title: Direct intramyocardial plasmid vascular endothelial growth factor-A165 gene therapy in patients with stable severe angina pectoris A randomized double-blind placebo-controlled study: the Euroinject One trial.
abstract: OBJECTIVE
  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.
  
  
  BACKGROUND
  Evidence for safety and treatment efficacy have been presented in phase I therapeutic angiogenesis trials.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Cardiac Catheterization Laboratory, University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Kastrup
authors.forename: Erik
authors.initials: E
authors.lastname: Jørgensen
authors.forename: Andreas
authors.initials: A
authors.lastname: Rück
authors.forename: Kristina
authors.initials: K
authors.lastname: Tägil
authors.forename: Dietmar
authors.initials: D
authors.lastname: Glogar
authors.forename: Witold
authors.initials: W
authors.lastname: Ruzyllo
authors.forename: Hans Erik
authors.initials: HE
authors.lastname: Bøtker
authors.forename: Dariusz
authors.initials: D
authors.lastname: Dudek
authors.forename: Viktor
authors.initials: V
authors.lastname: Drvota
authors.forename: Birger
authors.initials: B
authors.lastname: Hesse
authors.forename: Leif
authors.initials: L
authors.lastname: Thuesen
authors.forename: Pontus
authors.initials: P
authors.lastname: Blomberg
authors.forename: Mariann
authors.initials: M
authors.lastname: Gyöngyösi
authors.forename: Christer
authors.initials: C
authors.lastname: Sylvén
mesh_terms: D000787:Angina Pectoris / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D004311:Double-Blind Method; D005060:Europe; D005080:Exercise Test; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging / Q000503:physiopathology; D010957:Plasmids / Q000008:administration & dosage / Q000627:therapeutic use*; D019275:Radiopharmaceuticals; D012720:Severity of Illness Index; D017256:Technetium Tc 99m Sestamibi; D015899:Tomography, Emission-Computed, Single-Photon; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage / Q000627:therapeutic use*; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000503:physiopathology
chemical_list: D019275:Radiopharmaceuticals; D042461:Vascular Endothelial Growth Factor A; D017256:Technetium Tc 99m Sestamibi