Menasché Philippe, Alfieri Ottavio, Janssens Stefan, McKenna William, Reichenspurner Hermann, Trinquart Ludovic, Vilquin Jean-Thomas, Marolleau Jean-Pierre, Seymour Barbara, Larghero Jérôme, Lake Stephen, Chatellier Gilles, Solomon Scott, Desnos Michel, Hagège Albert A
Département de Chirurgie Cardio-vasculaire, Hôpital Européen Georges Pompidou, 20, rue Leblanc, 75015 Paris, France.
Circulation. 2008 Mar 4;117(9):1189-200. doi: 10.1161/CIRCULATIONAHA.107.734103. Epub 2008 Feb 19.
Phase I clinical studies have demonstrated the feasibility of implanting autologous skeletal myoblasts in postinfarction scars. However, they have failed to determine whether this procedure was functionally effective and arrhythmogenic.
This multicenter, randomized, placebo-controlled, double-blind study included patients with left ventricular (LV) dysfunction (ejection fraction < or = 35%), myocardial infarction, and indication for coronary surgery. Each patient received either cells grown from a skeletal muscle biopsy or a placebo solution injected in and around the scar. All patients received an implantable cardioverter-defibrillator. The primary efficacy end points were the 6-month changes in global and regional LV function assessed by echocardiography. The safety end points comprised a composite index of major cardiac adverse events and ventricular arrhythmias. Ninety-seven patients received myoblasts (400 or 800 million; n=33 and n=34, respectively) or the placebo (n=30). Myoblast transfer did not improve regional or global LV function beyond that seen in control patients. The absolute change in ejection fraction (median [interquartile range]) between 6 months and baseline was 4.4% (0.2; 7.3), 3.4% (-0.3; 12.4), and 5.2% (-4.4; 11.0) in the placebo, low-dose, and high-dose groups, respectively (P=0.95). However, the high-dose cell group demonstrated a significant decrease in LV volumes compared with the placebo group. Despite a higher number of arrhythmic events in the myoblast-treated patients, the 6-month rates of major cardiac adverse events and of ventricular arrhythmias did not differ significantly between the pooled treatment and placebo groups.
Myoblast injections combined with coronary surgery in patients with depressed LV function failed to improve echocardiographic heart function. The increased number of early postoperative arrhythmic events after myoblast transplantation, as well as the capability of high-dose injections to revert LV remodeling, warrants further investigation.
I期临床研究已证明在梗死瘢痕中植入自体骨骼肌成肌细胞的可行性。然而，这些研究未能确定该手术在功能上是否有效以及是否会诱发心律失常。
这项多中心、随机、安慰剂对照、双盲研究纳入了左心室（LV）功能不全（射血分数≤35%）、心肌梗死且有冠状动脉手术指征的患者。每位患者接受从骨骼肌活检培养的细胞或注射在瘢痕及其周围的安慰剂溶液。所有患者均植入了植入式心律转复除颤器。主要疗效终点是通过超声心动图评估的6个月时左心室整体和局部功能的变化。安全终点包括主要心脏不良事件和室性心律失常的综合指数。97例患者接受了成肌细胞（4亿或8亿；分别为n = 33和n = 34）或安慰剂（n = 30）治疗。成肌细胞移植并未使局部或整体左心室功能改善超过对照组患者。安慰剂组、低剂量组和高剂量组在6个月和基线之间射血分数的绝对变化（中位数[四分位间距]）分别为4.4%（0.2；7.3）、3.4%（-0.3；12.4）和5.2%（-4.4；11.0）（P = 0.95）。然而，与安慰剂组相比，高剂量细胞组的左心室容积显著减小。尽管接受成肌细胞治疗的患者心律失常事件较多，但联合治疗组和安慰剂组之间6个月时主要心脏不良事件和室性心律失常的发生率并无显著差异。
在左心室功能低下的患者中，成肌细胞注射联合冠状动脉手术未能改善超声心动图检查的心脏功能。成肌细胞移植后术后早期心律失常事件增多，以及高剂量注射逆转左心室重构的能力，值得进一步研究。
