Effect of sildenafil on ventilatory efficiency and exercise tolerance in pulmonary hypertension

Background: The pulmonary vasculopathy in pulmonary arterial hypertension (PAH) results in increased resistance to pulmonary blood flow, limiting the cardiac output required for the increased O-2 demands of exercise. Aims: We sought to determine the physiologic basis for clinical improvement in PAH patients receiving sildenafil, hypothesizing that the key mechanisms of improvement are improved blood flow and ventilatory efficiency, leading to improved exercise capacity and O-2 pulse over time. Methods: We studied 28 PAH patients with (n = 14) and without (n = 14) sildenafil treatment. All received warfarin and diuretic therapy, and 13/14 sildenafil-treated patients were already receiving specific PAH drugs. Cardiopulmonary exercise testing was performed before and after sildenafil. Results: Peak VO2, peak O-2 pulse, VE/CO2 and PETCO2, were 0.84 +/- 0.1 L/min, 6.1 +/- 0.7 mL beat(-1), 49 +/- 2 and 26 +/- 1.5 mm Hg, and improved after adding sildenafil to 0.91 +/- 0.1 L/min, 6.8 +/- 0.8 mL beat(-1), 43 +/- 2, and 30 +/- 1.9, respectively, whereas control patients worsened (p=0.012, 0.008, 0.008 and 0.0002, treated vs. controls, respectively). Conclusions: Sildenafil improves PETCO2, VE/VCO2, peak O-2 pulse and peak VO2 during exercise compared to controls. A prospective, placebo-controlled study is needed to validate these findings. (C) 2007 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.