Myocarditis in children.Etiology. Pathogenesis. Epidemiology. Clinical presentation

Readers will be presented with a series of articles on myocarditis in children, which are based on clinical guidelines developed by a group of authors on this topic. Myocarditis is an inflammatory myocardial disease characterized by a wide range of clinical manifestations — from minor to sudden cardiac death. Given the absence of pathognomonic symptoms, as well as the similarity of manifestations in the onset with common childhood diseases such as respiratory distress, gastrointestinal diseases, infectious pathology, specialists often overlook the likelihood of a diagnosis of “myocarditis”, which causes a late start of therapy and an adverse outcome. Considering that myocarditis accounts for 12% of cases of sudden cardiac death in adolescents and young adults, suspicion of this disease in differential diagnosis in children with nonspecific symptoms and disease progression may be the key to the formation of a proper treatment strategy. Despite significant advances in the study of myocarditis in both adults and children, there are still many unresolved issues. The purpose of this article is to highlight the current view of the etiology, pathogenesis, epidemiology and clinical features in children with various types of myocarditis in order to increase the knowledge of practitioners for better clinical management of patients with myocarditis.

1. Richardson P, McKenna W, Bristow M, et al. Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the definition and classification of cardiomyopathies. Circulation. 1996;93(5):841–842. https://doi.org/10.1161/01.cir.93.5.841

2. Caforio AL, Pankuweit S, Arbustini E, 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):2636–2648, 2648a–2648d. https://doi.org/10.1093/eurheartj/eht210

3. Elamm C, Fairweather D, Cooper LT. Pathogenesis and diagnosis of myocarditis. Heart. 2012;98:835–840. https://doi.org/10.1136/heartjnl-2012-301686

4. Trachtenberg BH, Hare JM. Inflammatory cardiomyopathic syndromes. Circ Res. 2017;121(7):803–818. https://doi.org/10.1161/CIRCRESAHA.117.310221

5. Pollack A, Kontorovich AR, Fuster V, Dec GW. Viral myocarditisdiagnosis, treatment options, and current controversies. Nat Rev Cardiol. 2015;12(11):670–680. https://doi.org/10.1038/nrcardio.2015.108

6. Rroku A, Kottwitz J, Heidecker B. Update on myocarditis — what we know so far and where we may be heading. Eur Heart J Acute Cardiovasc Care. 2020;22:2048872620910109. https://doi.org/10.1177/2048872620910109

7. Schultz JC, Hilliard AA, Cooper LT Jr, Rihal CS. Diagnosis and treatment of viral myocarditis. Mayo Clin Proc. 2009;84(11):1001–1009. https://doi.org/10.1016/S0025-6196(11)60670-8

8. Canter CE, Simpson KE. Diagnosis and treatment of myocarditis in children in the current era. Circulation. 2014;129(1):115–128. https://doi.org/10.1161/CIRCULATIONAHA.113.001372

9. Breinholt JP, Moulik M, Dreyer WJ, et al. Viral epidemiologic shift in inflammatory heart disease: the increasing involvement of parvovirus B19 in the myocardium of pediatric cardiac transplant patients. J Heart LungTransplant.2010;29(7):739–746.https://doi.org/10.1016/j.healun.2010.03.003

10. Sleem B, Zareef R, Bitar F, Arabi M. Myocarditis in COVID-19: a focus on the pediatric population. Am J Cardiovasc Dis. 2023;13(3):138–151.

11. Dionne A, Dahdah N. Myocarditis and Kawasaki disease. Int J Rheum Dis. 2018;21(1):45–49. https://doi.org/10.1111/1756185X.13219

12. Bejiqi R, Retkoceri R, Maloku A, et al. The Diagnostic and Clinical Approach to Pediatric Myocarditis: A Review of the Current Literature. Open Access Maced J Med Sci. 2019;7(1):162–173. https://doi.org/10.3889/oamjms.2019.010

13. McMurray JC, May JW, Cunningham MW, Jones OY. Multisystem Inflammatory Syndrome in Children (MIS-C), a Post-viral Myocarditis and Systemic Vasculitis-A Critical Review of Its Pathogenesis and Treatment. Front Pediatr. 2020;8:626182. https://doi.org/10.3389/fped.2020.626182

14. Dhar D, Dey T, Samim MM, et al. Systemic inflammatory syndrome in COVID-19-SISCoV study: systematic review and metaanalysis. Pediatr Res. 2022;91(6):1334–1349. https://doi.org/10.1038/s41390-021-01545-z

15. Karatolios K, Pankuweit S, Maisch B. Diagnosis and treatment of myocarditis: the role of endomyocardial biopsy. Curr Treat Options Cardiovasc Med. 2007;9(6):473–481. https://doi.org/10.1007/s11936-007-0042-1

16. Curigliano G, Lenihan D, Fradley M, et al. ESMO Guidelines Committee. Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations. Ann Oncol. 2020;31(2):171–190. https://doi.org/10.1007/s11936-007-0042-1

17. Gauntt C. Coxsackievirus experimental heart diseases. Front Biosci. 2003;8(5):e23–e35. https://doi.org/10.2741/928

18. Engler RJM, Nelson MR, Collins LC Jr, et al. A Prospective Study of the Incidence of Myocarditis/Pericarditis and New Onset Cardiac Symptoms following Smallpox and Influenza Vaccination. PLoS One. 2015;10(3):e0118283. https://doi.org/10.1371/journal.pone.0118283

19. Mason JW. Myocarditis and dilated cardiomyopathy: an inflammatory link. Cardiovasc Res. 2003;60(1):5–10. https://doi.org/10.1016/s0008-6363(03)00437-1

20. Schultheiss HP, Baumeier C, Aleshcheva G, et al. Viral MyocarditisFrom Pathophysiology to Treatment. J Clin Med. 2021;10(22):5240. https://doi.org/10.3390/jcm10225240

21. Baggio С, Gagno G, Porcari A, et al. Myocarditis: Which Role for Genetics? Curr Cardiol Rep. 2021;23(6):58–63. https://doi.org/10.1007/s11886-021-01492-5

22. Ammirati E, Frigerio M, Adler ED, et al. Management of Acute Myocarditis and Chronic Inflammatory Cardiomyopathy: An Expert Consensus Document. Circ Heart Fail. 2020;13(11):e007405. https://doi.org/10.1161/CIRCHEARTFAILURE.120.007405

23. Caforio ALP, Malipiero G, Marcolongo R, Iliceto S. Myocarditis: A Clinical Overview. Curr Cardiol Rep. 2017;19:63. https://doi.org/10.1007/s11886-017-0870-x

24. Chang Y-J, Hsiao H-J, Hsia S-H, et al. Analysis of clinical parameters and echocardiography as predictors of fatal pediatric myocarditis. PLoS One. 2019;14(3):e0214087. https://doi.org/10.1371/journal.pone.0214087

25. Matsuura H, Ichida F, Saji T, et al. Clinical features of acute and fulminant myocarditis in children. Circ J. 2016;80(11):2362–2368. https://doi.org/10.1253/circj.CJ-16-0234

26. Arola A, Pikkarainen E, Sipila J, et al. Occurrence and Features of Childhood Myocarditis: A Nationwide Study in Finland. J Am Heart Assoc. 2017;6(11):e005306. https://doi.org/10.1161/JAHA.116.005306

27. Lipshultz SE, Sleeper LA, Towbin JA, et al. The incidence of pediatric cardiomyopathy in two regions of the United States. N Engl J Med. 2003;348(17):1647–1655. https://doi.org/10.1056/NEJMoa021715

28. Myocarditis in children: incidence, clinical characteristics and outcomes. In: Myocarditis Foundation: Official website. July 29, 2020. Available online: https://www.myocarditisfoundation.org/myocarditis-in-children-incidence-clinical-characteristics-andoutcomes. Accessed on January 08, 2024.

29. Butts RJ, Boyle GJ, Deshpande SR, et al. Characteristics of clinically diagnosed pediatric myocarditis in a contemporary multicenter cohort. PediatrCardiol.2017;38(6):1175–1182. https://doi.org/10.1007/s00246-017-1638-1

30. Ghelani SJ, Spaeder MC, Pastor W, et al. Demographics, trends, and outcomes in pediatric acute myocarditis in the United States, 2006 to 2011. Circ Cardiovasc Qual Outcomes. 2012;5(5):622– 627. https://doi.org/10.1161/CIRCOUTCOMES.112.965749

31. Klugman D, Berger JT, Sable CA, et al. Pediatric patients hospitalized with myocarditis: a multi-institutional analysis. Pediatr Cardiol. 2010; 31(2):222–228. https://doi.org/10.1007/s00246-009-9589-9

32. Durani Y, Giordano K, Goudie BW. Myocarditis and pericarditis in children. Pediatr Clin North Am.2010;57(6):1281–1303. https://doi.org/10.1016/j.pcl.2010.09.012

33. Neagu O, Rodríguez AF, Callon D, et al. Myocarditis Presenting as Sudden Death in Infants and Children: A Single Centre Analysis by ESGFOR Study Group. Pediatr Dev Pathol. 2021;24(4):327–336. https://doi.org/10.1177/10935266211007262

34. Meyer L, Stubbs B, Fahrenbruch C, et al. Incidence, causes, and survival trends from cardiovascular-related sudden cardiac arrest in children and young adults 0 to 35 years of age: a 30-year review. Circulation. 2012;126(11):1363–1372. https://doi.org/10.1161/CIRCULATIONAHA.111.076810

35. Nugent AW, Daubeney PE, Chondros P, et al. The epidemiology of childhoodcardiomyopathyinAustralia.NEnglJMed.2003;348(17):1639– 1646. https://doi.org/10.1056/NEJMoa021737

36. Vetter VL, Covington TM, Dugan PN, et al. Cardiovascular deaths in children: General overview from the National Center for the Review and Prevention of Child Deaths. Am Heart J. 2015;169(3):426–437. https://doi.org/10.1016/j.ahj.2014.11.014

37. Lv J, Han B, Wang C, et al. The Clinical Features of Children With Acute Fulminant Myocarditis and the Diagnostic and Follow-Up Value of Cardiovascular Magnetic Resonance. Front Pediatr. 2019;7:388. https://doi.org/10.3389/fped.2019.00388

38. Lieberman EB, Hutchins GM, Herskowitz A, et al. Clinicopathologic description of myocarditis. J Am Coll Cardiol. 1991;18(7):1617– 1626. https://doi.org/10.1016/0735-1097(91)90493-s

39. Ginsberg F, Parrillo JE. Fulminant myocarditis. Crit Care Clin. 2013;29(3):465–483. https://doi.org/10.1016/j.ccc.2013.03.004

40. Russo M, Ismibayli Z, Antonaci S, Piccinni GC. Eosinophilic myocarditis: from etiology to diagnostics and therapy. Minerva Cardiol Angiol. 2023. https://doi.org/10.23736/S27245683.23.06297-X

41. Abe T, Tsuda E, Miyazaki A, et al. Clinical characteristics and long-term outcome of acute myocarditis in children. Heart Vessels. 2013;28(5):632–638. https://doi.org/10.1007/s00380012-0296-8

42. Degener F, Opgen-Rhein B, Böhne M, et al. Four-Year Experience of the German Multicenter Registry for Pediatric Patients with Suspected Myocarditis: MYKKE. Thorac Cardiovasc Surg. 2018;66(S02):S111– S138. https://doi.org/10.1055/s-0038-1628324

43. Putschoegl A, Auerbach S. Diagnosis, Evaluation, and Treatment of Myocarditis in Children. Pediatr Clin N Am. 2020;67(5):855–874. https://doi.org/10.1016/j.pcl.2020.06.013

44. Arutyunov GP, Paleev FN, Moiseeva OM, et al. 2020 Clinical practice guidelines for Myocarditis in adults. Russian Journal of Cardiology. 2021;26(11):4790. (In Russ). https://doi.org/10.15829/1560-4071-2021-4790]

45. Bang V, Ganatra S, Shah SP, et al. Management of Patients With Giant Cell Myocarditis: JACC Review Topic of the Week. J Am Coll Cardiol. 2021;77(8):1122–1134. https://doi.org/10.1016/j.jacc.2020.11.074

46. Dinis P, Teixeira R, Puga L, et al. Eosinophilic Myocarditis: Clinical Case and Literature Review. Arq Bras Cardiol. 2018;110(6):597– 599. https://doi.org/10.5935/abc.20180089

47. Price S, Bodys A, Celinska A, et al. Interlibrary Loan The value of chosen diagnostic tools in evaluating myocarditis in children and adolescents. Pediatr Pol J Paediatr. 2018;93(5):389–395. https://doi.org/10.5114/polp.2018.78899

48. Rodriguez-Gonzalez M, Sanchez-Codez MI, LubianGutierrez M, et al. Clinical presentation and early predictors for poor outcomes in pediatric myocarditis: A retrospective study. World J Clin Cases. 2019;7(5):548–561. https://doi.org/10.12998/wjcc.v7.i5.548

49. Suthar D, Dodd DA, Godown J. Identifying Non-invasive Tools to Distinguish Acute Myocarditis from Dilated Cardiomyopathy in Children. Pediatr Cardiol. 2018;39(6):1134–1138. https://doi.org/10.1007/s00246-018-1867-y

50. Wu HP, Lin MJ, Yang WC, et al. Predictors of Extracorporeal Membrane Oxygenation Support for Children with Acute Myocarditis. Biomed Res Int. 2017;2017:8. https://doi.org/doi.org/10.1155/2017/2510695

51. Freund MW, Kleinveld G, Krediet TG, et al. Prognosis for neonates with enterovirus myocarditis. Arch Dis Child Fetal Neonatal Ed. 2010;95(3):F206–F212. https://doi.org/10.1136/adc.2009.165183

52. Tunuguntla H, Jeewa A, Denfield SW. Acute Myocarditis and Pericarditis in Children. Pediatr Rev. 2019;40(1):14–25. https://doi.org/10.1542/pir.2018-0044

53. Levine MC, Klugman D, Teach SJ. Update on myocarditis in children. Curr Opin Pediatr. 2010;22:278–283. https://doi.org/10.1097/MOP.0b013e32833924d2

54. Sagar S, Liu PP, Cooper LT Jr. Myocarditis. Lancet. 2012;379(9817): 738–747. https://doi.org/10.1016/S0140-6736(11)60648-X

55. Freedman SB, Haladyn JK, Floh A, et al. Pediatric myocarditis: emergency department clinical findings and diagnostic evaluation. Pediatrics. 2007;120(6):1278–1285. https://doi.org/10.1542/peds.2007-1073