Impact of Intravenous Iron Repletion On Mechanisms of Exercise InTolerance in HFpEF (IRONMET-HFpEF)

Inclusion Criteria: 1. Adult (≥18 years of age) able to provide informed consent. 2. Stable heart failure (NYHA II-IV) for at least 4 weeks 3. Heart Failure with Preserved left ventricular ejection fraction.(Left ventricular ejection fraction ≥ 50 % obtained within 6 months of informed consent. 4. NT-proBNP ≥ 125 pg/mL without ongoing atrial fibrillation/flutter. If ongoing atrial fibrillation/flutter at the time of sample collection, NT-proBNP must be ≥ 250 pg/mL OR patients must have a history of pulmonary capillary wedge pressure ≥ 15 mm Hg during rest or the slope of pulmonary capillary wedge pressure to cardiac output (PCWP/CO) ≥ 2.0 mmHg/L/min during upright exercise (Eisman et al., Circ Heart Fail. 2018 May;11(5):e004750.).OR subjects must have a heart failure hospitalization within the last 12 months prior to screening OR Chronic diastolic dysfunction on echocardiography as evidenced by: Left Atrial Enlargement (LAE): LA diameter ≥ 3.8cm in women, ≥ 4.0 cm in men or LA length ≥ 5.0 cm or LA area ≥ 20 cm2 OR LA volume ≥ 55mL or LA volume index ≥ 29ml/m2 or Left Ventricular Hypertrophy (LVH): septal thickness or posterior wall thickness ≥ 1.1 cm OR For patients in sinus rhythm: E/e' ratio ≥15 at septal annulus, or E/e' ratio ³13 at lateral annulus, or average E/e' ratio ³14. For patients in atrial fibrillation: E/e' ≥ 11 at the septal annulus. 5. Hemoglobin \>9.0 g/dL AND \<15.0 g/dL . 6. Serum ferritin \<100 ng/mL OR 100 to 300 ng/mL with TSAT \<20%, but NOT ferritin \< 15 ng/mL. 7. Demonstrate diminished exercise capacity: ≤ 75 % predicted peak VO2 as determined by a Cardiopulmonary Exercise Test (CPET) at the time of screening 8. Perform a maximal effort CPET by achieving a Respiratory Exchange Ratio (RER) of ≥ 1.05 Exclusion Criteria: 1. Current or planned intravenous iron supplementation. Iron-containing multivitamins (\<30 mgs /day) are permitted. 2. Known hypersensitivity reaction to any component of ferric derisomaltose (Monofer®) 3. History of acquired iron overload (e.g. hemochromatosis), or the recent receipt (within 3 months) of erythropoietin stimulating agent, IV iron therapy, or blood transfusion. 4. Documented active gastrointestinal bleeding 5. Anemia with known cause other than iron deficiency or chronic disease 6. Acute myocardial infarction, acute coronary syndrome, transient ischemic attack, or stroke within 3 months of enrollment. 7 Presence of any condition that precludes exercise testing such as: a. Claudication that limits exertion b. Uncontrolled bradyarrhythmia or tachyarrhythmia (according to Investigator judgment, pacemaker treatment is allowed as long as the same pacing mode/activity can be used at baseline and follow-up CPET) c. Clinically significant musculoskeletal disease or orthopedic conditions that limit the ability to perform the CPET (e.g., arthritis or injury in the foot, leg, knee or hip) d. Severe obesity (BMI \> 50.0 kg/m2) e. Any other non-heart failure condition that, in the opinion of the Investigator, that is the primary limitation to exercise. 8. Severe renal dysfunction (eGFR\< 20 ml/min/1.73m2) 9. Severe liver disease (ALT or AST \> 3x upper limit of normal, alkaline phosphatase or bilirubin \>2x upper limit of normal) 10. Active malignancy other than non-melanoma skin cancers 11. Female participant of child-bearing potential who is pregnant, lactating, or not willing to use adequate contraceptive precautions during the study and for up to 5 days after the last scheduled dose of study medication. 12\. Planned surgical procedure during the trial period 13. Inability to return for follow up visits