Progression of mild untreated heart failure purina six months follow-up and clinical and neurohumoral effects of ibopamine and digoxin as monotherapy

There is increasing evidence that clinical deterioration in manifest chronic heart failure is related to both hemodynamic and neurohumoral factors. Only few data are available, however, on the progression of disease in its early stages, when treatment has not yet been initiated. The aim of this study was therefore to examine the changes in clinical and neurohumoral variables that occur over 6 months in patients with clinically stable and untreated heart failure, and to evaluate the influence of drugs that may affect these variables. Accordingly, we studied 64 patients with heart failure who were in New York Heart Association functional class II (88%) and III (12%). They were randomized to doubleblind treatment with the oral dopamine agonist ibopamine (100 mg 3 times daily; n = 22), digoxin (0.25 mg once daily; n = 22) or placebo (n = 20). their age (mean ± SD) was 60 ± 8 years, and left ventricular ejection fraction (mean ± SD) was 0.33 ± 0.08. Of the 64 patients, 56 (88%) completed the 6-month study period (p = NS between groups). Exercise time decreased in patients treated with placebo after 6 months (median −62 seconds; p < 0.05 vs baseline), but it increased with ibopamine (+ 48 seconds), and digoxin (+ 17 seconds; bom p < 0.05 vs placebo). Plasma norepinephrine increased in the placebo group after 6 months (median + 31 pg/ml, p < 0.05 vs baseline), but decreased in patients receiving active drug treatment (ibopamine: −24 pg/ml, digoxin: −98 pg/ml, both p < 0.05 vs placebo). Plasma renin and aldosterone levels were unchanged after 6 months in the placebo group, but digoxin therapy slightly reduced plasma renin concentration (−5 (μU/ml; p < 0.05 vs placebo). In conclusion, even in stable, untreated heart failure, a small but significant progression of disease occurs during 6 months, as reflected by both clinical and neurohumoral changes. Both ibopamine and digoxin monotherapy may favorably affect these changes, and may thus be of value in this patient group.