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心脏移植中dd-cfDNA升高且心内膜活检结果令人安心时的诊断方法

Diagnostic approach to elevated dd-cfDNA with reassuring EMB in heart transplantation.

作者信息

Bahniwal Rupinder K, Mehta Aditya, Kennedy Jamie L W

机构信息

Department of Cardiovascular Disease, Inova Schar Heart and Vascular, Falls Church, VA, United States.

出版信息

Front Transplant. 2025 Aug 14;4:1623514. doi: 10.3389/frtra.2025.1623514. eCollection 2025.

DOI:10.3389/frtra.2025.1623514
PMID:40894346
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12391120/
Abstract

Despite significant advances in organ preservation, surgical techniques, and immunosuppressive regimens, rejection continues to pose a major challenge in the care of heart transplant patients. Endomyocardial biopsy (EMB) remains the gold standard test for surveillance and diagnosis of rejection, but is limited by its invasiveness, interobserver variability, procedural risk, and cost thus prompting the widespread use of non-invasive biomarkers such as donor-derived cell-free DNA (dd-cfDNA). Due to its high negative predictive value, dd-cfDNA is often routinely used for surveillance of asymptomatic patients. However, it is a non-specific marker of allograft injury and elevated levels in the presence of a reassuring EMB creates a diagnostic dilemma. This review explores the pathophysiological basis and clinical utility of dd-cfDNA in monitoring of heart transplant recipients with particular focus on evaluation and management of discordant findings.

摘要

尽管在器官保存、手术技术和免疫抑制方案方面取得了重大进展,但排斥反应仍然是心脏移植患者护理中的一个主要挑战。心内膜心肌活检(EMB)仍然是监测和诊断排斥反应的金标准测试,但受到其侵入性、观察者间差异、操作风险和成本的限制,因此促使非侵入性生物标志物如供体来源的游离DNA(dd-cfDNA)的广泛使用。由于其高阴性预测价值,dd-cfDNA通常被常规用于无症状患者的监测。然而,它是同种异体移植物损伤的非特异性标志物,在EMB结果令人放心的情况下水平升高会造成诊断困境。本综述探讨了dd-cfDNA在监测心脏移植受者中的病理生理基础和临床应用,特别关注不一致结果的评估和管理。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c920/12391120/ec77657e07a6/frtra-04-1623514-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c920/12391120/b352cbb1de08/frtra-04-1623514-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c920/12391120/ec77657e07a6/frtra-04-1623514-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c920/12391120/b352cbb1de08/frtra-04-1623514-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c920/12391120/ec77657e07a6/frtra-04-1623514-g002.jpg

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Diagnostic approach to elevated dd-cfDNA with reassuring EMB in heart transplantation.心脏移植中dd-cfDNA升高且心内膜活检结果令人安心时的诊断方法
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本文引用的文献

1
Using a combination of biomarkers to monitor allograft dysfunction in lung transplant recipients.联合使用生物标志物监测肺移植受者的移植物功能障碍。
Front Transplant. 2025 May 8;4:1574898. doi: 10.3389/frtra.2025.1574898. eCollection 2025.
2
Advances and challenges in the application of donor-derived cell-free DNA for diagnosis and treatment in liver transplantation: a narrative review.供体来源的游离DNA在肝移植诊断和治疗中的应用进展与挑战:一篇叙述性综述
BMC Surg. 2025 May 13;25(1):203. doi: 10.1186/s12893-025-02911-y.
3
Donor-derived cell-free DNA as a new biomarker for cardiac allograft rejection: A prospective study (FreeDNA-CAR).
供体来源的游离DNA作为心脏移植排斥反应的新型生物标志物:一项前瞻性研究(FreeDNA-CAR)
J Heart Lung Transplant. 2025 Apr;44(4):560-569. doi: 10.1016/j.healun.2024.11.009. Epub 2024 Nov 20.
4
Endomyocardial Biopsy Using Rigid Bioptome Technique and the Risk of Tricuspid Regurgitation after Heart Transplantation.使用硬性心内膜活检技术进行心内膜心肌活检与心脏移植术后三尖瓣反流的风险。
Arq Bras Cardiol. 2024 Oct 28;121(10):e20240223. doi: 10.36660/abc.20240223. eCollection 2024.
5
Pathologist interrater reliability and clinical implications of elevated donor-derived cell-free DNA beyond heart transplant rejection, on behalf of the GRAfT investigators.代表移植研究组,探讨病理学家评分者间可靠性以及心脏移植排斥反应之外供体来源游离DNA升高的临床意义。
J Heart Lung Transplant. 2025 May;44(5):803-812. doi: 10.1016/j.healun.2024.10.006. Epub 2024 Oct 17.
6
Clinical Examples of the Additive Value of Absolute Quantification of Cell-Free DNA After Heart Transplantation.心脏移植后游离 DNA 绝对定量的附加价值的临床实例。
Clin Transplant. 2024 Oct;38(10):e15477. doi: 10.1111/ctr.15477.
7
Clinical Utility of Donor-Derived Cell-Free DNA in Heart Transplant Recipients With Multi-Organ Transplants.多器官移植的心脏移植受者供体来源无细胞 DNA 的临床应用。
Clin Transplant. 2024 Oct;38(10):e15479. doi: 10.1111/ctr.15479.
8
Surveillance with dual noninvasive testing for acute cellular rejection after heart transplantation: Outcomes from the Surveillance HeartCare Outcomes Registry.心脏移植后采用双重非侵入性检测进行急性细胞排斥反应监测:来自 Surveillance HeartCare Outcomes 注册研究的结果。
J Heart Lung Transplant. 2024 Sep;43(9):1409-1421. doi: 10.1016/j.healun.2024.05.003. Epub 2024 May 15.
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Ten-Year Experience with Endomyocardial Biopsy after Orthotopic Heart Transplantation: Comparison between Trans-Jugular and Trans-Femoral Approach.原位心脏移植后心内膜心肌活检的十年经验:经颈静脉与经股动脉途径的比较
J Cardiovasc Dev Dis. 2024 Apr 3;11(4):115. doi: 10.3390/jcdd11040115.
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Am J Transplant. 2024 Aug;24(8):1414-1426. doi: 10.1016/j.ajt.2024.03.031. Epub 2024 Mar 26.