Comparison of two donor‐derived cell‐free DNA tests and a blood gene‐expression profile test in heart transplantation

Abstract Background Donor‐derived cell‐free DNA (dd‐cfDNA) testing is an emerging screening modality for noninvasive detection of acute rejection (AR). This study compared the testing accuracy for AR of two commercially available dd‐cfDNA and gene‐expression profiling (GEP) testing in heart transplant (HTx) recipients. Methods This is a retrospective, observational study of HTx only patients who underwent standard and expanded single nucleotide polymorphism (SNP) dd‐cfDNA between October 2020 to January 2022. Comparison with GEP was also performed. Assays were compared for correlation, accurate classification, and prediction for AR. Results A total of 428 samples from 112 unique HTx patients were used for the study. A positive standard SNP correlated with the expanded SNP assay ( p < .001). Both standard and expanded SNP tests showed low sensitivity (39%, p = 1.0) but high specificity (82% and 84%, p = 1.0) for AR. GEP did not improve sensitivity and showed worse specificity ( p < .001) compared to standard dd‐cfDNA. Conclusion We found no significant difference between standard and expanded SNP assays in detecting AR. We show improved specificity without change in sensitivity using dd‐cfDNA in place of GEP testing. Prospective controlled studies to address how to best implement dd‐cfDNA testing into clinical practice are needed.