To determine the clinical course of apical hypertrophic cardiomyopathy, 26 patients (mean age 45 years) with asymmetric apical hypertrophy diagnosed by echocardiography or angiography were followed up for an average of 7.3 years (range 1 to 22). Presenting symptoms included atypical chest pain (n = 10), typical angina (n = 6), dyspnea (n = 5) and palpitation (n = 8). Ten patients were asymptomatic. At follow-up all patients had inverted precordial T waves, and 14 had the syndrome of "giant T wave negativity" (greater than or equal to 10 mm). In six patients with electrocardiographic follow-up of greater than 10 years (mean 13.4), precordial T wave inversion had progressed from -0.8 +/- 3.9 to -11.2 +/- 8.0 mm in lead V4 in association with increased QRS amplitude. Episodic atrial fibrillation occurred in 4 of 10 patients with echocardiographic left atrial enlargement. Although left ventricular systolic function was normal, diastolic relaxation was impaired in comparison with values in 10 healthy control subjects: in all 18 patients studied peak filling rate was decreased (4.44 +/- 0.44 versus 6.13 +/- 1.54 stroke volumes/s); time to peak filling was increased (174 +/- 40 versus 147 +/- 32 ms); and atrial systolic contribution to ventricular end-diastolic volume was increased (21.5 +/- 6.8 versus 11.5 +/- 4.6 stroke volume %). During follow-up, 21 of the 26 patients remained in stable condition or were asymptomatic. One patient with normal coronary arteries had an apical myocardial infarction with development of a discrete apical aneurysm and loss of "giant T wave negativity." This patient was the only one to have documented life-threatening ventricular arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)