经冠状动脉骨髓单个核细胞移植治疗重度心力衰竭

目的本研究对比观察一组治疗上除心脏移植外,不能或难于从其他任何治疗中获益的重度缺血性心力衰竭(end-stage ischemia heart failure,EIHF)患者,给予经冠状动脉自体骨髓单个核细胞(bone marrow mononuclear cells,BM-MNCs)移植,探索其治疗的可行性、安全性及不良反应。方法30例EIHF患者入选。分为:细胞移植组(n=16)和常规治疗组(n=14)。细胞移植组和常规治疗组治疗前、后随访观察临床表现、实验室检查、二维超声心动图、正电子断层心肌显像(PET)、Holter、血管活性肽等。梯度密度法分离自体BM-MNCs。细胞移植组:经冠状动脉选择性细胞移植,平均BM-MNCs(5．0±0．7)×107。常规治疗组:除细胞移植外其他治疗均同细胞移植组。结果16例细胞移植手术均安全。2例于细胞注入后15-30 min感全身发冷,30 min后好转。1例细胞注入时出现短暂自限性室性早搏。术后48 h持续心电监测未出现新的心律失常。细胞移植组:术后观察半年患者均未再发急性肺水肿,心力衰竭症状明显改善。3个月NYHA分级明显改善[(3．4±0．1)级→(2．4±0．2)级,P<0．001];左心室射血分数(LVEF)于术后7天、3个月分别较术前增加9．6％(P<0．05)、9．9％(P<0．001);:PET显示代谢活力心肌增加(10．3±3．4)％(P<0．01)。血浆脑型利钠肽(brain-type natriuretic peptide,BNP)显著降低,3天、7天分别较术前下降69．2％(P<0．05)、70．4％(P<0．05);心房利钠肽(atrial natriuretic peptide,ANP)增加,术后第7天为术前1．3倍(P< 0．05);6个月随访无一例死亡,仅1例心力衰竭加重住院。而对照组3个月心功能检测明显恶化; NYHA分级下降[(3．5±0．1)级→(3．9±0．1)级,P<0．05];LVEF较术前减低7．2％(P<0．001),与细胞移植组相比差异有显著统计学意义(P<0．001);6个月随访死亡2例;因心力衰竭恶化再住院率71．4％(10／14)。结论自体BM-MNCs经冠状动脉移植治疗EIHF患者是安全有效的,显著改善了近期预后。

The autologous bone marrow mononuclear cell transplantation by intracoronary route treat patients with severe heart failure after myocardial infarction

OBJECTIVE: To investigate the chronic effects of intracoronary autologous bone marrow mononuclear cell (BM-MNCs) transplantation in patients with refractory heart failure (RIHF) after myocardial infarction. METHODS: Thirty patients with RIHF (LVEF < 40%) were enrolled in this nonrandomized study, autologous BM-MNCs (5.0 +/- 0.7) x 10(7) were transplanted with via infarct-related coronary artery in 16 patients and 14 patients received standard medical therapy served as control. Baseline and follow up evaluations included complete clinical evaluations, plasma BNP, ANP, ET-1 measurements, echocardiography, PET, and Holter monitoring. RESULTS: Baseline characteristics were similar between the 2 groups. There were no major periprocedural complications. One patient developed ventricular premature contractions during cell infusion for several seconds and recovered spontaneously. Compared to pre-transplantation, plasma BNP and ET-1 significantly decreased and plasma ANP significantly increased at 7 days post transplantation; 6 minutes walking distance increased from (72.1 +/- 31.5) to (201.6 +/- 23.3) m (P < 0.01), LVEF increased 9.9% (P < 0.001) and FDG-PET revealed vital myocardium area increased (10.3 +/- 3.4)% (P < 0.01) at 3 months after BM-MNCs transplantation. At 6 months follow up, the NYHA class improved from (3.4 +/- 0.1 to 2.4 +/- 0.2, P < 0.001) and no patient died and 1 patient rehospitalized due to lower extremities edema. In control group, LVEF decreased 7.2% compared to baseline (P < 0.001) and was significantly lower than transplantation group at 3 months (P < 0.001). At 6 months follow up, the NYHA class increased from (3.5 +/- 0.1 to 3.9 +/- 0.1, P < 0.05), 2 patients died and 10 patients rehospitalized due to aggravated heart failure. CONCLUSION: Present study demonstrates that intracoronary transplantation of autologous BM-MNCs is safe and effective for treating patients with RIHF after myocardial infarction.