Dear Editor,

We read with great interest the a.m. review which comes to the conclusion that immunosuppressive therapy does not significantly improve the outcome of children with acute myocarditis. This is in accordance with an important review concerning the adult age [1]. However, both reviews show one decisive drawback. They do not take the essential changes in pathogenetic considerations and diagnostic methods into account.

Today it is generally accepted, that virus genomes may persist in myocardial tissue and may maintain an inflammatory process [2]. In a significant number of patients this results in a loss of myocytes, degeneration of the contractile apparatus with reactive myocardial fibrosis up to a dilatation of the heart muscle and myocardial dysfunc-tion.

At the same time, virus genoma may nowadays be detected by in-situ- hybridization and PCR even in formaline-fixed endomyocardial specimen. Enteroviruses, including coxsackievirus B, adenoviruses, human herpes virus 6, Epstein-Barr virus, human cytomegalovirus, respiratory syncytial virus and herpes simplex virus can be detected routinely.

As the authors mention, immunosuppression in the presence of virus genomes may impede “innate host immune re-sponse to eliminate the virus and this would have detrimental effects”. The missing diagnostic distinction of patients with and without virus genomes means that patients with virus-caused chronic myocaritis and autoreactive myocarditis are not separated. This is the major disadvantage of all studies analysed. As the studies do not distinguish between the two causes of the disease, they offer no insight concerning the effectiveness of different treatments. Therefore, they have no explanatory value from a clinical point of view.

Already in 1998 we published the design of a multicenter treatment trial, in which this distinction was made by assess-ment of endomyocardial biopsies. Only patients with autoreactive myocarditis were treated by immunosuppression in a randomized manner, while patients with proven virus genoma were treated by interferone-alpha. Due to the delicate methods, the diagnostic evaluation is performed centrally by the department of molecular pathology at the University Hospital of Tuebingen. The study protocol was approved by several ethical committees in Germany at the beginning of the study and again this year. Because of scarce implementation of patients into the study, no statistically valid conclusions can be drawn at this time. However, we would like to open the study to departments of pediatric cardiology abroad and we will be pleased to supply all necessary information.

References

(1). Garg A, Shiau J, Guyatt G: The ineffectiveness of immunosuppressive therapy in lymphocytic myocarditis. Ann Intern Med 1998; 129: 317-322 Hia CPP, Yip WCL, Zhai BC, Quek SC: Immunosuppressive therapy in acute myocarditis: an 18 year systematic re-view . Arch Dis Child 2004; 89: 580- 584

(2). Klingel K, Selinka HC, Sauter M: Molecular mechanisms in enterovirus- and parvovirus B19-associated myocarditis and inflammatory cardiopmyopathy. Eur Heart J 2002; 4/1:8-12