Aims We evaluated for the first time the effects of angiogenic and lymphangiogenic AdVEGF-DDNDC gene therapy in patients\nwith refractory angina.\nMethods and\nresults\nThirty patients were randomized to AdVEGF-DDNDC (AdVEGF-D) or placebo (control) groups. Electromechanical\nNOGA mapping and radiowater PET were used to identify hibernating viable myocardium where treatment was\ntargeted. Safety, severity of symptoms, quality of life, lipoprotein(a) [Lp(a)] and routine clinical chemistry were\nmeasured. Myocardial perfusion reserve (MPR) was assessed with radiowater PET at baseline and after 3- and 12-\nmonths follow-up. Treatment was well tolerated. Myocardial perfusion reserve increased significantly in the treated\narea in the AdVEGF-D group compared with baseline (1.00 �± 0.36) at 3 months (1.31 �± 0.46, P = 0.045) and\n12 months (1.44 �± 0.48, P = 0.009) whereas MPR in the reference area tended to decrease (2.05 �± 0.69, 1.76 �± 0.62,\nand 1.87 �± 0.69; baseline, 3 and 12 months, respectively, P = 0.551). Myocardial perfusion reserve in the control\ngroup showed no significant change from baseline to 3 and 12 months (1.26 �± 0.37, 1.57 �± 0.55, and 1.48 �± 0.48; respectively,\nP = 0.690). No major changes were found in clinical chemistry but anti-adenovirus antibodies increased\nin 54% of the treated patients compared with baseline. AdVEGF-D patients in the highest Lp(a) tertile at baseline\nshowed the best response to therapy (MPR 0.94 �± 0.32 and 1.76 �± 0.41 baseline and 12 months, respectively,\nP = 0.023).\nConclusion AdVEGF-DDNDC gene therapy was safe, feasible, and well tolerated. Myocardial perfusion increased at 1 year in the\ntreated areas with impaired MPR at baseline. Plasma Lp(a) may be a potential biomarker to identify patients that\nmay have the greatest benefit with this therapy.
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