Multi-modality Imaging & Immunophenotyping of COVID-19 Related Myocardial Injury (MIIC-MI)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Cardiovascular Diseases; COVID19
• Intervention / Treatment: Diagnostic test: Non-invasive cardiac imaging

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 Type: Observational
• Enrollment (Anticipated): 20

Contacts and Locations

Study Locations

• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Cambridge Univeristy Hospitals NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with a history of COVID-19 and cardiovascular involvement

Description

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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Study group; Patients with COVID-19 and cardiac Troponin elevation	Diagnostic test: Non-invasive cardiac imaging; Cardiac MRI ± CT coronary angiography ± Cardiac PET/MRI (68Ga-DOTATATE or 18F-FDG)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Cambridge
• Collaborators: Cambridge University Hospitals NHS Foundation Trust; Wellcome Trust; British Heart Foundation

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Actual): December 1, 2022
• Study Completion (Anticipated): August 1, 2023

Study Registration Dates

• First Submitted: May 27, 2020
• First Submitted That Met QC Criteria: May 29, 2020
• First Posted (Actual): June 2, 2020

Study Record Updates

• Last Update Posted (Actual): March 29, 2023
• Last Update Submitted That Met QC Criteria: March 26, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Cardiovascular Diseases
• Other Study ID Numbers: A09565

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No