Novel risk stratification and non-invasive surveillance methods are needed in orthotopic heart transplant (OHT) to reduce morbidity and mortality post-transplant. Clonal hematopoiesis (CH) refers to the acquisition of specific gene mutations in hematopoietic stem cells linked to enhanced inflammation and worse cardiovascular outcomes. The purpose of this study was to investigate the association between CH and OHT. Blood samples were collected from 127 OHT recipients. Error-corrected sequencing was used to detect CH-associated mutations. We evaluated the association between CH and acute cellular rejection, CMV infection, cardiac allograft vasculopathy (CAV), malignancies, and survival. CH mutations were detected in 26 (20.5%) patients, mostly in DNMT3A, ASXL1, and TET2. Patients with CH showed a higher frequency of CAV grade 2 or 3 (0% vs. 18%, p < .001). Moreover, a higher mortality rate was observed in patients with CH (11 [42%] vs. 15 [15%], p = .008) with an adjusted hazard ratio of 2.9 (95% CI, 1.4–6.3; p = .003). CH was not associated with acute cellular rejection, CMV infection or malignancies. The prevalence of CH in OHT recipients is higher than previously reported for the general population of the same age group, with an associated higher prevalence of CAV and mortality.

中文翻译：

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克隆性造血增加了原位心脏移植受者的死亡风险

原位心脏移植 (OHT) 需要新的风险分层和非侵入性监测方法，以降低移植后的发病率和死亡率。克隆性造血 (CH) 是指在造血干细胞中获得特定基因突变，这与炎症增强和心血管结局恶化有关。本研究的目的是调查 CH 和 OHT 之间的关联。从 127 名 OHT 接受者收集了血样。纠错测序用于检测 CH 相关突变。我们评估了 CH 与急性细胞排斥反应、CMV 感染、心脏同种异体移植血管病变 (CAV)、恶性肿瘤和生存之间的关联。在 26 名 (20.5%) 患者中检测到 CH 突变，主要在DNMT3A、ASXL1和TET2中. CH 患者显示出更高频率的 CAV 2 级或 3 级（0% 对 18%，p  < .001）。此外，CH 患者的死亡率更高（11 [42%] 对 15 [15%]，p  = .008），调整后的风险比为 2.9（95% CI，1.4–6.3；p  = . 003). CH 与急性细胞排斥反应、CMV 感染或恶性肿瘤无关。OHT 接受者的 CH 患病率高于先前报告的同一年龄组的一般人群，CAV 患病率和死亡率也更高。