Effects of six-month afterload reduction therapy with hydralazine in chronic aortic regurgitation

Abstract

Seventeen patients with chronic asymptomatic aortic regurgitation (AR) were studied to determine whether 6 months of hydralazine therapy can reduce the severity of AR or reverse left ventricular (LV) enlargement and hypertrophy. Echocardiography, radionuclide angiography at rest and during exercise, and maximal treadmill exercise with respiratory gas analysis were performed at intake and after a 6-month double-blind treatment period. After dose titration with hydralazine, patients were randomized to their maximal tolerated hydralazine dose or to placebo. At intake, hydralazine and placebo groups were similar. Six patients taking hydralazine and 8 taking placebo completed the study protocol. One patient taking placebo died and 2 patients taking hydralazine withdrew with drug-related adverse effects. The mean titrated dose of hydralazine was 93 ± 9 mg, but the mean treatment dose was 63 ± 21 mg administered 3 times daily because of drug intolerance. After 6 months, mean systolic blood pressure with hydralazine therapy decreased from 136 to 125 mm Hg (p < 0.02), and end-systolic posterior wall thickness increased from 1.58 to 1.70 cm (p < 0.05), resulting in a significant reduction in M-mode meridional end-systolic stress (from 104 to 80 kdynes/cm 2) (p < 0.05). M-mode fractional shortening increased from 0.28 to 0.31 (p < 0.05) with hydralazine, but mean LV echocardiographic dimensions were unchanged. LV mass increased from 383 to 434 g (p < 0.05) with hydralazine primarily because of an increase In end-diastolic wall thickness. In the placebo group, there was no change in any of the hemodynamic or echocardiographic parameters at 6 months. Treadmill exercise variables, radionuclide ejection fraction and regurgitant fraction at rest were unchanged in either group at 6 months; however, in patients taking hydralazine, the ejection fraction during exercise increased from 64 ± 12 to 72 ± 9% (p < 0.02). It is concluded that 6 months of hydralazine therapy in maximal tolerated doses does not alter the severity of regurgitation or reduce LV enlargement and hypertrophy in chronic severe AR, although systolic function may be improved.