Iron deficiency may contribute to exercise intolerance by altering mitochondrial oxidative capacity in skeletal muscle. Functional iron deficiency is common in heart failure patients, but the relationship to exercise intolerance and mitochondrial oxidative capacity is unknown. This is a pilot study to determine the feasibility of the use of specialized 31P-MRS and MRI techniques for measurement of skeletal muscle bioenergetics in patients with heart failure with and without functional iron deficiency.

This study will obtain pilot feasibility data to explore the relationship between blood biomarkers of functional iron deficiency and skeletal muscle mitochondrial oxidative capacity with 31P-magnetic resonance spectroscopy (MRS) and imaging in heart failure patients.

Twenty (20) subjects will be recruited from the clinical practice of the NYU Advanced Cardiac Therapeutics group at NYU Langone Medical Center.

Twenty (20) subjects will be recruited from the practice of the NYU Advanced Cardiac Therapeutics group at NYU Langone Medical Center. The study will require a maximum of four (4) visits over a period of five (5) weeks. Eligibility for Visits 2-4 will be determined by the screening criteria in Visit 1. It is anticipated that 50% of the screened subjects at Visit 1 will be eligible to participate in Visit 2. Eligibility for participation in Visits 3 and 4 will be determined by the results of the iron biomarkers obtained at Visit 2. We anticipate that 50% of the subjects at Visit 2 will be eligible to participate in Visits 3 and 4. Only subject with functional iron deficiency will participate in Visits 3 and 4. There is no clinical care component for this study.

Inclusion Criteria:

• Able and willing to provide written informed consent
• Age 21-80 years
• Chronic heart failure >3 months with NYHA Class I-III symptoms

Exclusion Criteria:

• Presence of implantable defibrillator, permanent pacemaker not designed for safe use in 3T MRI stud
• Metallic implant or implants that are deemed not suitable for MRI scan on 3T
• Aneurysm clips, cochlear implants, presence of shrapnel in strategic locations, and metal in the eye
• Known claustrophobia or any other history of intolerance of MRI procedure
• Treated diabetes mellitus or hemoglobin A1c (HbA1c) >6.5%
• Any hospitalization <60 days
• Myocardial infarction or stroke < 6 months
• Estimated glomerular filtration rate <30 ml/min
• Weight <50 or >120 kg
• Systolic blood pressure <90 mmHg or > 160 mmHg
• Heart rate <50 or >100 beats per minute
• Resting oxygen saturation on room air <92%
• Hemoglobin <11 g/dl
• Serum phosphate below normal range (<2.4 mg/dl)
• Liver function tests (AST, ALT, Alk Phos, or Total Bilirubin) >twice upper limit of normal range
• Pregnancy or current breastfeeding
• Exercise limitation primarily due to valvular heart disease, lung disease, neuromuscular disease, or joint disease
• History of asthma
• History of anaphylaxis
• Known history of intolerance to any formulation of intravenous iron