Manganese-Enhanced Magnetic Resonance Imaging of the Myocardium

Inclusion criteria

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

Additionally, cohort-specific inclusion criteria as follows:

Healthy Volunteers

• Healthy adult with no known pre-existing medical conditions

Ischaemic Cardiomyopathy

• Ischaemic cardiomyopathy as diagnosed by reduced LV ejection fraction (≤40%) secondary to one or more ischaemic events
• Angiographically demonstrated LMS, LAD disease, or ≥2 vessel disease
• NHYA class I-III heart failure, with stable symptoms not requiring change to diuretic therapy in the preceding month

Dilated Cardiomyopathy

• Dilated cardiomyopathy characterised with echocardiography by reduced left ventricular systolic function with impaired systolic function (ejection fraction <40%).
• NHYA class I-III heart failure, with stable symptoms not requiring change to diuretic therapy in the preceding month

Hypertrophic Cardiomyopathy

• Established diagnosis of hypertrophic cardiomyopathy
• Left ventricular wall thickness ≥15mm in any segment
• Repolarisation abnormalities on 12-lead electrocardiogram NHYA class I-III heart failure, with stable symptoms not requiring change to diuretic therapy in the preceding month

Exclusion criteria

• 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 known hypersensitivity to ondansetron or other selective serotonin 5-HT3 receptor blockers
• have a history of ongoing drug abuse or alcoholism
• have a history of torsades or prolonged QT/QTc interval
• atrioventricular block (1st, 2nd or 3rd degree)
• atrial fibrillation or flutter
• have NYHA Grade IV heart failure
• have abnormal liver function tests or a history of liver disease
• have a baseline eGFR (estimated glomerular filtration rate) of <30 mL/min)
• have uncontrolled hypertension
• have any contraindications to MRI, including implanted devices/pacemakers
• be maintained on either a calcium channel blocker or digoxin
• known diagnosis of phaeochromocytoma

Additionally, cohort-specific exclusion criteria as follows:

Hypertrophic Cardiomyopathy

• Coronary artery stenosis >50% any vessel
• Previous myocardial infarction
• Previous alcohol septal ablation
• Moderate or severe aortic stenosis (mean gradient >25 mmHg, mean AVA ≤1.5 cm2 or peak velocity ≥3 m/sec),