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Hypertrophic Cardiomyopathy: Genetics, Pathogenesis, Clinical Manifestations, Diagnosis, and Therapy
Open accessAbstract
Hypertrophic cardiomyopathy (HCM) is a genetic disorder that is characterized by left ventricular hypertrophy unexplained by secondary causes and a nondilated left ventricle with preserved or increased ejection fraction. It is commonly asymmetrical with the most severe hypertrophy involving the basal interventricular septum. Left ventricular outflow tract obstruction is present at rest in about one third of the patients and can be provoked in another third. The histological features of HCM include myocyte hypertrophy and disarray, as well as interstitial fibrosis. The hypertrophy is also frequently associated with left ventricular diastolic dysfunction. In the majority of patients, HCM has a relatively benign course. However, HCM is also an important cause of sudden cardiac death, particularly in adolescents and young adults. Nonsustained ventricular tachycardia, syncope, a family history of sudden cardiac death, and severe cardiac hypertrophy are major risk factors for sudden cardiac death. This complication can usually be averted by implantation of a cardioverter-defibrillator in appropriate high-risk patients. Atrial fibrillation is also a common complication and is not well tolerated. Mutations in over a dozen genes encoding sarcomere-associated proteins cause HCM. MYH7 and MYBPC3 , encoding β-myosin heavy chain and myosin-binding protein C, respectively, are the 2 most common genes involved, together accounting for ≈50% of the HCM families. In ≈40% of HCM patients, the causal genes remain to be identified. Mutations in genes responsible for storage diseases also cause a phenotype resembling HCM (genocopy or phenocopy). The routine applications of genetic testing and preclinical identification of family members represents an important advance. The genetic discoveries have enhanced understanding of the molecular pathogenesis of HCM and have stimulated efforts designed to identify new therapeutic agents.
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“This clinical variability can, in part, be explained by the influence of modifiable cardiometabolic risk factors, such as obesity, diabetes, and hypertension [6].”
From Association of GLP-1 receptor agonist use with cardiovascular outcomes in patients with non-obstructive hypertrophic cardiomyopathy (2026) · cites this paper as [6]
Experimental — accuracy not yet measuredIn the citing paper
“Hypertrophic cardiomyopathy (HCM) is characterized by cardiac hypertrophy, a non-dilated left ventricle (LV), and a normal or increased EF.”
From Cardiovascular disease models: A game changing paradigm in drug discovery and screening (2019) · cites this paper as [52]
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Metadata
- Authors
- Marian, A. J., & Braunwald, E.
- Affiliations
- Brigham and Women's Hospital (US)
- From the Center for Cardiovascular Genetics, Institute of Molecular Medicine, Department of Medicine, University of Texas Health Sciences Center at Houston (A.J.M.); Texas Heart Institute, Houston (A.J.M.); and TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA (E.B.).
- ORCID
- Marian, Ali J.
- Venue
- Circulation Research
- Published
- 2017-09-15
- Volume
- 121
- Issue
- 7
- Pages
- 749-770
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- PMC
- PMC5654557
- OpenAlex
- W2756203218
- Cited by
- 1,403
- References
- 252
- Citations by year
- 2026: 175 · 2025: 226 · 2024: 219 · 2023: 199 · 2022: 153 · 2021: 174 · 2020: 103 · 2019: 83 · 2018: 61 · 2017: 6
- FWCI
- 9.75
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL088498, R01HL132401)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Effects of Exercise
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- hypertrophic cardiomyopathy, left ventricular hypertrophy, left ventricular outflow tract obstruction, sudden cardiac death, non-sustained ventricular tachycardia, syncope, cardioverter-defibrillator implantation, atrial fibrillation, sarcomere gene mutations, MYH7, MYBPC3, genetic testing, phenocopy, storage diseases, left ventricular diastolic dysfunction, interstitial fibrosis, molecular pathogenesis
- MeSH terms
- Animals, Biopsy, Cardiomyopathy, Dilated, DNA Mutational Analysis, Genetic Markers, Humans, Mutation, Myocardium, Phenotype, Predictive Value of Tests, Prognosis, Risk Factors, Ventricular Function, Left, Risk Assessment, Genetic Predisposition to Disease, Molecular Diagnostic Techniques, Cardiac Imaging Techniques
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