Kastrup Jens, Jørgensen Erik, Rück Andreas, Tägil Kristina, Glogar Dietmar, Ruzyllo Witold, Bøtker Hans Erik, Dudek Dariusz, Drvota Viktor, Hesse Birger, Thuesen Leif, Blomberg Pontus, Gyöngyösi Mariann, Sylvén Christer
Cardiac Catheterization Laboratory, University Hospital Rigshospitalet, Copenhagen, Denmark.
J Am Coll Cardiol. 2005 Apr 5;45(7):982-8. doi: 10.1016/j.jacc.2004.12.068.
In the Euroinject One phase II randomized double-blind trial, therapeutic angiogenesis of percutaneous intramyocardial plasmid gene transfer of vascular endothelial growth factor (phVEGF-A(165)) on myocardial perfusion, left ventricular function, and clinical symptoms was assessed.
Evidence for safety and treatment efficacy have been presented in phase I therapeutic angiogenesis trials.
Eighty "no-option" patients with severe stable ischemic heart disease, Canadian Cardiovascular Society functional class 3 to 4, were assigned randomly to receive, via the NOGA-MyoStar system (Cordis Corp., Miami Lakes, Florida), either 0.5 mg of phVEGF-A(165) (n = 40) or placebo plasmid (n = 40) in the myocardial region showing stress-induced myocardial perfusion defects on (99m)Tc sestamibi/tetrofosmin single-photon emission computed tomography.
No differences among the groups were recorded at baseline with respect to clinical, perfusion, and wall motion characteristics. After three months, myocardial stress perfusion defects did not differ significantly between the VEGF gene transfer and placebo groups (38 +/- 3% and 44 +/- 2%, respectively). Similarly, semiquantitative analysis of the change in perfusion in the treated region of interest did not differ significantly between the two groups. Compared with placebo, VEGF gene transfer improved the local wall motion disturbances, assessed both by NOGA (p = 0.04) and contrast ventriculography (p = 0.03). Canadian Cardiovascular Society functional class classification of angina pectoris improved significantly in both groups but without difference between the groups. No phVEGF-A(165)-related adverse events were observed; however, NOGA procedure-related adverse events occurred in five patients.
The VEGF gene transfer did not significantly improve stress-induced myocardial perfusion abnormalities compared with placebo; however, improved regional wall motion, as assessed both by NOGA and by ventriculography, may indicate a favorable anti-ischemic effect. This result should encourage more studies within the field. Transient VEGF overexpression seems to be safe.
在Euroinject One II期随机双盲试验中，评估经皮心肌内血管内皮生长因子（phVEGF-A(165)）质粒基因转移的治疗性血管生成对心肌灌注、左心室功能和临床症状的影响。
I期治疗性血管生成试验已提供了安全性和治疗效果的证据。
80例患有严重稳定型缺血性心脏病、加拿大心血管学会功能分级为3至4级的“无其他选择”患者，通过NOGA-MyoStar系统（Cordis公司，迈阿密湖，佛罗里达州）被随机分配，在（99m）Tc司他米比/替曲膦单光子发射计算机断层扫描显示应激诱导的心肌灌注缺损的心肌区域，接受0.5mg phVEGF-A(165)（n = 40）或安慰剂质粒（n = 40）。
在基线时，两组在临床、灌注和壁运动特征方面无差异。三个月后，VEGF基因转移组和安慰剂组之间的心肌应激灌注缺损无显著差异（分别为38±3%和44±2%）。同样，两组之间感兴趣治疗区域灌注变化的半定量分析也无显著差异。与安慰剂相比，VEGF基因转移改善了局部壁运动障碍，通过NOGA（p = 0.04）和对比心室造影（p = 0.03）评估均如此。两组加拿大心血管学会心绞痛功能分级均有显著改善，但两组之间无差异。未观察到与phVEGF-A(165)相关的不良事件；然而，有5例患者发生了与NOGA操作相关的不良事件。
与安慰剂相比，VEGF基因转移并未显著改善应激诱导的心肌灌注异常；然而，通过NOGA和心室造影评估，区域壁运动的改善可能表明有良好的抗缺血作用。这一结果应鼓励该领域进行更多研究。短暂的VEGF过表达似乎是安全的。
