Abstract 4138507: Uncovering Risk Factors for Myocarditis and Cardiac Arrhythmia in Youth Post-SARS-CoV-2 Infection: Insights from the N3C Database and Advanced Machine Learning

Background: SARS-CoV2 infection has been associated with cardiovascular consequences, including myocarditis and cardiac arrhythmias. Myocarditis secondary to SARS-CoV2 infection and cardiac arrhythmias may often go unrecognized and can present with late and nonspecific symptoms. Predicting those at risk allows for prompt treatment and prevention of their potentially life-threatening consequences. Methods: The National COVID Cohort Collaborative (N3C) database was used to identify patients aged 0-30 years with COVID-19 index date between 1/1/2020 and 3/31/2022, whose sites provided data for at least six months beyond the index date. Outcomes included myocarditis and new arrythmias within 6 months of the index visit. Patients with known cardiac comorbidities were excluded. Predictors included gender, race, COVID severity as an ordinal scale, vaccination status, clinical comorbidities, and Area Deprivation Index (ADI). The data were stratified by age groups (0-4, 5-17, 18-30). Random forest models were used for data analysis and SHapley Additive exPlanations (SHAP) method was applied to optimize results. These analyses were conducted using the NCATS N3C Data Enclave. Results: Of the 1,487,741 patients in our study population, 4,105 (0.28%) had the measured outcomes; 404 had myocarditis only, 3,634 had arrhythmia only and 67 had both. Severity of COVID (SHAP 0.2344 for 0-4 years, 0.2114 for 5-17, 0.1370 for 18-30) was identified as the most important risk factor for de-novo myocarditis and arrhythmias overall. Increase in ADI (indicating lower socioeconomic status) was the second most important risk factor for the 0-4 and 5-17 age groups (SHAP: 0.0370, 0.0223). Among the 18-30 age group, race (SHAP 0.0321) and gender (SHAP 0.0289) were the second and third most important risk factors, with White and Black patients more likely to develop an event and Hispanic patients less likely. Women were less likely to develop a cardiac outcome than men. Conclusion: The severity of COVID was identified as the most important risk factor for the occurrence of myocarditis or cardiac arrhythmia within 6 months of infection. ADI, race, and gender were also identified as important, though less influential, risk factors.