{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T18:30:19Z","timestamp":1787769019896,"version":"build-2784847793"},"reference-count":141,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T00:00:00Z","timestamp":1739750400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Sudden cardiac death (SCD), the most devastating complication of hypertrophic cardiomyopathy (HCM), is primarily triggered by ventricular tachycardia or fibrillation. Despite advances in knowledge, the mechanisms driving ventricular arrhythmia in HCM remain incompletely understood, stemming from an interplay of multiple pro-arrhythmic factors. Myocyte disarray and myocardial fibrosis form a structural substrate favorable to re-entrant arrhythmias by altering myocardial electrophysiological properties, while cellular abnormalities predominate in patients without evident structural remodeling. Traditional SCD risk prediction models rely on clinical risk factors and regression-based risk estimation, often overlooking specific arrhythmic substrates. Emerging techniques now allow for the direct assessment of these substrates, providing deeper insights into the arrhythmogenic mechanisms and paving the way for more personalized SCD risk stratification. This review explores the contribution of cellular, structural, and electrophysiological substrates to arrhythmic risk in HCM, emphasizing their distinct roles. Furthermore, it highlights the potential of substrate-based approaches to refining SCD prevention strategies and improving outcomes for patients with HCM.<\/jats:p>","DOI":"10.3390\/jcm14041331","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T07:48:22Z","timestamp":1739778502000},"page":"1331","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Substrates of Sudden Cardiac Death in Hypertrophic Cardiomyopathy"],"prefix":"10.3390","volume":"14","author":[{"given":"Matteo","family":"Sclafani","sequence":"first","affiliation":[{"name":"Royal Brompton and Harefield Hospitals, Guy\u2019s and St Thomas\u2019 NHS Foundation Trust, London SW3 6PY, UK"},{"name":"Cardiology Unit, Department of Clinical and Molecular Medicine, Sant\u2019Andrea University Hospital, Sapienza University, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7128-9911","authenticated-orcid":false,"given":"Giulio","family":"Falasconi","sequence":"additional","affiliation":[{"name":"Arrhythmia Department, Teknon Heart Institute, Teknon Medical Center, 08022 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Tini","sequence":"additional","affiliation":[{"name":"Cardiology Unit, Department of Clinical and Molecular Medicine, Sant\u2019Andrea University Hospital, Sapienza University, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4872-7981","authenticated-orcid":false,"given":"Beatrice","family":"Musumeci","sequence":"additional","affiliation":[{"name":"Cardiology Unit, Department of Clinical and Molecular Medicine, Sant\u2019Andrea University Hospital, Sapienza University, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Penela","sequence":"additional","affiliation":[{"name":"Arrhythmia Department, Teknon Heart Institute, Teknon Medical Center, 08022 Barcelona, Spain"},{"name":"IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9475-1507","authenticated-orcid":false,"given":"Andrea","family":"Saglietto","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Cardiovascular and Thoracic Department, \u201cCitta Della Salute e Della Scienza\u201d Hospital, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1410-6845","authenticated-orcid":false,"given":"Luca","family":"Arcari","sequence":"additional","affiliation":[{"name":"Cardiology Unit, Madre Giuseppina Vannini Hospital, 00177 Rome, Italy"},{"name":"Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Bucciarelli-Ducci","sequence":"additional","affiliation":[{"name":"Royal Brompton and Harefield Hospitals, Guy\u2019s and St Thomas\u2019 NHS Foundation Trust, London SW3 6PY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Barbato","sequence":"additional","affiliation":[{"name":"Cardiology Unit, Department of Clinical and Molecular Medicine, Sant\u2019Andrea University Hospital, Sapienza University, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Berruezo","sequence":"additional","affiliation":[{"name":"Arrhythmia Department, Teknon Heart Institute, Teknon Medical Center, 08022 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Francia","sequence":"additional","affiliation":[{"name":"Cardiology Unit, Department of Clinical and Molecular Medicine, Sant\u2019Andrea University Hospital, Sapienza University, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.jacc.2014.05.003","article-title":"Hypertrophic cardiomyopathy: Present and future, with translation into contemporary cardiovascular medicine","volume":"64","author":"Maron","year":"2014","journal-title":"J. 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