Iron repletion in heart failure: a symptomatic win, a survival miss

Iron is essential for the production of myocardial energy and proteins critical for metabolism. Iron deficiency is common in patients with heart failure and reduced ejection fraction (HFrEF) and is associated with a poor prognosis. However, whether intravenous iron replacement reduces the risk of adverse clinical events in HFrEF patients remains uncertain, despite several outcome trials being conducted. Furthermore, significant uncertainties persist in this setting regarding the most appropriate definition of iron deficiency and the optimal dosing regimen. Here, we critically discuss the findings of the recently published FAIR-HF2 (Ferric Carboxymaltose Assessment of Morbidity and Mortality in Patients with Iron Deficiency and Chronic Heart Failure) trial, which investigated the efficacy and safety of ferric carboxymaltose in patients with HF and iron deficiency, while positioning these results within the broader context of current evidence on intravenous iron supplementation in patients with HFrEF.