Levosimendan: from basic science to clinical practice

Abstract

Levosimendan is a new cardiac enhancer that exerts positive inotropic effects on the failing heart mediated by calcium sensitization of contractile proteins as well as peripheral vasodilatory effects mediated by opening of ATP-sensitive potassium channels in vascular smooth-muscle cells. Levosimendan is the most well-studied calcium sensitizer in the real clinical practice, producing greater hemodynamic and symptomatic improvement in patients with acute heart failure syndromes (AHFS) than those with traditional inotropes. Immunomodulatory and anti-apoptotic properties of levosimendan may be an additional biologic mechanism that prevents further cytotoxic and hemodynamic consequences of abnormal immune and neurohormonal responses in AHFS. Recent mortality trials showed that levosimendan does not improve short- and long-term prognosis in AHFS in comparison to dobutamine or placebo. However, in patients with a previous history of CHF and on beta-blocker on admission, levosimendan seems to have a beneficial effect on short-term mortality. According to the recent guidelines of the European Society of Cardiology, levosimendan is indicated in patients with symptomatic low cardiac output HF secondary to cardiac systolic dysfunction without severe hypotension (Class IIa, Level of Evidence B).

Effect of Levosimendan on Estimated Glomerular Filtration Rate in Hospitalized Patients with Decompensated Heart Failure and Renal Dysfunction

“…The positive inotropic action of levosimendan occurs as a result of the calcium-dependent binding to cardiac troponin C, while its vasodilative effect is mainly due to the opening of ATP-sensitive potassium channels in vascular smooth muscle [5,6]. To date, several clinical trials have already been preformed to verify the hemodynamic and clinical effects of levosimendan in patients with heart failure, and comparison with other standard inotropic agents, such as dobutamine [7][8][9][10].…”

Levosimendan accelerates recovery in patients with takotsubo cardiomyopathy

“…on myocardial function [19] as it protects the heart against ischaemia and reperfusion damage by the opening of cardiac mitochondrial ATP-sensitive potassium [mito.K (ATP)] channels, one of the main mediators of cell protection pathways [20]. This mechanism of positive inotrophic myocardial contraction strengthening occurs without increasing oxygen demand, intracellular cAMP or intracellular calcium concentration at clinically relevant doses [21][22][23]. Levosimendan activates the opening of ATP-sensitive K + channels of smooth muscle cells allowing their hyperpolarization by leveraging vasodilation [24,25].…”

Use of levosimendan in critically ill patients with severe aortic stenosis and left ventricular dysfunction

“…It sensitizes troponin C to calcium in a manner dependent on calcium concentration, improving contraction at low energy cost, and leads to vasodilatation through the opening of ATP-sensitive potassium channels. 8,11 Through the combined inotropic and vasodilatory effects, levosimendan increases cardiac output without significantly increasing myocardial oxygen demand. 8 The beneficial effect of levosimendan in the treatment of heart failure due to severe LV systolic dysfunction is already well documented.…”

“…6 However, nitroprusside's narrow therapeutic window and possibility of triggering cardiac ischemia mandates caution. 7 Being an inodilator, levosimendan has the potential benefit of adding an inotropic effect to the vasodilator action, 8 bringing together the best of dobutamine and nitroprusside.…”