Top

Forensic Science, Medicine and Pathology

Published in:

01-09-2014 | Original Article

The presence of enterovirus, adenovirus, and parvovirus B19 in myocardial tissue samples from autopsies: an evaluation of their frequencies in deceased individuals with myocarditis and in non-inflamed control hearts

Authors: Trine Skov Nielsen, Jakob Hansen, Lars Peter Nielsen, Ulrik Thorngren Baandrup, Jytte Banner

Published in: Forensic Science, Medicine and Pathology | Issue 3/2014

Abstract

Purpose

Multiple viruses have been detected in cardiac tissue, but their role in causing myocarditis remains controversial. Viral diagnostics are increasingly used in forensic medicine, but the interpretation of the results can sometimes be challenging. In this study, we examined the prevalence of adenovirus, enterovirus, and parvovirus B19 (PVB) in myocardial autopsy samples from myocarditis related deaths and in non-inflamed control hearts in an effort to clarify their significance as the causes of myocarditis in a forensic material.

Methods

We collected all autopsy cases diagnosed with myocarditis from 1992 to 2010. Eighty-four suicidal deaths with morphologically normal hearts served as controls. Polymerase chain reaction was used for the detection of the viral genomes (adenovirus, enterovirus, and PVB) in myocardial tissue specimens. The distinction between acute and persistent PVB infection was made by the serological determination of PVB-specific immunoglobulins M and G.

Results

PVB was detected in 33 of 112 (29 %) myocarditis cases and 37 of 84 (44 %) control cases. All of the samples were negative for the presence of adenovirus and enterovirus. Serological evidence of an acute PVB infection, determined by the presence of immunoglobulin M, was only present in one case. In the remaining cases, PVB was considered to be a bystander with no or limited association to myocardial inflammation.

Conclusion

In this study, adenovirus, enterovirus, and PVB were found to be rare causes of myocarditis. The detection of PVB in myocardial autopsy samples most likely represents a persistent infection with no or limited association with myocardial inflammation. The forensic investigation of myocardial inflammation demands a thorough examination, including special attention to non-viral causes and requires a multidisciplinary approach.

Doolan A, Langlois N, Semsarian C. Causes of sudden cardiac death in young Australians. Med J Aust. 2004;180(3):110–2.PubMed

Langlois NE. Sudden adult death. Forensic Sci Med Pathol. 2009;5(3):210–32.PubMedCrossRef

Diaz FJ, Loewe C, Jackson A. Death caused by myocarditis in Wayne County, Michigan: a 9-year retrospective study. Am J Forensic Med Pathol. 2006;27(4):300–3.PubMedCrossRef

Burke AP, Saenger J, Mullick F, Virmani R. Hypersensitivity myocarditis. Arch Pathol Lab Med. 1991;115(8):764–9.PubMed

Courand PY, Croisille P, Khouatra C, Cottin V, Kirkorian G, Bonnefoy E. Churg–Strauss syndrome presenting with acute myocarditis and cardiogenic shock. Heart Lung Circ. 2012;21(3):178–81.PubMedCrossRef

De BD, Serroni N, Campanella D, Olivieri L, Ferri F, Carano A, et al. Update on the adverse effects of clozapine: focus on myocarditis. Curr Drug Saf. 2012;7(1):55–62.CrossRef

Nicklin A, Byard RW. Lethal manifestations of systemic lupus erythematosus in a forensic context. J Forensic Sci. 2011;56(2):423–8.PubMedCrossRef

Phillips K, Luk A, Soor GS, Abraham JR, Leong S, Butany J. Cocaine cardiotoxicity: a review of the pathophysiology, pathology, and treatment options. Am J Cardiovasc Drugs. 2009;9(3):177–96.PubMedCrossRef

Pilgrim JL, Woodford N, Drummer OH. Cocaine in sudden and unexpected death: a review of 49 post-mortem cases. Forensic Sci Int. 2013;227(1–3):52–9.PubMedCrossRef

10.

Kawai C, Matsumori A. Dilated cardiomyopathy update: infectious-immune theory revisited. Heart Fail Rev. 2013;18(6):703–14.PubMedCrossRef

11.

Kindermann I, Barth C, Mahfoud F, Ukena C, Lenski M, Yilmaz A, et al. Update on myocarditis. J Am Coll Cardiol. 2012;59(9):779–92.PubMedCrossRef

12.

Yajima T, Knowlton KU. Viral myocarditis: from the perspective of the virus. Circulation. 2009;119(19):2615–24.PubMedCrossRef

13.

Byard RW. Forensic pathology and problems in determining cause of death. Forensic Sci Med Pathol. 2008;4(2):73–4.PubMedCrossRef

14.

Casali MB, Lazzaro A, Gentile G, Blandino A, Ronchi E, Zoja R. Forensic grading of myocarditis: an experimental contribution to the distinction between lethal myocarditis and incidental myocarditis. Forensic Sci Int. 2012;223(1–3):78–86.PubMedCrossRef

15.

Caforio AL, Pankuweit S, Arbustini E, Basso C, Gimeno-Blanes J, Felix SB, 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(33):2636–48.PubMedCrossRef

16.

Bowles NE, Ni J, Kearney DL, Pauschinger M, Schultheiss HP, McCarthy R, et al. Detection of viruses in myocardial tissues by polymerase chain reaction. Evidence of adenovirus as a common cause of myocarditis in children and adults. J Am Coll Cardiol. 2003;42(3):466–72.PubMedCrossRef

17.

Gaaloul I, Riabi S, Harrath R, Evans M, Salem NH, Mlayeh S, et al. Sudden unexpected death related to enterovirus myocarditis: histopathology, immunohistochemistry and molecular pathology diagnosis at post-mortem. BMC Infect Dis. 2012;12:212.PubMedCentralPubMedCrossRef

18.

Guarner J, Bhatnagar J, Shieh WJ, Nolte KB, Klein D, Gookin MS, et al. Histopathologic, immunohistochemical, and polymerase chain reaction assays in the study of cases with fatal sporadic myocarditis. Hum Pathol. 2007;38(9):1412–9.PubMedCrossRef

19.

Hufnagel G, Pankuweit S, Richter A, Schonian U, Maisch B. The European Study of Epidemiology and Treatment of Cardiac Inflammatory Diseases (ESETCID). First epidemiological results. Herz. 2000;25(3):279–85.PubMedCrossRef

20.

Kindermann I, Kindermann M, Kandolf R, Klingel K, Bultmann B, Muller T, et al. Predictors of outcome in patients with suspected myocarditis. Circulation. 2008;118(6):639–48.PubMedCrossRef

21.

Koepsell SA, Anderson DR, Radio SJ. Parvovirus B19 is a bystander in adult myocarditis. Cardiovasc Pathol. 2012;21(6):476–81.PubMedCrossRef

22.

Kyto V, Vuorinen T, Saukko P, Lautenschlager I, Lignitz E, Saraste A, et al. Cytomegalovirus infection of the heart is common in patients with fatal myocarditis. Clin Infect Dis. 2005;40(5):683–8.PubMedCrossRef

23.

Mahrholdt H, Wagner A, Deluigi CC, Kispert E, Hager S, Meinhardt G, et al. Presentation, patterns of myocardial damage, and clinical course of viral myocarditis. Circulation. 2006;114(15):1581–90.PubMedCrossRef

24.

Martin AB, Webber S, Fricker FJ, Jaffe R, Demmler G, Kearney D, et al. Acute myocarditis. Rapid diagnosis by PCR in children. Circulation. 1994;90(1):330–9.PubMedCrossRef

25.

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(1):106–10.PubMedCentralPubMedCrossRef

26.

Bultmann BD, Klingel K, Sotlar K, Bock CT, Baba HA, Sauter M, et al. Fatal parvovirus B19-associated myocarditis clinically mimicking ischemic heart disease: an endothelial cell-mediated disease. Hum Pathol. 2003;34(1):92–5.PubMedCrossRef

27.

Pankuweit S, Klingel K. Viral myocarditis: from experimental models to molecular diagnosis in patients. Heart Fail Rev. 2013;18(6):683–702.PubMedCrossRef

28.

Soderlund-Venermo M, Hokynar K, Nieminen J, Rautakorpi H, Hedman K. Persistence of human parvovirus B19 in human tissues. Pathol Biol (Paris). 2002;50(5):307–16.CrossRef

29.

Cassinotti P, Burtonboy G, Fopp M, Siegl G. Evidence for persistence of human parvovirus B19 DNA in bone marrow. J Med Virol. 1997;53(3):229–32.PubMedCrossRef

30.

Soderlund M, von ER, Haapasaari J, Kiistala U, Kiviluoto O, Hedman K. Persistence of parvovirus B19 DNA in synovial membranes of young patients with and without chronic arthropathy. Lancet. 1997;349(9058):1063–5.PubMedCrossRef

31.

Modrow S, Dorsch S. Antibody responses in parvovirus B19 infected patients. Pathol Biol (Paris). 2002;50(5):326–31.CrossRef

32.

Aretz HT. Myocarditis: the Dallas criteria. Hum Pathol. 1987;18(6):619–24.PubMedCrossRef

33.

Loewe R. RNA-Isolation aus FFPE-Gewebe: Säulchen- und Bead-basierte Methoden. Laborwelt. 2011;12(5):38–9.

34.

Heim A, Ebnet C, Harste G, Pring-Akerblom P. Rapid and quantitative detection of human adenovirus DNA by real-time PCR. J Med Virol. 2003;70(2):228–39.PubMedCrossRef

35.

Baylis SA, Shah N, Minor PD. Evaluation of different assays for the detection of parvovirus B19 DNA in human plasma. J Virol Methods. 2004;121(1):7–16.PubMedCrossRef

36.

Rotbart HA. Enzymatic RNA amplification of the enteroviruses. J Clin Microbiol. 1990;28(3):438–42.PubMedCentralPubMed

37.

Mohamed N, Elfaitouri A, Fohlman J, Friman G, Blomberg J. A sensitive and quantitative single-tube real-time reverse transcriptase-PCR for detection of enteroviral RNA. J Clin Virol. 2004;30(2):150–6.PubMedCrossRef

38.

Hansen J, Corydon TJ, Palmfeldt J, Durr A, Fontaine B, Nielsen MN, et al. Decreased expression of the mitochondrial matrix proteases Lon and ClpP in cells from a patient with hereditary spastic paraplegia (SPG13). Neuroscience. 2008;153(2):474–82.PubMedCrossRef

39.

Donoso MO, Meyer R, Prosch S, Nitsche A, Leitmeyer K, Kallies R, et al. High prevalence of cardiotropic viruses in myocardial tissue from explanted hearts of heart transplant recipients and heart donors: a 3-year retrospective study from a German patients’ pool. J Heart Lung Transplant. 2005;24(10):1632–8.CrossRef

40.

Kuethe F, Lindner J, Matschke K, Wenzel JJ, Norja P, Ploetze 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(11):1660–6.PubMedCrossRef

41.

Wang X, Zhang G, Liu F, Han M, Xu D, Zang Y. Prevalence of human parvovirus B19 DNA in cardiac tissues of patients with congenital heart diseases indicated by nested PCR and in situ hybridization. J Clin Virol. 2004;31(1):20–4.PubMedCrossRef

42.

Rohrer C, Gartner B, Sauerbrei A, Bohm S, Hottentrager B, Raab U, et al. Seroprevalence of parvovirus B19 in the German population. Epidemiol Infect. 2008;136(11):1564–75.PubMedCentralPubMedCrossRef

43.

Mahfoud F, Gartner B, Kindermann M, Ukena C, Gadomski K, Klingel K, et al. Virus serology in patients with suspected myocarditis: utility or futility? Eur Heart J. 2011;32(7):897–903.PubMedCrossRef

44.

Lamparter S, Schoppet M, Pankuweit S, Maisch B. Acute parvovirus B19 infection associated with myocarditis in an immunocompetent adult. Hum Pathol. 2003;34(7):725–8.PubMedCrossRef

45.

Why HJ, Meany BT, Richardson PJ, Olsen EG, Bowles NE, Cunningham L, et al. Clinical and prognostic significance of detection of enteroviral RNA in the myocardium of patients with myocarditis or dilated cardiomyopathy. Circulation. 1994;89(6):2582–9.PubMedCrossRef

46.

Mizuno T, Nagamura H, Iwamoto KS, Ito T, Fukuhara T, Tokunaga M, et al. RNA from decades–old archival tissue blocks for retrospective studies. Diagn Mol Pathol. 1998;7(4):202–8.PubMedCrossRef

47.

Farragher SM, Tanney A, Kennedy RD, Paul HD. RNA expression analysis from formalin fixed paraffin embedded tissues. Histochem Cell Biol. 2008;130(3):435–45.PubMedCrossRef

48.

Mason JW, O’Connell JB, Herskowitz A, Rose NR, McManus BM, Billingham ME, et al. A clinical trial of immunosuppressive therapy for myocarditis. The Myocarditis Treatment Trial Investigators. N Engl J Med. 1995;333(5):269–75.PubMedCrossRef

49.

Mintz L, Drew WL. Relation of culture site to the recovery of nonpolio enteroviruses. Am J Clin Pathol. 1980;74(3):324–6.PubMed

Title: The presence of enterovirus, adenovirus, and parvovirus B19 in myocardial tissue samples from autopsies: an evaluation of their frequencies in deceased individuals with myocarditis and in non-inflamed control hearts
Authors: Trine Skov Nielsen
Jakob Hansen
Lars Peter Nielsen
Ulrik Thorngren Baandrup
Jytte Banner
Publication date: 01-09-2014
Publisher: Springer US
Published in: Forensic Science, Medicine and Pathology / Issue 3/2014
Print ISSN: 1547-769X
Electronic ISSN: 1556-2891
DOI: https://doi.org/10.1007/s12024-014-9570-7

Keynote webinar | Spotlight on medication adherence

Springer Medicine

The presence of enterovirus, adenovirus, and parvovirus B19 in myocardial tissue samples from autopsies: an evaluation of their frequencies in deceased individuals with myocarditis and in non-inflamed control hearts

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 3/2014

The pathological features of Wernicke encephalopathy

Survival and development of the forensically important blow fly, Calliphora varifrons (Diptera: Calliphoridae) at constant temperatures

The role of histopathology in forensic practice: an overview

Sudden unexpected death in the setting of undiagnosed Graves’ disease

Immersion-related deaths in infants and children: autopsy experience from a specialist center

A case of suicide by ingestion of caffeine