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

Authors: Kenichiro Yamagata, Minoru Horie, Takeshi Aiba, Satoshi Ogawa, Yoshifusa Aizawa, Tohru Ohe, Masakazu Yamagishi, Naomasa Makita, Harumizu Sakurada, Toshihiro Tanaka, Akihiko Shimizu, Nobuhisa Hagiwara, Ryoji Kishi, Yukiko Nakano, Masahiko Takagi, Takeru Makiyama, Seiko Ohno, Keiichi Fukuda, Hiroshi Watanabe, Hiroshi Morita, Kenshi Hayashi, Kengo Kusano, Shiro Kamakura, Satoshi Yasuda, Hisao Ogawa, Yoshihiro Miyamoto, Jamie D. Kapplinger, Michael J. Ackerman, Wataru Shimizu - Circulation 2017 cited by 180

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.