on January 27, 2003
Circulation. 2003
Published online before print January 27, 2003, doi: 10.1161/01.CIR.0000048147.15962.31
Published online before print January 27, 2003, doi: 10.1161/01.CIR.0000048147.15962.31
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on July 31, 2002
From the Department of Cardiology, Catholic University, Rome (A.F., C.C., M.P.); the Department of Pathology, University of Padua, Padua (F.C., G.T.); and the Cardiothoracic and Vascular Department, University Vita e Salute, Milan (A.M.), Italy. * To whom correspondence should be addressed. E-mail: biocard{at}rm.unicatt.it.
Background--The beneficial effect of immunosuppressive treatment on myocarditis is still controversial, possibly because the immunologic and virological profile of potential candidates is largely unknown. Methods and Results--Out of 652 biopsied patients, 112 had a histological diagnosis of active lymphocytic myocarditis; 41 of these 112 patients were characterized by progressive heart failure despite conventional therapy and were treated with prednisone and azathioprine for 6 months. All were resubmitted to cardiac catheterization, angiography, and endomyocardial biopsy at 1 and 6 months and followed-up for 1 year. A total of 21 patients responded with prompt improvement in left ventricular ejection fraction from 25.7±4.1% to 47.1±4.4% and showed evidence of healed myocarditis at control biopsy. Conversely, 20 patients failed to respond and showed a histological evolution toward dilated cardiomyopathy: 12 remained stationary, 3 underwent cardiac transplantation, and 5 died. We retrospectively performed a polymerase chain reaction on frozen endomyocardial tissue for the most common cardiotropic viruses and assessed circulating serum cardiac autoantibodies. Viral genomes were present in biopsy specimens of 17 nonresponders (85%), including enterovirus (n=5), Epstein-Barr virus (n=5) adenovirus (n=4), both adenovirus and enterovirus (n=1), influenza A virus (n=1), parvovirus-B19 (n=1), and in 3 responders, who were all positive for hepatitis C virus. Cardiac autoantibodies were present in 19 responders (90%) and in none of the nonresponders. Conclusions--In patients with active lymphocytic myocarditis, those with circulating cardiac autoantibodies and no viral genome in the myocardium are the most likely to benefit from immunosuppression. The beneficial effect of immunosuppression in hepatitis C virus myocarditis suggests a relevant immunomediated component of damage.
Revised on October 22, 2002
Accepted on October 22, 2002
Immunosuppressive Therapy for Active Lymphocytic Myocarditis. Virological and Immunologic Profile of Responders Versus Nonresponders
Andrea Frustaci MD*,
Key words: myocarditis • heart failure • immunosuppression • viruses • autoimmunity
This article has been cited by other articles:
 |
|
 |
|
  H. Baccouche, H. Mahrholdt, G. Meinhardt, R. Merher, M. Voehringer, S. Hill, K. Klingel, R. Kandolf, U. Sechtem, and A. Yilmaz Diagnostic synergy of non-invasive cardiovascular magnetic resonance and invasive endomyocardial biopsy in troponin-positive patients without coronary artery disease Eur. Heart J., December 1, 2009; 30(23): 2869 - 2879. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Frustaci, M. A. Russo, and C. Chimenti Randomized study on the efficacy of immunosuppressive therapy in patients with virus-negative inflammatory cardiomyopathy: the TIMIC study Eur. Heart J., August 2, 2009; 30(16): 1995 - 2002. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. T. Cooper The heat is off: immunosuppression for myocarditis revisited Eur. Heart J., August 2, 2009; 30(16): 1936 - 1939. [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Kapoor, S. Szabo, T. Oikonomopoulos, H. M. Hoffmeister, H. Ammar, R. Fouda, and L. T. Cooper Jr. Myocarditis N. Engl. J. Med., July 23, 2009; 361(4): 422 - 424. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Noutsias, S. Pankuweit, B. Maisch, D. Huzly, M. Enders, and S. Pollak Pathophysiological Mechanisms of Parvovirus B19 Infection J. Clin. Microbiol., July 1, 2009; 47(7): 2358 - 2359. [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Hunt, W. T. Abraham, M. H. Chin, A. M. Feldman, G. S. Francis, T. G. Ganiats, M. Jessup, M. A. Konstam, D. M. Mancini, K. Michl, et al. 2009 Focused Update Incorporated Into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation J. Am. Coll. Cardiol., April 14, 2009; 53(15): e1 - e90. [Full Text] [PDF]
|
|
|
|
 |
|
 2005 WRITING COMMITTEE MEMBERS, S. A. Hunt, W. T. Abraham, M. H. Chin, A. M. Feldman, G. S. Francis, T. G. Ganiats, M. Jessup, M. A. Konstam, D. M. Mancini, et al. 2009 Focused Update Incorporated Into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: Developed in Collaboration With the International Society for Heart and Lung Transplantation Circulation, April 14, 2009; 119(14): e391 - e479. [Full Text] [PDF]
|
|
|
|
 |
|
 O. M. Hess, W. McKenna, and H.-P. Schultheiss CHAPTER 18 Myocardial Disease ESC Textbook of Cardiovascular Medicine, January 1, 2009; 2(1): med-9780199566990-chapter - med-9780199566990-chapter. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Holzmann, A. Nicko, U. Kuhl, M. Noutsias, W. Poller, W. Hoffmann, A. Morguet, B. Witzenbichler, C. Tschope, H.-P. Schultheiss, et al. Complication Rate of Right Ventricular Endomyocardial Biopsy via the Femoral Approach: A Retrospective and Prospective Study Analyzing 3048 Diagnostic Procedures Over an 11-Year Period Circulation, October 21, 2008; 118(17): 1722 - 1728. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Dennert, H. J. Crijns, and S. Heymans Acute viral myocarditis Eur. Heart J., September 1, 2008; 29(17): 2073 - 2082. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Valaperti, R. R. Marty, G. Kania, D. Germano, N. Mauermann, S. Dirnhofer, B. Leimenstoll, P. Blyszczuk, C. Dong, C. Mueller, et al. CD11b+ Monocytes Abrogate Th17 CD4+ T Cell-Mediated Experimental Autoimmune Myocarditis J. Immunol., February 15, 2008; 180(4): 2686 - 2695. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Gutberlet, B. Spors, T. Thoma, H. Bertram, T. Denecke, R. Felix, M. Noutsias, H.-P. Schultheiss, and U. Kuhl Suspected Chronic Myocarditis at Cardiac MR: Diagnostic Accuracy and Association with Immunohistologically Detected Inflammation and Viral Persistence Radiology, February 1, 2008; 246(2): 401 - 409. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Frustaci, M. A. Russo, and C. Chimenti Myocarditis in hypertrophic cardiomyopathy: reply Eur. Heart J., July 1, 2007; 28(13): 1664 - 1664. [Full Text] [PDF]
|
|
|
|
|
|
A. L.P. Caforio, F. Calabrese, A. Angelini, F. Tona, A. Vinci, S. Bottaro, A. Ramondo, E. Carturan, S. Iliceto, G. Thiene, et al. A prospective study of biopsy-proven myocarditis: prognostic relevance of clinical and aetiopathogenetic features at diagnosis Eur. Heart J., June 1, 2007; 28(11): 1326 - 1333. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-i. Suzuki, M. Ogawa, H. Futamatsu, H. Kosuge, Y. M. Sagesaka, and M. Isobe Tea catechins improve left ventricular dysfunction, suppress myocardial inflammation and fibrosis, and alter cytokine expression in rat autoimmune myocarditis Eur J Heart Fail, February 1, 2007; 9(2): 152 - 159. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. E. F. Daubeney, A. W. Nugent, P. Chondros, J. B. Carlin, S. D. Colan, M. Cheung, A. M. Davis, C.W. Chow, R. G. Weintraub, and on behalf of the National Australian Childhood Car Clinical Features and Outcomes of Childhood Dilated Cardiomyopathy: Results From a National Population-Based Study Circulation, December 12, 2006; 114(24): 2671 - 2678. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Rangachari, N. Mauermann, R. R. Marty, S. Dirnhofer, M. O. Kurrer, V. Komnenovic, J. M. Penninger, and U. Eriksson T-bet negatively regulates autoimmune myocarditis by suppressing local production of interleukin 17 J. Exp. Med., August 7, 2006; 203(8): 2009 - 2019. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K Komamura, T Sasaki, A Hanatani, J Kim, K Hashimura, Y Ishida, Y Ohkaru, K Asayama, T Tanaka, A Ogai, et al. Heart-type fatty acid binding protein is a novel prognostic marker in patients with non-ischaemic dilated cardiomyopathy Heart, May 1, 2006; 92(5): 615 - 618. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. De Cobelli, M. Pieroni, A. Esposito, C. Chimenti, E. Belloni, R. Mellone, T. Canu, G. Perseghin, C. Gaudio, A. Maseri, et al. Delayed Gadolinium-Enhanced Cardiac Magnetic Resonance in Patients With Chronic Myocarditis Presenting With Heart Failure or Recurrent Arrhythmias J. Am. Coll. Cardiol., April 18, 2006; 47(8): 1649 - 1654. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Magnani and G. W. Dec Myocarditis: Current Trends in Diagnosis and Treatment Circulation, February 14, 2006; 113(6): 876 - 890. [Full Text] [PDF]
|
|
|
|
 |
|
 L. T. Cooper, R. Virmani, N. M. Chapman, A. Frustaci, R. J. Rodeheffer, M. W. Cunningham, and D. M. McNamara National Institutes of Health-Sponsored Workshop on Inflammation and Immunity in Dilated Cardiomyopathy Mayo Clin. Proc., February 1, 2006; 81(2): 199 - 204. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Baughman Diagnosis of Myocarditis: Death of Dallas Criteria Circulation, January 31, 2006; 113(4): 593 - 595. [Full Text] [PDF]
|
|
|
|
|
|
R. R. Marty, S. Dirnhofer, N. Mauermann, S. Schweikert, S. Akira, L. Hunziker, J. M. Penninger, and U. Eriksson MyD88 Signaling Controls Autoimmune Myocarditis Induction Circulation, January 17, 2006; 113(2): 258 - 265. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Kuhl, M. Pauschinger, B. Seeberg, D. Lassner, M. Noutsias, W. Poller, and H.-P. Schultheiss Viral Persistence in the Myocardium Is Associated With Progressive Cardiac Dysfunction Circulation, September 27, 2005; 112(13): 1965 - 1970. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Developed in Collaboration With the American Colle, Endorsed by the Heart Rhythm Society, S. A. Hunt, W. T. Abraham, M. H. Chin, A. M. Feldman, G. S. Francis, T. G. Ganiats, M. Jessup, M. A. Konstam, et al. ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult--Summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure) J. Am. Coll. Cardiol., September 20, 2005; 46(6): 1116 - 1143. [Full Text] [PDF]
|
|
|
|
|
|
S. A. Hunt, W. T. Abraham, M. H. Chin, A. M. Feldman, G. S. Francis, T. G. Ganiats, M. Jessup, M. A. Konstam, D. M. Mancini, K. Michl, et al. ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult--Summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): Developed in Collaboration With the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: Endorsed by the Heart Rhythm Society Circulation, September 20, 2005; 112(12): 1825 - 1852. [Full Text] [PDF]
|
|
|
|
|
|
U. Kuhl, M. Pauschinger, M. Noutsias, B. Seeberg, T. Bock, D. Lassner, W. Poller, R. Kandolf, and H.-P. Schultheiss High Prevalence of Viral Genomes and Multiple Viral Infections in the Myocardium of Adults With "Idiopathic" Left Ventricular Dysfunction Circulation, February 22, 2005; 111(7): 887 - 893. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Pieroni, C. Chimenti, A. Frustaci, K. Nanthakumar, Y. R. Lau, V. J. Plumb, A. E. Epstein, and G. N. Kay Letter Regarding Article by Nanthakumar et al, "Electrophysiological Findings in Adolescents With Atrial Fibrillation Who Have Structurally Normal Hearts" * Response Circulation, January 25, 2005; 111(3): e27 - e27. [Full Text] [PDF]
|
|
|
|
|
|
C. Chimenti, A. Russo, M. Pieroni, F. Calabrese, R. Verardo, G. Thiene, M. A. Russo, A. Maseri, and A. Frustaci Intramyocyte Detection of Epstein-Barr Virus Genome by Laser Capture Microdissection in Patients With Inflammatory Cardiomyopathy Circulation, December 7, 2004; 110(23): 3534 - 3539. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Satoh, J. Iwasaka, M. Nakamura, T. Akatsu, Y. Shimoda, and K. Hiramori Increased expression of tumor necrosis factor-{alpha} converting enzyme and tumor necrosis factor-{alpha} in peripheral blood mononuclear cells in patients with advanced congestive heart failure Eur J Heart Fail, December 1, 2004; 6(7): 869 - 875. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Pieroni, R. Cavallaro, C. Chimenti, E. Smeraldi, and A. Frustaci Clozapine-Induced Hypersensitivity Myocarditis Chest, November 1, 2004; 126(5): 1703 - 1705. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M Burch Immune suppressive treatment in paediatric myocarditis: still awaiting the evidence Heart, October 1, 2004; 90(10): 1103 - 1104. [Full Text] [PDF]
|
|
|
|
|
|
M G. Gagliardi, M Bevilacqua, C Bassano, B Leonardi, R Boldrini, F D. Camassei, A Fierabracci, A G Ugazio, and G F Bottazzo Long term follow up of children with myocarditis treated by immunosuppression and of children with dilated cardiomyopathy Heart, October 1, 2004; 90(10): 1167 - 1171. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. T. Jaeggi, J.-C. Fouron, E. D. Silverman, G. Ryan, J. Smallhorn, and L. K. Hornberger Transplacental Fetal Treatment Improves the Outcome of Prenatally Diagnosed Complete Atrioventricular Block Without Structural Heart Disease Circulation, September 21, 2004; 110(12): 1542 - 1548. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Tsirka, K. Trinkaus, S.-C. Chen, S. E. Lipshultz, J. A. Towbin, S. D. Colan, V. Exil, A. W. Strauss, and C. E. Canter Improved outcomes of pediatric dilated cardiomyopathy with utilization of heart transplantation J. Am. Coll. Cardiol., July 21, 2004; 44(2): 391 - 397. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. E. Eckart, S. S. Love, J. E. Atwood, M. K. Arness, D. C. Cassimatis, C. L. Campbell, S. Y. Boyd, J. G. Murphy, D. L. Swerdlow, L. C. Collins, et al. Incidence and follow-up of inflammatory cardiac complications after smallpox vaccination J. Am. Coll. Cardiol., July 7, 2004; 44(1): 201 - 205. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C P P Hia, W C L Yip, B C Tai, and S C Quek Immunosuppressive therapy in acute myocarditis: an 18 year systematic review Arch. Dis. Child., June 1, 2004; 89(6): 580 - 584. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. C. Cassimatis, J. E. Atwood, R. M. Engler, P. E. Linz, J. D. Grabenstein, and M. N. Vernalis Smallpox vaccination and myopericarditis: a clinical review J. Am. Coll. Cardiol., May 5, 2004; 43(9): 1503 - 1510. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Taylor, E. Havari, M. F. McInerney, R. Bronson, K. W. Wucherpfennig, and M. A. Lipes A Spontaneous Model for Autoimmune Myocarditis Using the Human MHC Molecule HLA-DQ8 J. Immunol., February 15, 2004; 172(4): 2651 - 2658. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Calabrese and G. Thiene Myocarditis and inflammatory cardiomyopathy: microbiological and molecular biological aspects Cardiovasc Res, October 15, 2003; 60(1): 11 - 25. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Kuhl, M. Pauschinger, P. L. Schwimmbeck, B. Seeberg, C. Lober, M. Noutsias, W. Poller, and H.-P. Schultheiss Interferon-{beta} Treatment Eliminates Cardiotropic Viruses and Improves Left Ventricular Function in Patients With Myocardial Persistence of Viral Genomes and Left Ventricular Dysfunction Circulation, June 10, 2003; 107(22): 2793 - 2798. [Abstract] [Full Text] [PDF]
|
|