{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T18:02:16Z","timestamp":1781200936731,"version":"3.54.1"},"reference-count":89,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Background: Flecainide has remained largely excluded from use in structural heart disease for more than three decades, mainly because of the Cardiac Arrhythmia Suppression Trial, which showed excess mortality in post-myocardial infarction patients treated for ventricular ectopy. However, the influence of this trial has extended well beyond the population actually studied, fostering a broad safety paradigm that may not fully reflect contemporary clinical practice. Aim: This review aims to re-examine the role of flecainide in structural heart disease by examining the historical basis for its restriction and contrasting it with emerging contemporary evidence across specific structural substrates. Discussion: Flecainide remains one of the most effective antiarrhythmic drugs for rhythm control in atrial fibrillation and for the suppression of selected ventricular arrhythmias in patients without overt structural abnormalities. Emerging observational and early prospective data suggest that, in carefully selected patients with stable coronary artery disease without active ischemia, preserved left ventricular function, arrhythmogenic right ventricular cardiomyopathy, and premature ventricular complex-induced cardiomyopathy, flecainide may provide meaningful antiarrhythmic benefit without a clear signal of excess proarrhythmia or mortality. Advances in cardiac imaging, ischemia assessment, and phenotypic risk stratification further support a more individualized approach to candidate selection. Conclusions: Flecainide should not be considered uniformly contraindicated across all forms of structural heart disease. Rather than supporting indiscriminate use, the available evidence supports a mechanistically informed and phenotype-specific reassessment of its role in selected patients. Prospective studies are needed to determine whether current guideline restrictions remain justified in the modern era.<\/jats:p>","DOI":"10.3390\/life16050778","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T12:15:07Z","timestamp":1778156107000},"page":"778","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Flecainide in Structural Heart Disease: Reconsidering Its Role in Contemporary Arrhythmia Management"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3561-5713","authenticated-orcid":false,"given":"Paschalis","family":"Karakasis","sequence":"first","affiliation":[{"name":"Second Department of Cardiology, Hippokration General Hospital, Medical School, Aristotle University of Thessaloniki, Konstantinoupoleos 49, 54642 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6739-1024","authenticated-orcid":false,"given":"Konstantinos","family":"Grigoriou","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Athens, 75 Mikras Asias Avenue, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9260-6306","authenticated-orcid":false,"given":"Panagiotis","family":"Theofilis","sequence":"additional","affiliation":[{"name":"First Cardiology Department, School of Medicine, Hippokration General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5768-9125","authenticated-orcid":false,"given":"Panagiotis","family":"Iliakis","sequence":"additional","affiliation":[{"name":"First Cardiology Department, School of Medicine, Hippokration General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece"},{"name":"Department of Medicine, Division of Cardiology, Angiology and Internal Emergency Medicine, Ruhr University Bochum, Knappschaft Kliniken University Hospital Bochum, 44892 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0736-4942","authenticated-orcid":false,"given":"Panayotis K.","family":"Vlachakis","sequence":"additional","affiliation":[{"name":"First Cardiology Department, School of Medicine, Hippokration General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0995-7015","authenticated-orcid":false,"given":"Nikolaos","family":"Ktenopoulos","sequence":"additional","affiliation":[{"name":"First Cardiology Department, School of Medicine, Hippokration General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2616-7952","authenticated-orcid":false,"given":"Anastasios","family":"Apostolos","sequence":"additional","affiliation":[{"name":"First Cardiology Department, School of Medicine, Hippokration General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece"},{"name":"Department of Cardiology, Guy\u2019s and St Thomas\u2019 NHS Foundation Trust, Harefield Hospital, London UB9 6JH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6899-684X","authenticated-orcid":false,"given":"Dimitrios","family":"Patoulias","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Guy\u2019s and St Thomas\u2019 NHS Foundation Trust, Harefield Hospital, London UB9 6JH, UK"},{"name":"Second Propedeutic Department of Internal Medicine, Faculty of Medicine, School of Health Sciences Aristotle, University of Thessaloniki, 54642 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6604-5581","authenticated-orcid":false,"given":"Antonios P.","family":"Antoniadis","sequence":"additional","affiliation":[{"name":"Second Department of Cardiology, Hippokration General Hospital, Medical School, Aristotle University of Thessaloniki, Konstantinoupoleos 49, 54642 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7158-4950","authenticated-orcid":false,"given":"Nikolaos","family":"Fragakis","sequence":"additional","affiliation":[{"name":"Second Department of Cardiology, Hippokration General Hospital, Medical School, Aristotle University of Thessaloniki, Konstantinoupoleos 49, 54642 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3314","DOI":"10.1093\/eurheartj\/ehae176","article-title":"2024 ESC Guidelines for the management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS)","volume":"45","author":"Rienstra","year":"2024","journal-title":"Eur. 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