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.
"Patients living with HFpEF are burdened with severe limitations in exercise tolerance," said lead author Gregory D. Lewis, MD, director of Heart Failure at the Mass General Brigham Heart and Vascular Institute and professor of Medicine at Harvard Medical School. "In the first study to comprehensively evaluate exercise response patterns to iron repletion in patients with HFpEF and iron deficiency, we found that ferric derisomaltose improved multiple measures of exercise capacity."
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."
Authorship: In addition to Lewis and Malhotra, Mass General Brigham authors include Nora K. Horick, Fabely Moreno, Kenneth Lim, Diane Cocca-Spofford, Takenori Ikoma, Paridhi Gupta, Carly Camphausen, Laura Caccamo, Charounipha Soydara, Shaina McGinnis, Chloe Newlands, Skyler Williams, Alexandra Minasian, Nicholas Iskenderian, Isabela Landsteiner, Bhavani Iyer, Justin Joseph, Alvaro Delgado, Helena Tattersfield, Elizabeth Moore, Veronica Platt, and Sujin Lee.
Disclosures: Lewis and Malhotra have served as advisors for Pharmacosmos. Lewis has previously served on the scientific advisory board for American Regent.
Funding: This research was funded by the National Heart, Lung, and Blood Institute (R01HL159514, R01HL131029 and R01HL151841).
Paper cited: Lewis GD et al. "Iron Repletion in Heart Failure with Preserved Ejection Fraction: The IRONMET-HFpEF Randomized Trial," Circulation DOI: 10.1161/CIRCULATIONAHA.126.084009
