Effects of Levosimendan on Left Ventricular Relaxation and Early Filling at Maintained Preload and Afterload Conditions After Aortic Valve Replacement for Aortic Stenosis

BACKGROUND: We determined the effects of levosimendan, a calcium sensitizer, on left ventricular (LV) diastolic function in patients with LV hypertrophy. METHODS AND RESULTS: In this prospective, randomized, blinded study, 23 patients received either levosimendan (0.1 and 0.2 microg x kg(-1) x min(-1); n=12) or placebo (n=11) after aortic valve replacement for aortic stenosis. The effects on LV performance, dimensions, filling patterns, and isovolumic relaxation time, as well as systemic hemodynamics, were assessed by pulmonary artery thermodilution catheterization and transesophageal 2-dimensional Doppler echocardiography. To circumvent the confounding effects of the levosimendan-induced hemodynamic changes on Doppler echocardiographic indexes of LV early relaxation, heart rate and mean arterial and central venous pressures were kept constant during levosimendan/placebo infusion by atrial pacing, vasopressor, and colloid infusions. In the levosimendan group, dose-dependent increases in cardiac output (28%; P<0.001) and stroke volume (26%; P<0.001) and a decrease in systemic vascular resistance (-22%; P<0.001) were observed. There was a trend for an increase in LV ejection fraction (12%; P=0.058) with levosimendan. There were no significant differences in systolic, diastolic arterial, or LV filling pressures or LV end-diastolic area between the 2 groups. Isovolumic relaxation time decreased (-23%; P<0.001), as did the deceleration slope of early diastolic filling (-45%; P<0.01), whereas peak early diastolic filling velocity (16%, P<0.01) and peak late diastolic filling velocity (15%; P<0.001) increased after levosimendan compared with placebo. CONCLUSIONS: Levosimendan, in addition to its inotropic effects, exerts a direct positive lusitropic effect in patients with LV hypertrophy as it shortens isovolumic relaxation time and improves LV filling.