REVERSE REMODELING IN HEART-FAILURE WITH INTENSIFICATION OF VASODILATOR THERAPY

Background: Heart failure therapy with beta-receptor blockade has been shown to effect a partial reversal of left ventricular (LV) remodelin g in heart failure. Hypothesis: We tested the hypothesis that, in the absence of beta blockade, uptitration of angiotensin-converting enzyme (ACE) inhibitor and nitrate therapy over conventional dosages would i mprove symptoms as well as LV function in patients with severe heart f ailure. Methods: For patients with nonischemic or ischemic cardiomyopa thy, intensive high-dose angiotensin-converting enzyme inhibitor and n itrate therapy was uptitrated. Echocardiograms were obtained semiannua lly and evaluated in a blinded fashion. Of 99 patients in the study, a ged 55 +/- 13 years, with heart failure for 5.2 +/- 3.1 years, 74 were men, 69 were Caucasian, and 34 had ischemic cardiomyopathy. The final dosage of enalapril was 40 +/- 23 mg/day and of isosorbide dinitrate it was 153 +/- 127 mg/day. Results: Initial New York Heart Association classification improved from 2.8 +/- 0.9 to 1.7 +/- 0.9 (p < 0.001) i n 2.7 years of follow-up. Of the 99 patients, 72 further improved thei r ejection fraction. For the whole group, ejection fraction increased from 21 +/- 9% to 30 +/- 13% in 6 months (p<0.001), with a reduction i n LV end-diastolic size from 6.6 +/- 0.9 to 6.3 +/- 1.0 cm (p = 0.002) , and a decrease in the severity of mitral regurgitation from mild/mod erate to only mild. Resting heart rate declined with no change over ti me in systemic systolic blood pressure. Final ejection fraction for no nischemic patients (n = 65) was 36 +/- 16% versus 23 +/- 9% for the is chemic population. Conclusion: Uptitration of high-dose ACE inhibitor and nitrate therapy to higher doses is well tolerated in severe heart failure, further improves both clinical status and LV systolic functio n, and is more effective in nonischemic than in ischemic cardiomyopath y.