Myocardial Injury and Dysfunction Associated With COVID-19 Vaccination

NCT05359250 | Completed DMC

• 2 other identifiers: 21-40553UM1AI068614-14S1
• Study Type: observational
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Myocardial Injury; COVID-19; Vaccine Reaction

Keywords

COVID-19; mRNA vaccines; myocardial injury; myocarditis; gene expression

Outcome Measures

Primary Outcomes (3)

• Myocardial damage

  Initial clinical diagnosis of myocardial injury or myocarditis will be confirmed by cardiac MRI. Specific findings of late gadolinium enhancement and abnormal T1-signals within the myocardium consistent with acute injury, inflammation or edema will be evaluated.

  clinical follow up for at least 30 days following endomyocardial biopsy

• Histopathological changes assessed by light- and electron-microscopy in myocardial tissue

  Determining the histopathologic changes present in the endomyocardial biopsies of patients with COVID-19 vaccine-induced myocardial injury. Assessment of the standard H\&E stains will include evaluation for presence and degree of inflammation within the myocardium, presence of microvascular thrombi within vasculature, and evidence of myocardial damage. The trichrome, iron, and Congo red stains will be used to evaluate for the presence of fibrosis, iron, or amyloid, respectively. Electron microscopy will be employed to examine cardiac myocyte and small blood vessel architectures.

  clinical follow up for at least 30 days following endomyocardial biopsy

• Myocardial mRNA expression

  Measure myocardial mRNA expression of candidate genes involved in Spike protein binding and cell entry (ACE2 and ITGA5), the renin-angiotensin system (ACE, AGT, AGTR1), initiation of coagulation (F3/TF) and pathologic myocardial remodeling (NPPB).

  clinical follow up for at least 30 days following endomyocardial biopsy

Secondary Outcomes (1)

• Myocardial mRNA expression of additional genes measured by both RNA-Seq and microarray.

  clinical follow up for at least 30 days following endomyocardial biopsy

Study Arms (1)

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

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• age ≥18 years;
• clear evidence of myocardial involvement including:
• High Sensitivity Troponin I value of (≥0.05 ng/ml (the 99% upper bound)) OR
• an LVEF \< 50% OR
• ST-T change suggesting STEMI, NSTEMI or myopericarditis in the absence of coronary artery disease, OR
• new onset sustained VT or VF
• Late gadolinium enhancement or edema on cMRI consistent with myocardial injury or inflammation.
• Documentation of vaccination with mRNA-based COVID-19 vaccine.
• No history of COVID-19, or a negative SARS-CoV-2 PCR or other FDA approved laboratory test within 1 week of enrollment.
• Patient and/or legally authorized representative must be competent to understand and agree with informed consent form.

You may not qualify if:

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

Sponsors & Collaborators

• University of Colorado, Denver: lead
• American Heart Association: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Related Publications (2)

• 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.

  PMID: 34907393 BACKGROUND

• 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.

  PMID: 35076665 BACKGROUND

Biospecimen

Retention: NONE RETAINED

Right heart catheterization will be performed and a small sample from right ventricle distal septum will be collected. The endomyocardial biopsy sample will be processed for RNA extraction and gene expression.

MeSH Terms

Conditions

COVID-19; Myocarditis

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Cardiomyopathies; Heart Diseases; Cardiovascular Diseases

Study Officials

• Natasha Altman, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

• Bristow Michael, MD/PhD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2022
• First Posted: May 3, 2022
• Study Start: May 12, 2021
• Primary Completion: December 30, 2024
• Study Completion: December 30, 2024
• Last Updated: April 4, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)