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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| HFpEF with T2D | Participants with heart failure with preserved ejection fraction and type 2 diabetes |
| |
| HFpEF without T2D | Participants with heart failure with preserved ejection fraction but without type 2 diabetes |
| |
| Controls | Healthy volunteers without heart failure or type 2 diabetes |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Minnesota Living with Heart Failure Questionnaire | Other | Self-administered, validated questionnaire to assess symptoms of heart failure |
|
| Measure | Description | Time Frame |
|---|---|---|
| Ki | Manganese influx constant as measured by MEMRI scan | Baseline |
| Measure | Description | Time Frame |
|---|---|---|
| T1 values | T1 values measured at 30 minutes post contrast on MEMRI scan | Baseline |
| Myocardial PCr/ATP ratio | Phosphocreatine-to-ATP ratio as measured by 31P-magnetic resonance spectroscopy |
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Inclusion Criteria:
Exclusion Criteria:
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Primary and secondary care patients
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Gerry P McCann, MD | Contact | +44 (0)116 258 3038 | gpm12@leicester.ac.uk | |
| Abhishek Dattani, MBBS | Contact | ad530@leicester.ac.uk |
| Name | Affiliation | Role |
|---|---|---|
| Gerry P McCann, MD | University of Leicester | Principal Investigator |
| Abhishek Dattani, MBBS | University of Leicester | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Leicester | Recruiting | Leicester | United Kingdom |
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Plasma will be stored for future analyses including established biomarkers and discovery studies such as proteomic, lipidomic, metabolomic and genomic analyses and other new methodologies that may be developed
| Echocardiogram | Diagnostic Test | Resting transthoracic echocardiogram to exclude valvular pathology and the assess indices of systolic and diastolic function and speckle tracking for strain |
|
| Six-minute walk test | Diagnostic Test | Standardised, objective assessment of exercise capacity |
|
| Manganese-enhanced MRI and 31-P magnetic resonance spectroscopy | Diagnostic Test | Using a 3-Tesla scanner, 31P magnetic resonance spectroscopy will be performed to obtain information regarding cardiac energetics. An intravenous infusion of manganese dipyridoxyl diphosphate (mangafodipir, MnDPDP) will be commenced at a rate of 1mL/min using a dose of 5µmol/kg (0.1mL/kg). |
|
| Cardiovascular magnetic resonance scan | Diagnostic Test | Scan including adenosine stress perfusion |
|
| Blood tests | Diagnostic Test | Full blood count, Urea and electrolytes, Liver function tests, Glucose and HbA1c, Insulin and C-peptide, NTproBNP, High sensitive troponin I, storage of plasma for future analyses |
|
| Baseline |
| Left ventricular ejection fraction | %, measured by CMR | Baseline |
| LV global longitudinal strain | %, measured by CMR | Baseline |
| LV global circumferential strain | %, measured by CMR | Baseline |
| LV PEDSR | 1/s, measured by CMR | Baseline |
| LV mass | grams, measured by CMR | Baseline |
| LV mass/volume ratio | Measured by CMR | Baseline |
| Myocardial fibrosis | CMR assessed markers of LV myocardial fibrosis (extracellular volume) | Baseline |
| Myocardial Perfusion | CMR assessed markers of perfusion (myocardial perfusion reserve) | Baseline |
| Associations of Ki with resting PCr/ATP | Univariate and multivariate models to look for association between Ki and PCr/ATP ratio | Baseline |
| Associations of exercise capacity with Ki and PCr/ATP in HFpEF | 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. | Baseline |
| Plasma biomarkers of metabolic dysregulation, fibrosis and inflammation | This exploratory outcome will assess the differences in a wide range of plasma biomarkers between groups and their association with Ki | Baseline |
| 10-year outcomes | 10-year outcomes including HF hospitalisation (time to first event and cumulative) and all-cause death. | Baseline |
| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| D004452 | Echocardiography |
| D000070857 | Walk Test |
| D006403 | Hematologic Tests |
| ID | Term |
|---|---|
| D057791 | Cardiac Imaging Techniques |
| D003952 | Diagnostic Imaging |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D014463 | Ultrasonography |
| D006334 | Heart Function Tests |
| D003935 | Diagnostic Techniques, Cardiovascular |
| D005080 | Exercise Test |
| D019411 | Clinical Laboratory Techniques |
| D008919 | Investigative Techniques |
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