Background
Phosphodiesterase V (PDEV) is upregulated in
heart failure, leading to increased degradation of cGMP and impaired natriuresis. PDEV inhibition improves the renal response to
B-type natriuretic peptide in animal models. We tested the hypothesis that long-term PDEV inhibition would improve renal function and cardiorenal response after short-term volume load in subjects with pre-
heart failure. Methods and Results A total of 20 subjects with pre-
heart failure (defined as an ejection fraction ≤45% without previous diagnosis of
heart failure) and renal impairment were randomized in a 2:1 manner to
tadalafil or placebo. Baseline echocardiography and renal clearance study were performed, followed by a short-term saline load and repeated echocardiography and renal clearance study. Subjects then received either
tadalafil at a goal dose of 20 mg daily or placebo, and the study day was repeated after 12 weeks. Long-term
tadalafil did not improve glomerular filtration rate (median increase of 2.0 mL/min in the
tadalafil group versus 13.5 mL/min in the placebo group; P=0.54). There was no difference in urinary
sodium or cGMP excretion with PDEV inhibition following short-term saline loading. Conclusions Glomerular filtration rate and urinary
sodium/cGMP excretion were not significantly different after 12 weeks of
tadalafil compared with placebo. These results do not support the use of PDEV inhibition to improve renal response in patients with pre-
heart failure. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01970176.