Poke Not Prod: First Canadian Experience Using Donor-Derived Cell Free DNA to Replace Endomyocardial Biopsy During COVID-19

After a heart transplant (HT), non-invasive methods for rejection surveillance minimize the need for endomyocardial biopsies (EMBx). We describe the first experience with combined use of genetic expression profiling (GEP) and donor-derived cell-free DNA (dd-cfDNA) testing in Canada as part of a quality improvement project to minimize patient risk during the COVID pandemic. Adult outpatients at least 6 months after HT were screened from May 2021 to July 2021 to have their routine EMBx replaced by a combination of GEP and dd-cfDNA. Demographics, modification of immunosuppression (IS) and outcomes (hospital admission, rejection, and need for EMBx) were collected. Among 90 patients, 31 (33%) were enrolled, and 37 non-invasive tests were performed. The median time after HT was 2 years and patients were predominantly Caucasian (52%) and male (68%). 53% had a history of acute cellular rejection during the first year and 32% had cardiac allograft vasculopathy. Of the tests performed, 23 (60%) were - GEP / - dd-cfDNA, 10 (27%) were + GEP / - dd-cfDNA, 4 (11%) were - GEP / + dd-cfDNA and none were + GEP / + dd-cfDNA. Being bridged with a VAD (OR = 5.5, p=0.034) and a history of a previously treated CMV (OR = 16.0, p=0.003) were associated with a positive GEP and a negative dd-cfDNA result. Having received a COVID vaccine in the last 3 months did not affect GEP results (GEP was positive in 23.8% after vaccination vs 33.3% in non-vaccinated patients, p=0.690; average GEP score 29.8 vs 30.7, p=0.673). The 4 patients with a + dd-cfDNA (range 0.19 - 0.81%) underwent an EMBx with no significant cellular or antibody mediated rejection, thus avoiding 89% of the EMBx. No unscheduled clinic visits, emergency department or hospital admissions were recorded. After non-invasive testing, the IS was reduced in 16 cases (43.2%). IS was reduced in in 59% of patients with negative concordant tests (- GEP / - dd-cfDNA), 30% in patients with + GEP / - dd-cfDNA and no reduction in IS occurred in those with + dd-cfDNA. The combination of GEP and dd-cfDNA for rejection surveillance allowed for a marked reduction in EMBx (89%) and for a personalized downtitration of IS without adverse events in the short term. The use of non-invasive rejection surveillance testing was an effective strategy to avoid hospital contact for HT recipients during the COVID-19 pandemic.