Long-term outcome and therapeutic evolution in Brugada syndrome: A 30-year single-center experience

Brugada syndrome (BrS) continues to present clinical challenges, despite three decades of dedicated research and evolving therapeutic strategies. In patients at risk for ventricular arrhythmias (VAs) and sudden cardiac death, ICD remains the cornerstone of preventive therapy. Additional treatments—such as anti-arrhythmic drugs (AADs) and, more recently, epicardial substrate ablation—have been introduced over time, following updated consensus and guidelines. The debate on risk stratification and the therapeutic approach for primary prevention, especially in asymptomatic patients, remains active.

This study aimed to evaluate the clinical characteristics, management, and long-term outcomes of BrS patients treated at a single center over 30 years, with a specific focus on high-risk patients, assessing how these strategies have evolved over time and their impact on patient outcomes.

Patients diagnosed with BrS were prospectively enrolled. Inclusion criteria were: 1) a Brugada type 1 ECG pattern, either spontaneous or drug-induced, and 2) consistent follow-up. Risk stratification was based on clinical characteristics and prior arrhythmic events. Beginning in 2016, high-risk patients were also treated with video-thoracoscopic epicardial ablation. ICD implantation strategies evolved over time, adapting to each patient's clinical and demographic profile. Pharmacological therapy was classified into quinidine and other AADs.

A total of 1206 BrS patients were included, of whom 397 (33%) received at least one form of treatment: 306 (25.4%) received an ICD, 127 (12.4%) were treated with AADs (29 with quinidine [2.4%]), and 71 (5.9%) underwent epicardial substrate ablation. Treatment rates declined across the three decades (51% vs. 32% vs. 28%, p=0.02). Among ICD recipients, 84% were for primary prevention and 16% for secondary prevention. Over a mean follow-up of 113.7 months, 23.9% of patients experienced VAs, 15.4% had at least one inappropriate ICD shock, and 27.1% required device revision or lead replacement. Patients with secondary prevention ICDs had higher rates of ventricular and supraventricular arrhythmias. SCN5A loss-of-function mutations and prior non-sustained VAs were associated with an increased risk of VAs. Quinidine therapy was associated with a 40.3% non-significant reduction in VA episodes, while other AADs showed a slight, non-significant increase in VA burden. Ablation led to an 80% reduction in VA burden (annualized event rate [AER] pre 0.05, AER post 0.01; p=0.04). The overall mortality rate was 5.9%, with cardiac causes accounting for 22.2% of deaths.

This 30-year analysis underscores the evolution of BrS management, particularly in high-risk patients. ICD therapy remains essential in preventing fatal VAs, though frequent device-related complications may occur. Epicardial ablation significantly reduces VA incidence in high-risk patients, providing a promising adjunct to ICD therapy.

Evolution of risk factors and treatments