Heart Failure, Mechanical Circulatory Support & Transplant, Inova Schar Heart and Vascular, Falls Church, VA (P.S., S.S.S., L.H., E.M.).
Genomic Research Alliance for Transplantation (GRAfT), Bethesda, MD (P.S., S.A.-E., T.E.A., M.K.J., H.A.V.).
Circ Heart Fail. 2024 Apr;17(4):e011160. doi: 10.1161/CIRCHEARTFAILURE.123.011160. Epub 2024 Feb 20.
Black heart transplant patients are at higher risk of acute rejection (AR) and death than White patients. We hypothesized that this risk may be associated with higher levels of donor-derived cell-free DNA (dd-cfDNA) and cell-free mitochondrial DNA.
The Genomic Research Alliance for Transplantation is a multicenter, prospective, longitudinal cohort study. Sequencing was used to quantitate dd-cfDNA and polymerase chain reaction to quantitate cell-free mitochondrial DNA in plasma. AR was defined as ≥2R cellular rejection or ≥1 antibody-mediated rejection. The primary composite outcome was AR, graft dysfunction (left ventricular ejection fraction <50% and decrease by ≥10%), or death.
We included 148 patients (65 Black patients and 83 White patients), median age was 56 years and 30% female sex. The incidence of AR was higher in Black patients compared with White patients (43% versus 19%; =0.002). Antibody-mediated rejection occurred predominantly in Black patients with a prevalence of 20% versus 2% (<0.001). After transplant, Black patients had higher levels of dd-cfDNA, 0.09% (interquartile range, 0.001-0.30) compared with White patients, 0.05% (interquartile range, 0.001-0.23; =0.003). Beyond 6 months, Black patients showed a persistent rise in dd-cfDNA with higher levels compared with White patients. Cell-free mitochondrial DNA was higher in Black patients (185 788 copies/mL; interquartile range, 101 252-422 133) compared with White patients (133 841 copies/mL; interquartile range, 75 346-337 990; <0.001). The primary composite outcome occurred in 43% and 55% of Black patients at 1 and 2 years, compared with 23% and 27% in White patients, <0.001. In a multivariable model, Black patient race (hazard ratio, 2.61 [95% CI, 1.35-5.04]; =0.004) and %dd-cfDNA (hazard ratio, 1.15 [95% CI, 1.03-1.28]; =0.010) were associated with the primary composite outcome.
Elevated dd-cfDNA and cell-free mitochondrial DNA after heart transplant may mechanistically be implicated in the higher incidence of AR and worse clinical outcomes in Black transplant recipients.
URL: https://www.clinicaltrials.gov; Unique identifier: NCT02423070.
黑人心脏移植患者发生急性排斥反应（AR）和死亡的风险高于白人患者。我们假设这种风险可能与供体来源的无细胞 DNA（dd-cfDNA）和无细胞线粒体 DNA 的水平升高有关。
基因组移植研究联盟是一项多中心、前瞻性、纵向队列研究。使用测序来定量 dd-cfDNA，使用聚合酶链反应来定量血浆中的无细胞线粒体 DNA。AR 定义为≥2R 细胞排斥或≥1 抗体介导的排斥。主要复合结局是 AR、移植物功能障碍（左心室射血分数<50%和下降≥10%）或死亡。
我们纳入了 148 名患者（65 名黑人患者和 83 名白人患者），中位年龄为 56 岁，30%为女性。与白人患者相比，黑人患者 AR 的发生率更高（43%比 19%；=0.002）。抗体介导的排斥反应主要发生在黑人患者中，发生率为 20%，而白人患者为 2%（<0.001）。移植后，黑人患者的 dd-cfDNA 水平较高，为 0.09%（四分位距，0.001-0.30），而白人患者为 0.05%（四分位距，0.001-0.23；=0.003）。超过 6 个月后，黑人患者的 dd-cfDNA 持续升高，水平高于白人患者。黑人患者的无细胞线粒体 DNA 水平较高（185788 拷贝/ml；四分位距，101252-422133），而白人患者为 133841 拷贝/ml；四分位距，75346-337990；<0.001）。黑人患者在 1 年和 2 年时主要复合结局的发生率分别为 43%和 55%，而白人患者分别为 23%和 27%，<0.001。在多变量模型中，黑人患者种族（风险比，2.61[95%CI，1.35-5.04]；=0.004）和%dd-cfDNA（风险比，1.15[95%CI，1.03-1.28]；=0.010）与主要复合结局相关。
心脏移植后 dd-cfDNA 和无细胞线粒体 DNA 的升高可能与黑人移植受者 AR 发生率升高和临床结局恶化有关。
