Background: The meaning of viral nucleic acids in the myocardium in many cases is difficult for clinical interpretation, whereas the presence of viral nucleic acids in the serum is a marker of active infection. We determined the diagnostic value of viral nucleic acids in ventricular serum and peripheral serum samples in comparison with endomyocardial biopsy (EMB) specimens in patients with clinically suspected myocarditis. Methods: The viral nucleic acid evaluation was performed in serum samples and EMB specimens by real-time PCR in 70 patients (age: 47 ± 16 years). The biopsy specimens were examined by histo- and immunohistochemistry to detect inflammatory response. Results: The viral nucleic acids were detected in ventricular and peripheral serum, and EMB samples of 10 (14%), 14 (20%), and 32 (46%) patients, respectively. Notably, viral nucleic acids of the same virus as in the EMB sample were present more often in ventricular than in peripheral serum (60 vs. 7%, p = 0.01). A significant concurrence was observed between the positive and the negative results of viral nucleic acids present in EMB and ventricular serum (p = 0.0001). Conclusions: The detection of the same viral nucleic acid type in the myocardium and in ventricular serum being significantly more frequent than in the peripheral serum may suggest that the site of the blood collection is important for more precise and reliable confirmation of the active viral replication in the heart.

1.
Yajima T, Knowlton KU: Viral myocarditis: from the perspective of the virus. Circulation 2009;119:2615-2624.
2.
Kindermann I, Barth C, Mahfoud F, et al: Update on myocarditis. J Am Coll Cardiol 2012;59:779-792.
3.
Caforio ALP, Pankuweit S, Arbustini S, et al: Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J 2013;34:2636-2648.
4.
Schenk T, Enders M, Pollak S, Hahn R, Huzly D: High prevalence of human parvovirus B19 DNA in myocardial autopsy samples from subjects without myocarditis or dilative cardiomyopathy. J Clin Microbiol 2009;47:106-110.
5.
Kühl U, Pauschinger M, Noutsias M, et al: High prevalence of viral genomes and multiple viral infections in the myocardium of adults with ‘idiopathic' left ventricular dysfunction. Circulation 2005;111:887-893.
6.
Kindermann I, Kindermann M, Kandolf R, Klingel K, Bultmann B, Muller T, Lindinger A, Böhm M: Predictors of outcome in patients with suspected myocarditis. Circulation 2008;118:639-648.
7.
Kühl U, Noutsias M, Seeberg B, Schultheiss HP: Immunohistological evidence for a chronic intramyocardial inflammatory process in dilated cardiomyopathy. Heart 1996;75:295-300.
8.
Razonable RR, Brown RA, Wilson J, Groettum C, Kremers W, Espy M, Smith TF, Paya CV: The clinical use of various blood compartments for cytomegalovirus (CMV) DNA quantitation in transplant recipients with CMV disease. Transplantation 2002;73:968-973.
9.
Evans PC, Soin A, Wreghitt TG, Alexander GJ: Qualitative and semiquantitative polymerase chain reaction testing for cytomegalovirus DNA in serum allows prediction of CMV related disease in liver transplant recipients. J Clin Pathol 1998;51:914-921.
10.
Cunningham R, Harris A, Frankton A, Irving W: Detection of cytomegalovirus using PCR in serum from renal transplant recipients. J Clin Pathol 1995;48:575-577.
11.
Eckart P, Brouard J, Vabret A, Freymuth F, Guillot M, Ryckelynck JP, Hurault de Ligny B: Detection of human cytomegalovirus in renal transplantation: comparison of four diagnostic methods: DNA in sera by polymerase chain reaction (PCR), DNA in leukocyte by PCR, pp65 leukocytic antigenemia, and viremia. Transplant Proc 1997;29:2387-2389.
12.
Mahfoud F, Gärtner B, Kindermann M, et al: Virus serology in patients with suspected myocarditis: utility or futility? Eur Heart J 2011;32:897-903.
13.
Richardson P, McKenna W, Bristow M, Maisch B, Mautner B, O'Connell J, Olsen E, Thiene G, Goodwin J, Gyarfas I, Martin I, Nordet P: Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the Definition and Classification of cardiomyopathies. Circulation 1996;93:841-842.
14.
Leś K, Przybylski M, Dzieciątkowski T, et al: Zastosowanie metody real-time PCR do wykrywania HEV człowieka. Med Dosw Mikrobiol 2010;62:245-253.
15.
Dzieciątkowski T, Przybylski M, Gieryńska M, et al: Wykorzystanie metody real-time PCR do wykrywania DNA ludzkiego herpeswirusa typu 6. Med Dosw Mikrobiol 2008;60:259-265.
16.
Rola A, Przybylski M, Dzieciątkowski D, et al: Zastosowanie metody real-time PCR z użyciem sond Taqman do wykrywania zakażeń adenowirusami człowieka. Med Dosw Mikrobiol 2007;59:371-377.
17.
Kandolf R: Diagnosis of myocarditis. Dtsch Med Wochenschr 2011;136:829-835.
18.
Mella JR, Chiswick EL, King E, Remick DG: Location, location, location: cytokine concentrations are dependent on blood sampling site. Shock 2014;42:337-342.
19.
Jensen KJ, Garmaroudi FS, Zhang J, Lin J, Boroomand S, Zhang M, Luo Z, Yang D, Luo H, McManus BM, Janes KA: An ERK-p38 subnetwork coordinates host cell apoptosis and necrosis during coxsackievirus B3 infection. Cell Host Microbe 2013;13:67-76.
20.
Kuethe F, Lindner J, Matschke K, et al: Prevalence of parvovirus B19 and human bocavirus DNA in the heart of patients with no evidence of dilated cardiomyopathy or myocarditis. Clin Infect Dis 2009;49:1660-1666.
21.
Kühl U, Pauschinger M, Seeberg B, et al: Viral persistence in the myocardium is associated with progressive cardiac dysfunction. Circulation 2005;112:1965-1970.
22.
Dennert R, Crijns HJ, Heymans S: Acute viral myocarditis. Eur Heart J 2008;29:2073-2082.
23.
Mahrholdt H, Wagner A, Deluigi CC, et al: Presentation, patterns of myocardial damage, and clinical course of viral myocarditis. Circulation 2006;114:1581-1590.
24.
Donoso Mantke O, Nitsche A, Meyer R, Klingel K, Niedrig M: Analysing myocardial tissue from explanted hearts of heart transplant recipients and multi-organ donors for the presence of parvovirus B19 DNA. J Clin Virol 2004;31:32-39.
25.
Yaghobi R, Langari MJ, Ramzi M, Geramizadeh B, Zakerinia M, Khojasteh HN, Dehghani M: Molecular impact and inducible factors associated with adenovirus infection in hematopoietic stem [corrected] cell transplant patients. Transplant Proc 2011;43:644-646.
26.
Kühl U, Schultheiss HP: Viral myocarditis: diagnosis, aetiology and management. Drugs 2009;69:1287-1302.
27.
Bock CT, Klingel K, Kandolf R: Human parvovirus B19-associated myocarditis. N Engl J Med 2010;362:1248-1249.
28.
Lévêque N, Renois F, Talmud D, Nguyen Y, Lesaffre F, Boulagnon C, Bruneval P, Fornes P, Andréoletti L: Quantitative genomic and antigenomic enterovirus RNA detection in explanted heart tissue samples from patients with end-stage idiopathic dilated cardiomyopathy. J Clin Microbiol 2012;50:3378-3380.
29.
Jeserich M, Brunner E, Kandolf R, Olschewski M, Kimmel S, Friedrich MG, Föll D, Bode C, Geibel A: Diagnosis of viral myocarditis by cardiac magnetic resonance and viral genome detection in peripheral blood. Int J Cardiovasc Imaging 2013;29:121-129.
30.
Lisboa LF, Asberg A, Kumar D, Pang X, Hartmann A, Preiksaitis JK, Pescovitz MD, Rollag H, Jardine AG, Humar A: The clinical utility of whole blood versus plasma cytomegalovirus viral load assays for monitoring therapeutic response. Transplantation 2011;91:231-236.
31.
Emery VC, Sabin CA, Cope AV, Gor D, Hassan-Walker AF, Griffiths PD: Application of viral-load kinetics to identify patients who develop cytomegalovirus disease after transplantation. Lancet 2000;355:2032-2036.
32.
Basso C, Calabrese F, Angelini A, Carturan E, Thiene G: Classification and histological, immunohistochemical, and molecular diagnosis of inflammatory myocardial disease. Heart Fail Rev 2013;18:673-681.
33.
Adda J, Machado S, Eberst E, Roubille C, Macia JC, Roubille F: Parvovirus B19 infection and acute myocarditis. Inter Med 2010;49:79.
34.
Bültmann BD, Klingel K, Sotlar K, Bock CT, Baba HA, Sauter M, Kandolf R: Fatal parvovirus B19-associated myocarditis clinically mimicking ischemic heart disease: an endothelial cell-mediated disease. Hum Pathol 2003;34:92-95.
35.
Kühl U, Pauschinger M, Bock T, et al: Parvovirus B19 infection mimicking acute myocardial infarction. Circulation 2003;108:945-950.
36.
Schultheiss HP, Kühl U, Cooper LT: The management of myocarditis. Eur Heart J 2011;32:2616-2625.
37.
Suparno C, Milligan DW, Moss PA, Mautner V: Adenovirus infections in stem cell transplant recipients: recent developments in understanding of pathogenesis, diagnosis and management. Leuk Lymphoma 2004;45:873-885.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.