Gene therapy for myocardial angiogenesis - Initial clinical results with direct myocardial injection of phVEGF(165) as sole therapy for myocardial ischemia

Citation
Dw. Losordo et al., Gene therapy for myocardial angiogenesis - Initial clinical results with direct myocardial injection of phVEGF(165) as sole therapy for myocardial ischemia, CIRCULATION, 98(25), 1998, pp. 2800-2804
Citations number
19
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Journal title
CIRCULATION
ISSN journal
0009-7322 → ACNP
Volume
98
Issue
25
Year of publication
1998
Pages
2800 - 2804
Database
ISI
SICI code
0009-7322(199812)98:25<2800:GTFMA->2.0.ZU;2-C
Abstract
Background-We initiated a phase I clinical study to determine the safety an d bioactivity of direct myocardial gene transfer of vascular endothelial gr owth factor (VEGF) as sole therapy for patients with symptomatic myocardial ischemia. Methods and Results-VEGF gene transfer (GTx) was performed in 5 patients (a ll male, ages 53 to 71) who had failed conventional therapy; these men had angina (determined by angiographically documented coronary artery disease). Naked plasmid DNA encoding VEGF (phVEGF(165)) was injected directly into t he ischemic myocardium via a mini left anterior thoracotomy. Injections cau sed no changes in heart rate (pre-GTx = 75 +/- 15/min versus post-GTx = 80 +/- 16/min, P=NS), systolic BP (114+/-7 versus 118+/-7 mm Hg, P=NS), or dia stolic BP (57+/-2 versus 59+/-2 mm Hg, P=NS). Ventricular arrhythmias were limited to single unifocal premature beats at the moment of injection. Seri al ECGs showed no evidence of new myocardial infarction in any patient. Int raoperative blood loss was 0 to 50 cm(3), and total chest tube drainage was 110 to 395 cm(3). Postoperative cardiac output fell transiently but increa sed within 24 hours (preanesthesia=4.8+/-0.4 versus postanesthesia=4.1+/-0. 3 versus 24 hours postoperative=6.3+/-0.8, P=0.02). Time to extubation afte r closure was 18.4+/-1.4 minutes; average postoperative hospital stay was 3 .8 days. All patients had significant reduction in angina (nitroglycerin [N TG] use=53.9+/-10.0/wk pre-GTx versus 9.8+/-6.9/wk post-GTx, P<0.03). Posto perative left ventricular ejection fraction (LVEF) was either unchanged (n= 3) or improved (n=2, mean increase in LVEF=5%), Objective evidence of reduc ed ischemia was documented using dobutamine single photon emission computed tomography (SPECT)-sestamibi imaging in all patients. Coronary angiography showed improved Rentrop score in 5 of 5 patients. Conclusions-This initial experience with naked gene transfer as sole therap y for myocardial ischemia suggests that direct myocardial injection of nake d plasmid DNA, via a minimally invasive chest wall incision, is safe and ma y lead to reduced symptoms and improved myocardial perfusion in selected pa tients with chronic myocardial ischemia.