Early Experience in Correlation of Donor Derived, Cell Free DNA Testing with Intravascular Ultrasound Evidence and Overt Coronary Artery Vasculopathy

Abstract

Coronary artery vasculopathy (CAV) remains a significant limitation for long-term survival after heart transplantation (HT), observed in 30-45% of recipients by 5 years and 50-65% by 10 years post-HT. Despite the increased fidelity, the detection of CAV at the level of the vessel remains invasive and with various modalities used in CAV screening, the ability to detect sub-occlusive disease or disease in vessels less than 1.5 mm diameter remains problematic. Donor-derived, cell-free DNA (dd-cfDNA (AlloSure)), detected in recipient blood, has been established as a non-invasive marker of allograft injury, useful in the assessment of organ rejection. We aim to assess its ability to identify patients with early CAV, hypothesizing cell death due to impaired coronary blood flow from CAV may be associated with changes in dd-cfDNA. All patients were CAV negative at time of last screening (12 months prior) and had no other active pathology to account for the change in dd-cfDNA. Patients had angiography and IVUS performed to assess CAV, in response to changing dd-cfDNA levels. Patients were stratified by time since transplant (<12months post-transplant vs >12months post-transplant). 15 patients were identified where dd-cfDNA (AlloSure®; CareDx, Inc.) was used to detect changes. CAV was assessed on IVUS (7 patients) and coronary angiography (12 patients). All 15 patients were found to have new gross changes of CAV associated with an overall median AlloSure score of 0.68% (IQR: 0.34%, 4.30%). Patients <12months had a median AlloSure of 0.33% (IQR: 0.30%, 0.35%) with a median associated maximal intimal thickness (MIT) of 0.96 mm whereas patients >12months had median AlloSure of 2.13% and an associated median MIT change of 0.60 mm. 7 patients have changes detectable on IVUS that were missed on angiography showing a median new intimal thickening of 0.60 mm CONCLUSION: Increases in dd-cfDNA without demonstrable acute cellular rejection (ACR) or antibody mediated rejection (AMR) are likely to correlate with changes in CAV. IVUS was shown to be more sensitive to the detection of CAV than coronary angiogram and so should be considered in the presence of an elevated AS if angiogram is negative.