The purpose of this study is to determine if oral iron (Fe) polysaccharide is superior to oral placebo in improving functional capacity as measured by change in peak VO2 (oxygen uptake) by CPET (Cardiopulmonary Exercise Testing) , of a broad population of patients with HFrEF (Heart Failure with Reduced Ejection Fraction) and Fe deficiency at 16 weeks.

Hypothesis: In a broad population of HFrEF patients with Fe deficiency, compared to oral placebo, therapy with oral Fe polysaccharide will be associated with improvement in functional capacity at 16 weeks as assessed by CPET.

Therapeutic options to further improve functional capacity and symptoms in HF beyond neurohormonal antagonism are limited. Studies have demonstrated impaired oxidative capacity of skeletal muscle among HF patients, which may contribute to symptoms of breathlessness and persistent fatigue.

In addition to its role in erythropoiesis, iron (Fe) plays a critical role in skeletal muscle's oxygen (O2)-storage capacity (myoglobin) and systemic aerobic energy production. As Fe deficiency is common in patients with symptomatic HF, repletion of iron stores may improve submaximal exercise capacity among these patients beyond the effects on erythropoiesis.

While intravenous Fe repletion in HF patients with mild Fe-deficiency (i.e. Ferritin <100 or Ferritin 100-299 with transferrin saturation <20%) with or without anemia global well-being and functional status, oral Fe repletion has not been studied. Furthermore, the efficacy of oral Fe to replete iron stores in a similar population and its impact on functional capacity, measured objectively by peak VO2, remains unknown.

Inclusion Criteria:

1. Age >18 years

2. Previous clinical diagnosis of heart failure with current New York Heart Association (NYHA) Class II-IV symptoms LVEF≤0.40 within 2 years prior to consent, and ≥3 months after a major change in cardiac status (i.e. CABG or CRT).

3. Serum ferritin between 15-100 ng/ml or serum ferritin between 100-299 ng/ml with transferrin saturation <20%

4. Hemoglobin 9.0-13.5 g/dL (males), 9-13.5 (females) at time of enrollment

5. Stable evidence-based medical therapy for HF (including beta-blocker and ACE-inhibitor/ARB unless previously deemed intolerant, and diuretics as necessary) with </= 100% change in dose for 30 days prior to randomization

   a. Changes in diuretic dose guided by a patient-directed flexible dosing program are considered stable medical therapy

6. Willingness to provide informed consent

Exclusion Criteria:

1. Presence of a neuromuscular, orthopedic or other non-cardiac condition that prevents the patient from exercise testing on a bicycle/treadmill ergometer and/or inability to achieve an RER ≥ 1.0 on screening/baseline CPET
2. Severe renal dysfunction (eGFR< 20 ml/min/1.73m2)
3. Severe liver disease (ALT or AST > 3x normal, alkaline phosphatase or bilirubin >2x normal)
4. Gastrointestinal conditions known to impair Fe absorption (i.e. inflammatory bowel disease)
5. Known active infection as defined by current use of oral or intravenous antimicrobial agents
6. Documented active gastrointestinal bleeding
7. Active malignancy other than non-melanoma skin cancers
8. Anemia with known cause other than Fe deficiency or chronic disease
9. Fe overload disorders (i.e. hemochromatosis or hemosiderosis)
10. History of erythropoietin, IV or oral Fe therapy, or blood transfusion in previous 3 months.
11. Current ventricular assist device
12. Anticipated cardiac transplantation within the next 4 months
13. Primary hypertrophic cardiomyopathy, infiltrative cardiomyopathy, acute myocarditis, constrictive pericarditis or tamponade
14. Previous adverse reaction to study drug or other oral Fe preparation
15. Known or anticipated pregnancy in the next 4 months

After the study results have been published, site-specific participant data will be shared with sites upon request. Sites are expected to follow their specific institutional policies regarding sharing results with their participants.