Manganese-Enhanced Magnetic Resonance Imaging (MEMRI) in Ischaemic, Inflammatory and Takotsubo Cardiomyopathy (MEMORY)

NCT04623788 | Completed DMC

• 1 other identifier: MR/T029153/1
• Study Type: observational
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

Manganese is a calcium analogue which actively enters viable cells with intact calcium-handling mechanisms and its uptake is evident by an increase in MRI-detectable T1 relaxivity of tissues. Mangafodipir is a novel manganese-based magnetic resonance imaging (MRI) contrast medium with unique biophysical properties that are ideal for application to cardiac imaging. Recent studies in man have demonstrated the utility of manganese-enhanced MRI (MEMRI) in assessing infarct size more accurately than with standard cardiac MRI protocols using gadolinium enhancement and have shown reduced myocardial manganese uptake in patients with cardiomyopathies suggesting abnormal calcium handling. Understanding the potential for myocardial recovery is key in guiding revascularisation therapies in ischaemic cardiomyopathy, in addition to novel therapies used in heart failure. Being able to monitor calcium handling and therefore myocardial function in different types of cardiomyopathies has the potential to guide management in these patients. The investigators here propose an investigational observational study of MEMRI to assess myocardial calcium handling in reversible causes of cardiomyopathy, namely ischaemic cardiomyopathy, myocarditis and takotsubo cardiomyopathy.

Conditions

Myocarditis; Takotsubo Cardiomyopathy; Reversible Coronary Ischaemia

Keywords

MRI; Manganese-enhanced MRI

Outcome Measures

Primary Outcomes (2)

• Myocardial T1 relaxation (ms)

  Measure Manganese T1 values in different disease processes

  2 years

• Manganese uptake (Ki)

  Calculate myocardial manganese uptake using T1 maps

  2 years

Secondary Outcomes (3)

• LV function in Ejection Fraction (EF)

  2 years

• LV Mass (grams)

  2 years

• LV Relaxation

  2 years

Study Arms (4)

Myocarditis

Twenty patients with acute myocarditis will be recruited if the diagnosis has been made by a cardiologist based on clinical, biochemical, electrographic and imaging data. This reflects the diagnostic criteria set out by the European Society of Cardiology (ESC) Task force 2013.

Diagnostic Test: Cardiac MRI

Takotsubo Cardiomyopathy

Twenty patients with takotsubo cardiomyopathy will be recruited. The diagnosis will be made according to the Mayo clinic and the European Society of Cardiology (ESC) Heart Failure Association criteria, including a normal coronary angiogram, typical appearances on cardiac imaging including ventriculography, and no evidence of fibrosis on cardiac magnetic resonance imaging.

Diagnostic Test: Cardiac MRI

Reversible Ischaemia

Forty patients who have undergone stress echocardiography or magnetic resonance imaging; twenty with positive (areas of reversible akinesis/hypokinesis during pharmacological stress), and twenty with a negative stress result (no reversible wall motion abnormalities during pharmacological stress) as per international guidelines. They will be matched for age and sex.

Diagnostic Test: Cardiac MRI

Healthy Volunteer

Twenty healthy volunteers of comparable age and sex to the other cohorts.

Diagnostic Test: Cardiac MRI

Interventions

Cardiac MRI DIAGNOSTIC_TEST

Cardiac MRI with contrast

Healthy Volunteer; Myocarditis; Reversible Ischaemia; Takotsubo Cardiomyopathy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Cohort 1 • Healthy adult with no known pre-existing medical conditions Cohort 2 * Positive stress- akinesis/hypokinesis on pharmacological stress * Negative stress- no inducible regional wall motion abnormalities on pharmacological stress Cohort 3 * New LV/RV dysfunction; including regional wall motion abnormalities (RWMA's) * New abnormal ECG findings (conduction, AVB, ST/T wave changes) * Raised biomarkers (TnI) * Tissue characteristics on MRI (myocardial oedema and typical LGE pattern) Cohort 4 * Normal/ Non-obstructive coronaries on angiography * Typical RWMA's based on echocardiography, MRI or left ventriculography

You may qualify if:

• All subjects to be entered must:
• ≥ 18 years of age
• if female, be non-pregnant as evidenced by a urine pregnancy test or post-menopausal or surgically sterile
• provide written informed consent after having received oral and written information about the study
• Cohort 1
• Healthy adult with no known pre-existing medical conditions
• Cohort 2
• Positive stress- akinesia/hypokinesis on pharmacological stress
• Negative stress- no inducible regional wall motion abnormalities on pharmacological stress
• Cohort 3
• New left/right ventricular dysfunction; including regional wall motion abnormalities (RWMA's)
• New abnormal ECG findings (conduction, atrio-ventricular block, ST/T wave changes)
• Raised biomarkers (troponin, TnI)
• Tissue characteristics on MRI (myocardial oedema and typical late gadolinium enhancement pattern)
• Cohort 4

You may not qualify if:

• The following apply to all participants:
• have a positive pregnancy test
• women who are breast feeding
• received an investigational drug or device within 30 days prior to administration of Mangafodipir
• have a history of ongoing drug abuse or alcoholism
• have a history of torsades or prolonged QT/QT corrected interval
• high degree atrioventricular block (second or third degree)
• atrial fibrillation or flutter
• have New York Heart Failure Association (NYHA) Grade IV heart failure
• have abnormal liver function tests (\> x3 ULN) or a history of liver disease
• have a baseline estimated glomerular filtration rate (eGFR) of \<30 mL/min/1.73m2)
• have uncontrolled hypertension (systolic blood pressure \>200 mmHg)
• have any contraindications to MRI, including implanted devices/pacemakers
• be maintained on either a calcium channel blocker or digoxin
• known diagnosis of pheochromocytoma

Sponsors & Collaborators

• University of Edinburgh: lead

Study Sites (1)

Royal Infirmary of Edinburgh

Edinburgh, EH164SB, United Kingdom

Location

Related Publications (1)

• Singh T, Joshi S, Kershaw LE, Baker AH, McCann GP, Dawson DK, Dweck MR, Semple SI, Newby DE. Manganese-Enhanced Magnetic Resonance Imaging in Takotsubo Syndrome. Circulation. 2022 Dec 13;146(24):1823-1835. doi: 10.1161/CIRCULATIONAHA.122.060375. Epub 2022 Nov 1.

  PMID: 36317524 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Bloods tests- FBC, renal function, liver function.

MeSH Terms

Conditions

Myocarditis; Takotsubo Cardiomyopathy

Condition Hierarchy (Ancestors)

Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Ventricular Dysfunction, Left; Ventricular Dysfunction

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2020
• First Posted: November 10, 2020
• Study Start: February 20, 2020
• Primary Completion: June 2, 2023
• Study Completion: June 2, 2023
• Last Updated: May 23, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)