MYocarditis and/or Pericarditis Following mRNA COVID-19 VACCination National Surveillance Study

Study Overview
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Brief Summary
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Myocarditis is inflammation of the heart muscle. Pericarditis is inflammation of the lining surrounding the heart muscle. Symptoms of these conditions can include pain in the chest and rapid or irregular heartbeat. There are many different causes for myocarditis and pericarditis including COVID-19 infection. The MYCOVACC study will identify patients using local screening strategies, including research communications, care provider referrals, and medical record review. The retrospective component of the study will collect information about patients suffering from vaccine associated myopericarditis and COVID-19 associated myopericarditis. Consenting patients will then be prospectively followed according to standard of care protocols. The main objectives of MYCOVACC are to describe the rate of major adverse cardiovascular events, functional outcomes including quality of life, and myocardial recovery through imaging.

Official Title
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MYocarditis and/or Pericarditis Following mRNA COVID-19 VACCination National Surveillance Study

Conditions
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Myocarditis, Myocarditis Acute, Pericarditis, Pericarditis Acute

Intervention / Treatment
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* Diagnostic Test: Stand of care ECG, Holter, MRI, ECHO, Quality of life questionnaire
* Other: Baseline Quality of Life questionnaire


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion criteria for vaccine associated myocarditis/pericarditis. COVID-19 vaccination within previous 42 days. AND At least one cardiac symptom of suspected myocarditis/pericarditis (Appendix 5). OR At least two non-specific symptoms (Appendix 5). OR In infants and young children, at least two non-specific pediatric symptoms (Appendix 5). OR No symptoms, but abnormal histopathology or a combination of abnormal cardiac biomarkers with abnormal cardiac imaging (echo or MRI). AND At least one of the following objective findings (Brighton Criteria case definitions, Appendices 1 to 5): Histopathologic examination of myocardial tissue (autopsy or endomyocardial biopsy) showed myocardial inflammation. Elevated myocardial biomarker (Troponin T, Troponin I, or CK-MB). Cardiac MRI abnormality. Echocardiographic abnormality. New or worsening arrhythmia on electrocardiogram, Holter monitor, or telemetry. Elevated inflammation biomarkers: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), hs-CRP, or D-Dimer. Physical examination pericardial friction rub or pulsus paradoxus. Pericardial fluid or inflammation by imaging (echo, MRI, or CT). Enlarged heart on chest radiograph. AND No alternative cause of presentation. e.g. infectious or autoimmune myocarditis. Inclusion criteria for COVID-19 associated myocarditis/pericarditis COVID-19 infection within the previous 42 days. AND Myocarditis/pericarditis as per Brighton Criteria for vaccine associated myocarditis/pericarditis. AND No alternative cause of presentation. Inclusion criteria alternative etiology myocarditis. Myocarditis/pericarditis as per Brighton Criteria for vaccine associated myocarditis/pericarditis. AND No alternative cause of presentation. Exclusion Criteria: For prospective invitation and follow-up, inability to provide informed consent. Consent will be sought from patients or their authorised substitute decision maker. Patients not fulfilling Brighton Criteria levels 1-3 will be excluded if they are level 4 (insufficient evidence for myocarditis) or Level 5 (not myocarditis) or have an alternative diagnosis such as myocardial infarction.
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 |
| --- | --- |
| mRNA COVID-19 vaccine associated myocarditis<br>Participants who had developed myocarditis within 42 days of getting a mRNA COVID-19 vaccine | Diagnostic Test: Stand of care ECG, Holter, MRI, ECHO, Quality of life questionnaire<br>* Stand of care ECG, Holter, MRI, ECHO, Quality of life questionnaire will be used to follow the clinical outcomes and patient reported outcomes to assess for study objectives<br>|
| mRNA COVID-19 vaccine associated pericarditis<br>Participants who had developed pericarditis within 42 days of getting a mRNA COVID-19 vaccine | Diagnostic Test: Stand of care ECG, Holter, MRI, ECHO, Quality of life questionnaire<br>* Stand of care ECG, Holter, MRI, ECHO, Quality of life questionnaire will be used to follow the clinical outcomes and patient reported outcomes to assess for study objectives<br>|
| COVID-19 infection associated myocarditis<br>Participants who had developed myocarditis within 42 days of being infected with the SARS-COV-2 virus | Diagnostic Test: Stand of care ECG, Holter, MRI, ECHO, Quality of life questionnaire<br>* Stand of care ECG, Holter, MRI, ECHO, Quality of life questionnaire will be used to follow the clinical outcomes and patient reported outcomes to assess for study objectives<br>|
| COVID-19 infection associated pericarditis<br>Participants who had developed pericarditis within 42 days of being infected with the SARS-COV-2 virus | Diagnostic Test: Stand of care ECG, Holter, MRI, ECHO, Quality of life questionnaire<br>* Stand of care ECG, Holter, MRI, ECHO, Quality of life questionnaire will be used to follow the clinical outcomes and patient reported outcomes to assess for study objectives<br>|
| Alternative etiology myocarditis<br>Any participants with myocarditis that is not associated with the mRNA COVID-19 vaccine or SARS-COV-2 viral infection | Other: Baseline Quality of Life questionnaire<br>* Only baseline quality of life questionnaires will be utilized in the alternative etiology myocarditis cohort as they will not be followed up in the study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite Major Adverse Cardiac Event (MACE) at 30 days post vaccination (preferred by cardiovascular community) and at 42 days post vaccination (preferred by vaccine monitoring investigators) | Including any of: Death from any cause. Ventricular arrhythmia (ventricular fibrillation or ventricular tachycardia). Heart block (type II or type III block). Heart failure (national guideline criteria). Left ventricular systolic dysfunction (left ventricular ejection fraction [LVEF] <55%). Cardiac tamponade. | From date of vaccination and up to 3 years | 
| Recovery of cardiac function in patients with previously documented abnormal cardiac function | Patients with Left Ventricular Ejection Fraction (LVEF)<55% during anytime at baseline, with LVEF increase by 5% from worst baseline measurement | Through study completion, an average of 3 years | 
| Quality of life using validated instruments at baseline, 3 months, 12 months, and annually | Quality of life: EQ-5D-5L questionnaire for adults or EQ-5D-Y questionnaire for children. | Through study completion, an average of 3 years | 
| Depression and anxiety using validated instruments at baseline, 3 months, 12 months, and annually | Depression and anxiety data: PHQ-9 and GAD-7. | Through study completion, an average of 3 years | 
| Physical activity using validated instruments at baseline, 3 months, 12 months, and annually | Physical activity: International Activity Questionnaire. | Through study completion, an average of 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Individual components of primary composite endpoint at 30 days and 42 days post mRNA COVID-19 vaccination? |  | From date of vaccination for up to three years | 
| Rate of atrial arrhythmias after mRNA COVID-19 vaccination? |  | From date of vaccination for up to three years | 
| Rate of all-cause and cardiovascular mortality after mRNA COVID-19 vaccination? |  | From date of vaccination for up to three years | 
| Rate of all-cause and cardiovascular hospitalization after mRNA COVID-19 vaccination? |  | From date of vaccination for up to three years | 
| Rate of recurrence of myocarditis/pericarditis after mRNA COVID-19 vaccination? |  | From date of vaccination for up to three years | 
| Rate of constrictive pericarditis after mRNA COVID-19 vaccination? |  | From date of vaccination for up to three years |