Effects of levosimendan on flow-mediated vasodilation and soluble adhesion molecules in patients with advanced chronic heart failure

Abstract

Aim Endothelial activation and dysfunction may be an important contributor to chronic heart failure (CHF) progression. We sought to investigate whether the calcium sensitizer levosimendan affects beneficially endothelial function and attenuates the deleterious effects of soluble adhesion molecules in patients with advanced CHF. Methods Twenty-six advanced CHF patients (mean New York Heart Association class, 2.6 ± 0.3; ischemic/dilated, 18/8; mean left ventricular ejection fraction <35%) hospitalized due to syndrome worsening, were randomized (2:1) to receive either a 24-h levosimendan infusion of 0.1 μg/kg/min ( n = 17) or placebo ( n = 9). Endothelial function estimated by endothelial-dependent flow-mediated dilatation of the brachial artery (FMD), as well as plasma soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1), were assessed before and 48 h after therapy. Results Baseline characteristics and medications were well balanced in the two treatment groups. A significant improvement of FMD (6.4 ± 4.4% from 4.8 ± 3.0%; p < 0.05) with concomitant reduction of plasma concentrations of sICAM-1 (231 ± 75 pg/ml from 339 ± 157 pg/ml; p < 0.05) and sVCAM-1 (1134 ± 508 pg/ml from 1386 ± 602 pg/ml; p < 0.05) were observed only in levosimendan treated patients. Conclusion Levosimendan could be an effective treatment in improving the endothelial function and reducing the detrimental adhesion molecule activation in advanced CHF patients.