自体骨髓单个核细胞移植治疗心肌病疗效及安全性评估

Effect and safety of autologous intracoronary bone marrow mononuclear cells transplantation in dilated cardiomyopathy

目的观察经皮冠状动脉移植自体骨髓单个核细胞（BMMNCs）合并药物治疗扩张型心肌病疗效及安全性。方法采用对照、前瞻性临床研究的方法，收集2008年6月至2012年6月在我院住院的20例纽约心功能分级（NYHA）Ill～Ⅳ级扩张型心肌病患者，治疗组8例经冠状动脉移植BMMNCs2．90×10-9个／L（1．80×10-9～5．90×10-9个／L）合并药物治疗，另12例对照组单纯用常规药物治疗，观察两组患者6个月后左室舒张末期内径、射血分数（EF）值、6min步行距离、心肌核素CT（ECT）代谢情况等。结果治疗组与对照组术后6个月比较，左室舒张末期内径（LVEDd）[（50．3±4．2）mm比（55．4±3．7）mm]、EF[（45．4±5．2）％比（39．2±6．3）％]、6min步行距离[（76．6±5．8）m比（69．7±8．6）m]差异均有统计学意义（t=2．93、3．21、2．96，P=0．040、O．030、0．040）；治疗组术后6个月LVEDd由术前（57．2±6．5）mm缩小为（50．3±4．2）mm（t=5．60，P〈0．01），EF由（30．4±6．7）％提高至（45．4±5．2）％（t=6．30，P〈0．01）；对照组治疗6个月后EF由术前（31．1±5．9）％提高至（39．2±6．3）％（t=3．60，P〈0．05）。两组患者6min步行距离均较术前延长，治疗组分别为术后6个月（76．6±5．8）m，术前（54．0±6．2）rn；对照组术后6个月（69．7±8．6）m，术前（55．0±5．7）In（均P〈0．05）。术后6个月治疗组心肌放射性18氟脱氧葡萄糖（18-FDG）代谢密度在相同节段较术前明显增加，原放射性FDG代谢密度稀疏节段明显减少。随访6个月治疗组未出现与BMMNCs注射有关的室性心律失常、死亡等严重并发症。结论药物合并经皮冠状动脉移植自体BMMNCs治疗扩张型心肌病与单纯药物治疗比较术后6个月疗效更好，且较安全，但较长时间的疗效及安全性还有待进一步观察。

Objective To investigate the effect and safety of autologous bone marrow mononuclear cells（BMMNCs） transplantation in dilated cardiomyopathy. Methods 20 patients aged 18-67 years with dilated cardiomyopathy, who suffered from New York Heart Association class III to IV heart failure, left ventricular ejection fraction（LVEF） 〈35%, were randomized to transplantation group（intracoronary injection of autologous BMMNCs 1.80 × 10-9 ×5.90 × 10-9/L, combined with drug treatment, n= 8） or the control group（ordinary drugs treatment, n= 12）. The left ventricular end diastolic diameter（LVEDD）, ejection fraction（EF）, 6-minute walk test and myocardial metabolism detected by emission computed tomography（ECT） were observed after 6 months of treatment. Results There were significant differences in LVEDD, EF, 6- minute walk test between the transplantation group and the control group after 6 months of treatment [（50.3±2 4.2） mm vs. （55.4 ±3.7） mm,（45.4±5.2）% vs. （39.2±6.3）% ,（76.6±5.8） m vs. （69.7±8.6） m, t=2.93, 3.21, 2.96, respectively, all P〈0.05]. After 6 months of treatment, LVEDD was shorted from（57.2±2 6.5） mmto（50.3±4.2） mm to（t=5.60, P〈0.01） and EF was increased from（30.4±26.7） % to（45.4 ±5.2） %（t=6.30, P〈0.01） in the transplantation group, and EF was increased from（31. 125.9） to（39.2±6.3） %（t=3.60, P〈0.05） in the control group. Compared with pre-treatment, the 6- minute walk distance were increased in the two group after 6 months of treatment [transplantation group.. （76.6±5.8） m vs. （54.0±6.2） m, P〈0.05 control group.. （69.7±8.6） m vs. （55.0±5.7） m, P 〈 0.05]. Myocardialmetabolism density of radioactive 18-fluorodeoxyglucose （18-FDG） in the same segment was significantly increased, and the metabolic density of radioactive FDG in sparse segment was significantly reduced in transplantation group after 6 months of treatment as compared with pre-treatment. No serious complications associated with BMMNCs injection, including ventricular arrhythmia and death, were observed in transplantation group at 6-month follow-up. Conclusions Autologous intracoronary BMMNCs transplantation combined with drug treatment is more effective and safe than ordinary drug treatment. But the longer efficacy and safety of the intracoronary injection of autologous BMMNCs needs to be studied carefully.