Abstract
Hypertrophic cardiomyopathy (HCM) is characterized by unexplained left ventricular hypertrophy. This study aimed to reveal the clinical and genetic backgrounds of the unique HCM with mid-ventricular obstruction (HCM-MVO) subtype. We identified 34 patients with HCM-MVO in our cohort, and about half (47%) of these patients experienced adverse events. We analyzed 67 cardiomyopathy-associated genes in the patients. In total, 44% of patients with HCM-MVO carried the cardiomyopathy-associated genetic variant (CAGV) in 14 genes. Only 21% of patients carried HCM-associated CAGVs in major sarcomere-encoding genes, while 18% of patients carried CAGVs in dilated cardiomyopathy/arrhythmogenic right ventricular cardiomyopathy-associated genes. CAGVs were more frequent in patients with asymmetric septal hypertrophy (ASH) than in those without ASH. These findings suggest that HCM-MVO is a high-risk group and may have different etiologies from typical HCM.
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Gersh BJ, Maron BJ, Bonow RO, Dearani JA, Fifer MA, Link MS, et al. ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2011;2011:e783–831.
Minami Y, Kajimoto K, Terajima Y, Yashiro B, Okayama D, Haruki S, et al. Clinical implications of midventricular obstruction in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol. 2011;57:2346–55.
Efthimiadis GK, Pagourelias ED, Parcharidou D, Gossios T, Kamperidis V, Theofilogiannakos EK, et al. Clinical characteristics and natural history of hypertrophic cardiomyopathy with midventricular obstruction. Circ J. 2013;77:2366–74.
Hayashi T, Tanimoto K, Hirayama-Yamada K, Tsuda E, Ayusawa M.Nunoda S,et al. Genetic background of Japanese patients with pediatric hypertrophic and restrictive cardiomyopathy. J Hum Genet. 2018; Doi:10.1038/s10038-018-0479-y.
Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, Korbel JO, et al. A global reference for human genetic variation. Nature. 2015;526:68–74.
Lek M, Karczewski KJ, Minikel EV, Samocha KE, Banks E, Fennell T, et al. Analysis of protein-coding genetic variation in 60,706 humans. Nature. 2016;536:285–91.
Higasa K, Miyake N, Yoshimura J, Okamura K, Niihori T, Saitsu H, et al. Human genetic variation database, a reference database of genetic variations in the Japanese population. J Hum Genet. 2016;61:547–53.
Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17:405–24.
Marian AJ, Braunwald E. Hypertrophic cardiomyopathy: genetics, pathogenesis, clinical manifestations, diagnosis, and therapy. Circ Res. 2017;121:749–70.
Cahill TJ, Ashrafian H, Watkins H. Genetic cardiomyopathies causing heart failure. Circ Res. 2013;113:660–75.
Acknowledgements
We would like to thank Yukiko Ueda and Chinami Sonobe for their excellent technical assistance with respect to NGS. We also thank Akiko Ito, Reiko Makitani-Ishida, and Toyo Fukui for technical assistance with respect to Sanger sequencing. This work was supported by the Japan Society for the Promotion of Science KAKENHI grant number 258606625 (N.I.), 26460407 (T.H.), 17K08684 (T.H.), 15K15095 (A.K.), 16H05296 (A.K.), a grant from The Institute of Seizon and Life Science (T.H), and Nanken-Kyoten, Tokyo Medical and Dental University (TMDU).
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Inagaki, N., Hayashi, T., Takei, Y. et al. Clinical and genetic backgrounds of hypertrophic cardiomyopathy with mid-ventricular obstruction. J Hum Genet 63, 1273–1276 (2018). https://doi.org/10.1038/s10038-018-0509-9
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/s10038-018-0509-9
This article is cited by
-
Accurate Classification of Non-ischemic Cardiomyopathy
Current Cardiology Reports (2023)
-
Cardiac magnetic resonance in hypertrophic and dilated cardiomyopathies
La radiologia medica (2020)
