Calcium sensitization with pimobendan: pharmacology, haemodynamic improvement, and sudden death in patients with chronic congestive heart failure

Calcium sensitization increases myocardial contractility byimproving energy utlization of the myocardium, without an increasein intracellular concentrations of cyclic adenosine monophosphate.The calcium sensitizer most extensively studied up to now ispimobendan (UD-CG 115 BS). Vasodilatation results primarilyfrom phosphodiesterase III inhibition Orally administered pimobendan appears rapidly in plasma. Apeak concentration is reached 1.5 h after drug intake; eliminationfrom the plasma compartment has a half-life of 1.5 h. First-passhepatic O-desmethylation of pimobendan produces the active metaboliteUD-CG 212; plasma concentration curves of UD-CG 212 are similarto those of pimobendan, with apeak concentration 1–2 hlater than the peak concentration of the parent compound. In patients with chronic congestive heart failure, pimobendanproduces a dose-dependent and prolonged decrease in pulmonarycapillary wedge pressure and an increase in cardiac output.Maintenance doses ofpimobendan are well tolerated and may leadto lasting symptomatic improvement in patients with heart failure;open and blinded trials show that exercise tolerance increases.No attenuation of these effects is seen during long-term therapywith pimobendan. Patients in chronic congestive heart failure frequently diesuddenly; many inotropic agents increase the incidence of suddendeath in these patients. Although proarrhythmia has never beenobserved with pimobendan, arrhythmia suppression with amiodaroneseems prudent in heart failure patients receiving maintenancedoses of pimobendan.