Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2026
Clinical profile and prognosis of brugada syndrome SCN5A variant carriers with negative sodium channel blocker challenge.
СтатьяМногоцентровое исследованиеНазвание и аннотация: Перевод пока не подготовлен
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Surget Elodie, Clerici Gael, Sacher Frédéric, Martins Raphael, Maury Philippe, Denjoy Isabelle, Thollet Aurélie, Barc Julien, Schott Jean Jacques, Drapier Nathalie, Redon Richard, Gourraud Jean Baptiste, Probst Vincent
Аннотация
AIMS: Loss-of-function (LOF) variants in SCN5A are associated with Brugada syndrome (BrS), progressive conduction slowing, and other arrhythmias. While the prognosis of SCN5A carriers with a positive sodium channel blocker challenge (SCBC) is established, data on those with negative SCBC are limited.
OBJECTIVE: To assess the clinical presentation and prognosis of SCN5A variant carriers with negative SCBC, and compare them to relatives with positive SCBC.
METHODS AND RESULTS: We retrospectively included patients from five university hospitals (2000-2024) carrying a pathogenic or likely pathogenic SCN5A variant and negative SCBC. Relatives with the same variant and positive SCBC were also analysed. Patients with spontaneous type 1 ECG, gain-of-function variants, double variants, or ACMG class 1-3 variants were excluded. Clinical, ECG, genetic, and follow-up data were collected. Conduction slowing was evaluated using the PR interval and QRS duration. The cohort included 162 patients from 43 families (median age 37 ± 19 years, 46% male), of whom 69 (43%) had negative SCBC. Among these 69 patients, 25 (36%) had baseline intraventricular conduction defects, and 19 (28%) had first-degree AV block. After a median follow-up of 75 [40-168] months, 52% of patients developed progressive conduction slowing. Negative SCBC patients had fewer conduction defects (36% vs. 70%, p = 0.002) and ICD implantations (1% vs. 23%, P < 0.001). Non-missense variants were associated with more conduction slowing (71% vs. 42%, P = 0.04).
CONCLUSION: This multicentre study provides the largest analysis of SCN5A carriers with negative SCBC, showing excellent arrhythmic prognosis despite frequent progressive conduction slowing.
OBJECTIVE: To assess the clinical presentation and prognosis of SCN5A variant carriers with negative SCBC, and compare them to relatives with positive SCBC.
METHODS AND RESULTS: We retrospectively included patients from five university hospitals (2000-2024) carrying a pathogenic or likely pathogenic SCN5A variant and negative SCBC. Relatives with the same variant and positive SCBC were also analysed. Patients with spontaneous type 1 ECG, gain-of-function variants, double variants, or ACMG class 1-3 variants were excluded. Clinical, ECG, genetic, and follow-up data were collected. Conduction slowing was evaluated using the PR interval and QRS duration. The cohort included 162 patients from 43 families (median age 37 ± 19 years, 46% male), of whom 69 (43%) had negative SCBC. Among these 69 patients, 25 (36%) had baseline intraventricular conduction defects, and 19 (28%) had first-degree AV block. After a median follow-up of 75 [40-168] months, 52% of patients developed progressive conduction slowing. Negative SCBC patients had fewer conduction defects (36% vs. 70%, p = 0.002) and ICD implantations (1% vs. 23%, P < 0.001). Non-missense variants were associated with more conduction slowing (71% vs. 42%, P = 0.04).
CONCLUSION: This multicentre study provides the largest analysis of SCN5A carriers with negative SCBC, showing excellent arrhythmic prognosis despite frequent progressive conduction slowing.