Combining Donor Derived Cell-Free DNA and Gene Expression Profiling for Non-Invasive Surveillance after Heart Transplantation

Purpose Endomyocardial biopsy (EMBx) is the gold standard for acute cellular rejection (ACR) after heart transplantation (HTx). However, the limitations of EMBx has led to the adoption of non-invasive rejection surveillance. With the commercial introduction of gene-expression profiling (GEP) and more recently, donor-derived cell-free DNA (cfDNA), the predictive ability of cfDNA and its utility in combination with GEP are not well known. Methods This was a retrospective, single-center study of heart transplant recipients who had concomitant Allosure cfDNA and AlloMap GEP assays (CareDx). Results of both assays were then compared against EMBx to derive test sensitivity (SN), specificity (SP), positive predive value (PPV) and negative predictive values (NPV) for cfDNA using a threshold of 0.2%. Results The analysis included 131 patients (559 pairs of samples). This cohort was predominantly male (76.3%) and Caucasian (63.4%). The median (IQR) time to assay from date of transplant was 238 (123-385) days. When results were compared to EMBx, SN 0.5, SP 0.94, PPV 0.4 and NPV 0.96 to detect ACR grade 2 or above. cfDNA and GEP were concordant 87.3% of the time (Fig 1a). There were two instances where both cfDNA and GEP were negative, and patient had significant (>1R) rejection (Fig 1b). Of patients who were below threshold on both assays, 95% had no biopsy performed. Conclusion When monitoring patients with both cfDNA and GEP, the most common result was that both were below threshold. When the results were discordant and a biopsy was performed, no treatable ACR was observed. The use of combination non-invasive testing may allow for safe and complementary information for rejection surveillance after HT.