Pr. Vale et al., Left ventricular electromechanical mapping to assess efficacy of phVEGP(165) gene transfer for therapeutic angiogenesis in chronic myocardial ischemia, CIRCULATION, 102(9), 2000, pp. 965-974
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Background-NOGA left ventricular (LV) electromechanical mapping (EMM) can b
e used to distinguish among infarcted, ischemic, and normal myocardium. We
investigated the use of percutaneous LV EMM to assess the efficacy of myoca
rdial gene transfer (GTx) of naked plasmid DNA encoding for vascular endoth
elial growth factor (phVEGF(165)), administered during surgery by direct my
ocardial 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 documente
d coronary artery disease, all of whom had failed conventional therapy (dru
gs, PTCA, and/or CABG), were treated with direct myocardial injection of ph
VEGF(165) via a minithoracotomy. Foci of ischemic myocardium were identifie
d on LV EMM by preserved viability associated with an impairment in linear
local shortening, Myocardial viability, defined by mean unipolar and bipola
r voltage recordings greater than or equal to 5 and greater than or equal t
o 2 mV, respectively, did not change significantly after GTx. Analysis of l
inear 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 consequentl
y 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 calcu
lated from single-photon emission CT-sestamibi myocardial perfusion scans r
ecorded 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(16
5) GTx augments perfusion of ischemic myocardium. These findings, together
with reduction in the size of the defects documented at rest by serial sing
le-photon emission CT-sestamibi imaging, suggest that phVEGF(165) GTx may s
uccessfully rescue foci of hibernating myocardium.