ORCID

0000-0001-5947-4778 (Yehya)

Document Type

Article

Publication Date

2025

DOI

10.1016/j.jchf.2025.102716

Publication Title

JACC: Heart Failure

Pages

13 pp.

Abstract

Background

Donor-derived cell-free DNA (dd-cfDNA) has emerged as a biomarker for antibody-mediated rejection (AMR), but its performance characteristics have not been evaluated in a large contemporary heart transplant population.

Objectives

The study aimed to characterize the incidence and timing of biopsy-proven AMR and evaluate the performance characteristics of dd-cfDNA for AMR.

Methods

The authors included 2,240 subjects from the SHORE (Surveillance HeartCare Outcomes Registry) registry transplanted between 2017 and 2022 with verified biopsy, dd-cfDNA, echocardiographic, and donor-specific antibody (DSA) data. They evaluated the performance characteristics of dd-cfDNA for AMR and the incidence of AMR in different clinical contexts.

Results

AMR was present in 2.6% of biopsies with significant variability depending on the clinical context: AMR occurred in 1.1% of biopsies with normal graft function and no DSAs vs 20.4% of biopsies with known DSA and graft dysfunction. In patients with neither DSA nor graft dysfunction, the incidence of AMR was 0.7% for dd-cfDNA levels < 0.20%, 1.2% for levels between 0.20% and 0.49%, and 6.7% for dd-cfDNA levels ≥0.50%. In patients with known DSA but no graft dysfunction, the incidence of AMR was 1.4% for dd-cfDNA levels < 0.20%, 4.8% for levels between 0.20% and 0.49%, and 15.5% for dd-cfDNA levels ≥0.50%.

Conclusions

The authors document significant context dependent variability of AMR incidence and the utility of dd-cfDNA in predicting biopsy yield. These data complement prior studies on the interpretation of peripheral gene expression profiling and dd-cfDNA for rejection monitoring and should further obviate the need for surveillance biopsies.

Rights

© 2025 The Authors.

This is an open access article under the Creative Commons Attribution 4.0 International (CC BY 4.0) License.

Original Publication Citation

Kim, P. J., Alam, A. H., Teuteberg, J. J., Khush, K. K., Pinney, S. P., Cheng, R. K., Yehya, A., Kobulnik, J., Pinney, K. M., Oreschak, K. A., Ensor, C. R., Fan, S., Urey, M. A., Shah, P., & Hall, S. A. (2025). Donor-derived cell-free DNA in antibody-mediated rejection: An analysis of the Surveillance HeartCare Outcomes Registry. JACC: Heart Failure. Advance online publication. https://doi.org/10.1016/j.jchf.2025.102716

Additional Files
1-s2.0-S2213177925006468-mmc1.docx (394 kB)
Supplementary Tables 1-8 and Supplementary Figures 1-4
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