Genotype-Phenotype Correlation of SCN5A Mutation for the Clinical and Electrocardiographic Characteristics of Probands With Brugada Syndrome

Abstract

In Brugada syndrome（BrS）, SCN5A is found in 15 – 20％, though it is unknown whether it has a clinical impact for predicting future cardiac events. This multicenter registry enrolled 415 probands（n=403 ; men, 97％; age, 46±14 years）diagnosed with Brugada syndrome whose SCN5A gene was analyzed for mutations. The mean follow-up period was 72 months and the overall cardiac event rate was 2.5％/y. Probands without mutations（SCN5A（－）, n=355）experienced their first cardiac event at a younger age（34 versus 42 years, p=0.013）, had a higher positive rate of late potentials（89％ versus 73％, p=0.016）, exhibited longer P-wave, PQ, and QRS durations, and had a higher rate of cardiac events（p=0.017 by log-rank） compared to probands with SCN5A mutations（SCN5A（+）, n=60）. In multivariate analysis, only SCN5A mutation and history of aborted cardiac arrest were significant predictors of cardiac events（SCN5A（+）versus SCN5A（－）: hazard ratio, 2.0 and p=0.045 ; history of aborted cardiac arrest versus no such history : hazard ratio, 6.5 and p＜0.001）. In conclusion, BrS patients with SCN5A mutations exhibit more conduction abnormalities on ECG and have a higher risk for cardiac events.