Manganese-enhanced Magnetic Resonance Imaging (MEMRI) in Heart Failure With Preserved Ejection Fraction
- Conditions
- Heart Failure With Preserved Ejection FractionType 2 Diabetes
- Registration Number
- NCT06652763
- Lead Sponsor
- University of Leicester
- Brief Summary
Heart failure with preserved ejection fraction (HFpEF) is a condition in which the heart cannot fill with blood effectively. As a result, people with HFpEF suffer fatigue, breathlessness, and develop swollen limbs. The condition often requires multiple admissions to hospital and is associated with a marked loss of lifespan.
Despite being so common, very little is known about why people develop HFpEF and there are hardly any known treatments. Type 2 diabetes (T2D) is a major risk factor for HFpEF, and people with both HFpEF and diabetes are at a heightened risk of hospitalisation and premature death. It is unclear why the combination of diabetes and HFpEF is particularly harmful. This may be related to the hearts of people with type 2 diabetes being unable to take up the mineral calcium properly, as well as due to their hearts being less energy efficient. Both of these are vital to heart muscle pumping and filling, but until recently it has not been possible to assess these in humans.
New advances in heart MRI scans, with dedicated scanner techniques and dyes (manganese contrast), now allow extremely detailed pictures of heart structure, function, calcium uptake and energy efficiency, all during the same scan. The investigators will enlist 40 volunteers with HFpEF (20 with T2D and 20 without T2D), and up to 20 healthy volunteers, to undergo a heart MRI scan with manganese contrast to assess calcium uptake and energy efficiency. This will allow the comparison of people with HFpEF with and without T2D, to see how their hearts are different to healthy volunteers.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 60
- Capacity to provide informed consent
- Symptoms (e.g. breathlessness, orthopnoea, ankle swelling, fatigue), signs (e.g. elevated jugular venous pressure, peripheral oedema, third heart sound) or established diagnosis of HF with LV ejection fraction ≥ 50%, or
- Meets HFpEF diagnostic criteria in accordance with the HFA-PEFF diagnostic algorithm form the Heart Failure Association of the European Society of Cardiology, in which a score ≥5 points confirms diagnosis of HFpEF
- Known diagnosis of Type 1 Diabetes
- Pregnancy or breast-feeding or females of child bearing age without a negative pregnancy test
- Receiving an investigational drug or device within 30 days prior to participating in the study
- Decompensated heart failure or pulmonary oedema
- History of prolonged corrected QT interval or torsades de pointes
- Second- or third-degree atrioventricular block
- Abnormal liver function tests (> 3x upper limit of normal) or history of liver disease
- Baseline eGFR < 30mL/min/1.73m2
- Any contraindications to MRI including implanted devices/pacemakers
- Severe native valve disease, restrictive cardiomyopathy, constrictive pericarditis or hypertrophic cardiomyopathy, myocarditis or takotsubo cardiomyopathy.
- Recent myocardial infarction within the previous 3 months
- Known diagnosis of pheochromocytoma
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Ki Baseline Manganese influx constant as measured by MEMRI scan
- Secondary Outcome Measures
Name Time Method LV mass/volume ratio Baseline Measured by CMR
Myocardial fibrosis Baseline CMR assessed markers of LV myocardial fibrosis (extracellular volume)
Myocardial Perfusion Baseline CMR assessed markers of perfusion (myocardial perfusion reserve)
Associations of Ki with resting PCr/ATP Baseline Univariate and multivariate models to look for association between Ki and PCr/ATP ratio
LV mass Baseline grams, measured by CMR
T1 values Baseline T1 values measured at 30 minutes post contrast on MEMRI scan
Myocardial PCr/ATP ratio Baseline Phosphocreatine-to-ATP ratio as measured by 31P-magnetic resonance spectroscopy
Left ventricular ejection fraction Baseline %, measured by CMR
LV global longitudinal strain Baseline %, measured by CMR
LV global circumferential strain Baseline %, measured by CMR
LV PEDSR Baseline 1/s, measured by CMR
Associations of exercise capacity with Ki and PCr/ATP in HFpEF Baseline Ki values as assessed by MEMRI, myocardial PCr/ATP as measured by 31P-MRS and six minute walk test distance. Associations will be assessed using univariate and multivariate models.
Plasma biomarkers of metabolic dysregulation, fibrosis and inflammation Baseline This exploratory outcome will assess the differences in a wide range of plasma biomarkers between groups and their association with Ki
10-year outcomes Baseline 10-year outcomes including HF hospitalisation (time to first event and cumulative) and all-cause death.
Trial Locations
- Locations (1)
University of Leicester
🇬🇧Leicester, United Kingdom