Noninvasive diagnosis of cardiac allograft rejection in an orthotopic canine model

Background. A decline in the R wave voltage obtained from surface electrocardiograms once correlated with cardiac allograft rejection. With cyclosporine therapy, however, these electrocardiographic findings became inconsistent, occurring only during severe rejection episodes. Despite cyclosporine use, intramyocardial unipolar peak-to-peak amplitudes obtained from plunge electrodes are reported to be highly sensitive and specific for diagnosing rejection. These reports are based on heterotopic grafts, which atrophy over time, making long-term voltage changes during rejection difficult to interpret. The purpose of this study was to use analysis of unipolar peak-to-peak amplitudes as a prospective monitoring tool for diagnosing orthotopic cardiac allograft rejection. Methods. Ten adult mongrel dogs underwent orthotopic heart transplantation with the attachment of four intramyocardial leads. The unipolar peak-to-peak amplitudes were measured daily and compared with endomyocardial biopsy results. Results. We found that intramyocardial unipolar peak-to-peak amplitude analysis had a sensitivity and a specificity of 100% for diagnosing rejection. We also found that as the number of myocardial leads increased, the sensitivity of detecting rejection also increased. Conclusions. We conclude that unipolar peak-to-peak amplitude analysis is an accurate noninvasive means for early detection of cardiac allograft rejection in an orthotopic model. Its success should allow less frequent, more selective use of endomyocardial biopsy.