The following are key points to remember about the effects of angiogenic and lymphangiogenic AdVEGF-D^ΔNΔC gene therapy in patients with refractory angina:

1. Angina pectoris is the most common symptom of coronary artery disease (CAD). Despite improved medical and revascularization therapies, 5–10% of patients undergoing coronary angiography have refractory angina (RA), i.e. they are severely symptomatic while on optimal medical therapy and prior revascularization and not amenable to further revascularization procedures.
2. There are >200,000 new RA patients/year in the European Union and United States. Thus, an unmet clinical need exists for new therapies for RA patients.
3. Some CAD patients develop collateral arteries, which can rescue ischemic myocardium despite significant occlusions in coronary arteries and alleviate ischemic symptoms. Therapeutic vascular growth stimulates this natural process and offers a potential new treatment for RA.
4. Most previous cardiovascular proangiogenic trials have been unsuccessful, likely because of: (a) poor gene transfer efficiency in the myocardium, (b) growth factors that may not have been the most optimal ones, and (c) inability to target therapy into ischemic, but viable myocardium.
5. The current study used positron emission tomography (PET) perfusion imaging and an electromechanical catheter system for gene transfer to identify ischemic, hibernating myocardium with the lowest perfusion reserve for the targeted therapy. It also used VEGF-D^ΔNΔC, a new member of the VEGF family that stimulates both angiogenesis and lymphangiogenesis.
6. Lp(a) plasma levels were tested as a potential new biomarker to identify patients who might benefit from the induced therapeutic vascular growth since it is associated with pro-atherogenic, pro-inflammatory, and pro-thrombotic effects.
7. The main finding of this study was that intramyocardial AdVEGF-D^ΔNΔC gene therapy was safe, feasible, and well tolerated.
8. Although the primary target of the current study was the safety and feasibility, it is of interest that myocardial perfusion increased in the treated myocardial segments at 3 and 12 months.
9. Larger, randomized, blinded phase IIb/III trials are needed to confirm the safety and efficacy of gene therapy in RA patients and validate these preliminary findings.
10. The ongoing Adenovirus Vascular Endothelial Growth Factor D (AdvVEGF-D) Therapy for Treatment of Refractory Angina Pectoris (ReGenHeart) trial evaluating the safety and efficacy of catheter-mediated endocardial adenovirus-mediated vascular endothelial growth factor-D regenerative gene transfer in patients with refractory angina will provide additional insight.

Keywords: Angina Pectoris, Atherosclerosis, Biomarkers, Cardiac Imaging Techniques, Complement Factor B, Coronary Angiography, Coronary Artery Disease, Genetic Therapy, Lymphangiogenesis, Myocardial Revascularization, Myocardium, Perfusion Imaging, Positron-Emission Tomography, Vascular Diseases, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factor D

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