Amlodipine did not increase cardiovascular morbidity or mortality in patients with severe heart failure. The possibility that amlodipine prolongs survival in patients with nonischemic dilated cardiomyopathy requires further study.

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Background-Inhibition of the acyl coenzyme A:cholesterol acyltransferase (ACAT) enzyme may prevent excess accumulation of cholesteryl esters in macrophages. The ACAT inhibitor avasimibe was shown to reduce experimental atherosclerosis. This study was designed to investigate the effects of avasimibe on human coronary atherosclerosis. Methods and Results-This randomized, double-blind, placebo-controlled trial assessed the effects of avasimibe at dosages of 50, 250, and 750 mg QD on the progression of coronary atherosclerosis as assessed by intravascular ultrasound (IVUS). All patients received background lipid-lowering therapy if necessary to reach a target baseline LDL level Ͻ125 mg/dL (3.2 mmol/L). IVUS and coronary angiography were performed at baseline and repeated after up to 24 months of treatment. Approximately equal percentages of patients across groups received concurrent statin therapy (87% to 89%). The mean total plaque volume at baseline was Ϸ200 mm 3 , and the least squares mean change at end of treatment was 0.7 mm 3 for placebo and 7.7, 4.1, and 4.8 mm 3 for the avasimibe 50, 250, and 750 mg groups, respectively (adjusted Pϭ0.17 [unadjusted Pϭ0.057], 0.37, and 0.37, respectively). Percent atheroma volume increased by 0.4% with placebo and by 0.7%, 0.8%, and 1.0% in the respective avasimibe groups (PϭNS). LDL cholesterol increased during the study by 1.7% with placebo but by 7.8%, 9.1%, and 10.9% in the respective avasimibe groups (PϽ0.05 in all groups). Conclusions-Avasimibe did not favorably alter coronary atherosclerosis as assessed by IVUS. This ACAT inhibitor also caused a mild increase in

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...