Acute hemodynamic effects of conivaptan, a dual V-1A and V-2 vasopressin receptor antagonist, in patients with advanced heart failure

Background-Arginine vasopressin may contribute to abnormalities in hemodyna mics and fluid balance in heart failure through its actions on V-1A (vascul ar and myocardial effects) and V-2 receptors (renal effects). Inhibiting th e action of vasopressin may be beneficial in patients with heart failure. Methods and Results-A total of 142 patients with symptomatic heart failure (New York Heart Association class III and IV) were randomized to double-bli nd, short-term treatment with conivaptan, a dual V-1a/V-2 vasopressin recep tor antagonist, at a single intravenous dose (10, 20, or 40 in mg) or place bo, Compared with placebo, conivaptan at 20 and 40 mg significantly reduced pulmonary capillary wedge pressure (-2.6 +/-0.7, -5.4 +/-0.7, and -4.6 +/- 0.7 mm Hg for placebo and 20 and 40 mg groups, respectively; P <0.05) and r ight atrial pressure (-2.0 +/-0.4, -3.7 +/-0.4, and -3.5 +/-0.4 mm Hg for p lacebo and 20 and 40 mg groups, respectively; P <0.05) during the 3- to 6-h our interval after intravenous administration. Conivaptan significantly inc reased urine output in a dose-dependent manner (-11 +/- 17, 68 +/- 17, 152 +/- 19, and 176 +/- 18 mL/hour for placebo and 10, 20, and 40 mg groups, re spectively; P <0.001) during the first 4 hours after the dose. Changes in c ardiac index, systemic and pulmonary vascular resistance, blood pressure, a nd heart rate did not significantly differ from placebo. Conclusions-In patients with advanced heart failure, vasopressin receptor a ntagonism with conivaptan resulted in favorable changes in hemodynamics and urine output without affecting blood pressure or heart rate. These data su ggest that vasopressin is functionally significant in advanced heart failur e and that further investigations are warranted to examine the effects of c onivaptan on symptom relief and natural history in such patients.