Abstract 4146311: Cardiac Thickening, Cell Free DNA, and Rejection in the 2 ^nd Porcine Cardiac Xenograft

Introduction/Background: A 58-year-old man with inotrope dependent heart failure was declined for allotransplant and MCS at multiple centers and was transplanted with a 10 gene-edited porcine cardiac xenograft under FDA expanded access Investigational New Drug (eIND) approval. After requiring perioperative transfusions, by post operative day (POD) 13, endomyocardial biopsy revealed antibody and complement deposition without damage or cellular infiltrate. Hemodynamic decompensation on POD 29 prompted biopsy revealing antibody mediated rejection (AMR). The patient required ECMO support POD31 and chose comfort care POD 40.

Research Questions/Hypothesis: The cardiac xenograft doubled in mass from implant to autopsy. Donor derived cell free DNA (cfDNA) correlated temporally with the rejection findings. These processes are hypothesized to correlate.

Approach: Routine TTE measurements of diastolic LV posterior wall dimension (LVPWd), intraventricular septal dimension (IVSd), LV mass, and LV mass index were taken. Donor derived cfDNA was measured weekly and PRN (Care Dx Inc., Brisbane, CA). Pearson correlation coefficient analysis was conducted in GraphPad Prism 10 (Dotmatics, Boston, MA).

Results/Data: POD 26 TTE measurements indicated thickening graft. POD 30 cfDNA began elevating. cfDNA correlated moderately with LVPWd (r = 0.43, p=0.4) and IVSd (r= 0.5, p=0.31) less so with LV mass (r= 0.28, p=0.59) and LV mass index (r=0.34, p=0.51)

Conclusions: Xenograft cardiac thickening measured on TTE preceded elevation in cfDNA. Both were moderately correlated and temporally corresponded to biopsy diagnosed AMR and ultimate graft failure. Future xenograft surveillance will likely benefit from multimodal approach.