Transendocardial mesenchymal stem cells and mononuclear bone marrow cells for ischemic cardiomyopathy: the TAC-HFT randomized trial.
Transendocardial mesenchymal stem cells and mononuclear bone marrow cells for ischemic cardiomyopathy: the TAC-HFT randomized trial.
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DOI：
10.1001/jama.2013.282909
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发表时间：
2014-01-01
影响因子：
120.7
通讯作者：
Hare, Joshua M.
中科院分区：
文献类型：
--
作者：
Heldman, Alan W.;DiFede, Darcy L.;Fishman, Joel E.;Zambrano, Juan P.;Trachtenberg, Barry H.;Karantalis, Vasileios;Mushtaq, Muzammil;Williams, Adam R.;Suncion, Viky Y.;McNiece, Ian K.;Ghersin, Eduard;Soto, Victor;Lopera, Gustavo;Miki, Roberto;Willens, Howard;Hendel, Robert;Mitrani, Raul;Pattany, Pradip;Feigenbaum, Gary;Oskouei, Behzad;Byrnes, John;Lowery, Maureen H.;Sierra, Julio;Pujol, Mariesty V.;Delgado, Cindy;Gonzalez, Phillip J.;Rodriguez, Jose E.;Bagno, Luiza Lima;Rouy, Didier;Altman, Peter;Foo, Cheryl Wong Po;da Silva, Jose;Anderson, Erica;Schwarz, Richard;Mendizabal, Adam;Hare, Joshua M.
培养扩增的骨髓间充质干细胞或全骨髓单个核细胞治疗慢性缺血性心肌病（ICM）是否安全有效仍存在争议。目的：证实经内皮干细胞注射自体骨髓间充质干细胞（MSCs）和全骨髓单个核细胞（BMCs）治疗缺血性心肌病的安全性。一项I期和II期随机盲法安慰剂对照研究，纳入65例缺血性心肌病和左心室（LV）射血分数低于50%的患者（2009年9月1日至2013年7月12日）。该研究比较了MSC（N=19）和安慰剂（N=11）或BMC（N=19）与安慰剂（N=10）的注射以及1年的随访。用输注导管注射到10个LV部位。治疗后出现的30天严重不良事件发生率定义为死亡、心肌梗死、卒中、因心力衰竭恶化住院、穿孔、心包填塞或持续性室性心律失常的复合事件。在第30天，无患者发生治疗后出现的严重不良事件。1年严重不良事件的发生率为31.6%（95% CI，12.6%-56.6%），MSC为31.6%（95% CI，12.6%-56.6%），BMC为31.6%（95% CI，12.6%-56.6%），安慰剂为38.1%（95% CI，18.1%-61.6%）。1年后，使用MSC（重复测量ANOVA P= .02）和BMC（P= .005）而不是安慰剂（P= .38）的明尼苏达心力衰竭生活（MLHF）评分有所改善，仅使用MSC的6分钟步行距离增加（重复测量模型P= .03）。骨髓间充质干细胞（-18.9%; 95% CI，-30.4至-7.4;组内P= 0.004）降低了左室质量百分比的冠状动脉大小，但骨髓间充质干细胞（-7.0%; 95% CI，-15.7%-1.7%;组内P= 0.11）或安慰剂（-5.2; 95% CI，-16.8%-6.5%;组内P= 0.36）未降低冠状动脉大小。局部心肌功能，如注射部位的欧拉环向应变峰值，在MSC组得到改善（-4.9; 95% CI，-13.3-3.5;组内重复测量P= 0.03），但在BMC组（-2.1; 95% CI，-5.5-1.3; P= 0.21）或安慰剂组（-0.03; 95% CI，-1.9-1.9; P= 0.14）中没有改善。左心室腔容积和射血分数无变化。骨髓间充质干细胞或骨髓基质细胞的transendoorbital干细胞注射似乎是安全的慢性缺血性心肌病和左室功能不全的患者。尽管样本量和多重比较排除了关于安全性和临床效果的明确声明，但这些结果为更大规模的研究提供了基础，以提供关于安全性的明确证据并评估这种新治疗方法的疗效。
Whether culture expanded mesenchymal stem cells or whole bone marrow mononuclear cells are safe and effective in chronic ischemic cardiomyopathy (ICM) remains controversial. To demonstrate the safety of transendocardial stem cell injection with autologous mesenchymal stem cells (MSCs) and whole bone marrow mononuclear cells (BMCs) in patients with ischemic cardiomyopathy. A phase 1 and 2 randomized blinded placebo-controlled study involving 65 patients with ischemic cardiomyopathy and left ventricular (LV) ejection fraction less than50%(September 1, 2009-July 12, 2013). The study compared injection of MSCs (N=19) and placebo (N=11) or BMCs (N=19) with placebo (N=10) with 1-year of follow up. Injections into 10 LV sites with an infusion catheter. Treatment-emergent 30 day serious adverse event rate defined as composite of death, myocardial infarction, stroke, hospitalization for worsening heart failure, perforation, tamponade or sustained ventricular arrhythmias. No patient had a treatment-emergent serious adverse events at day 30. The 1-year incidence of serious adverse events was 31.6% (95% CI, 12.6%-56.6%) for MSCs, 31.6% (95% CI, 12.6%-56.6%) for BMCs, and 38.1% (95% CI, 18.1%-61.6%) for placebo. Over 1-year the Minnesota Living with Heart Failure (MLHF) score improved with MSCs (repeated measures ANOVA P= .02) and BMCs (P= .005) but not placebo (P= .38), and 6-minute walk distance increased with MSCs only (repeated measures model P= .03). Infarct size as a percentage of LV Mass was reduced by MSCs (-18.9%; 95% CI, -30.4 to -7.4; within-group P= .004) but not by BMCs (-7.0%; 95% CI, -15.7%-1.7%; within-group P= .11) or placebo (-5.2; 95% CI, -16.8%-6.5%; within-group P=.36). Regional myocardial function as peak Eulerian circumferential strain at the site of injection improved with MSCs (-4.9; 95% CI, -13.3-3.5; within-group repeated measures P=.03) but not BMCs (-2.1; 95% CI -5.5-1.3; P=.21) or placebo (-0.03; 95% CI, -1.9-1.9; P=.14). Left ventricular chamber volume and ejection fraction did not change. Transendocardial stem cell injection with MSCs or BMCs appeared to be safe for patients with chronic ischemic cardiomyopathy and LV dysfunction. Although the sample size and multiple comparisons preclude a definitive statement about safety and clinical effect, these results provide the basis for larger studies to provide definitive evidence about safety and to assess efficacy of this new therapeutic approach.
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影响因子：
24
作者：
Hare, Joshua M.;Traverse, Jay H.;Henry, Timothy D.;Dib, Nabil;Strumpf, Robert K.;Schulman, Steven P.;Gerstenblith, Gary;DeMaria, Anthony N.;Denktas, Ali E.;Gammon, Roger S.;Hermiller, James B., Jr.;Reisman, Mark A.;Schaer, Gary L.;Sherman, Warren
通讯作者：
Sherman, Warren
影响因子：
20.1
作者：
Hatzistergos KE;Quevedo H;Oskouei BN;Hu Q;Feigenbaum GS;Margitich IS;Mazhari R;Boyle AJ;Zambrano JP;Rodriguez JE;Dulce R;Pattany PM;Valdes D;Revilla C;Heldman AW;McNiece I;Hare JM
通讯作者：
Hare JM
影响因子：
37.8
作者：
Perin, EC;Dohmann, HFR;Willerson, JT
通讯作者：
Willerson, JT
影响因子：
168.9
作者：
Janssens, S;Dubois, C;Van de Werf, F
通讯作者：
Van de Werf, F
影响因子：
4.6
作者：
Hamamoto, Hirotsugu;Gorman, Joseph H., III;Ryan, Liam P.;Hinmon, Robin;Martens, Timothy P.;Schuster, Michael D.;Plappert, Theodore;Kiupel, Matti;John-Sutton, Martin G. St.;Itescu, Silviu;Gorman, Robert C.
通讯作者：
Gorman, Robert C.