PDE 5 inhibition with udenafil improves left ventricular systolic/diastolic functions and exercise capacity in patients with chronic heart failure with reduced ejection fraction; A12-week, randomized, double-blind, placebo-controlled trial

Background Impaired nitric oxide-mediated pulmonary vascular tone is commonly found in heart failure with reduced ejection fraction (HFrEF), and is associated with derangement of left ventricular (LV) hemodynamics and decreased exercise capacity, which may be reversed by PDE5 inhibitor. This study investigated the effects of a new, long-acting PDE5 inhibitor on LV hemodynamics and exercise capacity in HFrEF. Methods Patients with chronic HFrEF on optimal medical therapy for >30 days before enrollment were randomly assigned to placebo or udenafil at a dose of 50mg 2x/day for the first 4 weeks followed by 100mg 2x/day for the next 8 weeks. All patients underwent cardiopulmonary exercise echocardiography before and after the 12-week treatment. Results Improvement of subjective functional capacity was more frequently reported in the udenafil group (P = 0.002). Also, a higher increase in peak VO2 (Delta(peak) V-O2, 21.6% (6.9 similar to 106.4%) vs 1.9% (-15.7 similar to 21.0%) in the placebo group, P = 0.04) and a larger decrease in ventilatory efficiency were observed in the udenafil group (Delta-6.4 +/- 9.7 vs Delta 1.9 +/- 12.1 in the placebo group, P = 0.03). Regarding LV systolic function, the extent of increment in LV ejection fraction was significantly greater in the udenafil group (6.6 +/- 6.4% vs 2.3 +/- 4.8% in the placebo group, P = 0.02). In the udenafil group, an echocardiographic surrogate of LV filling pressure was more prominently decreased (P = 0.006) along with a significant reverse remodeling of left atrial volume index (57 +/- 25mL at baseline to 44 +/- 23 at 12th week, P = 0.04) and a progressive fall in B-type natriuretic peptide level (589 +/- 679pg/mL at baseline to 220 +/- 225pg/mL at 12th week, P < 0.001), indicating LV diastolic function improvement. Udenafil was well tolerated without excess of adverse events compared to placebo. Conclusions Udenafil improves LV systolic/diastolic functions and exercise capacity in conjunction with established conventional pharmacotherapy, without significant adverse events in HFrEF.