Management of Myocarditis in Children: The Current Situation

  • Brigitte Stiller
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 609)

Acute myocarditis is an important cause of morbidity and mortality in children. It is defined as inflammation of the myocardium in association with non-ischaemic myocellular necrosis (Aretz 1987). Despite its clear-cut definition, the classification, diagnosis and treatment of myocarditis remain the subject of ongoing debate. The use of endomyocardial biopsy, which has become routine, has helped to better define the natural history of human myocarditis and to clarify clinicopathological correlations.


Dilate Cardiomyopathy Immune Globulin Endomyocardial Biopsy Ventricular Assist Device Mechanical Circulatory Support 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Aretz HT. (1987). Myocarditis: the Dallas criteria. Hum Pathol, 18:619–624.PubMedCrossRefGoogle Scholar
  2. Badorff C and Knowlton KU. (2004). Dystrophin disruption in enterovirus-induced myocarditis and dilated cardiomyopathy: from bench to bedside. Med Microbiol Immunol (Berl), 193:121–126.CrossRefGoogle Scholar
  3. Bergelson JM, Cunningham JA, Droguett G, Kurt-Jones EA, Krithivas A, Hong JS, Horwitz MS, Crowell RL, and Finberg RW. (1997). Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5. Science, 275:1320–1323.PubMedCrossRefGoogle Scholar
  4. Chen JW, Zhou B, Yu QC, Shin SJ, Jiao K, Schneider MD, Baldwin HS, and Bergelson JM. (2006). Cardiomyocyte-specific deletion of the coxsackievirus and adenovirus receptor results in hyperplasia of the embryonic left ventricle and abnormalities of sinuatrial valves. Circ Res, 98:923–930.PubMedCrossRefGoogle Scholar
  5. Cook LN. (2004). Update on extracorporeal membrane oxygenation. Paediatr Respir Rev, 5(Suppl A):S329–S337.PubMedCrossRefGoogle Scholar
  6. Doolan A, Langlois N, and Semsarian C. (2004). Causes of sudden cardiac death in young Australians. Med J Aust, 180:110–112.PubMedGoogle Scholar
  7. Duggal B, Pratap U, Slavik Z, Kaplanova J, and Macrae D. (2005). Milrinone and low cardiac output following cardiac surgery in infants: is there a direct myocardial effect? Pediatr Cardiol, 26:642–645.PubMedCrossRefGoogle Scholar
  8. Duncan BW, Bohn DJ, Atz AM, French JW, Laussen PC, and Wessel DL. (2001). Mechanical circulatory support for the treatment of children with acute fulminant myocarditis. J Thorac Cardiovasc Surg, 122:440–448.PubMedCrossRefGoogle Scholar
  9. English RF, Janosky JE, Ettedgui JA, and Webber SA. (2004). Outcomes for children with acute myocarditis. Cardiol Young, 14:488–493.PubMedCrossRefGoogle Scholar
  10. Fabre A and Sheppard MN. (2006). Sudden adult death syndrome and other non-ischaemic causes of sudden cardiac death. Heart, 92:316–320.PubMedCrossRefGoogle Scholar
  11. Fenster BE, Chan FP, Valentine HA, Yang E, McConnell MV, Berry GJ, and Yang PC. (2006). Images in cardiovascular medicine. Cardiac magnetic resonance imaging for myocarditis: effective use in medical decision making. Circulation, 113:e842–e843.PubMedCrossRefGoogle Scholar
  12. Gullestad L, Aass H, Fjeld JG, Wikeby L, Andreassen AK, Ihlen H, Simonsen S, Kjekshus J, Nitter-Hauge S, Ueland T, Lien E, Froland SS, and Aukrust P. (2001). Immunomodulating therapy with intravenous immunoglobulin in patients with chronic heart failure. Circulation, 103:220–225.PubMedGoogle Scholar
  13. Hetzer R, Alexi-Meskishvili V, Weng Y, Hubler M, Potapov E, Drews T, Hennig E, Kaufmann F, and Stiller B. (2006). Mechanical cardiac support in the young with the Berlin Heart EXCOR pulsatile ventricular assist device: 15 years’ experience. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu, 2006:99–108.Google Scholar
  14. Hoffman TM, Wernovsky G, Atz AM, Kulik TJ, Nelson DP, Chang AC, Bailey JM, Akbary A, Kocsis JF, Kaczmarek R, Spray TL, and Wessel DL. (2003). Efficacy and safety of milrinone in preventing low cardiac output syndrome in infants and children after corrective surgery for congenital heart disease. Circulation, 107:996–1002.PubMedCrossRefGoogle Scholar
  15. Karjalainen J and Heikkila J. (1999). Incidence of three presentations of acute myocarditis in young men in military service. A 20-year experience. Eur Heart J, 20:1120–1125.PubMedCrossRefGoogle Scholar
  16. Kuhl U, Pauschinger M, Noutsias M, Seeberg B, Bock T, Lassner D, Poller W, Kandolf R, and Schultheiss HP. (2005). High prevalence of viral genomes and multiple viral infections in the myocardium of adults with “idiopathic” left ventricular dysfunction. Circulation, 111:887–893.PubMedCrossRefGoogle Scholar
  17. Laer S, Mir TS, Behn F, Eiselt M, Scholz H, Venzke A, Meibohm B, and Weil J. (2002). Carvedilol therapy in pediatric patients with congestive heart failure: a study investigating clinical and pharmacokinetic parameters. Am Heart J, 143:916–922.PubMedCrossRefGoogle Scholar
  18. Lieback E, Hardouin I, Meyer R, Bellach J, and Hetzer R. (1996). Clinical value of echocardiographic tissue characterization in the diagnosis of myocarditis. Eur Heart J, 17:135–142.PubMedGoogle Scholar
  19. Lieberman EB, Hutchins GM, Herskowitz A, Rose NR, and Baughman KL. (1991). Clinicopathologic description of myocarditis. J Am Coll Cardiol, 18:1617–1626.PubMedCrossRefGoogle Scholar
  20. Lin CH, Chang JS, and Li PC. (2005). The rescue of acute fulminant myocarditis by extracorporeal membrane oxygenation in pediatric patients. Acta Paediatr Taiwan, 46:201–205.PubMedGoogle Scholar
  21. Liu PP and Mason JW. (2001). Advances in the understanding of myocarditis. Circulation, 104:1076–1082.PubMedCrossRefGoogle Scholar
  22. Liu P and Sole MJ. (1999). What is the relevance of apoptosis to the myocardium? Can J Cardiol, 15(Suppl B):8B–10B.PubMedGoogle Scholar
  23. Magnani JW and Dec GW. (2006). Myocarditis: current trends in diagnosis and treatment. Circulation, 113:876–890.PubMedCrossRefGoogle Scholar
  24. Magnani JW, Danik HJ, Dec GW Jr., and DiSalvo TG. (2006). Survival in biopsy-proven myocarditis: a long-term retrospective analysis of the histopathologic, clinical, and hemodynamic predictors. Am Heart J, 151:463–470.PubMedCrossRefGoogle Scholar
  25. Maisch B, Ristic AD, Hufnagel G, Funck R, Alter P, Tontsch D, and Pankuweit S. (2002). Dilated cardiomyopathies as a cause of congestive heart failure. Herz, 27:113–134.PubMedCrossRefGoogle Scholar
  26. Maisch B, Hufnagel G, Kolsch S, Funck R, Richter A, Rupp H, Herzum M, and Pankuweit S. (2004). Treatment of inflammatory dilated cardiomyopathy and (peri) myocarditis with immunosuppression and i.v. immunoglobulins. Herz, 29:624–636.PubMedCrossRefGoogle Scholar
  27. Mason JW, O’Connell JB, Herskowitz A, Rose NR, McManus BM, Billingham ME, and Moon TE. (1995). A clinical trial of immunosuppressive therapy for myocarditis. The Myocarditis Treatment Trial Investigators. N Engl J Med, 333:269–275.PubMedCrossRefGoogle Scholar
  28. Matsumori A, Yamada T, Suzuki H, Matoba Y, and Sasayama S. (1994). Increased circulating cytokines in patients with myocarditis and cardiomyopathy. Br Heart J, 72:561–566.PubMedCrossRefGoogle Scholar
  29. Matsumori A, Igata H, Ono K, Iwasaki A, Miyamoto T, Nishio R, and Sasayama S. (1999). High doses of digitalis increase the myocardial production of proinflammatory cytokines and worsen myocardial injury in viral myoc arditis: a possible mechanism of digitalis toxicity. Jpn Circ J, 63:934–940.PubMedCrossRefGoogle Scholar
  30. McCarthy RE III, Boehmer JP, Hruban RH, Hutchins GM, Kasper EK, Hare JM, and Baughman KL. (2000). Long-term outcome of fulminant myocarditis as compared with acute (nonfulminant) myocarditis. N Engl J Med, 342:690–695.PubMedCrossRefGoogle Scholar
  31. McNamara DM, Holubkov R, Starling RC, Dec GW, Loh E, Torre-Amione G, Gass A, Janosko K, Tokarczyk T, Kessler P, Mann DL, and Feldman AM. (2001). Controlled trial of intravenous immune globulin in recent-onset dilated cardiomyopathy. Circulation, 103:2254–2259.PubMedGoogle Scholar
  32. Nakamura H, Yamamoto T, Yamamura T, Nakao F, Umemoto S, Shintaku T, Yamaguchi K, Liu P, and Matsuzaki M. (1999). Repetitive coxsackievirus infection induces cardiac dilatation in post-myocarditic mice. Jpn Circ J, 63:794–802.PubMedCrossRefGoogle Scholar
  33. Nishio R, Shioi T, Sasayama S, and Matsumori A. (2003). Carvedilol increases the production of interleukin-12 and interferon-gamma and improves the survival of mice infected with the encephalomyocarditis virus. J Am Coll Cardiol, 41:340–345.PubMedCrossRefGoogle Scholar
  34. Ono K, Matsumori A, Shioi T, Furukawa Y, and Sasayama S. (1998). Cytokine gene expression after myocardial infarction in rat hearts: possible implication in left ventricular remodeling. Circulation, 98:149–156.PubMedGoogle Scholar
  35. Packer M, Bristow MR, Cohn JN, Colucci WS, Fowler MB, Gilbert EM, and Shusterman NH. (1996). The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group. N Engl J Med, 334:1349–1355.PubMedCrossRefGoogle Scholar
  36. Parrillo JE, Cunnion RE, Epstein SE, Parker MM, Suffredini AF, Brenner M, Schaer GL, Palmeri ST, Cannon RO III, and Alling D et al. (1989). A prospective, randomized, controlled trial of prednisone for dilated cardiomyopathy. N Engl J Med, 321:1061–1068.PubMedGoogle Scholar
  37. Penninger JM, Pummerer C, Liu P, Neu N, and Bachmaier K. (1997). Cellular and molecular mechanisms of murine autoimmune myocarditis. Apmis, 105:1–13.PubMedCrossRefGoogle Scholar
  38. Shioi T, Matsumori A, Nishio R, Ono K, Kakio T, and Sasayama S. (1997). Protective role of interleukin-12 in viral myocarditis. J Mol Cell Cardiol, 29:2327–2334.PubMedCrossRefGoogle Scholar
  39. Stiller B, Dähnert I, Weng Y, Hennig E, Hetzer R, and Lange P. (1999). Children may survive severe myocarditis with prolonged use of biventricular assist devices. Heart, 82:237–240.PubMedGoogle Scholar
  40. Stiller B, Hetzer R, Weng Y, Hummel M, Hennig E, Nagdyman N, Ewert P, Lehmkuhl H, and Lange P. (2003). Heart transplantation in children after mechanical circulatory support with pulsatile pneumatic assist device. J Heart Lung Transplant, 22:1201–1208.PubMedCrossRefGoogle Scholar
  41. Stiller B, Lemmer J, Merkle F, Alexi-Meskishvili V, Weng Y, Hübler M, Koster A, Drews T, Lange P, and Hetzer R. (2004). Consumption of blood products during mechanical circulatory support in children: comparison between ECMO and a pulsatile ventricular assist device. Intensive Care Medicine, 30:1814–1820.PubMedCrossRefGoogle Scholar
  42. Stiller B, Weng Y, Hubler M, Lemmer J, Nagdyman N, Redlin M, Lange P, and Hetzer R. (2005). Pneumatic pulsatile ventricular assist devices in children under 1 year of age. Eur J Cardiothorac Surg, 28:234–239.PubMedCrossRefGoogle Scholar
  43. Towbin J. (2001). Myocarditis. In: Allen HD GH, Clarc EB, and Driscoll D, (eds.), Moss and Adams’ Heart Disease in Infants, Children, and Adolescents. Lippincott Williams and Wilkins, Philadelphia, PA.Google Scholar
  44. Wakafuji S and Okada R. (1986). Twenty year autopsy statistics of myocarditis incidence in Japan. Jpn Circ J, 50:1288–1293.PubMedGoogle Scholar
  45. Yamada T, Matsumori A, and Sasayama S. (1994). Therapeutic effect of anti-tumor necrosis factor-alpha antibody on the murine model of viral myocarditis induced by encephalomyocarditis virus. Circulation, 89:846–851.PubMedGoogle Scholar

Copyright information

© Springer 2008

Authors and Affiliations

  • Brigitte Stiller
    • 1
  1. 1.Department of Congenital Heart DefectsDeutsches Herzzentrum BerlinBerlinGermany

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