Inotropic therapy for heart failure: paradise lost.

The effort to demonstrate efficacy and safety of an oral phosphodiesterase III (PDE3)-inhibiting inotropic drug in patients with chronic heart failure has been long, arduous, and largely unsuccessful.1–6 The persistence of the effort is based on the widely held perception that heart failure is precipitated and sustained by a left ventricular contractile deficit and that PDE3 inhibitors can correct that deficit, improve haemodynamics, hopefully improve symptoms, and perhaps even prolong life. The results of the ESSENTIAL trials, reported by Metra et al. ,7 once again threaten this hypothesis. This class of drug was introduced clinically >25 years ago.1,2 Since that time we have learned much about the left ventricular functional and structural contributions to symptoms and progression of heart failure, and have gained insights into the therapeutic potential for vasodilator, nitric oxide-enhancing, neurohormonal-inhibiting. and positive inotropic agents. It should now be possible to design studies of experimental interventions in populations likely to respond and with endpoints likely to be achieved if the intervention is effective. The investigators took advantage of this prior experience in designing the … *Corresponding author. Tel: +1 612 625 5646, Fax: +1 612 624 2174, Email: cohnx001{at}umn.edu