Effects of levosimendan on coronary artery flow and cardiac performance in patients with advanced heart failure

Abstract

Background: Levosimendan has inotropic and vasodilatory effects. We investigated the effects of levosimendan on coronary flow and associated changes in neurohormonal activation and cardiac performance in patients with advanced heart failure. Methods: Forty-two patients with NYHA III-IV and a left ventricular ejection fraction (EF) 25 ± 6%, were randomised to levosimendan 0.1 μg/kg/min (n = 21) or placebo for 24 h. Before and 24 h after each treatment, we assessed: the maximal velocity (Vmax), time integral (VTI) and deceleration time (DT) of the diastolic coronary flow wave (CF) in LAD using transthoracic Doppler echocardiography, pulmonary artery systolic pressure by Doppler echocardiography, E/E' ratio using Doppler imaging of mitral inflow velocity, tissue Doppler imaging of the mitral annulus and B-type natriuretic peptide (BNP) levels. Results: By ANOVA, there was a greater increase in CF-Vmax (43 ± 23 vs.25 ± 8 cm/s), CF-DT (904 ± 250 vs. 667 ± 151 ms), and EF and a greater decrease in BNP, pulmonary artery systolic pressure and E/E′ after levosimendan than after placebo (p b 0.05). Compared to baseline, the percent changes in CF-VTI were related to the concomitant changes in EF, E/E′, and BNP after treatment with levosimendan (r = 0.69, r = −0.51 and r = −0.80, p b 0.05 respectively). Conclusion: Treatment with levosimendan improves coronary flow and microcirculation in parallel with an improvement in cardiac performance and neurohormonal activation in patients with advanced heart failure.

Levosimendan: from basic science to clinical practice

“…A recent study [56] has shown that 24 h levosimendan infusion induces improvement in echocardiographic indexes of coronary flow in patients with ADHF. In particular, it increased the maximal velocity and the deceleration time of diastolic coronary flow wave in left anterior descending coronary artery, whereas it reduced BNP levels, pulmonary artery systolic pressure and E/E 0 at greater extent than the placebo treatment.…”

Use of levosimendan in patients with ischemic heart disease following mechanical reperfusion

“…12 Of these benefi cial effects, peripheral vasodilatation is achieved by acting on adenosine triphosphate (ATP)-dependent K + channels. 5 An ischemic reperfusion study has suggested that levosimendan improves myocardial function by limiting the myocardial infarct zone. 13 In another ischemic reperfusion model, however, levosimendan is reported to improve hemodynamic parameters but produces limited decreases in the infarct zone in the absence of coronary collateral.…”

“…Levosimendan treatment produces improvements in cardiac performance and neurohumoral activation in parallel with its positive effects on coronary circulation. 5 These effects result is an increased left ventricular systolic function. 6 Although baseline studies have reported positive results for the effectiveness of levosimendan in acute cardiac failure, 7,8 two recent large studies failed to show a superiority to placebo and dobutamine.…”

Efficacy of Intravenous Levosimendan in Patients with Heart Failure Complicated by Acute Myocardial Infarction

“…Levosimendan is a calcium sensitizer that increases the contractile force of the myocardium by enhancing the sensitivity of myofilaments to calcium without increasing intracellular calcium concentration [2,3]. It has been reported that levosimendan improves certain aspects of cardiac function and is effective for treating acute cardiac failure [4,5,6]. However, in other studies, levosimendan has not been found to be any more effective for survival than placebo or dobutamine.…”