title: Effects of intramyocardial injection of phVEGF-A165 as sole therapy in patients with refractory coronary artery disease--12-month follow-up: angiogenic gene therapy.
abstract: OBJECTIVE
  To test the safety and bioactivity of phVEGF-A165 after intramyocardial injection during 12-month follow-up.
  
  
  METHODS
  Open-labelled study.
  
  
  METHODS
  Inclusion criteria were angina pectoris, Canadian Cardiovascular Society (CCS) class III-IV, unamenable to further revascularization, ejection fraction (EF) >30%, perfusion defects extending over >10% of the anterolateral left ventricle wall detectable with adenosine single photon emission computerized tomography (SPECT) and at least one patent vessel visible by coronary angiography. Seven of 39 patients referred for gene therapy were included.
  
  
  METHODS
  Via a mini-thoracotomy under general anaesthesia. phVEGF-A165 was injected directly into the myocardium at four sites in the anterolateral region of the left ventricle.
  
  
  RESULTS
  Operative procedures were uneventful. Perioperative release of myocardial markers and electrocardiogram (ECG) changes were detected in two patients. There were no perioperative deaths but one patient died 7 months postoperatively because of myocardial infarction. Plasma vascular endothelial growth factor (VEGF)-A levels increased two to threefold peaking 6 days postoperatively (P < 0.004) and returning to baseline by day 30. A significant reduction in angina pectoris was reported. The CCS class improved from 3.3+/-0.2 to 1.9+/-0.3 (P < 0.01) and nitroglycerine intake decreased from 39+/-15 to 12+/-5 tablets week(-1) (P < 0.001) 2 months after gene transfer. Improvements remained after 12 months when nitroglycerine consumption approached zero. Improved myocardial function in the phVEGF-A165 injection region was documented in all patients (P < 0.016) by tissue velocity imaging (TVI). Reduced reversible ischaemia was detected by adenosine SPECT in four patients. Improved collateralization was detected in four patients with coronary angiography.
  
  
  CONCLUSIONS
  Intramyocardial injection of phVEGF-A165 is safe and may lead to improved myocardial perfusion and function with longstanding symptomatic relief in end-stage angina pectoris. Based on these results this therapeutic potential is being tested in a double-blind placebo controlled multicentre trial.
authors.affiliation: Department of Cardiology, Karolinska Institute, Huddinge University Hospital, Novum, Stockholm, Sweden.
authors.forename: N
authors.initials: N
authors.lastname: Sarkar
authors.forename: A
authors.initials: A
authors.lastname: Rück
authors.forename: G
authors.initials: G
authors.lastname: Källner
authors.forename: S
authors.initials: S
authors.lastname: Y-Hassan
authors.forename: P
authors.initials: P
authors.lastname: Blomberg
authors.forename: K B
authors.initials: KB
authors.lastname: Islam
authors.forename: J
authors.initials: J
authors.lastname: van der Linden
authors.forename: D
authors.initials: D
authors.lastname: Lindblom
authors.forename: A T
authors.initials: AT
authors.lastname: Nygren
authors.forename: B
authors.initials: B
authors.lastname: Lind
authors.forename: L A
authors.initials: LA
authors.lastname: Brodin
authors.forename: V
authors.initials: V
authors.lastname: Drvota
authors.forename: C
authors.initials: C
authors.lastname: Sylvén
mesh_terms: D000368:Aged; D000787:Angina Pectoris / Q000175:diagnosis / Q000188:drug therapy* / Q000601:surgery; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000601:surgery; D016228:Endothelial Growth Factors / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D010957:Plasmids / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D013908:Thoracotomy; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A
chemical_list: D016228:Endothelial Growth Factors; D042461:Vascular Endothelial Growth Factor A