Detection of enteroviral RNA in idiopathic dilated cardiomyopathy and other human cardiac tissues.

Weiss, Lawrence M.; Liu, Xian‐Fang; Chang, KC; Billingham, M. E.

doi:10.1172/jci115830

Cited by 86 publications

(21 citation statements)

References 14 publications

(13 reference statements)

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“…It is the task of future clinical trials to show whether these findings will have an impact on further risk stratifications and the development of future therapeutic options. (6,9,11,13,14,16,18,29,30,43,44). Serologische und histologische Untersuchungen deuten darauf hin, daß ein Zusammenhang zwischen einer Virusmyokarditis und dem Entstehen einer dilatativen Kardiomyopathie besteht.…”

Section: Discussionunclassified

“…Versuche, Viren mittels Elektronenmikroskopie zu identifizieren, Viren aus dem Myokardgewebe anzuzüchten oder eine direkte Detektion virusspezifischer Antigene mittels immunhistologischer Techniken durchzuführen, sind bisher nur in Einzelfällen erfolgreich gewesen (10,24,41). Erst durch die Einführung hochsensitiver und spezifischer molekularbiologischer Techniken wie slot-blot, In-situ-Hybridisierung sowie RT-PCR gelang es, enterovirales Genom im Myokard nachzuweisen und somit die Infektion zu verifizieren (6,9,11,13,14,16,18,29,30,43,44).…”

Section: Diskussionunclassified

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Nachweis enteroviraler RNA in endomyokardialen Biopsien bei inflammatorischer Kardiomyopathie und idiopathischer dilatativer Kardiomyopathie

et al. 1998

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The role of enteroviral myocardial infection in the development of dilated cardiomyopathy could only be substantiated after the introduction of molecular biological techniques (polymerase chain reaction, in-situ hybridization) in virological diagnostics of dilated cardiomyopathy. By using histological and especially immunohistological techniques for the detection of myocardial inflammation in patients with the tentative clinical diagnosis of dilated cardiomyopathy, a differentiation between inflammatory cardiomyopathy and idiopathic dilated cardiomyopathy on the basis of the WHO classification 1995 (31) was made. Inflammatory cardiomyopathy is defined by myocarditis in association with cardiac dysfunction and is diagnosed by established histological and especially immunohistological techniques. The combination of histological, immunohistological, and molecularbiological techniques enabled a subgroup analysis of the incidence of enteroviral myocardial RNA in patients with inflammatory cardiomyopathy in comparison to patients with idiopathic dilated cardiomyopathy. The study involved a total of 75 patients with impaired left ventricular function (EF < 50%) and the tentative clinical diagnosis of dilated cardiomyopathy. Right ventricular endomyocardial biopsies were obtained from all patients for further clarification of the cause of left ventricular functional disorder. All biopsies were analyzed for the presence of acute and chronic inflammatory myocardial alterations by histological ("Dallas" criteria) and immunohistological techniques (lymphocytic infiltrates, MHC antigen expression). Furthermore, each biopsy was examined by reverse transcriptase polymerase chain reaction (RT-PCR) in combination with Southern blot hybridization for the presence of enteroviral RNA. Active myocarditis was excluded in all patients by histological examination according to the "Dallas" criteria. Using immunohistological techniques, 26/75 patients (35%) had evidence for chronic inflammatory myocardial alterations in the sense of lymphocytic infiltrates (> or = 2,0 CD3 T-lymphocytes/ visual field at 400 magnification (HPF); > or = 7 CD3 T-lymphocytes/mm2). These patients were diagnosed as having inflammatory cardiomyopathy. To differentiate between patients with and without myocardial inflammation, cases with focal cellular infiltration and an average cell number between 2.5 and 2.0 CD3 T-lymphocytes/HPF and an increased expression of additional immune markers, i.e., MHC antigens, were not addressed in the group of patients with inflammatory cardiomyopathy. This is in contrast to Kühl et al (19). Consequently these patients were classified as patients with idiopathic dilated cardiomyopathy. These criteria of diagnosing myocardial inflammation were based on published results (20, 23, 26, 27, 49) and on our own control group (n = 85) (19) in which mean CD3 T-lymphocyte count/HPF in normal myocardial tissue were 0.7 (range 0.0-1.4). In addition, a subgroup analysis was performed of patients with a CD3 T-lymphocyte count > or = 3 CD3 T-lym...

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Section: Discussionunclassified

Section: Diskussionunclassified

Nachweis enteroviraler RNA in endomyokardialen Biopsien bei inflammatorischer Kardiomyopathie und idiopathischer dilatativer Kardiomyopathie

et al. 1998

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“…The discrepancy can be explained partly by marked variability in the sensitivity and specificity of the tests used as well as by differences in patient materials, diagnostic criteria, and prevalence of enteroviral infections in local populations. As some of these studies have also detected enteroviral RNA in a number of patients with other cardiac conditions and even in normal hearts Weiss et al, 1992;Andreoletti et al, 1995], it is likely that the mere presence of enteroviral RNA in the myocardium cannot be equated with disease. Therefore, it has been speculated that only certain enterovirus types are probably capable of causing chronic myocardial injury [Weiss et al, 1992]; however, no studies supporting this hypothesis have been published to date.…”

Section: Discussionmentioning

confidence: 99%

Detection of enteroviral RNA in end-stage dilated cardiomyopathy in children and adolescents

et al. 1998

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Medical records and archival myocardial specimens of 33 children and adolescents with end-stage idiopathic dilated cardiomyopathy (IDCM) were collected to evaluate retrospectively the potential role of enteroviral persistence in the pathogenesis of IDCM. The clinical history and laboratory assessment of each patient were reviewed carefully in order to obtain information on the nature and etiology of infections in the past and at the time of diagnosis of cardiomyopathy. Sixty-four formaldehyde-fixed, paraffin-embedded myocardial specimens, obtained from endomyocardial biopsies (n = 5), explanted hearts (n = 10), or autopsies (n = 49), were studied by the polymerase chain reaction (PCR) and by in situ hybridization to detect enteroviral RNA in the specimens. Control specimens included 34 formaldehyde-fixed, paraffin-embedded myocardial specimens from children with other cardiomyopathies, metabolic diseases, structural heart defects, or various noncardiac malignancies. The presence of cellular RNA in the specimens was confirmed by amplification of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA or beta-actin mRNA as positive controls. Only one specimen from the 32 IDCM patients with appropriate myocardial specimens was positive for enteroviral RNA by PCR. Sequence analysis of the amplified viral segment showed a significant degree of homology between the viral sequence and echovirus 1. One specimen from the control patients also appeared positive by PCR, but sequence analysis of the amplified viral segment revealed it as rhinovirus 16. The results do not indicate any significant role for enteroviral persistence in end-stage childhood IDCM, although they need to be confirmed using a prospective study with fresh frozen specimens. However, mechanisms other than viral persistence may be more important in the progression of IDCM to end-stage heart failure in this age group.

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“…Die Durchsicht der Literatur zeigt derzeit dementsprechend widersprüchliche Ergebnisse mit dem Nachweis einer enteroviralen Infektion in Endomyokardbiopsien bei 0-45% der untersuchten Patienten. Zudem wurde auch der Nachweis enteroviraler RNA bei Patienten mit nicht primär viral assoziierten myokardialen Erkrankungen berichtet [95], was die Notwendigkeit einer strikten Qualitäts-kontrolle bei der PCR-Diagnostik unterstreicht. Bei strikter Einhaltung der Qualitätskontrollen ist eine Validierung der PCR-Ergebnisse durch In-situ-Hybridisierung nicht notwendig.…”

Section: Invasive Diagnostikunclassified

Update 2001¶Myokarditis – Kardiomyopathie

Kandolf²,

Mall

et al. 2001

Med Klin

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Myocarditis is a common cardiological disease. New molecular biological and immunohistological methods have confirmed the persistence of viral infection and chronic myocardial inflammation in a considerable number of patients. A causal link between viral myocarditis and the development of dilated cardiomyopathy has been recognized. This has prognostic implications and helps for the decision of a specific immunosuppressive, immunomodulatory and antiviral therapy.

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Detection of enteroviral RNA in idiopathic dilated cardiomyopathy and other human cardiac tissues.

Cited by 86 publications

References 14 publications

Nachweis enteroviraler RNA in endomyokardialen Biopsien bei inflammatorischer Kardiomyopathie und idiopathischer dilatativer Kardiomyopathie

Nachweis enteroviraler RNA in endomyokardialen Biopsien bei inflammatorischer Kardiomyopathie und idiopathischer dilatativer Kardiomyopathie

Detection of enteroviral RNA in end-stage dilated cardiomyopathy in children and adolescents

Update 2001¶Myokarditis – Kardiomyopathie

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