The aim of this study is to observe the effect of intravenous ferric derisomaltose in participants with non-ischaemic heart failure (LVEF<40%), iron deficiency (TSATS<20%) and established on heart failure therapy including Sodium-glucose cotransporter 2 inhibitors (SGLT2i). Participants will undergo baseline laboratory blood tests, cardiac magnetic resonance imaging (cMRI), six-minute walk test, musculoskeletal function test and Kansas City Cardiomyopathy Questionnaire (KCCQ). These investigations will be repeated at 24 hours and 30 days after the administration of intravenous ferric derisomaltose.

Heart failure is a neuro-endocrine syndrome in which patients report symptoms of breathlessness and lethargy accompanied with signs of fluid overload.

Iron deficiency is very common in heart failure, affecting up to 50% of patients. Its presence in this population is associated with worsening symptoms and increased risk of death. Human clinical trials have shown that administering intravenous iron improves quality of life and exercise tolerance. The European Society Guidelines gives a 1A class recommendation for intravenous iron replacement in symptomatic heart failure patients.

Iron is an essential micro-nutrient required in mitochondrial metabolism, handling of reactive oxygen species and cellular metabolism. Heart failure leads to a pro inflammatory state, resulting in reduced gastrointestinal absorption, and inhibition of iron mobilisation. Mouse models have shown reversal of cardiac fibrosis, cardiac remodelling, and reduction in the pro inflammatory state when treated with intravenous iron. Similarly iron deficient human cardiomyocytes show adverse remodelling and altered function reversed with iron repletion.

The investigators aim to recruit 16 participants with non-ischaemic heart failure, established on optimal medical therapy, including SGLT2i therapy, for four weeks prior to the start of the trial. Initial baseline investigations will include: cMRI, six-minute walk test, hand grip strength test, laboratory blood tests and a KCCQ-12. Intravenous ferric derisomaltose will be given as standard of care. These investigations will be repeated at 24 hours and at 30 days after the administration of intravenous ferric derisomaltose.

The study aims to observe changes pre and post administration of intravenous derisomaltose in the following:

• Changes in cardiac function and parametric measurements (T1/T2) as assessed by cardiac magnetic resonance imaging.
• Changes in high sensitivity troponin, N Terminal pro-Brain Natriuretic Peptide (NT pro-BNP) and serum phosphate levels.
• Changes in the submaximal exercise test (six-minute walk) and musculoskeletal function test (hand grip test).
• Changes in heart failure symptoms as assessed by KCCQ Questionnaire.

Inclusion Criteria:

• Participants capable of giving informed consent.
• Aged 18yrs and above.
• Diagnosed with heart failure and a reduction of their ejection fraction < 40% by any modality.
• Non ischaemic cardiomyopathy as determined by baseline cardiac magnetic resonance imaging.
• Iron deficient per this definition: Transferrin saturations < 20%.
• Established on Heart failure therapy including SGLT2i therapy for a minimum of four weeks prior to recruitment.
• New York Heart Association score of I - III class.

Exclusion Criteria:

• New York Heart Association classification Score >IV
• Ischaemic cardiomyopathy
• Chronic kidney stage: Estimated Glomerular Filtration Rate (eGFR) < 30
• Requirement for renal dialysis
• Atrial fibrillation / atrial flutter
• Non cardiac and cardiac palliative diagnosis
• Active cancer diagnosis
• Moderate to severe valvular heart disease
• Cardiac electronic implantable device: Cardiac resynchronization therapy, Implantable cardioverter-defibrillator, left ventricular assist device
• Cardiac & non cardiac transplant participants
• Myocardial infarction, Percutaneous Coronary Intervention, Coronary Artery Bypass Graft surgery in the last 30 days
• Complex congenital heart disease
• Pregnancy

Participants with non-ischaemic cardiomyopathy with a left ventricular function less than 40% and iron deficient as per the following criteria: Transferrin saturations < 20%