{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T18:53:24Z","timestamp":1789757604739,"version":"4.0.1"},"reference-count":145,"publisher":"Oxford University Press (OUP)","issue":"26","license":[{"start":{"date-parts":[[2024,5,11]],"date-time":"2024-05-11T00:00:00Z","timestamp":1715385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Current understanding of iron-deficient heart failure is based on blood tests that are thought to reflect systemic iron stores, but the available evidence suggests greater complexity. The entry and egress of circulating iron is controlled by erythroblasts, which (in severe iron deficiency) will sacrifice erythropoiesis to supply iron to other organs, e.g. the heart. Marked hypoferraemia (typically with anaemia) can drive the depletion of cardiomyocyte iron, impairing contractile performance and explaining why a transferrin saturation &amp;lt; \u224815%\u201316% predicts the ability of intravenous iron to reduce the risk of major heart failure events in long-term trials (Type 1 iron-deficient heart failure). However, heart failure may be accompanied by intracellular iron depletion within skeletal muscle and cardiomyocytes, which is disproportionate to the findings of systemic iron biomarkers. Inflammation- and deconditioning-mediated skeletal muscle dysfunction\u2014a primary cause of dyspnoea and exercise intolerance in patients with heart failure\u2014is accompanied by intracellular skeletal myocyte iron depletion, which can be exacerbated by even mild hypoferraemia, explaining why symptoms and functional capacity improve following intravenous iron, regardless of baseline haemoglobin or changes in haemoglobin (Type 2 iron-deficient heart failure). Additionally, patients with advanced heart failure show myocardial iron depletion due to both diminished entry into and enhanced egress of iron from the myocardium; the changes in iron proteins in the cardiomyocytes of these patients are opposite to those expected from systemic iron deficiency. Nevertheless, iron supplementation can prevent ventricular remodelling and cardiomyopathy produced by experimental injury in the absence of systemic iron deficiency (Type 3 iron-deficient heart failure). These observations, taken collectively, support the possibility of three different mechanistic pathways for the development of iron-deficient heart failure: one that is driven through systemic iron depletion and impaired erythropoiesis and two that are characterized by disproportionate depletion of intracellular iron in skeletal and cardiac muscle. These mechanisms are not mutually exclusive, and all pathways may be operative at the same time or may occur sequentially in the same patients.<\/jats:p>","DOI":"10.1093\/eurheartj\/ehae284","type":"journal-article","created":{"date-parts":[[2024,5,11]],"date-time":"2024-05-11T10:14:27Z","timestamp":1715422467000},"page":"2281-2293","source":"Crossref","is-referenced-by-count":34,"title":["Identification of three mechanistic pathways for iron-deficient heart failure"],"prefix":"10.1093","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1828-2387","authenticated-orcid":false,"given":"Milton","family":"Packer","sequence":"first","affiliation":[{"name":"Baylor Heart and Vascular Institute, Baylor University Medical Center , 621 North Hall Street, Dallas, TX 75226 , USA"},{"name":"Imperial College , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan D","family":"Anker","sequence":"additional","affiliation":[{"name":"Department of Cardiology of German Heart Center Charit\u00e9, Institute of Health Center for Regenerative Therapies, German Centre for Cardiovascular Research, partner site Berlin, Charit\u00e9 Universit\u00e4tsmedizin , Berlin , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7683-4720","authenticated-orcid":false,"given":"Javed","family":"Butler","sequence":"additional","affiliation":[{"name":"Baylor Scott and White Research Institute, Baylor University Medical Center , Dallas, TX , USA"},{"name":"University of Mississippi Medical Center , Jackson, MS , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John G F","family":"Cleland","sequence":"additional","affiliation":[{"name":"British Heart Foundation Centre of Research Excellence, School of Cardiovascular and Metabolic Health, University of Glasgow , Glasgow , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul R","family":"Kalra","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Portsmouth Hospitals University NHS Trust , Portsmouth , UK"},{"name":"College of Medical, Veterinary & Life Sciences, University of Glasgow , Glasgow , UK"},{"name":"Faculty of Science and Health, University of Portsmouth , Portsmouth , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J","family":"Mentz","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Duke University School of Medicine , Durham, NC , USA"},{"name":"Duke Clinical Research Institute , Durham, NC , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Ponikowski","sequence":"additional","affiliation":[{"name":"Institute of Heart Diseases, Wroclaw Medical University , Wroclaw , Poland"},{"name":"Institute of Heart Diseases, University Hospital , Wroclaw , Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,5,11]]},"reference":[{"key":"2024070911263625300_ehae284-B1","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1161\/CIRCULATIONAHA.122.060511","article-title":"Iron deficiency in heart failure and effect of dapagliflozin: findings from DAPA-HF","volume":"146","author":"Docherty","year":"2022","journal-title":"Circulation"},{"key":"2024070911263625300_ehae284-B2","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1111\/bjh.12311","article-title":"British Committee for Standards in Haematology. 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