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PET for Evaluation of Differential Myocardial Perfusion Dynamics After VEGF Gene Therapy and Laser Therapy in End-Stage Coronary Artery Disease

¹ Department of Cardiology, University Hospital Groningen, Groningen, The Netherlands
² Trial Coordination Center, University Hospital Groningen, Groningen, The Netherlands
³ Department of Nuclear Medicine, University Hospital Groningen, Groningen, The Netherlands
⁴ PET Center, University Hospital Groningen, Groningen, The Netherlands
⁵ Department of Medical Oncology, University Hospital Groningen, Groningen, The Netherlands

The purpose of this study was to appraise the value of PET in the assessment of the effect of supposedly proangiogenic new therapies such as gene therapy with vascular endothelial growth factor (VEGF) gene and endomyocardial laser therapy. Methods: Thirty-five patients with end-stage coronary artery disease and class III (Canadian Cardiovascular Society) angina were included. Myocardial ischemia was evaluated with dipyridamole PET scanning and exercise tolerance with bicycle ergometry. Ten patients were treated with naked plasmid DNA encoding for human VEGF₁₆₅ (VEGF) and 12 patients were treated with laser therapy (direct myocardial revascularization [DMR]) using an electromechanical mapping system. Thirteen patients were treated with standard medical therapy (control). Results: In both active treatment groups, angina was reduced in most subjects, except in 2 VEGF and 5 DMR patients. In the control group, no improvement in anginal classification was found, except in 3 subjects. On the PET scan, solely in the VEGF group, the stress perfusion was significantly improved (from 57 ± 33 to 81 ± 55 mL/min/100 g; P = 0.031). Furthermore, in the VEGF group, the number of ischemic segments was reduced from 274 ± 41 to 234 ± 48 segments (P = 0.004) but not in the DMR group (from 209 ± 43 to 215 ± 52 segments) or in the control group (from 218 ± 18 to 213 ± 28 segments). Bicycle exercise duration showed slight nonsignificant changes in the VEGF group (from 3.6 ± 2.0 to 4.6 ± 2.1 min), in the DMR group (from 5.1 ± 1.5 to 4.7 ± 1.3 min), and in the control group (from 3.3 ± 1.8 to 3.5 ± 2.3 min). Conclusion: PET showed that intramyocardial gene therapy with the human VEGF₁₆₅ gene in contrast to laser DMR treatment effectively reduces myocardial ischemia.

Key Words: angiogenesis • coronary artery disease • endothelium • gene therapy • PET • refractory angina pectoris

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