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%/year. Compared with probands without mutations (SCN5A (-), n=355), probands with SCN5A mutations (SCN5A(+), n=60) experienced their first cardiac event at a younger age (34 vs. 42 years, P=0.013), had a higher positive rate of late potentials (89% vs. 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(+) vs. SCN5A(-): hazard ratio, 2.0 and P=0.045; history of aborted cardiac arrest vs. no such history: hazard ratio, 6.5 and P<0.001).
Conclusions—Brugada syndrome patients with SCN5A mutations exhibit more conduction abnormalities on electrocardiogram and have higher risk for cardiac events.
- In silico prediction
- Genotype-phenotype correlation
- Brugada syndrome
- sudden cardiac death
- risk stratification
- Received February 28, 2017.
- Accepted March 13, 2017.