CLINICAL STUDY
Detection of viruses in myocardial tissues by polymerase chain reaction
evidence of adenovirus as a common cause of myocarditis in children and adults
Neil E. Bowles, PhD*,
Jiyuan Ni, MD*,
Debra L. Kearney, MD* ,
Matthias Pauschinger, MD ,
Heinz-Peter Schultheiss, MD,
Robert McCarthy, MD¶,
Joshua Hare, MD, FACC ,
J. Timothy Bricker, MD, FACC*,
Karla R. Bowles, PhD* and
Jeffrey A. Towbin, MD, FACC*||,*
* Departments of Pediatrics, Houston, Texas, USA
Pathology, Houston, Texas, USA
|| Molecular and Human Genetics, Houston, Texas, USA
¶ Cardiovascular Sciences, Baylor College of Medicine, Houston, Texas, USA
Medical Clinic II, University Hospital Benjamin Franklin, Berlin, Germany
Department of Internal Medicine, Division of Cardiology, The Johns Hopkins Hospital, Baltimore, Maryland, USA
Manuscript received October 14, 2002;
revised manuscript received February 24, 2003,
accepted March 12, 2003.
* Reprint requests and correspondence: Dr. Jeffrey A. Towbin, Department of Pediatrics (Cardiology), Baylor College of Medicine, 6621 Fannin, Room FC.430.09, Houston, Texas 77030, USA.
jtowbin{at}bcm.tmc.edu
OBJECTIVES: The purpose of this study was to analyze cardiac tissue and blood for viral genomes using polymerase chain reaction (PCR) to define the common viral etiologies of myocarditis by age group.
BACKGROUND: Enteroviruses are considered the most common cause of myocarditis at all ages. Diagnosis relies on viral cultures, serology, and cardiac histology, which lack sensitivity, as well as PCR. However, in many cases enteroviruses are not detected.
METHODS: Cardiac samples were obtained for PCR analysis from patients with myocarditis (n = 624) and dilated cardiomyopathy (DCM) (n = 149). Patients were analyzed by age group, including neonates (n = 116), infants (n = 191), toddlers (n = 87), children (n = 110), adolescents (n = 92), and adults (n = 177). After nucleic acids had been extracted from an endomyocardial biopsy, an explant, or autopsy samples, PCR and reverse transcription PCR were performed to detect the genomic sequences of enterovirus, adenovirus, cytomegalovirus (CMV), herpes simplex virus (HSV), Epstein-Barr virus (EBV), parvovirus, respiratory syncytial virus (RSV), and influenza A virus.
RESULTS: Viral genome was amplified (adenovirus = 142, enterovirus = 85, CMV = 18, parvovirus = 6, influenza A = 5, HSV = 5, EBV = 3, RSV = 1) from 239 (38%) of the 624 samples from myocarditis patients, including 26 patient samples in which dual infection was found. Virus was detected in 30 (20%) of 149 DCM patient samples; only adenovirus (n = 18) and enterovirus (n = 12) were detected.
CONCLUSIONS: Polymerase chain reaction identified adenovirus as the most common virus in the myocardium of children and adults with myocarditis and DCM. Although enteroviruses are also found in these patients, they appear to be a less common cause of myocarditis than adenovirus.
|
Abbreviations and Acronyms
| | CHF | | congestive heart failure | | CMV | | cytomegalovirus | | DCM | | dilated cardiomyopathy | | EBV | | Epstein-Barr virus | | EFE | | endocardial fibroelastosis | | EMB | | endomyocardial biopsy | | HSV | | herpes simplex virus | | LV | | left ventricle/ventricular | | OHT | | orthotopic heart transplantation | | PCR | | polymerase chain reaction | | RNA | | ribonucleic acid | | RSV | | respiratory syncytial virus | | RV | | right ventricle/ventricular |
|
This article has been cited by other articles:
|
|
|
|
 
J. C. Schultz, A. A. Hilliard, L. T. Cooper Jr, and C. S. Rihal
Diagnosis and Treatment of Viral Myocarditis
Mayo Clin. Proc.,
November 1, 2009;
84(11):
1001 - 1009.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N H Prakken, B K Velthuis, M J Cramer, and A Mosterd
Advances in cardiac imaging: the role of magnetic resonance imaging and computed tomography in identifying athletes at risk
Br. J. Sports Med.,
September 1, 2009;
43(9):
677 - 684.
[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]
|
|
|
|
|
|
|
T. Yajima and K. U. Knowlton
Viral Myocarditis: From the Perspective of the Virus
Circulation,
May 19, 2009;
119(19):
2615 - 2624.
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. T. Garnett, G. Talekar, J. A. Mahr, W. Huang, Y. Zhang, D. A. Ornelles, and L. R. Gooding
Latent Species C Adenoviruses in Human Tonsil Tissues
J. Virol.,
March 15, 2009;
83(6):
2417 - 2428.
[Abstract]
[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 Comar, P D'Agaro, C Campello, A Poli, J P Breinholt III, J A Towbin, and M Vatta
Human herpes virus 6 in archival cardiac tissues from children with idiopathic dilated cardiomyopathy or congenital heart disease
J. Clin. Pathol.,
January 1, 2009;
62(1):
80 - 83.
[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]
|
|
|
|
|
|
|
M A Weber, M T Ashworth, R A Risdon, M Malone, M Burch, and N J Sebire
Clinicopathological features of paediatric deaths due to myocarditis: an autopsy series
Arch. Dis. Child.,
July 1, 2008;
93(7):
594 - 598.
[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]
|
|
|
|
|
|
|
L. T. Cooper, K. L. Baughman, A. M. Feldman, A. Frustaci, M. Jessup, U. Kuhl, G. N. Levine, J. Narula, R. C. Starling, J. Towbin, et al.
The role of endomyocardial biopsy in the management of cardiovascular disease: A Scientific Statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology Endorsed by the Heart Failure Society of America and the Heart Failure Association of the European Society of Cardiology
Eur. Heart J.,
December 2, 2007;
28(24):
3076 - 3093.
[Full Text]
[PDF]
|
|
|
|
|
|
|
U Sechtem, H Mahrholdt, and H Vogelsberg
Cardiac magnetic resonance in myocardial disease
Heart,
December 1, 2007;
93(12):
1520 - 1527.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. T. Cooper, K. L. Baughman, A. M. Feldman, A. Frustaci, M. Jessup, U. Kuhl, G. N. Levine, J. Narula, R. C. Starling, J. Towbin, et al.
The Role of Endomyocardial Biopsy in the Management of Cardiovascular Disease: A Scientific Statement From the American Heart Association, the American College of Cardiology, and the European Society of Cardiology Endorsed by the Heart Failure Society of America and the Heart Failure Association of the European Society of Cardiology
J. Am. Coll. Cardiol.,
November 6, 2007;
50(19):
1914 - 1931.
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. T. Cooper, K. L. Baughman, A. M. Feldman, A. Frustaci, M. Jessup, U. Kuhl, G. N. Levine, J. Narula, R. C. Starling, J. Towbin, et al.
The Role of Endomyocardial Biopsy in the Management of Cardiovascular Disease: A Scientific Statement From the American Heart Association, the American College of Cardiology, and the European Society of Cardiology
Circulation,
November 6, 2007;
116(19):
2216 - 2233.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Hausler, B. Sellhaus, S. Scheithauer, B. Gaida, S. Kuropka, K. Siepmann, A. Panek, W. Berg, A. Teubner, K. Ritter, et al.
Myocarditis in newborn wild-type BALB/c mice infected with the murine gamma herpesvirus MHV-68
Cardiovasc Res,
November 1, 2007;
76(2):
323 - 330.
[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]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
J. Kilo, G. Laufer, and H. Antretter
Endomyocardial biopsy - jugular/subclavian vein approach
MMCTS,
November 10, 2006;
2006(1110):
1149.
[Abstract]
[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]
|
|
|
|
|
|
|
G. F. Cox, L. A. Sleeper, A. M. Lowe, J. A. Towbin, S. D. Colan, E. J. Orav, P. R. Lurie, J. E. Messere, J. D. Wilkinson, and S. E. Lipshultz
Factors Associated With Establishing a Causal Diagnosis for Children With Cardiomyopathy
Pediatrics,
October 1, 2006;
118(4):
1519 - 1531.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N Amabile, A Fraisse, J Bouvenot, P Chetaille, and C Ovaert
Outcome of acute fulminant myocarditis in children
Heart,
September 1, 2006;
92(9):
1269 - 1273.
[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]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
H. Abdel-Aty, P. Boye, A. Zagrosek, R. Wassmuth, A. Kumar, D. Messroghli, P. Bock, R. Dietz, M. G. Friedrich, and J. Schulz-Menger
Diagnostic Performance of Cardiovascular Magnetic Resonance in Patients With Suspected Acute Myocarditis: Comparison of Different Approaches
J. Am. Coll. Cardiol.,
June 7, 2005;
45(11):
1815 - 1822.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. P. Liu and A. T. Yan
Cardiovascular Magnetic Resonance for the Diagnosis of Acute Myocarditis: Prospects for Detecting Myocardial Inflammation
J. Am. Coll. Cardiol.,
June 7, 2005;
45(11):
1823 - 1825.
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. J. Maron, M. J. Ackerman, R. A. Nishimura, R. E. Pyeritz, J. A. Towbin, and J. E. Udelson
Task Force 4: HCM and other cardiomyopathies, mitral valve prolapse, myocarditis, and Marfan syndrome
J. Am. Coll. Cardiol.,
April 19, 2005;
45(8):
1340 - 1345.
[Full Text]
[PDF]
|
|
|
|
|
|
|
N Spanakis, E N Manolis, A Tsakris, S Tsiodras, T Panagiotopoulos, G Saroglou, and N J Legakis
Coxsackievirus B3 sequences in the myocardium of fatal cases in a cluster of acute myocarditis in Greece
J. Clin. Pathol.,
April 1, 2005;
58(4):
357 - 360.
[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]
|
|
|
|
|
|
|
C. Tschope, C.-T. Bock, M. Kasner, M. Noutsias, D. Westermann, P.-L. Schwimmbeck, M. Pauschinger, W.-C. Poller, U. Kuhl, R. Kandolf, et al.
High Prevalence of Cardiac Parvovirus B19 Infection in Patients With Isolated Left Ventricular Diastolic Dysfunction
Circulation,
February 22, 2005;
111(7):
879 - 886.
[Abstract]
[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]
|
|
|
|
|
|
|
K. Pehler-Harrington, M. Khanna, C. R. Waters, and K. J. Henrickson
Rapid Detection and Identification of Human Adenovirus Species by Adenoplex, a Multiplex PCR-Enzyme Hybridization Assay
J. Clin. Microbiol.,
September 1, 2004;
42(9):
4072 - 4076.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. N. DeMaria, O. Ben-Yehuda, D. Berman, G. K. Feld, B. H. Greenberg, J. D. Knoke, K. U. Knowlton, W. Y. W. Lew, and S. Tsimikas
Highlights of the year in JACC 2003
J. Am. Coll. Cardiol.,
December 17, 2003;
42(12):
2156 - 2166.
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Baboonian and W. McKenna
Eradication of viral myocarditis: Is there hope?
J. Am. Coll. Cardiol.,
August 6, 2003;
42(3):
473 - 476.
[Full Text]
[PDF]
|
|
|
|
