Iron Repletion in Heart Failure With Preserved Ejection Fraction: The IRONMET-HFpEF Randomized Trial
Year: 2026
Type: article
Study design: Clinical Trial
Abstract: BACKGROUND: Iron deficiency is present in >50% of patients with heart failure with preserved ejection fraction and is associated with reduced exercise capacity and survival. Whether iron repletion improves exercise capacity as objectively measured by peak oxygen uptake ([Formula: see text]) is unknown. The IRONMET-HFpEF trial (Impact of Intravenous Iron Repletion on Mechanisms of Exercise Intolerance in HFpEF) sought to determine whether ferric derisomaltose (FDI) compared with placebo improves peak [Formula: see text] in heart failure with preserved ejection fraction with iron deficiency. METHODS: This was a double-blind, placebo-controlled randomized clinical trial of patients with heart failure with preserved ejection fraction and iron deficiency, defined as ferritin <100 ng/mL or <300 ng/mL with transferrin saturation <20%. Participants were enrolled between December 2021 and April 2026. Single-dose ferric derisomaltose (1000 mg; n=44) or placebo (n=21) was administered once intravenously. The primary end point was the change in peak [Formula: see text] from baseline to 12 weeks with an analysis of covariance model including terms for treatment group, baseline peak [Formula: see text], and sex. Secondary end points included changes in [Formula: see text] at the anaerobic threshold, 6-minute walk test distance, New York Heart Association class, health status assessed by the Kansas City Cardiomyopathy Questionnaire-Overall Summary Score, and iron biomarkers at 12 weeks. RESULTS: <0.001 for both). There were no serious adverse events related to FDI administration. CONCLUSIONS: In the largest trial to date of iron repletion in heart failure with preserved ejection fraction with iron deficiency, FDI improved multiple measures of exercise capacity. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04945707.
Source: Circulation
Authors: Gregory D. Lewis, 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, Sujin Lee, Rajeev Malhotra
Institutions: Mass General Brigham, Massachusetts General Hospital
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W7225573181