May 13, 2026EP Europace0 citationsOpen Access
Ventricular conduction is a marker for arrhythmic risk in SCN5A- E1784K overlap sodium channel disease
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Resultado clave
Age-corrected QRS duration was significantly associated with lethal and cardiac event-free survival in patients with the SCN5A-E1784K variant, among whom 6% experienced a lethal event.
Puntos clave
- This study aims to describe clinical and ECG characteristics in SCN5A-E1784K patients and identify risk markers associated with arrhythmic events.
- Conducted a retrospective observational multicentre study of 231 subjects with SCN5A-E1784K from Europe, USA, and Japan.
- Collected comprehensive demographic and clinical data including ECG parameters and follow-up.
- Defined lethal events as sudden death and non-fatal cardiac arrest; cardiac events included arrhythmic syncope.
- 14 (6%) subjects experienced a lethal event and 45 (19%) a cardiac event.
- Both PR interval and QRS duration were associated with lethal events; QRS duration was also associated with cardiac events.
- Age-corrected QRS was linked to lethal and cardiac event-free survival after correction for multiple testing.
Diseño del estudio
Tipo
Observational (n=231)
Multicéntrico
Sí
PICO estructurado
P
Población
231 subjects with SCN5A-E1784K overlap sodium channel disease (associated with long QT and Brugada syndromes) from Europe, USA and Japan
O
Resultado
Lethal events (sudden death, non-fatal cardiac arrest, and documented sustained VT or VF) and Cardiac events (arrhythmic syncope plus any lethal events)composite
Ventricular conduction parameters, specifically age-corrected QRS duration, serve as important risk markers for lethal and cardiac events in patients with the SCN5A-E1784K variant.
Resumen
Abstract Background and Aims SCN5A-E1784K (c.5350GA) 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.