title: 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.
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.
  
  
  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.
authors.affiliation: Departments of Medicine, Cardiovascular Research, Cardiothoracic Surgery, St Elizabeth's Medical Center, Tufts Medical School, Boston, Massachusetts, USA. vdavila@im.wustl.edu
authors.forename: P R
authors.initials: PR
authors.lastname: Vale
authors.forename: D W
authors.initials: DW
authors.lastname: Losordo
authors.forename: C E
authors.initials: CE
authors.lastname: Milliken
authors.forename: M C
authors.initials: MC
authors.lastname: McDonald
authors.forename: L M
authors.initials: LM
authors.lastname: Gravelin
authors.forename: C M
authors.initials: CM
authors.lastname: Curry
authors.forename: D D
authors.initials: DD
authors.lastname: Esakof
authors.forename: M
authors.initials: M
authors.lastname: Maysky
authors.forename: J F
authors.initials: JF
authors.lastname: Symes
authors.forename: J M
authors.initials: JM
authors.lastname: Isner
mesh_terms: D000368:Aged; D006328:Cardiac Catheterization; D004274:DNA, Recombinant / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use; D005240:Feasibility Studies; D005260:Female; D006352:Heart Ventricles / Q000503:physiopathology; D006801:Humans; D008297:Male; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000628:therapy*; D018919:Neovascularization, Physiologic / Q000235:genetics*; D010865:Pilot Projects; D012449:Safety; D015899:Tomography, Emission-Computed, Single-Photon; D014162:Transfection; D016896:Treatment Outcome; D042442:Vascular Endothelial Growth Factors / Q000235:genetics / Q000627:therapeutic use*; D016277:Ventricular Function, Left
chemical_list: D004274:DNA, Recombinant; D042442:Vascular Endothelial Growth Factors