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' myo cytes and myocardial detection of enterovirus RNA often associated with dil ated cardiomyopathy (DCM). Design In patients with idiopathic DCM, endomyocardial biopsy samples were studied for enteroviral RNA by one step reverse transcription-polymerase ch ain reaction (PCR) and a subsequent hybridization of the PCR product using a Southern blot technique. The endomyocardial biopsies were further investi gated for markers of cell damage and apoptosis: DNA fragmentation and expre ssion of tissue-transglutaminase (TTG) in the myocytes; using the in-situ e ndlabelling method or an anti-TTG-staining, respectively. To assess the pro gnostic significance of these two markers the correlation between the perce ntage 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%) we re enterovirus-negative. In enterovirus-positive patients, the index of 'da maged' myocytes was significantly lower (10.7 +/- 4.9% vs. 19.2 +/- 8.8%, P = 0.002) and the left ventricular ejection fraction (LVEF) improved signif icantly (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). Conclusion Our results favour the view that enterovirus-positive patients w ith DCM have less damaged myocytes and a better haemodynamic course than en terovirus-negative patients.