Evolving the surveillance and workup of heart transplant rejection: A real‐world analysis of the Molecular Microscope Diagnostic System. Issue 10 (24th May 2022)

• Record Type: Journal Article
• Authors: Alam, Amit; Van Zyl, Johanna; Paul Milligan, Gregory; Michelle McKean, Staci; Patel, Raksha; Anne Hall, Shelley
• Is Part Of: American journal of transplantation. Volume 22:Issue 10(2022)
• Page Start: 2443
• Page End: 2450
• Publication Date: 2022-05-24
• Subjects: clinical research/practice -- heart transplantation/cardiology -- molecular biology: mRNA/mRNA expression -- microarray/gene array -- rejection -- rejection: antibody‐mediated (ABMR) -- rejection: T cell mediated (TCMR); Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.17087
• Languages: English
• ISSNs: 1600-6135

Abstract

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. Abstract : The investigators analyze endomyocardial biopsy results and donor‐derived cell‐free DNA levels from adult heart transplant recipients to compare the performance of the Molecular Microscope Diagnostic System to established modalities.