{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T19:11:41Z","timestamp":1780686701766,"version":"3.54.1"},"reference-count":15,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"James Lancaster Memorial Fund"},{"name":"McColl\u2019s RG Ltd"},{"DOI":"10.13039\/501100000272","name":"National Institute of Health Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100011722","name":"Higher Education Funding Council for England","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011722","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Mayo Clinic Windland Smith Rice Comprehensive Sudden Cardiac Death Program"},{"DOI":"10.13039\/501100016394","name":"ANR JCJC","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100016394","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013289","name":"LEARN","doi-asserted-by":"publisher","award":["R21006NN"],"award-info":[{"award-number":["R21006NN"]}],"id":[{"id":"10.13039\/100013289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013289","name":"LEARN","doi-asserted-by":"publisher","award":["RPV21014NNA"],"award-info":[{"award-number":["RPV21014NNA"]}],"id":[{"id":"10.13039\/100013289","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ANR European Joint Programme"},{"name":"LQTS-NEXT"},{"DOI":"10.13039\/501100003100","name":"F\u00e9d\u00e9ration Fran\u00e7aise de Cardiologie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003100","id-type":"DOI","asserted-by":"publisher"}]},{"name":"French Ministry of Health"},{"name":"Clinical Research Hospital Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>SCN5A-E1784K (c.5350G&amp;gt;A) is the most common variant associated with the long QT (LQTS) and Brugada syndromes (BrS). It can manifest variably as LQTS, BrS, and\/or conduction disorders. This presents a challenge for risk stratification. We aimed to describe clinical and ECG characteristics and identify risk markers that associate with arrhythmic events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>We undertook a retrospective observational multicentre study of a large cohort of 231 subjects with SCN5A-E1784K from Europe, USA, and Japan. Comprehensive demographic and clinical data, including initial presentation ECG and follow-up, were collected. \u2018Lethal events\u2019 were defined as sudden death, non-fatal cardiac arrest, and documented sustained VT or VF. \u2018Cardiac events\u2019 were defined as arrhythmic syncope plus any lethal events. Clinical characteristics and ECG parameters corrected for age were investigated for association with lethal and\/or cardiac events. Fourteen (6%) subjects experienced a lethal event and 45 (19%) a cardiac event. PR interval and QRS duration were associated with lethal and cardiac events. In multivariable models, both PR interval and QRS duration were associated with lethal events, but only QRS duration was associated with cardiac events. Only age-corrected QRS (rQRS) was associated with lethal and cardiac event-free survival from birth after correction for multiple testing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Ventricular myocardial conduction appears likely to play a role in the risk of arrhythmic events in patients with SCN5A-E1784K. This provides an important opportunity for the personalization of management and has the potential to guide preventative therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/europace\/euag113","type":"journal-article","created":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T11:44:00Z","timestamp":1778327040000},"source":"Crossref","is-referenced-by-count":0,"title":["Ventricular conduction is a marker for arrhythmic risk in\n                    <i>SCN5A-<\/i>\n                    E1784K overlap sodium channel disease"],"prefix":"10.1093","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9828-4459","authenticated-orcid":false,"given":"Michael W T","family":"Tanck","sequence":"first","affiliation":[{"name":"Amsterdam UMC, University of Amsterdam , Epidemiology and Data Science, Amsterdam Public Health, Meibergdreef 9, Amsterdam ,","place":["Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0656-5769","authenticated-orcid":false,"given":"Yanushi D","family":"Wijeyeratne","sequence":"additional","affiliation":[{"name":"Cardiovascular and Genomics Research Institute, School of Health and Medical Sciences, City St George\u2019s University of London , London SW17 0RE ,","place":["UK"]},{"name":"St George\u2019s University Hospitals National Health Service (NHS) Foundation Trust , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4106-5946","authenticated-orcid":false,"given":"Julien","family":"Barc","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Nantes Universit\u00e9, CNRS, INSERM, L\u2019institut du Thorax , Nantes F-44000 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Muir","sequence":"additional","affiliation":[{"name":"Belfast Health and Social Care Trust , Belfast ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1779-7282","authenticated-orcid":false,"given":"Takeshi","family":"Aiba","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center , Osaka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3635-2003","authenticated-orcid":false,"given":"J Martijn","family":"Bos","sequence":"additional","affiliation":[{"name":"Departments of Cardiovascular Medicine (Division of Heart Rhythm Services), Pediatric and Adolescent Medicine (Division of Pediatric Cardiology), and Molecular Pharmacology & Experimental Therapeutics (Windland Smith Rice Sudden Death Genomics Laboratory), Mayo Clinic , Rochester, MN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7587-1124","authenticated-orcid":false,"given":"Christian","family":"Veltmann","sequence":"additional","affiliation":[{"name":"Center of Electrophysiology Bremen , Bremen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3617-8738","authenticated-orcid":false,"given":"Joseph","family":"Galvin","sequence":"additional","affiliation":[{"name":"Mater Misericordiae University Hospital , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8739-6527","authenticated-orcid":false,"given":"Lia","family":"Crotti","sequence":"additional","affiliation":[{"name":"Istituto Auxologico Italiano IRCCS, Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics , Milan ,","place":["Italy"]},{"name":"Department of Medicine and Surgery, University of Milano-Bicocca , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8195-4700","authenticated-orcid":false,"given":"Taisuke","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center , Osaka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1209-8896","authenticated-orcid":false,"given":"Seiko","family":"Ohno","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center , Osaka ,","place":["Japan"]},{"name":"Shiga University of Medical Science , Shiga ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen 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Pharmacology & Experimental Therapeutics (Windland Smith Rice Sudden Death Genomics Laboratory), Mayo Clinic , Rochester, MN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0675-4845","authenticated-orcid":false,"given":"Matteo","family":"Pedrazzini","sequence":"additional","affiliation":[{"name":"Istituto Auxologico Italiano IRCCS, Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4727-0994","authenticated-orcid":false,"given":"Chiara","family":"Alberio","sequence":"additional","affiliation":[{"name":"Istituto Auxologico Italiano IRCCS, Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1090-3292","authenticated-orcid":false,"given":"Federica","family":"Dagradi","sequence":"additional","affiliation":[{"name":"Istituto Auxologico Italiano IRCCS, Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0616-2353","authenticated-orcid":false,"given":"Michael","family":"Papadakis","sequence":"additional","affiliation":[{"name":"Cardiovascular and Genomics Research Institute, School of Health and Medical Sciences, City St George\u2019s University of London , London SW17 0RE ,","place":["UK"]},{"name":"St George\u2019s University Hospitals National Health Service (NHS) Foundation Trust , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3630-6138","authenticated-orcid":false,"given":"Sanjay","family":"Sharma","sequence":"additional","affiliation":[{"name":"Cardiovascular and Genomics Research Institute, School of Health and Medical Sciences, City St George\u2019s University of London , London SW17 0RE ,","place":["UK"]},{"name":"St George\u2019s University Hospitals National Health Service (NHS) Foundation Trust , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8600-0813","authenticated-orcid":false,"given":"Edward","family":"Petzer","sequence":"additional","affiliation":[{"name":"Darent Valley Hospital, Dartford and Gravesham NHS Trust , Dartford ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6302-0389","authenticated-orcid":false,"given":"Dan M","family":"Roden","sequence":"additional","affiliation":[{"name":"Vanderbilt University School of Medicine , Nashville ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9029-2339","authenticated-orcid":false,"given":"Minoru","family":"Horie","sequence":"additional","affiliation":[{"name":"Shiga University of Medical Science , Shiga ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0367-1048","authenticated-orcid":false,"given":"Peter J","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Istituto Auxologico Italiano IRCCS, Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1807-672X","authenticated-orcid":false,"given":"Naomasa","family":"Makita","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center , Osaka ,","place":["Japan"]},{"name":"Sapporo Teishinkai Hospital , Sapporo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3206-934X","authenticated-orcid":false,"given":"Martin M","family":"Borggrefe","sequence":"additional","affiliation":[{"name":"Department of Medicine, University Medical Centre Mannheim (UMM), Faculty of Medicine Mannheim, University of Heidelberg, European Center for AngioScience (ECAS), and DZHK (German Center for Cardiovascular Research) Partner Site Heidelberg\/Mannheim , Mannheim ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J","family":"Ackerman","sequence":"additional","affiliation":[{"name":"Departments of Cardiovascular Medicine (Division of Heart Rhythm Services), Pediatric and Adolescent Medicine (Division of Pediatric Cardiology), and Molecular Pharmacology & Experimental Therapeutics (Windland Smith Rice Sudden Death Genomics Laboratory), Mayo Clinic , Rochester, MN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9941-8973","authenticated-orcid":false,"given":"Wataru","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center , Osaka ,","place":["Japan"]},{"name":"Department of Cardiovascular Medicine, Nippon Medical School , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal P","family":"McKeown","sequence":"additional","affiliation":[{"name":"Belfast Health and Social Care Trust , Belfast ,","place":["UK"]},{"name":"Queen\u2019s University Belfast , Belfast ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5492-8619","authenticated-orcid":false,"given":"Vincent","family":"Probst","sequence":"additional","affiliation":[{"name":"Nantes Universit\u00e9, CHU Nantes, CNRS, INSERM, L\u2019institut du Thorax , Nantes F-44000 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8731-2853","authenticated-orcid":false,"given":"Elijah R","family":"Behr","sequence":"additional","affiliation":[{"name":"Cardiovascular and Genomics Research Institute, School of Health and Medical Sciences, City St George\u2019s University of London , London SW17 0RE ,","place":["UK"]},{"name":"St George\u2019s University Hospitals National Health Service (NHS) Foundation Trust , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,5,11]]},"reference":[{"key":"2026060514574444600_euag113-B1","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.hrthm.2009.09.069","article-title":"An international compendium of mutations in the SCN5A-encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing","volume":"7","author":"Kapplinger","year":"2010","journal-title":"Heart Rhythm"},{"key":"2026060514574444600_euag113-B2","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.hrthm.2005.01.020","article-title":"Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing","volume":"2","author":"Tester","year":"2005","journal-title":"Heart 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a clinical consensus statement of the European heart rhythm association of the European Society of Cardiology","volume":"27","author":"Merino","year":"2025","journal-title":"Europace"},{"key":"2026060514574444600_euag113-B10","doi-asserted-by":"crossref","first-page":"3997","DOI":"10.1093\/eurheartj\/ehac262","article-title":"2022 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death","volume":"43","author":"Zeppenfeld","year":"2022","journal-title":"Eur Heart J"},{"key":"2026060514574444600_euag113-B11","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.hrthm.2008.11.009","article-title":"Type of SCN5A mutation determines clinical severity and degree of conduction slowing in loss-of-function sodium channelopathies","volume":"6","author":"Meregalli","year":"2009","journal-title":"Heart 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