Is Donor-Derived Cell Free DNA a Useful Biomarker of Cardiac Allograft Vasculopathy? (FreeDNA-CAV Study)

Purpose To evaluate the performance of Donor-derived Cell Free DNA (ddcf-DNA) as a biomarker of cardiac allograft vasculopathy (CAV) in a cohort of heart transplant (HT) recipients undergoing routine coronary angiography. Methods We prospectively obtained ddcf-DNA levels in all patients who underwent routine coronary angiography > 1 year after HT in our center between Jan 2019 and Sept 2020. Patients with concomitant acute rejection (n=10), circulating HLA-antibodies (n=1) or multiorgan transplant (n=8) were excluded. Ddcf-DNA levels were correlated with CAV degree (ISHLT 2010 classification). Results We included 82 HT recipients, median age 56 years (IQR 49.3-66), 68% men, a median of 10 years (IQR 4.2-17.7) after transplant. Coronary angiogram revealed CAV0 in 68%, CAV1 in 13%, CAV2 in 5% and CAV3 in 13%. Median ddcf-DNA values in each group are shown in Figure 1A. Ddcf-DNA levels did not differ significantly between patients with and without CAV (Table 1 and Figure 1B). No significant differences were found between patients with “stable CAV” (no new significant coronary lesions since previous angiogram, n=67) and “progressive CAV” (those with new coronary stenosis, n=15), median values were 0.8% (IQR 0.26-2.0) and 0.87% (IQR 0.12-4.2) respectively, p=0.635 (Figure 1C). No correlation was found between ddcf-DNA and troponin I (ρ=0.086, p=0.568) or NTproBNP levels (ρ=-0.137, p=0.238). Conclusion In this preliminary experience, ddcf-DNA level did not seem to correlate with CAV presence, severity or progression. We hope that ongoing recruiting will help to establish a definitive conclusion in this topic.