Benefit of cardiopoietic mesenchymal stem cell therapy on left ventricular remodelling: results from the Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) study
Benefit of cardiopoietic mesenchymal stem cell therapy on left ventricular remodelling: results from the Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) study
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DOI：
10.1002/ejhf.898
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发表时间：
2017-11-01
影响因子：
18.2
通讯作者：
Cotter, Gad
中科院分区：
文献类型：
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作者：
Teerlink, John R.;Metra, Marco;Cotter, Gad
目的左心室（LV）反向重构是晚期心力衰竭（HF）患者预后改善的重要标志。我们研究了心肌内给药骨髓来源的、谱系导向的、自体心脏造血间充质干细胞（C3BS-CQR-1）对参加图表1研究的晚期HF患者左室重构的影响。方法和结果有症状的晚期心力衰竭继发于缺血性心脏病，左室射血分数降低（LVEF < 35%）的患者（n= 351）随机接受C3BS-CQR-1或假手术。在一项事后分析中，我们检查了C3BS-CQR-1在手术后1年内对左室反向重构的影响，以及在随机治疗的271例患者中C3BS-CQR-1剂量的影响。C3BS-CQR-1的递送与治疗后52周内左室舒张末期容积（LVEDV）和收缩末期容积（LVESV）的进行性下降有关。1年时，治疗组LVEDV和LVESV分别比对照组下降17.0 mL和12.8 mL （P= 0.006和P= 0.017）。在基线年龄、收缩压、LVEDV、LVEF和心肌梗死史等多变量调整后，对LVEDV的影响维持不变。在接受适量注射（< 20）的患者中，最大的反向重构是明显的。在图1中，通过52周的随访，LVEDV和LVESV的显著进行性降低证明了心肌内给药可导致反向重构。需要进一步的研究来探讨剂量对细胞数量和注射体积的影响，以及反向重构。
Aims Left ventricular (LV) reverse remodelling is an important marker of improved outcomes in patients with advanced heart failure (HF). We examined the impact of the intramyocardial administration of bone-marrow-derived, lineage-directed, autologous cardiopoietic mesenchymal stem cells (C3BS-CQR-1) on LV remodelling in patients with advanced HF enrolled in the CHART-1 study.Methods and results Patients (n= 351) with symptomatic advanced HF secondary to ischaemic heart disease, and reduced LV ejection fraction (LVEF < 35%) were randomized to receive C3BS-CQR-1 or a sham procedure. In a post hoc analysis we examined the effect of C3BS-CQR-1 on LV reverse remodelling within 1 year of the procedure and the influence of C3BS-CQR-1 dosing in the 271 patients treated as randomized. Delivery of C3BS-CQR-1 was associated with a progressive decrease in both LV end-diastolic volume (LVEDV) and end-systolic volume (LVESV) within 52 weeks after treatment. At 1 year, the LVEDV and LVESV of treated patients decreased by 17.0 mL and 12.8 mL greater than controls (P= 0.006 and P= 0.017, respectively). The effect on LVEDV was maintained after multivariable adjustment for baseline age, systolic blood pressure, LVEDV, LVEF and history of myocardial infarction. The largest reverse remodelling was evident in the patients receiving a moderate number of injections (< 20).Conclusion In CHART-1, intramyocardial administration of cardiopoietic stem cells led to reverse remodelling as evidenced by significant progressive decreases in LVEDV and LVESV through the 52 weeks of follow-up. Further studies are needed to explore the dose response with regard to cell number and injected volume, and reverse remodelling.