Journal
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Volume 73, Issue 15, Pages 1978-1986Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacc.2019.01.061
Keywords
genetics; hypertrophic cardiomyopathy; network medicine
Categories
Funding
- NHGRI NIH HHS [U01 HG007690] Funding Source: Medline
- NHLBI NIH HHS [R37 HL061795, R01 HL139613, R56 HL131787, R21 HL145420, U54 HL119145] Funding Source: Medline
- NIGMS NIH HHS [P50 GM107618] Funding Source: Medline
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Hypertrophic cardiomyopathy (HCM) has been considered a heterogeneous cardiac disease ascribed solely to single sarcomere gene mutations. However, limitations of this hypothesis suggest that sarcomere mutations alone do not adequately explain all HCM clinical and pathobiological features. Disease-causing sarcomere mutations are absent in similar to 70% of patients with established disease, and sarcomere gene carriers can live to advanced ages without developing HCM. Some features of HCM are also inconsistent with the single sarcomere gene hypothesis, such as regional left ventricular hypertrophy and myocardial fibrosis, as well as structurally abnormal elongated mitral valve leaflets and remodeled intramural coronary arterioles, which involve tissue types that do not express cardiomyocyte sarcomere proteins. It is timely to expand the HCM research focus beyond a single molecular event toward more inclusive models to explain this disease in its entirety. The authors chart paths forward addressing this knowledge gap using novel analytical approaches, particularly network medicine, to unravel the pathobiological complexity of HCM. (C) 2019 by the American College of Cardiology Foundation.
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