Angiotensin II Type 1 Receptor Antibody Mediated Rejection Following Orthotopic Heart Transplant: A Single Center Experience.

Abstract

BACKGROUND\nAntibody mediated rejection (AMR) following orthotopic heart transplant (OHT) causes significant morbidity and mortality. There is limited data on antibodies to the angiotensin II type 1 receptor (AT1R-Ab) causing rejection following OHT.\n\n\nMETHODS\nThis is a retrospective, single center study that presents our 2-year experience with a series of 11 patients with evidence of nonspecific graft dysfunction and pathologic levels of AT1R-Ab. The clinical outcomes and treatments were compared to a group of 10 patients, also with evidence of nonspecific graft dysfunction, but who had nonsignificant AT1R-Ab titers.\n\n\nRESULTS\nThe mean age of the AT1R-Ab cohort was 52 and 73% were bridged to transplant with an LVAD. The average LVEF at presentation was 45%, and most were not on an angiotensin receptor blocker (ARB). Endomyocardial biopsies in those with elevated AT1R-Ab levels frequently showed reactive endothelium/endocardium without C4d or intravascular CD68 staining. Ten patients (91%) were started on an ARB. Other therapies included plasmapheresis and IVIg (64%), with 4 patients also receiving rituximab. Most patients had symptom improvement, but minimal change in graft function at an average 6 months of follow-up.\n\n\nCONCLUSIONS\nThe role of AT1R-Ab mediated rejection in OHT recipients remains poorly understood. More than half of patients at our center who presented with graft dysfunction in the absence of ACR or AMR were found to have elevated AT1R-Ab titers. Empiric AMR treatment in conjunction with ARB therapy may improve patient outcomes. Future studies are needed to better define the optimal treatment modalities for ATR1-Ab mediated AMR.