Long-term performance of different treatment approaches in Brugada Syndrome
C Monaco, M Cespon-Fernandez, K Kneizeh, K Benali, A Del Monte, D Della Rocca, K Vlachos, L Pannone, T Pambrun, J Duchateau, N Derval, G B Chierchia, F Sacher, C De Asmundis, M HaissaguerreAbstract
Introduction
Brugada syndrome (BrS) is associated with ventricular arrhythmias (VAs) and sudden cardiac death in predisposed individuals. Over three decades, therapeutic strategies have evolved, but long-term comparative data on treatment performance in real-world populations remain limited.
Purpose
We evaluated, in a single pooled cohort from two centres, the temporal evolution of BrS management and the long-term effectiveness of available therapies.
Methods
We reviewed consecutive BrS patients enrolled from 1992 to 2025 and recorded prospectively in institutional registries. Inclusion required a spontaneous or drug-induced type-1 ECG pattern, exclusion of structural heart disease, and follow-up >12 months. Indications and methodologies for risk stratification evolved in accordance with consensus documents and guidelines. Management of high-risk patients included antiarrhythmic drugs (AADs; analysed as quinidine vs other AADs), implantable cardioverter-defibrillator (ICD), and epicardial substrate ablation. The primary endpoint was the change in VA burden before versus after therapy, quantified as annualised event rate (AER). The secondary endpoint compared epicardial substrate ablation with conventional management for reduction in VA burden. To mitigate confounding by indication, we used 1:2 nearest-neighbour propensity-score matching. Variables were summarised as mean±SD, median [IQR] or n (%). Parametric or non-parametric tests were used as appropriate; significance was set at two-sided p<0.05. AER analyses were restricted to single-therapy cohorts (quinidine-only, other AADs-only, ablation-only).
Results
Among 2011 BrS patient enrolled (37.8±17.8 years, 52.4% male), approximately one-third underwent at least one treatment, with the proportion declining from the first to subsequent decades, consistent with expanding identification of low- and intermediate-risk phenotypes through broader screening. Over a mean follow-up of 113.7±74.6 months, 4.6% experienced sustained VA, more frequent among treated individuals (12.1%)—reflecting higher baseline risk—than among those initially classified as low/medium risk (0.98%). Quinidine was associated with a 40% reduction in VA burden (AER 0.030 to 0.018; p=0.04), whereas other AADs showed no significant change (AER 0.012 to 0.014; p=0.78), aligned with their frequent use for concomitant indications other than VAs prevention. Epicardial substrate ablation yielded a 71.4% AER reduction (0.035 to 0.010; p=0.03). In the propensity-matched comparison, 5-year VA-free survival remained higher after ablation (96.0%; 95%CI 90.5–97.7) than with conventional management (88.9%; 95%CI 83.4–90.5; p=0.045), supporting a treatment effect beyond baseline selection.
Conclusion
Across three decades, epicardial ablation showed the most favourable arrhythmic results. Clinical practice has moved towards more selective intervention in high-risk patients as the wider BrS population has expanded with lower-risk profiles.Ventricular arrhythmia burdenPropensity score matching