(498) Diagnostic Performance of Molecular Microscope Diagnostic System in Addition to Cell Free DNA in Heart Transplant Rejection

PurposeWe assess the diagnostic performance of the Molecular Microscope Diagnostic System (MMDx) and the AlloSure donor-derived cell-free DNA Fraction (dd-cfDNA%) in diagnosing heart transplant (HT) rejection compared to the gold standard of histopathology (HP).MethodsWe reviewed biopsies from HT patients at Houston Methodist Hospital who had MMDx, HP and peripheral blood sample of donor-derived cell-free DNA (dd-cfDNA) drawn at the same time point as the endomyocardial biopsy (EMBx). We evaluated the additive performance of MMDx combined with elevated dd-cfDNA% in diagnosing rejection in HT patients with elevated dd-cfDNA% when compared to EMBx HP.ResultsWe included 113 biopsies from 54 HT patients. The median time of biopsy post-transplantation was 108.0 (IQR 29.0, 307.0) days. Median age was 57.0 (IQR 48.0, 63.0) years and 38/54 (70.4%) were males. Rejection was classified on EMBx in 16 specimens (n=13 ACR ≥ 2R, n=3 AMR ≥ 50% C4d) and on MMDx in 18 specimens (n=9 ACR, n=8 AMR, n=1 ACR+AMR). The AlloSure dd-cfDNA was ≥0.12% in n=48 (42.5%) biopsies and out of these 11 (9 ACR, 2 AMR) had HP rejection on EMBx and 13/48 had rejection on MMDx (7 AMR, 5ACR and 1 mixed rejection) The diagnostic performance of MMDx to predict rejection showed high specificity and negative predictive value (NPV) compared to sensitivity and positive predictive value (PPV). When testing the additive effect of AlloSure to MMDx in diagnostic performance to predict rejection compared with HP, MMDx alone showed higher specificity compared to AlloSure ≥0.12% alone. Although the addition of AlloSure to MMDx does not increases the sensitivity, it appears to increase the specificity (Table 1).ConclusionMMDx and blood-based dd-cfDNA add diagnostic value to the histopathological diagnosis of rejection in HT recipients. We assess the diagnostic performance of the Molecular Microscope Diagnostic System (MMDx) and the AlloSure donor-derived cell-free DNA Fraction (dd-cfDNA%) in diagnosing heart transplant (HT) rejection compared to the gold standard of histopathology (HP). We reviewed biopsies from HT patients at Houston Methodist Hospital who had MMDx, HP and peripheral blood sample of donor-derived cell-free DNA (dd-cfDNA) drawn at the same time point as the endomyocardial biopsy (EMBx). We evaluated the additive performance of MMDx combined with elevated dd-cfDNA% in diagnosing rejection in HT patients with elevated dd-cfDNA% when compared to EMBx HP. We included 113 biopsies from 54 HT patients. The median time of biopsy post-transplantation was 108.0 (IQR 29.0, 307.0) days. Median age was 57.0 (IQR 48.0, 63.0) years and 38/54 (70.4%) were males. Rejection was classified on EMBx in 16 specimens (n=13 ACR ≥ 2R, n=3 AMR ≥ 50% C4d) and on MMDx in 18 specimens (n=9 ACR, n=8 AMR, n=1 ACR+AMR). The AlloSure dd-cfDNA was ≥0.12% in n=48 (42.5%) biopsies and out of these 11 (9 ACR, 2 AMR) had HP rejection on EMBx and 13/48 had rejection on MMDx (7 AMR, 5ACR and 1 mixed rejection) The diagnostic performance of MMDx to predict rejection showed high specificity and negative predictive value (NPV) compared to sensitivity and positive predictive value (PPV). When testing the additive effect of AlloSure to MMDx in diagnostic performance to predict rejection compared with HP, MMDx alone showed higher specificity compared to AlloSure ≥0.12% alone. Although the addition of AlloSure to MMDx does not increases the sensitivity, it appears to increase the specificity (Table 1). MMDx and blood-based dd-cfDNA add diagnostic value to the histopathological diagnosis of rejection in HT recipients.