Calcium Sensitizers as a New Inotropic Drugs

Abstract

The clinician's primary objective in treating a patient with decompensated heart failure is rapid and effective stabilization. This goal often is achieved through the use of inotropic support. Classic inotropic agents (beta-adrenergic agonists and phosphodiesterase III inhibitors) can provide short-term hemodynamic benefits, but their long-term use has been correlated with poor survival rates. Currently available inotropic drugs enhance myocardial contractility by increasing cAMP concentration as with PDEIII inhibitors, which ultimately increases the myocardial concentration of calcium. This effect is associated with an increase in myocardial oxygen consumption, which may further alter the already compromised myocardial oxygen balance in patients with preexisting ventricular dysfunction. Calcium sensitizers comprise a new drug class that offers hemodynamic and symptomatic improvements without increasing cAMP and intracellular calcium concentrations. These agents enhance contractility without a concurrent increase in the risk of cardiac events and thus represent a significant improvement over classic positive inotropic agents. Levosimendan is a novel potent calcium sensitizer, exhibiting a unique dual mechanism of action that combines a positive inotropic action mediated via calcium sensitization by binding to cardiac troponin C. It enhances myofilament responsiveness to calcium, thereby increasing myocardial contraction without increasing oxygen consumption. In addition to a vasodilator property via ATP-dependent potassium channels in vascular smooth muscle cells. Levosimendan have a potential benefit for patients with myocardial oxygen imbalance requiring inotropic support. Available clinical data suggest that calcium sensitizer agents represent a promising class of inotropic agents in a field that has seen few advances in recent decades.