Use of Levosimendan in Patients with Advanced Heart Failure: An Update

Abstract

Levosimendan is an inodilator drug that, given its unique pharmacological actions and safety profile, represents a viable therapeutic option in patients with heart failure with reduced ejection fraction in the advanced stage of the disease (advHFrEF). Pulsed levosimendan infusion in patients with advHFrEF improves symptoms and clinical and hemodynamic status, prevents recurrent hospitalizations, and enables optimization of guidelines-directed medical therapy. Furthermore, considering its proprieties on right ventricular function and pulmonary circulation, levosimendan could be helpful for the prevention and treatment of the right ventricular dysfunction post-implanting a left ventricular assist device. However, to date, evidence on this issue is scarce and has yielded mixed results. Finally, preliminary experiences indicate that treatment with levosimendan at scheduled intervals may serve as a "bridge to transplant" strategy in patients with advHFrEF. In this review, we summarized the clinical pharmacology of levosimendan, the available evidence in the treatment of patients with advHFrEF, as well as a hypothesis for its use in patients with advanced heart failure with preserved ejection fraction.

Keywords: advanced heart failure; inodilators; levosimendan; pharmacologic therapy.

Figure 1

Metabolic pathway of transformation of levosimendan in its active metabolites.

Figure 2

Therapeutic algorithm for the use of pulsed infusion of levosimendan in patients with advHFrEF. SBP: systolic blood pressure, eGFR: estimated glomerular filtration rate. a: Indication to pulsed infusion of levosimendan INTERMACS Class IV (frequent-flyers patients), progressive deterioration of kidney function, combined precapillary and post-capillary pulmonary hypertension, persistently high levels of NT-proBNP despite guidelines-directed medical therapy. b: subjective reduction of symptoms and improvement of quality of life; in doubtful cases, the assessment of NT-proBNP plasma values (palliative purpose); improvement of biventricular systolic function and reduction of pulmonary circulation pressures.