ArticleEuropean journal of heart failure2018
Iron deficiency impairs contractility of human cardiomyocytes through decreased mitochondrial function.
Article in European journal of heart failure, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 182 papers, 3 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
182 citing papers in PubMed, 3 syntheses or guidelines pooled it, 318 citations in OpenAlex.
- Intravenous iron therapy for patients with heart failure: a meta-analysis stratified by chronic kidney disease status.BMC cardiovascular disorders · 2026Pooled it
- Efficacy of ferric carboxymaltose in heart failure with iron deficiency: an individual patient data meta-analysis.European heart journal · 2023Pooled it
- Highlights in heart failure.ESC heart failure · 2019Pooled it
- Anaemia predicts iron homoeostasis dysregulation and modulates the response to empagliflozin in heart failure with reduced ejection fraction: the EMPATROPISM-FE trial.European heart journal · 2025Trial
- Improvement in left atrial strain following ferric carboxymaltose in heart failure: an analysis of the Myocardial-IRON trial.ESC heart failure · 2024Trial
- Intravenous iron supplementation improves energy metabolism of exercising skeletal muscles without effect on either oxidative stress or inflammation in male patients with heart failure with reduced ejection fraction.Cardiology journal · 2024Trial
- Empagliflozin effects on iron metabolism as a possible mechanism for improved clinical outcomes in non-diabetic patients with systolic heart failure.Nature cardiovascular research · 2023Trial
- Ferric Carboxymaltose in Iron-Deficient Patients with Hospitalized Heart Failure and Reduced Kidney Function.Clinical journal of the American Society of Nephrology : CJASN · 2023Trial
- Trial
- Intravenous iron supplement for iron deficiency in patients with severe aortic stenosis scheduled for transcatheter aortic valve implantation: results of the IIISAS randomised trial.European journal of heart failure · 2022Trial
- Short-Term Changes in Left and Right Ventricular Cardiac Magnetic Resonance Feature Tracking Strain Following Ferric Carboxymaltose in Patients With Heart Failure: A Substudy of the Myocardial-IRON Trial.Journal of the American Heart Association · 2022Trial
- The effect of intravenous ferric carboxymaltose on cardiac reverse remodelling following cardiac resynchronization therapy-the IRON-CRT trial.European heart journal · 2021Trial
- Safety and efficacy of iron isomaltoside 1000/ferric derisomaltose versus iron sucrose in patients with chronic kidney disease: the FERWON-NEPHRO randomized, open-label, comparative trial.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2021Trial
- Noninvasive Imaging Estimation of Myocardial Iron Repletion Following Administration of Intravenous Iron: The Myocardial-IRON Trial.Journal of the American Heart Association · 2020Trial
- Iron, Copper, and Zinc Dyshomeostasis in Cardiovascular and Cerebrovascular Diseases: Redox Mechanisms, Evidence Levels, and Translational Prospects.International journal of molecular sciences · 2026Review
- Ferric Carboxymaltose Therapy Improves the Index of Cardiac Electrophysiological Balance in Iron-Deficient Heart Failure with Reduced Ejection Fraction.Medicina (Kaunas, Lithuania) · 2026Article
- Intravenous ferric carboxymaltose and exercise capacity in iron-deficient kidney transplant recipients: a randomised, placebo-controlled trial in the Netherlands.EClinicalMedicine · 2026Article
- Ferroptosis-related stress during aging and its relevance to disease.GeroScience · 2026Review
- Relationship between iron deficiency and corrected QT-interval prolongation in Japanese patients undergoing maintenance hemodialysis.Clinical and experimental nephrology · 2026Article
- New-Onset Acute Heart Failure With Reduced Ejection Fraction Associated With Severe Microcytic Anemia.Clinical case reports · 2026Article
122 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsIron deficiency is common in patients with heart failure and associated with a poor cardiac function and higher mortality. How iron deficiency impairs cardiac function on a cellular level in the human setting is unknown. This study aims to determine the direct effects of iron deficiency and iron repletion on human cardiomyocytes. METHODS AND
resultsHuman embryonic stem cell-derived cardiomyocytes were depleted of iron by incubation with the iron chelator deferoxamine (DFO). Mitochondrial respiration was determined by Seahorse Mito Stress test, and contractility was directly quantified using video analyses according to the BASiC method. The activity of the mitochondrial respiratory chain complexes was examined using spectrophotometric enzyme assays. Four days of iron depletion resulted in an 84% decrease in ferritin (P < 0.0001) and significantly increased gene expression of transferrin receptor 1 and divalent metal transporter 1 (both P < 0.001). Mitochondrial function was reduced in iron-deficient cardiomyocytes, in particular ATP-linked respiration and respiratory reserve were impaired (both P < 0.0001). Iron depletion affected mitochondrial function through reduced activity of the iron-sulfur cluster containing complexes I, II and III, but not complexes IV and V. Iron deficiency reduced cellular ATP levels by 74% (P < 0.0001) and reduced contractile force by 43% (P < 0.05). The maximum velocities during both systole and diastole were reduced by 64% and 85%, respectively (both P < 0.001). Supplementation of transferrin-bound iron recovered functional and morphological abnormalities within 3 days.
conclusionIron deficiency directly affects human cardiomyocyte function, impairing mitochondrial respiration, and reducing contractility and relaxation. Restoration of intracellular iron levels can reverse these effects.
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