Iron Deficiency and Anemia in Heart Failure

Anemia and iron deficiency are highly prevalent and prognostically important comorbidities among patients with heart failure. Iron deficiency, in both the absolute and functional forms, affects up to 50-60% of patients with heart failure, even in the absence of anemia, and contributes to worsening symptoms, impaired exercise capacity, and increased morbidity and mortality. Iron plays central roles in oxygen transport, myocardial energetics, and skeletal muscle function. Mechanistically, inflammation, impaired iron absorption, hepcidin overproduction, and reduced erythropoiesis contribute to the complex pathophysiology of iron deficiency in heart failure. The diagnostic criteria for anemia are generally serum ferritin < 100 ng/mL or ferritin 100-299 ng/mL with transferrin saturation < 20%. Although oral iron supplementation has shown limited efficacy in clinical trials, intravenous iron therapy -particularly ferric carboxymaltose and ferric derisomaltose therapy- has demonstrated benefits in improving symptom burden and quality of life and reducing hospitalization for heart failure in patients with reduced or mildly reduced ejection fraction. However, large trials such as the HEART-FID and FAIRHF2 failed to show significant reductions in cardiovascular events, highlighting the need for further research. Moreover, key challenges remain, including identifying responders, optimizing iron dosing and monitoring strategies, and evaluating the long-term effects of iron repletion on clinical outcomes. This review summarizes the current evidence and emphasizes the need for more refined diagnostic criteria, individualized treatment approaches, and robust long-term data to guide iron therapy in cases of heart failure.