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

• Stand of care ECG, Holter, MRI, ECHO, Quality of life questionnaire (Diagnostic test): 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
• Baseline Quality of Life questionnaire (Other): 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

Primary outcomes

• 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) [From date of vaccination and up to 3 years]: 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.
• Recovery of cardiac function in patients with previously documented abnormal cardiac function [Through study completion, an average of 3 years]: Patients with Left Ventricular Ejection Fraction (LVEF)<55% during anytime at baseline, with LVEF increase by 5% from worst baseline measurement
• Quality of life using validated instruments at baseline, 3 months, 12 months, and annually [Through study completion, an average of 3 years]: Quality of life: EQ-5D-5L questionnaire for adults or EQ-5D-Y questionnaire for children.
• Depression and anxiety using validated instruments at baseline, 3 months, 12 months, and annually [Through study completion, an average of 3 years]: Depression and anxiety data: PHQ-9 and GAD-7.
• Physical activity using validated instruments at baseline, 3 months, 12 months, and annually [Through study completion, an average of 3 years]: Physical activity: International Activity Questionnaire.

Secondary outcomes

• 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]

Sex: All

Inclusion Criteria:

* Inclusion criteria for vaccine associated myocarditis/pericarditis.

  1. COVID-19 vaccination within previous 42 days. AND
  2. 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
  3. At least one of the following objective findings (Brighton Criteria case definitions, Appendices 1 to 5):

     1. Histopathologic examination of myocardial tissue (autopsy or endomyocardial biopsy) showed myocardial inflammation.
     2. Elevated myocardial biomarker (Troponin T, Troponin I, or CK-MB).
     3. Cardiac MRI abnormality.
     4. Echocardiographic abnormality.
     5. New or worsening arrhythmia on electrocardiogram, Holter monitor, or telemetry.
     6. Elevated inflammation biomarkers: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), hs-CRP, or D-Dimer.
     7. Physical examination pericardial friction rub or pulsus paradoxus.
     8. Pericardial fluid or inflammation by imaging (echo, MRI, or CT).
     9. Enlarged heart on chest radiograph.

     AND
  4. No alternative cause of presentation. e.g. infectious or autoimmune myocarditis.
* Inclusion criteria for COVID-19 associated myocarditis/pericarditis

  1. COVID-19 infection within the previous 42 days.

     AND
  2. Myocarditis/pericarditis as per Brighton Criteria for vaccine associated myocarditis/pericarditis.

     AND
  3. No alternative cause of presentation.

Inclusion criteria alternative etiology myocarditis.

1. Myocarditis/pericarditis as per Brighton Criteria for vaccine associated myocarditis/pericarditis.

   AND
2. 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.

• Study Protocol (PDF, 2023-04-12)

• Nathaniel Hawkins, MD, Principal investigator, Vancouver General Hospital