Left ventricular electromechanical mapping to assess efficacy of phVEGF(165) gene transfer for therapeutic angiogenesis in chronic myocardial ischemia.
BACKGROUND
NOGA left ventricular (LV) electromechanical mapping (EMM) can be used to distinguish among infarcted, ischemic, and normal myocardium. We investigated the use of percutaneous LV EMM to assess the efficacy of myocardial gene transfer (GTx) of naked plasmid DNA encoding for vascular endothelial growth factor (phVEGF(165)), administered during surgery by direct myocardial injection in patients with chronic myocardial ischemia.


RESULTS
A total of 13 consecutive patients (8 men, mean age 60.1+/-2. 3 years) with chronic stable angina due to angiographically documented coronary artery disease, all of whom had failed conventional therapy (drugs, PTCA, and/or CABG), were treated with direct myocardial injection of phVEGF(165) via a minithoracotomy. Foci of ischemic myocardium were identified on LV EMM by preserved viability associated with an impairment in linear local shortening. Myocardial viability, defined by mean unipolar and bipolar voltage recordings >/=5 and >/=2 mV, respectively, did not change significantly after GTx. Analysis of linear local shortening in areas of myocardial ischemia, however, disclosed significant improvement after (15.26+/-0.98%) versus before (9.94+/-1.53%, P:=0. 004) phVEGF(165) GTx. The area of ischemic myocardium was consequently reduced from 6.45+/-1.37 cm(2) before GTx to 0.95+/-0. 41 cm(2) after GTx (P:=0.001). These findings corresponded to improved perfusion scores calculated from single-photon emission CT-sestamibi myocardial perfusion scans recorded at rest (7.4+/-2.1 before GTx versus 4.5+/-1.4 after GTx, P:=0.009) and after pharmacological stress (12.8+/-2.7 before GTx versus 8.5+/-1.7 after GTx, P:=0.047).


CONCLUSIONS
The results of EMM constitute objective evidence that phVEGF(165) GTx augments perfusion of ischemic myocardium. These findings, together with reduction in the size of the defects documented at rest by serial single-photon emission CT-sestamibi imaging, suggest that phVEGF(165) GTx may successfully rescue foci of hibernating myocardium.
Vale
P R
PR
Division of Cardiology and Vascular Medicine, St. Elizabeth's Medical Center, Boston, MA 02135, USA.
Losordo
D W
DW
Milliken
C E
CE
Maysky
M
M
Esakof
D D
DD
Symes
J F
JF
Isner
J M
JM
D043925:Angiogenesis Inducing Agents / Q000627:therapeutic use; D003326:Coronary Circulation / Q000187:drug effects; D004562:Electrocardiography / Q000379:methods; D016228:Endothelial Growth Factors / Q000235:genetics* / Q000627:therapeutic use; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006321:Heart / Q000000981:diagnostic imaging / Q000503:physiopathology; D006801:Humans; D008222:Lymphokines / Q000235:genetics* / Q000627:therapeutic use; D008297:Male; D008845:Microinjections; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000628:therapy*; D018919:Neovascularization, Physiologic; D010957:Plasmids / Q000627:therapeutic use; D011877:Radionuclide Imaging; D013908:Thoracotomy; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016277:Ventricular Function, Left
D043925:Angiogenesis Inducing Agents; D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors