Validation of myocarditis diagnoses in the Swedish patient register for analyses of potential adverse reactions to COVID-19 vaccines

  • Rolf Gedeborg Department of Efficacy and Safety 1, Division of Licensing, Medical Products Agency, Uppsala, Sweden; and Department of Surgical Sciences, Uppsala University, Sweden https://orcid.org/0000-0002-8850-7863
  • Lennart Holm Office of Use and Information, Division of Use and Information, Medical Products Agency, Uppsala, Sweden
  • Nils Feltelius Office of Use and Information, Division of Use and Information, Medical Products Agency, Uppsala, Sweden https://orcid.org/0000-0003-1460-4078
  • Anders Sundström Department of Drug Safety, Division of Use and Information, Medical Products Agency, Uppsala, Sweden https://orcid.org/0000-0003-2337-3371
  • Kai M. Eggers Department of Medical Sciences, Uppsala University, Uppsala, Sweden https://orcid.org/0000-0002-8806-5778
  • Marja-Leena Nurminen Department of Drug Safety, Division of Use and Information, Medical Products Agency, Uppsala, Sweden
  • Maria Grünewald Statistics group, Department of Efficacy and Safety 2, Division of Licensing, Medical Products Agency, Uppsala, Sweden https://orcid.org/0000-0002-9280-8140
  • Nicklas Pihlström Statistics group, Department of Efficacy and Safety 2, Division of Licensing, Medical Products Agency, Uppsala, Sweden
  • Björn Zethelius Office of Use and Information, Division of Use and Information, Medical Products Agency, Uppsala, Sweden https://orcid.org/0000-0002-1738-0834
  • Rickard Ljung Office of Use and Information, Division of Use and Information, Medical Products Agency, Uppsala, Sweden; and Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden https://orcid.org/0000-0002-0654-4530
Keywords: COVID-19 vaccines, myocarditis, diagnosis, validation study

Abstract

Background: Coronavirus disease 2019 (COVID-19) mRNA vaccines are associated with an increased risk of myocarditis using hospital discharge diagnoses as an outcome. The validity of these register-based diagnoses is uncertain.

Methods: Patient records for subjects < 40 years of age and a diagnosis of myocarditis in the Swedish National Patient Register were manually reviewed. Brighton Collaboration diagnosis criteria for myocarditis were applied based on patient history, clinical examination, laboratory data, electrocardiograms, echocardiography, magnetic resonance imaging and myocardial biopsy. Poisson regression was used to estimate incidence rate ratios, comparing the register-based outcome variable to validated outcomes. Interrater reliability was assessed by a blinded re-evaluation.

Results: Overall, 95.6% (327/342) of cases registered as myocarditis were confirmed (definite, probable or possible myocarditis according to Brighton Collaboration diagnosis criteria, positive predictive value 0.96 [95% CI 0.93–0.98]). Of the 4.4% (15/342) cases reclassified as no myocarditis or as insufficient information, two cases had been exposed to the COVID-19 vaccine no more than 28 days before the myocarditis diagnosis, two cases were exposed >28 days before admission and 11 cases were unexposed to the vaccine. The reclassification had only minor impact on incidence rate ratios for myocarditis following COVID-19 vaccination. In total, 51 cases were sampled for a blinded re-evaluation. Of the 30 randomly sampled cases initially classified as either definite or probably myocarditis, none were re-classified after re-evaluation. Of the in all 15 cases initially classified as no myocarditis or insufficient information, 7 were after re-evaluation re-classified as probable or possible myocarditis. This re-classification was mostly due to substantial variability in electrocardiogram interpretation.

Conclusion: This validation of register-based diagnoses of myocarditis by manual patient record review confirmed the register diagnosis in 96% of cases and had high interrater reliability. Reclassification had only a minor impact on the incidence rate ratios for myocarditis following COVID-19 vaccination.

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Published
2023-05-11
How to Cite
Gedeborg R., Holm L., Feltelius N., Sundström A., Eggers K. M., Nurminen M.-L., Grünewald M., Pihlström N., Zethelius B., & Ljung R. (2023). Validation of myocarditis diagnoses in the Swedish patient register for analyses of potential adverse reactions to COVID-19 vaccines. Upsala Journal of Medical Sciences, 128(1). https://doi.org/10.48101/ujms.v128.9290
Section
Original Articles