Randomized, single-blind, placebo-controlled pilot study of catheter-basedmyocardial gene transfer for therapeutic angiogenesis using left ventricular electromechanical mapping in patients with chronic myocardial ischemia

Background-Catheter-based myocardial gene transfer (GTx) has not been previ ously tested in human subjects. Accordingly, we performed a pilot study to investigate the feasibility and safety of catheter-based myocardial GTx of naked plasmid DNA encoding vascular endothelial growth factor-2 (phVEGF-2) in patients with chronic myocardial ischemia. Methods and Results-A steerable, deflectable 8F catheter incorporating a 27 -guage needle was advanced percutaneously to the left ventricular myocardiu m of 6 patients with chronic myocardial ischemia. Patients were randomized (1:1) to receive phVEGF-2 (total dose, 200 mug), which was administered as 6 injections into ischemic myocardium (total, 6.0 mt), or placebo (mock pro cedure). Injections were guided by NOGA left ventricular electromechanical mapping. Patients initially randomized to placebo became eligible for phVEG F-2 GTx if they had no clinical improvement 90 days after their initial pro cedure. Catheter injections (n=36) caused no changes in heart rate or blood pressure. No sustained ventricular arrhythmias, ECG evidence of infarction , or ventricular perforations were observed. phVEGF-2-transfected patients experienced reduced angina (before versus after GTx, 36.2 +/-2.3 versus 3.5 +/-1.2 episodes/week) and reduced nitroglycerin consumption (33.8 +/-2.3 v ersus 4.1 +/-1.5 tablets/week) for up to 360 days after GTx; reduced ischem ia by electromechanical mapping (mean area of ischemia, 10.2 +/-3.5 versus 2.8 +/-1.6 cm(2), P=0.04); and improved myocardial perfusion by SPECT-sesta mibi scanning for up to 90 days after GTx when compared with images obtaine d after control procedure. Conclusions-This randomized trial of catheter-based phVEGF-2 myocardial GTx provides preliminary indications regarding the feasibility, safety, and po tential efficacy of percutaneous myocardial GTx to human left ventricular m yocardium.