SCN5A gene variants and arrhythmic risk in Brugada syndrome: An updated systematic review and meta-analysis

Background A rare gene variant in SCN5A can be found in approximately 20-25% of patients with Brugada syndrome (BrS). Objective The aim of this systematic review and meta-analysis is to evaluate: (1) differences in clinical characteristics of BrS patients with and without SCN5A rare variants and (2) the prognostic role of SCN5A for ventricular arrhythmias in BrS. Methods PubMed and Cochrane Central Register of Controlled Trials (CENTRAL) were systematically searched from inception to January 2024 to identify all relevant studies. Studies were analyzed if including patients diagnosed with BrS in whom genetic testing for SCN5A variants was performed and arrhythmic outcomes were reported. Results A total of 17 studies with 3568 BrS patients, of whom 3030 patients undergone to genetic testing for SCN5A variants, fulfilled the eligibility criteria and were included. Compared with SCN5A- patients, SCN5A+ BrS patients had more frequently spontaneous type I ECG, history of syncope and documented arrhythmias. Furthermore, higher PQ and QRS intervals in SCN5A+ BrS patients, compared with SCN5A- have been found. The pooled analysis demonstrated a significant association between the presence of SCN5A rare variants in BrS patients and the risk of MAEs, with a pooled OR of 2.14 (95% CI: 1.53; 2.99, I2 = 29%). Conclusion SCN5A+ BrS patients showed a worse clinical phenotype compared with SCN5A-. The pooled analysis demonstrated a significant association between SCN5A+ mutation status and the risk of MAEs in BrS patients.