Hypertrophic Cardiomyopathy: Genetics, Pathogenesis, Clinical Manifestations, Diagnosis, and Therapy

Circ Res. 2017 Sep 15;121(7):749-770. doi: 10.1161/CIRCRESAHA.117.311059.


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.

Keywords: cardiomyopathy; cardiomyopathy, hypertrophic; death, sudden, cardiac; heart failure; human; mutation; myosin heavy chains.

Publication types

  • Review

MeSH terms

  • Animals
  • Biopsy
  • Cardiac Imaging Techniques*
  • Cardiomyopathy, Dilated* / genetics
  • Cardiomyopathy, Dilated* / pathology
  • Cardiomyopathy, Dilated* / physiopathology
  • Cardiomyopathy, Dilated* / therapy
  • DNA Mutational Analysis
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Humans
  • Molecular Diagnostic Techniques*
  • Mutation*
  • Myocardium / pathology*
  • Phenotype
  • Predictive Value of Tests
  • Prognosis
  • Risk Assessment
  • Risk Factors
  • Ventricular Function, Left*


  • Genetic Markers