Management of heart transplant recipients with hemodynamically significant clinical rejection in the presence of antibodies against angiotensin II type 1 receptor: A retrospective study

Abstract

Antibodies against Angiotensin II Type 1 Receptor (AT1R-Abs) have been associated with allograft rejection in heart transplantation. Data is lacking for modalities to mitigate their effect on cardiac function. We describe a case series consisting of patients with clinical and/or biopsy indication of rejection with detectable AT1R-Ab and present treatment regimen and outcome. Clinical dysfunction was defined as hemodynamically significant cardiac dysfunction on echocardiogram including a decrease in ejection fraction greater than or equal to 20%, shortness of breath, palpitations, chest tightness, and/or prolonged inotrope/vasopressor requirements during hospitalization. All patients selected for AT1R-Ab assessment had very low level or no donor specific HLA antibodies. Five of 9 patients with positive AT1R-Ab recovered good graft function following treatment with either losartan alone or in combination with plasmapheresis and IVIG. Two patients did not recover normal graft function and died despite the use of similar treatments. Losartan and plasmapheresis are obvious therapeutic approaches for heart transplant recipients with clinical dysfunction and positive AT1R-Ab. Losartan blocks activation of AT1 receptor, and plasmapheresis reduces circulating antibodies. Additional considerations such as patient characteristics, comorbidities, the use of ARBs other than losartan and appropriate time for treatment administration need to be evaluated in larger studies.

A Comprehensive Overview of the Clinical Relevance and Treatment Options for Antibody-mediated Rejection Associated With Non-HLA Antibodies

“…Additionally, kidney transplant patients with vascular rejection remained rejection free and had fewer AT1R antibodies after treatment involving PP, 100 mg of losartan daily plus IVIG, 107 or 4 mg of candesartan daily plus 6 sessions PP, 3 d of 1 g/d methylprednisolone, and 6 doses of 1.5 mg/kg/d ATG. 108 Furthermore, in a case series, 109 it was reported that 9 of the 12 (75%) heart transplant recipients had AT1R antibodies, and 6 out of these 9 developed AMR or mild rejection. Seven patients were treated with 25–100 mg losartan and/or PP and IVIG, and 71% (5 of 7) recovered good graft function.…”

Impact of pretransplant antibodies on outcomes after heart transplantation

“…These antibodies can bind to the vascular endothelium and induce apoptosis independent of CDC. Representative examples include MHC I chain-related gene A (MICA) [47,48], angiotensin II type I receptor (AT1R) [49,50 ▪▪ ], endothelin-1 type A receptor (ETAR) [51], endothelial cell antigens [52], vimentin [53], K-α-1-tubulin [54], collagen-V [55], anticardiac myosin antibody [56], and other non-HLA IgM antibodies. In cardiac transplantation, anti-MICA and antiendothelial antibodies have been associated with increased AMR [57] and the development of CAV [47,56].…”