Abstract 14557: Prognostic Role of Pathogenic Mutations in Brugada Syndrome: Results From Wide Gene Testing

Abstract

Introduction: A pathogenic/likely pathogenic (P/LP) mutation can be found in 20-25% of patients with Brugada syndrome (BrS) and a P/LP mutation in SCN5A is associated with a worse prognosis. However, the prognosis of non SCN5A genes mutations is unclear. Methods: All BrS patients, were prospectively enrolled in the UZB registry between 1992 and 2022. Inclusion criteria for this study were: 1) BrS diagnosis; 2) Genetic analysis performed with a wide gene panel; 3) Classification of variants following ACMG guidelines. Patients with a P/LP variant in SCN5A were defined as (P+/SCN5A+); patients with a P/LP variant in a gene different from SCN5A were defined as (P+/SCN5A-). All other patients were classified as (P-). Results: A total of 452 BrS patients were analyzed. Any P/LP mutation was found in 108 (23.9%) patients, 94 (20.8%) patients P+/SCN5A+ and 14 (3.1%) patients P+/SCN5A-. Compared with P- patients, P+ patients were younger, more frequently had a spontaneous BrS type I ECG, sinus node dysfunction, aborted sudden cardiac death history and longer PQ interval, Table 1. After a mean follow-up of 116.7 months, 47 patients (10.4%) experienced a ventricular arrhythmia (VA). At survival analysis, P- patients had higher VA free survival, compared with P+/SCN5A+ (93% vs 81.9%, p=0.023) and with P+/SCN5A- (93% vs 57.1%, p<0.001). Among P+ patients, P+/SCN5A+ patients had higher VA free survival compared with P+/SCN5A- (81.9% vs 57.1%, p=0.023), Figure 2. At Cox multivariate analysis, P+ was an independent predictor of VA occurrence (HR= 2.23, CI 95% 1.10-4.58, p=0.027). Conclusions: In a large BrS cohort, the diagnostic yield for P/LP mutations is 23.9%. P+ is an independent predictor of VA.