Circulation, Vol 90, 2761-2771, Copyright © 1994 by American Heart Association
SP Friedrich, BH Lorell, MF Rousseau, W Hayashida, OM Hess, PS Douglas, S Gordon, CS Keighley, C Benedict and HP Krayenbuehl
BACKGROUND: Cardiac hypertrophy is associated with elevated intracardiac
angiotensin-converting enzyme activity, which may contribute to diastolic
dysfunction. METHODS AND RESULTS: We infused enalaprilat (0.05 mg/min) for
15 minutes into the left coronary arteries of 20 adult patients with left
ventricular (LV) hypertrophy due to aortic stenosis (mean aortic valve
area, 0.7 +/- 0.2 cm2) and 10 patients with dilated cardiomyopathy (mean
ejection fraction, 35 +/- 4%) and assessed (1) simultaneous changes in LV
micromanometer pressure and dimensions, (2) LV regional wall motion
analyzed by the area method, and (3) Doppler flow-velocity 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 atrial natriuretic peptide. In
patients with aortic stenosis, LV end-diastolic pressure declined from 25
+/- 2 to 20 +/- 2 mm Hg (P < .05). LV pressure-volume and LV pressure-
dimension relations showed downward shifts by ventriculography and
echocardiography, respectively, indicating improved diastolic
distensibility. Regional area change during isovolumic relaxation increased
in the anterior segments perfused with enalaprilat but decreased in the
inferior segments, indicating acceleration of isovolumic 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 output, or right atrial pressure, excluding
alterations in right ventricular/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 pericardial constraint. The patients with
dilated cardiomyopathy showed no improvement in regional diastolic
relaxation, filling, or distensibility. 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 intracoronary enalaprilat on
diastolic function were not observed in patients with dilated
cardiomyopathy who did not have concentric hypertrophy. These observations
support the hypothesis that the cardiac renin-angiotensin system is
activated in patients with concentric pressure-overload hypertrophy and
that this activation may contribute to impaired diastolic function.
ARTICLES
Intracardiac angiotensin-converting enzyme inhibition improves diastolic function in patients with left ventricular hypertrophy due to aortic stenosis
Charles A. Dana Research Institute, Boston, Mass.
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