Mass General Brigham: one IV iron dose raised peak VO2 about 10% in a 65-patient HFpEF trial
In a randomized trial of 65 patients with HFpEF and iron deficiency, one ferric derisomaltose infusion improved exercise capacity at 12 weeks compared with placebo.
Investigators from the Mass General Brigham Heart and Vascular Institute report that a single intravenous iron infusion improved exercise capacity in people with heart failure with preserved ejection fraction (HFpEF) and iron deficiency, according to a EurekAlert release. The results were presented at the 2026 American Heart Association Scientific Sessions and published simultaneously in Circulation on 8 November 2026 eurekalert.org
EurekAlerteurekalert.orgOpen source ↗.
Trial design and participants
The IRONMET-HFpEF trial enrolled 65 participants with symptomatic HFpEF and iron deficiency. Iron deficiency affects more than 50% of patients with HFpEF. The median age of participants was 68 years, and 72% were women.
A total of 44 participants were randomized to receive one 1,000-mg intravenous dose of ferric derisomaltose, and 21 received placebo. Iron was given intravenously because earlier studies showed that oral iron was not beneficial in patients with other forms of heart failure, likely due to poor gastrointestinal absorption. All participants underwent cardiopulmonary exercise testing before the infusion and 12 weeks after it.
Results and limitations
At 12 weeks, peak oxygen uptake (VO2), a key indicator of cardiorespiratory fitness, improved by approximately 10% in the intervention group and was unchanged in the placebo group eurekalert.org
EurekAlerteurekalert.orgOpen source ↗. Blood measures of iron bioavailability improved with intravenous iron. So did the pre-specified secondary measures of exercise capacity: 6-minute walk distance, VO2 at the anaerobic threshold and New York Heart Association functional class, compared with placebo.
Patient-reported health scores, based on a comprehensive questionnaire, did not differ significantly between the groups. No serious adverse events were associated with the iron supplementation, the authors report.
The study was small and the population predominantly white, and participants were assessed only at 12 weeks. The authors call for further studies to determine whether intravenous iron benefits diverse populations and whether the effect lasts over longer periods.
Lead author Gregory D. Lewis said this was the first study to comprehensively evaluate exercise response patterns to iron repletion in HFpEF with iron deficiency. Senior author Rajeev Malhotra described the change in peak VO2 as a clinically meaningful increment for patients with heart failure. He said the next step is to determine whether intravenous iron can improve long-term clinical outcomes in HFpEF.
