Abstract 3165: Acute Administration of Sildenafil Improves Peak VO2 Proportionate to Pulmonary Vasodilation in Patients with Heart Failure
Background. Acute administration of the oral type 5 phosphodiesterase (PDE 5) inhibitor sildenafil has been observed to improve exercise capacity in patients with pulmonary arterial hypertension (PH) and in those with heart failure (HF) due to left ventricular systolic dysfunction (LVSD). There are several potential mechanisms by which augmentation of NO-cGMP signaling may improve exercise capacity. We hypothesized that sildenafil-induced selective pulmonary vasodilation is a mechanism by which PDE 5 inhibition improves peak oxygen consumption (VO2) in HF.
Methods and Results. Thirteen patients with NYHA Class III HF underwent assessment of right heart hemodynamics and gas exchange at rest and with cycle ergometry before and 60 minutes after administration of 50 mg of oral sildenafil. The administration of sildenafil reduced resting mean (± SEM) pulmonary artery pressure (PAP, 14 ± 5%), pulmonary vascular resistance (PVR, 21 ± 7%), and systemic vascular resistance (SVR, 19 ± 4%) and increased cardiac index (20 ± 2%) (all p < 0.05) but did not alter resting heart rate, mean arterial pressure, pulmonary capillary wedge pressure, right atrial pressure, oxygen extraction, or PVR/SVR ratio. Sildenafil also reduced mean exercise PAP and PVR (11 ± 3% and 21 ± 5% respectively, both p < 0.05) and decreased PVR/SVR ratio by 11 ± 8% (p = 0.05) without affecting SVR, indicating a selective pulmonary vasodilator effect with exercise. The magnitude of reduction in exercise PVR/SVR following sildenafil administration correlated directly with resting PAP (r = 0.73, p < 0.01). Peak VO2 increased 15 ± 9% and ventilatory response to CO2 output (VE/VCO2 slope) decreased 16 ± 5% following sildenafil treatment. Augmentation of peak VO2 with sildenafil correlated with reduction in exercise PVR following sildenafil administration (r = 0.58, p 0.02).
Conclusions. In patients with systolic HF and secondary PH, the PDE 5 inhibitor sildenafil augments exercise capacity proportionate to resting PH and the change in pulmonary vascular tone with exercise . This data suggests that PDE 5 inhibition may be of utility in treating patients who develop secondary PH in the setting of chronic LVSD.