Abstract

Conventional echocardiography is not considered reliable for rejection-surveillance in pediatric heart transplant (HT) recipients. Pulse-wave tissue Doppler imaging (TDI) is geometry-independent and more sensitive than conventional imaging to evaluate bi-ventricular function. The purpose of this study was to assess TDI findings during biopsy-proven rejection in pediatric HT recipients and to develop TDI criteria for absence of rejection with high predictive accuracy. Methods: All HT recipients in follow-up at our center were included (N=122, median age at transplant 8.7 yrs, range 2 weeks-22 yrs). We identified all echocardiograms with TDI imaging performed within 24 hrs of an endomyocardial biopsy during 2005-2011. Rejection was defined as ISHLT Grade ≥2R cellular rejection or antibody-mediated rejection. Paired comparisons of TDI velocities were made using each patient’s baseline TDI as control. Results: Overall, 650 biopsy-pairs were identified where there was no rejection by biopsy at baseline (median duration between paired biopsies 4.3 mo, 25th-75th percentile 1-8.7 mo). In 25 of these pairs, the second biopsy demonstrated cellular or antibody mediated rejection. Rejection was associated with 27±17 % decline in LV S’ (P<0.001), 17±25 % decline in RV S’ (P<0.001) and a 16±18 % decline in septal S’ velocity (P<0.001). Using a receiver-operating characteristic curve, <24% decline in LV S’, <15% decline in RV S’ and <12% decline in septal S’ were all individually associated with a negative predictive value (NPV) of 98% for rejection. When all three criteria were met, the NPV was 98.5% (95% CI 96.9%, 99.4%) for rejection. Overall, 83% of biopsy pairs met criteria of 98.5% NPV for rejection. Conclusions: Biopsy-proven rejection in pediatric HT recipients is associated with significant and easily measured changes in ventricular function using TDI echocardiography. Using well-defined TDI criteria to predict absence of rejection, over 80% of planned biopsies may be deferred or avoided at minimal risk to pediatric HT recipients.

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