Treatment of Angiotensin Type 1 Receptor Antibody Mediated Rejection in a Heart Transplant Recipient

Abstract

Introduction The diagnosis, impact, and treatment of angiotensin type 1 receptor (AT1R) antibody mediated rejection (AMR) in solid organ transplant remains unclear. This represents a case of successful treatment and removal of AT1R antibodies in a heart transplant recipient. Case Report A 25 year old Caucasian female with a past medical history of idiopathic cardiomyopathy, status post left ventricular assist device and subsequent heart transplant in 2016, immunosuppressed on tacrolimus XR, mycophenolate sodium, and prednisone presented with increased peripheral edema, shortness of breath, and dyspnea. On admission, LVEF dropped from baseline 54-74 % to 45% with a right atrial pressure of 32 mmHg on right heart catheterization. An endometrial biopsy was conducted and reported as 1R/1B without signs of AMR. Anti-HLA screen was sent with no significant DSA. An AT1R antibody test resulted positive with a titer of 40 U/mL. Patient was started on dobutamine, IV furosemide, and irbesartan. She received 3 days of 1000 mg methylprednisolone, five treatments of total plasma exchange, 500 mg/kg of IVIG, 8 mg/kg of tocilizumab, and her mycophenolate sodium was replaced by everolimus. Patient reported subjective improvement after treatment and appropriate diaresis. Patient was able to wean from dobutamine however repeat echocardiogram showed no change in LVEF. Post-pheresis AT1R antibody test proved successful removal by plasmapheresis with a titer or 21 U/mL. Patient went on to receive monthly tocilizumab infusions with a marked improvement in her LVEF at one month post treatment to > 54 %. At two months post treatment, she was hospitalization for volume overload with a normal LVEF thought to be due to under dieresis and atrial tachycardia. She remained on tacrolimus XR, everolimus, prednisone, monthly tocilizumab, and irbesartan. At four months post treatment, her echocardiogram showed an EF of 65 %, however her AT1R antibody levels returned to 40 U/mL. The patient expired due to suspected arrhythmia at home six months post-treatment. Summary This report is the first case to show successful removal of AT1R antibodies by plasmapheresis. AT1R antibody AMR still remains difficult to diagnose due to uncertain histological findings or appropriate screening. More study is needed to determine clinical impact of titer levels and appropriate treatment of AT1R antibody AMR.