Iron Deficiency in Heart Failure: Cellular Mechanisms and Therapeutic Implications

Iron deficiency (ID) is a prevalent comorbidity in heart failure (HF), affecting 37-75% of patients and contributing significantly to symptom burden and adverse outcomes independent of anemia status. Current diagnostic criteria for ID in HF include absolute deficiency (ferritin <100 μg/L) and functional deficiency (ferritin 100-299 μg/L with transferrin saturation <20%). Major clinical trials including AFFIRM-AHF, IRONMAN, HEART-FID, and FAIR-HF2 have demonstrated that intravenous iron therapy, particularly ferric carboxymaltose, reduces HF hospitalizations and improves quality of life and exercise capacity. The 2023 European Society of Cardiology guidelines recommend intravenous ferric carboxymaltose for symptomatic iron-deficient patients with heart failure with reduced ejection fraction. Despite these advances, significant knowledge gaps remain regarding optimal diagnostic approaches, the relationship between ID and ferroptosis in cardiac tissue, and the efficacy of newer iron formulations. This review synthesizes current understanding of ID in HF and highlights emerging therapeutic strategies.