Abstract 11987: Adenoviral Intramyocardial VEGF-D Gene Transfer Increases Myocardial Perfusion in Refractory Angina Patients

Abstract

Background: There is a rapidly growing number of refractory angina patients who in spite of the optimal medical therapy are severely symptomatic and who are not suitable for revascularization. Proangiogenic gene therapy is a potential new treatment for these patients. We evaluated for the first time safety, feasibility and efficacy of adenoviral (Ad) gene therapy using a new member of the VEGF family, VEGF-D, in the treatment of refractory angina. Methods and Results: KAT301 trial is a randomized, placebo-controlled, single-blinded phase I/II study. A total of 30 patients were randomized to intramyocardial AdVEGF-D gene transfer (VEGF group) or placebo (control group) with a 4:1 ratio. VEGF group underwent transseptal puncture and electroanatomical mapping of left ventricle with NOGA system (Cordis Corp), followed by intramyocardial injection of AdVEFG-D in the ischemic areas. The control group underwent transseptal puncture, left ventricle mapping and intracardiac saline infusion. Vital signs and laboratory assessments were measured at baseline and at 1, 2, 7,14 days and 3 months after the gene therapy to evaluate the safety and feasibility. Twenty patients underwent assessment of myocardial perfusion and blood flow reserve at rest and during adenosine induced exercise with positron emission tomography (15O-PET) at baseline and three months after the procedure. Mild transient elevation in body temperature and CRP and moderate hypotension was detected in VEGF group after the procedure. Troponine-T was elevated in both groups after the procedure but was normalized in two days. Perfusion reserve at 3 months in the myocardial segment with the lowest perfusion reserve at baseline increased significantly in the VEGF group (0.93±0.30 to 1.21±0.39, p=0.035) but not in the controls (1.21±0.63 to 1.53±0.67, p=0.343). No antibody responses were found against the transgene in the VEGF group after the treatment. Conclusion: Intramyocardial AdVEGF-D gene therapy is well tolerated in refractory angina patients. Changes in PET analysis at 3 months indicate that gene therapy can enhance myocardial perfusion in segments with the lowest perfusion reserve. Based on the results a randomized, controlled, blinded phase II/III trial is justified.