Inotropic Agents for Heart Failure - Wishful Thinking?
Calcium activation and calcium sensitivity
in the failing myocardium. "Classical" inotropic agents of the types of cardiac glycosides, adrenergic agonists, and PDE inhibitors are acutely aiding heart failure patients, but fail in chronic application. As far as current clinical experience with those PDE inhibitors is concerned which concomitantly increase calcium sensitivity, PDE inhibition appears to, at least partially, blunt the inotropic effect of calcium sensitisation. Next to the novel myosin activators (Cleland et al. 2011), it will, therefore, be important to investigate "pure" calcium sensitisers like CGP 48506 clinically, in order to understand the true potential of the concept of calcium sensitisation, including its impact on myocardial energy demand (Salzmann et al. 1985), independent of other inotropic mechanisms. Such studies are still missing and should be undertaken with priority. With such information, inotropic agents for heart failure may, in the end, become more than just wishful thinking.