Abstract
Strategies for immunosuppressive treatment of chronic inflammatory myocardial diseases are still a controversial issue. This dilemma is still unresolved despite the “American Myocarditis Trial ” which, as many other studies before, could not demonstrate any positive therapeutic effects of the immunosuppressive therapy [1]. This, however, is not due to a general unresponsiveness of cardiac inflammation to immunosuppressive therapy, but rather reflects an inappropriate study design, that did not select the optimal group of patients for therapy. Histological diagnosis of the inflammatory process may have been inaccurate and the study did not take into consideration the spontaneous course of the disease or a possible viral persistence [2–8]. Though the prerequisites for diagnosing virus-induced myocardial disease have been considerably improved by new diagnostic techniques in recent years, there have not yet been any prospective randomized therapeutic studies with precisely characterized patient populations. Ultimately decisive for the development of adequate therapeutic strategies, however, is a precise clinical evaluation of the patients to be treated. Besides documenting the clinical status, it is extremely important to differentially analyze the inflammatory reaction and possible viral persistence in the myocardial tissue by histological, immunohistological and molecular-biological techniques [8]. The histological and particularly the immunohistological techniques accurately detect both the acute and chronic myocardial inflammatory process [9,10]. New highly sensitive molecular-biological methods such as in situ hybridization and the polymerase chain reaction (PCR) now detect the viral genome (e.g., enteroviruses) even for latent infection with restricted replication [11–15]. Only these differential diagnostics enable precise characterization of the disease process, which is now a prerequisite for the appropriate selection of patients for treatment.
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References
Mason JW, O’Connell JB, Herskowitz A et al. (1995) A clinical trial of immunosuppressive therapy for myocarditis. N Engl J Med 333:269–275.
Hahn EA, Hartz VL, Moon TE, O’Connell JB, Herskowitz A, McManus BM, Mason JW, for the Myocarditis Treatment Trial Investigators (1995): The Myocarditis Treatment Trial: design, methods and patient enrollment. Eur Heart J 16 [Suppl 0]:162–167
McKenna WJ, Davies MJ (1995) Immunosuppression for myocarditis. N Engl J Med 333:312–313
Maisch B, Camerini F, Schultheiss HP (1995a) Immunosuppressive therapy for myocarditis [letter]. N Engl J Med 333:1714
Cunnion RE, Parillo JE (1995) Immunosuppression for myocarditis [letter]. N Engl J Med 333:1713
Cooper LT, Shabetai R (1995) Immunosuppression for myocarditis [letter]. N Engl J Med 333:1713–1714
Mason JW, O’Connell JB, McManus BM (1995) Immunosuppression for myocarditis N Engl J Med 333:1714
Kuhl U, Noutsias M, Seeberg B, Schultheiss HP (1996) Immunohistological evidence for a chronic intramyocardial inflammatory process in dilated cardiomyopathy. Heart 75:295–300
Kuhl U, Noutsias M, Seeberg B, Schannwell M, Welp LB and Schultheiss HP (1994) Chronic inflammation in the myocardium of patients with clinically suspected dilated cardiomyopathy. J Card Failure 1:13–27
Kuhl U, Noutsias M, Seeberg B, Schannwell M, Welp LB and Schultheiss H. (1994) Immunohistological evaluation of myocardial biopsies from patients with dilated cardiomyopathy. J Heart Failure 9:231–245
Bowles NE, Richardson PJ, Olson EGJ, Archard LC (1986) Detection of coxsackie-B-virus-specific RNA sequences in myocardial biopsy samples from patients with myocarditis and dilated cardiomyopathy. Lancet 17:1120–1123
Jin O, Sole MJ, Butany JW, Chia W-K, McLaughlin PR, Liu P, Liew CC (1990) Detection of enterovirus RNA in myocardial biopsies from patients with myocarditis and cardiomyopathy using gene amplification by polymerase chain reaction. Circulation 82:8–16
Kandolf R, Ameis D, Kirschner P, Canu A, Hofschneider PH (1987) In situ detection of enteroviral genomes in myocardial cells by nucleic acid hybridization: an approach to the diagnosis of viral heart diesease. Proc Natl Acad Sci 84:6272–6276
Tracy S, Chapmann NM, McManus BM, Pallansch MA, Beck MA, Carstens J (1990) A molecular and serologic evaluation of enteroviral involvement in human myocarditis. J Mol Cell Cardiol 22:403–414
Weiss LM, Movahed LA, Billingham ME, Cleary ML (1991) Detection of coxsackievirus B3 RNA in myocardial tissues by the polymerase chain reaction. Am J Pathol 138:497–503
WHO (1996) Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the Definition and Classification of Cardiomyopathies. Circulation 93:841–842
Kandolf R, Klingel K, Zell R, Selinka HC, Raab U, Schneider-Brachert W, Bultmann B (1993) Molecular pathogenesis of enterovirus-induced myocarditis: virus persistence and chronic inflammation. Intervirology 35:140–151
Pauschinger M, Preis S, Triesch A, Doerner A, Schultheiss H-P (1994) Detection of enteroviral RNA in patients having chronic myocarditis respectively dilated cardiomyopathy. Circulation 90 [Suppl I]:1174
Archard LC, Bowles NE, Cunningham L, Freeke CA, Olsen EG, Rose ML, Meany B, Why HJF, Richardson FJ (1991) Molecular probes for detection of persisting enterovirus infection of human heart and their prognostic value. Eur Heart J 12 [Suppl D]:56–59
Tracy S, Wiegand V, McManus B, Gauntt C, Pallansch M, Beck M, Chapman N (1990) Molecular approaches to enteroviral diagnosis in idiopathic cardiomyopathy and myocarditis. J Am Coll Cardiol 15:1688–1694
Martin AB, Webber S, Fricker FJ, Jaffe R, Demmler G, Kearny D, Zhang Y-H, Bodurtha J, Gelb B, Ni J, Bricker JT, Towbin JA (1994) Acute myocarditis, rapid diagnosis by PCR in children. Circulation 90:330–339
Schönian U, Crombach M, Maisch B (1993) Assessment of cytomegalovirus DNA and protein expression in patients with myocarditis. Clin Immunol Immunopathol 68:229–233
Matsumori A, Matoba Y, Sasayama S (1995) Dilated cardiomyopathy associated with hepatitis C virus infection. Circulation 92:2519–2525
Caforio ALP (1994) Role of autoimmunity in dilated cardiomyopathy. Br Heart J 72:S30–S34
Schultheiss HP (1987) The mitochondrium as antigen in inflammatory heart disease. Eur Heart J 8 [Suppl J]:203–210
Schultheiss HP (1993) Disturbance of the myocardial energy metabolism in dilated cardiomyopathy due to autoimmunological mechanisms. Circulation 87 [Suppl 5]:IV43–IV48
Schultheiss HP, Schulze K, Schauer R, Witzenbichler B, Strauer BE (1995) Antibodymediated imbalance of myocardial energy metabolism, a causal factor of cardiac failure. Circ Res 76:64–72
Limas CJ, Goldenberg IF, Limas C (1984) Autoantibodies against adrenoceoptors in human idiopathic dilated cardiomyopathy. Eur Heart J 5:97–103
Schultheiss HP (1992) Dysfunction of the ADP/ATP carrier as a causative factor for the disturbance of the myocardial energy metabolism in dilated cardiomyopathy. Basic Res Cardiol 87:311–320
Schultheiss HP, Schulze K, Dorner A (1996) Significance of the adenine nucleotide translocator in the pathogenesis of viral heart disease Molec Cell Biochem 163/164:319–327
Schulze K, Becker BF, Schultheiss HP (1989) Antibodies to the ADP/ATP carrier, an autoantigen in myocarditis and dilated cardiomyopathy, penetrate into myocardial cells and disturb energy metabolism in vivo. Circ Res 64:179–253
Kuhl U, Melzner B, Schafer B, Schulteiss HP, Strauer BE (1991) The Ca-channel as cardiac autoantigen. Eur Heart J 12:99–104
Schultheiss HP, Janda I, Kuhl U, Ulrich G, Morad M (1988) Antibodies against the ADP/ATP carrier interact with the calcium channel and induce cytotoxicity by enhancement of calcium permeability. In: The Calcium Channel: Structure, Function and Implications. Eds.: Morad M, Nayler W, Kazda S, Schramm M. Springer-Verlag, Berlin, Heidelberg, New York, pp 619–631
Schultheiss, H-P, Kuhl, U, Schulze, K, Schwimmbeck, P, Strauer, BE (1990) Biomolecular changes in dilated cardiomyopathy. In: Baroldi G, Camerini F, Goodwin JF (eds) Advances in Cardiomyopathies. Springer Verlag Berlin, Heidelberg, New York, pp 221–234
Wolff P, Kuhl U, Schultheiss HP (1989) Laminin distribution and autoantibodies to laminin in dilated cardiomyopathy and myocarditis. Am Heart J 117:1303–1309
Matsumori A, Yamada T, Suzuki H, Matoba Y, Sasayama S (1994) Increased circulating cytokines in patients with myocarditis and cardiomyopathy. Br Heart J 72:561–566
Matsumori A (1996) Cytokines in myocarditis and cardiomyopathies. Current Opinion in Cardiol 11:302–309
Kuhl U, Pauschinger M, Schultheiss HP (1997) Äthiopathogenetische Differenzierung der entzündlichen Kardiomyopathie. Internist 38:590–601
Aretz HT (1987) Myocarditis, the Dallas Criteria. Human Pathol 18:619–624
Billingham ME (1987) Acute myocarditis: a diagnostic dilemma. Brit Heart J 58:6–8
Hauck AJ, Kearney DL, Edwards WD (1989) Evaluation of postmortem endomyocardial biopsy specimen from 38 patients with lymphocytic myocarditis: Implication for role of sampling error. Mayo Clin Proc 64:1235–1245
Shanes JG, Ghali J, Billingham ME, Ferrans VJ, Fenoglio JJ, Edwards WD, Tsai CC, Saffitz JE, Isner J, Furner S, Subramanian R (1987) Interobserver variability in the pathologic interpretation of endomyocardial biopsy results. Circulation 75:401–405
Chow LH, Ye Y, Linder J, McManus BM (1989) Phenotypic analysis of infiltrating cells in human myocarditis. Arch Pathol Lab Med 113:1357–1362
Kuhl U, Pauschinger M, Schultheiss HP (1997) Neue Konzepte zur Diagnostik der entzündlichen Herzmuskelerkrankung. DMW 122:690–698
Kawai C, Matsumori A, Fujiwara H (1987) Myocarditis and dilated cardiomyopathy. Ann Rev Med 38:221–239
Tomioka N, Kishimoto C, Matsumori A, Kawai C (1986) Effects of prednisolone on acute viral myocarditis in mice. J Am Coll Cardiol 7:868–872
Schultheiss H-P (1992) Immunsuppressive Therapie bei Myokarditis und dilatativer Kardiomyopathie. Internist 33:650–662
Kuhl U, Schultheiss H-P, Strauer BE (1994) Methylprednisolone in chronic myocarditis. Postgrad Med J 70 [Suppl 1]:S35–S42
Maisch B, Herzum M, Hufnagel G, Bethge C, Schönian U (1995b) Immunosuppressive treatment for myocarditis and dilated cardiomyopathy. Eur Heart J 16 [Suppl O]:153–161
Koide H, Kitaura Y, Deguchi H (1992) Genomic detection of enteroviruses in the myocardium-studies on animal hearts with coxsackievirus B3 myocarditis and dilated cardiomyopathy. Jpn Circ J 56:1081–1083
Kandolf R, Kirschner P, Ameis D, Canu A, Erdmann E, Schulteiss HP, Kempkes B, Hofschneider PH (1988) Enteroviral heart disease: diagnosis by in situ hybridization. In: Schulteiss H (ed) New Concepts in Viral Heart Disease. Springer-Verlag, Berlin Heidelberg New York, pp 337–348
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Kühl, U., Pauschinger, M., Schultheiss, HP. (1998). Inflammatory Cardiomyopathy: Diagnostic and Therapeutical Options. In: Camerini, F., Gavazzi, A., De Maria, R. (eds) Advances in Cardiomyopathies. Springer, Milano. https://doi.org/10.1007/978-88-470-2155-6_16
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DOI: https://doi.org/10.1007/978-88-470-2155-6_16
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