Our findings indicate that despite its beneficial hemodynamic actions, long-term therapy with oral milrinone increases the morbidity and mortality of patients with severe chronic heart failure. The mechanism by which the drug exerts its deleterious effects is unknown.

Six months of therapy with 60 mg of vesnarinone per day resulted in lower morbidity and mortality and improved the quality of life of patients with congestive heart failure. However, a higher dose of vesnarinone (120 mg per day) increased mortality, suggesting that this drug has a narrow therapeutic range; the long-term effects of vesnarinone are unknown.

Background-Arginine vasopressin may contribute to abnormalities in hemodynamics and fluid balance in heart failure through its actions on V 1A (vascular and myocardial effects) and V 2 receptors (renal effects). Inhibiting the 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-blind, short-term treatment with conivaptan, a dual V 1a /V 2 vasopressin receptor antagonist, at a single intravenous dose (10, 20, or 40 mg) or placebo. Compared with placebo, conivaptan at 20 and 40 mg significantly reduced pulmonary capillary wedge pressure (Ϫ2.6Ϯ0.7, Ϫ5.4Ϯ0.7, and Ϫ4.6Ϯ0.7 mm Hg for placebo and 20 and 40 mg groups, respectively; PϽ0.05) and right atrial pressure (Ϫ2.0Ϯ0.4, Ϫ3.7Ϯ0.4, and Ϫ3.5Ϯ0.4 mm Hg for placebo and 20 and 40 mg groups, respectively; PϽ0.05) during the 3-to 6-hour interval after intravenous administration. Conivaptan significantly increased urine output in a dose-dependent manner (Ϫ11Ϯ17, 68Ϯ17, 152Ϯ19, and 176Ϯ18 mL/hour for placebo and 10, 20, and 40 mg groups, respectively; PϽ0.001) during the first 4 hours after the dose. Changes in cardiac index, systemic and pulmonary vascular resistance, blood pressure, and heart rate did not significantly differ from placebo. Conclusions-In patients with advanced heart failure, vasopressin receptor antagonism with conivaptan resulted in favorable changes in hemodynamics and urine output without affecting blood pressure or heart rate. These data suggest that vasopressin is functionally significant in advanced heart failure and that further investigations are warranted to examine the effects of conivaptan on symptom relief and natural history in such patients. Key Words: heart failure Ⅲ hemodynamics Ⅲ hormones A rginine vasopressin is a peptide hormone with significant cardiovascular and renal effects. 1-3 These effects are mediated through at least 2 receptor subtypes: the V 1A receptor, which is found on vascular smooth muscle cells and in the myocardium, and V 2 receptors, which are found in the distal tubule of the kidney. 2,3 Stimulation of the V 1A receptor results in vasoconstriction in the peripheral and coronary circulations and has other effects, including increasing intracellular calcium levels in cardiac myocytes. [2][3][4] Recent studies have also demonstrated that arginine vasopressin increases the rate of protein synthesis in the myocardium, leading to myocyte hypertrophy, a direct effect mediated by the V 1A receptor. [5][6][7] The V 2 receptor mediates renal water retention and is predominantly responsible for the antidiuretic effect of this hormone. 2,3 Under normal circumstances, vasopressin release is predominantly influenced by small changes in plasma osmolality, resulting in tight regulation of serum osmolality and serum sodium levels. 3 In heart failure and left ventricular (LV) dysfunction, however, numerous nonosmotic mechanisms assume a more prominent role in the contro...