Lifelong Clinical Impact of the Presence of Sarcomere Gene Mutation in Japanese Patients With Hypertrophic Cardiomyopathy

• Nakashima Yasuteru

  Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University

• Kubo Toru

  Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University

• Sugiura Kenta

  Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University

• Ochi Yuri

  Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University

• Takahashi Asa

  Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University

• Baba Yuichi

  Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University

• Hirota Takayoshi

  Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University

• Yamasaki Naohito

  Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University

• Kimura Akinori

  Department of Molecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University

• Doi Yoshinori L.

  Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University

• Kitaoka Hiroaki

  Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University

Abstract

Background:Hypertrophic cardiomyopathy (HCM) is mainly caused by mutations in sarcomere genes. Regarding the clinical implications of genetic information, little is known about the lifelong clinical effect of sarcomere mutations in Japanese HCM patients. Methods and Results:We studied 211 consecutive Japanese patients with HCM who had agreed to genetic testing between 2003 and 2013. Genetic analyses were performed by direct DNA sequencing in the 6 common sarcomere genes (MYH7,MYBPC3,TNNT2,TNNI3,TPM1,ACTC). Through variant filtering, 21 mutations were identified in 67 patients. After excluding 8 patients whose variants were determined as having uncertain significance, finally 203 patients (130 men, age at study entry: 61.8±14.1 years) were investigated for clinical presentation and course. At the time of study entry, patients with mutations were younger, had more frequent non-sustained ventricular tachycardia, had greater interventricular wall thickness, were more frequently in the dilated phase and less frequently had apical HCM. Through their lifetimes, a total of 98 HCM-related morbid events occurred in 72 patients. Survival analysis revealed that patients with sarcomere gene mutations experienced those morbid events significantly more frequently, and this tendency was more prominent for lethal arrhythmic events. Conclusions:In our HCM cohort, patients with sarcomere gene mutations had poorer lifelong outcome. Genetic information is considered important for better management of HCM.

Journal

• Circulation Journal

  Circulation Journal 84 (10), 1846-1853, 2020-09-25

  The Japanese Circulation Society

Keywords

• Hypertrophic cardiomyopathy
• Sarcomere mutations

Details

• CRID: 1390004222622204160
• NII Article ID: 130007907598
• NII Book ID: AA11591968
• DOI: 10.1253/circj.cj-20-0027
• ISSN: 13474820
• ISSN: 13469843
• NDL BIB ID: 030648515
• PubMed: 32830170
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I030648515
• Web Site: https://www.jstage.jst.go.jp/article/circj/84/10/84_CJ-20-0027/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2021183024
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed