Donor-Recipient Size Mismatch, Age at Transplant, and Elevated Donor-Derived Cell-Free DNA % Early After Pediatric...

Acute rejection (AR) is a major cause of graft loss after orthotopic heart transplant (OHT). Donor-derived cell-free DNA fraction (dd-cfDNA%) is a noninvasive biomarker for AR but may be elevated without AR. We evaluated associations of donor-recipient size mismatch and recipient age with early dd-cfDNA% in pediatric OHT recipients without AR.

This single-center retrospective study evaluated initial dd-cfDNA% testing in pediatric OHT recipients without AR. Size mismatch was assessed using donor-to-recipient body surface area (BSA) ratio, weight ratio, and allograft left ventricular (LV) mass z-score. Associations with dd-cfDNA% were assessed using Spearman correlation and Mann-Whitney U tests; multivariable linear regression adjusted for age. Analyses of size mismatch and recipient age were repeated at the second post-OHT dd-cfDNA assessment.

Between 2022 and 2025, 58 pediatric OHT recipients underwent dd-cfDNA% testing; 39 had no rejection. After excluding 2 outliers, 37 remained. Higher first dd-cfDNA% was associated with larger BSA ratio (p = 0.039), BSA ratio ≥ 1.5 (median 0.17% vs. 0.06%, p = 0.0185), larger weight ratio (p = 0.016), LV mass oversizing (median 0.17% vs. 0.06%, p = 0.0196), and younger age (p = 0.008). After age adjustment, neither size mismatch nor age was independently associated with first dd-cfDNA%. No significant associations were observed at the second assessment.

Greater donor-recipient size mismatch and younger recipient age were associated with higher first dd-cfDNA% in unadjusted analyses, but not after age adjustment. These exploratory findings support further investigation of size mismatch, recipient age, and early allograft adaptation as potential non-rejection contributors to dd-cfDNA elevation.