(1018) A Case for a Novel Use of Donor-Derived Cell-Free DNA in Heart Transplantation: Detecting AT1R Antibody-Associated Injury

IntroductionAmong heart transplant (HT) recipients, anti-angiotensin II type 1 receptor antibodies (AT1R-Ab) have been implicated in non-HLA antibody-mediated rejection (AMR). Donor-derived cell free DNA (dd-cfDNA) is increasingly being used to detect both subclinical and overt cardiac allograft injury. We present a case of using dd-cfDNA in suspected AT1R-Ab-associated cardiac allograft dysfunction.Case ReportA 38-year-old male with a history of HVAD implantation complicated by driveline infection and pump thrombosis underwent an uncomplicated HT. He received standard immunosuppression: basiliximab induction, mycophenolate mofetil (MMF 1000mg BID), tacrolimus (goal trough 10-12 ng/ml), and prednisone taper. Three months post-HT, right heart catheterizations revealed normal filling pressures and persistently low cardiac indices (3-5-month post-HT mean thermodilution, TDCI = 1.9 L/min/m2). Serial transthoracic echocardiograms showed normal function. Biopsies were repeatedly negative for both acute cellular rejection (grade 0) and pathologic AMR. Donor-specific antibodies were negative. Non-HLA antibody testing showed elevated AT1R-Ab titers (12 U/ml, normal <10). Due to the unrevealing work-up, dd-cfDNA was checked and found to be elevated (0.66%, normal <0.12%). Given his clinical stability, we opted to increase MMF to 1250mg BID and initiated losartan 50mg daily. Though AT1R-Ab titers remained elevated, his TDCI significantly improved (6-9-month post-HT mean = 2.4 L/min/m2), and dd-cfDNA normalized (Fig. 1).SummaryOur case raises the possibility that among certain HT recipients, AT1R-Ab may cause subclinical dysfunction whose etiology eludes traditional testing methods. In cases of suspected AT1R-associated graft dysfunction, dd-cfDNA may have utility in 1) detecting allograft injury and 2) monitoring for treatment response. Further study is necessary to understand AT1R-Ab-associated injury and the use of dd-cfDNA in these cases.