Impact of Proactive Intravenous Iron Repletion on Exercise Capacity and Quality of Life in Non-Anemic Heart Failure Patients

Abstract

Background and Purpose: Iron deficiency (ID) is highly prevalent in chronic Heart Failure (HF) and correlates strongly with poor outcomes, even when patients are not anemic. Current clinical practice often struggles with systematic ID screening and adherence to intravenous iron (IV-Iron) repletion guidelines. This management gap hinders patient improvement. This study assessed whether a strictly applied, systematic IV-Iron intervention improves functional capacity and symptomatic status in a carefully screened, non-anemic HFrEF cohort.

Methods: A prospective, single-blind, randomized controlled trial (RCT) enrolled 260 symptomatic HFrEF patients (NYHA Class II-III, LVEF <40%). Inclusion required documented iron deficiency (Ferritin <100 μg/L or Ferritin 100-300 μg/L with transferrin saturation <20%) but excluded anemia (Hb >120 g/L). Participants were randomized 1:1 to receive guideline-directed care plus IV ferric carboxymaltose or guideline-directed care plus placebo. The primary endpoint was change in 6-minute walk distance (6MWD) at 6 months. Secondary endpoints included Quality of Life (QoL) metrics. Statistical analysis utilized independent t-tests and correlation analysis to assess outcomes and treatment efficacy.  

Results: At 6 months, the IV-Iron group demonstrated a highly significant mean increase in 6MWD of 48±15 meters from baseline, compared to a non-significant change of 5±12 meters in the placebo group (p<0.001). Furthermore, the IV-Iron cohort reported substantial improvement in HF-specific Quality of Life scores (MLHFQ score mean difference: -12 points; p=0.004). Analysis revealed a significant correlation between successful correction of transferrin saturation and symptomatic improvement (r=0.62). No significant difference was observed in rates of hospitalization or serious adverse events between the two arms (p=0.41).

Conclusion: Proactive, systematic intravenous iron repletion significantly improves exercise capacity and quality of life in non-anemic HFrEF patients. This evidence reinforces the crucial need for strict adherence to ID screening protocols, positioning IV-Iron as a fundamental, high-impact management strategy that enhances quality of care in regional HF clinics.