In hypertrophic cardiomyopathy, the magnitude of hypertrophy is directly related to the risk of sudden death and is a strong and independent predictor of prognosis. Young patients with extreme hypertrophy, even those with few or no symptoms, appear to be at substantial long-term risk and deserve consideration for interventions to prevent sudden death. The majority of patients with mild hypertrophy are at low risk and can be reassured regarding their prognosis.

Background-End stage (ES) is a recognized part of the hypertrophic cardiomyopathy (HCM) disease spectrum.Frequency, clinical profile and course, and treatment strategies in these patients remain incompletely defined. Methods and Results-Three HCM cohorts comprised 1259 patients, including 44 (3.5%) characterized as ES with systolic dysfunction (ejection fraction Ͻ50% at rest; range 15% to 49%). ES developed at a wide age range (14 to 74 years), with 45% of patients Յ40 years old. Although 29 patients (66%) died of progressive heart failure, had sudden death events, or underwent heart transplantation, 15 (34%) survived with medical management over 3Ϯ3 years. Duration from onset of HCM symptoms to ES identification was considerable (14Ϯ10 years), but ES onset to death/transplantation was brief (2.7Ϯ2 years). ES occurred with similar frequency in patients with or without prior myectomy (Pϭ0.84). Appropriate defibrillator interventions were 10% per year in patients awaiting donor hearts. Most ES patients (nϭ23; 52%) showed substantial left ventricular (LV) remodeling with cavity dilatation. Less complete remodeling occurred in 21 patients (48%), including 5 with persistence of a nondilated and markedly hypertrophied LV. Pathology and magnetic resonance imaging showed extensive (transmural) fibrosis in 9 of 11 ES patients. At initial evaluation, patients who developed ES were younger with more severe symptoms, had a larger LV cavity, and more frequently had a family history of ES than other HCM patients. Conclusions-ES of nonobstructive HCM has an expanded and more diverse clinical expression than previously appreciated, including occurrence in young patients, heterogeneous patterns of remodeling, frequent association with atrial fibrillation, and impaired LV contractility that precedes cavity dilatation, wall thinning, and heart failure symptoms. ES is an unfavorable complication (mortality rate 11% per year) and a sudden death risk factor; it requires vigilance to permit timely recognition and the necessity for defibrillator implantation and heart transplantation.