Hypertrophic Cardiomyopathy: Cell-to-Cell Imbalance in Gene Expression and Contraction Force as Trigger for Disease Phenotype Development

Hypertrophic cardiomyopathy (HCM) is an inherited cardiac disease with an incidence of about 1 in 500 individuals.(1) It is characterized by asymmetrical hypertrophy of the left ventricle in the absence of other causes for hypertrophy. HCM can vary from essentially asymptomatic to highly malignant up to end-stage heart failure or cause life-threatening arrhythmias with sudden cardiac death particularly in young adults. In most familial HCM cases, heterozygous mutations in sarcomeric proteins have been identified as underlying cause. About one third of the patients are heterozygous for mutations in the beta-cardiac myosin heavy chain gene MYH7, another third in cardiac myosin-binding protein C (cMyBPC).(2) Few mutations were found in nonsarcomeric proteins. Cardiomyocyte and myofibrillar disarray with interstitial fibrosis and hypertrophy are hallmarks of HCM.(3) The degree of myocardial disarray correlates with risk factors for sudden cardiac death,(4) and it was suggested that myocyte disarray directly results from functional changes induced by the HCM-related mutations at the sarcomeric level.(5)