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- Sarkar, N., et al.
(författare)
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Effects of intramyocardial injection of phVEGF-A(165) as sole therapy in patients with refractory coronary artery disease - 12-month follow-up : Angiogenic gene therapy
- 2001
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 250:5, s. 373-381
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To test the safety and bioactivity of phVEGF-A(165) after intramyocardial injection during 12-month follow-up. Design. Open-labelled study. Subjects. Inclusion criteria were angina pectoris, Canadian Cardiovascular Society (CCS) class III-IV, unamenable to further revascularization, ejection fraction (EF) >30%, perfusion defects extending over >10% of the anterolateral left ventricle wall detectable with adenosine single photon emission computerized tomography (SPECT) and at least one patent vessel visible by coronary angiography. Seven of 39 patients referred for gene therapy were included. Intervention. Via a mini-thoracotomy under general anaesthesia, phVEGF-A(165) was injected directly into the myocardium at four sites in the anterolateral region of the left ventricle. Results. Operative procedures were uneventful. Perioperative release of myocardial markers and electrocardiogram (ECG) changes were detected in two patients. There were no perioperative deaths but one patient died 7 months postoperatively because of myocardial infarction. Plasma vascular endothelial growth factor (VEGF)-A levels increased two to threefold peaking 6 days postoperatively (P<0.004) and returning to baseline by day 30. A significant reduction in angina pectoris was reported. The CCS class improved from 3.30.2 to 1.9 +/-0.3 (P<0.01) and nitroglycerine intake decreased from 3915 to 12 +/-5 tablets week(-1) (P<0.001) 2 months after gene transfer. Improvements remained after 12 months when nitroglycerine consumption approached zero. Improved myocardial function in the phVEGF-A(165) injection region was documented in all patients (P<0.016) by tissue velocity imaging (TVI). Reduced reversible ischaemia was detected by adenosine SPECT in four patients. Improved collateralization was detected in four patients with coronary angiography. Conclusion. Intramyocardial injection of phVEGF-A(165) is safe and may lead to improved myocardial perfusion and function with longstanding symptomatic relief in end-stage angina pectoris. Based on these results this therapeutic potential is being tested in a double-blind placebo controlled multicentre trial, EUROINJECT ONE.
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| 2. |
- Sylven, C., et al.
(författare)
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Myocardial Doppler tissue velocity improves following myocardial gene therapy with VEGF-A(165) plasmid in patients with inoperable angina pectoris
- 2001
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Ingår i: Coronary Artery Disease. - : Ovid Technologies (Wolters Kluwer Health). - 0954-6928 .- 1473-5830. ; 12:3, s. 239-243
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Tidskriftsartikel (refereegranskat)abstract
- Background Myocardial tissue velocity and perfusion were studied in patients with severe angina pectoris following gene therapy by intramyocardial injection of phVEGF-A(165) via thoracotomy. Plasma concentrations of VEGF-A increased postoperatively. Two months after treatment anginal status and myocardial tissue velocity improved and perfusion showed a tendency to improve. Tissue velocity imaging appears to be a sensitive, objective method for detecting changes in myocardial function following gene therapy. Objective To study effects on myocardial tissue velocity and perfusion in patients with angina pectoris following intramyocardial injection of phVEGF-A(165) via thoracotomy. Design Open label, phase I/II. Methods Six patients with Canadian Cardiovascular Society (CCS) angina pectoris functional Glass III - IV and with major defects at adenosine stress single-photon emission computerized tomography (SPECT) were studied. In addition to SPECT, coronary angiography and dobutamine stress echocardiography with tissue Doppler velocity imaging were performed before and two months after gene transfer. Results Plasma concentrations of VEGF-A increased 2 to 3 times (P < 0.04) over baseline from 2 to 14 days after injection with normalization after 4 weeks. The CCS class improved about 40%, from 3.3 +/- 0.2 to 2.0 +/- 0.3 (P < 0.02) and nitroglycerine consumption decreased 30 - 40%, from 44 +/- 17 to 15 +/- 5 tablets per week (P < 0.05). The maximal systolic myocardial tissue velocity increased in all patients about 25% (P < 0.02) but did not reach the reference range. Myocardial perfusion at SPECT improved in four of the six patients. Conclusions Anginal status, myocardial tissue velocity and perfusion can be improved by phVEGF-A(165) intramyocardial injection. Tissue velocity imaging appears to be a sensitive, objective method for detecting changes in myocardial function following gene therapy. Coron Artery Dis 12:239-243
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