Early Use of Donor Derived Cell-Free DNA (dd-cfDNA) in Heart Transplantation

Abstract

Purpose Novel non-invasive cardiac allograft surveillance methods such as dd-cfDNA has emerged as a viable noninvasive tool for rejection surveillance, however, with limited data for early use. We sought to describe the incidence and outcomes of early dd-cfDNA use (< 14 days) for HT rejection surveillance. Methods Consecutive adult HT recipients were identified retrospectively from a single center (n=66). Patients were included if heart-only with at least one dd-cfDNA drawn within 14-days post HT between 8/2/2019 and 10/1/2021 (n=45). Baseline donor/recipient demographics, clinical characteristics, serial echocardiographic parameters, laboratory testing, medication regimens, and clinical course were collected over a 6-month period. The composite endpoint was defined as graft dysfunction (LVEF < 40% or >=25% decline in consecutive visit) triggering EMB, rejection >= 2R, development of de-novo donor specific antibodies (DSAs), or death. Results 45 HT recipients were identified. The cohort was predominantly male (71%), non-Caucasian (67%) with DM (40%) and HTN (38%), and had a mean follow up time of 273-days. Donors were male (33%) with mean ischemic time and donor age of 2.9h and 29.5y, respectively. Mean number of biopsies performed in the first 6 months was 1.6 and mean initial dd-cfDNA (obtained <14d) was 0.3 ± 0.2% (NL <0.12). Overall, there was no difference in baseline demographics by composite endpoint. Eleven patients (24%) met the composite endpoint (rejection >= 2R (n=4), de-novo DSAs (n=6), graft dysfunction (n=4)). Biopsy frequency was increased in those meeting the endpoint (2.4 vs 1.4, p<0.004). There were no deaths during the study period. No significant association was demonstrated between dd-cfDNA < 14 d and the composite endpoint p=0.547) at time of interim analysis. Conclusion Early use of dd-cfDNA (< 14 d) for rejection surveillance is effective in lieu of protocol endomyocardial biopsy. Interim analysis demonstrates significant reduction in protocol biopsy frequency with no deaths in this cohort to date. Completion of follow up is expected in March 2022. Novel non-invasive cardiac allograft surveillance methods such as dd-cfDNA has emerged as a viable noninvasive tool for rejection surveillance, however, with limited data for early use. We sought to describe the incidence and outcomes of early dd-cfDNA use (< 14 days) for HT rejection surveillance. Consecutive adult HT recipients were identified retrospectively from a single center (n=66). Patients were included if heart-only with at least one dd-cfDNA drawn within 14-days post HT between 8/2/2019 and 10/1/2021 (n=45). Baseline donor/recipient demographics, clinical characteristics, serial echocardiographic parameters, laboratory testing, medication regimens, and clinical course were collected over a 6-month period. The composite endpoint was defined as graft dysfunction (LVEF < 40% or >=25% decline in consecutive visit) triggering EMB, rejection >= 2R, development of de-novo donor specific antibodies (DSAs), or death. 45 HT recipients were identified. The cohort was predominantly male (71%), non-Caucasian (67%) with DM (40%) and HTN (38%), and had a mean follow up time of 273-days. Donors were male (33%) with mean ischemic time and donor age of 2.9h and 29.5y, respectively. Mean number of biopsies performed in the first 6 months was 1.6 and mean initial dd-cfDNA (obtained <14d) was 0.3 ± 0.2% (NL <0.12). Overall, there was no difference in baseline demographics by composite endpoint. Eleven patients (24%) met the composite endpoint (rejection >= 2R (n=4), de-novo DSAs (n=6), graft dysfunction (n=4)). Biopsy frequency was increased in those meeting the endpoint (2.4 vs 1.4, p<0.004). There were no deaths during the study period. No significant association was demonstrated between dd-cfDNA < 14 d and the composite endpoint p=0.547) at time of interim analysis. Early use of dd-cfDNA (< 14 d) for rejection surveillance is effective in lieu of protocol endomyocardial biopsy. Interim analysis demonstrates significant reduction in protocol biopsy frequency with no deaths in this cohort to date. Completion of follow up is expected in March 2022.