Intravenous Iron Supplementation in Heart Failure with Preserved Ejection Fraction: A Systematic Review.

Iron deficiency affects approximately half of patients with heart failure with preserved ejection fraction (HFpEF) and impairs functional capacity, yet evidence for intravenous (IV) iron in this population is limited. We evaluated the effect of IV iron on functional, biochemical, biomarker, and clinical outcomes in HFpEF. This systematic review followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 and was prospectively registered [International Prospective Register of Systematic Reviews (PROSPERO) CRD420261360828]. Four databases were searched on April 11, 2026. Eligible studies enrolled adults with HFpEF and iron deficiency receiving IV iron, with at least 4 weeks of follow-up. Two reviewers independently screened records, extracted data, and assessed risk of bias. Because few studies were eligible and heterogeneity was substantial, findings were synthesized narratively without meta-analysis in accordance with the synthesis without meta-analysis guideline, and certainty was rated using the Grading of Recommendations Assessment, Development and Evaluation framework. Seven reports of 6 studies were included: 1 randomized trial, 2 controlled observational studies, and 3 single-arm before-after studies. Across studies, IV iron consistently increased ferritin, transferrin saturation, and hemoglobin. The randomized trial improved 6-minute walking distance but not functional class or quality of life, and was stopped early. Effects on natriuretic peptide concentrations were inconsistent. The 2 controlled studies disagreed on clinical events: a propensity-matched analysis reported fewer hospitalizations, whereas a registry found no benefit. Certainty of evidence ranged from very low to moderate. In HFpEF, IV iron reliably corrects iron indices, but a clinical benefit remains unproven, and the evidence base is sparse and largely uncontrolled. Adequately powered randomized trials are required.