Early detection of acute allograft rejection by linear and nonlinear analysis of heart rate variability

Objective: The first months after orthotopic heart transplantation are asso ciated with the highest risk of acute allograft rejection. This study explo res the utility and reliability of linear and novel nonlinear metrics of he art rate variability as predictors of graft rejection. The underlying hypot hesis is that the transplanted heart, in response to inflammatory mediators , alters the dynamic properties of its rhythm-generating system. Methods: In a cross-sectional study of 45 patients who had undergone heart transplantation, spanning a period of 4 months after the operation, heart r ate variability was examined by time- and frequency-domain analysis. The no nlinear features of heart rate variability were studied by computing a poin twise correlation dimension of R-R interval time series. The results of hea rt rate variability analysis were compared with those of endomyocardial sur veillance biopsy studies using the International Society for Heart and Lung Transplantation scoring system. Results: Duration of heart transplantation itself exhibited a significant ( P <.05) association with the onset of rejection. Specific predictors of acu te rejection based on heart rate variability were identified, including sho rtening of the R-R interval (from 700 +/- 68 to 648 +/- 72 ms), an increase in the ratio of low-frequency (0.04-0.15 Hz) to high-frequency (0.15-0.40 Hz) spectral power (from 0.3 +/- 0.2 to 0.6 +/- 0.4), and a decrease in poi ntwise correlation dimension values (from 1.7 +/- 0.7 to 0.9 +/- 0.3 units) . Multivariable logistic regression analysis (R-2 = 0.4) revealed that the only significant independent risk predictors were pointwise correlation dim ension (odds ratio, 2.2 per 0.1 unit) and duration of heart transplantation (odds ratio, 1.7 per week). Conclusion: Nonlinear measures of heart rate variability provide noninvasiv e means for identifying patients undergoing cardiac transplantation with ac ute rejection, thereby enabling the assessment of the time-dependent adapti ve response of the donor heart to its host.