Association between enterovirus endomyocardial infection and late severe cardiac events in some adult patients receiving heart transplants

Enteroviruses and other cardiotropic viruses have been associated with the development of late severe adverse cardiac events in infants receiving heart transplants. However, the source and the chronology of cardiac allograft infection by an enterovirus in patients receiving heart transplants remain unknown. Using RT-PCR and immunohistochemistry assays, endomyocardial tissue samples of 30 adult patients were tested to detect the presence of specific enterovirus 5' non-coding (5'NC) sequences and of VP1 capsid protein, and this at the time of cardiac transplantation and at the 12-month biopsy for graft rejection control. Moreover, the endomyocardial detection of genomic sequences of entero-viruses, Epstein-Barr virus, herpes simplex virus, cytomegalovirus (CMV), varicella-zoster virus, adenoviruses, and parvovirus B19 was carried out by RT-PCR and polymerase chain reaction (PCR) assays at the time of late severe cardiac events. Enterovirus RNA and VP1 antigen were both detected in 4 (13%) of 30 patients at the time of the 12-month biopsy for graft rejection control, whereas no enterovirus component was detected in the explanted and implanted heart tissues taken from these 4 patients at the time of transplantation. At the time when severe cardiac events were developed, within 3 months after the positive enterovirus cardiac detection, these four patients demonstrated the presence of endomyocardial enterovirus RNA sequences whereas they were tested negative for the endomyocardial detection of genomic sequences from DNA viruses (except for CMV in two cases), and for a significant level of pp65 CMV antigenemia. Taken together, these findings indicate that enteroviruses could be acquired as a new endomyocardial infection within 12 months after transplantation in adults receiving heart transplants, and suggest that this infection might be anetiological cause for unexplained late severe adverse cardiac events in the heart-transplantated adults. (C) 2005 Wiley-Liss, Inc.