Coexistence of sudden cardiac death and end-stage heart failure in familial hypertrophic cardiomyopathy

OBJECTIVES: The purpose of this study was to determine the occurrence of sudden cardiac death or end-stage heart failure, two phases of the natural history of hypertrophic cardiomyopathy, in closely related relatives. BACKGROUND: Hypertrophic cardiomyopathy is a genetically transmitted cardiac disease with a particularly diverse clinical and morphologic spectrum. Premature death usually occurs either suddenly or as a result of progressive congestive heart failure. METHODS: We describe seven families with genetically transmitted hypertrophic cardiomyopathy that were studied with echocardiography or necropsy, or both, and were selected because they were known to include relatives who had incurred either premature sudden cardiac death or the end-stage phase of the disease. RESULTS: The seven families comprised 128 relatives; 26 died suddenly, and 9 developed end-stage heart failure (including 2 with heart transplantation) associated with left ventricular cavity enlargement, wall thinning or decreased contractility, alone or in combination, as well as loss of outflow obstruction. Patients who died suddenly did so at younger ages (23 +/- 10 years) than did patients who died or required heart transplantation in the end-stage phase of hypertrophic cardiomyopathy (42 +/- 8 years, p < 0.001). CONCLUSIONS: This study demonstrates that family members with hypertrophic cardiomyopathy, despite a common genetic substrate, may exhibit markedly diverse and distinct expressions of the natural history of their disease, which occur at widely separated periods of life.