683 The Natural History of Biopsy Negative Rejection after Heart Transplantation

Abstract

.Purpose. The most recent International Society for Heart and Lung Transplantation (ISHLT) biopsy scale classifies cellular and antibody-mediated rejections. However, there are cases with acute decline in left ventricular ejection fraction (LVEF ≤ 45%) but no evidence of rejection on biopsy. Characteristics and treatment response of this biopsy negative rejection (BNR) have yet to be elucidated. Methods. Between 2002 and 2012, we found 12 cases of BNR in 11 heart transplant patients as previously defined. One of the 11 patients was treated a second time for BNR. Characteristics and response to treatment were noted. Results. 12 cases (of 11 patients) were reviewed and 11 occurred during the first year after transplant. 8 cases without heart failure symptoms were treated with an oral corticosteroids bolus and taper or intravenous immunoglobulin. Four cases with heart failure symptoms were treated with thymoglobulin, intravenous immunoglobulin, and intravenous methylprednisolone followed by an oral corticosteroids bolus and taper. Overall, 7 cases resulted in return to normal left ventricular function within a mean of 14 ± 10 days from the initial biopsy. Conclusion. BNR includes cardiac dysfunction and can be a severe form of rejection. Characteristics of these cases of rejection are described with most cases responding to appropriate therapy.

Advanced Morphologic Analysis for Diagnosing Allograft Rejection

“…Interobserver variability has been a widely recognized limitation of the morphologic assessment of CAR since the widespread adaption of the EMB procedure. 3 , 10 - 14 In a study by Angelini et al, 13 a combined κ statistic of 0.39 was calculated for grades assigned by the 18 study pathologists using the 2004 ISHLT criteria. Although this represented a small improvement over the 1990 criteria (κ = 0.31), this is still far from the degree of reproducibility one would expect from a gold standard test.…”

“…Indeed, the concept of ‘biopsy negative rejection’ to describe cases of clear clinical rejection in the absence of histologic evidence of significant cellular rejection has been a source of concern and investigation for years. 12 , 14 , 22 , 23 Also, although updates to ISHLT grading criteria in 2004 and the subsequent addition of more refined antibody-mediated rejection criteria have helped reduce the burden of biopsy negative rejection cases, there remains a number of false-negative EMBs in the setting of clinically important rejection. 22 , 23 Although each of these examples represents a small case series of select patients, they suggest that the features currently used to assess rejection severity may not be optimal, and that new approaches to identifying other features might achieve better diagnostic accuracy.…”