{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T21:09:12Z","timestamp":1787864952489,"version":"build-2784847793"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":609,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2024,6,19]],"date-time":"2024-06-19T00:00:00Z","timestamp":1718755200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016473","name":"American Regent","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016473","id-type":"DOI","asserted-by":"publisher"}]},{"name":"American Regent, a Daiichi Sankyo Group company"},{"DOI":"10.13039\/100016473","name":"American Regent","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016473","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Ferric carboxymaltose (FCM) is guideline-recommended for iron deficiency (ID) in heart failure with reduced ejection fraction (HFrEF). Despite a well-established safety profile, the magnitude and clinical significance of FCM-induced hypophosphataemia in HFrEF remains unclear. This pre-specified substudy of HEART-FID evaluated serum phosphate, 1,25-dihydroxyvitamin D, and plasma parathyroid hormone (PTH) subsequent to FCM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>HEART-FID was a randomized, double-blind, placebo-controlled trial of ambulatory patients with HFrEF and ID randomized to FCM versus placebo. This substudy assessed mean change from baseline across eight visits over 6\u2009months for the following endpoints: serum phosphate, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and PTH, in addition to the clinical severity of potential hypophosphataemia. Overall, 133 patients (n\u2009=\u200962 FCM, n\u2009=\u200971 placebo) were prospectively enrolled. Mean\u2009age was 68\u2009\u00b1\u200911\u2009years, 55 (41.4%) were women, and 29 (21.8%) had chronic kidney disease. Phosphate levels decreased in 34 (57.6%) patients in the FCM group compared with 7 (10.3%) in the placebo group. Mean change in phosphate levels reached a nadir at day 21 (\u22120.36\u2009\u00b1\u20090.27\u2009mmol\/L) subsequent to FCM infusion with 28 (51%) having moderate-to-severe hypophosphataemia. Reductions in 1,25-dihydroxyvitamin D were also observed, whilst PTH increased. These biochemical changes returned to baseline levels by day 91. Serum levels of 25-hydroxyvitamin D remained stable throughout the study. No serious adverse events associated with hypophosphataemia were reported.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Transient moderate-to-severe hypophosphataemia was frequent subsequent to FCM infusion, accompanied by 1,25-dihydroxyvitamin D decrease and PTH increase. Serum levels of 25-hydroxyvitamin D remained stable. No evidence of symptomatic hypophosphataemia was reported, collectively indicating FCM-related hypophosphataemia to be clinically benign and transient in HFrEF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.3348","type":"journal-article","created":{"date-parts":[[2024,6,19]],"date-time":"2024-06-19T08:28:35Z","timestamp":1718785715000},"page":"872-880","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Characterization of Serum Phosphate Levels Over Time with Intravenous Ferric Carboxymaltose Versus Placebo as Treatment for Heart Failure with Reduced Ejection Fraction and Iron Deficiency: An Exploratory Prospective Substudy From HEART-FID"],"prefix":"10.1093","volume":"27","author":[{"given":"Nina","family":"Nouhravesh","sequence":"first","affiliation":[{"name":"Duke Clinical Research Institute , Durham, NC ,","place":["USA"]},{"name":"Department of Cardiology, Herlev-Gentofte University Hospital , Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jyotsna","family":"Garg","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute , Durham, NC ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank W.","family":"Rockhold","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute , Durham, NC ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmine G.","family":"De Pasquale","sequence":"additional","affiliation":[{"name":"Flinders Medical Centre , Adelaide, SA ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen","family":"O'Meara","sequence":"additional","affiliation":[{"name":"Montreal Heart Institute and Universit\u00e9 de Montr\u00e9al , Quebec ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory D.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Massachusetts General Hospital , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javed","family":"Butler","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Mississippi , Jackson, MS ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephine","family":"Harrington","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute , Durham, NC ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin A.","family":"Ezekowitz","sequence":"additional","affiliation":[{"name":"Canadian VIGOUR Centre, University of Alberta , Edmonton, AB ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Ponikowski","sequence":"additional","affiliation":[{"name":"The Center for Heart Diseases, University Hospital, Wroclaw Medical University , Wroclaw ,","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard W.","family":"Troughton","sequence":"additional","affiliation":[{"name":"Department of Medicine, Christchurch Heart Institute, University of Otago , Christchurch ,","place":["New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yee Weng","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Mayo Clinic , Rochester, MN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Blackman","sequence":"additional","affiliation":[{"name":"American Regent , Shirley, NY ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed","family":"Numan","sequence":"additional","affiliation":[{"name":"American Regent , Shirley, NY ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Adamczyk","sequence":"additional","affiliation":[{"name":"American Regent , Shirley, NY ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian F.","family":"Hernandez","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute , Durham, NC ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Mentz","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute , Durham, NC ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,6,19]]},"reference":[{"key":"2026021721484575000_ejhf3348-bib-0001","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1038\/nrcardio.2011.77","article-title":"Anemia and iron deficiency in heart failure: Mechanisms and therapeutic approaches","volume":"8","author":"Van Veldhuisen","year":"2011","journal-title":"Nat Rev Cardiol"},{"key":"2026021721484575000_ejhf3348-bib-0002","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.ahj.2013.01.017","article-title":"Iron deficiency in chronic heart failure: An international pooled analysis","volume":"165","author":"Klip","year":"2013","journal-title":"Am Heart J"},{"key":"2026021721484575000_ejhf3348-bib-0003","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1093\/eurheartj\/ehw128","article-title":"2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC","volume":"37","author":"Ponikowski","year":"2016","journal-title":"Eur Heart J"},{"key":"2026021721484575000_ejhf3348-bib-0004","doi-asserted-by":"crossref","DOI":"10.3390\/nu14153214","article-title":"Neglected comorbidity of chronic heart failure: Iron deficiency","volume":"14","author":"Manceau","year":"2022","journal-title":"Nutrients"},{"key":"2026021721484575000_ejhf3348-bib-0005","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1002\/ejhf.2333","article-title":"2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). With the special contribution of the Heart Failure Association (HFA) of the ESC","volume":"24","author":"McDonagh","year":"2022","journal-title":"Eur J Heart Fail"},{"key":"2026021721484575000_ejhf3348-bib-0006","doi-asserted-by":"crossref","first-page":"2199","DOI":"10.1016\/S0140-6736(22)02083-9","article-title":"Intravenous ferric derisomaltose in patients with heart failure and iron deficiency in the UK (IRONMAN): An investigator-initiated, prospective, randomised, open-label, blinded-endpoint trial","volume":"400","author":"Kalra","year":"2022","journal-title":"Lancet"},{"key":"2026021721484575000_ejhf3348-bib-0007","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1016\/S0140-6736(20)32339-4","article-title":"Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: A multicentre, double-blind, randomised, controlled trial","volume":"396","author":"Ponikowski","year":"2020","journal-title":"Lancet"},{"key":"2026021721484575000_ejhf3348-bib-0008","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1002\/ejhf.3193","article-title":"Iron replacement therapy in heart failure: Contextualizing the results of the HEART-FID trial","volume":"26","author":"Butler","year":"2024","journal-title":"Eur J Heart Fail"},{"key":"2026021721484575000_ejhf3348-bib-0009","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1056\/NEJMoa2304968","article-title":"Ferric carboxymaltose in heart failure with iron deficiency","volume":"389","author":"Mentz","year":"2023","journal-title":"N Engl J Med"},{"key":"2026021721484575000_ejhf3348-bib-0010","doi-asserted-by":"crossref","DOI":"10.1155\/2012\/172104","article-title":"Safety and efficacy of intravenous ferric carboxymaltose (750\u2009mg) in the treatment of iron deficiency anemia: Two randomized, controlled trials","volume":"2012","author":"Barish","year":"2012","journal-title":"Anemia"},{"key":"2026021721484575000_ejhf3348-bib-0011","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1111\/j.1572-0241.2007.01744.x","article-title":"A novel intravenous iron formulation for treatment of anemia in inflammatory bowel disease: The ferric carboxymaltose (FERINJECT) randomized controlled trial","volume":"103","author":"Kulnigg","year":"2008","journal-title":"Am J Gastroenterol"},{"key":"2026021721484575000_ejhf3348-bib-0012","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1038\/ncpneph0124","article-title":"Hypophosphatemia: An evidence-based approach to its clinical consequences and management","volume":"2","author":"Amanzadeh","year":"2006","journal-title":"Nat Clin Prac Nephrol"},{"key":"2026021721484575000_ejhf3348-bib-0013","doi-asserted-by":"crossref","DOI":"10.1161\/CIRCHEARTFAILURE.120.008100","article-title":"Randomized placebo-controlled trial of ferric carboxymaltose in heart failure with iron deficiency: Rationale and design","volume":"14","author":"Mentz","year":"2021","journal-title":"Circ Heart Fail"},{"key":"2026021721484575000_ejhf3348-bib-0014","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1001\/jama.2019.22450","article-title":"Effects of iron isomaltoside vs ferric carboxymaltose on hypophosphatemia in iron-deficiency anemia: Two randomized clinical trials","volume":"323","author":"Wolf","year":"2020","journal-title":"JAMA"},{"key":"2026021721484575000_ejhf3348-bib-0015","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1002\/jbmr.1923","article-title":"Effects of iron deficiency anemia and its treatment on fibroblast growth factor 23 and phosphate homeostasis in women","volume":"28","author":"Wolf","year":"2013","journal-title":"J Bone Mineral Res"},{"key":"2026021721484575000_ejhf3348-bib-0016","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1002\/phar.1729","article-title":"A randomized noninferiority trial of intravenous iron isomaltoside versus oral iron sulfate in patients with nonmyeloid malignancies and anemia receiving chemotherapy: The PROFOUND trial","volume":"36","author":"Birgeg\u00e5rd","year":"2016","journal-title":"Pharmacotherapy"},{"key":"2026021721484575000_ejhf3348-bib-0017","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1080\/00365521.2016.1196496","article-title":"High-dose fast infusion of parenteral iron isomaltoside is efficacious in inflammatory bowel disease patients with iron-deficiency anaemia without profound changes in phosphate or fibroblast growth factor 23","volume":"51","author":"Dahlerup","year":"2016","journal-title":"Scand J Gastroenterol"},{"key":"2026021721484575000_ejhf3348-bib-0018","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1038\/ajg.2013.335","article-title":"A randomized, open-label, non-inferiority study of intravenous iron isomaltoside 1000 (Monofer) compared with oral iron for treatment of anemia in IBD (PROCEED)","volume":"108","author":"Reinisch","year":"2013","journal-title":"Am J Gastroenterol"},{"key":"2026021721484575000_ejhf3348-bib-0019","doi-asserted-by":"crossref","first-page":"2719","DOI":"10.1111\/j.1537-2995.2009.02327.x","article-title":"Large-dose intravenous ferric carboxymaltose injection for iron deficiency anemia in heavy uterine bleeding: A randomized, controlled trial","volume":"49","author":"Van Wyck","year":"2009","journal-title":"Transfusion"},{"key":"2026021721484575000_ejhf3348-bib-0020","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1002\/ehf2.14286","article-title":"Hypophosphataemia risk associated with ferric carboxymaltose in heart failure: A pooled analysis of clinical trials","volume":"10","author":"Rosano","year":"2023","journal-title":"ESC Heart Fail"},{"key":"2026021721484575000_ejhf3348-bib-0021","doi-asserted-by":"crossref","first-page":"2270","DOI":"10.1016\/j.jacc.2018.03.448","article-title":"High-dose ferric carboxymaltose in patients with HFrEF induces significant hypophosphatemia","volume":"71","author":"St\u00f6hr","year":"2018","journal-title":"J Am Coll Cardiol"},{"key":"2026021721484575000_ejhf3348-bib-0022","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1002\/jcph.1754","article-title":"Hypophosphatemia is common after intravenous ferric carboxymaltose infusion among patients with symptomatic heart failure with reduced ejection fraction","volume":"61","author":"Dashwood","year":"2021","journal-title":"J Clin Pharmacol"},{"key":"2026021721484575000_ejhf3348-bib-0023","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1161\/CIRCULATIONAHA.117.027497","article-title":"Effect of ferric carboxymaltose on exercise capacity in patients with chronic heart failure and iron deficiency","volume":"136","author":"Veldhuisen","year":"2017","journal-title":"Circulation"},{"key":"2026021721484575000_ejhf3348-bib-0024","doi-asserted-by":"crossref","first-page":"2436","DOI":"10.1056\/NEJMoa0908355","article-title":"Ferric carboxymaltose in patients with heart failure and iron deficiency","volume":"361","author":"Anker","year":"2009","journal-title":"N Engl J Med"},{"key":"2026021721484575000_ejhf3348-bib-0025","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1093\/eurheartj\/ehu385","article-title":"Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiency","volume":"36","author":"Ponikowski","year":"2015","journal-title":"Eur Heart J"},{"key":"2026021721484575000_ejhf3348-bib-0026","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41581-019-0189-5","article-title":"FGF23 at the crossroads of phosphate, iron economy and erythropoiesis","volume":"16","author":"Edmonston","year":"2020","journal-title":"Nat Rev Nephrol"},{"key":"2026021721484575000_ejhf3348-bib-0027","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.124486","article-title":"Randomized trial of intravenous iron-induced hypophosphatemia","volume":"3","author":"Wolf","year":"2018","journal-title":"JCI Insight"},{"key":"2026021721484575000_ejhf3348-bib-0028","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1038\/bonekey.2013.231","article-title":"Phosphate metabolism and vitamin D","volume":"3","author":"Fukumoto","year":"2014","journal-title":"Bonekey Rep"},{"key":"2026021721484575000_ejhf3348-bib-0029","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1053\/j.ajkd.2012.03.024","article-title":"Approach to treatment of hypophosphatemia","volume":"60","author":"Felsenfeld","year":"2012","journal-title":"Am J Kidney Dis"},{"key":"2026021721484575000_ejhf3348-bib-0030","doi-asserted-by":"crossref","first-page":"R147","DOI":"10.1186\/cc9215","article-title":"Treatment of hypophosphatemia in the intensive care unit: A review","volume":"14","author":"Geerse","year":"2010","journal-title":"Crit Care"}],"container-title":["European Journal of Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/27\/5\/872\/66831832\/eurjhf_27_5_872.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/27\/5\/872\/66831832\/eurjhf_27_5_872.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T02:48:57Z","timestamp":1771382937000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eurjhf\/article\/27\/5\/872\/8469721"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,19]]},"references-count":30,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,6,19]]},"published-print":{"date-parts":[[2025,5,1]]}},"URL":"https:\/\/doi.org\/10.1002\/ejhf.3348","relation":{},"ISSN":["1388-9842","1879-0844"],"issn-type":[{"value":"1388-9842","type":"print"},{"value":"1879-0844","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,5]]},"published":{"date-parts":[[2024,6,19]]},"assertion":[{"value":"2023-12-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}