***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background —Catheter-based intracoronary vascular endothelial growth factor ( VEGF ) gene transfer is a potential treatment for coronary heart disease . However , only limited data are available about local VEGF gene transfer given during angioplasty ( PTCA ) and stenting . Methods and Results — Patients with coronary heart disease ( n=103 ; Canadian Cardiovascular Society class II to III ; mean age , 58±6 years ) were recruited in this r and omized , placebo-controlled , double-blind phase II study . PTCA was performed with st and ard methods , followed by gene transfer with a perfusion-infusion catheter .  Ninety percent of the patients were given stents ;  37 patients received VEGF adenovirus ( VEGF-Adv , 2 × 1010 pfu ) , 28 patients received VEGF plasmid liposome ( VEGF-P/L ; 2000 & mgr;g of DNA with 2000 & mgr;L of DOTMA : DOPE [ 1:1 wt/wt ] ) , and 38 control patients received Ringer ’s lactate . Follow-up time was 6 months . Gene transfer to coronary arteries was feasible and well tolerated . The overall clinical restenosis rate was 6 % . In quantitative coronary angiography analysis , the minimal lumen diameter and percent of diameter stenosis did not significantly differ between the study groups . However , myocardial perfusion showed a significant improvement in the VEGF-Adv-treated patients after the 6-month follow-up . Some inflammatory responses were transiently present in the VEGF-Adv group , but no increases were detected in the incidences of serious adverse events in any of the study groups . Conclusions —Gene transfer with VEGF-Adv or VEGF-P/L during PTCA and stenting shows that ( 1 ) intracoronary gene transfer can be performed safely ( no major gene transfer-related adverse effects were detected ) , ( 2 ) no differences in clinical restenosis rate or minimal lumen diameter were present after the 6-month follow-up , and ( 3 ) a significant increase was detected in myocardial perfusion in the VEGF-Adv-treated patients Background —This phase 1/2 study investigated the safety of percutaneous catheter-based gene transfer of naked plasmid DNA encoding for vascular endothelial growth factor 2 ( phVEGF2 ) to left ventricular ( LV ) myocardium in a prospect i ve , r and omized , double-blind , placebo-controlled , dose-escalating study of inoperable patients with class III or IV angina . Methods and Results —A steerable deflectable 8F catheter with a 27-gauge needle at its distal tip was advanced percutaneously to the endocardial surface of the LV in 19 patients ( age , 61±2 years ) with chronic myocardial ischemia who were not c and i date s for conventional revascularization . Patients were r and omized in a double-blind fashion to receive 6 injections ( total volume , 6.0 mL ) of placebo or phVEGF2 in doses of 200 & mgr;g ( n=9 ) , 800 & mgr;g ( n=9 ) , or 2000 & mgr;g ( n=1 ) guided by LV electromechanical ( NOGA ) mapping with a gene-to-placebo ratio of 2:1 . A total of 114 LV injections were delivered and caused no hemodynamic alterations , sustained ventricular arrhythmias , ECG evidence of infa rct ion , or ventricular perforation . End-point analysis at 12 weeks disclosed a statistically significant improvement in Canadian Cardiovascular Society ( CCS ) angina class in phVEGF2-treated versus placebo-treated patients ( −1.3 versus −0.1 , P = 0.04 ) . Remaining efficacy end points — including change in exercise duration ( 91.8 versus 3.9 seconds ) , functional improvement by ≥2 CCS classes ( 9 of 12 versus 1 of 6 ) , and Seattle Angina Question naire data —all showed strong trends favoring efficacy of phVEGF2 versus placebo treatment . Conclusions —This phase 1/2 , double-blind , r and omized trial provides preliminary data that support safety of phVEGF2 catheter-mediated myocardial gene transfer . The statistically significant reduction in anginal class and strong positive trends for remaining end points suggest that a larger phase 2/3 trial is warranted Abstract Aims We evaluated for the first time the effects of angiogenic and lymphangiogenic AdVEGF-DΔNΔC gene therapy in patients with refractory angina . Methods and results Thirty patients were r and omized to AdVEGF-DΔNΔC ( AdVEGF-D ) or placebo ( control ) groups . Electromechanical NOGA mapping and radiowater PET were used to identify hibernating viable myocardium where treatment was targeted . Safety , severity of symptoms , quality of life , lipoprotein(a ) [ Lp(a ) ] and routine clinical chemistry were measured . Myocardial perfusion reserve ( MPR ) was assessed with radiowater PET at baseline and after 3- and 12-months follow-up . Treatment was well tolerated . Myocardial perfusion reserve increased significantly in the treated area in the AdVEGF-D group compared with baseline ( 1.00 ± 0.36 ) at 3 months ( 1.31 ± 0.46 , P = 0.045 ) and 12 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 , and 1.87 ± 0.69 ; baseline , 3 and 12 months , respectively , P = 0.551 ) . Myocardial perfusion reserve in the control group 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 , P = 0.690 ) . No major changes were found in clinical chemistry but anti-adenovirus antibodies increased in 54 % of the treated patients compared with baseline . AdVEGF-D patients in the highest Lp(a ) tertile at baseline showed the best response to therapy ( MPR 0.94 ± 0.32 and 1.76 ± 0.41 baseline and 12 months , respectively , P = 0.023 ) . Conclusion AdVEGF-DΔNΔC gene  therapy was safe , feasible , and well tolerated . Myocardial perfusion increased at 1 year in the treated areas with impaired MPR at baseline . Plasma Lp(a ) may be a potential biomarker to identify patients that may have the greatest benefit with this therapy AIMS Genes encoding vascular endothelial growth factor ( VEGF ) can potentially augment myocardial perfusion in patients with coronary artery disease ( CAD ) . We conducted a r and omised , double-blind , placebo-controlled gene therapy study with the adenovirus carrying VEGF121 ( BIOBYPASS [ AdGVVEGF121.10NH ] ) . METHODS AND RESULTS Seventeen patients with severe CAD were 2:1 r and omised to BIOBYPASS ( n=12 ; 61 years ) or placebo ( n=5 ; 64 ) as 12 intra-myocardial injections into the ischaemic area using the NOGA XP ® system . The study was terminated prematurely due to a company product portfolio decision . Mean change in total exercise duration from baseline to 12 , 26 and 52 weeks was 20.2 , 21.4 and 16.4 sec in BIOBYPASS treated and 46.2 , 31.4 and 12.4 sec in placebo ( NS ) . Change from baseline to at least 1 mm ST depression during exercise at 12 , 26 and 52 weeks did not differ between BIOBYPASS and placebo . Change in stress-induced ischaemia score was similar in the BIOBYPASS ( 3.4 % ) and placebo ( 2.0 % ) groups . An improvement in symptoms was seen in patients treated with BIOBYPASS , but no difference between the groups . CONCLUSIONS Direct intramyocardial injection of BIOBYPASS ( AdGVVEGF121.10NH ) was safe but did not improve exercise capacity , time to ischaemic threshold or myocardial perfusion compared to sham injection in patients with refractory myocardial ischaemia BACKGROUND VIF-CAD r and omized , placebo-controlled , double-blind trial was an attempt to induce therapeutic angiogenesis by percutaneous intramyocardial transfer of bicistronic ( vascular endothelial growth factor/fibroblast growth factor [ VEGF/FGF ] ) plasmid ( pVIF ) in patients with refractory heart ischemia .  Myocardial perfusion , clinical symptoms , exercise tolerance , left ventricular function , and safety were assessed . METHODS Fifty-two patients with refractory coronary artery disease were r and omized to receive VEGF/FGF plasmid ( n = 33 ) or placebo plasmid ( n = 19 ) into myocardial region showing stress-induced perfusion defects . Repeat stress and rest technetium Tc 99 m sestamibi single-photon emission computed tomography at 5 months was the primary efficacy measure . Secondary assessment included Canadian Cardiovascular Society class and exercise tolerance at 5 and 12 months . RESULTS Rest- and stress-induced perfusion defects did not differ between groups . Canadian Cardiovascular Society functional class improved after 5 ( P = .0210 ) and 12 months ( P = .0607 ) in the treatment group . The exercise tolerance of treated patients improved : total exercise time increased marginally ( P = .0541 ) ; maximum workload ( P = .0419 ) and total test distance ( P = .0473 ) increased significantly , compared to placebo . CONCLUSION Bicistronic VEGF/FGF plasmid therapy did not improve myocardial perfusion measured by single-photon emission computed tomography . However , treated patients experienced improvement with respect to exercise tolerance and clinical symptoms . Intramyocardial VEGF/FGF bicistronic plasmid transfer seemed safe throughout the follow-up period of 1 year The demonstration that angiogenic growth factors can stimulate new blood vessel growth and restore perfusion in animal models of myocardial ischemia has led to the development of strategies design ed for the local production of angiogenic growth factors in patients who are not c and i date s for conventional revascularization . The results of recent clinical trials of proangiogenesis gene therapy have been disappointing ; however , significant limitations in experimental design , in particular in gene transfer strategies , preclude drawing definitive conclusions . In the REVASC study cardiac gene transfer was optimized by direct intramyocardial delivery of a replication-deficient adenovirus-containing vascular endothelial growth factor ( AdVEGF121 , 4 × 1010 particle units ( p.u . ) ) . Sixty-seven patients with severe angina due to coronary artery disease and no conventional options for revascularization were r and omized to AdVEGF121 gene transfer via mini-thoracotomy or continuation of maximal medical treatment .  Exercise time to 1 mm ST-segment depression , the predefined primary end-point analysis , was significantly increased in the AdVEGF121 group compared to control at 26 weeks ( P=0.026 ) , but not at 12 weeks . As well , total exercise duration and time to moderate angina at weeks 12 and 26 , and in angina symptoms as measured by the Canadian Cardiovascular Society Angina Class and Seattle Angina Question naire were all improved by VEGF gene transfer ( all P-values at 12 and 26 weeks ⩽0.001 ) . However , if anything the results of nuclear perfusion imaging favored the control group , although the AdVEGF121 group achieved higher workloads . Overall there was no significant difference in adverse events between the two groups , despite the fact that procedure-related events were seen only in the thoracotomy group . Therefore , administration of AdVEGF121 by direct intramyocardial injections result ed in objective improvement in exercise-induced ischemia in patients with refractory ischemic heart disease OBJECTIVES In the Euroinject One phase II r and omized double-blind trial , therapeutic angiogenesis of percutaneous intramyocardial plasmid gene transfer of vascular endothelial growth factor ( phVEGF-A(165 ) ) on myocardial perfusion , left ventricular function , and clinical symptoms was assessed . BACKGROUND Evidence for safety and treatment efficacy have been presented in phase I therapeutic angiogenesis trials . METHODS Eighty " no-option " patients with severe stable ischemic heart disease , Canadian Cardiovascular Society functional class 3 to 4 , were assigned r and omly to receive , via the NOGA-MyoStar system ( Cordis Corp. , Miami Lakes , Florida ) , either 0.5 mg of phVEGF-A(165 ) ( n = 40 ) or placebo plasmid ( n = 40 ) in the myocardial region showing stress-induced myocardial perfusion defects on (99m)Tc sestamibi/tetrofosmin single-photon emission computed tomography . RESULTS No differences among 
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Furthermore , VEGF gene therapy using adenoviral vectors showed more potential benefit in terms of the risk of serious cardiac events , ΔLVEF , and Canadian Cardiovascular Society angina class .
Nevertheless , mortality and angina frequency scores were not different .
CONCLUSIONS Vascular endothelial growth factor gene therapy appears to be safe and effective regarding serious cardiac events , with greater benefit when using adenoviral vectors .