IMPROVEMENT OF THE AGE-RELATED IMPAIRMENT IN LEFT-VENTRICULAR DIASTOLIC FILLING WITH VERAPAMIL IN THE NORMAL HUMAN HEART

Background Left ventricular (LV) diastolic function declines with the normal aging process. Because these changes are related to impaired ac tive LV relaxation as well as to structural alterations, we hypothesiz ed that verapamil might improve LV filling in elderly normal subjects compared with young normal subjects. Methods and Results We studied 27 normal volunteers (between 20 and 71 years old), with normal exercise tests and echocardiograms, by radionuclide angiography before and aft er 3 to 4 days of oral verapamil therapy. Indexes of global LV functio n were derived from analysis of background-corrected time-activity cur ves. Subjects were recruited from three age groups: young (26+/-4 year s, n=10), middle-aged (46+/-5 years, n=9), and elderly (66+/-3 years, n=8). Baseline resting heart rate, blood pressure, peak systolic wall stress, and LV ejection fraction did not differ among groups. Baseline peak LV filling rate (expressed in fractional stroke volume per secon d) was reduced in the middle-aged group (5.8+/-1.2, P<.01) and the eld erly group (4.3+/-1.0, P<.01) compared with the young group (7.8+/-1.2 ). With verapamil, resting heart rate, peak systolic wall stress, LV e jection fraction, and peak ejection rate did not change in any group. Peak filling rate increased in the middle-aged group (to 6.8+/-1.5 SV/ s, P<.01) and the elderly group (to 5.7+/-1.0 SV/s, P<.01) but did not change in the young group (8.0+/-1.4 SV/s). Also, time to peak fillin g rate decreased with verapamil in the elderly group (from (1)85+/-31 to 147+/-15 milliseconds, P<.01). The magnitude of change in filling r ate was correlated positively with age (r=.55, P<.005). Conclusion Ver apamil selectively enhances LV diastolic filling in middle-aged and el derly subjects, compared with young adults, without affecting systolic function. This observation supports the hypothesis that the impairmen t of LV filling accompanying the normal aging process is, at least in part, a reversible phenomenon.