JACC Vol. 15, No. 7 June 1990:3535-6
J Lorrdon, England
une complex disorder i
congenital) and 41 patients with he myocardial infarction were studi
s with progressloa of n accord with the doubt that there are ma titative absorption studies. Sera giving d staining of both atria1and ventricular m were negative on skeletal muscle, were classified as organ specific. These organ-specific cardiac autoantibodies were present more frequently in patients with dilated cardiomyopathy (26%)than in normal subjects (3.5%)or patients with other cardiac disease (1%) or heart failure (0%). Sera that gave immunofluorescence on skeletal muscle as well as myocytes were classified as being cross-reactive autoantibodies and were found in 11% of patients with dilated cardiomyopathy, 7% of patients with other heart disease, 2% of patients with heart failure and 5.5% of normal subjects. Other organ-specificantibodies such as islet cell and gastric
rent causes of dilated cardio-
demonstration that organ-specific cardiac antibodies were present in a significant number of patients with dilated cardiomyopathy and to a degree far in excess of such antibodiesfound in patients with other forms of heart disease and in control subjects. These findingsstrongly suggest that some autoimmuneprocess is involved in causation, although the antibodies may, of course, be markers of risk rather than the actual cause. tion.Experimental and clinical work le of vir (49 has suggested that viral my une reaction that leads to
viral infection, although *Editorials published in Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represenl lhe views of JACC or the American College of Cardiology. From the Royal Postgraduate Medical School, London, Englnnd. Addressfor John F. Goodwin, MD, 2 Pine Grove, Lake Road, Wimbledon, London, England SW19 7HE. Ql990 by the American
College of Cardiology
hybridizationprobes specificfor enteroviral ~bo~~cleicacid (RNA), detected viral RNA sequences in 55%of hearts with dilated cardiomyopathyas well as in those with myocarditis. 073%1097/90/$3.50
1536
GOODWIN EDITORIAL COMMENT
The RNA fragments persisted until end-stage disease but without necessarily eliciting a full immunologic response. The proportion of probe-positive biopsy specimens was higher in patients with dilated cardiomyopathy (41%)than in explanted hearts (2%). This findingmight suggest, in accord with the results of Caforio et al. (I), that virus may be eliminated late in the disease. The evidence provided by progression from myocarditis to dilated cardiomyopathy clinically and hemodynamically, together with the molecular biologic data and immunologic studies, strongly suggests a causal role of viral infection. However, caution is still necessary because association does not inevitably imply causation and the virus-immunetheory would explain no more than about 50% of cases of dilated cardiomyopathy. Because autoimmune disturbance can be inherited, Caforio et al. (I) should study relatives of their patients with dilated cardiomyopathy. It might be that there is a genetic basis in some patients with dilated cardiomyopathy and that viral infection acts as the trigger to precipitate a latent autoimmunologic destructive cardiac response. Conclusions. The enigma of dilated cardiomyopathy is not solved, although the work of Caforio and colleagues (1) provides an important landmark of progress both in the experimental field and in the clinical realm. The place of immunologic therapy and viral chemotherapy is being explored and myocarditis is treated (sometimes incorrectly) with steroids. Furthermore, because patients after cardiac transplantation are immunologically depressed, it will be vitally important to determine whether the presence of viral particles in the myocardium of the explanted heart has any implications for the transplant patient’s management and prognosis.
JACC Vol. IS. No. 7 June 1990:1535-6
Caforio ALP, Bonifacic E, Stewart JT, et J. Novel organ-specific circulating cardiac autoantibodies in dilated cardiomyopathy. J Am COB Cardiol 1990;15:1527-34. Fowles RE, Bieber CP, Stinson EB. Defective in-vitro suppressor cell dysfunction in idiopathic congestive cardiomyopathy. Circulation 1979; 59:483-91. Anderson JL. Bieber CP. Fowles RE, Stinson EB. Idiopathic cardiomyopathy, age and suppressor cell dysfunction as risk determinent of lymphoma after cardiac transplantation. Lancet 1978;2:1174. Wong CY, Woodruff JJ. Woodruff JF. Generation of cytotoxic T lymphocytes during coxsackie B infection. II. Characterisation of effector cells and demonstration of cytotoxicity against viral infected myofibers. J lmmunol 1977;118:1165-9. 5. Kishimoto C, Kuribayashi K, Masuda T, Tomioka N, Kawai C. Immunologic behavior of lymphocytes in experimental virus myocarditis; significance of T lymphocytes in severity of myocarditis and silent myocarditis in BALBk-nulnu mice. Circulation 1985;71:1247-54. 6. Quigley PJ, Richardson PJ, Meany BT. et al. Long term followup with acute myocarditis; correlation of ventricular function and outcome. Eur Heart J 1987;8(suppl J):39-42. 7. Cambridge Cl, MacArthur CGC, Waterson AP, Goodwin JF, Oakley CM. Antibodies to coxsackie B virus in congestive cardiomyopathy. dr Heart J 1979;41:693-6. 8. Maisch B, Schwab D. Bauer E. Sondhage K. Smaltz AA. Antimyolemmal antibodies in myocarditis in children. Em Heart J 1987;8(suppl J):l67-73. 9. Archard LC, Bowles NE, Olsen EGJ, Richardson PJ. Detection of persistent coxsackie B virus RNA in dilated cardiomyopathy and myocarditis. Eur Heart J 1987;8(suppl J):437-40. 10. Archard LC. Freeke CA, Richardson PJ. et al. Persistence of enterovirus RNA in dilated cardiomyopathy: a progression from myocarditis. In: Schultheiss H-P, ed. New Concepts of Viral Heart Disease. Heidelberg: Springer-Verlag, 1988;349-62. Il. Archard LC. Banner NR. Bowles L, et al. Enterovirus RNA sequences in hearts with dilated cardiomyopathy: a pathogenetic link between virus infection and dilated cardiomyopathy. In: Baroldi G, Camerini F, Goodwin JF, eds. Advances in Cardiomyopathies. Heidelberg: Springer-Verlag tin press).
J Lorrdon, England
une complex disorder i
congenital) and 41 patients with he myocardial infarction were studi
s with progressloa of n accord with the doubt that there are ma titative absorption studies. Sera giving d staining of both atria1and ventricular m were negative on skeletal muscle, were classified as organ specific. These organ-specific cardiac autoantibodies were present more frequently in patients with dilated cardiomyopathy (26%)than in normal subjects (3.5%)or patients with other cardiac disease (1%) or heart failure (0%). Sera that gave immunofluorescence on skeletal muscle as well as myocytes were classified as being cross-reactive autoantibodies and were found in 11% of patients with dilated cardiomyopathy, 7% of patients with other heart disease, 2% of patients with heart failure and 5.5% of normal subjects. Other organ-specificantibodies such as islet cell and gastric
rent causes of dilated cardio-
demonstration that organ-specific cardiac antibodies were present in a significant number of patients with dilated cardiomyopathy and to a degree far in excess of such antibodiesfound in patients with other forms of heart disease and in control subjects. These findingsstrongly suggest that some autoimmuneprocess is involved in causation, although the antibodies may, of course, be markers of risk rather than the actual cause. tion.Experimental and clinical work le of vir (49 has suggested that viral my une reaction that leads to
viral infection, although *Editorials published in Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represenl lhe views of JACC or the American College of Cardiology. From the Royal Postgraduate Medical School, London, Englnnd. Addressfor John F. Goodwin, MD, 2 Pine Grove, Lake Road, Wimbledon, London, England SW19 7HE. Ql990 by the American
College of Cardiology
hybridizationprobes specificfor enteroviral ~bo~~cleicacid (RNA), detected viral RNA sequences in 55%of hearts with dilated cardiomyopathyas well as in those with myocarditis. 073%1097/90/$3.50
1536
GOODWIN EDITORIAL COMMENT
The RNA fragments persisted until end-stage disease but without necessarily eliciting a full immunologic response. The proportion of probe-positive biopsy specimens was higher in patients with dilated cardiomyopathy (41%)than in explanted hearts (2%). This findingmight suggest, in accord with the results of Caforio et al. (I), that virus may be eliminated late in the disease. The evidence provided by progression from myocarditis to dilated cardiomyopathy clinically and hemodynamically, together with the molecular biologic data and immunologic studies, strongly suggests a causal role of viral infection. However, caution is still necessary because association does not inevitably imply causation and the virus-immunetheory would explain no more than about 50% of cases of dilated cardiomyopathy. Because autoimmune disturbance can be inherited, Caforio et al. (I) should study relatives of their patients with dilated cardiomyopathy. It might be that there is a genetic basis in some patients with dilated cardiomyopathy and that viral infection acts as the trigger to precipitate a latent autoimmunologic destructive cardiac response. Conclusions. The enigma of dilated cardiomyopathy is not solved, although the work of Caforio and colleagues (1) provides an important landmark of progress both in the experimental field and in the clinical realm. The place of immunologic therapy and viral chemotherapy is being explored and myocarditis is treated (sometimes incorrectly) with steroids. Furthermore, because patients after cardiac transplantation are immunologically depressed, it will be vitally important to determine whether the presence of viral particles in the myocardium of the explanted heart has any implications for the transplant patient’s management and prognosis.
JACC Vol. IS. No. 7 June 1990:1535-6
Caforio ALP, Bonifacic E, Stewart JT, et J. Novel organ-specific circulating cardiac autoantibodies in dilated cardiomyopathy. J Am COB Cardiol 1990;15:1527-34. Fowles RE, Bieber CP, Stinson EB. Defective in-vitro suppressor cell dysfunction in idiopathic congestive cardiomyopathy. Circulation 1979; 59:483-91. Anderson JL. Bieber CP. Fowles RE, Stinson EB. Idiopathic cardiomyopathy, age and suppressor cell dysfunction as risk determinent of lymphoma after cardiac transplantation. Lancet 1978;2:1174. Wong CY, Woodruff JJ. Woodruff JF. Generation of cytotoxic T lymphocytes during coxsackie B infection. II. Characterisation of effector cells and demonstration of cytotoxicity against viral infected myofibers. J lmmunol 1977;118:1165-9. 5. Kishimoto C, Kuribayashi K, Masuda T, Tomioka N, Kawai C. Immunologic behavior of lymphocytes in experimental virus myocarditis; significance of T lymphocytes in severity of myocarditis and silent myocarditis in BALBk-nulnu mice. Circulation 1985;71:1247-54. 6. Quigley PJ, Richardson PJ, Meany BT. et al. Long term followup with acute myocarditis; correlation of ventricular function and outcome. Eur Heart J 1987;8(suppl J):39-42. 7. Cambridge Cl, MacArthur CGC, Waterson AP, Goodwin JF, Oakley CM. Antibodies to coxsackie B virus in congestive cardiomyopathy. dr Heart J 1979;41:693-6. 8. Maisch B, Schwab D. Bauer E. Sondhage K. Smaltz AA. Antimyolemmal antibodies in myocarditis in children. Em Heart J 1987;8(suppl J):l67-73. 9. Archard LC, Bowles NE, Olsen EGJ, Richardson PJ. Detection of persistent coxsackie B virus RNA in dilated cardiomyopathy and myocarditis. Eur Heart J 1987;8(suppl J):437-40. 10. Archard LC. Freeke CA, Richardson PJ. et al. Persistence of enterovirus RNA in dilated cardiomyopathy: a progression from myocarditis. In: Schultheiss H-P, ed. New Concepts of Viral Heart Disease. Heidelberg: Springer-Verlag, 1988;349-62. Il. Archard LC. Banner NR. Bowles L, et al. Enterovirus RNA sequences in hearts with dilated cardiomyopathy: a pathogenetic link between virus infection and dilated cardiomyopathy. In: Baroldi G, Camerini F, Goodwin JF, eds. Advances in Cardiomyopathies. Heidelberg: Springer-Verlag tin press).
