供体来源的游离DNA水平升高与心肌血流减少相关，但与心脏移植血管造影血管病变无关：EVIDENT研究
Elevated Donor-Derived Cell-Free DNA Levels Are Associated With Reduced Myocardial Blood Flow but Not Angiographic Cardiac Allograft Vasculopathy: The EVIDENT Study.
作者信息
Moeller Cathrine M, Oren Daniel, Fernandez Valledor Andrea, Rubinstein Gal, DeFilippis Ersilia M, Rahman Salwa, Mehlman Yonatan, Donald Elena M, Lotan Dor, Lin Edward, Oh Kyung T, Lee Sun H, Raikhelkar Jayant K, Fried Justin A, Majure David, Latif Farhana, Sayer Gabriel T, Uriel Nir, Clerkin Kevin J
机构信息
Milstein Division of Cardiology, Department of Medicine, NewYork-Presbyterian/Columbia University Irving Medical Center (C.M.M., D.O. A.F.V., G.R., E.M. DeFilippis, S.R., Y.M., E.M. Donald, D.L., E.F.L., K.T.O., S.H.L., J.K.R., J.A.F., F.L., G.T.S., N.U., K.J.C.).
Greenberg Division of Cardiology, Department of Medicine, NewYork-Presbyterian/Weill Cornell Medical College (D.M.).
出版信息
Circ Heart Fail. 2025 Jan;18(1):e011756. doi: 10.1161/CIRCHEARTFAILURE.124.011756. Epub 2024 Dec 10.
BACKGROUND
Cardiac allograft vasculopathy (CAV) leads to impaired myocardial blood flow (MBF), increasing the risk of cardiovascular death or retransplant among heart transplantation (HT) recipients. Data on elevation in donor-derived cell-free DNA (dd-cfDNA) and CAV in the absence of rejection are mixed. We sought to test the hypothesis that CAV with reduced MBF (RMBF) is associated with elevated dd-cfDNA.
METHODS
A retrospective review was conducted on HT recipients at a high-volume center who underwent dd-cfDNA testing between September 2019 and November 2022. Inclusion criteria included undergoing CAV screening with cardiac positron emission tomography scans and coronary angiograms. Patients were grouped by the presence of angiographic CAV diagnosis and MBF reserve evaluated through cardiac positron emission tomography. The latter was subdivided into normal MBF or RMBF, with RMBF defined as an MBF reserve ≤2. Elevated dd-cfDNA was defined as ≥0.12%.
RESULTS
Two hundred fifty-six HT recipients were included (median age, 55 years; 27.6% female; median, 8 years [interquartile range (IQR), 5-14] post-HT). Ischemic etiology of heart failure was more prevalent in the RMBF group (36%) compared with the normal MBF group (20%; =0.02). The prevalence and magnitude of a positive dd-cfDNA test with angiographic CAV (29%; median, 0.26% [IQR, 0.15%-0.62%]) were not significantly different from those without CAV (30%; =0.94; median, 0.31% [IQR, 0.17%-0.71%]; =0.38). However, RMBF patients exhibited significantly higher dd-cfDNA prevalence and levels (51%; median, 0.81% [IQR, 0.48%-1.11%]) compared with normal MBF patients (27%; <0.001; median, 0.25% [IQR, 0.15%-0.52%]; <0.001).
CONCLUSIONS
HT recipients with angiographic CAV had similar dd-cfDNA levels and rates as those without. Notably, dd-cfDNA levels and rates were significantly elevated in patients with RMBF assessed by positron emission tomography compared with those with normal MBF.
背景
心脏移植血管病变（CAV）会导致心肌血流（MBF）受损，增加心脏移植（HT）受者心血管死亡或再次移植的风险。关于在无排斥反应情况下供体来源的游离DNA（dd-cfDNA）升高与CAV的数据并不一致。我们试图验证CAV伴MBF降低（RMBF）与dd-cfDNA升高相关的假设。
方法
对一家大型中心在2019年9月至2022年11月期间接受dd-cfDNA检测的HT受者进行回顾性研究。纳入标准包括通过心脏正电子发射断层扫描和冠状动脉造影进行CAV筛查。根据血管造影CAV诊断的存在情况以及通过心脏正电子发射断层扫描评估的MBF储备对患者进行分组。后者分为正常MBF或RMBF，RMBF定义为MBF储备≤2。dd-cfDNA升高定义为≥0.12%。
结果
共纳入256例HT受者（中位年龄55岁；27.6%为女性；HT后中位时间8年[四分位间距（IQR），5 - 14年]）。与正常MBF组（20%）相比，RMBF组心力衰竭的缺血性病因更为普遍（36%；P = 0.02）。血管造影显示有CAV时dd-cfDNA检测阳性的患病率和幅度（29%；中位值0.26%[IQR，0.15% - 0.62%]）与无CAV时（30%；P = 0.94；中位值0.31%[IQR，0.17% - 0.71%]；P = 0.38）无显著差异。然而，与正常MBF患者（27%；P < 0.001；中位值0.25%[IQR，0.15% - 0.52%]；P < 0.001）相比，RMBF患者的dd-cfDNA患病率和水平显著更高（51%；中位值0.81%[IQR，0.48% - 1.11%]）。
结论
血管造影显示有CAV的HT受者的dd-cfDNA水平和比率与无CAV者相似。值得注意的是，与正常MBF患者相比，通过正电子发射断层扫描评估为RMBF的患者的dd-cfDNA水平和比率显著升高。
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