Myocardial Injury and Dysfunction Associated With COVID-19 Vaccination (MIDAVAX)

University of Colorado Denver (CU Denver)

Status: Completed

Conditions: COVID-19; Vaccine Reaction; Myocardial Injury

Study type: Observational

Funder types: Other; NIH

Identifiers

NCT05359250

3UM1AI068614-14S1 (U.S. NIH Grant/Contract)

21-4055

Details and patient eligibility

About

The overall goal of the study is to investigate the characteristics and potential mechanisms responsible for myocardial injury and dysfunction in patients after COVID-19 vaccination. Cardiac damage will be assessed with cardiac MRI and endomyocardial biopsy (EmBx) histopathology. Myocardial gene expression will be measured in RNA extracted from EmBxs mRNA abundance compared to nonfailing and failing control hearts.

Full description

To determine whether there is microvascular thrombosis-associated myocardial damage and dysfunction vs. inflammation or other changes in patients who, following administration of SARS-CoV-2 mRNA vaccine, develop evidence of myocardial injury typically diagnosed as "myocarditis" based on cardiac MRI findings.

Further, the degree of inflammatory reaction vs. microthrombotic injury to cardiac myocytes from biopsied myocardial tissue will be compared with biopsied myocardial tissue from control hearts. mRNA expression of the ACE2 and ITGA5 binding targets of SARS-Cov-2 Spike protein encoded by mRNA vaccines, as well as expression of other genes that may contribute to post-vaccine pro-thrombotic and pro-inflammatory states including Coagulation Factor 3 (F3, also known as tissue factor), ACE, AGTR1 and AGT) or a dysfunctional cardiac state (NPPB as a marker of pathologic remodeling) will be examined as candidate genes. Additional, global gene expression is being measured by RNA-Seq and microarray.

Enrollment: 10 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. age ≥18 years;

2. clear evidence of myocardial involvement including:

   1. High Sensitivity Troponin I value of (≥0.05 ng/ml (the 99% upper bound)) OR
   2. an LVEF < 50% OR
   3. ST-T change suggesting STEMI, NSTEMI or myopericarditis in the absence of coronary artery disease, OR
   4. new onset sustained VT or VF

3. Late gadolinium enhancement or edema on cMRI consistent with myocardial injury or inflammation.

4. Documentation of vaccination with mRNA-based COVID-19 vaccine.

5. No history of COVID-19, or a negative SARS-CoV-2 PCR or other FDA approved laboratory test within 1 week of enrollment.

6. Patient and/or legally authorized representative must be competent to understand and agree with informed consent form.

Exclusion criteria

1. Hemodynamic instability as evidenced by escalating doses of inotropic agents or vasopressors within the prior 24 hours
2. Respiratory instability as evidenced by increasing oxygen requirements over the 24 hours prior to consent or FiO2 requirement ≥ 60 %.
3. evidence that respiratory failure is the primary reason for myocardial dysfunction;
4. Moderate to severe pulmonary hypertension (mean PAP ≥35 mmHg);
5. INR >1.8 on no anticoagulation or contraindication to withdrawing anticoagulation;
6. platelets <100,000/mm3.
7. History of laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain reaction (PCR) testing or other commercial or public health assay.
8. Acute or chronic kidney disease with glomerular filtration rate < 30 ml/min.1.72m2

Trial design

10 participants in 1 patient group

Patients with evidence of myocardial injury related to vaccination with a SARS-CoV-2 mRNA vaccine

Description:

Patients who present with new symptoms of chest pain within 2-10 days following SARS-CoV-2 mRNA vaccination will be recruited up to 180 days following diagnosis. Patients will be screened using multiple methods and then provided informed consent. If patients are unable to consent, health care decision makers of patients who meet initial inclusion criteria will be approached for consent. Following informed consent, a cardiac MRI will be performed (if not performed prior) to assess myocardial function and potential damage. Patients will qualify on the basis of the presence of late-gadolinium enhancement and/or abnormal T1 mapping on MRI. The patient will then be taken to the cardiac catheterization lab where he/she will undergo endomyocardial biopsy and right heart catheterization (RHC) for candidate gene analysis. A blood sample will be collected to analyze circulating biomarkers associated with myocardial injury.