Electrocardiographic Features in SCN5A Mutation-Positive Patients with Brugada and Early Repolarization Syndromes: A Systematic Review and Meta-Analysis

Abstract Background: Early repolarization syndrome (ERS) and Brugada syndrome (BrS) are both J-wave syndromes. Both can involve mutations in the SCN5A gene but may exhibit distinct electrocardiographic (ECG) differences. The aim of this systematic review and meta-analysis is to investigate possible differences in ECG markers between SCN5A positive patients with ERS and BrS. Methods: PubMed and Embase, were searched from their inception to October 20th, 2021 for human studies containing the search terms “SCN5A” and “variant” and “early reporlarization” or “Brugada”, with no language restrictions. Results: A total of 328 studies were identified. After full text screening, 12 studies met our inclusion criteria and were included in this present study. 104 ERS patients (mean age: 30.86 ±14.45) and 2000 BrS patients (mean age: 36.17 ±11.39) were studied. Our meta-analysis found that ERS patients had a significantly lower heart rate (standardized mean difference [SMD]a= 14.69, 95% confidence interval [CI] = 21.43, 7.94, P = 0.0001), shorter QRS duration (SMD = 13.90, 95% CI = 17.16, 10.65, P = 0.0001) and shorter QTc [corrected QT interval] (SDM = 21.52, 95% CI = 33.77, 9.26, P = 0.0006) than BrS patients. Conclusion: BrS patients with positive SCN5A mutations exhibited prolonged QRS, indicating conduction abnormalities, whereas ERS patients with positive SCN5A mutations showed normal QRS. By contrast, whilst QTc intervals were longer in BrS than in ERS SCN5A positive patients, they were within normal limits. Further studies are needed to examine the implications of these findings for arrhythmic risk stratification.