Left Ventricular Electromechanical Mapping to Assess Efficacy of phVEGF165 Gene Transfer for Therapeutic Angiogenesis in Chronic Myocardial Ischemia

PR Vale, DW Losordo, CE Milliken, M Maysky… - Circulation, 2000 - Am Heart Assoc
PR Vale, DW Losordo, CE Milliken, M Maysky, DD Esakof, JF Symes, JM Isner
Circulation, 2000Am Heart Assoc
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 (phVEGF165), 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) …
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 (phVEGF165), 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 phVEGF165 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) phVEGF165 GTx. The area of ischemic myocardium was consequently reduced from 6.45±1.37 cm2 before GTx to 0.95±0.41 cm2 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 phVEGF165 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 phVEGF165 GTx may successfully rescue foci of hibernating myocardium.
Am Heart Assoc