{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:51:38Z","timestamp":1791175898441,"version":"4.1.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontierspartnerships.org"],"crossmark-restriction":true},"short-container-title":["Transpl. Int."],"abstract":"<jats:p>Endomyocardial biopsy (EMB) is the gold standard for diagnosing post-heart transplant acute rejection (AR) but is invasive. Donor-derived cell-free DNA (dd-cfDNA) is a promising noninvasive biomarker, yet thresholds for Asian recipients remain undefined. This prospective study enrolled 80 patients, with 299 dd-cfDNA specimens analyzed via a novel Chinese-developed next-generation sequencing assay targeting 48 Indel sites. A reference cohort (n = 42) established post-transplant dd-cfDNA kinetics, while a biopsy cohort (n = 41, 18 acute cellular rejection [ACR], 9 antibody-mediated rejection [AMR], 14 no rejection [NR]) paired with EMB evaluated diagnostic performance. dd-cfDNA peaked at week 1, with a stable trend emerging from week 4 and stable levels reached by week 8. AR patients had significantly higher dd-cfDNA levels than NR patients (0.87% vs. 0.23%, P &amp;lt; 0.001). The optimal composite AR threshold was 0.33% (AUC = 0.874, sensitivity 81.0%, specificity 85.7%). dd-cfDNA decreased post-therapy (P = 0.011) and showed an inverse association with left ventricular ejection fraction (LVEF) (P = 0.004). This study provides initial evidence for an assay- and cohort-specific dd-cfDNA threshold (0.33%) for AR detection in Chinese recipients. Given the modest NPV (75.0%), this threshold is better suited for a \u201crule-in\u201d strategy, and low values should not be used in isolation to defer biopsy. External validation in multicenter cohorts is required before routine clinical implementation.<\/jats:p>","DOI":"10.3389\/ti.2026.16415","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:10:14Z","timestamp":1791173414000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Prospective evaluation of donor-derived cell-free DNA for noninvasive detection of acute rejection in an Asian heart transplant population"],"prefix":"10.3389","volume":"39","author":[{"given":"Shanshan","family":"Zheng","sequence":"first","affiliation":[{"name":"Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, 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