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Compared to the many unsettled questions regarding the mechanisms and predisposing factors of myocarditis associated with COVID-19 mRNA vaccines, the actual cardiac presentation and clinical management of these cases were relatively straightforward.

Based on published reports and passive surveillance data, patients with myocarditis "invariably" present with chest pain approximately 2-3 days after their second mRNA vaccine dose, according to Biykem Bozkurt, MD, PhD, of Baylor College of Medicine and DeBakey VA Medical Center in Houston, and colleagues.

Other typical aspects of their cardiac presentation include:

• Elevated cardiac troponin levels hit their peak at around 3 days post-vaccination and fell over time
• C-reactive protein levels largely elevated, later decreasing alongside troponin
• Abnormal ECGs with ST-segment elevations in most cases
• Cardiac MRI findings suggestive of myocarditis (e.g., late gadolinium enhancement and myocardial edema)
• Echocardiograms abnormal only in 40% of cases, with few people having left ventricular ejection fractions under 50%
• BNP or NT-proBNP levels only mildly elevated in two-thirds of patients
• No evidence of thrombotic events, thrombocytopenia, or disseminated intravascular coagulation

With or without treatment, the "clinical course appears mild" and almost all patients had their symptoms resolve, and imaging and lab findings improve, Bozkurt and colleagues reported in a review in .

Patients commonly received NSAIDs, steroids, and colchicine for treatment of vaccine-associated myocarditis. A few were treated with IV immunoglobulin and aspirin, and others were given beta-blocker and angiotensin converting enzyme inhibitor therapy for left ventricular systolic dysfunction.

"Though there are no prospective or randomized studies, it is reasonable to consider these therapies, especially in patients with significant symptoms and findings," the authors said.

They added that it would be "reasonable" to restrict strenuous physical activity until all abnormalities resolve.

Myocarditis and pericarditis are rare events after coronavirus vaccination: rates are approximately 12.6 chart-confirmed cases per million doses of second dose mRNA vaccine among 12- to 39-year-olds, according to a CDC estimate cited by Bozkurt's group.

In data from the Vaccine Adverse Event Reporting System (VAERS) through June 11, there were 1,226 reports of probable myocarditis or pericarditis cases after approximately 300 million COVID-19 mRNA vaccine doses were administered.

Ultimately, despite the likely link between mRNA vaccines and myocarditis, the mRNA vaccines continue to show a favorable benefit-risk profile and are still recommended for individuals age 12 years and older, Bozkurt and colleagues said.

COVID-19 infection itself is associated with myocarditis and long-lasting illness in some individuals.

Yet questions remain as to why myocarditis would develop in uninfected patients getting an mRNA vaccine.

One theory is that some people have immune systems that may detect the mRNA as an antigen, resulting in "activation of pro-inflammatory cascades and immunological pathways, which may play a role in development of myocarditis as part of a systemic reaction in certain individuals," Bozkurt's group wrote.

It is also unclear why vaccinated men appear to be more susceptible to myocarditis -- or if such a sex difference really exists.

Bozkurt and colleagues' analysis of VAERS through June 6 revealed 6,235 reported cases of chest pain, with 69% of these cases reported in women as opposed to men.

"Despite a higher prevalence of chest pain in women, diagnostic evaluation, including ECG, laboratory biomarkers, echocardiography and MRI was performed and reported more often in males compared with female patients presenting with chest pain after COVID vaccination," the group observed.

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