Patients with heart failure with reduced ejection fraction and iron deficiency will be randomized to either receive iron infusion or be in the control group. The study is looking at how iron replacement affects exercise capacity as measured by peak oxygen uptake.

Currently 5.7 million people in the United States (US) have Heart Failure and it is expected that by 2030 more than 8 million people will have this condition, accounting for a 46 % increase in prevalence. Iron deficiency and anemia are both common findings in patients with heart failure and contribute to morbidity and mortality. The average cost of hospital admissions for heart failure are about $17,000-25,000; creating a large burden on health-care resources and iron replacement may serve to reduce readmissions at less than a tenth of the cost.

The working hypothesis to support Iron supplementation is that it improves oxygen carrying capacity, thereby improving exercise tolerance. Exercise tolerance in patients with heart failure is an important prognostic indicator.

Role of iron supplementation has been investigated to improve quality of life and outcomes in patients with heart failure and two large multi-centric trails. FAIR-HF and CONFIRM-HF have both showed significant improvement in symptoms and six-minute walk distances in patients with HFrEF after IV iron supplementation. This was found to be true for both anemic and non-anemic patients. Despite the current data, IV iron supplementation is currently only a class IIb recommendation for HFrEF and routine testing of iron studies, is not a part of practice guidelines for heart failure management.

Part of what makes the existing data less compelling is that exercise tolerance was assessed using a 6-minute walk test and though it correlates with functional capacity, it is a sub-maximal exercise test and cannot assess the peak oxygen uptake. Individuals with heart failure are often unable to attain this peak oxygen uptake. The inability to increase O2 uptake with exercise is what affects exercise capacity.

The study aims to bridge the gap between the response seen after IV iron supplementation and the change in physiology we attribute to it using a formal Cardiopulmonary exercise testing. A peak VO2 provides the most objective assessment of functional capacity in patients with HF. This parameter is a surrogate marker for the maximal cardiac output that an individual can achieve. A modest increase in peak VO2 of 6% at 3 months of exercise training has been associated with a reduction in mortality by 5 %.

Inclusion Criteria:

• Age 18-90 years
• New York Heart Association Class II-III heart failure
• Left ventricular dysfunction with left ventricular ejection fraction ≤ 40%
• Ferritin < 100 ng/mL or 100-300 ng/mL with transferrin saturation (TSAT) < 20%
• Patients deemed by an attending physician to require intravenous iron therapy
• The patient is willing and able to comply with the protocol and has provided written informed consent

Exclusion Criteria:

• Iron overload disorders or allergy, concomitant nutritional deficiencies- B12 and folate
• Recent Acute Coronary Syndrome
• Physical barriers to exercise capacity
• Currently presenting in heart failure exacerbation
• Declined participation
• Chronic liver disease
• NYHA class IV
• Active bleeding
• Pregnancy
• Life expectancy ≤ 12 months

Only coded research data will be shared for data analysis by study team. Only limited data set may be shared with sponsor if requested according to data agreement. Future use data will be de-identified and stored in REDCap and only utilized by the investigator's department researchers. Publications and reports will be de-identified.