The impact of active cytomegalovirus infection on donor-derived cell-free DNA testing in heart transplant recipients

Background: Little is known about the relationship between cytomegalovirus (CMV) infections and donor-derived cell-free DNA (dd-cfDNA) in heart transplant recipients.

Methods: In our study, CMV and dd-cfDNA results were prospectively collected on single-organ heart transplant recipients. If the CMV study was positive, a CMV study with dd-cfDNA was repeated 1-3 months later. The primary aim was to compare dd-cfDNA between patients with positive and negative CMV results.

Results: Of 44 patients enrolled between August 2022 and April 2023, 12 tested positive for CMV infections, 25 were included as controls, and seven patients with a viral infection without CMV were excluded. Baseline characteristics did not differ significantly between CMV-positive and CMV-negative patients with the exception of a later median time post-transplant in the CMV-positive group (253 days vs. 120 days, p = .03). Dd-cfDNA levels were significantly higher in patients with CMV infections compared to those without (p < .001) with more patients in the CMV positive group showing dd-cfDNA results ≥.12% (75% vs. 8%, p < .001) and ≥.20% (58% vs. 8%, p = .002). Each 1 log₁₀ copy/ml reduction in CMV viral load from visit 1 to visit 2 was associated with a.23% reduction in log₁₀ dd-cfDNA (p = .002).

Conclusion: Our findings suggest that active CMV infections may raise dd-cfDNA levels in patients following heart transplantation. Larger studies are needed to validate these preliminary findings.