{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:14:13Z","timestamp":1787066053851,"version":"build-2736575974"},"reference-count":79,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["AHA20SCG35540034"],"award-info":[{"award-number":["AHA20SCG35540034"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL155197"],"award-info":[{"award-number":["R01HL155197"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["."],"award-info":[{"award-number":["."]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia worldwide, typically driven by age, obesity, and other conventional cardiovascular risk factors. However, a subset of patients develop early-onset AF\u2014often before 65 years of age in the absence of structural heart disease\u2014suggesting alternative mechanisms beyond acquired risk. Emerging evidence implicates pathogenic variants in cardiomyopathy-associated genes as key drivers in this population. This review synthesizes contemporary evidence linking cardiomyopathy gene variants, particularly in TTN, LMNA, MYH7, and PKP2, to early-onset AF. Across multiple sequencing cohorts, pathogenic or likely pathogenic variants are identified in 5\u201320% of young AF patients, with prevalence rising sharply at younger ages. TTN truncating variants confer up to a two-fold increased risk of AF and a 10-fold higher risk of subsequent dilated cardiomyopathy, whereas LMNA mutations are associated with aggressive atrial fibrosis, conduction disease, and early recurrence after catheter ablation. Longitudinal studies demonstrate that genotype-positive AF patients face higher risks of heart failure, sudden cardiac death, and progression to overt cardiomyopathy. These findings redefine early-onset AF as a potential sentinel manifestation of inherited myocardial disease rather than an isolated electrical disorder. Genetic testing\u2014especially in individuals with AF onset \u226445 years or a family history of cardiomyopathy\u2014enables early detection, cascade screening, and personalized surveillance. Integrating genomics, advanced imaging, and electrophysiological management supports a precision medicine framework that may improve outcomes by identifying and intervening before structural disease develops.<\/jats:p>","DOI":"10.1093\/ehjqcco\/qcag113","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T11:36:19Z","timestamp":1784633779000},"source":"Crossref","is-referenced-by-count":1,"title":["A review of cardiomyopathy gene variants as drivers of early-onset atrial fibrillation: linking genotype to phenotype in precision medicine"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2412-2574","authenticated-orcid":false,"given":"Johannes","family":"Reinhold","sequence":"first","affiliation":[{"name":"Department of Cardiology, Norfolk and Norwich University Hospital , Colney Lane, Norwich NR4 7UY ,","place":["UK"]},{"name":"Faculty of Medicine and Health Sciences, Norwich Medical School, University of East Anglia , Norwich NR4 7TJ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0024-9116","authenticated-orcid":false,"given":"Paris","family":"Chrysostomou","sequence":"additional","affiliation":[{"name":"Bedford Hospital South Wing , Kempston Road, Bedford MK42 9DJ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick M","family":"Heck","sequence":"additional","affiliation":[{"name":"Royal Papworth Hospital , Papworth Road, Trumpington, Cambridge CB2 0AY ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A","family":"Begley","sequence":"additional","affiliation":[{"name":"Royal Papworth Hospital , Papworth Road, Trumpington, Cambridge CB2 0AY ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos P","family":"Letsas","sequence":"additional","affiliation":[{"name":"Department of Cardiac Electrophysiology, Onassis Cardiac Surgery Centre , 356 Syngrou Avenue, Athens 17674 ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris J","family":"Kapelios","sequence":"additional","affiliation":[{"name":"Heart Failure Unit, Department of Cardiology, Attikon University Hospital, National and Kapodistrian University of Athens \u00a0 Rimini 1, Haidari, Athens 12462 ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire A","family":"Martin","sequence":"additional","affiliation":[{"name":"Royal Papworth Hospital , Papworth Road, Trumpington, Cambridge CB2 0AY ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J","family":"Pettit","sequence":"additional","affiliation":[{"name":"Royal Papworth Hospital , Papworth Road, Trumpington, Cambridge CB2 0AY ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6824-7155","authenticated-orcid":false,"given":"M Benjamin","family":"Shoemaker","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center , Nashville, TN 37232 \u00a0","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1647-920X","authenticated-orcid":false,"given":"Charikleia","family":"Papadopoulou","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Norfolk and Norwich University Hospital , Colney Lane, Norwich NR4 7UY ,","place":["UK"]},{"name":"Royal Papworth Hospital , Papworth Road, Trumpington, Cambridge CB2 0AY ,","place":["UK"]},{"name":"Department of Medicine, University of Cambridge , Cambridge CB2 0AW 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