Pharmacologic treatment of heart failure due to ventricular dysfunction by myocardial stunning: potential role of levosimendan.

The treatment of heart failure continues to pose a real challenge for clinicians. This condition is sometimes reversible and therapy should therefore pursue this outcome. In the context of coronary ischemic syndromes, myocardial stunning can cause heart failure and even cardiogenic shock, with important prognostic repercussions. Myocardial stunning is mainly due to calcium overload in the cytosol of myocardial cells, the loss of myofilaments and their reduced sensitivity to calcium. Enhanced immune activation with inflammatory phenomena also plays an important role in the pathophysiology of cardiac dysfunction. Increasing evidence has shown that the myocardial ATP-dependent potassium channel (K(ATP)) plays an important role in many myocardial cell functions and that it is involved in ischemia-reperfusion injury and myocardial stunning. K(ATP) is thus considered a therapeutic target in this setting. Currently used inotropic drugs improve contractility by increasing intracellular concentrations of free calcium, but they increase myocardial consumption of energy and even produce arrhythmia; therefore, in this clinical context, they do not seem to be 'pathophysiologically correct' drugs. Levosimendan, a new calcium-sensitizing agent, increases contractility by enhancing the sensitivity of myofilaments to calcium by binding to the C cardiac troponin in cardiac muscle in a calcium-dependent way. Levosimendan also exerts a coronary and systemic vasodilatory effect through its K(ATP) channel-opening properties and may exert other cardioprotective actions through this mechanism. Levosimendan produces positive hemodynamic effects without increasing myocardial oxygen demand or causing arrhythmias. Intravenous levosimendan is generally well tolerated and has been approved by several European countries, and recently recommended in European Society of Cardiology guidelines, as inotropic therapy for the short-term treatment of acute severe decompensated heart failure in adults. Randomized, double-blind trials have shown that levosimendan is not only more clinically and hemodynamically effective but also that it significantly reduces morbidity and mortality when compared with dobutamine or placebo. Clinical trials addressing the use and efficacy of intravenous levosimendan in acute heart failure in patients with systolic dysfunction or cardiogenic shock due to myocardial stunning are scarce. Beneficial effects on myocardial contractility in patients with myocardial stunning have only been shown in small clinical trials. A positive experience with levosimendan in a small series of patients with cardiogenic shock complicating ST-elevation myocardial infarction suggests that the use of this drug in cardiogenic shock should be further evaluated.