Circulation：急性心梗后骨髓单核细胞移植对左室功能无改善

冠脉内注射自体骨髓单核细胞（BM-MNC）可改善急性心肌梗死后的左室（LV）重构。目前冠脉内注射BM-MNC的最佳时机目前仍有争议，而这方面的前瞻性随机对照研究较少。来自瑞士苏黎世大学医院的Daniel Sürder博士等研究人员进行了一多中心前瞻性研究——SWISS-AMI研究（Swiss Multicenter Intracoronary Stem Cells Study in Acute Myocardial Infarction），在急性心肌梗死后的两个时间点与予以冠脉内注射BM-MNC：心梗后早期（5-7天）和晚期（3-4周）。其结果发现冠脉内注射BM-MNC不管是在心梗后早期还是晚期，在第四个月时的随访时左室功能较原来无明显改善。
研究结果发表在2013年5月14日的Circulation杂志上。
该研究随机入选200名ST段抬高型心肌梗死且成功实现再灌注的患者，按照1:1:1比例随机分配至开放对照组和2个BM-MNC治疗组。2个BM-MNC组中，细胞的注射时间为心肌梗死后早期（5-7天）或晚期（3-4周）。在研究开始时和4个月时进行行心脏核磁共振检查。研究主要终点事件是2个治疗组和对照组之间第4个月和基线比较整个左室功能的变化情况。研究发现：在对照组第4个月时和基线比较左室射血分数的变化值为？0.4±8.8% （mean±SD; P=0.74 ，与基线比较），心梗后早期治疗组的变化值为1.8±8.4% （P=0.12，与基线比较），心梗后晚期治疗组的变化值为0.8±7.6%（P=0.45，与基线比较）。BM-MNC的治疗疗效采用ANCOVA分析评估，心梗后早期治疗组的ANCOVA值为1.25（95% CI, ?1.83 to 4.32; P=0.42），心梗后晚期治疗组的ANCOVA值为0.55（95% CI, ?2.61 to 3.71; P=0.73）。
研究人员指出，对于成功再灌注的ST抬高的心肌梗死和左室功能不全的患者，不管是在急性心肌梗死后5-7天还是3-4周予以冠脉内BM-MNC注射治疗，在4个月后的随访中左室功能无明显改善。
骨髓的采集相对来说比较容易，在急性心肌梗死后进行冠脉内BM-MNC治疗安全可行。 不少随机试验表明急性心肌梗死后予以BM-MNC治疗有望改善左室射血分数。然而由于在后来的试验研究中发现通过核磁共振评价的左室功能未能证实这一结果。最近的其他两项关于BM-MNC相似的研究结果也表明BM-MNC对左室重构以及整体或部分左室功能无明显改善。尽管有meta分析显示BM-MNC治疗可能获益。该研究并不能对BM-MNC是否为合适的细胞类型作出回答，以及选择左室射血分数作为观察指标是否合适，是否还有更好的观察指标等问题，这期待进一步的研究。

Intracoronary injection of bone marrow-derived mononuclear cells early or late after acute myocardial infarction: effects on global left ventricular function.
BACKGROUND
Intracoronary administration of autologous bone marrow-derived mononuclear cells (BM-MNC) may improve remodeling of the left ventricle (LV) after acute myocardial infarction. The optimal time point of administration of BM-MNC is still uncertain and has rarely been addressed prospectively in randomized clinical trials.
METHODS AND RESULTS
In a multicenter study, we randomized 200 patients with large, successfully reperfused ST-segment elevation myocardial infarction in a 1:1:1 pattern into an open-labeled control and 2 BM-MNC treatment groups. In the BM-MNC groups, cells were administered either early (ie, 5 to 7 days) or late (ie, 3 to 4 weeks) after acute myocardial infarction. Cardiac magnetic resonance imaging was performed at baseline and after 4 months. The primary end point was the change from baseline to 4 months in global LV ejection fraction between the 2 treatment groups and the control group. The absolute change in LV ejection fraction from baseline to 4 months was -0.4±8.8% (mean±SD; P=0.74 versus baseline) in the control group, 1.8±8.4% (P=0.12 versus baseline) in the early group, and 0.8±7.6% (P=0.45 versus baseline) in the late group. The treatment effect of BM-MNC as estimated by ANCOVA was 1.25 (95% confidence interval, -1.83 to 4.32; P=0.42) for the early therapy group and 0.55 (95% confidence interval, -2.61 to 3.71; P=0.73) for the late therapy group.
CONCLUSIONS
Among patients with ST-segment elevation myocardial infarction and LV dysfunction after successful reperfusion, intracoronary infusion of BM-MNC at either 5 to 7 days or 3 to 4 weeks after acute myocardial infarction did not improve LV function at 4-month follow-up.