Department of Internal Medicine I, Division of Cardiology, University Hospital Jena, FSU Jena, Am Klinikum 1, 07747, Jena, Germany.
Clinic for Cardiology, Angiology and Pneumology, University Hospital Magdeburg A.ö.R, Magdeburg, Germany.
ESC Heart Fail. 2022 Dec;9(6):3954-3960. doi: 10.1002/ehf2.14115. Epub 2022 Aug 18.
Clonal haematopoiesis of indeterminate potential (CHIP)-associated mutation is a risk factor for the development of ischaemic cardiomyopathy (ICM), but its association with non-ischaemic dilated cardiomyopathy (DCM) remains unclear. We aimed to determine the prevalence of CHIP in patients with DCM and define its risk for disease progression.
Next-generation sequencing targeting 54 common CHIP-associated genes was performed in 48 ICM and 52 DCM patients. The patients were monitored for a median of 3.1 years, and a COX proportional hazards model was used to examine the association between CHIP and adverse clinical outcome with regard to all-cause death or all-cause hospitalization. Overall, the prevalence of CHIP mutations was 19% and 13% in DCM and ICM, respectively. Seventeen per cent of ICM patients over 75 years were CHIP carriers. In DCM cohort, mutation event had already been observed in the patients who were under the age of 45 (13%). Among 54 genes analysed, DNMT3A had the highest mutation frequency, followed by TET2 and CUX1. Kaplan-Meier curve over a median of 3.1 year tracking period showed a trend towards poor clinical outcome in the DCM patients who carried DNMT3A or TET2 mutation; however, such association was not statistically significant.
The prevalence of CHIP is detected at a young age in DCM, and accumulation of mutational frequency in DCM patients is independent of age. However, a larger patient cohort is required to validate the association between CHIP and clinical progression in the DCM patients.
不确定潜能的克隆性造血（CHIP）相关突变是缺血性心肌病（ICM）发展的危险因素，但它与非缺血性扩张型心肌病（DCM）的关系尚不清楚。我们旨在确定 DCM 患者中 CHIP 的患病率，并确定其疾病进展的风险。
对 48 例 ICM 和 52 例 DCM 患者进行了针对 54 种常见 CHIP 相关基因的下一代测序。对患者进行了中位数为 3.1 年的监测，并使用 COX 比例风险模型来检查 CHIP 与全因死亡或全因住院的不良临床结局之间的关联。总体而言，DCM 和 ICM 中 CHIP 突变的患病率分别为 19%和 13%。75 岁以上的 ICM 患者中有 17%是 CHIP 携带者。在 DCM 队列中，已经在 45 岁以下的患者中观察到突变事件（13%）。在分析的 54 个基因中，DNMT3A 的突变频率最高，其次是 TET2 和 CUX1。Kaplan-Meier 曲线在中位数为 3.1 年的追踪期内显示，携带 DNMT3A 或 TET2 突变的 DCM 患者的临床结局有变差的趋势；然而，这种关联没有统计学意义。
在 DCM 中，CHIP 的患病率在年轻时就已被检测到，并且 DCM 患者的突变频率积累与年龄无关。然而，需要更大的患者队列来验证 CHIP 与 DCM 患者临床进展之间的关联。
