EFFECTS OF ENALAPRILAT ON HEMODYNAMICS AND VENTRICULAR ACTIVATION DURATION IN HYPERTENSIVE PATIENTS WITH LEFT-VENTRICULAR HYPERTROPHY - CLINICAL-EVIDENCE OF IMPROVED EXCITATION-CONTRACTION COUPLING WITH ANGIOTENSIN-CONVERTING ENZYME-INHIBITION IN HUMAN HYPERTENSION

Hypertension is a major risk factor for the development of heart failu re. Despite significant progress in our knowledge of the physiopatholo gy of heart failure, the cause for decompensation in patients with lef t ventricular hypertrophy (LVH) is still obscure. The angiotensin conv erting enzyme inhibitor enalaprilat has been found to improve electrom echanical coupling of heart cells in animal models. To assess the effe cts of enalaprilat on ventricular electromechanical coupling in humans , we studied the His bundle electrograms and hemodynamics in 22 hypert ensive patients with LVH. Patients received either 2.5 mg enalaprilat or saline placebo intravenously in a double-blind protocol. There were no significant changes in heart rate, and atrioventricular and His-Pu rkinje conduction times. Ventricular activity duration was reduced fro m 110 +/- 11 msec to 88 +/- 13 msec after enalaprilat administration ( P < .01). Enalaprilat decreased peak-systolic and end-diastolic left v entricular pressures, and arterial and pulmonary pressures, as well as pulmonary and systemic vascular resistances. End-systolic wall stress decreased 18% (P < .01), ejection fraction increased 11% (P < .01), a nd end-diastolic pressure-volume ratio decreased 50% (P < .001) after enalaprilat administration. There were no significant changes in these parameters after saline infusion. It is concluded that enalaprilat re duces ventricular activation duration and improves ventricular perform ance in hypertensive patients with LVH. Data suggest that enalaprilat significantly improves excitation-contraction coupling in these patien ts.