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

Completed

• Conditions: Cardiovascular Diseases; COVID19
• Interventions: Diagnostic Test: Non-invasive cardiac imaging

• Registration Number: NCT04412369
• Lead Sponsor: University of Cambridge

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2020-05-27
• Study First Submitted QC: 2020-05-29
• Study First Posted: 2020-06-02
• Study Start: 2020-07-01
• Primary Completion: 2022-12-01
• Study Completion: 2023-08-01
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-18
• Last Update Posted: 2024-07-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 21

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Study group	Non-invasive cardiac imaging	Patients with COVID-19 and cardiac Troponin elevation

Primary Outcome Measures

Name	Time	Method
Diagnosis	Baseline	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.

Secondary Outcome Measures

Name	Time	Method
Coagulation markers	Baseline	Comparison of a panel of blood coagulation markers in patients stratified by cardiac diagnosis/imaging findings
Immune markers	Baseline	Comparison of a panel of inflammatory cytokines and immune cell profiles in patients stratified by cardiac diagnosis/imaging findings

Trial Locations

Locations (1)

Cambridge Univeristy Hospitals NHS Foundation Trust; 🇬🇧 Cambridge, United Kingdom