Document Detail

Left ventricular electromechanical mapping to assess efficacy of phVEGF(165) gene transfer for therapeutic angiogenesis in chronic myocardial ischemia.
MedLine Citation:
PMID:  10961959     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: NOGA left ventricular (LV) electromechanical mapping (EMM) can be used to distinguish among infarcted, ischemic, and normal myocardium. We investigated the use of percutaneous LV EMM to assess the efficacy of myocardial gene transfer (GTx) of naked plasmid DNA encoding for vascular endothelial growth factor (phVEGF(165)), administered during surgery by direct myocardial injection in patients with chronic myocardial ischemia. METHODS AND RESULTS: A total of 13 consecutive patients (8 men, mean age 60.1+/-2. 3 years) with chronic stable angina due to angiographically documented coronary artery disease, all of whom had failed conventional therapy (drugs, PTCA, and/or CABG), were treated with direct myocardial injection of phVEGF(165) via a minithoracotomy. Foci of ischemic myocardium were identified on LV EMM by preserved viability associated with an impairment in linear local shortening. Myocardial viability, defined by mean unipolar and bipolar voltage recordings >/=5 and >/=2 mV, respectively, did not change significantly after GTx. Analysis of linear local shortening in areas of myocardial ischemia, however, disclosed significant improvement after (15.26+/-0.98%) versus before (9.94+/-1.53%, P:=0. 004) phVEGF(165) GTx. The area of ischemic myocardium was consequently reduced from 6.45+/-1.37 cm(2) before GTx to 0.95+/-0. 41 cm(2) after GTx (P:=0.001). These findings corresponded to improved perfusion scores calculated from single-photon emission CT-sestamibi myocardial perfusion scans recorded at rest (7.4+/-2.1 before GTx versus 4.5+/-1.4 after GTx, P:=0.009) and after pharmacological stress (12.8+/-2.7 before GTx versus 8.5+/-1.7 after GTx, P:=0.047). CONCLUSIONS: The results of EMM constitute objective evidence that phVEGF(165) GTx augments perfusion of ischemic myocardium. These findings, together with reduction in the size of the defects documented at rest by serial single-photon emission CT-sestamibi imaging, suggest that phVEGF(165) GTx may successfully rescue foci of hibernating myocardium.
P R Vale; D W Losordo; C E Milliken; M Maysky; D D Esakof; J F Symes; J M Isner
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Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Circulation     Volume:  102     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2000 Aug 
Date Detail:
Created Date:  2000-09-14     Completed Date:  2000-09-14     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  965-74     Citation Subset:  IM    
Division of Cardiology and Vascular Medicine, St. Elizabeth's Medical Center, Boston, MA 02135, USA.
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MeSH Terms
Angiogenesis Inducing Agents / therapeutic use
Coronary Circulation / drug effects
Electrocardiography / methods
Endothelial Growth Factors / genetics*,  therapeutic use
Gene Therapy / methods*
Gene Transfer Techniques
Heart / physiopathology,  radionuclide imaging
Lymphokines / genetics*,  therapeutic use
Middle Aged
Myocardial Ischemia / physiopathology,  radionuclide imaging,  therapy*
Neovascularization, Physiologic*
Plasmids / therapeutic use
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
Ventricular Function, Left
Reg. No./Substance:
0/Angiogenesis Inducing Agents; 0/Endothelial Growth Factors; 0/Lymphokines; 0/Vascular Endothelial Growth Factor A; 0/Vascular Endothelial Growth Factors
Comment In:
Circulation. 2000 Aug 29;102(9):940-2   [PMID:  10961953 ]

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