The inodilator levosimendan: 20 years of experience in various settings of cardiac care

Levosimendan emerged in the 1990s as a first-in-class inotrope and vasodilator that enhances cardiac contractility by sensitizing the contractile response to cardiac troponin C and causes vasodilatation by opening potassium-dependent ATP channels on vascular smooth muscle cells. Since its clinical debut in 2000, it has established itself as a valuable resource in the management of acute decompensated heart failure and is one of very few successful medical innovations of its kind in that field in recent decades. Its pharmacology is notable for delivering inotropy without an increase in myocardial oxygen consumption and for an array of secondary (‘pleiotropic’) effects that include an anti-ischemic effect, pre-conditioning and post-conditioning and cardioprotective effects and anti-oxidative effects. Proceeding from those properties it has been proposed that in addition to its use in various scenarios of low cardiac output levosimendan may be beneficial in other conditions associated with acutely decompensated heart failure, including right ventricular failure, subarachnoid hemorrhage, and cardiogenic shock with multi-organ dysfunction. The potential of levosimendan for kidney protection in situations of the cardio-renal syndrome has been identified. Additional lines of investigation include the use of levosimendan for perioperative hemodynamic support, its administration as repeated intermittent infusions to sustain patients with advanced heart failure and its application in a range of critical care settings. Levosimendan has also provided a template and a starting point for the development of a new generation of cardio-active drugs and is currently being evaluated in advanced clinical trials for the management of pulmonary hypertension in patients with heart failure with preserved ejection fraction.