The emerging role for type 5 phosphodiesterase inhibition in heart failure

Patients with heart failure (HF) due to left ventricular (LV) systolic dysfunction have abnormal endothelium-dependent, nitric oxide-cyclic guanosine monophosphate-mediated vasodilation in the pulmonary and skeletal muscle vasculature. Therefore, inhibition of type 5 phosphodiesterase (PDE5), the principle enzyme responsible for cyclic guanosine monophosphate catabolism in the lungs and skeletal muscle, has been targeted in an effort to counteract vasoconstriction that contributes to increased right and LV afterload in HF. The efficacy of PDE5 inhibition in the treatment of pulmonary arterial hypertension has led to the investigation of its potential utility in the treatment of HF patients with secondary pulmonary hypertension. Moreover, recent preclinical studies suggest direct myocardial effects of PDE5 inhibition that may counteract beta-adrenergic, hypertrophic, and pro-apoptotic signaling, three critical pathways in the development of LV dysfunction. This review outlines both the underlying rationale and the results of initial studies of the therapeutic effects of PDE5 inhibition in HF.