Endomyocardial Biopsy Microscopic Molecular Profiling Correlates with Donor Derived Cell Free DNA and Histopathology.

Cardiac allograft rejection (AR) diagnosis has historically relied on endomyocardial biopsy (EMBx) and histopathology (HP). Quantifying donor-derived cell free DNA (ddcfDNA) has recently offered a non-invasive alternative for detecting graft injury. EMBx mRNA analysis via the molecular microscope profiles (MMP) quantifies AR probability not subject to HP interpretation. Our aim was to evaluate the clinical role of MMP in cardiac transplant recipients (HTx) with positive ddcfDNA. We identified 39 patients with ddcfDNA testing and subsequent EMBx for HP (n=36) and MMP (n=39) analysis. MMP was conducted by the molecular microscope diagnostic system (MMDX™). Patients with multi-organ transplantation or coronary allograft vasculopathy were excluded. MMP, HP, echo and ddcfDNA association were assessed using logistical regression (SPSS™). Average time post-transplant was 1585 ±1435 days, average LVEF 55%, and average ddcfDNA 0.81 ± 1.1. Donor specific antibodies were present in 14/39 of patients. MMP was abnormal in 18/39 patients and correlated with ddcfDNA levels (p=0.007) and HP (p=0.05), but not with LVEF (p=0.71). MMP abnormalities included 9 antibody mediated rejection (AMR), 5 acute cellular rejection (ACR), and 4 injury patterns. By HP, biopsies were abnormal in 18/36 patients: 18 ACR (grade 1) and 1 AMR (grade 2). Abnormal HP did not correlate with ddcfDNA levels (p= 0.07). HP and MMP are often discordant, Table 1. Abnormal MMP correlated with both ddcfDNA and HP, but not with LVEF. Large prospective clinical trials are needed to define clinical outcomes from treatment strategies based on biopsy results. Multi-modality testing may be necessary to monitor cardiac transplant patients for rejection and avoid misclassification. [ABSTRACT FROM AUTHOR]