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

Circulation. 2001 May 1;103(17):2138-43. doi: 10.1161/01.cir.103.17.2138.

Abstract

Background: Catheter-based myocardial gene transfer (GTx) has not been previously 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 myocardium of 6 patients with chronic myocardial ischemia. Patients were randomized (1:1) to receive phVEGF-2 (total dose, 200 microgram), which was administered as 6 injections into ischemic myocardium (total, 6.0 mL), or placebo (mock procedure). Injections were guided by NOGA left ventricular electromechanical mapping. Patients initially randomized to placebo became eligible for phVEGF-2 GTx if they had no clinical improvement 90 days after their initial procedure. 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 versus 4.1+/-1.5 tablets/week) for up to 360 days after GTx; reduced ischemia 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-sestamibi scanning for up to 90 days after GTx when compared with images obtained after control procedure. Conclusions-This randomized trial of catheter-based phVEGF-2 myocardial GTx provides preliminary indications regarding the feasibility, safety, and potential efficacy of percutaneous myocardial GTx to human left ventricular myocardium.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cardiac Catheterization*
  • DNA, Recombinant / administration & dosage*
  • DNA, Recombinant / genetics
  • DNA, Recombinant / therapeutic use
  • Feasibility Studies
  • Female
  • Heart Ventricles / physiopathology
  • Humans
  • Male
  • Myocardial Ischemia / diagnostic imaging
  • Myocardial Ischemia / physiopathology
  • Myocardial Ischemia / therapy*
  • Neovascularization, Physiologic / genetics*
  • Pilot Projects
  • Safety
  • Tomography, Emission-Computed, Single-Photon
  • Transfection*
  • Treatment Outcome
  • Vascular Endothelial Growth Factors / genetics
  • Vascular Endothelial Growth Factors / therapeutic use*
  • Ventricular Function, Left*

Substances

  • DNA, Recombinant
  • Vascular Endothelial Growth Factors