Department of Cardiology, Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, the Netherlands.
Department of Cardiology, Maastricht University Medical Center, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, the Netherlands; Centre for Molecular and Vascular Biology, Department of Cardiovascular Sciences, KU Leuven, Belgium.
JACC Heart Fail. 2024 May;12(5):905-914. doi: 10.1016/j.jchf.2023.06.037. Epub 2023 Aug 25.
Clonal hematopoiesis (CH) gives rise to mutated leukocyte clones that induce cardiovascular inflammation and thereby impact the disease course in atherosclerosis and ischemic heart failure. CH of indeterminate potential refers to a variant allele frequency (VAF) (a marker for clone size) in blood of ≥2%. The impact of CH clones-including small clone sizes (VAF <0.5%)-in nonischemic dilated cardiomyopathy (DCM) remains largely undetermined.
The authors sought to establish the prognostic impact of CH in DCM including small clones.
CH is determined using an ultrasensitive single-molecule molecular inversion probe technique that allows detection of clones down to a VAF of 0.01%. Cardiac death and all-cause mortality were analyzed using receiver-operating characteristic curve-optimized VAF cutoff values.
A total of 520 DCM patients have been included. A total of 109 patients (21%) had CH driver mutations, of which 45 had a VAF of ≥2% and 31 <0.5%. The median follow-up duration was 6.5 years (IQR: 4.7-9.7 years). DCM patients with CH have a higher risk of cardiac death (HR: 2.33 using a VAF cutoff of 0.36%, 95% CI: 1.24-4.40) and all-cause mortality (HR: 1.72 using a VAF cutoff of 0.06%, 95% CI: 1.10-2.69), independent of age, sex, left ventricular ejection fraction, and NYHA functional classification.
CH predicts cardiac death and all-cause mortality in DCM patients with optimal thresholds for clone size of 0.36% and 0.06%, respectively. Therefore, CH is prognostically relevant, independent of clone size in patients with DCM.
克隆性造血（CH）会产生突变的白细胞克隆，引发心血管炎症，从而影响动脉粥样硬化和缺血性心力衰竭的疾病进程。不确定潜能的 CH 是指血液中的变异等位基因频率（VAF）（克隆大小的标志物）≥2%。在非缺血性扩张型心肌病（DCM）中，CH 克隆（包括小克隆大小[VAF<0.5%]）的影响在很大程度上仍未确定。
作者旨在确定包括小克隆在内的 DCM 中 CH 的预后影响。
采用超灵敏单分子分子反转探针技术确定 CH，该技术允许检测 VAF 低至 0.01%的克隆。使用接受者操作特征曲线优化的 VAF 截断值分析 CH 与心脏死亡和全因死亡率的关系。
共纳入 520 例 DCM 患者。共有 109 例（21%）患者存在 CH 驱动突变，其中 45 例 VAF≥2%，31 例 VAF<0.5%。中位随访时间为 6.5 年（IQR：4.7-9.7 年）。患有 CH 的 DCM 患者发生心脏死亡的风险更高（VAF 截断值为 0.36%时 HR：2.33，95%CI：1.24-4.40）和全因死亡率（VAF 截断值为 0.06%时 HR：1.72，95%CI：1.10-2.69），与年龄、性别、左心室射血分数和 NYHA 功能分级无关。
在 DCM 患者中，CH 分别以 0.36%和 0.06%的最佳克隆大小阈值预测心脏死亡和全因死亡率。因此，CH 与克隆大小无关，在 DCM 患者中具有预后相关性。
