Clinical trial NCT05359250: Myocardial Injury and Dysfunction Associated With COVID-19 Vaccination
Official title: Evaluation of Myocardial Dysfunction Due to mRNA-based SARS-CoV-2 Vaccines
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Myocardial Injury
COVID-19
Vaccine Reaction
Keywords: COVID-19
mRNA vaccines
myocardial injury
myocarditis
gene expression
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: American Heart Association
name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2022-05-03
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Ten patients with new symptoms of chest discomfort and biomarkers of myocardial injury that occurred 2-10 days following SARS-CoV-2 mRNA vaccination will be recruited up to 180 days following diagnosis. Patients will have no other known etiology for myocardial injury other than recent mRNA COVID vaccine exposure. Patients may be referred from inpatient or outpatient settings, from across the UCHealth system, but will be recruited in-person at University of Colorado Hospital.

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Myocardial damage
timeFrame: clinical follow up for at least 30 days following endomyocardial biopsy
measure: Histopathological changes assessed by light- and electron-microscopy in myocardial tissue
timeFrame: clinical follow up for at least 30 days following endomyocardial biopsy
measure: Myocardial mRNA expression
timeFrame: clinical follow up for at least 30 days following endomyocardial biopsy
Secondary outcomes:
measure: Myocardial mRNA expression of additional genes measured by both RNA-Seq and microarray.
timeFrame: clinical follow up for at least 30 days following endomyocardial biopsy
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Natasha Altman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Colorado, Denver
name: Bristow Michael, MD/PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Patone M, Mei XW, Handunnetthi L, Dixon S, Zaccardi F, Shankar-Hari M, Watkinson P, Khunti K, Harnden A, Coupland CAC, Channon KM, Mills NL, Sheikh A, Hippisley-Cox J. Risks of myocarditis, pericarditis, and cardiac arrhythmias associated with COVID-19 vaccination or SARS-CoV-2 infection. Nat Med. 2022 Feb;28(2):410-422. doi: 10.1038/s41591-021-01630-0. Epub 2021 Dec 14.
citation: Oster ME, Shay DK, Su JR, Gee J, Creech CB, Broder KR, Edwards K, Soslow JH, Dendy JM, Schlaudecker E, Lang SM, Barnett ED, Ruberg FL, Smith MJ, Campbell MJ, Lopes RD, Sperling LS, Baumblatt JA, Thompson DL, Marquez PL, Strid P, Woo J, Pugsley R, Reagan-Steiner S, DeStefano F, Shimabukuro TT. Myocarditis Cases Reported After mRNA-Based COVID-19 Vaccination in the US From December 2020 to August 2021. JAMA. 2022 Jan 25;327(4):331-340. doi: 10.1001/jama.2021.24110.