Genotype-Phenotype Correlation of <i>SCN5A</i> Mutation for the Clinical and Electrocardiographic Characteristics of Probands With Brugada Syndrome: A Japanese Multicenter Registry.

Abstract

The genotype-phenotype correlation of <i>SCN5A</i> mutations as a predictor of cardiac events in Brugada syndrome remains controversial. We aimed to establish a registry limited to probands, with a long follow-up period, so that the genotype-phenotype correlation of <i>SCN5A</i> mutations in Brugada syndrome can be examined without patient selection bias. This multicenter registry enrolled 415 probands (n=403; men, 97%; age, 46±14 years) diagnosed with Brugada syndrome whose <i>SCN5A</i> gene was analyzed for mutations. During a mean follow-up period of 72 months, the overall cardiac event rate was 2.5%/y. In comparison with probands without mutations (<i>SCN5A</i> (-), n=355), probands with <i>SCN5A</i> mutations (<i>SCN5A</i> (+), n=60) experienced their first cardiac event at a younger age (34 versus 42 years, <i>P</i>=0.013), had a higher positive rate of late potentials (89% versus 73%, <i>P</i>=0.016), exhibited longer P-wave, PQ, and QRS durations, and had a higher rate of cardiac events (<i>P</i>=0.017 by log-rank). Multivariate analysis indicated that only <i>SCN5A</i> mutation and history of aborted cardiac arrest were significant predictors of cardiac events (<i>SCN5A</i> (+) versus <i>SCN5A</i> (-): hazard ratio, 2.0 and <i>P</i>=0.045; history of aborted cardiac arrest versus no such history: hazard ratio, 6.5 and <i>P</i><0.001). Brugada syndrome patients with <i>SCN5A</i> mutations exhibit more conduction abnormalities on ECG and have higher risk for cardiac events.