This investigation was undertaken to assess the prevalence of systolic dysfunction, left ventricular (LV) wall thinning and cavity enlargement in a large population of patients with hypertrophic cardiomyopathy (HC), and to determine the role of these conditions in the natural history of this disease. Of 217 consecutively studied patients with HC, most of whom were severely symptomatic, 197 (91%) had an LV ejection fraction of 50% or more and 20 (9%) had an ejection fraction of less than 50% as assessed with radionuclide angiography. Changes in LV wall thickness and cavity dimension were evaluated using serial M-mode and 2-dimensional echocardiography over an average follow-up of 3.6 years in 67 of the 217 patients (54 with ejection fraction of greater than or equal to 50% and 13 with ejection fraction less than 50%). A substantial decrease (at least 5 mm) in LV wall thickness was seen in 8 of the 13 patients (62%) with an ejection fraction greater than or equal to 50%, but in only 2 of the 54 patients (4%) with an ejection fraction greater than or equal to 50% (p less than 0.001). LV cavity dimension increased significantly over the period of follow-up in the 13 patients with depressed ejection fraction (from 44 +/- 5 to 49 +/- 7 mm, p less than 0.005); however, absolute cavity size remained normal (less than or equal to 52 mm or less) in 10 of these 13 patients.(ABSTRACT TRUNCATED AT 250 WORDS)