Randomized Placebo-controlled Trial of FCM as Treatment for Heart Failure With Iron Deficiency / and Sub-Study

Inclusion Criteria:

1. Adult (≥18 years of age) able to provide signed, written informed consent.

2. Stable heart failure (NYHA II-IV) on maximally-tolerated background therapy (asdetermined by the site Principle Investigator) for at least 2 weeks prior torandomization.

3. Able and willing to perform a six-minute walk test (6MWT) at the time ofrandomization.

4. Reduced left ventricular ejection fraction. Assessment must be performed at least 12weeks after major cardiac surgical intervention including coronary artery bypassgraft (CABG), valvular repair/replacement, or cardiac resynchronization therapy (CRT) device implantation. a. Left ventricular ejection fraction ≤ 40% obtained during the screening visit OReither of the following i. Historical value of ejection fraction ≤ 40% within 24months of screening visit ii. Historical value of ejection fraction ≤ 30% within 36months of screening visit

5. Hemoglobin >9.0 g/dL and < 13.5 g/dL (females) or <15.0 g/dL (males) within 28 daysof randomization.

6. Serum ferritin <100 ng/mL or 100 to 300 ng/mL with TSAT <20%.Patients with screeningferritin <15 ng/mL must have documentation of an appropriate evaluation, asdetermined by the Principle Investigator, within 3 months of screening and prior torandomization.

7. Either documented hospitalization for heart failure within 12 months of enrollmentor elavated N-terminal-pro-brain natriuretic peptide (NT-proBNP) within 90 days ofrandomization. a. For patients in normal sinus rhythm: N-terminal-pro-brainnatriuretic peptide (NT- proBNP) > 600 pg/mL (or BNP >200 pg/mL) . b . For patientsin atrial fibrillation: NT-proBNP >1000 pg/mL (or BNP >400 pg/mL) .

Exclusion Criteria:

1. Known hypersensitivity reaction to any component of FCM.

2. History of acquired iron overload, or the recent receipt (within 3 months) oferythropoietin stimulating agent, IV iron therapy, or blood transfusion.

3. Acute myocardial infarction, acute coronary syndrome, transient ischemic attack, orstroke within 30 days of enrollment.

4. Uncorrected severe aortic stenosis, severe valvular regurgitation (except mitralregurgitation due to left ventricular dilatation without planned intervention), orleft ventricular outflow obstruction requiring intervention.

5. Current atrial fibrillation or atrial flutter with a mean ventricular response rate >100 per minute (at rest).

6. Current or planned mechanical circulatory support or heart transplantation.

7. Hemodialysis or peritoneal dialysis (current or planned within the next 6 months).

8. Documented liver disease, or active hepatitis (i.e. alanine transaminase oraspartate transaminase >3 times the upper limit of normal range).

9. Current or recent (within 3 years) malignancy with exception of basal cell carcinomaor squamous cell carcinoma of the skin, or cervical intraepithelial neoplasia.

10. Active gastrointestinal bleeding.

11. Female participant of child-bearing potential who is pregnant, lactating, or notwilling to use adequate contraceptive precautions during the study and for up to 5days after the last scheduled dose of study medication.

12. Inability to return for follow up visits within the necessary windows

13. Concurrently in a study with investigational product.

14. No participants with Current Coronavirus Disease-19 (COVID-19) Infection into thestudy.