title: Long-term (2-year) clinical events following transthoracic intramyocardial gene transfer of VEGF-2 in no-option patients.
abstract: BACKGROUND
  The short-term clinical impact of intramyocardial gene transfer (GT) of the angiogenic protein vascular endothelial growth factor-2 (VEGF-2) has been previously reported to significantly reduce Canadian Cardiovascular Society (CCS) angina class and to prolong exercise treadmill test (ETT) time. We describe the safety and long-term events (>1 year) in consecutive, nonrandomized, patients who received intramyocardial VEGF-2.
  
  
  METHODS
  Thirty patients with intractable CCS class III or IV angina and no options for revascularization underwent direct intramyocardial GT of VEGF-2 naked DNA via limited thoracotomy at total doses of 0.2, 0.8, or 2.0 mg. Patients were followed for clinical events after 1 year by hospital records, follow-up visits or telephone contact. Due to one perioperative death, 29 patients were followed.
  
  
  RESULTS
  At a mean follow-up of 751 +/- 102.5 days (range 459-959) there were four deaths (13.8%), five myocardial infarctions (MIs) (17.2%), and seven revascularization procedures (24.1%). There were 15 hospitalizations in 12 patients. At the end of the follow-up period no patient (0%) had CCS class IV angina, 3 patients (11.5%) had class III angina, and 23 (88.5%) had class I to II angina. There were two new diagnoses of cancer.
  
  
  CONCLUSIONS
  Transthoracic intramyocardial injection of VEGF-2 is associated with an improvement of symptoms of angina in the majority of patients beyond the first year of treatment. Major clinical events such as death, MI, and repeat revascularization are uncommon during the first year but more frequent after 1 year at a rate consistent with the severity of underlying disease in this population with advanced atherosclerosis. The majority of events were the result of progression of disease in areas of the heart remote from the site of GT. A large randomized trial is planned to determine the efficacy of intramyocardial VEGF-2 injections in inoperable patients.
authors.affiliation: Scripps Clinic, Interventional Cardiology, La Jolla, California, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Reilly
authors.forename: Mark A
authors.initials: MA
authors.lastname: Grise
authors.forename: F David
authors.initials: FD
authors.lastname: Fortuin
authors.forename: Peter R
authors.initials: PR
authors.lastname: Vale
authors.forename: Gary L
authors.initials: GL
authors.lastname: Schaer
authors.forename: John
authors.initials: J
authors.lastname: Lopez
authors.forename: Joseph R
authors.initials: JR
authors.lastname: VAN Camp
authors.forename: Timothy
authors.initials: T
authors.lastname: Henry
authors.forename: Wayne E
authors.initials: WE
authors.lastname: Richenbacher
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Losordo
authors.forename: Richard A
authors.initials: RA
authors.lastname: Schatz
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Isner
mesh_terms: D000328:Adult; D000368:Aged; D000787:Angina Pectoris / Q000628:therapy*; D005260:Female; D018014:Gene Transfer Techniques; D006801:Humans; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D016896:Treatment Outcome; D042442:Vascular Endothelial Growth Factors / Q000235:genetics*
chemical_list: D042442:Vascular Endothelial Growth Factors