Clinical and Molecular Genetic Aspects of Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is a fascinating disease with diverse phenotypic expression that spans from minimal hypertrophy to severe heart failure and sudden cardiac death (SCD). HCM is the most common cause of sudden cardiac death (SCD) in the young competitive athletes and a major cause of morbidity and mortality in elderly. Molecular genetic basis of HCM is all but elucidated by identification of several hundred different mutations in 11 different genes, all encoding sarcomeric proteins. The emphasis of current research is to develop genetic screening techniques in order to identify the mutation carriers prior to and independent of the clinical manifestations of HCM; to identify genetic and non-genetic determinants of clinical outcome in HCM; and to identify novel drug targets in order to prevent, attenuate or reverse the evolving phenotype. Recent studies have led to partial understanding of the molecular pathogenesis of HCM phenotypes and consequently, identification of new therapeutic targets, which have been tested in animal models of human HCM with promising results. Studies in transgenic animal models have shown the treatment with statins or blockade of renin-angiotensin-aldosterone system could attenuate and mitigate evolving cardiac phenotypes in HCM. Studies in human patients with HCM are needed to determine whether the observed beneficial effects of new pharmacological interventions also extend to humans with HCM.