Regression of myocardial cellular hypertrophy with vasodilator therapy in chronic congestive heart failure associated with idiopathic dilated cardiomyopathy

Forty-nine patients with idiopathic dilated cardiomyopathy (IDC) were evaluated to determine the hemodynamic and morphologic effects of vasodilator therapy. Hydralazine (225 mg/day, H), isosorbide dinitrate (160 mg/day, I), and combination H + I therapy were compared with placebo (P) at baseline and after 3 months of continuous therapy. Thirty-three randomly assigned patients completed the study. Hemodynamic parameters included the echocardiographic percent change of left ventricular diameter (%ΔD), the systolic time intervals ratio of preelection period to left ventricular ejection time (PEP/LVET), the pulmonary capillary wedge pressure, mean pulmonary artery pressure, cardiac index, systemic vascular resistance, and pulmonary vascular resistance. An endomyocardial biopsy was performed at baseline and after 3 months; the myocardial cell diameter of 50 cells per biopsy was measured. During the 3-month study 5 patients died; there was not a significant difference among the groups in the number of deaths. The %ΔD and PEP/LVET did not change in the P or I groups but did improve significantly from baseline in the H and H + I groups. The pulmonary capillary wedge and mean pulmonary artery pressures and the pulmonary vascular resistance did not change in the P or H groups but did decrease significantly in the I and H + I groups. The P and I groups did not have improvement in systemic vascular resistance or cardiac index, whereas the H group had a decrease in systemic vascular resistance and an increase in cardiac index from 2.5 ± 0.4 to 3.1 ± 0.4 liters/min/m2 (p < 3.05). The H + I group also had a decrease in systemic vascular resistance; the cardiac index increased from 2.3 ± 0.4 to 3.1 ± 0.4 liters/min/m2 (p < 0.01). Myocardial cell diameter did not change in the P or I group. Cell diameter of the H group decreased from 25.4 ± 3.1 μm at baseline to 23.1 ± 3.8 μm (p < 0.05) after 3 months of continuous therapy. The H + I group decreased its cell diameter from 23.9 ± 3.7 to 22.2 ± 2.2 μm (p < 0.05). Compared with P and H, patients treated with I alone or H + I had a significant reduction of preload. In contrast to P and I, H alone and H + I elicited improvement in parameters of inotropy and after-load, and this improvement was accompanied by a reduction in cell diameter. Chronic therapy of heart failure with H and H + I effects a persistent augmentation of cardiac function and improvement of myocardial cellular morphology.