Damaged myocytes as detected by the colocalization of DNA fragmentation and tissue transglutaminase and their prognostic significance in enterovirus-associated dilated cardiomyopathy.
BACKGROUND
Apoptotic cardiac myocytes have been described in chronic heart failure, but no data exist on the relationship between these 'damaged' myocytes and myocardial detection of enterovirus RNA often associated with dilated cardiomyopathy (DCM).


METHODS
In patients with idiopathic DCM, endomyocardial biopsy samples were studied for enteroviral RNA by one step reverse transcription-polymerase chain reaction (PCR) and a subsequent hybridization of the PCR product using a Southern blot technique. The endomyocardial biopsies were further investigated for markers of cell damage and apoptosis: DNA fragmentation and expression of tissue-transglutaminase (TTG) in the myocytes using the in-situ endlabelling method or an anti-TTG-staining, respectively. To assess the prognostic significance of these two markers the correlation between the percentage of myocytes positive both for DNA fragmentation and TTG (the index of damaged myocytes) and the hemodynamic course of the patients during a mean follow-up period of 15.9 +/- 6.2 months was investigated prospectively by echocardiography.


RESULTS
In 14 (45%) of the 31 patients with idiopathic DCM, enteroviral RNA was found in the endomyocardial biopsy samples, while 17 patients (55%) were enterovirus-negative. In enterovirus-positive patients, the index of 'damaged' myocytes was significantly lower (10.7 +/- 4.9% vs. 19.2 +/- 8.8%, P = 0.002) and the left ventricular ejection fraction (LVEF) improved significantly (P = 0.00017 vs. P = 0.13) during long-term follow-up. In addition, a weak negative correlation was seen between the index of damaged myocytes and the changes in LVEF in all patients during long-term follow-up (r = - 0.48, P = 0.004).


CONCLUSIONS
Our results favour the view that enterovirus-positive patients with DCM have less damaged myocytes and a better haemodynamic course than enterovirus-negative patients.
Lotze
U
U
Hospital Waltershausen-Friedrichroda, Friedrichroda, Germany, Friedrich-Schiller-University, Jena, Germany. Med1.Lotze@krankenhaus-waltershausen-friedrichroda.de
Busch
H J
HJ
Aschoff
A
A
Glück
B
B
Sigusch
H
H
Jirikowski
G
G
Stelzner
A
A
Figull
H R
HR
D000328:Adult; D001706:Biopsy; D002311:Cardiomyopathy, Dilated / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D053938:DNA Fragmentation; D004770:Enterovirus / Q000235:genetics / Q000302:isolation & purification*; D004769:Enterovirus Infections / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D019204:GTP-Binding Proteins / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000201:enzymology / Q000473:pathology; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012367:RNA, Viral / Q000032:analysis; D011503:Transglutaminases / Q000032:analysis*
D012367:RNA, Viral; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins