Myocardial Doppler tissue velocity improves following myocardial gene therapy with VEGF-A165 plasmid in patients with inoperable angina pectoris.
BACKGROUND
Myocardial tissue velocity and perfusion were studied in patients with severe angina pectoris following gene therapy by intramyocardial injection of phVEGF-A165 via thoracotomy. Plasma concentrations of VEGF-A increased postoperatively. Two months after treatment anginal status and myocardial tissue velocity improved and perfusion showed a tendency to improve. Tissue velocity imaging appears to be a sensitive, objective method for detecting changes in myocardial function following gene therapy.


OBJECTIVE
To study effects on myocardial tissue velocity and perfusion in patients with angina pectoris following intramyocardial injection of phVEGF-A165 via thoracotomy.


METHODS
Open label, phase I/II.


METHODS
Six patients with Canadian Cardiovascular Society (CCS) angina pectoris functional class III - IV and with major defects at adenosine stress single-photon emission computerized tomography (SPECT) were studied. In addition to SPECT, coronary angiography and dobutamine stress echocardiography with tissue Doppler velocity imaging were performed before and two months after gene transfer.


RESULTS
Plasma concentrations of VEGF-A increased 2 to 3 times (P < 0.04) over baseline from 2 to 14 days after injection with normalization after 4 weeks. The CCS class improved about 40%, from 3.3 +/- 0.2 to 2.0 +/- 0.3 (P < 0.02) and nitroglycerine consumption decreased 30 - 40%, from 44 +/- 17 to 15 +/- 5 tablets per week (P < 0.05). The maximal systolic myocardial tissue velocity increased in all patients about 25% (P < 0.02) but did not reach the reference range. Myocardial perfusion at SPECT improved in four of the six patients.


CONCLUSIONS
Anginal status, myocardial tissue velocity and perfusion can be improved by phVEGF-A165 intramyocardial injection. Tissue velocity imaging appears to be a sensitive, objective method for detecting changes in myocardial function following gene therapy.
Sylvén
C
C
Karolinska Institute, Department of Cardiology, Huddinge University Hospital, Novum, Stockholm, Sweden. christer.sylven@medhs.ki.se
Sarkar
N
N
Rück
A
A
Drvota
V
V
Hassan
S Y
SY
Lind
B
B
Nygren
A
A
Källner
Q
Q
Blomberg
P
P
van der Linden
J
J
Lindblom
D
D
Brodin
L A
LA
Islam
K B
KB
D000368:Aged; D000787:Angina Pectoris / Q000000981:diagnostic imaging* / Q000503:physiopathology / Q000628:therapy*; D003326:Coronary Circulation / Q000502:physiology; D015150:Echocardiography, Doppler; D016228:Endothelial Growth Factors / Q000097:blood / Q000627:therapeutic use*; D015316:Genetic Therapy; D006801:Humans; D008875:Middle Aged; D010957:Plasmids / Q000097:blood / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A
D016228:Endothelial Growth Factors; D042461:Vascular Endothelial Growth Factor A