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

A Japanese Multicenter Registry

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 & 9 others Kenshi Hayashi, Kengo Kusano, Shiro Kamakura, Satoshi Yasuda, Hisao Ogawa, Yoshihiro Miyamoto, Jamie D. Kapplinger, Michael J. Ackerman, Wataru Shimizu

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2255-2270
Number of pages16
JournalCirculation
Volume135
Issue number23
DOIs
Publication statusPublished - 2017 Jun 6

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Brugada Syndrome
Genetic Association Studies
Registries
Mutation
Heart Arrest
Selection Bias
Patient Selection
Electrocardiography
Multivariate Analysis
History

Keywords

  • Brugada syndrome
  • Computer similation
  • Death
  • Genetic association studies
  • NAV1.5 voltage-gated sodium channel
  • Risk assessment
  • Sudden

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Genotype-Phenotype Correlation of SCN5A Mutation for the Clinical and Electrocardiographic Characteristics of Probands with Brugada Syndrome : A Japanese Multicenter Registry. / Yamagata, Kenichiro; Horie, Minoru; Aiba, Takeshi; Ogawa, Satoshi; Aizawa, Yoshifusa; Ohe, Tohru; Yamagishi, Masakazu; Makita, Naomasa; Sakurada, Harumizu; Tanaka, Toshihiro; Shimizu, Akihiko; Hagiwara, Nobuhisa; Kishi, Ryoji; Nakano, Yukiko; Takagi, Masahiko; Makiyama, Takeru; Ohno, Seiko; Fukuda, Keiichi; Watanabe, Hiroshi; Morita, Hiroshi; Hayashi, Kenshi; Kusano, Kengo; Kamakura, Shiro; Yasuda, Satoshi; Ogawa, Hisao; Miyamoto, Yoshihiro; Kapplinger, Jamie D.; Ackerman, Michael J.; Shimizu, Wataru.

In: Circulation, Vol. 135, No. 23, 06.06.2017, p. 2255-2270.

Research output: Contribution to journalArticle

Yamagata, K, Horie, M, Aiba, T, Ogawa, S, Aizawa, Y, Ohe, T, Yamagishi, M, Makita, N, Sakurada, H, Tanaka, T, Shimizu, A, Hagiwara, N, Kishi, R, Nakano, Y, Takagi, M, Makiyama, T, Ohno, S, Fukuda, K, Watanabe, H, Morita, H, Hayashi, K, Kusano, K, Kamakura, S, Yasuda, S, Ogawa, H, Miyamoto, Y, Kapplinger, JD, Ackerman, MJ & Shimizu, W 2017, 'Genotype-Phenotype Correlation of SCN5A Mutation for the Clinical and Electrocardiographic Characteristics of Probands with Brugada Syndrome: A Japanese Multicenter Registry', Circulation, vol. 135, no. 23, pp. 2255-2270. https://doi.org/10.1161/CIRCULATIONAHA.117.027983
Yamagata, Kenichiro ; Horie, Minoru ; Aiba, Takeshi ; Ogawa, Satoshi ; Aizawa, Yoshifusa ; Ohe, Tohru ; Yamagishi, Masakazu ; Makita, Naomasa ; Sakurada, Harumizu ; Tanaka, Toshihiro ; Shimizu, Akihiko ; Hagiwara, Nobuhisa ; Kishi, Ryoji ; Nakano, Yukiko ; Takagi, Masahiko ; Makiyama, Takeru ; Ohno, Seiko ; Fukuda, Keiichi ; Watanabe, Hiroshi ; Morita, Hiroshi ; Hayashi, Kenshi ; Kusano, Kengo ; Kamakura, Shiro ; Yasuda, Satoshi ; Ogawa, Hisao ; Miyamoto, Yoshihiro ; Kapplinger, Jamie D. ; Ackerman, Michael J. ; Shimizu, Wataru. / Genotype-Phenotype Correlation of SCN5A Mutation for the Clinical and Electrocardiographic Characteristics of Probands with Brugada Syndrome : A Japanese Multicenter Registry. In: Circulation. 2017 ; Vol. 135, No. 23. pp. 2255-2270.
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abstract = "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.",
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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

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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