INTRACARDIAC ANGIOTENSIN-CONVERTING ENZYME-INHIBITION IMPROVES DIASTOLIC FUNCTION IN PATIENTS WITH LEFT-VENTRICULAR HYPERTROPHY DUE TO AORTIC-STENOSIS

Background Cardiac hypertrophy is associated with elevated intracardia c angiotensin-converting enzyme activity, which may contribute to dias tolic dysfunction. Methods and Results We infused enalaprilat (0.05 mg /min) for 15 minutes into the left coronary arteries of 20 adult patie nts with left ventricular (LV) hypertrophy due to aortic stenosis (mea n aortic valve area, 0.7+/-0.2 cm(2)) and 10 patients with dilated car diomyopathy (mean ejection fraction, 35+/-4%) and assessed (1) simulta neous changes in LV micromanometer pressure and dimensions, (2) LV reg ional wall motion analyzed by the area method, and (3) Doppler flow-ve locity profiles. Systemic neurohormonal activation did not occur with the selective left coronary artery infusion; there were no changes in plasma renin activity, angiotensin-converting enzyme activity, or atri al natriuretic peptide. In patients with aortic stenosis, LV end-diast olic pressure declined from 25+/-2 to 20+/-2 mm Hg (P<.05). LV pressur e-volume and LV pressure-dimension relations showed downward shifts by ventriculography and echocardiography, respectively, indicating impro ved diastolic distensibility. Regional area change during isovolumic r elaxation increased in the anterior segments perfused with enalaprilat but decreased in the inferior segments, indicating acceleration of is ovolumic relaxation in the anterior segments and reciprocal shortening in the inferior segments. Regional peak filling rate increased in the anterior segments but not in the inferior segments, and the regional area stiffness constant decreased in the anterior segments but not in the inferior segments. There were no changes in heart rate, cardiac ou tput, or right atrial pressure, excluding alterations in right ventric ular/pericardial constraint. In contrast, in the patients with dilated cardiomyopathy the decrease in LV end-diastolic pressure from 22+/-2 to 18+/-2 mm Hg (P<.05) was accompanied by a significant fall in right atrial pressure (9+/-1 to 6+/-1 mm Hg), implicating alterations in pe ricardial constraint. The patients with dilated cardiomyopathy showed no improvement in regional diastolic relaxation, filling, or distensib ility. Conclusions Intracoronary enalaprilat at a dosage that did not cause systemic neurohormonal activation improved LV diastolic chamber distensibility and regional relaxation and filling in patients with LV hypertrophy due to aortic stenosis. In contrast, these effects of int racoronary enalaprilat on diastolic function were not observed in pati ents with dilated cardiomyopathy who did not have concentric hypertrop hy. These observations support the hypothesis that the cardiac renin-a ngiotensin system is activated in patients with concentric pressure-ov erload hypertrophy and that this activation may contribute to impaired diastolic function.