Cardiorenal Effects of Long-Term Phosphodiesterase V Inhibition in Pre-Heart Failure

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...

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Published inJournal of the American Heart Association Vol. 11; no. 2; p. e022126
Main Authors Hubers, Scott A, Wan, Siu-Hin, Adel, Fadi W, Benike, Sherry L, Burnett, Jr, John C, Scott, Christopher, Chen, Horng H
Format Journal Article
LanguageEnglish
Published England John Wiley and Sons Inc 18.01.2022
Wiley
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Summary: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; =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.
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Supplementary Material for this article is available at https://www.ahajournals.org/doi/suppl/10.1161/JAHA.121.022126
For Sources of Funding and Disclosures, see page 8.
ISSN:2047-9980
2047-9980
DOI:10.1161/JAHA.121.022126