Combining donor derived cell free DNA and gene expression profiling for non‐invasive surveillance after heart transplantation

Abstract

Background Donor‐derived cell free DNA (dd‐cfDNA) and gene expression profiling (GEP) offer noninvasive alternatives to rejection surveillance after heart transplantation; however, there is little evidence on the paired use of GEP and dd‐cfDNA for rejection surveillance. Methods A single center, retrospective analysis of adult heart transplant recipients. A GEP cohort, transplanted from January 1, 2015 through December 31, 2017 and eligible for rejection surveillance with GEP was compared to a paired testing cohort, transplanted July 1, 2018 through June 30, 2020, with surveillance from both dd‐cfDNA and GEP. The primary outcomes were survival and rejection‐free survival at 1 year post‐transplant. Results In total 159 patients were included, 95 in the GEP and 64 in the paired testing group. There were no differences in baseline characteristics, except for less use of induction in the paired testing group (65.6%) compared to the GEP group (98.9%), P < .01. At 1‐year, there were no differences between the paired testing and GEP groups in survival (98.4% vs. 94.7%, P = .23) or rejection‐free survival (81.3% vs. 73.7% P = .28). Conclusions Compared to post‐transplant rejection surveillance with GEP alone, pairing dd‐cfDNA and GEP testing was associated with similar survival and rejection‐free survival at 1 year while requiring significantly fewer biopsies.

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

“…Additionally, it was reassuring to see the majority of the deaths in our matched cohort were not due to AR. This is consistent with recent literature showing low mortality due to AR in the current era 13,14 . Of note, at UC San Diego Health, a weekly pathologic review of all EMB samples are performed by a panel of three anatomic pathologists, led by our senior pathologist, in addition to our HTx cardiologist group for more consistent pathologic reads.…”

“…Because of the low prevalence of AR, the NPV without testing already starts very high at 97% in our study and 98.4% in a recent large, multi‐center observational study 14 . The low PPV has also been observed in other recent studies for dd‐cfDNA 13,28,29 . In our study, the probability of rejection for the expanded SNP assay moves from 3.0% pretest to 7.5% post‐test for a positive test and 2.2% post‐test for a negative test.…”

“…Thus, we did not find any benefit for detection of ACR with GEP on top of dd‐cfDNA testing. Recently, Henricksen and coauthors showed similar survival with dd‐cfDNA + GEP testing compared to GEP alone 13 . However, our findings suggest that dd‐cfDNA testing, without GEP, is sufficient.…”

“…This was a retrospective, observational study of HTx patients at the University of California, San Diego Health (UC San Diego Health) who had an EMB and both standard and expanded SNP dd‐cfDNA testing in the 14 days preceding the EMB. Inclusion of an EMB performed within 14 days is based on previous literature and it also represents real world practice 13,14 . Eligible subjects were HTx only recipients, 18 years of age or older, and at least 28 days post‐HTx.…”

“…Inclusion of an EMB performed within 14 days is based on previous literature and it also represents real world practice. 13,14…”