TY - JOUR
T1 - Genotype-Phenotype Correlation of SCN5A Mutation for the Clinical and Electrocardiographic Characteristics of Probands with Brugada Syndrome
T2 - A Japanese Multicenter Registry
AU - Yamagata, Kenichiro
AU - Horie, Minoru
AU - Aiba, Takeshi
AU - Ogawa, Satoshi
AU - Aizawa, Yoshifusa
AU - Ohe, Tohru
AU - Yamagishi, Masakazu
AU - Makita, Naomasa
AU - Sakurada, Harumizu
AU - Tanaka, Toshihiro
AU - Shimizu, Akihiko
AU - Hagiwara, Nobuhisa
AU - Kishi, Ryoji
AU - Nakano, Yukiko
AU - Takagi, Masahiko
AU - Makiyama, Takeru
AU - Ohno, Seiko
AU - Fukuda, Keiichi
AU - Watanabe, Hiroshi
AU - Morita, Hiroshi
AU - Hayashi, Kenshi
AU - Kusano, Kengo
AU - Kamakura, Shiro
AU - Yasuda, Satoshi
AU - Ogawa, Hisao
AU - Miyamoto, Yoshihiro
AU - Kapplinger, Jamie D.
AU - Ackerman, Michael J.
AU - Shimizu, Wataru
N1 - Publisher Copyright:
© 2017 American Heart Association, Inc.
PY - 2017/6/6
Y1 - 2017/6/6
N2 - 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.
AB - 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.
KW - Brugada syndrome
KW - Computer similation
KW - Death
KW - Genetic association studies
KW - NAV1.5 voltage-gated sodium channel
KW - Risk assessment
KW - Sudden
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UR - http://www.scopus.com/inward/citedby.url?scp=85018802794&partnerID=8YFLogxK
U2 - 10.1161/CIRCULATIONAHA.117.027983
DO - 10.1161/CIRCULATIONAHA.117.027983
M3 - Article
C2 - 28341781
AN - SCOPUS:85018802794
SN - 0009-7322
VL - 135
SP - 2255
EP - 2270
JO - Circulation
JF - Circulation
IS - 23
ER -