| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2003;107:2793.)
© 2003 American Heart Association, Inc.
Clinical Investigation and Reports |
From the Department of Cardiology and Pneumology, University Hospital Benjamin-Franklin, Freie Universität Berlin, Germany.
Correspondence to Uwe Kühl, PhD, Medizinische Klinik II, Abteilung für Kardiologie und Pneumologie, Benjamin-Franklin-Klinikum, Freie Universität Berlin, Hindenburgdamm 30, D-12200 Berlin, Germany. E-mail dcmkuehl{at}zedat.fu-berlin.de
Background Viral infections are important causes of myocarditis and may induce cardiac dysfunction and finally lead to dilated cardiomyopathy. We investigated whether interferon (IFN)-ß therapy is safe and may achieve virus clearance and prevent deterioration of left ventricular (LV) function in patients with myocardial virus persistence.
Methods and Results In this phase II study, 22 consecutive patients with persistence of LV dysfunction (history of symptoms, 44±27 months) and polymerase chain reactionproven enteroviral or adenoviral genomes were treated with 18x106 IU/week IFN-ß (Beneferon) subcutaneously for 24 weeks. Histological and immunohistological analysis of endomyocardial biopsies was used to characterize myocardial inflammation. LV diameters and ejection fraction were assessed by echocardiography and angiography, respectively. During the treatment period, IFN-ß was well tolerated by all patients. No patient deteriorated. Clearance of viral genomes was observed in 22 of 22 of patients after antiviral therapy. Virus clearance was paralleled by a significant decrease of LV end diastolic and end systolic diameters, decreasing from 59.7±11.1 to 56.5±10.0 mm (P<0.001) and 43.2±13.6 to 39.4±12.1 mm (P<0.001), respectively. LV ejection fraction increased from 44.6±15.5% to 53.1±16.8% (P<0.001).
Conclusions A 6 months, IFN-ß treatment was safe in patients with myocardial enteroviral or adenoviral persistence and LV dysfunction and resulted in elimination of viral genomes (22 of 22 patients) and improved LV function (15 of 22 patients).
Key Words: cardiomyopathy viruses biopsy heart failure
This article has been cited by other articles:
![]() |
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] |
||||
![]() |
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., June 25, 2009; (2009) ehp249v1. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. RAMARAJ and V. L. SORRELL Peripartum cardiomyopathy: Causes, diagnosis, and treatment Cleveland Clinic Journal of Medicine, May 1, 2009; 76(5): 289 - 296. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. T. Cooper Jr. Myocarditis N. Engl. J. Med., April 9, 2009; 360(15): 1526 - 1538. [Full Text] [PDF] |
||||
![]() |
S. Heymans, E. Hirsch, S. D. Anker, P. Aukrust, J.-L. Balligand, J. W. Cohen-Tervaert, H. Drexler, G. Filippatos, S. B. Felix, L. Gullestad, et al. Inflammation as a therapeutic target in heart failure? A scientific statement from the Translational Research Committee of the Heart Failure Association of the European Society of Cardiology Eur J Heart Fail, February 1, 2009; 11(2): 119 - 129. [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] |
||||
![]() |
I. Kindermann, M. Kindermann, R. Kandolf, K. Klingel, B. Bultmann, T. Muller, A. Lindinger, and M. Bohm Predictors of Outcome in Patients With Suspected Myocarditis Circulation, August 5, 2008; 118(6): 639 - 648. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Dennert, H. J. Crijns, and S. Heymans Acute viral myocarditis Eur. Heart J., July 9, 2008; (2008) ehn296v1. [Abstract] [Full Text] [PDF] |
||||
![]() |
Z. Shijie, J. Moriya, J. Yamakawa, R. Chen, T. Takahashi, H. Sumino, T. Nakahashi, K. Iwai, S. Morimoto, N. Yamaguchi, et al. Mao-to Prolongs the Survival of and Reduces TNF-{alpha} Expression in Mice with Viral Myocarditis Evid. Based Complement. Altern. Med., February 24, 2008; (2008) nen010v1. [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] |
||||
![]() |
L. Brunetti and E. R. H. DeSantis Treatment of viral myocarditis caused by coxsackievirus B Am. J. Health Syst. Pharm., January 15, 2008; 65(2): 132 - 137. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Zurney, K. E. Howard, and B. Sherry Basal Expression Levels of IFNAR and Jak-STAT Components Are Determinants of Cell-Type-Specific Differences in Cardiac Antiviral Responses J. Virol., December 15, 2007; 81(24): 13668 - 13680. [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] |
||||
![]() |
Y.-X. Wang, V. da Cunha, J. Vincelette, K. White, S. Velichko, Y. Xu, C. Gross, R. M. Fitch, M. Halks-Miller, B. R. Larsen, et al. Antiviral and myocyte protective effects of murine interferon-beta and -{alpha}2 in coxsackievirus B3-induced myocarditis and epicarditis in Balb/c mice Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H69 - H76. [Abstract] [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] |
||||
![]() |
Y. Maekawa, M. Ouzounian, M. A. Opavsky, and P. P. Liu Connecting the Missing Link Between Dilated Cardiomyopathy and Viral Myocarditis: Virus, Cytoskeleton, and Innate Immunity Circulation, January 2, 2007; 115(1): 5 - 8. [Full Text] [PDF] |
||||
![]() |
M. W. Cunningham T Regulatory Cells: Sentinels Against Autoimmune Heart Disease Circ. Res., November 10, 2006; 99(10): 1024 - 1026. [Full Text] [PDF] |
||||
![]() |
H. Mahrholdt, A. Wagner, C. C. Deluigi, E. Kispert, S. Hager, G. Meinhardt, H. Vogelsberg, P. Fritz, J. Dippon, C. -T. Bock, et al. Presentation, Patterns of Myocardial Damage, and Clinical Course of Viral Myocarditis Circulation, October 10, 2006; 114(15): 1581 - 1590. [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] |
||||
![]() |
O. Zimmermann, O. Grebe, N. Merkle, T. Nusser, M. Kochs, M. Bienek-Ziolkowski, V. Hombach, and J. Torzewski Myocardial biopsy findings and gadolinium enhanced cardiovascular magnetic resonance in dilated cardiomyopathy Eur J Heart Fail, March 1, 2006; 8(2): 162 - 166. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Rutschow, J. Li, H.-P. Schultheiss, and M. Pauschinger Myocardial proteases and matrix remodeling in inflammatory heart disease Cardiovasc Res, February 15, 2006; 69(3): 646 - 656. [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] |
||||
![]() |
Y. Asaumi, S. Yasuda, I. Morii, H. Kakuchi, Y. Otsuka, A. Kawamura, Y. Sasako, T. Nakatani, H. Nonogi, and S. Miyazaki Favourable clinical outcome in patients with cardiogenic shock due to fulminant myocarditis supported by percutaneous extracorporeal membrane oxygenation Eur. Heart J., October 2, 2005; 26(20): 2185 - 2192. [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] |
||||
![]() |
R. Wessely Interference by interferons: Janus faces in vascular proliferative diseases Cardiovasc Res, June 1, 2005; 66(3): 433 - 443. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. J. Stewart, K. Smoak, M. A. Blum, and B. Sherry Basal and Reovirus-Induced Beta Interferon (IFN-{beta}) and IFN-{beta}-Stimulated Gene Expression Are Cell Type Specific in the Cardiac Protective Response J. Virol., March 1, 2005; 79(5): 2979 - 2987. [Abstract] [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 Burch Immune suppressive treatment in paediatric myocarditis: still awaiting the evidence Heart, October 1, 2004; 90(10): 1103 - 1104. [Full Text] [PDF] |
||||
![]() |
U. Kuhl, M. Pauschinger, T. Bock, K. Klingel, C. P. L. Schwimmbeck, B. Seeberg, L. Krautwurm, W. Poller, H.-P. Schultheiss, and R. Kandolf Parvovirus B19 Infection Mimicking Acute Myocardial Infarction Circulation, August 26, 2003; 108(8): 945 - 950. [Abstract] [Full Text] [PDF] |
||||
|
Circulation Home | Subscriptions | Archives | Feedback | Authors | Help | AHA Journals Home | Search Copyright © 2003 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited. |