In many patients with coronary artery disease or hypertrophic cardiomyopathy, reduced left ventricular rapid diastolic filling is related to asynchronous left ventricular regional diastolic function. Because left ventricular filling also declines with aging in normal subjects, in this study the influence of regional ventricular diastolic asynchrony on global ventricular filling as a function of age was investigated in 66 normal volunteers aged 19 to 77 years (mean 42) by radionuclide angiography. No subject had systemic hypertension or left ventricular hypertrophy. Indexes of left ventricular systolic function at rest did not vary with age, but rapid diastolic filling significantly declined with age: peak filling rate decreased (r = 0.69), time to peak filling rate increased (r = 0.53) and magnitude of rapid filling (% of left ventricular end-diastolic volume) decreased (r = 0.76) with aging. Left ventricular synchrony was assessed from regional volume curves derived by dividing the global ventricular region of interest into four quadrants. Indexes of systolic synchrony were unaffected by age, but regional variation in time to peak filling rate, an index of diastolic asynchrony, increased with aging (r = 0.51, p less than 0.001). Moreover, variation in time to peak filling rate correlated with global peak filling rate and magnitude of rapid filling (r = 0.48 and 0.54, p less than 0.001 for both). Multivariate analysis indicated that these effects were independent of age-related changes in blood pressure. Thus, aging alters left ventricular diastolic function, with reduced rate and extent of the rapid filling phase related to increased regional diastolic asynchrony.(ABSTRACT TRUNCATED AT 250 WORDS)