Cardiopoietic cell therapy for advanced ischaemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial.
Cardiopoietic cell therapy for advanced ischaemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial.
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晚期缺血性心力衰竭的心脏生成细胞疗法：前瞻性、随机、双盲、假对照 CHART-1 临床试验 39 周的结果。
DOI：
10.1093/eurheartj/ehw543
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发表时间：
2017-03-01
影响因子：
39.3
通讯作者：
CHART Program
中科院分区：
文献类型：
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作者：
Bartunek J;Terzic A;Davison BA;Filippatos GS;Radovanovic S;Beleslin B;Merkely B;Musialek P;Wojakowski W;Andreka P;Horvath IG;Katz A;Dolatabadi D;El Nakadi B;Arandjelovic A;Edes I;Seferovic PM;Obradovic S;Vanderheyden M;Jagic N;Petrov I;Atar S;Halabi M;Gelev VL;Shochat MK;Kasprzak JD;Sanz-Ruiz R;Heyndrickx GR;Nyolczas N;Legrand V;Guédès A;Heyse A;Moccetti T;Fernandez-Aviles F;Jimenez-Quevedo P;Bayes-Genis A;Hernandez-Garcia JM;Ribichini F;Gruchala M;Waldman SA;Teerlink JR;Gersh BJ;Povsic TJ;Henry TD;Metra M;Hajjar RJ;Tendera M;Behfar A;Alexandre B;Seron A;Stough WG;Sherman W;Cotter G;Wijns W;CHART Program
通过对患者间充质干细胞进行心原性调理而产生的心肌细胞已显示出初步功效。充血性心力衰竭心脏再生治疗 (CHART-1) 试验旨在在更大的心力衰竭队列中验证基于心脏再生的生物疗法。这项跨国、随机、双盲、假对照研究在 39 家医院进行。对接受指南指导治疗的症状性缺血性心力衰竭患者（n = 484）进行了筛查； n = 348 接受了骨髓采集和间充质干细胞扩增。那些获得> 2400万个间充质干细胞（n = 315）的人被随机分配到通过保留增强导管（n = 157）或假手术（n = 158）通过心内膜心肌递送的心肌细胞。对 271 名患者进行了随机手术（n = 120 个心肌细胞，n = 151 个假手术）。主要疗效终点是 39 周时的 Finkelstein-Schoenfeld 分层综合指标（全因死亡率、心力衰竭恶化、明尼苏达心力衰竭生活问卷评分、6 分钟步行距离、左心室收缩末期容积和射血分数）。主要结果是中性的（Mann-Whitney 估计量 0.54，95% 置信区间 [CI] 0.47–0.61 [值 > 0.5 有利于细胞治疗]，P = 0.27）。探索性分析表明，对于基线左心室舒张末期容积为 200–370mL 的患者（60% 的患者），细胞治疗对主要复合材料有益处（Mann–Whitney 估计值 0.61，95% CI 0.52–0.70，P = 0.015）。在严重不良事件方面没有观察到差异。 1 名（0.9%）心肌细胞患者和 9 名（5.4%）假手术患者经历了流产或心源性猝死。主要终点是中性的，在整个队列中都证明了安全性。有必要对舒张末期容量升高的患者的心脏生成细胞疗法进行进一步评估。
Cardiopoietic cells, produced through cardiogenic conditioning of patients’ mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort. This multinational, randomized, double-blind, sham-controlled study was conducted in 39 hospitals. Patients with symptomatic ischaemic heart failure on guideline-directed therapy (n = 484) were screened; n = 348 underwent bone marrow harvest and mesenchymal stem cell expansion. Those achieving > 24 million mesenchymal stem cells (n = 315) were randomized to cardiopoietic cells delivered endomyocardially with a retention-enhanced catheter (n = 157) or sham procedure (n = 158). Procedures were performed as randomized in 271 patients (n = 120 cardiopoietic cells, n = 151 sham). The primary efficacy endpoint was a Finkelstein–Schoenfeld hierarchical composite (all-cause mortality, worsening heart failure, Minnesota Living with Heart Failure Questionnaire score, 6-min walk distance, left ventricular end-systolic volume, and ejection fraction) at 39 weeks. The primary outcome was neutral (Mann–Whitney estimator 0.54, 95% confidence interval [CI] 0.47–0.61 [value > 0.5 favours cell treatment], P = 0.27). Exploratory analyses suggested a benefit of cell treatment on the primary composite in patients with baseline left ventricular end-diastolic volume 200–370 mL (60% of patients) (Mann–Whitney estimator 0.61, 95% CI 0.52–0.70, P = 0.015). No difference was observed in serious adverse events. One (0.9%) cardiopoietic cell patient and 9 (5.4%) sham patients experienced aborted or sudden cardiac death. The primary endpoint was neutral, with safety demonstrated across the cohort. Further evaluation of cardiopoietic cell therapy in patients with elevated end-diastolic volume is warranted.