Prognosis of Brugada patients according to their SCN5A genetic status

Background Brugada syndrome (BrS) is an inherited arrhythmia syndrome with an increased risk of of syncope and sudden cardiac death (SCD). A pathogenic/likely pathogenic variant in SCN5A is found in 20-25% of patients with BrS. The aim of this study is to compare the prognosis of BrS patient according to their genetic status. Methods Consecutive patients affected with BrS were recruited in a multicentric prospective registry in France (15 centers) between 1994 and 2024. Patients were enrolled if they have a minimal follow-up of one year. The INSEE death registry was used to report deaths. Lethal arrhythmic event (LAE) was defined as sudden cardiac death, appropriate ICD therapy or sustained ventricular arrhythmias. Results Atotal of 2184 patients (mean age 46 [35-56] years; 1466 males, 67%) were enrolled. Among them, 636 (29%) present with a spontaneous type 1 ECG pattern. Six hundred and fifty-nine patients (32%) were symptomatic. Four hundred and thirty-one patients (19,7%) were carriers of a pathogenic/likely pathogenic variant in SCN5A gene. Mean follow-up were 7,9 [3,7-12,8] years (8,7 [4,4-14,1] for SCN5A carrier and 7,7 [3,7-12,4] for SCN5A non carrier, p=0,004). During the follow-up, 119 patients (5,4%) deceased (mean age 69 [60-80]) without difference between SCN5A patients and non-carriers (respectively 21 (4,9%) vs 98 (5,6%), p=0,6; mean age 68 [54-82] vs 69 [61-79], p=0,8). Additionally, 99 patients (4,5%) underwent LAE including 30 (7%) in SCN5A carriers and 69 (3,9%) in non-carrier (p=0.017). The annual rate of event was 0,8%/year for SCN5A carrier patients versus 0,5%/year for non-carrier patients. Conclusion In the largest BrS patients cohort ever described, SCN5A carrier patients represent a higher-risk group than non-carrier patients with a respective annual rate of event of 0,8%/year and 0,5%/year.