Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disorder caused by mutations in genes encoding sarcomere proteins. Myocyte hypertrophy, myofibrillar fibrosis and disarray are the pathologic hallmarks of this disease and are traditionally thought to contribute to the development of diastolic dysfunction, a characteristic feature of HCM We postulate that abnormal diastolic function in fact procedures the onset of morphologic changes, reflecting the altered contractility of mutant sarcomeres. This proposal will utilize aq genotyped population to test the hypothesis that diastolic abnormalities are the earliest manifestation of HCM and are present before the development of left ventricular hypertrophy (LVH). Detailed echocardiographic studies will be performed on genotype- positive individuals who do not yet demonstrates LVH (i.e., phenotype- negative). These examinations will include meticulous assessment of diastolic function with Doppler tissue imaging and color M-mode. Indices of diastolic function from study subjects will be compared with age-matched normal controls. Such genotype-phenotype correlations have the potential to improve our ability to risk stratify and monitor patients, and may ultimately inspire noel approaches to management.
