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

BACKGROUND: The genotype-phenotype correlation of SCN5A 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 SCN5A mutations in Brugada syndrome can be examined without patient selection bias.

METHODS: 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.

RESULTS: During a mean follow-up period of 72 months, the overall cardiac event rate was 2.5%/y. In comparison with probands without mutations ( SCN5A (-), n=355), probands with SCN5A mutations ( SCN5A (+), n=60) 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). Multivariate analysis indicated that 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).

CONCLUSIONS: Brugada syndrome patients with SCN5A mutations exhibit more conduction abnormalities on ECG and have higher risk for cardiac events.