Abstract
Aside from enteroviruses and other viruses, e.g., adenoviruses, which are known to be associated with idiopathic dilated cardiomyopathy (IDC), a cardiac tropism is also attributed to parvovirus B19 (PVB19). The purpose of the present study was to determine the prevalence of enterovirus, adenovirus and PVB19 genomes in the myocardium of adult patients with IDC and to analyze the significance of PVB19 with regard to the course of the disease, as compared to the other cardiotropic viruses. In 52 adult patients with IDC and 10 control patients with normal left ventricular ejection fraction (≥55%) undergoing coronary artery bypass surgery, myocardial tissue samples were investigated for enteroviral RNA using polymerase chain reaction (PCR) and Southern blot hybridization of the PCR product. Specific nested PCR was used to assess the prevalence of adenovirus and PVB19 DNA, in addition to sequencing of the latter. The clinical and echocardiographic course of the disease was followed for a mean (± SD) period of 21.1±9.5 months. Fourteen of the 52 patients (27%) were enterovirus-positive, 2/52 (4%) patients were adenovirus-positive, 14/52 (27%) patients were PVB19-positive, 8/52 (15%) patients were enterovirus plus PVB19-positive, and in 14/52 (27%) patients no viral genomes were found. Six patients died during the follow-up period, without any significant difference between the patient groups: 1/14 (7%) in the enterovirus-positive, 0/2 (0%) in the adenovirus-positive, 2/14 (14%) in the PVB19-positive, 1/8 (12.5%) in the enterovirus plus PVB19-positive, and 2/14 (14%) in the virus-negative group. PVB19 genome was found in 4 of the 10 (40%) control patients, but no enterovirus or adenovirus genomes were detected in these patients. In conclusion, in the myocardium of patients with IDC, PVB19 is detectable as frequently as enteroviral genome. PVB19-positive patients with IDC have a rather favorable prognosis and do not differ significantly from the other virus-positive or virus-negative patient groups with respect to survival. Finally, the pathogenetic and prognostic significance of PVB19 in IDC still remains unclear.
Similar content being viewed by others
References
Amiot L, Langnay T, Drenou B, Lelong B, Le Prise PY, Logeais Y, Fauchet R (1998) Spontaneous recovery from severe parvovirus B19 pure red cell aplasia, in a heart transplant recipient, as demonstrated my marrow culture. Hematol Cell Ther 40:71–73
Anderson MJ, Khousam MN, Maxwell DJ, Gould SJ, Happerfield LC, Smith WJ (1988) Human parvovirus B19 and hydrops fetalis. Lancet I:535
Andreoletti L, Hober D, Becquart P, Belaich S, Copin MC, Lambert V, Wattre P (1997) Experimental CVB3-induced chronic myocarditis in two murine strains: evidence of interrelationships between virus replication and myocardial damage in persistent cardiac infection. J Med Virol 52:206–214
Archard LC, Bowles NE, Cunningham L, Freeke CA, Olsen EGJ, Rose ML, Meany B, Why HJF, Richardson PJ (1991) Molecular probes for detection of persisting enterovirus infection of human heart and their prognostic value. Eur Heart J 12 (Suppl 12):56–59
Aretz HT, Billingham ME, Edwards WD, Factor SM, Fallon JT, Fenoglio JF, Olsen EGJ, Schoen FJ (1987) Myocarditis. A histopathologic definition and classification. Am J Cardiovasc Pathol 1:3–14
Beland SS, Danile GK, Menard LC, Miller NM (1997) Aplastic crisis with parvovirus B19 in an adult heriditary spherocytosis. J Ark Med Soc 94:163–164
Bertoni E, Rosati A, Zanazzi M, Azzi A, Zakrzewska K, Guidi S, Fanci R, Salvadori M (1997) Aplastic anemia due to B19 parvovirus infection in cadaveric renal recipients: an underestimated infectious disease in the immunocompromised host. J Nephrol 10:152–156
Borreda D, Palomera S, Gilbert B, Lienhardt A, Lumley L de (1992) A propos de vingt-quatre observations d’infections a parvovirus humain B19 chez l’enfant (24 cases of human parvovirus B19 infection in children). Ann Pediatr (Paris) 3:543–549
Bowles NE, Richardson PJ, Olson EGJ, Archard LC (1986) Detection of coxsackie-B-virus-specific RNA sequences in myocardial biopsy samples from patients with myocarditis and dilated cardiomyopathy. Lancet 17:1120–1123
Brandenburg H, Los FJ, Cohen-Overbeck TE (1996) A case of early intrauterine parvovirus B19 infection. Prenat Diagn 16:75–77
Brown KE, Young NS (1997) Parvovirus B19 in human disease. Annu Rev Med 48:59–67
Brown KE, Anderson SM, Young NS (1993) Erythrocyte P antigen: cellular receptor for B19 parvovirus. Science 262:114–117
Brown KE, Hibbs JR, Gallinella G, Anderson SM, Lehmann ED, Mc Carthy P, Young NS (1994) Resistance to parvovirus B19 infection due to lack of virus receptor (erythrocyte P antigen). N Engl J Med 330:1192–1196
Calvet A, Pujol MO, Bertocchi M, Bastien O, Boissonat P, Mornex JF (1999) Parvovirus B19 infection in thoracic organ transplant recipients. J Clin Virol 13:37–42
Chomczynski P, Sacchi N (1987) Single step method of RNA isolation by guanidium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156–162
Dogde HT, Sheehan FH (1983) Quantitative contrast angiography for assessment of ventricular performance in heart disease. J Am Coll Cardiol 1:73–81
Enders G, Dötsch J, Bauer J, Nützenadel W, Hengel H, Haffner D, Schalasta G, Searle K, Brown KE (1998) Life-threatening parvovirus B19-associated myocarditis and cardiac transplantation as possible therapy: two case reports. Clin Infect Dis 26:355–358
Figulla HR, Stille-Siegener M, Mall G, Heim A, Kreuzer H (1995) Myocardial enterovirus infection with left ventricular dysfunction: a benign disease compared with idiopathic dilated cardiomyopathy. J Am Coll Cardiol 74:1170–1175
Grumbach IM, Heim A, Pring-Akerblom P, Vonhof S, Hein WJ, Müller G, Figulla HR (1999) Adenoviruses and enteroviruses as pathogens in myocarditis and dilated cardiomyopathy. Acta Cardiol 54:83–88
Heegaard ED, Hornsleth A (1995) Parvovirus: the expanding spectrum of disease. Acta Paediatr 84:109–117
Heegaard ED, Eiskjaer H, Baandrup U, Hornsleth A (1998) Parvovirus B19 infection associated with myocarditis following adult cardiac transplantation. Scand J Infect Dis 30:607–610
Hohenadl C, Klingel K, Mertsching J, Hofschneider PH, Kandolf R (1991) Strand-specific detection of enteroviral RNA in myocardial tissue by in situ hybridization. Mol Cell Probes 5:11–20
Hornsleth A, Carlsen KM, Christensen LS, Gundestrup M, Heegaard ED, Myhre J (1994) Estimation of serum concentration of parvovirus B19 DNA by PCR in patients with chronic anaemia. Res Virol 145:379–386
Janner D, Bork J, Baum M, Chinnock R (1994) Severe pneumonia after heart transplantation as a result of human parvovirus B19. J Heart Lung Transplant 13:336–338
Jin O, Sole MJ, Butany JW, Chia WK, McLaughlin PR, Liu P, Liew CC (1990) Detection of enterovirus RNA in myocardial biopsies from patients with myocarditis and cardiomyopathy using gene amplification by polymerase chain reaction. Circulation 82:8–16
Kämmerer U, Kunkel B, Korn K (1994) Nested PCR for specific detection and rapid identification of human picornaviruses. J Clin Microbiol 32:285–291
Kandolf R, Ameis D, Kirschner P, Canu A, Hofschneider PH (1987) In situ detection of enteroviral genomes in myocardial cells by nucleic acid hybridization: an approach to the diagnosis of viral heart disease. Proc Natl Acad Sci USA 84:6272–6276
Kariyawasam HH, Gyi KM, Hodson ME, Cohen BJ (2000) Anaemia in lung transplant patient caused by parvovirus B19. Thorax 55:619–620
Klingel K, Selinka HC, Sauter M, Bock CT, Szalay G, Kandolf R (2002) Molecular mechanisms in enterovirus and parvovirus B19 associated myocarditis and inflammatory cardiomyopathy. Eur Heart J Supplements 4 (Suppl I):I8-I12
Knisely AS, O’Shea PA, Anderson LJ, Gary GW (1988) Parvovirus B19 infection, myocarditis and death in a 3-year old boy. Pediatr Pathol 8:665
Marchand S, Tchernia G, Hiesse C, Tertian G, Cartron J, Kriaa F, Boubenider S, Goupy C, Lecointe D, Charpentier B (1999) Human parvovirus B19 infection in organ transplant recipients. Clin Transplant 13:17–24
Morey AL, Keeling JW, Porter HJ, Fleming KA (1992) Clinical and histopathological features of parvovirus B19 infection in the human fetus. Br J Obstet Gynaecol 99:566–574
Moudgil A, Shidban H, Nast CC, Bagga A, Aswad S, Grahma SL, Mendez R, Jordan SC (1997) Parvovirus B19 infection-related complications in renal transplant recipients: treatment with intravenous immunoglobulin. Transplantation 64:1847–1850
Naides SJ, Weiner CP (1989) Antenatal diagnosis and palliative treatment of non-immune hydrops fetalis secondary to fetal parvovirus B19 infection. Prenat Diagn 9:105–114
Nour B, Green M, Michaelis M, Reyes J, Tzakis A, Gartner JC, McLoughlin L, Starzl TE (1993) Parvovirus B19 infection in pediatric transplant patients. Transplantation 56:835–838
Pankuweit S, Portig I, Eckhardt H, Crombach M, Hufnagel G, Maisch B (2000) Prevalence of viral genome in endomyocardial biopsies from patients with inflammatory heart disease. Herz 25:221–226
Pauschinger M, Bowles NE, Fuentes-Garcia FJ, Pham V, Kühl U, Schwimmbeck PL, Schultheiss H-P, Towbin JA (1999) Detection of adenoviral genome in the myocardium of adults with idiopathic left ventricular dysfunction. Circulation 99:1348–1354
Pauschinger M, Dörner A, Kühl U, Schwimmbeck PL, Poller W, Kandolf R, Schultheiss H-P (1999) Enteroviral RNA replication in the myocardium of patients with left ventricular dysfunction and clinically suspected myocarditis. Circulation 99:889–895
Petitjean J, Kopecka H, Freymuth F, Langlard JM, Scanu P, Galateau F, Bouhour JB, Ferriere M, Charbonneau P, Komajada M (1992) Detection of enteroviruses in endomyocardial biopsy by molecular approach. J Med Virol 37:76–82
Porter HJ, Quantrill AM, Fleming KA (1988) B19 parvovirus infection of myocardial cells. Lancet I:535–536
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 (1996) Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the Definiton and Classification of Cardiomyopathies. Circulation 93:841–842
Rouger P, Gane P, Salmon C (1987) Tissue distribution of H, Lewis and P antigen as shown by a panel of 18 monoclonal antibodies. Rev Fr Transfus Immunohematol 30:699–708
Saint-Martin J, Choulot JJ, Bonnaud E (1990) Myocarditis caused by parvovirus. J Pediatr 116:1007–1008
Salimans MM, Holsappel S, Rijke FM van de, Jiwa NM, Raap AK, Weiland HT (1989) Rapid detection of human parvovirus B19 DNA by dot-hybridization and the polymerase chain reaction. J Virol methods 23:19–28
Schowengerdt KO, Ni J, Denfield SW, Gajarski RJ, Radovancevic B, Frazier OH, Demmler GJ, Kearney D, Bricker JT, Towbin JA (1996) Diagnosis, surveillance, and epidemiologic evaluation of viral infections in pediatric cardiac transplant recipients with the use of the polymerase chain reaction. J Heart Lung Transplant 15:111–123
Schowengerdt KO, Ni J, Denfield SW, Gajarski RJ, Bowles NE, Rosenthal G, Kearney DL, Price JK, Rogers BB, Schauer GM, Chinnock RE, Towbin JA (1997) Association of parvovirus B19 genome in children with myocarditis and cardiac allograft rejection: diagnosis using the polymerase chain reaction. Circulation 96:3549–3554
Tanawattanacharoen S, Falk RJ, Jenette JC, Kopp JB (2000) Parvovirus B19 DNA in kidney tissue of patients with focal segmental glomerulosclerosis. Am J Kidney Dis 35:1166–1174
Weiss LW, Liu XF, Chang KL, Billingham ME (1992) Detection of enteroviral RNA in idiopathic dilated cardiomyopathy and other human cardiac tissue. J Clin Invest 90:156–159
Why HJF, Meany BT, Richardson PJ, Olsen EGJ, Bowles NE, Cunningham L, Freeke CA, Archard LC (1994) Clinical and prognostic significance of detection of enteroviral RNA in the myocardium of patients with myocarditis and dilated cardiomyopthy. Circulation 89:2582–2589
Wicki J, Samii K, Cassinotti P, Voegeli J, Rochat T, Beris P (1997) Parvovirus B19-induced red cell aplasia in solid organ transplant recipients. Two case reports and review of the literature. Hematol Cell Ther 39:199–204
Yaegashi N (2000) Pathogenesis of nonimmune hydrops fetalis caused by intrauterine B19 infection. Tokuyu J Exp Med 190:65–82
Zell R, Klingel K, Bültmann B, Kandolf R (1995) Detection of enteroviral RNA from formalin-fixed paraffin-embedded myocardial specimens by nested PT-PCR. Pathol Res Pract 191:196
Zolnourian ZR, Curran MD, Rima BK, Coyle PV, O’Neill HJ, Middleton D (2000) Parvovirus B19 in kidney transplant patients. Transplantation 69:2198–2202
Acknowledgements
We are grateful to Roland Zell, PhD (Institute of Virology and Antiviral Therapy, Friedrich-Schiller-University, Jena, Germany) for performing the sequence analysis of 11 positive PVB19 isolates. We are indebted to Prof. Gerhard Mall, MD (Department of Pathology, Städtische Kliniken Darmstadt, Germany) for histological and immunohistological investigations of the cardiac tissue samples and for assessing the myocyte diameter and the volume fraction of interstitial fibrosis. Furthermore, we are grateful to Prof. Thorsten Wahlers, MD and colleagues (Department of Cardiothoracic and Vascular Surgery, Friedrich-Schiller-University, Jena, Germany) for providing myocardial tissue samples from patients undergoing coronary artery bypass surgery. Finally, we thank Mrs. Birgit Lotze for her help in the preparation of the manuscript.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lotze, U., Egerer, R., Tresselt, C. et al. Frequent detection of parvovirus B19 genome in the myocardium of adult patients with idiopathic dilated cardiomyopathy. Med Microbiol Immunol 193, 75–82 (2004). https://doi.org/10.1007/s00430-003-0211-0
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00430-003-0211-0