Manganese-enhanced Magnetic Resonance Imaging (MEMRI) in Heart Failure With Preserved Ejection Fraction (MEMRI in HFpEF)

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.

Study Overview

• Status: Recruiting
• Conditions: Type 2 Diabetes; Heart Failure With Preserved Ejection Fraction
• Intervention / Treatment: Other: Minnesota Living with Heart Failure Questionnaire; Diagnostic test: Echocardiogram; Diagnostic test: Six-minute walk test; Diagnostic test: Manganese-enhanced MRI and 31-P magnetic resonance spectroscopy; Diagnostic test: Cardiovascular magnetic resonance scan; Diagnostic test: Blood tests

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

• Study Contact: Name: Gerry P McCann, MD; Phone Number: +44 (0)116 258 3038; Email: gpm12@leicester.ac.uk
• Study Contact Backup: Name: Abhishek Dattani, MBBS; Email: ad530@leicester.ac.uk

Study Locations

• United Kingdom
  • Leicester, United Kingdom
    • Recruiting
    • University of Leicester
    • Contact: Abhishek Dattani, MBBS; Email: ad530@leicester.ac.uk
    • Contact: Gerry P McCann, MD; Phone Number: 0116 2583038; Email: gpm12@leicester.ac.uk
    • Principal Investigator: Gerry P McCann, MD
    • Sub-Investigator: Abhishek Dattani, MBBS
    • Sub-Investigator: Gaurav S Gulsin, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Primary and secondary care patients

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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 Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
HFpEF with T2D; Participants with heart failure with preserved ejection fraction and type 2 diabetes	Other: Minnesota Living with Heart Failure Questionnaire; Self-administered, validated questionnaire to assess symptoms of heart failure; Diagnostic test: Echocardiogram; Resting transthoracic echocardiogram to exclude valvular pathology and the assess indices of systolic and diastolic function and speckle tracking for strain; Diagnostic test: Six-minute walk test; Standardised, objective assessment of exercise capacity; Diagnostic test: Manganese-enhanced MRI and 31-P magnetic resonance spectroscopy; 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).; Diagnostic test: Cardiovascular magnetic resonance scan; Scan including adenosine stress perfusion; Diagnostic test: Blood tests; 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
HFpEF without T2D; Participants with heart failure with preserved ejection fraction but without type 2 diabetes	Other: Minnesota Living with Heart Failure Questionnaire; Self-administered, validated questionnaire to assess symptoms of heart failure; Diagnostic test: Echocardiogram; Resting transthoracic echocardiogram to exclude valvular pathology and the assess indices of systolic and diastolic function and speckle tracking for strain; Diagnostic test: Six-minute walk test; Standardised, objective assessment of exercise capacity; Diagnostic test: Manganese-enhanced MRI and 31-P magnetic resonance spectroscopy; 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).; Diagnostic test: Cardiovascular magnetic resonance scan; Scan including adenosine stress perfusion; Diagnostic test: Blood tests; 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
Controls; Healthy volunteers without heart failure or type 2 diabetes	Other: Minnesota Living with Heart Failure Questionnaire; Self-administered, validated questionnaire to assess symptoms of heart failure; Diagnostic test: Echocardiogram; Resting transthoracic echocardiogram to exclude valvular pathology and the assess indices of systolic and diastolic function and speckle tracking for strain; Diagnostic test: Six-minute walk test; Standardised, objective assessment of exercise capacity; Diagnostic test: Manganese-enhanced MRI and 31-P magnetic resonance spectroscopy; 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).; Diagnostic test: Cardiovascular magnetic resonance scan; Scan including adenosine stress perfusion; Diagnostic test: Blood tests; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ki	Manganese influx constant as measured by MEMRI scan	Baseline

Secondary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: University of Leicester
• Investigators: Principal Investigator: Gerry P McCann, MD, University of Leicester; Principal Investigator: Abhishek Dattani, MBBS, University of Leicester

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): February 1, 2036

Study Registration Dates

• First Submitted: November 27, 2023
• First Submitted That Met QC Criteria: October 21, 2024
• First Posted (Actual): October 22, 2024

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 2; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Imaging; Diagnostic Techniques, Cardiovascular; Heart Function Tests; Cardiac Imaging Techniques; Ultrasonography; Exercise Test; Hematologic Tests; Echocardiography; Walk Test
• Other Study ID Numbers: 0883

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No