Validation of myocarditis diagnoses in the Swedish patient register for analyses of potential adverse reactions to COVID-19 vaccines
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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References
2. Caforio AL, Pankuweit S, Arbustini E, Basso C, Gimeno-Blanes J, Felix SB, et al. Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J 2013; 34(33): 2636–48, doi: 10.1093/eurheartj/eht210
3. Sexson Tejtel SK, Munoz FM, Al-Ammouri I, Savorgnan F, Guggilla RK, Khuri-Bulos N, et al. Myocarditis and pericarditis: case definition and guidelines for data collection, analysis, and presentation of immunization safety data. Vaccine 2022; 40(10): 1499–511. doi: 10.1016/j.vaccine.2021.11.074
4. Ljung R, Sundström A, Grünewald M, Backman C, Feltelius N, Gedeborg R, et al. The profile of the COvid-19 VACcination register SAFEty study in Sweden (CoVacSafe-SE). Ups J Med Sci 2021; 126, e8136. doi: 10.48101/ujms.v126.8136
5. Ludvigsson JF, Andersson E, Ekbom A, Feychting M, Kim JL, Reuterwall C, et al. External review and validation of the Swedish national inpatient register. BMC Public Health 2011; 11: 450. doi: 10.1186/1471-2458-11-450
6. The National Board of Health and Welfare (Socialstyrelsen). Classification ICD-10 Stockholm, Sweden. 2022. Available from: https://www.socialstyrelsen.se/statistik-och-data/klassifikationer-och-koder/icd-10/ [cited 13 September 2022].
7. Fu M, Kontogeorgos S, Thunström E, Zverkova Sandström T, Kroon C, Bollano E, et al. Trends in myocarditis incidence, complications and mortality in Sweden from 2000 to 2014. Sci Rep 2022; 12(1): 1810. doi: 10.1038/s41598-022-05951-z
8. Ammirati E, Lupi L, Palazzini M, Hendren NS, Grodin JL, Cannistraci CV, et al. Prevalence, characteristics, and outcomes of COVID-19-associated acute myocarditis. Circulation 2022; 145(15): 1123–39. doi: 10.1161/circulationaha.121.056817
9. Husby A, Hansen JV, Fosbøl E, Thiesson EM, Madsen M, Thomsen RW, et al. SARS-CoV-2 vaccination and myocarditis or myopericarditis: population based cohort study. BMJ (Clin Res ed) 2021; 375: e068665. doi: 10.1136/bmj-2021-068665
10. Gargano JW, Wallace M, Hadler SC, Langley G, Su JR, Oster ME, et al. Use of mRNA COVID-19 vaccine after reports of myocarditis among vaccine recipients: update from the advisory committee on immunization practices - United States, June 2021. Morb Mortal Wkly Report 2021; 70(27): 977–82. doi: 10.15585/mmwr.mm7027e2
11. Cooper LT, Baughman KL, Feldman AM, Frustaci A, Jessup M, Kuhl U, et al. The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology Endorsed by the Heart Failure Society of America and the Heart Failure Association of the European Society of Cardiology. Eur Heart J 2007; 28(24): 3076–93. doi: 10.1093/eurheartj/ehm456
12. Ferreira VM, Schulz-Menger J, Holmvang G, Kramer CM, Carbone I, Sechtem U, et al. Cardiovascular magnetic resonance in nonischemic myocardial inflammation: expert recommendations. J Am Coll Cardiol 2018; 72(24): 3158–76. doi: 10.1016/j.jacc.2018.09.072
13. Pawlukiewicz AJ, Geringer MR, Davis WT, Nassery DR, April MD, Streitz MJ, et al. Interrater agreement of the HEART score history component: a chart review study. J Am Coll Emerg Physicians Open 2022; 3(3): e12732. doi: 10.1002/emp2.12732
14. Mehta S, Granton J, Lapinsky SE, Newton G, Bandayrel K, Little A, et al. Agreement in electrocardiogram interpretation in patients with septic shock. Crit Care Med 2011; 39(9): 2080–6. doi: 10.1097/CCM.0b013e318222720e
15. Cook DA, Oh S-Y, Pusic MV. Accuracy of physicians’ electrocardiogram interpretations: a systematic review and meta-analysis. JAMA Intern Med 2020; 180(11): 1461–71. doi: 10.1001/jamainternmed.2020.3989
16. Sharff KA, Dancoes DM, Longueil JL, Johnson ES, Lewis PF. Risk of myopericarditis following COVID-19 mRNA vaccination in a large integrated health system: a comparison of completeness and timeliness of two methods. Pharmacoepidemiol Drug Saf 2022; 31(2): 921–925. doi: 10.1002/pds.5439
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