Heart failure & cardiomyopathies
Donor-Derived Cell-Free DNA as a Prognostic Biomarker After Heart Transplantation: The DEFINE-HT Study
Authors' conclusion
DEFINE-HT supports the potential role of dd-cfDNA as a prognostic biomarker of graft health
Study context
- Population
- Adult heart transplant recipients followed for 1 year post-transplant
- Participants
- 110 recipients
- Exposure
- Association of donor-derived cell-free DNA (dd-cfDNA) with 1-year outcomes
- Outcome
- Composite of:
- Treated rejection
- Graft dysfunction
- Retransplantation
- Death
- Follow-up
- 1 year post-HT
Methodological detailsmulticentre, 10 US centres
- Multicentre
- 10 US centres
Main finding
As reported in the abstract
Primary composite endpoint
- Met primary composite endpoint
- 38 (34.5%)
- Treated rejection
- 20%
- Graft dysfunction
- 10.9%
- Death
- 3.6%
- Retransplantation
- 0%
- Higher risk of primary endpoint per 1-intrapatient-SD increase in dd-cfDNA% (P < 0.001)
- 19%
- Higher risk of primary endpoint per 1-intrapatient-SD increase in donor quantity score (DQS) (P < 0.001)
- 12%
- Increased risk of composite endpoint with above-threshold dd-cfDNA (P < 0.001)
- 4.42-fold
Observational data: associations, not effects.
Further findings
| Outcome | Values | P value |
|---|---|---|
| dd-cfDNA% in treated vs untreated biopsy-positive rejection | Treated 0.23% · Untreated 0.085% | P = 0.045 |
| DQS in treated vs untreated biopsy-positive rejection | Treated 27 copies/mL · Untreated 9 copies/mL | P = 0.012 |
Biopsy and dd-cfDNA results
- Endomyocardial biopsies demonstrating rejection
- 4.6%
- dd-cfDNA results below threshold
- 90%
- No patients with graft dysfunction had biopsy-positive rejection despite elevated dd-cfDNA
Original publication
Donor-Derived Cell-Free DNA as a Prognostic Biomarker After Heart Transplantation: The DEFINE-HT Study. JACC Heart Fail. Published 5 June 2026. doi:10.
Summarised from the published abstract; every number is checked against it