Iron Deficiency in Heart Failure: A Scientific Statement from the Heart Failure Society of America

Beavers, Craig J.; Ambrosy, Andrew P.; Butler, Javed; Davidson, Beth Towery; Gale, Stormi E; Piña, Ileana L.; Mastoris, Ioannis; Reza, Nosheen; Mentz, Robert J; Lewis, Gregory D.

doi:10.1016/j.cardfail.2023.03.025

Cited by 28 publications

(12 citation statements)

References 129 publications

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“…The use of IV iron plays an essential role in managing HF and is supported by consistent data which demonstrated benefit in those with iron deficiency (Table 2) [7,8,9 ▪ ,38,39 ▪ ,48–50,51 ▪ ]. Early trial data revealed an association between IV iron administration and improved peak Vo 2 [38,49,50] Evidence suggests there is a correlation between improved peak Vo2 and a lower risk of death or hospitalization in individuals with HF [52–54]. Improvement in left ventricular ejection fraction following IV iron administration has also been reported [48].…”

Section: Clinical Evidencementioning

confidence: 86%

Intravenous iron in patients with iron deficiency and heart failure: a review of modern evidence

Gale,

Willeford,

Sandquist

et al. 2024

Current Opinion in Cardiology

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Purpose of review Iron deficiency is common in patients with heart failure, affecting up to half of ambulatory patients and an even greater percentage of patients admitted for acute decompensation. Iron deficiency in this population is also associated with poor outcomes, including worse quality of life in addition to increased hospitalizations for heart failure and mortality. Evidence suggests that patients with iron deficiency in heart failure may benefit from repletion with IV iron. Recent findings In this review, we outline the etiology and pathophysiology of iron deficiency in heart failure as well as various iron formulations available. We discuss evidence for intravenous iron repletion with a particular focus on recent studies that have evaluated its effects on hospitalizations and mortality. Finally, we discuss areas of uncertainty and future study and provide practical guidance for iron repletion. Summary In summary, there is overwhelming evidence that intravenous iron repletion in patients with iron deficiency in heart failure is both beneficial and safe. However, further evidence is needed to better identify which patients would most benefit from iron repletion as well as the ideal repletion strategy.

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Section: Clinical Evidencementioning

confidence: 86%

Intravenous iron in patients with iron deficiency and heart failure: a review of modern evidence

Gale,

Willeford,

Sandquist

et al. 2024

Current Opinion in Cardiology

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“…Many studies provide evidence of how iron deficiency may contribute to worse HF outcomes. 3,4 The reduction in oxygen carrying capacity related to anaemia taxes a failing heart. But the causal link can be explained at a more generalized level as iron is an essential cofactor for multiple enzymatic functions across organ systems, for example, soluble guanylate cyclase activity.…”

Section: Is There Biologic Plausibility Causally Linking Iron Deficie...mentioning

confidence: 99%

“…In prior trials, the magnitude of improvement in 6MWD with iron replacement in HF was greater than what is typically observed with drug therapy for HF. 3 Notably, none of the trials to date have compared oral versus intravenous iron and it has been challenging to identify specific subgroups who respond to oral iron. 5 Also, clear data are not available demonstrating that intravenous iron increases peak oxygen consumption.…”

Section: Is Iron Replacement Associated With Improved Functional Status?mentioning

confidence: 99%

“…TSAT <20%). 3 Abnormal iron indices may also be a marker of HF exacerbation rather than a cause or mediator. The dose of ferric carboxymaltose and dosing scheduling also differed from prior trials (up to 1500 mg every 6 months in HEART-FID vs. up to 1000 mg at baseline followed by weeks 6, 12, and 24 in AFFIRM-AHF)-the repletion strategy varied.…”

Section: What Did the Heart-fid Trial Show And How To Interpret The R...mentioning

confidence: 99%

“…2 This result contrasted with previous studies that showed improvement in functional capacity and health status, and in exploratory analyses, risk reduction for HF hospitalization, with iron replacement in HF with iron deficiency. 3 Considering the purpose and nature of HEART-FID, it is important to contextualize these results to understand the role of iron therapy in patients with HF.…”

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confidence: 99%

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Iron replacement therapy in heart failure: Contextualizing the results of the HEART‐FID trial

Butler,

Mentz,

Hernandez

2024

European J of Heart Fail

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HEART-FID was the largest randomized trial of intravenous iron replacement therapy in patients with heart failure (HF) and iron deficiency. 1 This trial showed a modest benefit with intravenous iron replacement therapy on the hierarchical composite endpoint of all-cause mortality, HF hospitalization risk, or 6-min walk distance (6MWD) that did not achieve the pre-specified significance level. 2 This result contrasted with previous studies that showed improvement in functional capacity and health status, and in exploratory analyses, risk reduction for HF hospitalization, with iron replacement in HF with iron deficiency. 3 Considering the purpose and nature of HEART-FID, it is important to contextualize these results to understand the role of iron therapy in patients with HF.

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Prognostic impact of iron deficiency in new‐onset chronic heart failure: Danish Heart Failure Registry insights

Mohamed,

Christensen,

Mohammad

et al. 2024

ESC Heart Failure

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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.

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Iron Deficiency in Heart Failure: A Scientific Statement from the Heart Failure Society of America

Cited by 28 publications

References 129 publications

Intravenous iron in patients with iron deficiency and heart failure: a review of modern evidence

Intravenous iron in patients with iron deficiency and heart failure: a review of modern evidence

Iron replacement therapy in heart failure: Contextualizing the results of the HEART‐FID trial

Prognostic impact of iron deficiency in new‐onset chronic heart failure: Danish Heart Failure Registry insights

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