1. Evolving the surveillance and workup of heart transplant rejection: A real-world analysis of the Molecular Microscope Diagnostic System.
- Author
-
Alam A, Van Zyl J, Paul Milligan G, Michelle McKean S, Patel R, and Anne Hall S
- Subjects
- Adult, Antibodies, Doxorubicin analogs & derivatives, Graft Rejection diagnosis, Graft Rejection etiology, Humans, Postoperative Complications, RNA, Retrospective Studies, Cell-Free Nucleic Acids genetics, Heart Diseases, Heart Transplantation adverse effects, Kidney Transplantation
- Abstract
The Molecular Microscope Diagnostic System (MMDx) analyzes RNA transcripts of transplanted heart tissue to differentiate among T cell-mediated rejection (TCMR), antibody-mediated rejection (AMR), injury, and healthy tissue. However, little is known about its performance in relation to other modalities in a real-world heart transplant population. We evaluated whether MMDx performs in agreement with other validated modalities. Two hundred and twenty-eight corresponding endomyocardial biopsies (EMBx) and MMDx specimens from 135 adult heart transplant patients were retrospectively reviewed with correlating donor-derived cell-free DNA (dd-cfDNA). Rejection was classified on EMBx in 29 specimens (TCMR ≥ 2R and/or AMR ≥ 1), on MMDx in 56 specimens, and in 74 values with dd-cfDNA ≥0.20%. Despite moderate agreement between EMBx and MMDx (84% agreement, Cohen's kappa, 0.48, p < .001), systematic differences were observed (McNemar's test, p < .001) where MMDx classified 32 of 37 discordant cases as rejection. MMDx and dd-cfDNA demonstrated slight agreement (72% agreement, Cohen's kappa, 0.39, p < .001); however, systematic differences were also apparent where MMDx classified 12 of 50 discordant specimens as rejection when dd-cfDNA was <0.20% (McNemar's test, p < .001). Our findings provide insight on the performance of MMDx relative to other modalities in a heart transplant cohort and have implications on the surveillance and workup of allograft rejection in heart transplantation., (© 2022 The American Society of Transplantation and the American Society of Transplant Surgeons.)
- Published
- 2022
- Full Text
- View/download PDF