DETECTING ACUTE GRAFT-REJECTION IN PATIENTS AFTER ORTHOTOPIC HEART-TRANSPLANTATION - ANALYSIS OF HEART-RATE-VARIABILITY IN THE FREQUENCY-DOMAIN

Background: Acute transplant rejection is a major complication after h eart transplantation. To treat patients with rejection, early detectio n is necessary before fatal heart dysfunction. Because of its invasive aspect, endomyocardial biopsy is limited with respect to its frequenc y and complication rate. Little work has been done so far to develop n oninvasive methods for detecting rejection, and, hence, investigation for such methods would seem to be of considerable value. Methods: Afte r routine endomyocardial biopsy in 117 heart transplant recipients (ag e 49 rt 13 years time after transplantation 6 to 38 months), electroca rdiography results were recorded with the patient in a supine position at a controlled respiratory rate (0.25 Hz) over 10 minutes. Patients with an artificial pacemaker or severe arrhythmia were excluded. On th e basis of endomyocardial biopsy reports, two groups of patients were defined: patients without rejection (ARO, n = 73) and patients with se vere rejection (AR1b to AR4, n = 32). The spectra of R-wave to R-wave intervals were calculated, and different spectral components were eval uated: low frequency (LF, 0.05 to 0.18 Hz), high frequency (HF, 0.18 t o 0.5 Hz), LF + HF, LF + HF minus the respiratory peak (RP) (LF + HF - RP), and the total power (0 to 0.5 Hz). Results: All frequency domain parameters except HF were significantly higher in patients with sever e rejection than in patients without rejection. By means of the calcul ation of receiver operating characteristic curves, LF + HF - RP was th e most reliable frequency domain parameter for the detection of severe rejection. Setting its threshold value to 5 msec(2), 77% sensitivity, and 76% specificity could be achieved. Conclusions: Spectral analysis of heart rate variability may be used as a noninvasive tool to detect severe rejection episodes.