Iron Infusion Improved Fitness in Small Trial of Heart Failure With Iron Deficiency

The IRONMET-HFpEF trial, published on November 8, 2026, was double-blind and placebo-controlled. It enrolled 65 people with heart failure with preserved ejection fraction (HFpEF) and iron deficiency between December 2021 and April 2026. In this form of heart failure, the heart squeezes out a normal proportion of blood but does not fill or relax normally. Their median age was 68 years, and 72% were women. Forty-four received a single 1,000 mg dose of ferric derisomaltose through a vein. Twenty-one received placebo.

Iron deficiency is present in more than half of people with HFpEF, the authors write, and is associated with reduced exercise capacity and survival. In this trial, it was defined by blood tests: ferritin below 100 ng/mL, or below 300 ng/mL with transferrin saturation under 20%. Ferritin reflects the body's iron stores. Transferrin saturation reflects how much of the iron-carrying protein in blood is loaded.

The main measure was peak oxygen uptake, the most oxygen the body can use during hard exercise. It is a standard gauge of aerobic fitness. At the start, the median was 12.7 mL per kilogram per minute in the iron group and 12.2 in the placebo group. After 12 weeks, the iron group improved by 1.2 (95% CI, 0.6 to 1.7). The placebo group was essentially unchanged, at 0.1. The adjusted difference between groups was 1.1 (95% CI, 0.2 to 1.9; P=0.02). The original Mass General Brigham press release on the study described this as roughly a 10% gain.

Other exercise measures also improved with iron compared with placebo: oxygen uptake at the anaerobic threshold, distance covered in a 6-minute walk, and New York Heart Association class, a clinical rating of symptom severity. All differences had P values below 0.05. Scores on the Kansas City Cardiomyopathy Questionnaire, which captures how patients say they feel, did not differ significantly between groups.

The infusion raised iron markers as intended. Transferrin saturation rose by 9.4 percentage points and ferritin by 183 ng/mL relative to placebo. Of the 65 participants, 64 completed the study. The authors report no serious adverse events related to the iron.

For older adults with heart failure with preserved ejection fraction and low iron, the trial points to iron status as a measurable factor in exercise capacity. The authors call it the largest trial to date of iron repletion in HFpEF with iron deficiency. "We found that ferric derisomaltose improved multiple measures of exercise capacity," lead author Gregory D. Lewis said in the Mass General Brigham press release.

According to the press release, the authors note that the group was small and predominantly white, and that follow-up lasted 12 weeks.

Next, researchers want to know whether the fitness gains translate into better health over time. Senior author Rajeev Malhotra said the next question is whether intravenous iron improves longer-term clinical outcomes. This trial did not establish a reduction in hospitalization or death.

The study was funded by the National Heart, Lung, and Blood Institute. Lewis and Malhotra disclosed advisory roles with Pharmacosmos; Lewis also disclosed a past scientific advisory role with American Regent.

Sources: Lewis and colleagues, Circulation, November 8, 2026. Mass General Brigham original release.