Myocardial transfection of hypoxia inducible factor-1alpha via an adenoviral vector during coronary artery bypass grafting. - A multicenter phase I and safety study -.
BACKGROUND
Increasing numbers of patients with advanced coronary artery disease have limited options for percutaneous and/or surgical revascularization. A prospective, randomized, phase I clinical multicenter trial was performed to assess the feasibility and safety of delivering a pro-angiogenic transcription factor termed "hypoxia inducible factor-1alpha", delivered to ischemic cardiac muscle via a type 2 adenoviral (Ad2HIF) vector.


RESULTS
The 13 patients were included under the following criteria: 1 hypoperfused area of viable ventricular muscle without options for revascularization and left ventricular ejection fraction > or =30%. After coronary artery bypass grafting was completed, 10 injections of the study drug (n=10), in 3 escalating doses up to 1 x 10(11) viral particles or saline (n=3) as a placebo control, were injected intramyocardially. After completion of the 1-year follow-up, all patients had uncomplicated postoperative courses, are alive and feeling well; 1 patient had a self-limited run of tachycardia postoperatively and at 6 months, 1 patient developed recurrent angina. Positron emission tomography perfusion analysis revealed improvement in the Ad2HIF injected areas in selected patients.


CONCLUSIONS
These data support the feasibility and preliminary safety of adenoviral transfection with Ad2HIF in regions of viable myocardium. Additional studies will be required to determine the efficacy and safety of Ad2HIF.
Kilian
Eckehard Gerd
EG
Department of Cardiac Surgery, University of Munich, Germany. Ec.Ki@web.de
Sadoni
Sebastian
S
Vicol
Calin
C
Kelly
Ralph
R
van Hulst
Karen
K
Schwaiger
Markus
M
Kupatt
Christian
C
Boekstegers
Peter
P
Pillai
Ravi
R
Channon
Keith
K
Hetzer
Roland
R
Reichart
Bruno
B
D000256:Adenoviridae; D000368:Aged; D001026:Coronary Artery Bypass; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006352:Heart Ventricles / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000628:therapy*; D011446:Prospective Studies; D014161:Transduction, Genetic; D014162:Transfection
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit