Iron Deficiency and its Relationship with Chronic Heart Failure- A Review.

Targeting Iron Deficiency in Heart Failure: Existing Evidence and Future Expectations.

The Impact of Intravenous Iron on Renal Injury and Function Markers in Patients With Chronic Kidney Disease and Iron Deficiency Without Anemia

Transferrin saturation is a superior prognostic biomarker for iron deficiency after acute decompensated heart failure: a retrospective clinical real-world cohort study

Intravenous Versus Oral Iron Replacement in Patients with a Continuous-Flow Left Ventricular Assist Device.

Patients with heart failure with reduced ejection fraction are at high risk for iron deficiency (ID) due to low intake and high losses. Randomized controlled trials show intravenous (IV) iron improves quality of life and lowers readmissions. Suboptimal ID screening may stem from limited awareness of ID thresholds and guidelines in heart failure. We hypothesized that implementing provider education and optimized EHR notification would improve ID screening and IV iron infusion rates over 6 months among inpatients at a community hospital. Presentations were delivered to the Internal Medicine Residents, Hospitalists, and Cardiologists, reviewing key trials and recommendations for ID in CHF from the European Society of Cardiology (ESC), the American College of Cardiology (ACC), and the American Heart Association (AHA). A flyer summarizing diagnostic criteria and IV iron treatment was then posted in high-traffic provider areas. A Best Practice Alert (BPA) was also implemented, which triggered if a patient had heart failure and no iron studies in the past 6 months, automatically adding iron study orders unless removed. IV iron was recommended through education via presentations and flyers, using criteria of ferritin <100 ng/mL or 100–299 ng/mL with TSAT <20%. Pre-intervention data (PRE) were collected from 10/1/2024 - 2/13/2025, and post-intervention (POST) from 2/14 - 5/20/2025. Exclusions included previous iron studies or iron supplementation within 6 months. A chi-square test of independence was performed to measure if there was a statistically significant difference between PRE and POST for ID screening, IV infusion, and oral iron rates. 2,461 encounters met inclusion criteria (PRE: 1,507, POST: 954). Prior to the intervention, 12.8% were screened for ID compared to 24.1% after intervention with an Absolute Benefit Increase of 11.3% (p < 0.001). The rate of IV iron repletion increased significantly (PRE: 4.8% vs. POST: 6.8%, p < 0.05). Oral iron repletion rates were not significantly different in PRE vs. POST (4.5% to 4.8%, p > 0.05). ID screening improved with minimal burden via provider education and BPAs. IV iron use rose modestly, limited by reliance on education alone and brief hospital stays with competing clinical priorities. Future efforts should target education on oral iron absorption limitations, investigate barriers to IV iron infusion, and optimize the outpatient transition for continued ID management.

Intravenous iron therapy for patients with heart failure: expanding body of evidence.

Anemia and iron deficiency are common in heart failure (HF) and chronic kidney disease (CKD). These conditions are associated with upregulation of hepcidin, which impairs the enteric absorption of iron, limiting the use of oral iron formulations in these populations. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are associated with enhanced erythropoiesis and have been shown to augment the erythropoietic response to intravenous iron. The effect of baseline SGLT2i therapy in the erythropoietic response following oral iron supplementation is currently not known. To compare the erythropoietic response to oral iron supplementation in patients with HF or CKD, using and not using SGLT2i as background therapy. This is a retrospective analysis of ambulatory patients with HF or CKD followed in cardio-kidney-metabolic clinics from a quaternary care hospital in Canada and a tertiary care hospital from Portugal. An age- and sex-matched population of patients using (n = 76) and not using (n = 76) a SGLT2i was compared for changes in hemoglobin and hematocrit following oral iron supplementation. Secondary outcomes included changes in iron biomarkers, natriuretic peptides and kidney function. Overall, the mean age was 75 ± 9years, 49% were men, 119 (78%) had CKD, 107 (70%) HF, and 113 (74%) had anemia. After adjustment for baseline differences, SGLT2i users experienced a greater increase in hemoglobin and hematocrit compared to SGLT2i non-users: hemoglobin + 0.80g/dL (95% confidence interval [CI] 0.39-1.21g/dL, p < 0.001); hematocrit + 3.0% (95% CI 1.0-4.0%, p < 0.001). No significant differences on iron biomarkers or any of the secondary outcomes were found between the groups. Oral iron supplementation in patients with background therapy including a SGLT2i (vs. SGLT2i non-users) was associated with a greater increase in hemoglobin and hematocrit. These results suggest that patients with HF or CKD patients treated with SGLT2i might have an enhanced erythropoietic response to oral iron supplementation.

Iron deficiency (ID) is common in patients with heart failure (HF) and is associated with poor outcomes, regardless of anaemia status. Iron supplementation has been demonstrated to improve exercise capacity and quality of life in patients with HF with an ejection fraction <50% and ID. This survey aimed to provide data on real-world practices related to ID screening and management. We designed and distributed an online survey (23 questions) regarding ID screening and management in the HF setting. Overall, 256 cardiologists completed the survey (59.8% male, mostly between 30 and 50 years). The majority of physicians defined ID according to the most recent HF recommendations (98.4%) and reported screening for ID in more than half of their patients (68.4%). However, only 54.3% of the respondents performed periodic screening (every 6 months to 1 year). A total of 93.0% of participants prescribed and/or administered iron supplementation, using intravenous iron as the preferred method of administration (86.3%). After iron supplementation, 96.1% of the respondents reassessed ID, most frequently at 3-6 months (67.6%). Most physicians (93.8%) perceived ID as an underestimated comorbidity in HF. Cardiologists' age, training status, subspecialty and work setting (academic vs. non-academic hospitals) were associated with heterogeneity in the answers. The results of this survey highlight the need for more consistent strategies of ID screening and treatment for patients with HF.

Comparison of Efficacy of Oral and Intravenous Iron Replacement Therapy in Children with Systolic Heart Failure and Iron Deficiency

Anemia is common in Congestive Heart Failure (CHF) and is associated with an increased mortality, morbidity and progressive renal failure. The most common causes of the anemia in CHF are (1) the associated Chronic Kidney Disease (CKD), which causes depression of erythropoietin (EPO) production in the kidney, and (2) excessive cytokine production in CHF, which can cause both depression of erythropoietin production in the kidney and depression of erythropoietin response in the bone marrow. The cytokines can also induce iron deficiency by increasing hepcidin production from the liver, which both reduces gastrointestinal iron absorption and reduces iron release from iron stores located in the macrophages and hepatocytes. It appears that iron deficiency is very common in CHF and is rarely recognized or treated. The iron deficiency can cause a thrombocytosis that might contribute to cardiovascular complications in both CHF and CKD and is reversible with iron treatment. Thus, attempts to control this anemia in CHF will have to take into consideration both the use of both Erythropoiesis Stimulating Agents (ESA) such as EPO and oral and, probably more importantly, intravenous (IV) iron. Many studies of anemia in CHF with ESA and oral or IV iron and even with IV iron without ESA have shown a positive effect on hospitalization, New York Heart Association functional class, cardiac and renal function, quality of life, exercise capacity and reduced Beta Natriuretic Peptide and have not demonstrated an increase in cardiovascular damage related to the therapy. However, adequately powered long-term placebo-controlled studies of ESA and of IV iron in CHF are still needed and are currently being carried out.

Background: Iron deficiency (ID) is common amongst patients with heart failure (HF). The European Society of Cardiology (ESC) guidelines recommends intravenous (IV) Iron supplementation in symptomatic HF patients with reduced left ventricular ejection fraction (LVEF) and ID to alleviate HF symptoms and improve quality of life. The current study aims to assess adherence to the latest ESC guidelines in treatment of ID in HF patients admitted to non-cardiac (outlier) wards at St. George's University Hospital (SGH), London. The results were compared to standard practice at a dedicated heart failure unit (HFU) at SGH. Methods: Retrospective data was collected on consecutive HF patients, admitted to SGH between September 2022 and September 2023. 386 patients met the inclusion criteria, defined as HF with LVEF &lt; 50% and ID according to ESC guidelines. Of total population, 190/386 patients were admitted to the outlier wards and 196/386 to the HFU. Patients considered ineligible for administration of IV Iron therapy, were those not meeting the guideline thresholds for treatment of ID, patients with active cancer or bleeding and patients on oral Iron supplementation. Results: The mean age of patients admitted to HFU was 71 +/- 13 SD, 66% male. 72% (141/196) of the patients were tested for ID, of which 51% (72/141) had ID as per inclusion criteria. 57% (41/72) of those with ID were prescribed IV Iron, whilst 43% (31/72) were not treated. The reason for not treating patients identified as Iron deficient was presence of active infection (19/31) or bleeding (3/31). In 9/31 of untreated patients with ID, the reason for not being prescribed with IV Iron was not identifiable through review of medical notes. It is important to note that 28% (55/196) were not tested for ID during their hospitalisation and missed the opportunity for treatment. (Figure 1) In outlier wards, mean age was 77 +/- 14 SD, 66% male. 46% (87/190) patients were tested for ID, of which 16% (14/87) were identified as Iron deficient and were prescribed IV Iron. 4% (12/87) were not treated for no obvious reason and 18% (16/87) met the criteria for ID, but due to presence of contraindication did not receive IV Iron. Missed opportunity was 54% in outlier population. (Figure 2) Conclusion: This study demonstrated that patients admitted to HFU, were more likely to be tested for ID and receive IV Iron, compared to patients admitted to outlier wards but there is still room for considerable improvement in both settings.

Background and Aims In the AFFIRM-AHF trial, treatment with intravenous (IV) ferric carboxymaltose (FCM) reduced the risk of heart failure (HF) hospitalisations vs placebo in patients with iron deficiency after an episode of acute HF. Of these patients, 41% had a medical history of chronic kidney disease (CKD). This prespecified subanalysis of AFFIRM-AHF data was performed to investigate the effect of renal function on FCM efficacy. Methods In AFFIRM-AHF, patients stabilised following hospitalisation for acute HF with concomitant iron deficiency (defined as ferritin &amp;lt;100 μg/L, or 100–299 μg/L with transferrin saturation &amp;lt;20%) were randomised to receive either IV FCM or placebo before discharge for the index hospitalisation. In this analysis, patients who had received at least one dose of the study drug, and who had at least one post-randomisation data point and a baseline value for estimated glomerular filtration rate (eGFR; calculated using the CKD-EPI formula and baseline creatinine value), were stratified into tertiles according to baseline eGFR. The primary outcome was a composite of total HF hospitalisations and CV death. Secondary outcomes included total HF hospitalisations, CV death, time to first HF hospitalisation or CV death, composite of total CV hospitalisations and CV death, and days lost due to HF hospitalisations or CV death. All outcomes were evaluated up to 52 weeks post-randomisation. Results Of the 1,108 patients included in primary AFFIRM-AHF analyses, 967 (FCM: 487; placebo: 480) had a baseline eGFR value and were included in this analysis. In both groups, 60% of patients had an eGFR &amp;lt;60 mL/min/1.73 m2 following the index acute HF episode. Patients were divided into eGFR tertiles 1, 2 and 3, with corresponding respective baseline eGFR values of &amp;lt;42.96, 42.96 to &amp;lt;64.32, and ≥64.32 mL/min/1.73 m2. At baseline, the mean age, proportion of females, and proportions of patients with ischaemic HF aetiology, a documented history of HF, and a medical history of percutaneous coronary intervention, coronary artery bypass graft and/or cardiac resynchronisation therapy, were highest in eGFR tertile 1 and lowest in eGFR tertile 3. In eGFR tertiles 1, 2 and 3, the number of total HF hospitalisations and CV deaths in the FCM group vs placebo group were, respectively, 115 vs 152, 76 vs 83, and 56 vs 79, with respective annualised rate ratios (95% confidence interval [CI]) of 0.76 (0.50, 1.16), 0.76 (0.48, 1.22) and 0.69 (0.42, 1.12) (Figure). In eGFR tertile 3, the total number of CV hospitalisations and CV deaths was significantly lower in the FCM group vs the placebo group (69 vs 107; rate ratio [95% CI] 0.60 [0.39, 0.93]), with a nominally lower number of total HF hospitalisations with FCM vs placebo (44 vs 66; rate ratio [95% CI] 0.62 [0.38, 1.01]). In the time to first event analysis, FCM significantly reduced HF hospitalisation or CV death vs placebo in eGFR tertile 3 (hazard ratio [95% CI] 0.64 [0.42, 0.98]). In eGFR tertiles 1 and 2, differences between FCM and placebo arms for secondary endpoints did not reach statistical significance. The p-trend for treatment by baseline eGFR subgroup was non-significant for the primary outcome (0.941) and also for the secondary outcomes specified here. Conclusion In patients with iron deficiency who were stabilised after an episode of acute HF, numerically fewer primary and secondary events, endpoints or outcomes were consistently observed with FCM vs placebo across the eGFR tertiles. In addition, no significant interaction between kidney function and FCM efficacy was noted. Given that this analysis was limited by small patient numbers following subgroup stratification, further studies in larger cohorts with CKD may help to clarify the effect of IV FCM in this patient population.

Iron deficiency is common and associated with adverse outcomes in heart failure, regardless of anemia. Iron deficiency, absolute and functional, with and without anemia, is associated with adverse outcomes in chronic kidney disease (CKD). Heart failure and CKD frequently occur together. Intravenous iron therapy has been shown to reduce heart failure symptoms and improve physical function in heart failure with reduced ejection fraction with iron deficiency. In CKD, intravenous or oral iron therapy are often used for management of anemia, along with erythropoiesis stimulating agents, yet the risks and benefits of intravenous iron use is controversial. In this review, we survey available evidence and ongoing studies of iron deficiency and iron supplementation in heart failure, and integrate with recent evidence on effectiveness and safety of intravenous iron therapy in CKD. Intravenous iron therapy improves heart failure symptoms and physical function in heart failure with reduced ejection fraction and iron deficiency, regardless of anemia, and may reduce heart failure hospitalizations and cardiovascular mortality. Sustained intravenous iron therapy regardless of hemoglobin level in selected patients with end-stage kidney disease receiving hemodialysis improves outcomes, and does not appear to cause infectious complications. Iron therapy has important effects in heart failure and CKD, and appears safe in the short term. Ongoing trials will provide additional important information.

Iron Repletion Aided Heart Failure in Elders

Dear editor, Heart failure is a debilitating life sentence plagued with multifactorial variables that greatly influence the morbidity and mortality of the patient. Iron deficiency, one of these variables, is a leading contributor to anaemia among individuals with stable chronic heart failure, affecting approximately 30% to 50% of this population irrespective of left ventricular ejection fraction or demographic variables such as gender and race.(1,2) Intriguingly, even among those without overt anaemia, more than 40% display laboratory evidence of depleted iron stores. Moreover, in acute decompensated heart failure (HF), iron deficiency (ID) can be identified in as many as 80% of assessed patients, emphasizing the significance of research initiatives aimed at understanding the underlying cause of ID in HF patients and enhancing their clinical management.(3) A survey conducted in the region of South Asia revealed that 46% of Pakistani heart failure patients and 58.8% of those in India were affected by iron deficiency(4). Implementing simple practices to treat the underlying anaemia can massively improve the quality of life and reduce rehospitalization rates.(1–3,5) Notably, in Pakistan, the rehospitalization rate sits at a staggering 81%. Ferric carboxy-maltose is an intravenous iron formulation which has been extensively explored in clinical studies such as the IRON-CRT, IRONMAN and AFFIRM-AHF trials. The trials displayed promising outcomes with marked improvement in general well-being and physical capacities including 6-minute exercise tolerance as well as lowering the need for hospitalisation independent of baseline haemoglobin levels.(1,2,5) Ferric carboxy-maltose has demonstrated superiority over oral iron supplements and other treatments, such as erythropoietin stimulating medications, making it a recommended and successful alternative for iron deficiency therapy according to both European and American guidelines.(1–3,5) The latest heart failure guidelines emphasize the importance of screening for iron deficiency in every patient diagnosed with heart failure.(2) Unfortunately, the implementation of this practice is not consistently applied in developing countries, as observed in our own experiences in Pakistan. In conclusion, establishing Ferric Carboxy-maltose as the standard treatment for iron deficiency is recommended due to its cost-effective nature and the near instant improvement in patients health and morale. This approach would contribute to a more productive and fulfilling life for patients, even enabling them to regain some level of autonomy in their daily activities. ---Continue