Effect of Iron Isomaltoside on Skeletal Muscle Energetics in Patients with Chronic Heart Failure and Iron Deficiency: The FERRIC-HF II Randomized Mechanistic Trial

Background: Iron repletion augments exercise capacity in chronic heart failure (HF) but there is a lack of mechanistic data explaining how iron could increment exercise performance despite minimal changes in hemoglobin (Hb). Besides Hb, iron is an obligate component of mitochondrial enzymes that generate cellular energy in the form of adenosine triphosphate and phosphocreatine (PCr). Dynamic phosphorus magnetic resonance spectroscopy (31P MRS) is a noninvasive tool that quantifies in vivo muscle energetics by measuring the kinetics of PCr recovery after exertion. We tested the hypothesis that intravenous (IV) iron repletion in chronic HF enhances skeletal muscle energetics as reflected by shorter PCr recovery half-times (PCr t1/2) on 31P MRS. Methods: We enrolled 40 patients (50% anemic) with chronic HF, NYHA class≥ II, LVEF≤ 45%, and iron deficiency (ferritin<100μg/L or 100-300μg/L with transferrin saturation [TSAT]< 20%). Subjects underwent stratified (anemic vs non-anemic) randomization (1:1) to a sing...