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Tadalafil, a once-daily PDE5 inhibitor, did not slow loss of ambulation in a phase 3 placebo-controlled trial. This report details the cardiac findings from this study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Patients with DMD (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u2009331) aged 7 to 14 years on stable glucocorticoids were randomized to tadalafil 0.3\u00a0mg\/kg\/day, 0.6\u00a0mg\/kg\/day, or placebo. Ejection fraction (EF), fractional shortening, and M-mode ventricular dimensions were measured on echocardiograms. 12-lead ECGs were centrally evaluated for heart rate and intervals, and qualitative diagnoses. Vital signs and unsolicited adverse events were collected throughout the study. Cardiac MRI (CMR) was collected in a subset of 27 patients. Z-scores for ventricular dimensions and volumes were calculated based on published age-normative reference values. Treatment differences for change in continuous ECG parameters and vital signs were compared using Wilcoxon rank-sum tests. Echocardiogram and CMR parameters were analyzed with an ANCOVA model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Tadalafil had no adverse effects on echocardiographic left ventricular (LV) EF or fractional shortening, ECG findings, or vital signs. Mean diastolic LV internal dimension (LVIDd) was increased in the tadalafil 0.6\u00a0mg\/kg group versus placebo at Week 24 (+\u20090.13\u00a0cm,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=.019) and Week 48 (+\u20090.18\u00a0cm,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=.008), with a similar pattern observed for LV systolic dimensions (LVIDs). Mean LV end diastolic volume (EDV) measured by CMR also increased at Week 48 in the tadalafil 0.3\u00a0mg\/kg (+\u200913.0\u00a0ml,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=.047 vs. placebo) and 0.6\u00a0mg\/kg (+\u200912.0\u00a0ml,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=.08 vs. placebo) groups, with numerically smaller increases in LV EDV and commensurate increases in stroke volume and cardiac output. Z-scores for LVIDd and LV EDV were generally below the normal range at baseline and increased toward or within the normal range in the tadalafil groups but not in the placebo group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>No adverse effects of tadalafil on cardiovascular function were evident based on adverse events, echocardiograms, ECG, or vital sign measurements through 48 weeks in patients with DMD. The small mean increases in LVID and LV volume observed with tadalafil are consistent with PDE5 inhibitor pharmacology, but their clinical relevance in the context of LV tonic contraction in DMD is unknown and deserve further study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>ClinicalTrials.gov identifier<\/jats:title>\n                    <jats:p>NCT01865084 (first registration date: 24-May-2013).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12872-025-04727-3","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T23:28:11Z","timestamp":1744327691000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Effect of Tadalafil on cardiac function and left ventricular dimensions in Duchenne muscular dystrophy: safety and cardiac MRI substudy results from a randomized, placebo-controlled trial"],"prefix":"10.1186","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2052-9836","authenticated-orcid":false,"given":"David","family":"Cox","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry","family":"Byrne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W.","family":"Hammers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Landry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. 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The protocol and consent forms were approved by local institutional review boards at each study site. Written informed consent was obtained from at least 1 parent or guardian, and written assent was obtained from patients per local regulations, before any study procedures were performed. All animals were handled in compliance with National Institutes of Health and institutional guidelines that were approved by the institutional animal care and use committees of the University of Pennsylvania and University of Florida, as previously documented (Hammers et al. 2016).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"DC is a full-time employee and shareholder of Eli Lilly and Company. At the time the study was performed and this manuscript was initiated, JL (retired) was a full-time employee of Eli Lilly Canada. BJB has received research support from Sarepta Therapeutics, Pfizer and is a member of the Global Pompe Advisory Board supported by Sanofi. BJB has received consulting fees from Amicus Therapeutics, Rocket Pharma, and Tenaya. BJB is a co-founder of Ventura Life Sciences. BJB is an uncompensated member of the MDA Board or Directors. DWH and HLS declared no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"276"}}