{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:30:38Z","timestamp":1753889438658,"version":"3.41.2"},"reference-count":14,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2022,1,18]]},"abstract":"\n Background<\/jats:title>\n 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\u2010type natriuretic peptide in animal models. We tested the hypothesis that long\u2010term PDEV inhibition would improve renal function and cardiorenal response after short\u2010term volume load in subjects with pre\u2013heart failure.<\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n A total of 20 subjects with pre\u2013heart failure (defined as an ejection fraction \u226445% 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\u2010term saline load and repeated echocardiography and renal clearance study. Subjects then received either tadalafil at a goal dose of 20\u00a0mg daily or placebo, and the study day was repeated after 12\u00a0weeks. Long\u2010term tadalafil did not improve glomerular filtration rate (median increase of 2.0\u00a0mL\/min in the tadalafil group versus 13.5\u00a0mL\/min in the placebo group;\n P<\/jats:italic>\n =0.54). There was no difference in urinary sodium or cGMP excretion with PDEV inhibition following short\u2010term saline loading.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Glomerular filtration rate and urinary sodium\/cGMP excretion were not significantly different after 12\u00a0weeks of tadalafil compared with placebo. These results do not support the use of PDEV inhibition to improve renal response in patients with pre\u2013heart failure.<\/jats:p>\n <\/jats:sec>\n \n Registration<\/jats:title>\n \n URL:\n https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n ; Unique identifier: NCT01970176.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.121.022126","type":"journal-article","created":{"date-parts":[[2022,1,9]],"date-time":"2022-01-09T03:09:41Z","timestamp":1641697781000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Cardiorenal Effects of Long\u2010Term Phosphodiesterase V Inhibition in Pre\u2013Heart Failure"],"prefix":"10.1161","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8129-2452","authenticated-orcid":false,"given":"Scott A.","family":"Hubers","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine Mayo Clinic Rochester MN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siu\u2010Hin","family":"Wan","sequence":"additional","affiliation":[{"name":"Division of Cardiology University of Texas Southwestern Medical Center Dallas TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2143-6826","authenticated-orcid":false,"given":"Fadi W.","family":"Adel","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Mayo Clinic Rochester MN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sherry L.","family":"Benike","sequence":"additional","affiliation":[{"name":"Cardiorenal Research Laboratory Mayo Clinic Rochester MN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr","given":"John C.","family":"Burnett","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Mayo Clinic Rochester MN"},{"name":"Cardiorenal Research Laboratory Mayo Clinic Rochester MN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1340-0647","authenticated-orcid":false,"given":"Christopher","family":"Scott","sequence":"additional","affiliation":[{"name":"Department of Biomedical Statistics and Informatics Mayo Clinic Rochester MN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2315-0330","authenticated-orcid":false,"given":"Horng H.","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Mayo Clinic Rochester MN"},{"name":"Cardiorenal Research Laboratory Mayo Clinic Rochester MN"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000085166.44904.79"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2011.07.042"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2006020161"},{"key":"e_1_3_2_5_2","first-page":"408","article-title":"Regulator of G protein signaling 2 mediates cardiac compensation to pressure overload and antihypertrophic effects of PDE5 inhibition in mice","volume":"119","author":"Takimoto E","year":"2009","unstructured":"Takimoto E, Koitabashi N, Hsu S, Ketner EA, Zhang M, Nagayama T, Bedja D, Gabrielson KL, Blanton R, Siderovski DP, et al. 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