Left ventricular electromechanical mapping to assess efficacy of phVEGF(165) gene transfer for therapeutic angiogenesis in chronic myocardial ischemia.

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
Abstract/OtherAbstract:	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.

Authors:	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
Affiliation:	Division of Cardiology and Vascular Medicine, St. Elizabeth's Medical Center, Boston, MA 02135, USA.
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MeSH Terms
Descriptor/Qualifier:	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 Humans Lymphokines / genetics, therapeutic use Male Microinjections Middle Aged Myocardial Ischemia / physiopathology, radionuclide imaging, therapy Neovascularization, Physiologic* Plasmids / therapeutic use Thoracotomy Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors Ventricular Function, Left
Chemical
Reg. No./Substance:	0/Angiogenesis Inducing Agents; 0/Endothelial Growth Factors; 0/Lymphokines; 0/Vascular Endothelial Growth Factor A; 0/Vascular Endothelial Growth Factors
Comments/Corrections
Comment In:	Circulation. 2000 Aug 29;102(9):940-2 [PMID: 10961953 ]

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