背景:用基因表达谱(GEP)和供体来源的无细胞DNA(dd-cfDNA)进行分子检测越来越多地用于监测心脏移植后的急性细胞排斥反应(ACR)。然而,双重测试在每个单独测试中的性能尚未确定。Further,双重无创监测对临床决策的影响尚未得到广泛研究.
方法:我们评估了SHORE注册中心的2077名受试者,这些受试者在2018年至2021年之间注册,并具有验证的活检数据,被归类为双重阴性,GEP阳性/dd-cfDNA阴性,GEP阴性/dd-cfDNA阳性,或双重积极。评估各组的ACR发生率和随访检测率。计算阳性似然比(LR),并分析活检率随时间的变化。
结果:双阴性的ACR发生率为1.5%,GEP阳性/dd-cfDNA阴性1.9%,GEP阴性/dd-cfDNA阳性组4.3%,双阳性组9.2%。双阴性患者在8.8%后进行了后续活检,GEP阳性/dd-cfDNA阴性14.2%,GEP阴性/dd-cfDNA阳性结果为22.8%,双重阳性结果为35.4%。GEP阳性时,ACR的LR分别为1.37、2.91和3.90,dd-cfDNA阳性和双重阳性检测,分别。从2018-2021年,第一年活检率从5.9下降到5.3活检/患者,第二年从1.5到0.9活检/患者。两年后,生存率为94.9%,只有2.7%有移植物功能障碍.
结论:与单分子检测相比,双分子检测证明了ACR监测的性能提高。随着时间的推移,使用双重非侵入性检测与较低的活检率相关。优秀的生存,移植物功能障碍的发生率低。
BACKGROUND: Molecular testing with gene-expression profiling (GEP) and donor-derived cell-free DNA (dd-cfDNA) is increasingly used in the surveillance for acute cellular rejection (ACR) after heart transplant. However, the performance of dual testing over each test individually has not been established. Further, the impact of dual noninvasive surveillance on clinical decision-making has not been widely investigated.
METHODS: We evaluated 2,077 subjects from the Surveillance HeartCare Outcomes Registry registry who were enrolled between 2018 and 2021 and had verified biopsy data and were categorized as dual negative, GEP positive/dd-cfDNA negative, GEP negative/dd-cfDNA positive, or dual positive. The incidence of ACR and follow-up testing rates for each group were evaluated. Positive likelihood ratios (LRs+) were calculated, and biopsy rates over time were analyzed.
RESULTS: The incidence of ACR was 1.5% for dual negative, 1.9% for GEP positive/dd-cfDNA negative, 4.3% for GEP negative/dd-cfDNA positive, and 9.2% for dual-positive groups. Follow-up biopsies were performed after 8.8% for dual negative, 14.2% for GEP positive/dd-cfDNA negative, 22.8% for GEP negative/dd-cfDNA positive, and 35.4% for dual-positive results. The LR+ for ACR was 1.37, 2.91, and 3.90 for GEP positive, dd-cfDNA positive, and dual-positive testing, respectively. From 2018 to 2021, biopsies performed between 2 and 12-months post-transplant declined from 5.9 to 5.3 biopsies/patient, and second-year biopsy rates declined from 1.5 to 0.9 biopsies/patient. At 2 years, survival was 94.9%, and only 2.7% had graft dysfunction.
CONCLUSIONS: Dual molecular testing demonstrated improved performance for ACR surveillance compared to single molecular testing. The use of dual noninvasive testing was associated with lower biopsy rates over time, excellent survival, and low incidence of graft dysfunction.