{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T19:54:03Z","timestamp":1791575643121,"version":"4.3.4"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T00:00:00Z","timestamp":1768694400000},"content-version":"vor","delay-in-days":2235,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2019,12,6]],"date-time":"2019-12-06T00:00:00Z","timestamp":1575590400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["FP7-242209-BIOSTAT-CHF"],"award-info":[{"award-number":["FP7-242209-BIOSTAT-CHF"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["FP7\u2010242209\u2010BIOSTAT\u2010CHF"],"award-info":[{"award-number":["FP7\u2010242209\u2010BIOSTAT\u2010CHF"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Severe deficiency of the essential trace element selenium can cause myocardial dysfunction although the mechanism at cellular level is uncertain. Whether, in clinical practice, moderate selenium deficiency is associated with worse symptoms and outcome in patients with heart failure is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>BIOSTAT-CHF is a multinational, prospective, observational cohort study that enrolled patients with worsening heart failure. Serum concentrations of selenium were measured by inductively coupled plasma mass spectrometry. Primary endpoint was a composite of all-cause mortality and hospitalization for heart failure; secondary endpoint was all-cause mortality. To investigate potential mechanisms by which selenium deficiency might affect prognosis, human cardiomyocytes were cultured in absence of selenium, and mitochondrial function and oxidative stress were assessed. Serum selenium concentration (deficiency) was &amp;lt;70\u2009\u03bcg\/L in 485 (20.4%) patients, who were older, more often women, had worse New York Heart Association class, more severe signs and symptoms of heart failure and poorer exercise capacity (6-min walking test) and quality of life (Kansas City Cardiomyopathy Questionnaire). Selenium deficiency was associated with higher rates of the primary endpoint [hazard ratio (HR) 1.23; 95% confidence interval (CI) 1.06\u20131.42] and all-cause mortality (HR 1.52; 95% CI 1.26\u20131.86). In cultured human cardiomyocytes, selenium deprivation impaired mitochondrial function and oxidative phosphorylation, and increased intracellular reactive oxygen species levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Selenium deficiency in heart failure patients is independently associated with impaired exercise tolerance and a 50% higher mortality rate, and impaired mitochondrial function in vitro, in human cardiomyocytes. Clinical trials are needed to investigate the effect of selenium supplements in patients with heart failure, especially if they have low plasma concentrations of selenium.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.1644","type":"journal-article","created":{"date-parts":[[2019,12,6]],"date-time":"2019-12-06T03:39:17Z","timestamp":1575603557000},"page":"1415-1423","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":136,"title":["Selenium and Outcome in Heart Failure"],"prefix":"10.1093","volume":"22","author":[{"given":"Nils","family":"Bomer","sequence":"first","affiliation":[{"name":"Department of Experimental Cardiology, University of Groningen, University Medical Center Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels","family":"Grote Beverborg","sequence":"additional","affiliation":[{"name":"Department of Experimental Cardiology, University of Groningen, University Medical Center Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martijn F.","family":"Hoes","sequence":"additional","affiliation":[{"name":"Department of Experimental Cardiology, University of Groningen, University Medical Center Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koen W.","family":"Streng","sequence":"additional","affiliation":[{"name":"Department of Experimental Cardiology, University of Groningen, University Medical Center Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathilde","family":"Vermeer","sequence":"additional","affiliation":[{"name":"Department of Experimental Cardiology, University of Groningen, University Medical Center Groningen , Groningen ,","place":["The 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G.F.","family":"Cleland","sequence":"additional","affiliation":[{"name":"BIOSTAT-CHF"},{"name":"National Heart & Lung Institute, Royal Brompton and Harefield Hospitals, Imperial College, London, and University of Hull , Kingston-upon-Hull ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans L.","family":"Hillege","sequence":"additional","affiliation":[{"name":"BIOSTAT-CHF"},{"name":"Department of Cardiology, University of Groningen, University Medical Center Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chim C.","family":"Lang","sequence":"additional","affiliation":[{"name":"BIOSTAT-CHF"},{"name":"School of Medicine Centre for Cardiovascular and Lung Biology, Division of Medical Sciences, University of Dundee, Ninewells Hospital & Medical School , Dundee ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leong L.","family":"Ng","sequence":"additional","affiliation":[{"name":"BIOSTAT-CHF"},{"name":"Department of Cardiovascular Sciences, University of Leicester, and NIHR Leicester Biomedical Research Centre, Glenfield Hospital , Leicester ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilesh J.","family":"Samani","sequence":"additional","affiliation":[{"name":"BIOSTAT-CHF"},{"name":"Department of Cardiovascular Sciences, University of Leicester, and NIHR Leicester Biomedical Research Centre, Glenfield Hospital , Leicester ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasper","family":"Tromp","sequence":"additional","affiliation":[{"name":"Department of Experimental Cardiology, University of Groningen, University Medical Center Groningen , Groningen ,","place":["The Netherlands"]},{"name":"National Heart Centre Singapore \u00a0","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk J.","family":"van Veldhuisen","sequence":"additional","affiliation":[{"name":"Department of Experimental Cardiology, University of Groningen, University Medical Center Groningen , Groningen ,","place":["The Netherlands"]},{"name":"BIOSTAT-CHF"},{"name":"Department of Cardiology, University of Groningen, University Medical Center Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daan J.","family":"Touw","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriaan A.","family":"Voors","sequence":"additional","affiliation":[{"name":"Department of Experimental Cardiology, University of Groningen, University Medical Center Groningen , Groningen ,","place":["The 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