For increasing myocardial contractility in patients with
cardiac failure,
catecholamines,
phosphodiesterase-III (PDE) inhibitors, and
calcium sensitizers are available. Improving myocardial performance with
catecholamines and PDE inhibitors leads to increased intracellular
calcium concentration as an unavoidable side effect. An increase in intracellular
calcium can induce harmful arrhythmias and increases the energetic demands of the myocardium. Long-term trials with PDE inhibitors have raised concerns about the safety of positive inotropic treatment for
cardiac failure.
Calcium sensitizers are a new class of inotropic drugs. They improve myocardial performance by directly acting on
contractile proteins without increasing intracellular
calcium load. Thus, they avoid the undesired effects of an increased intracellular
calcium load.
Calcium sensitizers may enhance myocardial performance without increasing myocardial oxygen consumption and without provoking fatal arrhythmias. Two
calcium sensitizers are available for the treatment of
cardiac failure in men.
Pimobendan is a drug with positive inotropic effects that additionally inhibits the production of proinflammatory
cytokines. However, it exerts a significant inhibition of PDE at clinically relevant doses.
Levosimendan is a
calcium sensitizer with no major inhibition of PDE at clinically relevant doses. It opens
ATP-dependent
potassium channels and thus has vasodilating and cardioprotective effects. The most important studies of the long-term treatment of stable
cardiac failure with
pimobendan and on the short-term treatment of unstable
cardiac failure with
levosimendan are presented.