Defective Iron Utilization in Heart Failure: A Prevalent Phenotype with Less Frequent Iron Therapy

Background/Objectives: Iron deficiency (ID) in heart failure (HF) can be classified as low iron storage (LIS) or defective iron utilization (DIU). Whether these phenotypes differ in clinical characteristics, outcomes, and treatment patterns in a real-world decompensated HF population remains unclear. Methods: In this population-based retrospective cohort study, 4818 adults with decompensated HF and available iron indices were classified as LIS (TSAT < 20%, ferritin < 100 µg/L), DIU (TSAT < 20%, ferritin ≥ 100 µg/L), or no ID (TSAT ≥ 20%). All-cause mortality, cardiovascular (CV) hospitalization, HF hospitalization, and initiation of iron therapy were assessed over a median follow-up of 24 months. Outcomes were analyzed using Cox proportional hazards models adjusted for pre-specified covariates, with Fine–Gray competing-risk models for hospitalization and iron therapy initiation, and no ID as the reference group. Results: DIU was present in 30.2% of patients, compared with 38.7% with LIS and 31.1% with no ID. Iron therapy was initiated in 21.5% of patients with DIU compared with 32.0% with LIS, and intravenous (IV) iron in 2.7% versus 4.3%, respectively. After adjustment, DIU was associated with modestly higher CV hospitalization rates (aHR 1.15; 95% CI 1.03–1.28) and with the composite of CV hospitalization or all-cause mortality (aHR 1.09; 95% CI 1.00–1.19), but not with all-cause mortality (aHR 1.03; 95% CI 0.93–1.14) or HF hospitalization (aHR 1.10; 95% CI 0.93–1.27) compared with no ID. LIS was associated with higher risk of HF hospitalization (aHR 1.38; 95% CI 1.19–1.59). Patients with LIS were more likely to initiate iron therapy than those with DIU (adjusted sHR 1.49; 95% CI 1.29–1.71). Conclusions: DIU is a prevalent phenotype of ID in decompensated HF that is less frequently treated with iron than LIS, despite a largely similar prognosis, and is associated with modestly higher CV hospitalization and the composite of CV hospitalization or death, but not independently with mortality. Prospective evaluation of iron replacement strategies, particularly IV iron, in patients with DIU is warranted.