Ventricular conduction is a marker for arrhythmic risk in SCN5A- E1784K overlap sodium channel disease
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ID: 313893
2026
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Abstract
BACKGROUND AND 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: 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. RESULTS: 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 personalisation of management and has the potential to guide preventative therapies.
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| Authors | Michael W T Tanck, Yanushi D. Wijeyeratne, Julien Barc, A.J.L. Muir, Takeshi Aiba, Martijn Bos, Christian Veltmann, Joseph Galvin, Lia Crotti, Taisuke Ishikawa, Seiko Ohno, Stephen P Page, I 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 Borggrefe, Michael J. Ackerman, Wataru Shimizu, Pascal McKeown, Vincent Probst, Elijah R Behr |
| Journal | EP Europace |
| Year | 2026 |
| DOI |
10.1093/europace/euag113
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| URL | |
| Keywords | Keywords not found |
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