比较间充质干细胞在缺血性与非缺血性扩张型心肌病中的疗效。
Comparison of Mesenchymal Stem Cell Efficacy in Ischemic Versus Nonischemic Dilated Cardiomyopathy.
机构信息
Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL.
Department of Surgery, University of Miami Miller School of Medicine, Miami, FL.
出版信息
J Am Heart Assoc. 2018 Jul 12;7(14):e008460. doi: 10.1161/JAHA.117.008460.
BACKGROUND
Ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) differ in histopathology and prognosis. Although transendocardial delivery of mesenchymal stem cells is safe and provides cardiovascular benefits in both, a comparison of mesenchymal stem cell efficacy in ICM versus DCM has not been done.
METHODS AND RESULTS
We conducted a subanalysis of 3 single-center, randomized, and blinded clinical trials: (1) TAC-HFT (Transendocardial Autologous Mesenchymal Stem Cells and Mononuclear Bone Marrow Cells in Ischemic Heart Failure Trial); (2) POSEIDON (A Phase I/II, Randomized Pilot Study of the Comparative Safety and Efficacy of Transendocardial Injection of Autologous Mesenchymal Stem Cells Versus Allogeneic Mesenchymal Stem Cells in Patients With Chronic Ischemic Left Ventricular Dysfunction Secondary to Myocardial Infarction); and (3) POSEIDON-DCM (Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis in Dilated Cardiomyopathy). Baseline and 1-year cardiac structure and function and quality-of-life data were compared in a post hoc pooled analysis including ICM (n=46) and DCM (n=33) patients who received autologous or allogeneic mesenchymal stem cells. Ejection fraction improved in DCM by 7% (within-group, =0.002) compared to ICM (1.5%; within-group, =0.14; between-group, =0.003). Similarly, stroke volume increased in DCM by 10.59 mL (=0.046) versus ICM (-0.2 mL; =0.73; between-group, =0.02). End-diastolic volume improved only in ICM (10.6 mL; =0.04) and end-systolic volume improved only in DCM (17.8 mL; =0.049). The sphericity index decreased only in ICM (-0.04; =0.0002). End-diastolic mass increased in ICM (23.1 g; <0.0001) versus DCM (-4.1 g; =0.34; between-group, =0.007). The 6-minute walk test improved in DCM (31.1 m; =0.009) and ICM (36.3 m; =0.006) with no between-group difference (=0.79). The New York Heart Association class improved in DCM (=0.005) and ICM (=0.02; between-group =0.20). The Minnesota Living with Heart Failure Questionnaire improved in DCM (-19.5; =0.002) and ICM (-6.4; =0.03; δ between-group difference =0.042) patients.
CONCLUSIONS
Mesenchymal stem cell therapy is beneficial in DCM and ICM patients, despite variable effects on cardiac phenotypic outcomes. Whereas cardiac function improved preferentially in DCM patients, ICM patients experienced reverse remodeling. Mesenchymal stem cell therapy enhanced quality of life and functional capacity in both etiologies.
CLINICAL TRIAL REGISTRATION
URL: http://www.clinicaltrials.gov. Unique identifiers: TAC-HFT: NCT00768066, POSEIDON: NCT01087996, POSEIDON-DCM: NCT01392625.
背景
缺血性心肌病 (ICM) 和扩张型心肌病 (DCM) 在组织病理学和预后方面存在差异。尽管经心内膜递送间充质干细胞在这两种疾病中均安全且提供心血管益处，但尚未比较间充质干细胞在 ICM 与 DCM 中的疗效。
方法和结果
我们对 3 项单中心、随机、双盲临床试验进行了亚组分析：（1）TAC-HFT（经心内膜自体间充质干细胞和单核骨髓细胞治疗缺血性心力衰竭试验）；（2）POSEIDON（一项 I/II 期、随机、单盲研究，比较经心内膜注射自体间充质干细胞与同种异体间充质干细胞治疗心肌梗死后慢性缺血性左心室功能障碍患者的安全性和疗效）；和（3）POSEIDON-DCM（经皮干细胞注射输送对扩张型心肌病新生肌的影响）。对接受自体或同种异体间充质干细胞的 ICM（n=46）和 DCM（n=33）患者进行了基于队列的事后汇总分析，比较了基线和 1 年时的心脏结构和功能以及生活质量数据。结果显示，与 ICM（1.5%；组内，=0.14；组间，=0.003）相比，DCM 的射血分数增加了 7%（组内，=0.002）。同样，DCM 的每搏量增加了 10.59 mL（=0.046），而 ICM 则减少了 0.2 mL（=0.73；组间，=0.02）。仅在 ICM 中观察到舒张末期容积改善（10.6 mL；=0.04），仅在 DCM 中观察到收缩末期容积改善（17.8 mL；=0.049）。仅在 ICM 中观察到球形指数降低（-0.04；=0.0002）。ICM 的舒张末期质量增加（23.1 g；<0.0001），而 DCM 则减少（4.1 g；=0.34；组间，=0.007）。DCM（31.1 m；=0.009）和 ICM（36.3 m；=0.006）的 6 分钟步行试验均有改善，且组间无差异（=0.79）。DCM（=0.005）和 ICM（=0.02；组间，=0.20）的纽约心脏协会心功能分级均有改善。DCM（-19.5；=0.002）和 ICM（-6.4；=0.03；组间差值=0.042）患者的明尼苏达心力衰竭生活质量问卷均有改善。
结论
尽管对心脏表型结局的影响不同，但间充质干细胞治疗对 DCM 和 ICM 患者均有益。尽管 DCM 患者的心脏功能改善更为明显，但 ICM 患者经历了逆向重构。间充质干细胞治疗增强了两种病因的生活质量和功能能力。
临床试验注册
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