Ventricular conduction is a marker for arrhythmic risk in SCN5A- E1784K overlap sodium channel disease
Year: 2026
Type: article
Study design: Observational Study
Abstract: AIMS: SCN5A-E1784K (c.5350G>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. METHODS AND RESULTS: 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. 'Lethal events' were defined as sudden death, non-fatal cardiac arrest, and documented sustained VT or VF. 'Cardiac events' 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. CONCLUSION: 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.
Source: EP Europace
Authors: Michael W T Tanck, Yanushi D Wijeyeratne, Julien Barc, Alison Muir, Takeshi Aiba, J Martijn Bos, Christian Veltmann, Joseph Galvin, Lia Crotti, Taisuke Ishikawa, Seiko Ohno, Stephen P Page, Isabelle Denjoy, David J Tester, Martina Muggenthaler, Kazuhiro Takahashi, Hariharan Raju, Jean Baptiste Gourraud, Richard Redon, Jean-Jacques Schott, Carla Haglund-Turnquist, Matteo Pedrazzini, Chiara Alberio, Federica Dagradi, Michael Papadakis, Sanjay Sharma, Edward Petzer, Dan M Roden, Minoru Horie, Peter J Schwartz, Naomasa Makita, Martin M Borggrefe, Michael J Ackerman, Wataru Shimizu, Pascal P McKeown, Vincent Probst, Elijah R Behr
Institutions: Amsterdam Public Health, Amsterdam University Medical Centers, University of Amsterdam, National Health Service, St George’s University Hospitals NHS Foundation Trust, City St George's, University of London, Centre National de la Recherche Scientifique, Inserm, Institut du Thorax, Université de Nantes, Nantes Université, Belfast Health and Social Care Trust, National Cerebral and Cardiovascular Center, Mayo Clinic, Mater Misericordiae University Hospital, IRCCS Istituto Auxologico Italiano, University of Milano-Bicocca, Shiga University of Medical Science, Leeds Teaching Hospitals NHS Trust, Université Paris Cité, Assistance Publique – Hôpitaux de Paris, Hôpital Bichat-Claude-Bernard, Royal Devon University Healthcare NHS Foundation Trust, Kizawa Memorial Hospital, Macquarie University, Centre Hospitalier Universitaire de Nantes, Darent Valley Hospital, Dartford And Gravesham NHS Trust, Vanderbilt University, Sapporo Teishinkai Hospital, Heidelberg University, University Medical Centre Mannheim, Medizinische Fakultät Mannheim, Nippon Medical School, Queen's University Belfast
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,909
Funders: Higher Education Funding Council for England, National Institute for Health and Care Research, British Heart Foundation, Agence Nationale de la Recherche, Fédération Française de Cardiologie, Association Neurofibromatoses et Recklinghause, Medical Research Council, H2020 Public-public partnerships
OpenAlex ID: W7160859031
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