Abstract

BACKGROUND: Atrial fibrillation (AF) occurs in up to 20% of patients with Brugada syndrome (BrS), yet its risk factors and prognostic implications remain uncertain. OBJECTIVES: This study sought to identify risk factors for AF in patients with non-high-risk BrS and to evaluate the impact of AF on ventricular arrhythmias (VAs), sick sinus syndrome (SSS), and stroke in non-high-risk BrS. METHODS: This was a multicenter, retrospective study conducted across 20 international centers. Non-high-risk BrS patients were stratified based on the presence or absence of AF. The primary endpoint was the occurrence of VAs, defined as sustained ventricular tachycardia, ventricular fibrillation, or arrhythmic sudden cardiac death. RESULTS: A total of 686 BrS patients were analyzed (39.3 years of age, 33.1% female, 31.8% spontaneous type 1 electrocardiogram, 36.0% pathogenic/likely pathogenic SCN5A variant), including 280 with AF (40.8%). Proband status and older age were associated with AF at Cox regression analysis. Over a median follow-up of 48.8 months, the incidence of VAs was 0.26% per year, with no significant difference between patients with and without AF (HR: 0.67; P = 0.58). Early-onset AF (<20 years) was associated with significantly higher risk of VAs (P < 0.001). SSS was twice as prevalent in BrS patients with AF (10.0% vs 6.2%; P = 0.047), and stroke occurred exclusively in the AF group (2.5%), despite low CHA2DS2-VA (mean 0.5). CONCLUSIONS: The presence of AF in non-high-risk BrS does not identify patients with higher risk of VAs. However, early-onset AF (<20 years) defines a distinct subgroup with elevated risk. Patients with AF and BrS have a significantly higher risk of SSS and stroke.