Peripheral Blood Biomarkers Associated With Improved Functional Outcome in Patients With Chronic Left Ventricular Dysfunction: A Biorepository Evaluation of the FOCUS-CCTRN Trial.
Peripheral Blood Biomarkers Associated With Improved Functional Outcome in Patients With Chronic Left Ventricular Dysfunction: A Biorepository Evaluation of the FOCUS-CCTRN Trial.
复制标题
与慢性左心室功能障碍患者功能改善相关的外周血生物标志物：FOCUS-CCTRN 试验的生物样本库评估。
DOI：
10.3389/fcvm.2021.698088
复制
发表时间：
2021
影响因子：
3.6
通讯作者：
Taylor DA
中科院分区：
文献类型：
--
作者：
Chacon Alberty L;Perin EC;Willerson JT;Gahremanpour A;Bolli R;Yang PC;Traverse JH;Lai D;Pepine CJ;Taylor DA
心力衰竭（HF）的细胞治疗试验显示出适度的改善;然而，一些患者而不是其他患者的改善机制尚不清楚。虽然免疫细胞在HF的过程中是重要的，但我们对HF中的免疫过程的理解是有限的。本研究的目的是评估外周血（PB）细胞亚群的时间变化与慢性缺血性心肌病患者接受骨髓源性单核细胞治疗或安慰剂治疗后结局改善之间的相关性。在第0、1、30、90和180天从知情同意的参与者采集外周血。我们使用流式细胞术比较了PB人群中三个主要终点的最佳（队列1）或最差功能结局（队列2）患者：左心室（LV）射血分数、LV收缩末期容积和最大耗氧量（VO 2 max）。使用线性混合模型评估32个细胞群随时间的变化。每个时间点与基线之间的差异计算为线性对比度。与队列2相比，改善的患者（队列1）在第0、1、90和180天的CD 45 + CD 19 + B细胞频率更高。在第1天，两个队列中的CD 11B+细胞均高于基线，并且在队列2中保持较高水平，直至第30天。在第1组中，第30天时，CD 45 + CD 133+祖细胞相对于基线减少。我们确定了与慢性左室功能不全患者心功能改善相关的特定细胞亚群。这些发现可能会改善细胞治疗试验中的患者选择和结果预测。
Cell therapy trials for heart failure (HF) have shown modest improvement; however, the mechanisms underlying improvement in some patients but not others are not well understood. Although immune cells are important in the course of HF, our understanding of the immune processes in HF is limited. The objective of this study was to evaluate associations between temporal changes in peripheral blood (PB) cell subpopulations and improved outcome in patients with chronic ischemic cardiomyopathy after bone marrow-derived mononuclear cell therapy or placebo in the FOCUS-CCTRN trial. Peripheral blood was collected at days 0, 1, 30, 90, and 180 from consented participants. We used flow cytometry to compare PB populations in patients with the best (cohort 1) or worst functional outcome (cohort 2) in three primary endpoints: left ventricular (LV) ejection fraction, LV end-systolic volume, and maximal oxygen consumption (VO2 max). A linear mixed model was used to assess changes over time in 32 cell populations. The difference between each time point and baseline was calculated as linear contrast. Compared with cohort 2, patients who improved (cohort 1) had a higher frequency of CD45+CD19+ B cells at days 0, 1, 90, and 180. CD11B+ cells increased over baseline at day 1 in both cohorts and remained higher in cohort 2 until day 30. CD45+CD133+ progenitor cells decreased over baseline at day 30 in cohort 1. We identified specific cell subpopulations associated with improved cardiac function in patients with chronic LV dysfunction. These findings may improve patient selection and prediction of outcomes in cell therapy trials.