Multi-modality Imaging & Immunophenotyping of COVID-19 Related Myocardial Injury

Study Overview
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Brief Summary
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Cardiovascular involvement in coronavirus disease-2019 (COVID-19) encompasses a wide range of vascular and myocardial pathologies, including both acute and long-term sequelae. The MIIC-MI study aims to investigate mechanisms of cardiac injury in COVID-19 using multi-modality imaging and immunophenotyping to better understand the link with adverse patient outcomes.

Detailed Description
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Cardiovascular involvement in coronavirus disease-2019 (COVID-19) encompasses a wide range of vascular and myocardial pathologies, including both acute and long-term sequelae. Cardiac Troponin elevation, a marker of acute myocardial injury, has been identified in up to 28% of hospitalized patients with coronavirus disease 2019 (COVID-19) and is associated with an increased mortality risk. However, the predominant aetiology of myocardial injury relating to COVID-19 remains unclear. The Troponin leak could either signify direct cardiac involvement in COVID-19 or serve as a non-specific marker of a severe systemic insult. There have been numerous reports of acute myocarditis in patients with COVID-19. Other contributory mechanisms of cardiac Troponin elevation in patients with COVID-19 that are also driven by a proinflammatory state include acute myocardial infarction due to atherosclerotic plaque rupture (type 1) or demand ischemia (type 2), endothelial and microvascular dysfunction, immune-mediated activation of coagulation and fibrinolytic systems, and stress cardiomyopathy. Longer-term effects of COVID-19 on the cardiovascular system are also unknown. Many individuals with post-acute sequalae of SARS-CoV-2 infection (or 'long COVID') have unexplained cardiac symptoms. Patients may also present with new-onset heart failure after COVID-19, which is not attributed to another cause. We aim to identify patterns of myocardial injury in COVID-19 using non-invasive multi-modality cardiac imaging, paired with cytokine/chemokine testing, immunophenotyping of peripheral blood cells and coagulation profiles. A better understanding of the mechanisms underlying the excess mortality risk attributable to myocardial injury in COVID-19 is needed and may help to improve patient care.

Official Title
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Multi-modality Imaging & Immunophenotyping of COVID-19 Related Myocardial Injury

Conditions
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COVID19, Cardiovascular Diseases

Intervention / Treatment
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* Diagnostic Test: Non-invasive cardiac imaging


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients >18 years old Confirmed COVID-19 infection AND Troponin I elevation >99th percentile of upper reference limit OR new-onset heart failure OR unexplained cardiac symptoms Able to give written, informed consent Exclusion Criteria: Women of child-bearing potential not using adequate contraception Contra-indication to MRI scanning Contrast allergy or contrast-nephropathy Chronic kidney disease (eGFR <30 mL/min/1.73 m2) Previous myocardial infarction Uncontrolled atrial fibrillation Uncontrolled chronic inflammatory disease Severe lymphopenia (<0.2 x109/L) Treatment with immunomodulatory therapies within the last month (excluding inhaled or topical steroid therapy) Any medical condition, in the opinion of the investigator, that prevents the participant from lying flat during scanning, or from participating in the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Study group<br>Patients with COVID-19 and cardiac Troponin elevation | Diagnostic Test: Non-invasive cardiac imaging<br>* Cardiac MRI ± CT coronary angiography ± Cardiac PET/MRI (68Ga-DOTATATE or 18F-FDG)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnosis | Number of participants with a diagnosis of COVID-19 related myocarditis, Type 1 or 2 myocardial infarction and/or other mechanism of cardiac injury confirmed by multi-modality imaging. | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune markers | Comparison of a panel of inflammatory cytokines and immune cell profiles in patients stratified by cardiac diagnosis/imaging findings | Baseline | 
| Coagulation markers | Comparison of a panel of blood coagulation markers in patients stratified by cardiac diagnosis/imaging findings | Baseline |