272 - Single-Center Outcomes of Biopsy-Negative Rejection in Heart Transplantation

Abstract

Allograft rejection, defined as acute cellular rejection (ACR) or antibody-mediated rejection (AMR), carries significant morbidity and mortality after heart transplantation. Allograft dysfunction, characterized by left ventricular ejection fraction (EF) ≤ 45%, in the absence of ACR or AMR is termed biopsy-negative rejection (BNR). To date, little data exist regarding the outcomes of such patients, as BNR in the era of better-defined AMR criteria is rare. Treatment consensus is also lacking. We sought to describe our experience with BNR in a single center. Between 1992 and 2016 at the University of Maryland Medical Center, 6 patients were identified as having BNR. Mean time interval between transplant and date of BNR diagnosis was 76 ± 95 days. One was a heart-lung recipient, and 1 was a re-transplant patient. Standard immunosuppressant drugs included mycophenolate mofetil, prednisone and a calcineurin inhibitor. No one was treated for rejection before BNR, or had severe coronary allograft vasculopathy by coronary angiography with intravascular ultrasound. All had normal hemodynamics by right heart catheterization at the time of BNR diagnosis. One patient developed de novo donor-specific antibodies (DSA) prior to BNR onset. This patient received a prednisone burst with subsequent EF recovery. The heart-lung recipient did not receive BNR treatment out of concern for increased infection. His EF remained depressed (20–30%) after 6 months. One patient was also not treated at the time of BNR, only to develop grade 2R ACR 2 months later. He was then treated with a methylprednisolone burst with EF recovery. Two patients received a prednisone burst; one recovered and maintained EF > 45% (the re-transplant patient), the other's EF stayed low at 30–40%. The 6th patient had recurrent BNR in the span of 3 months, both episodes treated with methylprednisolone burst. After the 2nd episode, he had de novo DSA which prompted treatment with plasmapheresis and thymoglobulin. His EF normalized after each episode of treatment. Increased glucose uptake by PET and cardiac MRI are emerging as tools to detect rejection, so they were done for these patients but were unrevealing and did not contribute towards determining treatment. In conclusion, BNR was diagnosed within one year post transplant in all six patients. Four out of 5 patients treated for BNR recovered their heart functions. The most common treatment was steroid burst. Given the paucity of data concerning BNR, there needs to be a multi-centered study focused on non-invasive diagnostic modalities, treatments and outcomes to better serve this special heart transplant population.