{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:04:36Z","timestamp":1787313876164,"version":"build-2736575974"},"reference-count":103,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82570472"],"award-info":[{"award-number":["82570472"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Cardiac transplantation remains an important therapy for end-stage heart failure, although allograft rejection continues to pose significant clinical challenges. This review evaluates both established and emerging blood-based biomarkers for noninvasive monitoring of rejection in heart transplant recipients. Donor-derived cell-free DNA (ddcfDNA) and gene expression profiling (GEP) represent well-validated, commercially available molecular tools that demonstrate strong discriminative capacity for acute rejection episodes. Additionally, microRNAs (miRs) and extracellular vesicles (EVs) show considerable potential as novel biomarkers, although further validation is required. In contrast, conventional biomarkers such as B-type natriuretic peptide (BNP), cardiac troponins, and creatine kinase-MB (CK-MB) offer limited specificity in the context of rejection. This review synthesizes current evidence on the clinical utility, methodological challenges, and integration strategies of these biomarkers, highlighting a shift toward molecular-based approaches for improving post-transplant surveillance and patient outcomes.<\/jats:p>","DOI":"10.3390\/jcm15030986","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T09:21:40Z","timestamp":1769505700000},"page":"986","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Noninvasive Biomarkers for Cardiac Allograft Rejection Monitoring: Advances, Challenges, and Future Directions"],"prefix":"10.3390","volume":"15","author":[{"given":"Yijie","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junlin","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenghao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guohua","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1016\/j.healun.2025.04.014","article-title":"The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: 2025 Annual Report of Heart and Lung Transplantation","volume":"44","author":"Singh","year":"2025","journal-title":"J. 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