The emerging role of PDE5 inhibition in heart failure
© Lewis et al; licensee BioMed Central Ltd. 2007
Published: 25 July 2007
Heart failure (HF) is frequently associated with dysregulation of nitric oxide-mediated vascular tone. In HF patients with left ventricular systolic dysfunction (LVSD), right ventricular (RV) performance is an important determinant of exercise capacity and prognosis. Abnormal regulation of pulmonary vascular tone in these patients can lead to an increase in RV afterload and diminished function at rest and with exercise. The increased pulmonary vasomotor tone in HF patients is responsive to nitric oxide (NO), as administration of inhaled NO to patients with LVSD reduces pulmonary vascular resistance (PVR) and increases cardiac index (CI). As these beneficial effects of inhaled NO persist only briefly after cessation of its administration technically challenging to administercontinuously to ambulatory patients, the hydrolysis of its second messenger in vascular smooth muscle cells, cGMP, is an alternative target for pharmacologic augmentation through inhibition of phosphodiesterases (PDEs) responsible for its catabolism. Selective inhibition of Type 5 PDE, the predominant PDE isoform responsible for hydrolysis of cGMP in the lungs has been shown to lower resting PVR and pulmonary capillary wedge pressure (PCWP) and increase CI without causing systemichypotension in LVSD patients
Methods and results
The present study shows that in patients with systolic HF, PDE5 inhibition with sildenafil improves peak reduces VE/ slope, and acts as a selective pulmonary vasodilator during rest and exercise in patients with HF and pulmonary hypertension The results of a recently completed placebo-controlled study of chronic PDE5 inhibitor administration to HF patients with LVSD will be discussed.
The support of the NIH/NHLBI (KDB, MJS) and of a sponsored research agreement with Pfizer Inc is greatly appreciated.
This article is published under license to BioMed Central Ltd.