New study uncovers a higher prevalence of heart scarring in young males after COVID-19 mRNA vaccination, raising concerns about long-term outcomes despite mild initial symptoms of vaccine-associated myocarditis.

Study: Cardiac manifestations and outcomes of COVID-19 vaccine-associated myocarditis in the young in the USA: longitudinal results from the Myocarditis After COVID Vaccination (MACiV) multicenter study. Image Credit: pedro7merino/Shutterstock.com

In a recent study published in EClinicalMedicine, a team of scientists from the United States (U.S.) examined the longitudinal outcomes and clinical characteristics of coronavirus disease 2019 (COVID-19) vaccine-associated myocarditis or C-VAM and evaluated the risk of myocardial injury and cardiovascular outcomes due to C-VAM in the pediatric population and young adults.

Background

The rapid development of COVID-19 vaccines has been instrumental in controlling the spread and severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and mitigating the COVID-19 pandemic.

One type of COVID-19 vaccine used widely in the U.S. was the messenger ribonucleic acid (mRNA) vaccine, in which a copy of the viral mRNA that encodes a viral protein, such as the SARS-CoV-2 spike protein, is used to trigger a long-lasting immune response.

One of the rare complications of the COVID-19 mRNA vaccine is myocarditis, especially in the pediatric population. Furthermore, cardiac magnetic resonance (CMR) images involving late gadolinium enhancement or LGE are being used increasingly to study the chronic scarring and myocardial injury that occurs in cases of childhood myocarditis.

While the implications and overall prognosis for myocardial injury linked to C-VAM in young patients are unclear, LGE is believed to be associated with a high risk of arrhythmia, heart failure, cardiomyopathy, and even cardiac death.

About the study

In the present study, the researchers examined the cardiac characteristics of C-VAM based on LGE observed in CRM images and evaluated the clinical features and cardiovascular outcomes of C-VAM in a cohort of young adults, adolescents, and children.

This retrospective observational study was conducted in 38 institutions in the U.S. It involved individuals below the age of 30 years who were diagnosed with acute myocarditis after they received the COVID-19 mRNA vaccine.

The diagnosis of acute myocarditis was based on abnormal biomarkers, clinical symptoms, and cardiovascular imaging. The study excluded any individuals with alternate causes for the myocarditis diagnosis.

The researchers obtained demographic data, medical history, and hospital records of the participants. The participants were characterized into younger and older age groups corresponding to between 5 and 15 years and between 16 and 30 years, respectively, based on the vaccine roll-out phases.

They also compared the cases of pediatric myocarditis with another pediatric COVID-19 complication — multisystem inflammatory syndrome in children (MIS-C).

The researchers analyzed various clinical biomarkers, such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), to detect systemic inflammation, brain natriuretic peptide (BNP), and N-terminal pro-B-type natriuretic peptide indicative of heart failure, and troponin levels to detect heart damage.

Furthermore, CMR scans and Holter monitoring results were examined for indicators such as hyperemia, scarring, injury, and myocardial edema.

The findings from the CMR scans were cross-verified by a team of expert cardiologists, and LGE and other imaging parameters were used to assess the extent of myocardial injury.

The researchers then used statistical analyses to investigate the association between LGE in CMR scans and patient characteristics. Additionally, outcomes such as arrhythmia, cardiac symptoms, heart failure, transplantation, and mortality were also examined.

Results

The study found that a majority of the C-VAM patients were adolescents, of which 95% had received the Pfizer-BioNTech mRNA vaccine.

In comparison, the remaining 5% had received the Moderna COVID-19 mRNA vaccine. The symptoms of myocarditis commonly appeared after the second dose of the vaccine and included elevated levels of troponin and chest pain in 96% of the cases.

The patients generally presented with symptoms within a week of vaccination, and most of them (90%) required hospitalization for close to three days.

However, only 2% of the hospitalized patients required mechanical ventilation or inotropic support. Furthermore, none of the patients tested positive for SARS-CoV-2 infections, needed a heart transplant, or died.

Close to 60% of the patients had abnormalities in the electrocardiographs (ECG), and 17% showed mild ventricular systolic dysfunction. Additionally, the CMR scans of almost 72% of the patients showed signs of LGE and myocardial edema.

The LGE was more likely to be found in older and male patients, and elevated levels of CRP and troponin were associated with a higher probability of LGE and a decrease in the left ventricular ejection fraction.

Compared to patients with MIS-C, C-VAM patients were older and male. Furthermore, while MIS-C patients had higher levels of systemic inflammation and needed more intensive care than those with C-VAM, myocardial scarring was more severe, and LGE was more common in patients with C-VAM.

Conclusions

Overall, the results showed that C-VAM had milder clinical characteristics and was more common in older male adolescents after the second dose of the mRNA vaccine.

However, the persistent presence of myocardial scarring raises concerns about the long-term outcomes of C-VAM, highlighting the need for more research on the implications of LGE in C-VAM patients.