Cardiovascular Medicine, Intermountain Medical Center, Murray, Utah, USA.
Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, USA.
Clin Transplant. 2024 Jul;38(7):e15416. doi: 10.1111/ctr.15416.
Cardiac allograft vasculopathy (CAV) is a leading cause of death after heart transplantation (HT). We evaluated donor-derived cell-free DNA (dd-cfDNA) as a noninvasive biomarker of CAV development after HT. The INSPIRE registry at the Intermountain Medical Center was queried for stored plasma samples from HT patients with and without CAV. At Stanford University, HT patients with CAV (cases) and without CAV (controls) were enrolled prospectively, and blood samples were collected. All the samples were analyzed for dd-cfDNA using the AlloSure assay (CareDx, Inc.). CAV was defined per the ISHLT 2010 standardized classification system. Univariate associations between patient demographics and clinical characteristics and their CAV grade were tested using chi-square and Wilcoxon rank sum tests. Associations between their dd-cfDNA levels and CAV grades were examined using a nonparametric Kruskal-Wallis test. A total of 69 pts were included, and 101 samples were analyzed for dd-cfDNA. The mean age at sample collection was 58.6 ± 13.7 years; 66.7% of the patients were male, and 81% were White. CAV 0, 1, 2, and 3 were present in 37.6%, 22.8%, 22.8%, and 16.8% of included samples, respectively. The median dd-cfDNA level was 0.13% (0.06, 0.33). The median dd-cfDNA level was not significantly different between CAV (-) and CAV (+): 0.09% (0.05%-0.32%) and 0.15% (0.07%-0.33%), respectively, p = 0.25 and with similar results across all CAV grades. In our study, dd-cfDNA levels did not correlate with the presence of CAV and did not differ across CAV grades. As such, dd-cfDNA does not appear to be a reliable noninvasive biomarker for CAV surveillance.
心脏移植后，心脏同种异体移植物血管病（CAV）是导致死亡的主要原因。我们评估了供体无细胞游离 DNA（dd-cfDNA）作为心脏移植后 CAV 发展的非侵入性生物标志物。在 Intermountain 医疗中心的 INSPIRE 注册中心中，检索了患有和不患有 CAV 的心脏移植患者的储存血浆样本。在斯坦福大学，前瞻性地招募了患有 CAV（病例）和没有 CAV（对照组）的心脏移植患者，并采集了血液样本。所有样本均使用 AlloSure 检测法（CareDx，Inc.）进行 dd-cfDNA 分析。CAV 采用 ISHLT 2010 标准化分类系统进行定义。使用卡方检验和 Wilcoxon 秩和检验测试患者人口统计学和临床特征与 CAV 分级之间的单变量相关性。使用非参数 Kruskal-Wallis 检验检查它们的 dd-cfDNA 水平与 CAV 分级之间的相关性。共纳入 69 例患者，对 101 例样本进行了 dd-cfDNA 分析。样本采集时的平均年龄为 58.6±13.7 岁；66.7%的患者为男性，81%为白人。纳入样本中 CAV 0、1、2 和 3 分别为 37.6%、22.8%、22.8%和 16.8%。dd-cfDNA 中位数为 0.13%（0.06，0.33）。CAV（-）和 CAV（+）之间的 dd-cfDNA 中位数水平没有显著差异：分别为 0.09%（0.05%-0.32%）和 0.15%（0.07%-0.33%），p=0.25，在所有 CAV 分级中均具有相似的结果。在我们的研究中，dd-cfDNA 水平与 CAV 的存在无关，并且在 CAV 分级之间没有差异。因此，dd-cfDNA 似乎不是 CAV 监测的可靠非侵入性生物标志物。
