Heart Failure, Iron Deficiencies
Conditions
Keywords
Ferric derisomaltose, Non-ischaemic heart failure, Chronic heart failure, Iron deficiency, Left ventricular failure, Iron homeostasis, Cardiac MRI, Cardiac Magnetic resonance imaging
Brief summary
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.
Detailed description
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.
Interventions
See group descriptions
Sponsors
Portsmouth Hospitals NHS Trust
University Hospital Southampton NHS Foundation Trust
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ejection Fraction quantified on Cardiac Magnetic Resonance Imaging | 24 Hours and 30 days | Changes in Ejection Fraction quoted in (%) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| T2 Mapping quantified on Cardiac Magnetic Resonance Imaging | 24 Hours and 30 Days | Changes in T2 Parametric Mapping quantified in (msec) |
| Extracellular Volume (ECV) Fraction quantified on Cardiac Magnetic Resonance Imaging | 24 Hours and 30 Days | Changes in ECV Fraction quoted in (%) |
| Ventricular Volumes quantified on Cardiac Magnetic Resonance Imaging | 24 Hours and 30 Days | Changes in left and right ventricular volumes quantified in (ml) |
| Indexed Ventricular Volume quantified on Cardiac Magnetic Resonance Imaging | 24 Hours and 30 Days | Changes in indexed left and right ventricular volumes. Weight and Height will be combined to calculate Body Surface Area (m2). Left Ventricular Volume in (ml) will be divided by Body Surface Area to give indexed value (ml/m2) |
| Strain analysis as quantified on Cardiac Magnetic Resonance Imaging | 24 Hours and 30 Days | Changes in strain as assessed by feature tracking on cardiac magnetic resonance imaging |
| Quality of Life assessment: KCCQ-12 questionnaire | 24 Hours and 30 Days | Changes in Kansas City Cardiomyopathy Questionnaire. Four sub-domains: Physical limitation, Symptom Frequency, Quality of life and social limitations. Scores range from 0 - 100, with higher scores reflecting a better heart status. |
| T1 Mapping quantified on Cardiac Magnetic Resonance Imaging | 24 Hours and 30 days | Changes in T1 Parametric Mapping quantified in (msec) |
| Musculoskeletal function test: Hand grip test | 24 Hours and 30 Days | Changes in Isometric Grip Force in (KG) |
| Haemoglobin | 30 Days | Laboratory Blood Test |
| High Sensitivity troponin | 24 Hours and 30 Days | Laboratory Blood Test |
| Phosphate | 24 Hours and 30 Days | Laboratory Blood Test |
| N-terminal pro B type natriuretic peptide (NTproBNP) | 30 Days | Laboratory Blood Test |
| Submaximal Exercise Test: Six Minute Walk Test | 24 Hours and 30 Days | Changes in distance walked (meters) in six minutes |
Countries
United Kingdom
Contacts
Primary ContactFlett
Backup ContactRachael Pulham
Outcome results
None listed