C092 - The Clinical Outcome of Pathology Antibody-Mediated Rejection 2 (pAMR2) in Heart Transplant Recipients: Is It Meaningful?

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Author Block: L. Marcos, A. Nikolova, M. Kittleson, J. Ferrall, P. Deckerman, K. Ghafourian, L. Stern, J. A. Kobashigawa, Cedars-Sinai Smidt Heart Institute, Los Angeles, CA
*Purpose: Previous studies have reported on the association of antibody mediated rejection (AMR) with cardiac allograft vasculopathy (CAV), graft dysfunction, and mortality in heart transplantation (HTx). Few studies have re-examined the prognosis of pAMR2 in the modern era of heightened recognition, expanded diagnostics, and new plasma cell-directed therapies. This study examines outcomes and characteristics of pAMR2.
*Methods: Between 2010 and 2024, 1,384 HTx patients (pts) at our center underwent 16,712 endomyocardial biopsies; of these, 52 pts had pAMR2 as their first AMR diagnosis (2013 ISHLT criteria). These pts were 2:1 matched by age, gender, date of HTx, and time since HTx to a control group with no pAMR2. Primary composite endpoint was subsequent 5-year survival and 5-year freedom from CAV (defined as ≥30% stenosis by angiography), redo-HTx, and non-fatal major adverse cardiac events (NF-MACE: MI, ICD/PPM implant, new CHF hospitalization, PCI, or stroke). Secondary outcomes included individual events from the primary endpoint and 1-year freedom from subsequent rejection. Persistent AMR (AMR-positive at 2-4 week follow up), donor-specific antibodies (DSA), and treatments for AMR were assessed.
*Results: The two cohorts were similar in most characteristics, apart from higher sensitization rates in the pAMR2 group (58% vs 28%, p=0.001). 43 cases (82.7%) were early AMR (within 1 year of HTx) with median time to pAMR2 of 10.5 days [7, 164]. DSAs were present in 35 (67.3%) pts with AMR. The pAMR2 and control groups did not differ in lower 5-year freedom from the composite primary endpoint. For secondary endpoints, the pAMR 2 group had significantly lower subsequent 1-year freedom from AMR and significantly lower subsequent 3-year and 5-year freedom from repeat rejection. In 19 (36.5%) pts, AMR2 was resolved by next biopsy while 33 (63.5%) had persistent AMR [16 (48.8%) pAMR1, 17 (51.5%) pAMR2]. No differences in other outcomes were observed. Treatment consisted of IVIG [38 (73.1%)], high-dose corticosteroids [30 (57.7%)], ATG [12 (23.1%)], rituximab [14 (26.9%)], and/or plasmapheresis [12 (23.1)].
*Conclusions: In our cohort of HTx pts, pAMR2 mostly occurred early after HTx (≤1year) and was not associated with excess risk of advanced CAV, death or re-do HTx at 5-year follow-up. However, repeat rejection was observed in pAMR2 group. Multi-center studies with larger sample size are needed to delineate prognosis of AMR as stratified by timing of occurrence, response to therapies, and concomitant elevation in other biomarkers.