haemodynamics.28 Despite promising early post-operative results, the development of second-degree autograft regurgitation within 4 years post-surgery suggests potential issues with using a quadricuspid pulmonary autograft in a Ross procedure. Therefore, pre-operative imaging assessment of pulmonary valve function and morphology is deemed necessary.29
Though QPV is underdiagnosed and rarely complicated, its identification is crucial, as it can avoid delayed diagnosis, which can lead to unrecognised cardiac complication based on variant type and cusp size, causing asymmetrical valve stress distribution, abnormal coaptation, and severe symptoms during stress conditions.4,23 Identifying anatomical variants can significantly impact clinical outcomes by reducing diagnostic delays. Lack of familiarity with anatomical variations may adversely affect medical, surgical, and imaging results, yet its importance in safe clinical practice is often overlooked.30 Enhanced awareness can facilitate early detection and effective management to prevent adverse clinical outcomes. This case report highlights a rare anatomical variant, offering valuable insights that contribute to medical knowledge, benefitting both education and clinical practice.
References
1. Hurwitz LE, Roberts WC. Quadricuspid semilunar valve. Am J Cardiol. 1973;31(5):623-6.
2. Jashari R et al. The incidence of congenital bicuspid or bileaflet and quadricuspid or quadrileaflet arterial valves in 3,861 donor hearts in the European Homograft Bank. J Heart Valve Dis. 2009;18(3):337-44.
3. Dunay SN et al. Quadricuspid pulmonic valve found on well exam. Mil Med Res. 201;2:10. Erratum in: Mil Med Res. 2015;2:16.
4. Iosifescu et al. Surgical treatment of a pulmonary artery aneurysm due to a regurgitant quadricuspid pulmonary valve. Interact Cardiovasc Thorac Surg. 2012;14(6):880-2.
5. Hedayat KM et al. A quadricuspid pulmonic valve diagnosed in a live newborn by two-dimensional echocardiography. Pediatr Cardiol. 2000;21(3):279-81.
6. Buijtendijk MFJ et al. Development of the human heart. Am J Med Genet C Semin Med Genet. 2020;184(1):7-22.
8. Fernández B et al. Anatomy and formation of congenital bicuspid and quadricuspid pulmonary valves in Syrian hamsters. Anat Rec.
CONCLUSION
QPV is a rare congenital cardiac anomaly that is usually clinically quiescent and asymptomatic, and rarely presents with clinical complications. The authors reported on a rare case of QPV that was asymptomatic. QPV might seem unimportant, but its potential role in complications might be underestimated due to its benign nature, as it is mostly diagnosed post-mortem. Identifying anatomical variants can significantly impact clinical outcomes by reducing diagnostic delays. Failure to recognise variant anatomy may adversely affect medical, surgical, and imaging results. This case report aims to increase awareness and enhance clinical practice outcome of patients with anatomic variants.
1998;250(1):70-9.
9. Phillips HM et al. Neural crest cells are required for correct positioning of the developing outflow cushions and pattern the arterial valve leaflets. Cardiovasc Res. 2013;99(3):452-60.
10. Ascione L et al. Quadricuspid pulmonary valve diagnosed by cardiac magnetic resonance. J Cardiovasc Med (Hagerstown). 2009;10(12):944-5.
11. Hirooka K et al. Combined abnormalities of semilunar valves: quadricuspid pulmonary and bicuspid aortic valves. Circulation. 2001;103(1):E7.
12. Kotani A et al. [Quadricuspid pulmonary valve with valvular stenosis and regurgitation identified by transthoracic echocardiography: a case report]. J Cardiol. 2002;39(6):313-9. (in Japanese).
13. Gentille Lorente D. The pulmonary valve and the pulmonary artery. Eur Heart J. 2009;30(19):2326.
14. Henriques de Gouveia RHAM, Corte Real Gonçalves FMA. Sudden cardiac death and valvular pathology. Forensic Sci Res. 2019;4(3):280-6.
15. Akerem Khan SK et al. Quadricuspid pulmonary valve: computed tomography case series and review of relevant literature. J Thorac Imaging. 2012;27(6):W171-3.
17. Olivares-Reyes A et al. Congenital quadricuspid pulmonary valve in an adult patient with double valvular lesions and poststenotic dilatation of the trunk and the left branch of the pulmonary artery: a case presentation and review of the literature. Congenit Heart Dis. 2012;7(6):E103-8.
18. Czekajska-Chehab E et al. Quadricuspid pulmonary valve complicated with aneurysm of pulmonary trunk diagnosed with ECGgated computed tomography. Folia Morphol (Warsz). 2009;68(4):290-3.
19. Kwon SH et al. Quadricuspid pulmonary valve in an adult patient: discovered incidentally upon multidetectorrow computed tomography. Arch Cardiovasc Dis. 2012;105(10):537-9.
20. Manuel AM et al. Quadricuspid pulmonary valve in a 50-year-old female with dyspnoea: innocent bystander or active player in disease?. Eur Heart J. 2019;40(47):3869.
21. Ansari-Gilani K et al. Multimodality imaging of quadricuspid pulmonary valve associated with pulmonary artery aneurysm. Echocardiography. 2019;36(11):2094-98.
16. Jung SY. Quadricuspid pulmonary valve in an adult patient identified by transthoracic echocardiography and multi-detector computed tomography. Hellenic J Cardiol. 2015;56(3):266-8.
22. Nollen GJ et al. Quadricuspid pulmonary valve and left pulmonary artery aneurysm in an asymptomatic patient assessed by cardiovascular
MRI. Neth Heart J. 2013;21(4):196-8.
23. Shimizu T et al. Quadricuspid pulmonary valve stenosis treated by transcatheter pulmonary valvuloplasty with inoue balloon catheter. J Cardiol Cases. 2018;18(6):204-6.
24. Harada T et al. A case of a quadricuspid pulmonary valve in a Japanese female. Anat Sci Int. 2016;91(4):419-22.
25. Marron K et al. Innervation of human atrioventricular and arterial valves. Circulation. 1996;94(3):368-75.
26. Feldman BJ et al. Incidence, description and functional assessment of isolated quadricuspid aortic valves. Am J Cardiol. 1990;65(13):937-8.
27. Pignatelli RH et al. Imaging of the pulmonary valve in the adults. Curr Opin Cardiol. 2017;32(5):529-40.
28. Berdajs D et al. The quadricuspid pulmonary valve: its importance in the Ross procedure. J Thorac Cardiovasc Surg. 2003;125(1):198-9.
29. Sommer SP et al. Ross procedure with a quadricuspid pulmonary autograft. J Thorac Cardiovasc Surg. 2005;130(1):212-3.
30. Kachlík D et al. Variant Anatomy and Its Terminology. Medicina (Kaunas). 2020;56(12):713.
Role of Coronary Physiology in the Modern Catheterisation Lab
Authors: Giovanni Occhipinti,1 *Salvatore Brugaletta1
1. Hospital Clínic, Cardiovascular Clinic Institute, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain *Correspondence to sabrugaletta@gmail.com
Disclosure: Brugaletta serves on the advisory board of Boston Scientific and Zoll; and has received speaker's fees from Abbott Vascular, GE HealthCare, and Siemens. The authors declare no conflicts of interest.
Citation: EMJ Int Cardiol. 2024;12[1]:87-92. https://doi.org/10.33590/emjintcardiol/STMU5809.
Abstract
Over the past two decades, invasive coronary physiology assessment has advanced significantly. Despite the proven prognostic significance provided by invasive physiological assessment of lesions by means of fractional flow reserve or adenosine-free non-hyperaemic pressure ratios, challenges in clinical practice hinder widespread adoption and limit additional value for optimising percutaneous coronary intervention decisions. Despite notable progress, uncertainties persist, emphasising the need for further research to establish a single numerical parameter in the diagnosis of a functionally significant disease, clarify the impact of longitudinal vessel analysis, and support the relevance of pressure indices in postintervention optimisation.
Key Points
1. This manuscript aims to increase awareness of recent advancements in coronary physiology, highlighting the valuable role of integrating physiology indices into daily practice.
2. The development of a single numerical parameter (one-point number), along with the default performance of longitudinal physiological vessel analysis, could improve daily efficiency of percutaneous interventions and inform future clinical outcomes. Post-percutaneous coronary intervention physiology indices are able to guide optimisation strategies; nevertheless, a certain degree of uncertainty persists, especially for optimal cut-off points.
3. Significant advances in coronary physiology have been made. Their comprehensive application in modern catheterisation labs is crucial at every stage of coronary interventions. Future insights will further refine clinical decision-making processes.
INTRODUCTION
In the past two decades, since Andreas Gruentzig’s pioneering work introducing trans-lesional pressure gradient assessment as index of percutaneous coronary intervention (PCI) success,1 invasive coronary physiology assessment has witnessed a marked improvement.2 Various indexes derived from coronary blood pressure have been developed, with randomised trials supporting their use to improve PCI-related clinical benefits.3-7 Despite the established prognostic significance outlined in the current guidelines,8,9 there are still challenges in clinical practice, either hindering its widespread adoption or limiting its additional value for deciding and optimising PCI. Addressing these uncertainties is of paramount importance for increasing their application and improving patient outcomes, bringing coronary physiology to a modern role in the catheterisation (cath) lab.
Ongoing investigations primarily focus on three pivotal aspects to bridge the historical role of coronary physiology in the modern cath lab: 1) the meaning of a singular numerical parameter (i.e., onepoint number); 2) the value of longitudinal physiological vessel analysis; and 3) the role of pressure indices in post-PCI optimisation (Figure 1).
THE MEANING OF A SINGULAR NUMERICAL PARAMETER
Current guidelines advocate for invasive physiological assessment using fractional flow reserve (FFR) to identify ischaemiacausing coronary stenosis in patients with intermediate lesions or uncertain evidence for lesion-based ischaemia, guiding revascularisation decisions.8,9 Adenosine-free non-hyperaemic pressure ratios (NHPR) have emerged as a simpler alternative to FFR, supported by two large randomised trials demonstrating no significant difference in 5-year hard clinical endpoints between instantaneousfree ratio (iFR)-guided and FFR-guided PCI strategies.6,7 Notably, as an answer to address the perceived underuse of wire-
based physiological assessments, attributed to longer procedural time, need for adequate training, potential complications from pressure wire instrumentation, and costs,10 consistent advances have been made with the development of wirefree image-based approaches.11 Among the available computational solutions providing acceptable diagnostic accuracy (quantitative flow ratio [QFR], coronary angiography-derived fractional flow reserve, vessel fractional flow reserve, and Murray law-based quantitative flow ratio), QFR, derived from three-dimensional coronary reconstruction and fluid dynamics computations from the angiogram, stands out as the sole angiography-based physiological index with prospective validation; demonstrating a substantial lesion reclassification (~20%) and improved 1-year and 2-year clinical outcomes compared to conventional angiography in different subsets.12-16 However, limitations such as manual vessel contouring, proprietary software, nitrate dependency, single-vessel analysis, inapplicability to ostial lesions or major bifurcations, and reliance on optimal projections should be acknowledged. Interestingly, an ancillary analysis from the FAVOR-III China, although not depicting any statistical significance among pre-specified subgroups, showed a trend toward increased beneficial effect when the evaluation was performed in experienced centres.12
In this field, further improvements are expected, such as the broad application and clinical validation of intracoronary imagingbased protocols (optical flow ratio [OFR] and ultrasonic flow ration [UFR]), or the use of artificial intelligence, improving the quality of the measurements and reducing intra- and inter-observer limitations.11,17
Notably, approximately 20% of cases exhibit discordant results between FFR and NHPRs, attributed to variations in measuring the non-true resting state or to the insufficient hyperaemia, thus limiting the reliability on their results.11 Observational studies of iFR/FFR discordance suggest impaired clinical outcomes only when both parameters are abnormal, while lesions with discordant results have similar outcomes to
lesions with concordant negative results, emphasising that the independent choice of one test may offer diagnostic adequacy for clinical decisions, but at the cost of eventually different approaches (i.e., PCI) based on the choice of the test.1820 Nevertheless, the overall clinical and prognostic implications of these lesions remain unclear and open to further daily uncertainty.
On this background, future investigations should focus on anticipating clinical outcomes linked to between-tests discordance and develop a singular numerical parameter, such as a one-point number, to mitigate the intra-technique variability evident in randomised clinical trials; the inter-technique dissimilarities that contribute to overall perplexity in daily clinical practice; along with the aim to further reduce manual interactions and
improve overall efficiency and global reproducibility.
LONGITUDINAL PHYSIOLOGICAL VESSEL ANALYSIS
The evolution of invasive pressure-derived indexes assessment has progressed from recognising a single value reflecting the haemodynamic impact of an index lesion, to the comprehensive analysis of the entire vessel physiology.21 In practice, the assessment of pressure variations along the entire vessel length can offer valuable insights into final PCI results and subsequent outcomes.22-25 Nevertheless, in presence of sequential lesions (i.e., tandem stenoses), accurate estimation of physiological indexes may be compromised by the “crosstalk phenomenon” among lesions (i.e., caused by the relative
Figure 1: Coronary physiology in the modern catheterisation lab.
haemodynamic interdependence of stenoses), potentially leading to suboptimal procedural planning.2,11 In this setting, the longitudinal physiological vessel analysis may help to characterise the disease pattern (focal, tandem, diffuse) through the distribution of pressure losses along the epicardial vessel.22 Traditionally, this analysis can be performed subjectively by visual inspection of the pullback tracing, or through the pressure pullback pressure gradient (PPG) index,22 and dFFR(t)/ dt index.26 The ability to discriminate between different patterns of coronary atherosclerosis carries immediate and relevant clinical implications: a focal pattern is often associated with an optimal postPCI physiological result, since PCI results effective in removing focal flow-limiting stenosis. Conversely, a diffuse pattern of disease is frequently associated with suboptimal post-PCI results, and requires considerations on further medical therapy optimisation or surgical intervention rather than PCI.2 Notably, a sub-analysis of the TARGET-FFR trial showed that residual angina after PCI was almost twice as likely in patients with a diffuse disease, identified by a low PPG, than in patients with a focal disease (i.e., high PPG of ~1), who reported greater improvement in angina and quality of life.26-28
However, current definitions of diffuse disease are largely qualitative, and rely solely on clinical consensus statements, thus requiring further validation to provide formal and universal definitions.2,11 Importantly, most studies supporting definitions of focal, tandem and diffuse disease patterns are retrospective and relied on different diagnostic techniques, thus resulting in multiple cut-off definitions. Moreover, it has been ascertained that coronary physiology indexes, especially FFR, have a complementary role on defining plaque morphological characteristics with precise lesion features (i.e., vulnerable plaque), given the peculiar environmental composition (i.e., inflammatory mediators, etc.) and the impact on the macrovascular and microvascular circulations.29
On this background, while identifying the lesion pattern is becoming central,
consensus on thresholds and techniques able to predict future outcomes remains controversial. In addition, the identification of the benefit from an integrative assessment of coronary anatomy, plaque characteristics, and physiological aspects need more research to better predict events and improve the treatment strategies.
THE ROLE OF PRESSURE INDICES IN POST-PCI OPTIMISATION
Despite the established clinical significance of pre-procedural pressure-derived indexes in assessing the functional severity of coronary stenosis, contemporary reports reveal that 20–30% of cases yield suboptimal post-PCI results, reflected by FFR values <0.8 and iFR values <0.9.30-32 Although postPCI FFR values have been associated with future target vessel failure, cardiac death, and myocardial infarction, it is something not usually performed; moreover, there is still controversy over the optimal cut-off for defining an optimal PCI result.31,33 In case of NHPRs, a post-PCI iFR >0.95 has been related to improved outcomes in the DEFINE PCI study.31 However, universal agreement on this cut-off remains elusive. The lack of consensus stems from the fact that, although post-PCI pressure-guided optimisation can be adopted through repeated balloon inflation or stent employment, FFR-guided optimisation strategies do not often increase the proportion of patients with a final optimal FFR result (>0.90).30 Various factors may contribute to suboptimal post-PCI outcomes, including stent malapposition, plaque protrusion, thrombus within the stent, inadequate lesion coverage, incorrect stent sizing, and edge dissection.2 Nevertheless, suboptimal physiologic results after PCI may often be an epiphenomenon of diffuse atherosclerosis (bystander diffuse disease), challenging adequate revascularisation by means of PCI.2 The FFR SEARCH registry34 and reports by Piroth and colleagues35 emphasise that stent under-expansion, although not associated with a significant FFR drop, could indicate future clinical events across the entire coronary artery tree, including non-target vessels, as a result of a bystander diffuse disease. Importantly, the role of post-PCI physiology evaluation can
play a crucial role in improving final results, since precise findings (i.e., location of pressure index loss) provide valid indications on the role of further stent optimisation and anomaly correction in case of in-stent or out-of-stent (i.e., proximal or distal) pressure losses, or can suggest the acceptance of the result, thus embracing alternative non-PCI approaches according to the clinical situation (i.e., no focal pressure drop).2
In this context, post-PCI assessment undeniably demands significant attention as it may provide an index for future events. However, the debate over the optimal consideration of pressure-based indexes persists, necessitating further research in this field.
References
1. Grüntzig AR et al. Nonoperative dilatation of coronary-artery stenosis: percutaneous transluminal coronary angioplasty. N Engl J Med. 1979;301(2):61-8.
2. Escaned J et al. Applied coronary physiology for planning and guidance of percutaneous coronary interventions. a clinical consensus statement from the European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the European Society of Cardiology. EuroIntervention. 2023;19(6):464-81.
3. Zimmermann FM et al. Deferral vs. performance of percutaneous coronary intervention of functionally non-significant coronary stenosis: 15year follow-up of the DEFER trial. Eur Heart J. 2015;36(45):3182-8.
4. Xaplanteris P et al. Five-year outcomes with pci guided by fractional flow reserve. N Engl J Med. 2018;379(3):250-9.
5. van Nunen LX et al. Fractional flow reserve versus angiography for guidance of PCI in patients with multivessel coronary artery disease (FAME): 5-year follow-up of a randomised controlled trial. Lancet. 2015;386(10006):1853-60.
6. Gotberg M et al. Instantaneous wave-free ratio versus fractional flow reserve to guide PCI. N Engl J Med. 2017;376(19):1813-23.
7. Davies JE et al. Use of the Instantaneous wave-free ratio or fractional flow reserve in PCI. N Engl J Med. 2017;376:1824-34.
8. Neumann FJ et al. 2018 ESC/ EACTS guidelines on myocardial
CONCLUSIONS
Significant advances have been made in the field of coronary physiology; nevertheless, notable uncertainties persist. Subsequent investigations, emphasising the establishment of singular numerical parameters (i.e., one-point number), elucidating the consequence of longitudinal physiological vessel analysis in procedural planning, and affirming the pertinence of pressure indices in post-PCI optimisation, are imperative. This ongoing research aims to resolve current discrepancies, validate quantitative definitions, and challenge controversies related to optimal cut-off points, ultimately driving forward the field of coronary physiology in the modern cath lab.
9. Lawton JS et al. 2021 ACC/AHA/ SCAI Guideline for Coronary Artery Revascularization: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol 2022;79:197-215. Erratum in: J Am Coll Cardiol. 2022;19;79(15):1547.
10. Kogame N et al. The impact of coronary physiology on contemporary clinical decision making. JACC Cardiovasc Interv. 2020;13(14):161738.
11. Koo BK et al. Practical application of coronary physiologic assessment: Asia-Pacific expert consensus document: part 1. JACC Asia. 2023;3(5):689-706.
12. Xu B et al. Angiographic quantitative flow ratio-guided coronary intervention (FAVOR III China): a multicentre, randomised, sham-controlled trial. Lancet. 2021;398(10317):2149-59.
13. Xu B et al. Diagnostic accuracy of angiography-based quantitative flow ratio measurements for online assessment of coronary stenosis. J Am Coll Cardiol. 2017;70(25):3077-87.
14. Westra J et al. Diagnostic performance of in-procedure angiography-derived quantitative flow reserve compared to pressure-derived fractional flow reserve: the FAVOR II EuropeJapan study. J Am Heart Assoc. 2018;7(14):e009603.
15. Song L et al. 2-year outcomes of angiographic quantitative flow ratioguided coronary interventions. J Am Coll Cardiol. 2022;80(22):2089-101.
16. Jin Z et al. Coronary intervention guided by quantitative flow ratio vs angiography in patients with or without diabetes. J Am Coll Cardiol. 2022;80(13):1254-64.
17. Koo BK et al. Practical application of coronary physiologic assessment: Asia-Pacific expert consensus document: part 2. JACC Asia. 2023;3(6):825-42.
18. Lee JM et al. Clinical outcome of lesions with discordant results among different invasive physiologic indicesresting distal coronary to aortic pressure ratio, resting full-cycle ratio, diastolic pressure ratio, instantaneous wave-free ratio, and fractional flow reserve. Circ J. 2019;83(11):2210-21.
19. Lee JM et al. Clinical outcomes according to fractional flow reserve or instantaneous wave-free ratio in deferred lesions. JACC Cardiovasc Interv. 2017;10:2502-10.
20. Lee SH et al. physiologic characteristics and clinical outcomes of patients with discordance between FFR and iFR. JACC Cardiovasc Interv. 2019;12(20):2018-31.
21. Sonck J et al. Development, validation, and reproducibility of the pullback pressure gradient (PPG) derived from manual fractional flow reserve pullbacks. Catheter Cardiovasc Interv. 2022;99(5):1518-25.
22. Collet C et al. Measurement of hyperemic pullback pressure gradients to characterize patterns of coronary atherosclerosis. J Am Coll Cardiol. 2019;74(14):1772-84.
23. Candreva A et al. Hyperemic hemodynamic characteristics of serial coronary lesions assessed by
24. van Beek KAJ et al. Single center experience in the treatment of hemodynamically significant diffuse coronary artery disease of the left anterior descending. Int J Cardiol. 2022;352:40-4.
25. Omori H et al. Comparisons of nonhyperemic pressure ratios: predicting functional results of coronary revascularization using longitudinal vessel interrogation. JACC Cardiovasc Interv. 2020;13(22):2688-98.
26. Lee SH et al. Automated algorithm using pre-intervention fractional flow reserve pullback curve to predict post-intervention physiological results. JACC Cardiovasc Interv. 2020;13(22):2670-84.
27. Lee JM et al. Physiology-based revascularization: a new approach to plan and optimize percutaneous coronary intervention. JACC Asia. 2021;1(1):14-36.
28. Collet C et al. Differential improvement in angina and health-related quality of life after pci in focal and diffuse coronary artery disease. JACC Cardiovasc Interv. 2022;15(24):250618.
29. Yang S et al. Interactions between morphological plaque characteristics and coronary physiology: from pathophysiological basis to clinical implications. JACC Cardiovasc Imaging. 2022;15(6):1139-51.
30. Collison D et al. Post-stenting fractional flow reserve vs coronary angiography for optimization of percutaneous coronary intervention (TARGET-FFR). Eur Heart J. 2021;42(45):4656-68.
31. Jeremias A et al. Blinded physiological assessment of residual ischemia after
32. Uretsky BF et al. prospective evaluation of the strategy of functionally optimized coronary intervention. J Am Heart Assoc. 2020;9(3):e015073.
33. Hwang D et al. Prognostic implications of fractional flow reserve after coronary stenting: a systematic review and meta-analysis. JAMA Netw Open. 2022;5(9):e2232842.
34. van Zandvoort LJC et al. Explanation of postprocedural fractional flow reserve below 0.85. Circ Cardiovasc Interv. 2019;12(2):e007030.
35. Piroth Z et al. prognostic value of fractional flow reserve measured immediately after drug-eluting stent implantation. Circ Cardiovasc Interv. 2017;10(8):e005233.
Percutaneous Coronary Intervention For Treatment of Unusual Origin of the Left Main Artery: A Case Report
Citation: EMJ Int Cardiol. 2024;12[1]:93-100. https://doi.org/10.33590/emjintcardiol/10301047.
Abstract
The left main coronary artery originating from the right sinus of Valsalva is a rare congenital anomaly. A 62-year-old male came in with recurring exertional chest discomfort, as observed by the authors. He was referred to the catheterisation laboratory for coronary angiography, which revealed the presence of a left main coronary artery coming from the right coronary sinus. In the proximal portion of the left anterior ascending coronary artery, a critical stenotic lesion was identified. The cardiac CT angiography demonstrated a benign retroaortic course. The lesion was effectively treated utilising three drug-eluting stents.
Key Points
1. A 62-year-old male presented with recurring exertional chest discomfort. Coronary angiography confirmed the existence of a left main coronary artery originating from the right coronary sinus.
2. The report details the patient's clinical presentation, diagnostic workup, treatment strategy, and follow-up. It also emphasises the significance of early detection and therapy of this condition to avoid negative results.
3. Congenital anomalies of the origin and/or course of the coronary arteries are a key differential diagnosis for exertion angina. Multimodal coronary imaging is essential for determining the best course of action.
BACKGROUND
Multiple studies indicate that the incidence of congenital coronary artery anomalies ranges between 0.3–5.6%.1,2 Due to the wide availability of cardiac CT angiography (CCTA), however, a new study estimates the
incidence to be 7.9%.3 The most prevalent categorisation scheme is Angelini’s 1999 proposal, which separates anomalous coronary arteries into three primary categories: anomalies of origin and course, anomalies of termination, and anomalies of intrinsic coronary artery architecture.4
Anomalies of origin and course are differences in the location of origin and course of the coronary arteries. They are further categorised into two subtypes: anomalies of opposite sinus of Valsalva (OSV) origin, and anomalies of interarterial course.5
Anomalies of OSV origin are coronary arteries that emerge from the opposite aortic sinus and run between the aorta and the pulmonary artery. This subtype comprises an anomalous LM from the right sinus, an anomalous right coronary artery from the left sinus, and an anomalous left circumflex artery from the right sinus.6
Anomalies of interarterial course are coronary arteries that run between the aorta and the pulmonary artery, regardless of their origin. This subtype consists of anomalous left main coronary artery (LM) from the right sinus, an anomalous right coronary artery from the left sinus, and the aberrant origin of both coronary arteries from the same aortic sinus.6
The abnormality may be classified into five clusters based on the anatomical link between the abnormal vessel, the aorta, and the pulmonary trunk. In a preaortic (interarterial) course, the aberrant vessel travels between the aorta and pulmonary artery. A pre-pulmonic (anterior) anomalous vessel follows the outflow of the right ventricle anteriorly, a subpulmonic (septal) anomalous vessel takes an intramyocardial path before reappearing in the proximal part of the interventricular groove, and a retroaortic (posterior) anomalous vessel travels posteriorly around the aortic root. In a retrocardiac course, an abnormal vessel flows behind the heart, as opposed to in front of it. The first aberrant pattern is regarded as the most threatening, since it raises the risk of sudden cardiac death (SCD) in those individuals.5-10
Anomalies of termination relate to variations in the distribution and termination of the coronary arteries. They are further categorised into ALCAPA and coronary artery fistulas.11 ALCAPA refers to an aberrant left coronary artery that terminates in the pulmonary artery, as opposed to the aorta.
This condition, also known as Bland-WhiteGarland syndrome, has the potential to produce left ventricular dysfunction and heart failure.12
Fistulas of the coronary arteries are aberrant connections between the coronary arteries and other heart chambers or vessels. These connections may result in ischaemia, myocardial infarction, or heart failure by diverting blood away from the myocardium.13
Abnormalities of intrinsic coronary artery anatomy include size, shape, and distribution variations in the coronary arteries. They can be further divided into two subgroups: myocardial bridging and aneurysms in the coronary arteries.11 Myocardial bridging refers to a part of a coronary artery that runs through the myocardium, as opposed to above it. This condition can cause ischaemia during exercise or stress.14-16 Coronary artery aneurysms refer to localised dilations of the coronary arteries that can be congenital or acquired. They are commonly seen in patients with Kawasaki disease.17
Based on the patient’s clinical history, symptoms, and risk factors, the diagnosis of aberrant coronary arteries needs a high level of suspicion. In the majority of instances, imaging techniques like echocardiography, CCTA, cardiac MRI (CMRI), and coronary angiography are used to confirm the diagnosis.18,19
Echocardiography is a non-invasive imaging modality that can be used to detect anomalous coronary arteries, especially when combined with colour Doppler imaging. However, its sensitivity and specificity are limited, and it may not be able to detect all types of anomalous coronary arteries.20
CCTA is a highly sensitive imaging modality that can produce detailed images of the coronary arteries and their course. It is particularly useful for detecting anomalous origins of the coronary arteries from the OSV, or interarterial course, as well as coronary artery fistulas. CCTA can also be used to assess the severity of stenosis or obstruction of the coronary arteries.
CCTA is a very sensitive imaging technique that can map the coronary arteries in great detail. Coronary artery fistulas and abnormal origins of the coronary arteries from the OSV can be detected using this technique, as well as assessment of coronary artery stenosis or occlusion.21
CMRI is a non-invasive imaging technique that creates pictures of the heart’s internal structures using magnetic fields and radio waves. It can be used to detect anomalous coronary arteries, especially when combined with contrast-enhanced angiography. CMRI can also provide information about myocardial perfusion and function.22
Invasive coronary angiography is the diagnostic imaging modality of choice for coronary artery anomalies because of the wealth of information it provides regarding the coronary arteries’ anatomy, course, and distribution. Nonetheless, there is a small possibility of repercussions.23
Coronary artery anomalies can range from being completely incidental to being potentially fatal. This depends on the severity of the anomaly, and how it affects the arteries’ origin, course, and distribution. It is important to take the patient’s clinical condition and symptoms into account when deciding how to treat aberrant coronary arteries. In many cases, no treatment is necessary for asymptomatic people who have benign abnormalities, such as myocardial bridging or minor coronary artery aneurysms.24
A surgical or interventional procedure may be necessary for individuals who are experiencing symptoms, or who have highrisk abnormalities such as ALCAPA, or an interarterial course of the coronary arteries. Improving myocardial perfusion and avoiding ischemia, myocardial infarction, and SCD are therapy goals.23,24
Reimplantation of the anomalous coronary artery into the proper aortic sinus or bypass grafting of the aberrant section may constitute surgical therapy. This method can give a permanent cure and enhance longterm outcomes, but it has a greater risk of complications and a longer recovery time.25-27
Interventional therapy may entail percutaneous coronary intervention (PCI) or stent implantation; this procedure is less invasive than surgery, and can provide rapid symptom alleviation. When contemplating PCI, it is crucial to evaluate the course of these anomalies, and rule out malevolent ones. It may not be appropriate for all types of aberrant coronary arteries, and is linked to an increased risk of restenosis or thrombosis.28,29
The prognosis of aberrant coronary arteries depends on the type and severity of the anomaly, as well as the promptness and adequacy of treatment. Benign anomalies, such as myocardial bridging or small coronary artery aneurysms, have an excellent prognosis, and may not require any intervention.4,24
High-risk anomalies, such as ALCAPA or the interarterial course of the coronary arteries, have a poorer prognosis, and may require prompt intervention to prevent ischaemia, myocardial infarction, or SCD. In general, the long-term results of surgical or interventional therapy are favourable, although they are dependent on the patient’s clinical condition and the efficacy of the surgery.30,31
The authors describe a patient with an abnormal LM originating from the right coronary cusp, who suffered from recurrent chest pain, and his treatment.
CASE PRESENTATION
A 62-year-old male, with a past medical history of sensorineural deafness, hypertension, and Type 2 diabetes on oral hypoglycaemic medications, had reported to the cardiology clinic after several months of chest pain during exertion, which was deemed to be ischaemic in origin. A clinical examination, ECG, and echocardiography were done, showing normal findings.
Despite beginning treatment with antiischaemic medication, the patient continued to experience symptoms consistent with Canadian Cardiovascular Society (CCS) Grade II angina pectoris; as a result, the decision was made to perform coronary
angiography after obtaining informed consent for the procedure. The right radial approach was used, using a 5F Judkins right coronary catheter.
After engaging the right coronary sinus and contrast injection (Figure 1), a small non-dominant right coronary artery (RCA) was revealed, and the LM was found to arise from the right coronary ostium, which subsequently divided into the left circumflex artery and the diseased left anterior descending artery (LAD).
MANAGEMENT
Since coronary angiography revealed a significant proximal lesion in the LAD, there was a need to delineate the course of the coronary arteries, for fear of an intra-arterial course with a high risk of SCD. If present, such a malignant course would require a different management strategy. This led to the decision to opt for CCTA. After receiving the patient’s informed consent, a CCTA was performed, which revealed an anomalous LM originating from the right sinus of Valsalva. This aberrant LM followed
a retroaortic course, and was the source of both the LAD and the left circumflex artery. The RCA was shown to originate from the more proximal part of the LM (Figure 2).
The patient underwent PCI to LAD through right radial using a 6F MPA1 guide catheter (Medtronic, Watford, Hertfordshire, UK) and BMW wire (Asahi Intecc, Nagoya, Japan), pre-dilatation with non-compliant balloons of 2.25×15 mm and 2.5×20 mm, followed by deployment of three overlapping drug-eluting stents: XIENCE Skypoint™ Stent (Abbott Vascular, Abbott Park, Illinois, USA) 3.0×28 mm; SYNERGY™ (Boston Scientific, Marlborough, Massachusetts, USA) 2.75×16 mm, and XIENCE Skypoint™ Stent (Abbott Vascular) 2.75×12 mm, followed by post-dilation with stent balloon up to 26 ATM with excellent results achieving TIMI III flow (Figure 3).
The patient went home on the same day of the procedure on dual antiplatelet, β-blocker, and statins as part of anti-ischaemic treatment, as well as angiotensin receptor blockers for control of hypertension, and empagliflozin with linagliptin for diabetes management.
Figure 1: Coronary angiography showing the right and left coronary arteries arising from the right sinus of Valsalva demonstrating significant proximal left anterior descending coronary artery lesion.
Figure 2: Cardiac CT angiography 3D volume-rendered image demonstrating the retroaortic course of the left main coronary artery from the right sinus of Valsalva after removing the right atrium and left atrium.
Figure 3: Left anterior descending coronary artery post-stenting with TIMI III flow.
DISCUSSION
It is challenging to determine the burden of the aberrant origin of the left coronary artery from the right sinus of Valsalva since this abnormality is uncommon, and data from observational studies are very variable.32 However, it accounts for 0.3–1.0% of cases in the dataset of Angelini,1 with a retroaortic course being the most prevalent subtype (prevalence: 0.28%; 95% confidence interval: 0.21–0.35%).7
Anomalous coronary arteries have been reported to be susceptible to atherosclerosis, even at younger ages.33,34 Coronary blood flow would be hampered if aberrant coronary arteries emerged from the other side of the coronary sinus, which is positioned between the pulmonary trunk and the ascending aorta, especially if high-risk criteria are present in the form of a slit-like opening in the proximal vessel morphology, acute angle takeoff, and interarterial course, which was not present in the authors’ patient.35-37
By the time they are 20 years old, many individuals with aberrant LM coming from the opposite right coronary artery and the previously indicated high risk criteria have already passed away, usually during, or shortly after, strenuous exercise, which is characteristic of young, ‘healthy’ athletes.38,39 However, the authors’ patient presented with significant atherosclerotic changes in the LAD originating from the anomalous LM. The retroaortic route of the aberrant coronary artery suggested that the atherosclerotic changes in the coronary arteries were the true culprit in this patient’s case of chest pains, rather than the abnormal artery itself.40-44
Despite advances in interventional technology and procedural improvements, coronary artery anomalies remain a challenge for interventional cardiologists. The use of PCI as a treatment for aberrant coronary arteries appears promising; nevertheless, proper topographical identification of the anomalous vessel’s origin and proximal course is essential.38,45,46
Particularly in the setting of coronary anomalies, the long-term care of patients who have had PCI often entails a variety of interventions, including pharmaceutical therapies, lifestyle changes, and routine follow-up visits.47
Changes in lifestyle, such as exercise, good nutrition, smoking cessation, and a healthy weight, contribute to heart health. Exercise improves quality of life, cardiovascular health, and the risk of future cardiac events. A healthy diet reduces cholesterol, blood pressure, and heart disease. Stopping smoking improves long-term PCI outcomes, since heart disease is a major risk factor. Maintaining a healthy weight improves overall health and reduces the chance of heart issues.48 However, the authors’ patient was not overweight, or a smoker.
Pharmacological treatments to avoid stent thrombosis include PCI followed by dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor. The patient’s health, stent type, and bleeding risk will determine the DAPT length. Statins, β-blockers, and angiotensin–converting enzyme inhibitors may be administered as well. Statins, β-blockers, and angiotensin–converting enzyme inhibitors can decrease cholesterol, blood pressure, and heart rate, respectively.49 The authors’ patient was kept on all these medications and DAPT for 12 months.
Regular follow-up meetings with the healthcare practitioner are crucial for monitoring the patient’s condition, reviewing the treatment plan’s efficacy, and managing problems. Follow-up appointments are usually planned at regular intervals for the first year following the treatment and less often after that. At follow-up sessions, the doctor will examine the patient, check their prescriptions, and prescribe any required tests or imaging investigations. The authors’ patient had his first clinic appointment after 1 month, where he was asymptomatic, and in a compensated state. The authors planned for a 3-month follow-up interval for the first year if he remained asymptomatic.47
Stress testing can measure symptoms, and stratify people who may be at higher risk for cardiac events. Echocardiography may assess heart function, particularly the ejection fraction. CCTA or coronary angiography can be utilised to visualise any possible anomalies in the coronary
References
1. Angelini P. Coronary artery anomalies: an entity in search of an identity. Circulation. 2007;115(10):1296-305.
2. Garg N et al. Primary congenital anomalies of the coronary arteries: a coronary arteriographic study. Int J Cardiol. 2000;74(1):39-46.
3. Gentile F et al. Coronary artery anomalies. Circulation. 2021;144(12):983-96.
4. Villa AD et al. Coronary artery anomalies overview: the normal and the abnormal. World J Radiol. 2016;8(6):537-55.
5. Lanjewar CP et al. Anomalous origin of coronary artery from the opposite aortic sinus of valsalva-a single center experience with a therapeutic conundrum. Indian Heart J. 2021;73(3):289-94.
6. Peñalver JM et al. Anomalous aortic origin of coronary arteries from the opposite sinus: a critical appraisal of risk. BMC Cardiovasc Disord. 2012;12:83.
7. Cheezum MK et al. Anomalous aortic origin of a coronary artery from the inappropriate sinus of valsalva. J Am Coll Cardiol. 2017;69(12):1592-608.
8. Krasuski RA et al. Long-term outcome and impact of surgery on adults with coronary arteries originating from the opposite coronary cusp. Circulation. 2011;123(2):154-62.
9. Moore KL et al. "Thorax,” Clinically Oriented Anatomy (2018) 8th edition, Philadelphia: Wolters Kluwer, pp.78-126.
10. Kejriwal NK et al. Retroaortic course of the anomalous left main coronary artery: is it a benign anomaly? A case report and review of literature. Heart Lung Circ. 2004;13(1):97-100.
11. Kastellanos S et al. Overview of coronary artery variants, aberrations and anomalies. World J Cardiol. 2018;10(10):127-40.
12. Yau JM et al. Anomalous origin of the left coronary artery from the pulmonary artery in adults: a comprehensive review of 151 adult cases and a new diagnosis in a 53-year-old woman. Clin Cardiol. 2011;34(4):204-10.
anatomy and evaluate the patency of any stents or grafts inserted during PCI. These imaging scans can be repeated to evaluate the patient’s status and therapy efficacy.49 However, because the authors’ patient was asymptomatic, no additional evaluation was required.
13. Sunkara A et al. Coronary artery fistula. Methodist DeBakey Cardiovasc J. 2017;13(2):78-80.
14. Roberts W et al. Myocardial bridges: a meta-analysis. Clin Anat. 2021;34(5):685–709.
15. Loukas M et al. Myocardial bridges: a review. Clin Anat. 2011;24(6):675-83.
16. Corban MT et al. Myocardial bridging: contemporary understanding of pathophysiology with implications for diagnostic and therapeutic strategies. J Am Coll Cardiol. 2014;63(22):2346-55.
17. Sheikh AS et al. Coronary artery aneurysm: evaluation, prognosis, and proposed treatment strategies. Heart Views. 2019;20(3):101-8.
18. Angelini P et al. Coronary anomalies: incidence, pathophysiology, and clinical relevance. Circulation. 2002;105(20):2449-54.
19. Kim SY et al. Coronary artery anomalies: classification and ECGgated multi-detector row CT findings with angiographic correlation. Radiographics. 2006;26(2):317-33.
20. Warnes CA et al. ACC/AHA 2008 guidelines for the management of adults with congenital heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Develop Guidelines on the Management of Adults With Congenital Heart Disease). Developed in Collaboration With the American Society of Echocardiography, Heart Rhythm Society, International Society for Adult Congenital Heart Disease, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2008;52(23):e143-263.
21. Oikonomou E et al. Current concepts and future applications of non-invasive functional and anatomical evaluation of coronary artery disease. Life (Basel). 2022;12(11):1803.
22. Elmadi J et al. Cardiovascular magnetic resonance imaging: a prospective modality in the diagnosis and prognostication of heart failure. Cureus. 2022;14(4):e23840.
23. Brothers JA et al. Expert consensus
guidelines: anomalous aortic origin of a coronary artery. J Thorac Cardiovasc Surg. 2017;153(6):1440-57.
24. Grau JB et al. Reimplantation for anomalous right coronary artery. JTCVS Tech. 2021 Jun;7:226-8.
25. Jegatheeswaran A et al. Outcomes after anomalous aortic origin of a coronary artery repair: a Congenital Heart Surgeons' Society Study. J Thorac Cardiovasc Surg. 2020;160(3):757-71.e5.
26. Lorber R et al.; AAOCA Working Group of the Congenital Heart Surgeons Society. Anomalous aortic origin of coronary arteries in the young: echocardiographic evaluation with surgical correlation. JACC Cardiovasc Imaging. 2015;8(11):1239-49.
27. Molossi I et al. Anomalous coronary arteries: a state-of-the-art approach. Cardiol Clin. 2023;41(1):51-69.
28. Hauser M. Congenital anomalies of the coronary arteries. Heart. 2005;91(9):1240-5.
29. Al Umairi RS et al. Anomalous origin of the left coronary artery from the pulmonary artery: the role of multislice computed tomography (MSCT). Oman Med J. 2016;31(5):387-9.
30. Leong SW et al. Anomalous left coronary artery from the pulmonary artery: case report and review of the literature. Int J Cardiol. 2009;133(1):132-4.
31. Khan MS et al. Anomalous origin of left main coronary artery from the right sinus of valsalva: a case series-based review. Cureus. 2020;12(4):e7777.
32. Kapoor A et al. An unusual coronary trinity: single left coronary artery with the right coronary artery originating from the left main coronary artery and following a retro-aortic course. J Invasive Cardiol. 2011;23(6):E156-7.
33. Park E et al. Atherosclerotic coronary artery disease in a younger adult with transseptal anomalous left coronary artery. JACC Case Rep. 2022;4(16):1060-4.
34. Lee BY. Anomalous right coronary artery from the left coronary sinus with an interarterial course: is it really dangerous? Korean Circ J.
2009;39(5):175-9.
35. Park JH et al. Prevalence of congenital coronary artery anomalies of Korean men detected by coronary computed tomography. Korean Circ J. 2013;43(1):7-12.
36. Rizzo S et al. Sudden death and coronary artery anomalies. Front Cardiovasc Med. 2021;8:636589.
37. Finocchiaro G et al. Anomalous coronary artery origin and sudden cardiac death: clinical and pathological insights from a national pathology registry. JACC Clin Electrophysiol. 2019;5(4):516-22.
38. Niwa K. Coronary artery anomaly and sudden death–especially focus on anomalous left coronary artery arising from the right sinus. J Cardiol Cases. 2013;7(3):e86-8.
39. Nogic J et al. Anomalous coronary arteries on computer tomography angiography: a pictorial review. Curr Cardiovasc Imaging Rep. 2017;10:35.
40. Sousa E, Casanova J. Coronary artery abnormalities: Current clinical issues. Rev Port Cardiol (Engl Ed). 2018;37(3):227-35.
41. Halabchi F et al. Sudden cardiac death in young athletes: a literature review
and special considerations in Asia. Asian J Sports Med. 2011;2(1):1-15.
42. Graidis C et al. Percutaneous coronary intervention and stenting in a single coronary artery originating from the right sinus of valsalva. Hellenic J Cardiol. 2013;54(5):401-7.
43. Constantinides SS et al. Transradial primary percutaneous intervention in a rare case of anomalous origination of the left coronary artery system from the right aortic sinus. JACC Cardiovasc Interv. 2014;7(11):e179-81.
44. Koza Y et al. Percutaneous coronary intervention in a rare case of single coronary ostium presented with ST elevation myocardial infarction. Eurasian J Med. 2019;51(3):307-9.
45. Han J et al. Sudden cardiac death in athletes: facts and fallacies. J Cardiovasc Dev Dis. 2023;10(2):68.
46. Neumann FJ et al.; ESC Scientific Document Group. 2018 ESC/ EACTS guidelines on myocardial revascularization. Eur Heart J. 2019;40(2):87-165.
47. Eckel RH et al.; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 AHA/ACC guideline on lifestyle
management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129 (25 Suppl 2):S76-99.
48. Levine GN et al. 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: a report of the American College of Cardiology/ American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2016;68(10):1082-115.
49. Patel MR et al. ACC/AATS/AHA/ ASE/ASNC/SCAI/SCCT/STS 2017 appropriate use criteria for coronary revascularization in patients with stable ischemic heart disease: a report of the American College of Cardiology Appropriate Use Criteria Task Force, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2017;69(17):2212-41.
