Iron Deficiency in Heart Failure

von Haehling S, Ebner N, Evertz R, Ponikowski P, Anker SD.
Iron Deficiency in Heart Failure: An Overview. JACC Heart Fail 2019;7:36-46.

The following are key points to remember from this review on iron deficiency in heart failure:

  1. Iron deficiency anemia is widely present in patients with heart failure with an estimated prevalence of over 50% in ambulatory patients. It is an independent predictor of worse functional capacity and survival.
  2. Risk factors for iron deficiency include female sex, advanced heart failure, and higher levels of N-terminal pro–B-type natriuretic peptide and C-reactive protein.
  3. Definition of iron deficiency in heart failure differs from other conditions of chronic inflammation and is defined as: ferritin <100 µg/L or ferritin of 100-299 µg/L with a transferrin saturation <20%.
  4. At present, intravenous (IV) iron is the preferred route for treatment in heart failure patients. Most studies have used IV iron sucrose (maximum dose of 200 mg per setting) or ferric carboxymaltose (maximum dose of 1000 mg per week).
  5. Multiple placebo-controlled, randomized clinical trials have been conducted with IV iron in patients with New York Heart Association class II-III heart failure with an ejection fraction ≤45% who met criteria for iron deficiency, regardless of whether anemia was present. IV iron administration was associated with improvement in patient-reported outcomes and functional capacity. However, these trials did not examine the impact of IV iron on mortality and hospitalizations.
  6. In two separate meta-analyses, IV iron use in heart failure patients with iron deficiency was associated with a reduced risk for the composite endpoint of all-cause mortality and cardiovascular hospitalization. There is currently an ongoing, large clinical trial that aims at examining efficacy of IV iron in reducing cardiovascular mortality and recurrent hospitalizations in heart failure patients.
  7. To date, no clinical trial has proven the efficacy of oral iron in patients with heart failure with reduced ejection fraction. Furthermore, oral iron preparations are associated with a high incidence of adverse effects (in up to 40% of patients), are poorly absorbed due to gut wall edema, and can take up to 6 months to replenish iron stores.
  8. The European Society of Cardiology heart failure guidelines recommend that all patients with heart failure should be tested for anemia and iron deficiency with serum ferritin and transferrin saturations. The European guidelines recommend treatment with IV ferric carboxymaltose in symptomatic heart failure patients with iron deficiency to improve heart failure symptoms and quality of life (Class IIa, Level of Evidence A recommendation). The US guidelines do not recommend any specific formulation, but recommend IV iron in patients with heart failure and iron deficiency as a Class IIb, Level of Evidence B recommendation.
  9. The role of iron in patients with heart failure and preserved ejection fraction has not been established. There is currently an ongoing clinical trial evaluating this.

Clinical Topics: Anticoagulation Management, Dyslipidemia, Heart Failure and Cardiomyopathies, Lipid Metabolism, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Anemia, Iron-Deficiency, Edema, Ferric Compounds, Ferritins, Heart Failure, Inflammation, Iron, Maltose, Natriuretic Peptide, Brain, Peptide Fragments, Quality of Life, Risk Factors, Stroke Volume, Transferrins

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