Recent studies have shown that treatment with intravenous iron in patients with iron deficiency (ID) and heart failure with reduced ejection fraction (HFrEF) improves symptomatology, functional capacity, quality of life, and decreases hospitalizations regardless of anemia. In addition, a decrease in myocardial iron content has been observed in patients with chronic HFrEF. This preliminary evidence has led to postulate that myocardial iron deficiency could play a direct role in the pathogenesis and progression of the disease.

The investigators hypothesize that the repletion of myocardial iron would explain part of the benefit of this treatment. Thus, the investigators postulate that cardiac magnetic resonance (CMR) (T2* and T1-mapping sequences) will be sensible enough to detect changes in myocardial iron content as a result of intravenous iron administration, and that such changes will correlate with simultaneous changes in parameters of heart failure severity.

In this double-blind 1:1 randomized study controlled by placebo the investigators aim to determine the changes in myocardial iron content after treatment with intravenous ferric carboxymaltose (FCM) by CMR at 7 and 30 days in patients with stable HFrEF and ID.

Inclusion Criteria:

• Patients with ambulatory chronic heart failure
• Older than 18 years
• Patients in NYHA class II-III on optimal background therapy (as determined by the investigator) for at least 4 weeks with no dose changes of HF drugs during the last 2 weeks (with the exception of diuretics)
• Elevated natriuretic peptides levels (NT-proBNP >400 pg/ml) at the screening visit
• Left ventricle ejection fraction <50% documented in the last 12 months
• Iron deficiency defined as: serum ferritin level <100 μg/L or ferritin level 100-299 μg/L when TSAT is less than 20%, and hemoglobin <15 g/dL (all at screening)
• Participant is willing and able to give informed consent for participation in the study

Exclusion Criteria:

• Known sensitivity to any of the products to be administered per protocol.
• History of acquired iron overload.
• Severe valve disease, or being scheduled for cardiac surgery within the next 30 days.
• Acute myocardial infarction or acute coronary syndrome, transient ischemic attack, or stroke within the last 3 months prior to randomization.
• Coronary artery bypass graft, percutaneous intervention (e.g. cardiac, cerebrovascular, and aortic; diagnostic catheters are allowed), or major surgery, including thoracic and cardiac surgery, within the last 3 months prior to randomization.
• Ischemic heart disease scheduled for revascularization procedures within the next 30 days.
• HF scheduled for cardiac resynchronization therapy within the next 30 days.
• Patients with active bleeding in the last 30 days.
• Known active infection or active malignancy.
• Subject at an immediate need of transfusion or hemoglobin ≥15 g/dL.
• Anemia due to reasons other than iron deficiency
• Immunosuppressive therapy or renal dialysis
• History of erythropoietin, intravenous iron therapy, and blood transfusion in the previous 12 weeks.
• Oral iron therapy at doses >100 mg/day in previous 1 week prior to randomization.
• Subjects with an immediate need for transfusion.
• Pregnant or breastfeeding women.
• Subject of childbearing potential who is not willing to use adequate contraceptive precautions during the study and for up to 5 days after the last scheduled dose of study medication.
• Subject currently enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study, or subject is receiving other investigational agent(s).
• Any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures.

Because ferric carboxymaltose is a dark-brown solution that is easily distinguishable from the saline placebo, study personnel responsible for the preparation and administration of the study drug will aware of the group assignments and therefore, not involved in any study assessments. To ensure that patients will be unaware of the study drug, materials used in drug administration will be covered with aluminum foil or other opaque material and the injection site shield from the patient view. Once treatment is allocated, the investigators team will ensure that patients are blinded to the treatment received.