24 Anaemia in heart failure unit St. Michaels hospital dun laoghaire

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

In Reply to ‘Intravenous Iron, Inflammation, and Ventricular Dysfunction During Hemodialysis’

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

Aim: To evaluate the economic efficiency of using ferric carboxymaltose (FCM) in patients with chronic heart failure with reduced left ventricular ejection fraction (CHFrEF) and iron deficiency (ID) in the Russian Federation Methods: The analysis of the cost of maintaining CHFrEF with ID was carried out and an analytical decision-making model was built in MS Excel, which allows estimating the costs from the position of the state in the management of patients with CHFrEF with ID when using FCM in comparison with placebo. Results: The use of FCM in 633,301 patients with CHFrEF and ID for 1 year will prevent 72,386 hospitalizations for CHF and reduce the number of days spent by patients in the hospital by 1,136,141 days. Taking into account the direct costs of stopping adverse events, as well as the indirect costs of paying disability benefits and GDP losses, the potential economic benefit of using FCV when prescribing 633,301 CHFrEF and DJ to patients for 1 year can be 4.280 million rubles. per year of therapy. The use of FCM in patients with CHFrEF and ID is advisable immediately after an episode of CHF decompensation in order to reduce the risk of subsequent hospitalizations for worsening CHF and increase the cost per patient by only 4 642 rubles. per year (18 %), while significantly improving the prognosis of patients and their quality of life. Conclusion: FCM can be recommended for inclusion in the standards of medical care, clinical guidelines, formularies of healthcare facilities, application templates within the framework of the regional (RLO) and federal drug benefits, as well as federal and regional programs aimed at improving the control of the clinical course CHFrEF with ID.

Iron deficiency (ID) is common among patients with heart failure (HF), and it is associated with poor functional outcomes, increased hospitalizations, and higher mortality. This meta-analysis evaluates the efficacy of intravenous ferric carboxymaltose (FCM) in HF patients with ID. We conducted a literature search of major bibliographic databases up to 15 April 2025, to identify randomized controlled trials (RCTs) comparing FCM with placebo or standard care in HF patients with ID. The primary outcome was a composite of recurrent hospitalizations for heart failure (HHF) or cardiovascular (CV) death assessed at 1-year and complete follow-up. Risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) were estimated using a random-effects model. Eleven RCTs enrolling 6493 patients (3329 FCM; 3164 control) were included. The mean age of patients was 66.7 ± 10.6 years, 34.4% were women, mean left ventricular ejection fraction was 33.7 ± 8.8%, mean haemoglobin was 12.4 ± 1.8 g/dL, and mean transferrin saturation was 18.9 ± 10.1%. FCM significantly reduced the composite of recurrent HHF or CV death at 1-year (RR 0.73, 95% CI 0.62-0.85) and over maximum follow-up (RR 0.80, 95% CI 0.68-0.94) compared to control. Recurrent HHF was significantly reduced with FCM administration (1-year RR 0.69, 95% CI 0.57-0.84; complete follow-up RR 0.75, 95% CI 0.60-0.94). FCM demonstrated a trend towards reduced all-cause (RR: 0.86, 95% CI: 0.74-1.00) and CV mortality at 1-year (RR: 0.86, 95% CI: 0.72-1.02), but this effect was attenuated over longer follow-up. FCM significantly improved 6-minute walk test performance (MD 29.19 m, 95% CI 11.95-46.43). The trial sequential analysis confirmed robust evidence for the primary outcome. Intravenous FCM in HF patients is associated with reduced risk of adverse cardiovascular events and improved functional capacity. Further trials are needed to clarify its long-term survival impact.

Background: Iron deficiency (ID) is common among patients with heart failure (HF), and it is associated with poor functional outcomes, increased hospitalizations, and higher mortality. This meta-analysis evaluates the efficacy of intravenous ferric carboxymaltose (FCM) in HF patients with ID. Methods: We conducted a literature search of major bibliographic databases up to April 15, 2025, to identify randomized controlled trials (RCTs) comparing FCM with placebo or standard care in HF patients with ID. The primary outcome was a composite of recurrent hospitalizations for heart failure (HHF) or cardiovascular (CV) death assessed at 1-year and complete follow-up. Risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) were estimated using a random-effects model. Results: Eleven RCTs (6,493 patients) were included in the review. FCM significantly reduced the composite of recurrent HHF or CV death at 1-year (RR 0.73, 95% CI 0.62–0.85) and over maximum follow-up (RR 0.80, 95% CI 0.68–0.94) compared to control. Recurrent HHF was significantly reduced with FCM administration (1-year RR 0.69, 95% CI 0.57–0.84; complete follow-up RR 0.75, 95% CI 0.60–0.94). FCM demonstrated a trend toward reduced all-cause (RR: 0.86, 95% CI: 0.74–1.00) and CV mortality at 1-year (RR: 0.86, 95% CI: 0.72–1.02), but this effect was attenuated over longer follow-up. FCM significantly improved 6-minute walk test performance (MD 29.19 m, 95% CI 11.95–46.43). The trial sequential analysis confirmed robust evidence for the primary outcome. Conclusion: Intravenous FCM in HF patients is associated with reduced risk of adverse cardiovascular events and improved functional capacity. Further trials are needed to clarify its long-term survival impact.

In addition to other complications, heart failure (HF) is strongly associated with iron deficiency. Iron deficiency has been linked to decreased health-related quality of life (HRQoL) and has been suggested as an independent prognostic factor for mortality.1 Furthermore, the use of intravenous iron in patients with HF is associated with reductions in hospitalizations, increases in quality of life, and improvement in functional assessments.2,3 To date, supplementation with oral iron has not shown a similar benefit.4 Iron deficiency remains common after continuous-flow left ventricular assist devices (LVAD) implantation, affecting over half of patients on long-term support.5 Patients with an LVAD and concomitant anemia are more likely to be hospitalized and demonstrate higher mortality rates.6,7 It is currently unknown whether patients with an LVAD experience the same benefits associated with correction of iron deficiency as the general HF population. In accordance with the ACC/AHA/HFSA 2017 focused update to the 2013 Guideline for the Management of Heart Failure, our institution uses intravenous (IV) iron in HF patients with iron deficiency.8 It has been our practice to prescribe oral iron for patients after LVAD, but more recently, institutional IV iron prescribing guidelines for patients with HF were extended to our LVAD population. Given the novelty of this strategy, we conducted an institutional review board (IRB)-approved, prospective, observational analysis shortly after to compare the efficacy of IV versus oral iron supplementation in correcting iron deficiency in HF patients with durable LVADs. Methods As is established in the general HF population, iron deficiency was defined as ferritin <100 ng/ml or transferrin saturation (Tsat) <20% with ferritin 100–300 ng/ml. Iron-deficient patients were treated off-label with IV iron during an inpatient admission or in the outpatient clinic provided that they had no blood transfusions within the previous 90 days, signs of pump thrombosis (lactate dehydrogenase (LDH) >3 times the upper limit of normal), active bleeding, or infection. Providers engaged in shared decision making with eligible patients regarding treatment with IV or oral iron, with factors such as cost and distance to clinic taken into consideration. Patients who did not receive IV iron were prescribed oral iron. In the inpatient setting, IV ferric gluconate dosed according to the Ganzoni equation was given in increments of 250 mg every 12 hours until total dose was administered.9 In the outpatient clinic, patients were repleted with ferumoxytol 1020 mg IV once administered over 30 minutes.10 Dosing of oral ferrous sulfate was in increments of 325 mg with frequency determined by the prescriber, though prescribing guidance recommended 325 mg daily to maximize absorption. Providers were encouraged to recheck iron parameters during clinic follow-up between 4 and 12 weeks after iron administration. The primary outcome was the rate of resolution of iron deficiency, defined as no longer meeting criteria for iron deficiency (ferritin ≥100 ng/ml and Tsat ≥20% or ferritin >300 ng/ml). Secondary outcomes included change in ferritin, Tsat%, hemoglobin, and New York Heart Association (NYHA) symptom class (Baseline characteristics Table 1). Changes in HRQoL, as assessed by Kansas City Cardiomyopathy Questionnaire Short Form (KCCQ-12) when available, were compared in stable patients receiving IV iron as an outpatient.Table 1.: Baseline CharacteristicsResults Of 108 patients eligible for inclusion, the iron status of 82 patients was evaluated between June 2017 and February 2018. Of those, 67 (62%) were iron deficient, and 31 patients were treated with iron products and had complete follow-up with iron-specific laboratory data. Ten patients received IV iron, and 21 received oral iron. The median IV iron dose was 1037 mg, and the median time to follow-up iron studies was 42 days (interquartile range [IQR]: 33–64 days) after IV iron administration. Of the patients receiving oral iron, 43% were prescribed ferrous sulfate 325 mg once daily and 48% twice daily. Median time to follow-up iron studies while receiving oral iron therapy was 237 days (IQR: 81–436 days). Resolution of iron deficiency occurred in 40% of patients receiving IV iron vs. 0% receiving oral iron (Fisher exact test, p = 0.008). Additionally, the median increase in ferritin in the IV group was 165.2 vs. 8.65 ng/ml in the oral group (Wilcoxon rank-sum test, p = 0.0006). Changes in Tsat% (+5.5 vs. +6.0; p = 1.0) and hemoglobin (+2.2 vs. +1.8 g/dl; p = 0.386) were not different. Decreases in serum creatinine were greater (−0.1 vs. −0.02 mg/dl; p = 0.024) in the IV iron group. Changes in total bilirubin (−0.15 vs. −0.2 mg/dl; p = 0.97) were not different. There was no significant difference in NYHA symptom class. Five patients who received IV iron had paired KCCQ-12 data with a median increase of 9.38 (p = 0.075) after treatment. One patient had a vasovagal episode during infusion of ferric gluconate that prevented administration of the complete dose (patient 6 in Table 2).Table 2.: Patients with LVAD Receiving IV Iron ReplacementDiscussion This is the first study to describe the results of IV iron supplementation in patients with a durable LVAD, demonstrating it to be significantly more effective than oral supplementation in correcting iron deficiency in this population. Importantly, our results also indicate that oral iron supplementation in durable LVAD patients is ineffective, a finding that aligns with that seen in the general HF population. Although the decrease in serum creatinine after IV iron was statistically significant, this finding requires additional study before interpretation. Additionally, although sample size may have precluded statistical significance in KCCQ-12 change, the qualitative improvement in HRQoL merits additional investigation. Limitations of this study include its small, single-center cohort, as well as possible variability in iron parameters based on clinical setting. Additionally, patients received only one-time repletion of IV iron, potentially underestimating the full effect of IV iron if multiple doses were given. Regardless, our study adopted current best practices for the diagnosis and treatment of iron deficiency associated with HF, and we propose that IV iron replacement is a safe and reasonably effective method for correction of iron deficiency in LVAD patients. Given the significant burden of ongoing iron deficiency anemia after LVAD and its association with poor outcomes, as well as the previously published efficacy of IV iron in the general HF population, additional research is clearly warranted.

AimsThis analysis aims to evaluate the budget impact of intravenous iron therapy with ferric carboxymaltose for patients with systolic chronic heart failure and iron deficiency, from the perspective of the French public health insurance.Methods and resultsA budget impact model was adapted to forecast the budget impact over 5 years, according to two scenarios: one where patients receive ferric carboxymaltose according to market share forecast and another where patients are not treated for iron deficiency. Clinical data were extrapolated from pooled data from four randomized controlled trials. The time horizon was extended to 5 years by applying transition probabilities estimated from the CONFIRM‐HF trial. Epidemiological parameters for France were derived from the literature. Cost parameters were derived from national available databases.In the base case analysis, the modelled 5 year cost difference between the scenarios with ferric carboxymaltose vs. no iron deficiency treatment in a population of 189 334 prevalent and incident patients led to €0.8m savings. The cumulative savings resulted from a reduction in the hospitalization costs associated with worsening heart failure (€−35.8m) as well as a reduction in the follow‐up costs (€−2.9m). These cost savings outweighed the costs of ferric carboxymaltose treatment (€37.7m). Sensitivity analyses showed that the budget impact varied from €−34m to €+146m. Parameters with the most impact on the budget were the hospitalization rate for patients not treated for iron deficiency, the number of ambulatory sessions needed, the absence of hospitalization cost differentiation between New York Heart Association classes, and administration settings costs.ConclusionsIron deficiency treatment with ferric carboxymaltose in systolic chronic heart failure patients results in an improvement of New York Heart Association class and thereby increases the well‐being of the patients, while providing an overall cost saving for the French national health insurance.

Does myocardial iron load determine the severity of heart insufficiency?

Relation of Longitudinal Changes in Quality of Life Assessments to Changes in Functional Capacity in Patients With Heart Failure With and Without Anemia

A Cost-effectiveness Analysis of Ferric Carboxymaltose in Patients With Iron Deficiency and Chronic Heart Failure in Spain

Iron deficiency may impair aerobic performance. This study aimed to determine whether treatment with intravenous iron (ferric carboxymaltose) would improve symptoms in patients who had heart failure, reduced left ventricular ejection fraction, and iron deficiency, either with or without anemia. We enrolled 459 patients with chronic heart failure of New York Heart Association (NYHA) functional class II or III, a left ventricular ejection fraction of 40% or less (for patients with NYHA class II) or 45% or less (for NYHA class III), iron deficiency (ferritin level <100 microg per liter or between 100 and 299 microg per liter, if the transferrin saturation was <20%), and a hemoglobin level of 95 to 135 g per liter. Patients were randomly assigned, in a 2:1 ratio, to receive 200 mg of intravenous iron (ferric carboxymaltose) or saline (placebo). The primary end points were the self-reported Patient Global Assessment and NYHA functional class, both at week 24. Secondary end points included the distance walked in 6 minutes and the health-related quality of life. Among the patients receiving ferric carboxymaltose, 50% reported being much or moderately improved, as compared with 28% of patients receiving placebo, according to the Patient Global Assessment (odds ratio for improvement, 2.51; 95% confidence interval [CI], 1.75 to 3.61). Among the patients assigned to ferric carboxymaltose, 47% had an NYHA functional class I or II at week 24, as compared with 30% of patients assigned to placebo (odds ratio for improvement by one class, 2.40; 95% CI, 1.55 to 3.71). Results were similar in patients with anemia and those without anemia. Significant improvements were seen with ferric carboxymaltose in the distance on the 6-minute walk test and quality-of-life assessments. The rates of death, adverse events, and serious adverse events were similar in the two study groups. Treatment with intravenous ferric carboxymaltose in patients with chronic heart failure and iron deficiency, with or without anemia, improves symptoms, functional capacity, and quality of life; the side-effect profile is acceptable. (ClinicalTrials.gov number, NCT00520780).

Heart failure: focus on co-morbidities, inflammation, and heart rate.

Reply to the letter regarding the article ‘Natural history and prognostic significance of iron deficiency and anaemia in ambulatory patients with chronic heart failure’

Many patients with heart failure (HF) are iron-deficient. Intravenous (IV) iron therapy improves symptoms and reduces hospitalizations for HF. Several mechanisms have been proposed, including myocardial iron repletion. However, it is unknown if serum iron markers predict the extent of this repletion. To address this question, data from two clinical studies that evaluated changes in myocardial iron using cardiac magnetic resonance (CMR) were harnessed. The Myocardial-IRON trial measured change in myocardial iron, denoted by a decrease in CMR T1 and T2*, at 7 and 30 days after IV ferric carboxymaltose (FCM) in patients with iron deficiency (ID) and HF (n = 53). The STUDY trial measured myocardial and spleen iron at multiple timepoints after FCM in patients with ID without HF (n = 12). In this post-hoc analysis, we examined the association between baseline serum iron markers (transferrin saturation and ferritin) and change in myocardial iron in the weeks after FCM therapy. Changes in spleen iron were also examined, due its role as an intermediary in the redistribution of iron from iron-carbohydrate complexes such as FCM. In patients with or without HF, higher serum ferritin at baseline predicted lower rise in myocardial iron in the weeks after therapy with FCM. In contrast, higher serum ferritin at baseline predicted a greater rise in spleen iron. These data point towards the hypothesis that functional ID, which is characterized by elevated ferritin, could limit myocardial iron repletion after IV iron therapy, by favouring iron trapping in the spleen.