Intervention: Injectafer
Trial phase: Phase 2
SMILES: O.O=C([O-])C(O)C(O)C(OC1OC(CO)C(OC2OC(CO)C(OC3OC(CO)C(O)C(O)C3O)C(O)C2O)C(O)C1O)C(O)CO.[Fe+3].[O-2].[OH-]
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 3
Group description: HF patients with functional iron deficiency assigned to receive one-time dose of Ferric Carboxymaltose 750 mg. Participants will undergo serial assessment before and 4 weeks after study drug administration

Ferric Carboxymaltose: Intravenous Ferric Carboxymaltose 750 mg mixed under sterile conditions in 100 ml of normal saline for final concentration of 7.5 mg/ml and administered via volumetric infusion pump over 15 minutes.

31P MRS/MRI: Each participant will perform the same rhythmic plantar extension exercise protocol twice, for sequential acquisition of magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) measurements. For the exercise protocol, the participant will lay supine on the scanning table with the right leg inside the volume coil. The exercise consists of repeated plantar flexion movements using resistance bands at a frequency of one repetition per second for 1-2 minutes. Data are collected continuously for 2 minutes before the exercise (baseline), during exercise, and 5 minutes after the exercise for the MRS and MRI experiments.
Eligibility criteria:
Inclusion Criteria:

Symptomatic NYHA Class II-III heart failure >3 months
Guideline-recommended heart failure treatment for > 3 months
Hemoglobin >13 g/dl for men and >12 g/dl for women
Functional iron deficiency (defined as serum ferritin level <100 ng/ml or between 100 and 299 ng/ml with transferrin saturation <20%)
Left ventricular ejection fraction <40%, or left ventricular ejection fraction ≥40% with left atrial enlargement (left atrial volume index >28 ml/m2) and/or left ventricular hypertrophy (left ventricular mass index >95 g/m2 (women) or >115 g/m2 (men) determined by echocardiogram within last 24 months.
Able and willing to provide written informed consent

Exclusion Criteria:

Presence of implantable defibrillator, permanent pacemaker, other metal implant not compatible with 3TMRS/MRI, or other contraindication to 3T MRS/MRI procedures
Heart failure due to infiltrative cardiomyopathy, restrictive cardiomyopathy, or hypertrophic cardiomyopathy
Weight <50 kg or >120 kg
Coronary or cerebral atherothrombotic events in the past 6 months
Hospitalization of emergency room visit for heart failure within past 3 months
ICD shock in last 3 months
Known peripheral artery disease or ankle-brachial index <0.9 at screening visit
Exercise primarily limited by angina, lung disease or neuromuscular disease
Systolic blood pressure <100 or >160 mmHg
Heart rate <50 or >110 min-1
Estimated glomerular filtration rate <30 ml/min
Liver function tests >3 times upper limit of normal
Serum phosphate below normal limit
Pregnant or breast-feeding women
Women of child-bearing potential unwilling to use recommended contraception methods during the study
Treatment with oral iron supplements (except multivitamins) in past year
Treatment with intravenous iron in past year
Treatment with erythropoiesis stimulating agents in the past year
Known intolerance of intravenous iron
History of anaphylaxis
Participation in another clinical trial within last 30 days.