Long-Term Use of Sildenafil in the Therapeutic Management of Heart Failure Marco Guazzi, Michele Samaja, Ross Arena, Marco Vicenzi, Maurizio D. Guazzi We tested whether chronic phosphodiesterase 5 inhibition by sildenafil is beneficial in heart failure. A total of 46 heart failure patients were randomly assigned to placebo (23 patients) or sildenafil (23 patients), with 3- and 6-month assessments of cardiopulmonary exercise test performance, brachial artery flow-mediated maximal dilatation, and ergoreflex responses. Sildenafil and not placebo improved flow-mediated maximal dilatation, ergoreflex effect on ventilation, exercise ventilation to CO2 production slope, and breathlessness, at both 3 and 6 months (p < 0.01). Findings suggest that benefits of sildenafil in heart failure are sustained and that an endothelium-mediated modulation of the muscle ergoreflex oversignaling may be at work.