Short‐term clinical outcomes and predicted cost savings of dd‐cfDNA‐led surveillance after pediatric heart transplantation

Abstract

Background Endomyocardial biopsy (EMB)‐led surveillance is common after pediatric heart transplantation (HT), with some centers performing periodic surveillance EMBs indefinitely after HT. Donor derived cell‐free DNA (dd‐cfDNA)‐led surveillance offers an alternative, but knowledge about its clinical and economic outcomes, both key drivers of potential utilization, are lacking. Methods Using single‐center recipient and center‐level data, we describe clinical outcomes prior to and since transition from EMB‐led surveillance to dd‐cfDNA‐led surveillance of pediatric and young adult HT recipients. These data were then used to inform Markov models to compare costs between EMB‐led and dd‐cfDNA‐led surveillance strategies. Results Over 34.5 months, dd‐cfDNA‐led surveillance decreased the number of EMBs by 81.8% (95% CI 76.3%–86.5%) among 120 HT recipients (median age 13.3 years). There were no differences in the incidences of graft loss or death among all recipients followed at our center prior to and following implementation of dd‐cfDNA‐led surveillance (graft loss: 2.9 vs. 1.5 per 100 patient‐years; p = .17; mortality: 3.7 vs. 2.2 per 100 patient‐years; p = .23). Over 20 years from HT, dd‐cfDNA‐led surveillance is projected to cost $8545 less than EMB‐led surveillance. Model findings were robust in sensitivity and scenario analyses, with cost of EMB, cost of dd‐cfDNA testing, and probability of elevated dd‐cfDNA most influential on model findings. Conclusions dd‐cfDNA‐led surveillance shows promise as a less invasive and cost saving alternative to EMB‐led surveillance among pediatric and young adult HT recipients.

Histopathology, mRNA expression profile, and donor‐derived cell‐free DNA for assessment of rejection in pediatric heart transplantation

“…Several HT studies have demonstrated noninferiority of a ddcfDNA-based surveillance protocol compared with EMB due to its high negative predictive value (NPV) for clinically meaningful AR. [3][4][5][6] Additionally, the degree of ddcfDNA elevation correlates with severity and type of AR, and treatment of AR is followed by predictable decreases in ddcfDNA levels. 7,8 Data in adult HT recipients suggest that ddcfDNA may rise before histologic changes of AR, therefore capturing early rejection.…”