Levosimendan: What Have We Learned So Far?

Abstract

Purpose of Review: Vasoactive therapy represents a pivotal yet debated topic in critically ill patients and in those with chronic heart failure. Levosimendan, a calcium sensitizer agent with inodilating properties, has been in the market for 27 years and new indications came out over time. The aim of the present review is to highlight what is actually proven and what is debated on the use of levosimendan in light of its pharmacologic features and the pathophysiological evidence. Recent Findings: Levosimendan was firstly seen as an inodilator acting through calcium sensitization in myocytes both in the myocardium and in vascular smooth muscle. Over the years, its anti-inflammatory properties became clearer and a role in preconditioning and weaning from mechanical circulatory support was postulated. More recently, a possible action on other muscular fibers, namely, diaphragmatic myocytes, was observed, leading to a possible application in mechanical ventilation-related diaphragmatic dysfunction. Summary: Preliminary data showed promising effects of levosimendan in patients with sepsis-related and stress-related (Takotsubo) myocardial dysfunction, in those difficult-to-wean from mechanical circulatory support and in ventilator-associated diaphragmatic dysfunction. Moreover, its vasodilating, anti-oxidant, and neuroendocrine properties pave the way to a number of additional possible applications. Larger studies yielding to more conclusive results on these indications are under way or need to be planned in the future.