Iron Deficiency in Heart Failure with Reduced Ejection Fraction: Prevalence and Response to Supplementation

Abstract

Introduction: Iron deficiency (ID), even without anemia, is common in heart failure with reduced ejection fraction (HFrEF) and impairs exercise capacity. This review examines ID prevalence and efficacy of intravenous iron.
Methods: Systematic review of cross-sectional studies and RCTs. Inclusion criteria: HFrEF (LVEF ≤40%), ID defined as ferritin <100 μg/L or 100–299 μg/L with transferrin saturation <20%. Outcomes: prevalence in stable vs. acute HF, and for RCTs: change in 6-minute walk distance (6MWD) and HF hospitalization.
Results: 25 prevalence studies (n=12,300) found overall ID prevalence 55% (95%CI 50–60%), higher in acute decompensated HF (61%) vs. stable (48%). Female sex and advanced NYHA class predicted ID. 8 RCTs (n=2,219) of IV ferric carboxymaltose vs. placebo pooled improvement in 6MWD: mean difference 34 meters (95%CI 22–46). HF hospitalization reduction: RR 0.72 (0.58–0.88). Oral iron showed no benefit in 3 trials. Adverse events similar except hypophosphatemia (15% with IV iron).
Discussion: ID in HFrEF is prevalent and independently prognostic. Despite inconsistent effects on hemoglobin, iron improves mitochondrial function and energy metabolism. Limitations include short follow-up (≤1 year) and exclusion of patients with recent IV iron.
Conclusions: Intravenous ferric carboxymaltose improves functional capacity and reduces HF hospitalizations in iron-deficient HFrEF patients. Routine screening for ID with ferritin and transferrin saturation is recommended.