Single iron infusion improves exercise capacity in HFpEF patients

A new study by investigators from the Mass General Brigham Heart and Vascular Institute found that a single iron infusion improved exercise capacity in people with heart failure with preserved ejection fraction (HFpEF) and iron deficiency. The findings suggest that replenishing iron could help address the physical limitations associated with this condition. Results were presented at the 2026 American Heart Association Scientific Sessions and published simultaneously in Circulation.

The IRON-MET HFpEF trial enrolled 65 participants with symptomatic HFpEF and iron deficiency, which affects more than 50% of patients with HFpEF. Their median age was 68 years, and 72% of participants were women. 44 participants were randomized to receive one 1,000-mg IV dose of ferric derisomaltose and 21 to receive placebo. Iron was administered intravenously because previous studies have demonstrated that oral iron is not beneficial in patients with other forms of heart failure, likely due to poor gastrointestinal absorption.

All participants underwent cardiopulmonary exercise testing before and 12 weeks after the infusion. At 12 weeks, peak oxygen uptake or VO₂ - which is a key indicator of cardiorespiratory fitness - improved by approximately 10% in the intervention group and was unchanged in the placebo group.

Measurements of the bioavailability of iron in the blood improved with intravenous iron, as did pre-specified secondary measures of exercise capacity, including 6-minute walk distance, VO₂ at the anaerobic threshold, and New York Heart Association Functional Class, compared with those who received placebo. However, the authors note that patient-reported health scores, based on a comprehensive questionnaire, did not differ significantly between groups. There were no serious adverse events associated with the iron supplementation.

As the study was conducted in a small, predominantly white population and participants were assessed at 12 weeks, the authors advocate for further studies to determine whether IV iron has benefits in diverse populations and whether these benefits last over longer time periods.

"The improvement we observed in peak VO₂ represents a clinically meaningful increment for patients with heart failure," said senior author Rajeev Malhotra, MD, who is Associate Director of the Cardiopulmonary Exercise Laboratory at the Mass General Brigham Heart and Vascular Institute and associate professor of Medicine at Harvard Medical School. "The next step is to determine whether IV iron can improve long-term clinical outcomes in patients with HFpEF."

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Mass General Brigham

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