{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:13:58Z","timestamp":1790115238861,"version":"4.0.1"},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T00:00:00Z","timestamp":1644969600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Cardiology"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Melatonin, the major secretion of the pineal gland, has beneficial effects on the cardiovascular system and might advantage heart failure with reduced ejection fraction (HFrEF) by attenuating the effects of the renin\u2013angiotensin\u2013aldosterone and sympathetic system on the heart besides its antioxidant and anti\u2010inflammatory effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Hypothesis<\/jats:title>\n                    <jats:p>We hypothesized that oral melatonin might improve echocardiographic parameters, serum biomarkers, and a composite clinical outcome (including quality of life, hospitalization, and mortality) in patients with HFrEF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A placebo\u2010controlled double\u2010blinded randomized clinical trial was conducted on patients with stable HFrEF. The intervention was 10\u2009mg melatonin or placebo tablets administered every night for 24 weeks. Echocardiography and measurements of N\u2010terminal pro\u2010B\u2010type natriuretic peptide (NT\u2010Pro BNP), high\u2010sensitivity C\u2010reactive protein, lipid profile, and psychological parameters were done at baseline and after 24 weeks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Overall, 92 patients were recruited, and 85 completed the study (melatonin: 42, placebo: 43). Serum NT\u2010Pro BNP decreased significantly in the melatonin compared with the placebo group (estimated marginal means for difference [95% confidence interval]: 111.0 [6.2\u2013215.7],\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.044). Moreover, the melatonin group had a significantly better clinical outcome (0.93 [0.18\u20131.69],\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.017), quality of life (5.8 [0.9\u201312.5],\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.037), and New York Heart Association\u00a0class (odds ratio: 12.9 [1.6\u2013102.4];\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.015) at the end of the trial. Other studied outcomes were not significantly different between groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Oral melatonin decreased NT\u2010Pro BNP and improved the quality of life in patients with HFrEF. Thus it might be a beneficial supplement in HFrEF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/clc.23796","type":"journal-article","created":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T05:45:21Z","timestamp":1644990321000},"page":"417-426","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Melatonin supplementation improves N\u2010terminal pro\u2010B\u2010type natriuretic peptide levels and quality of life in patients with heart failure with reduced ejection fraction: Results from MeHR trial, a randomized clinical trial"],"prefix":"10.1002","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4340-8949","authenticated-orcid":false,"given":"Shervin G.","family":"Hoseini","sequence":"first","affiliation":[{"name":"Isfahan Cardiovascular Research Center, Cardiovascular Research Institute Isfahan University of Medical Sciences  Isfahan Iran"},{"name":"Department of Physical Medicine and Rehabilitation, School of Medicine Isfahan University of Medical Sciences  Isfahan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyan","family":"Heshmat\u2010Ghahdarijani","sequence":"additional","affiliation":[{"name":"Heart Failure Research Center, Cardiovascular Research Institute Isfahan University of Medical Sciences  Isfahan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saeid","family":"Khosrawi","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, School of Medicine Isfahan University of Medical Sciences  Isfahan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Garakyaraghi","sequence":"additional","affiliation":[{"name":"Heart Failure Research Center, Cardiovascular Research Institute Isfahan University of Medical Sciences  Isfahan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7999-2393","authenticated-orcid":false,"given":"Davood","family":"Shafie","sequence":"additional","affiliation":[{"name":"Heart Failure Research Center, Cardiovascular Research Institute Isfahan University of Medical Sciences  Isfahan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjan","family":"Mansourian","sequence":"additional","affiliation":[{"name":"Isfahan Cardiovascular Research Center, Cardiovascular Research Institute Isfahan University of Medical Sciences  Isfahan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamidreza","family":"Roohafza","sequence":"additional","affiliation":[{"name":"Cardiac Rehabilitation Research Center, Cardiovascular Research Institute Isfahan University of Medical Sciences  Isfahan 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