HISTOLOGIC AND MOLECULAR DIAGNOSIS OF MYOCARDIAL HUMAN CYTOMEGALOVIRUS-INFECTION AFTER HEART-TRANSPLANTATION

A total of 879 paraffin-embedded endomyocardial biopsy specimens from 69 heart transplant recipients were studied. In 30 biopsy specimens, t he presence of human cytomegalovirus was investigated by routine histo logic and immunohistochemical evaluation, in situ hybridization, and p olymerase chain reaction. These 30 biopsies were performed in seven pa tients with clinical human cytomegalovirus infection (four primary and three recurrent infections) and in eight patients with asymptomatic h uman cytomegalovirus recurrent infection. These endomyocardial biopsy specimens showed grade 0 (n = 9), 1A (n = 12), 1B (n = 7), or 2 (n = 2 ) acute rejection. No myocarditis with human cytomegalovirus-like incl usion bodies was observed by routine histologic evaluation. Human cyto megalovirus DNA or antigens were not shown by in situ hybridization or by immunohistochemical evaluation, respectively. Viral DNA was detect ed by polymerase chain reaction in two grade 1A endomyocardial biopsy specimens from two patients with systemic human cytomegalovirus primar y infection. These two biopsy specimens were shown to be positive by p olymerase chain reaction at the time of the acute phase of the infecti on as shown by laboratory findings. Therefore cytomegalovirus DNA dete cted by polymerase chain reaction could result from viral carriers, th at is, leukocytes of rejection-related infiltrates or within intramyoc ardial vessels as a result of a more aggressive expression of the syst emic infection in seronegative recipients with cytomegalovirus seropos itive donors. Polymerase chain reaction is the most sensitive method f or viral DNA detection on paraffin-embedded biopsy specimens, but a mu ltitechnologic approach, including routine histologic evaluation, is r equired for a proper diagnosis of human cytomegalovirus myocardial inf ection.