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Prognostic predictive value of gene mutations in Japanese patients with hypertrophic cardiomyopathy

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Abstract

Although some studies have attempted to find useful prognostic factors in hypertrophic cardiomyopathy (HCM), those results are not fully helpful for use in actual clinical practice. Furthermore, several genetic abnormalities associated with HCM have been identified. However, the genotype–phenotype correlation in HCM remains to be elucidated. Here, we attempted to assess patients with different types of gene mutations causing HCM and investigate the prognosis. A total of 140 patients with HCM underwent a screening test for myofilament gene mutations by direct sequencing of eight sarcomeric genes. Patients with a single mutation in cardiac troponin T, cardiac troponin I, α-tropomyosin, and regulatory and essential light chains were excluded from the study because the number of cases was too small. The clinical presentations and outcomes of the remaining 127 patients with HCM, 31 β-myosin heavy chain (MYH7) mutation carriers, 19 cardiac myosin-binding protein C (MYBPC3) mutation carriers, and 77 mutation non-carriers were analyzed retrospectively. MYBPC3 mutation carriers had a high frequency of ventricular arrhythmia and syncope. Kaplan–Meier curves revealed no significant difference in prognosis among the three groups, but a lack of family history of sudden death (SD) and a past history of syncope were significantly related to poor prognosis. An absence of family history of SD and past history of syncope are useful prognostic factors in patients with HCM. MYH7 and MYBPC3 mutations did not significantly influence prognosis compared to non-carriers. However, patients with the MYBPC3 mutation should be closely followed for the possibility of SD.

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Acknowledgements

The authors thank the patients and their family members. They also thank the health-care providers of Asahikawa Medical University Hospital, Yokohama Municipal Citizen’s Hospital, Iwate Medical University Hospital, University of Miyazaki Hospital, Kyushu University Hospital, Gunma University Hospital, Keio University Hospital, Sakakibara Memorial Hospital, Sapporo Medical University Hospital, The Jikei University School of Medicine, Saitama Medical Center Jichi Medical University, Kagoshima Cooperative Hospital, Medical Corporation Kyojinkai Komatsu Hospital, Showa University Northern Yokohama Hospital, Shinmatsudo Central General Hospital, Kanagawa Children’s Medical Center, St. Marianna University School of Medicine Hospital, Seirei Hamamatsu General Hospital, Aoyama Hospital Tokyo Women’s Medical University, Sendai Cardiovascular Center, Chiba Cerebral and Cardiovascular Center, Ogaki Municipal Hospital, Osaka University Hospital, Nagano Children’s Hospital, Medical Corporation Bokoi Tenshi Hospital, Tsuchiura Kyodo General Hospital, University of Tokyo Hospital, University of Tokyo Branch Hospital, Toho University Omori Medical Center, Nihon University Itabashi Hospital, University of Toyama Hospital, Hyogo Prefectural Kobe Children’s Hospital, Toyohashi Municipal Hospital, and Hokkaido University Hospital for agreeing to collaborate for this study.

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Authors and Affiliations

  1. Department of Pediatrics, National Defense Medical College, Tokorozawa, Japan

    Ayako Chida, Yoichi Kawamura & Shigeaki Nonoyama

  2. Department of Pediatric Cardiology, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan

    Ayako Chida, Kei Inai, Eriko Shimada, Mitsuyo Shimada, Michiko Furutani, Yoshiyuki Furutani & Toshio Nakanishi

  3. Department of Preventive Medicine and Public Health, National Defense Medical College, Tokorozawa, Japan

    Hiroki Sato

  4. International Research and Educational Institute for Integrated Medical Sciences (IREIIMS), Tokyo Women’s Medical University, Tokyo, Japan

    Tsutomu Nishizawa & Rumiko Matsuoka

  5. Department of Pediatrics, Asahikawa Medical University Hospital, Asahikawa, Japan

    Masaya Sugimoto

  6. Department of Pediatrics, Yokohama Municipal Citizen’s Hospital, Yokohama, Japan

    Jun Ishihara

  7. Department of Pediatrics, The Jikei University School of Medicine, Minato, Japan

    Masako Fujiwara

  8. Showa University Northern Yokohama Hospital Children’s Medical Center, Shinagawa, Japan

    Takashi Soga

  9. Department of General Medicine, Tokyo Women’s Medical University, Tokyo, Japan

    Masatoshi Kawana

  10. Department of Cardiology, Sendai Cardiovascular Center, Sendai, Japan

    Shinya Fuji

  11. Department of Adult Congenital Heart Disease and Pediatric Cardiology, Chiba Cerebral and Cardiovascular Center, Ichihara, Japan

    Shigeru Tateno

  12. Department of Pediatric Cardiology and Neonatology, Ogaki Municipal Hospital, Ogaki, Japan

    Kenji Kuraishi

  13. Department of Pediatrics, Osaka University Hospital, Suita, Japan

    Shigetoyo Kogaki

  14. Department of Cardiology, Social Medical Corporation Bokoi Tenshi Hospital, Sapporo, Japan

    Mitsuhiro Nishimura

  15. Department of Pediatrics and Child Health, Nihon University School of Medicine, Tokyo, Japan

    Mamoru Ayusawa

  16. Department of Pediatrics, University of Toyama Hospital, Toyama, Japan

    Fukiko Ichida

  17. Department of Pediatrics, Hokkaido University Hospital, Hokkaido, Japan

    Hirokuni Yamazawa

  18. International Center for Molecular, Cellular and Immunological Research (IMCIR), Tokyo Women’s Medical University, Tokyo, Japan

    Rumiko Matsuoka

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  1. Ayako Chida
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  2. Kei Inai
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Corresponding author

Correspondence to Toshio Nakanishi.

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Conflict of interest

This work was supported by the program for promoting the Establishment of Strategic Research Centers, Special Coordination Funds for Promoting Science and Technology, Ministry of Education, Culture, Sports, Science and Technology, Japan. The authors have no conflicts of interest to disclose.

Electronic supplementary material

Below is the link to the electronic supplementary material. Pedigrees of the HCM families with sarcomeric gene mutations. (a) MYH7, (b) MYBPC3, (c) TNNT2, (d) TNNI3, (e) TPM1 and (f) MYL2. Arrow indicates a proband patient. Filled square and circle indicate a HCM patient. Shadowed square and circle indicate a patient with heart disease without detailed information. Mutation carrier and non-carrier are indicated by (+) and (−), respectively.

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Chida, A., Inai, K., Sato, H. et al. Prognostic predictive value of gene mutations in Japanese patients with hypertrophic cardiomyopathy. Heart Vessels 32, 700–707 (2017). https://doi.org/10.1007/s00380-016-0920-0

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