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经冠状动脉内 CD34+ 干细胞移植治疗非缺血性扩张型心肌病患者:5 年随访结果。

Effects of intracoronary CD34+ stem cell transplantation in nonischemic dilated cardiomyopathy patients: 5-year follow-up.

机构信息

Advanced Heart Failure and Transplantation Center, Department of Cardiology, Ljubljana University Medical Center, Zaloska 7, Ljubljana, MC SI-1000, Slovenia.

出版信息

Circ Res. 2013 Jan 4;112(1):165-73. doi: 10.1161/CIRCRESAHA.112.276519. Epub 2012 Oct 12.

DOI:10.1161/CIRCRESAHA.112.276519
PMID:23065358
Abstract

RATIONALE

CD34+ transplantation in dilated cardiomyopathy was associated with short-term improvement in left ventricular ejection fraction and exercise tolerance.

OBJECTIVE

We investigated long-term effects of intracoronary CD34+ cell transplantation in dilated cardiomyopathy and the relationship between intramyocardial cell homing and clinical response.

METHODS AND RESULTS

Of 110 dilated cardiomyopathy patients, 55 were randomized to receive CD34+ stem cell transplantation (SC group) and 55 received no cell therapy (controls). In the SC group, CD34+ cells were mobilized by granulocyte colony-stimulating factor and collected via apheresis. Patients underwent myocardial scintigraphy and cells were injected in the artery supplying segments with the greatest perfusion defect. At baseline, 2 groups did not differ in age, sex, left ventricular ejection fraction, or N-terminal B-type natriuretic peptide levels. At 5 years, stem cell therapy was associated with increased left ventricular ejection fraction (from 24.3 ± 6.5% to 30.0 ± 5.1%; P=0.02), increased 6-minute walk distance (from 344 ± 90 m to 477 ± 130 m; P<0.001), and decreased N-terminal B-type natriuretic peptide (from 2322 ± 1234 pg/mL to 1011 ± 893 pg/mL; P<0.01). Left ventricular ejection fraction improvement was more significant in patients with higher myocardial homing of injected cells. During follow-up, 27 (25%) patients died and 9 (8%) underwent heart transplantation. Of the 27 deaths, 13 were attributed to pump failure and 14 were attributed to sudden cardiac death. Total mortality was lower in the SC group (14%) than in controls (35%; P=0.01). The same was true of pump failure (5% vs. 18%; P=0.03), but not of sudden cardiac death (9% vs. 16%; P=0.39).

CONCLUSIONS

Intracoronary stem cell transplantation may be associated with improved ventricular function, exercise tolerance, and long-term survival in patients with dilated cardiomyopathy. Higher intramyocardial homing is associated with better stem cell therapy response.

摘要

背景

CD34+ 移植治疗扩张型心肌病可短期改善左心室射血分数和运动耐量。

目的

我们研究了经冠状动脉 CD34+ 细胞移植治疗扩张型心肌病的长期疗效,以及细胞归巢与临床反应的关系。

方法和结果

110 例扩张型心肌病患者中,55 例随机分为 CD34+ 干细胞移植组(SC 组),55 例未接受细胞治疗(对照组)。SC 组患者采用粒细胞集落刺激因子动员外周血干细胞,通过血细胞分离机采集 CD34+细胞。所有患者均接受心肌闪烁显像检查,并将细胞注射到灌注缺损最大的供血节段动脉内。基线时,两组患者的年龄、性别、左心室射血分数或 N 末端 B 型利钠肽水平无差异。5 年后,干细胞治疗组左心室射血分数增加(从 24.3%±6.5%增加至 30.0%±5.1%;P=0.02),6 分钟步行距离增加(从 344±90 m 增加至 477±130 m;P<0.001),N 末端 B 型利钠肽降低(从 2322±1234 pg/ml 降低至 1011±893 pg/ml;P<0.01)。注射细胞的心肌归巢率较高的患者左心室射血分数改善更显著。随访期间,27 例(25%)患者死亡,9 例(8%)患者接受心脏移植。27 例死亡患者中,13 例归因于泵衰竭,14 例归因于心脏性猝死。SC 组总死亡率(14%)低于对照组(35%;P=0.01)。泵衰竭发生率(5% vs. 18%;P=0.03)也低于对照组,但心脏性猝死发生率(9% vs. 16%;P=0.39)无差异。

结论

经冠状动脉干细胞移植可能改善扩张型心肌病患者的心室功能、运动耐量和长期生存率。心肌内归巢率较高与更好的干细胞治疗反应相关。

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