| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2851257 | American Heart Journal | 2009 | 7 Pages |
BackgroundIstaroxime is a novel intravenous agent with inotropic and lusitropic properties related to inhibition of the Na+/K+ adenosine triphosphatase and stimulation of sarcoplasmic reticulum calcium adenosine triphosphatase activity. We analyzed data from HORIZON-HF, a randomized, controlled trial evaluating the short-term effects of istaroxime in patients hospitalized with heart failure and left ventricular ejection fraction ≤35% to test the hypothesis that istaroxime improves diastolic stiffness in acute heart failure syndrome.MethodsOne hundred twenty patients were randomized 3:1 (istaroxime/placebo) to a continuous 6-hour infusion of 1 of 3 doses of istaroxime or placebo. All patients underwent pulmonary artery catheterization and comprehensive 2-dimensional/Doppler and tissue Doppler echocardiography at baseline and at the end of the 6-hour infusion. We quantified diastolic stiffness using pressure-volume analysis and tissue Doppler imaging of the lateral mitral annulus (E′).ResultsBaseline characteristics were similar among all groups, with mean age 55 ± 11 years, 88% men, left ventricular ejection fraction 27% ± 7%, systolic blood pressure (SBP) 116 ± 13 mm Hg, and pulmonary capillary wedge pressure (PCWP) 25 ± 5 mm Hg. Istaroxime administration resulted in an increase in E′ velocities, whereas there was a decrease in E′ in the placebo group (P = .048 between groups). On pressure-volume analysis, istaroxime decreased end-diastolic elastance (P = .0001). On multivariate analysis, increasing doses of istaroxime increased E′ velocity (P = .043) and E-wave deceleration time (P = .001), and decreased E/E′ ratio (P = .047), after controlling for age, sex, baseline ejection fraction, change in PCWP, and change in SBP.ConclusionsIstaroxime decreases PCWP, increases SBP, and decreases diastolic stiffness in patients with acute heart failure syndrome.
