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(Circulation. 2005;112:I-157 – I-165.)
© 2005 American Heart Association, Inc.

Cell Transplantation and Tissue Engineering

NOGA-Guided Analysis of Regional Myocardial Perfusion Abnormalities Treated With Intramyocardial Injections of Plasmid Encoding Vascular Endothelial Growth Factor A-165 in Patients With Chronic Myocardial Ischemia

Subanalysis of the EUROINJECT-ONE Multicenter Double-Blind Randomized Study

Mariann Gyöngyösi, MD, PhD; Aliasghar Khorsand, BS; Sholeh Zamini, BS; Wolfgang Sperker, MD; Christoph Strehblow, MD; Jens Kastrup, MD; Eric Jorgensen, MD; Birger Hesse, MD; Kristina Tägil, MD; Hans Erik Bøtker, MD; Witold Ruzyllo, MD; Anna Teresiñska, MD; Dariusz Dudek, MD; Alicja Hubalewska, MD; Andreas Rück, MD; Søren Steen Nielsen, MD; Senta Graf, MD; Gerald Mundigler, MD; Jacek Novak, MD; Heinz Sochor, MD, FESC; Gerald Maurer, MD; Dietmar Glogar, MD, FESC; Christer Sylven, MD

From the Division of Cardiology, Department of Internal Medicine II, University of Vienna, Vienna, Austria (M.G., A.K., S.Z., W.S., C. Strehblow, S.G., G. Mundigler, H.S., G. Maurer, D.G.); Cardiac Catheterization Laboratory (J.K., E.J.) and Department of Clinical Physiology (B.H., K.T.), University Hospital Rigshospitalet, Copenhagen, Denmark; Department of Cardiology, Skejby Sygehus, Aarhus, Denmark (H.E.B., S.S.N.); Institute of Cardiology, Warsaw, Poland (W.R., A.T.); Institute of Cardiology, Krakow, Poland (D.D., A.H.); and Department of Physiology (J.N.) and Department of Cardiology and Gene Therapy Center (A.R., C. Sylven), Karolinska University Hospital at Huddinge, Karolinska Institutet, Stockholm, Sweden.

Correspondence to Mariann Gyöngyösi, MD, PhD, Division of Cardiology, Department of Internal Medicine II, University of Vienna, Wahringer Gürtel 18-20, A-1090 Vienna, Austria. E-mail mariann.gyongyosi{at}meduniwien.ac.at

Background— The aim of this substudy of the EUROINJECT-ONE double-blind randomized trial was to analyze changes in myocardial perfusion in NOGA-defined regions with intramyocardial injections of plasmid encoding plasmid human (ph)VEGF-A₁₆₅ using an elaborated transformation algorithm.

Methods and Results— After randomization, 80 no-option patients received either active, phVEGF-A₁₆₅ (n=40), or placebo plasmid (n=40) percutaneously via NOGA-Myostar injections. The injected area (region of interest, ROI) was delineated as a best polygon by connecting of the injection points marked on NOGA polar maps. The ROI was projected onto the baseline and follow-up rest and stress polar maps of the 99m-Tc-sestamibi/tetrofosmin single-photon emission computed tomography scintigraphy calculating the extent and severity (expressed as the mean normalized tracer uptake) of the ROI automatically. The extents of the ROI were similar in the VEGF and placebo groups (19.4±4.2% versus 21.5±5.4% of entire myocardium). No differences were found between VEGF and placebo groups at baseline with regard to the perfusion defect severity (rest: 69±11.7% versus 68.7±13.3%; stress: 63±13.3% versus 62.6±13.6%; and reversibility: 6.0±7.7% versus 6.7±9.0%). At follow-up, a trend toward improvement in perfusion defect severity at stress was observed in VEGF group as compared with placebo (68.5±11.9% versus 62.5±13.5%, P=0.072) without reaching normal values. The reversibility of the ROI decreased significantly at follow-up in VEGF group as compared with the placebo group (1.2±9.0% versus 7.1±9.0%, P=0.016). Twenty-one patients in VEGF and 8 patients in placebo group (P<0.01) exhibited an improvement in tracer uptake during stress, defined as a 5% increase in the normalized tracer uptake of the ROI.

Conclusions— Projection of the NOGA-guided injection area onto the single-photon emission computed tomography polar maps permits quantitative evaluation of myocardial perfusion in regions treated with angiogenic substances. Injections of phVEGF A₁₆₅ plasmid improve, but do not normalize, the stress-induced perfusion abnormalities.

Key Words: angiogenesis • mapping • gene therapy • perfusion • scintigraphy

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