Heart failure & cardiomyopathies

Significance of Elevated Donor-Derived Cell-Free DNA in Heart Transplant Recipients With Negative Endomyocardial Biopsies: A Dawn of a New Era

Circ Heart FailPublished Retrospective cohort study

Authors' conclusion

In our cohort, patients with positive dd-cfDNA levels and negative biopsy results had higher rates of adverse outcomes, including graft dysfunction and mortality.

Study context

Population
Heart transplant recipients, 2019–2023, excluding multiorgan transplants; Donor-derived cell-free DNA (dd-cfDNA) samples paired with endomyocardial biopsy (<30 days)643 dd-cfDNA samples
Participants
227 recipients
Exposure
Positive dd-cfDNA with negative endomyocardial biopsy vs negative dd-cfDNA
Outcome
Mortality and graft dysfunction (EF<50%)
Methodological detailsconsecutive patients, mixed model Cox regression
  • Consecutive patients
  • Mixed model Cox regression

Main finding

As reported in the abstract

Mortality and graft dysfunction, dd-cfDNA ≥0.20%
dd-cfDNA positive vs Negative dd-cfDNAHazard ratio (95% CI)P value
Mortality; dd-cfDNA ≥ 0.20%
4.6(1.6–13.4)
P = 0.005
Graft dysfunction; dd-cfDNA ≥ 0.20%
3.4(1.0–11.9)
P = 0.054

Observational data: associations, not effects.

Further findings

Outcomedd-cfDNA positivedd-cfDNA ≥0.20%Negative dd-cfDNAP value
Positive dd-cfDNA with negative biopsy · samples37%
Patients110Not reported in the abstractNot reported in the abstractdd-cfDNA ≥0.20%, Negative dd-cfDNA: not reported in the abstract
Median dd-cfDNA level0.24% (IQR 0.16%-0.53%)Not reported in the abstractNot reported in the abstractdd-cfDNA ≥0.20%, Negative dd-cfDNA: not reported in the abstract
Exceeding 0.20%63%Not reported in the abstractNot reported in the abstractdd-cfDNA ≥0.20%, Negative dd-cfDNA: not reported in the abstract
Prior treated antibody-mediated rejection15%Not reported in the abstract5%P = 0.002dd-cfDNA ≥0.20%: not reported in the abstract

Original publication

Significance of Elevated Donor-Derived Cell-Free DNA in Heart Transplant Recipients With Negative Endomyocardial Biopsies: A Dawn of a New Era. Circ Heart Fail. Published 30 September 2025. doi:10.1161/circheartfailure.125.012787

Summarised from the published abstract; every number is checked against it

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