Targeting Iron Deficiency in Heart Failure: Existing Evidence and Future Expectations.
Ontology highlight
ABSTRACT:
SUBMITTER: Ponikowski P
PROVIDER: S-EPMC8136459 | biostudies-literature | 2021 May
REPOSITORIES: biostudies-literature
Publications
Targeting Iron Deficiency in Heart Failure: Existing Evidence and Future Expectations.
Ponikowski Piotr P Jankowska Ewa A EA
Circulation. Heart failure 20210518 5
Similar Datasets
Project description:Iron deficiency is a major heart failure co-morbidity present in about 50% of patients with stable heart failure irrespective of the left ventricular function. Along with compromise of daily activities, it also increases patient morbidity and mortality, which is independent of anaemia. Several trials have established parenteral iron supplementation as an important complimentary therapy to improve patient well-being and physical performance. Intravenous iron preparations, in the first-line ferric carboxymaltose, demonstrated in previous clinical trials superior clinical effect in comparison with oral iron preparations, improving New York Heart Association functional class, 6 min walk test distance, peak oxygen consumption, and quality of life in patients with chronic heart failure. Beneficial effect of iron deficiency treatment on morbidity and mortality of heart failure patients is waiting for conformation in ongoing trials. Although the current guidelines for treatment of chronic and acute heart failure acknowledge importance of iron deficiency correction and recommend intravenous iron supplementation for its treatment, iron deficiency remains frequently undertreated and insufficiently diagnosed in setting of the chronic heart failure. This paper highlights the current state of the art in the pathophysiology of iron deficiency, associations with heart failure trajectory and outcome, and an overview of current guideline-suggested treatment options.
| S-EPMC8318436 | biostudies-literature
Project description:BackgroundThe recent AFFIRM-AHF trial assessing the effect of intravenous (IV) iron on outcomes in patients hospitalised with worsening heart failure who had iron deficiency (ID) narrowly missed its primary efficacy endpoint of recurrent hospitalisations for heart failure (HHF) or cardiovascular (CV) death. We conducted a meta-analysis to determine whether these results were consistent with previous trials.MethodsWe searched for randomised trials of patients with heart failure investigating the effect of IV iron vs placebo/control groups that reported HHF and CV mortality from 1st January 2000 to 5th December 2020. Seven trials were identified and included in this analysis. A fixed effect model was applied to assess the effects of IV iron on the composite of first HHF or CV mortality and individual components of these.ResultsAltogether, 2,166 patients were included (n = 1168 assigned to IV iron; n = 998 assigned to control). IV iron reduced the composite of HHF or CV mortality substantially [OR 0.73; (95% confidence interval 0.59-0.90); p = 0.003]. Outcomes were consistent for the pooled trials prior to AFFIRM-AHF. Whereas first HHF were reduced substantially [OR 0.67; (0.54-0.85); p = 0.0007], the effect on CV mortality was uncertain but appeared smaller [OR 0.89; (0.66-1.21); p = 0.47].ConclusionAdministration of IV iron to patients with heart failure and ID reduces the risk of the composite outcome of first heart failure hospitalisation or cardiovascular mortality, but this outcome may be driven predominantly by an effect on HHF. At least three more substantial trials of intravenous iron are underway.
| S-EPMC8318946 | biostudies-literature
Project description:Purpose of reviewHeart failure (HF) is commonly associated with iron deficiency (ID), defined as insufficient levels of iron to meet physiological demands. ID's association with anaemia is well understood but it is increasingly recognised as an important comorbidity in HF, even in the absence of anaemia. This review summarises contemporary evidence for the measurement and treatment of ID, in both HFrEF and HFpEF, and specific HF aetiologies, and highlights important gaps in the evidence-base.Recent findingsID is common among patients with HF and associated with increased morbidity and mortality. Correcting ID in patients with HF can impact upon functional status, exercise tolerance, symptoms, and overall quality of life, irrespective of anaemia status. ID is a modifiable comorbidity in HF. Therefore, recognising and treating ID has emerging therapeutic potential and is important for all clinicians who care for patients with HF to understand the rationale and approach to treatment.
| S-EPMC10307722 | biostudies-literature
Project description:The aim of this study was to characterize iron deficiency (ID) in acutely decompensated heart failure (ADHF) and identify whether ID is associated with dyspnea class, length of stay (LOS), biomarker levels, and echocardiographic indices of diastolic function in patients with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF). Consecutive patients admitted with ADHF at a single tertiary center were included. Demographic information, pathology investigations, and metrics regarding hospital stay and readmission were recorded. Patients were classified as having 'absolute' ID if they had a ferritin level <100 ng/mL; or 'functional' ID if they had a ferritin 100-200 ng/mL and a transferrin saturation <20%. Of 503 patients that were recruited, 270 (55%) had HFpEF, 160 (33%) had HFREF, and 57 (12%) had heart failure with mid-range ejection fraction. ID was present in 54% of patients with HFrEF and 56% of patients with HFpEF. In the HFpEF group, ID was associated with a LOS of 11 ± 7.7 vs. 9 ± 6 days in iron replete patients, p = 0.036, and remained an independent predictor of increased LOS in a multivariate linear regression incorporating comorbidities, age, and ID status. This study corroborates a high prevalence of ID in both HFrEF and HFpEF, and further shows that in patients with HFpEF there is a prolongation of LOS not seen in HFrEF which may indicate a more prominent role for ID in HFpEF.
| S-EPMC6832529 | biostudies-literature
Project description:BackgroundAlthough iron deficiency (ID) is an important and treatable risk factor for heart failure (HF), data on ID are scarce in Asian patients with HF. Therefore, we sought to determine the prevalence and clinical characteristics of ID in hospitalized Korean patients with HF.MethodsIn this prospective, multicenter cohort study, 461 patients with acute HF seen at five tertiary centers from January to November 2019 in Korea were enrolled. ID was defined as serum ferritin < 100 μg/L or ferritin 100-299 μg/L in combination with transferrin saturation < 20%.ResultsThe patients' mean age was 67.6 ± 14.9 years, and 61.8% were male. Among total 461 patients, ID was present in 248 patients (53.8%). The prevalence of ID was significantly higher in women than in men (65.3% vs. 47.3%, P < 0.001). In a multivariable logistic regression analysis, the independent predictors of ID were female sex (odds ratio [OR], 2.19; 95% confidence interval [CI], 1.47-3.30), valvular heart disease (OR, 2.10; 95% CI, 1.10-4.17), higher heart rate (OR, 1.10; 95% CI, 1.01-1.21), anemia (OR, 1.60; 95% CI, 1.07-2.40), and the use of clopidogrel (OR, 1.56; 95% CI, 1.00-2.45). Among women, the prevalence of ID did not significantly differ between younger and older women (< 65 years: 73.7% vs. ≥ 65 years: 63.0%, P = 0.222), those with low and high body mass index (BMI < 25 kg/m²: 66.2% vs. BMI ≥ 25 kg/m²: 69.6%, P = 0.703), or those with low and high natriuretic peptide (NP) levels (NP < median: 69.8% vs. NP ≥ median: 61.1%, P = 0.295). Only 0.2% patients with acute HF received intravenous iron supplementation in Korea.ConclusionThe prevalence of ID is high in hospitalized Korean patients with HF. Because ID cannot be diagnosed by clinical parameters, routine laboratory examinations are necessary to identify patients with ID.Trial registrationClinicalTrials.gov Identifier: NCT04812873.
| S-EPMC10261703 | biostudies-literature
Project description:Iron is an essential micronutrient for a myriad of physiological processes in the body beyond erythropoiesis. Iron deficiency (ID) is a common comorbidity in patients with heart failure (HF), with a prevalence reaching up to 59% even in non-anaemic patients. ID impairs exercise capacity, reduces the quality of life, increases hospitalisation rate and mortality risk regardless of anaemia. Intravenously correcting ID has emerged as a promising treatment in HF as it has been shown to alleviate symptoms, improve quality of life and exercise capacity and reduce hospitalisations. However, the pathophysiology of ID in HF remains poorly characterised. Recognition of ID in HF triggered more research with the aim to explain how correcting ID improves HF status as well as the underlying causes of ID in the first place. In the past few years, significant progress has been made in understanding iron homeostasis by characterising the role of the iron-regulating hormone hepcidin, the effects of ID on skeletal and cardiac myocytes, kidneys and the immune system. In this review, we summarise the current knowledge and recent advances in the pathophysiology of ID in heart failure, the deleterious systemic and cellular consequences of ID.
| S-EPMC8745653 | biostudies-literature
Project description:Iron is an element necessary for cells due to its capacity of transporting oxygen and electrons. One of the important co-morbidities in heart failure is iron deficiency. Iron has relevant biological functions, for example, the formation of haemoglobin, myoglobin and numerous enzymatic groups. The prevalence of iron deficiency increases with the severity of heart failure. For a long time, the influence of iron deficiency was underestimated especially in terms of worsening of cardiovascular diseases and of developing anaemia. In recent years, studies with intravenous iron agents in patients with iron deficiency and cardiovascular diseases indicated new insights in the improvement of therapy. Experimental studies support the understanding of iron metabolism. Many physicians remain doubtful of the use of intravenous iron due to reports of side effects. The aim of this review is to describe iron metabolism in humans, to highlight the influence of iron deficiency on the course and symptoms of heart failure, discuss diagnostic tools of iron deficiency and provide guidance on the use of intravenous iron.
| S-EPMC3798931 | biostudies-other
Project description:AimsIron deficiency (ID) is prevalent in chronic heart failure (HF) but lacks a consensus definition. This study evaluates the prevalence and the prognostic impact of ID using different criteria on all-cause and cardiovascular mortality, as well as first hospitalization for HF in patients with new-onset chronic HF.MethodsIn this nationwide registry-based cohort, we explored four definitions of ID: the current European Society of Cardiology (ESC) guidelines [ferritin <100 ng/mL or ferritin 100-299 ng/mL and transferrin saturation (TSAT) <20%], ferritin level <100 ng/mL, TSAT < 20% and serum iron ≤13 μmol/L. Patients were identified through the Danish Heart Failure Registry.ResultsOf 9477 new-onset chronic HF patients registered in the Danish Heart Failure Registry from April 2003 to December 2019, we observed ID prevalence rates ranging from 35.8% to 64.3% depending on the ID definition used. Among patients with ID defined by iron ≤13 μmol/L or TSAT < 20%, 26% and 15.5%, respectively, did not meet the ESC guidelines definition for ID. Conversely, 11% of patients meeting the ESC criteria exhibited serum iron >13 μmol/L and TSAT > 20%. Regardless of anaemia status, ID defined by TSAT < 20% or serum iron ≤13 μmol/L was associated with all-cause mortality [non-anaemic, hazard ratio (HR): 1.57, 95% confidence interval (CI): 1.30-1.89 and HR: 1.47, 95% CI: 1.24-1.73; anaemic, HR: 1.22, 95% CI: 1.07-1.38 and HR: 1.25, 95% CI: 1.09-1.44, respectively] and cardiovascular mortality (non-anaemic, HR: 2.21, 95% CI: 1.59-3.06 and HR: 1.47, 95% CI: 1.12-1.95; anaemic, HR: 1.37, 95% CI: 1.11-1.69 and HR: 1.28, 95% CI: 1.02-1.61, respectively), as well as increased risk of first hospitalization for HF (non-anaemic, HR: 1.28, 95% CI: 1.09-1.1.50 and HR: 1.27, 95% CI: 1.10-1.46; anaemic, HR: 1.25, 95% CI: 1.08-1.44 and HR: 1.22, 95% CI: 1.05-1.42, respectively). ID defined by ESC guidelines was associated with all-cause and cardiovascular mortality only in non-anaemic patients (HR: 1.41, 95% CI: 1.18-1.1.70 and HR: 1.58, 95% CI: 1.18-2.12.). Furthermore, the ESC guideline definition was associated with increased risk of first hospitalization for HF, regardless of anaemia status (non-anaemic, HR: 1.26, 95% CI: 1.08-1.1.47; anaemic, HR: 1.34, 95% CI: 1.17-1.53).ConclusionsID, when defined by TSAT < 20% or serum iron ≤13 μmol/L, is associated with increased risk of all-cause and cardiovascular mortality, as well as first hospitalization for HF in patients with new-onset chronic HF, regardless of anaemia status. Conversely, ID defined as ESC guidelines is associated with all-cause and cardiovascular mortality only in non-anaemic patients.
| S-EPMC11911571 | biostudies-literature
Project description:AimsFor patients with heart failure (HF) and iron deficiency (ID), randomized trials suggest that intravenous (IV) iron reduces hospitalizations for heart failure (HHF), but uncertainty exists about the effects in subgroups and the impact on mortality. We conducted a meta-analysis of randomized trials investigating the effect of IV iron on clinical outcomes in patients with HF.Methods and resultsWe identified randomized trials published between 1 January 2000 and 5 November 2022 investigating the effect of IV iron versus standard care/placebo in patients with HF and ID in any clinical setting, regardless of HF phenotype. Trials of oral iron or not in English were not included. The main outcomes of interest were a composite of HHF and cardiovascular death (CVD), on HHF alone and on cardiovascular and all-cause mortality. Ten trials were identified with 3373 participants, of whom 1759 were assigned to IV iron. IV iron reduced the composite of recurrent HHF and CVD (rate ratio 0.75, 95% confidence interval [CI] 0.61-0.93; p < 0.01) and first HHF or CVD (odds ratio [OR] 0.72, 95% CI 0.53-0.99; p = 0.04). Effects on cardiovascular (OR 0.86, 95% CI 0.70-1.05; p = 0.14) and all-cause mortality (OR 0.93, 95% CI 0.78-1.12; p = 0.47) were inconclusive. Results were similar in analyses confined to the first year of follow-up, which was less disrupted by the COVID-19 pandemic. Subgroup analyses found little evidence of heterogeneity for the effect on the primary endpoint, although patients with transferrin saturation <20% (OR 0.67, 95% CI 0.49-0.92) may have benefited more than those with values ≥20% (OR 0.99, 95% CI 0.74-1.30) (heterogeneity p = 0.07).ConclusionIn patients with HF and ID, this meta-analysis suggests that IV iron reduces the risk of HHF but whether this is associated with a reduction in cardiovascular or all-cause mortality remains inconclusive.
| S-EPMC10946839 | biostudies-literature
Project description:In patients with heart failure (HF), iron deficiency (ID) correlates with decreased exercise capacity and poor health-related quality of life, and predicts worse outcomes. Both absolute (depleted iron stores) and functional (where iron is unavailable for dedicated tissues) ID can be easily evaluated in patients with HF using standard laboratory tests (assessment of serum ferritin and transferrin saturation). Intravenous iron therapy in iron-deficient patients with HF and reduced ejection fraction has been shown to alleviate HF symptoms and improve exercise capacity and quality of life. In this paper, we provide information on how to diagnose ID in HF. Further we discuss pros and cons of different iron preparations and discuss the results of major trials implementing iron supplementation in HF patients, in order to provide practical guidance for clinicians on how to manage ID in patients with HF.
| S-EPMC5435776 | biostudies-literature