自体骨髓间充质干细胞治疗扩张性心肌病:安全和有效性的Meta分析

Safety and efficacy of autologous bone marrow mesenchymal stem cells for dilated cardiomyopathy: a Meta-analysis

背景:自体骨髓间充质干细胞已被用于扩张性心肌病的临床治疗,但其安全性和有效性存在争议。目的:运用Meta分析方法评价自体骨髓间充质干细胞移植治疗扩张性心肌病的安全性和有效性。方法:系统检索Pub Med、Cochrane Library(2016年第2期)、Embase、CNKI、CBM、维普、万方数据库中,有关自体骨髓间充质干细胞移植与常规药物治疗扩张性心肌病的临床随机对照试验。运用R3.1.0软件对两种治疗后的左室射血分数、左室舒张末期内径、6 min步行距离、心肌灌注缺损面积百分比、治疗及随访过程中患者死亡率、恶性心律失常发生率及心脏移植率进行Meta分析。结果与结论:纳入7个随机对照试验,合计341例扩张性心肌病患者。Meta分析结果显示:与常规药物疗法相比,自体骨髓间充质干细胞移植能增加扩张性心肌病患者左心室射血分数[1个月:MD=3.02,95%CI(1.55,4.49);3个月:MD=4.38,95%CI(3.55,5.52);6个月:MD=6.47,95%CI(4.78,8.15);≥12个月:MD=8.23,95%CI(5.15,9.19)],降低治疗3个月后的左室舒张末期内径[3个月:MD=-0.65,95%CI(-0.72,-0.59);6个月:MD=-0.12,95%CI(-0.21,-0.03);≥12个月:MD=-0.19,95%CI(-0.24,-0.13)],增加治疗6个月后6 min步行距离[6个月:MD=87.70,95%CI(51.55,123.85);≥12个月:MD=143.83,95%CI(122.73,164.93)],降低治疗3个月的心肌灌注缺血面积百分比[MD=-3.56,95%CI(-5.57,-1.55)],降低治疗及随访期间死亡率[RR=0.46,95%CI(0.24,0.89)];两种治疗在降低恶性心律失常及心脏移植率上无明显差异。研究结果提示,自体骨髓间充质干细胞移植治疗扩张性心肌病疗效优于常规药物疗法,且安全性良好。

BACKGROUND： Autologous bone marrow mesenchymal stem cells（BMSCs） transplantation has been used for clinical treatment of dilated cardiomyopathy. But the efficacy and safety of autologous BMSCs transplantation remains controversial.OBJECTIVE： To systematically assess the efficacy and safety of autologous BMSCs transplantation for treatment of dilated cardiomyopathy by using meta-analysis approach. METHODS： Pub Med, Cochrane Library（Issue 2, 2016）, Embase, CNKI, CBM, VIP, Wan Fang were systemically searched for relevant randomized controlled trials（RCTs） about autologous BMSCs transplantation and conventional drugs for the treatment of dilated cardiomyopathy. After information extracting and quality assessing, Meta-analysis of left ventricular ejection fraction, left ventricular end-diastolic diameter, 6-minute walking distance, percentage of myocardial perfusion defect, mortality, incidence of malignant arrhythmia events and heart transplantation rate during treatment and follow-up was performed using R3.1.0 software. RESULTS AND CONCLUSION： A total of 7 RCTs involving 341 patients were included. Meta-analysis results showed that for efficacy, compared with the conventional drugs, BMSCs can increase the left ventricular ejection fraction [1 month post-treatment： mean difference（MD）=3.02, 95% confidence interval（CI）（1.55, 4.49）; 3 months post-treatment： MD=4.38, 95%CI（3.55, 5.52）; 6 months post-treatment： MD=6.47, 95%CI（4.78, 8.15）; ≥ 12 months post-treatment： MD=8.23, 95%CI（5.15, 9.19）]; decrease the left ventricular end-diastolic diameter after 3 months [3 months post-treatment： MD=-0.65, 95%CI（-0.72,-0.59）; 6 months post-treatment： MD=-0.12, 95%CI（-0.21,-0.03）; ≥ 12 months post-treatment： MD=-0.19, 95%CI（-0.24,-0.13）]; increase 6-minute walking distance after 6 months [6 months post-treatment： MD=87.70, 95%CI（51.55, 123.85）; ≥ 12 months post-treatment： MD=143.83, 95%CI（122.73, 164.93）]; and decrease percentage of myocardial perfusion defect at 3 months [MD=-3.56, 95%CI（-5.57,-1.55）]. For safety, BMSCs can decrease the mortality [risk ratio=0.46, 95%CI（0.24, 0.89）], but there is no significant difference in the incidence of malignant arrhythmia events and heart transplantation rate between two treatment groups. To conclude, these results indicate that BMSCs transplantation for dilated cardiomyopathy is one of effective and safe treatments.