Should We Be Comforted by a “Negative” Endomyocardial Biopsy? Risk of Future Events with Donor Derived Cell Free DNA in the Setting of Histologic Quiescence

PurposeEndomyocardial biopsy (EMB) is considered the gold standard for screening rejection in heart transplant (HT) recipients. Lack of histological evidence on EMB has typically been reassuring to clinicians, but interpretation elevated levels donor-derived cell free DNA (dd-cfDNA) setting a “negative” unclear.MethodsPatients from multi-center Surveillance Using HeartCare Outcomes Registry (SHORE) database who had dd-cfDNA measured within 30 days negative (Grades 2R/AMR1 or higher rejection) first 100 were reviewed. These patients followed subsequent development significant and de novo donor-specific antibodies (dnDSA) over next 365 days.ResultsA total 648 HT recipients with mean age 57, 74% male, white 64%, 60% which PRA < 1% 982 paired biopsies median 0.05% those Grade 0R 0.06% 1R (Figure 1a). The was 112 post-transplant 109 1R. Despite histology EMB, cfDNA >= 0.20% at significantly risk (14.3% v 5.2%, p<0.01) dnDSA (11.3% v. 6.8%, year.ConclusionPatients dd-cfDNA, without prior are increased year. use may be better method determine true quiescence call into question utility as cardiac allograft monitoring. Endomyocardial unclear. Patients days. A