TCEP was safe, captured embolic debris in 99% of patients, and did not change neurocognitive function. Reduction in new lesion volume on magnetic resonance scans was not statistically significant. (Cerebral Protection in Transcatheter Aortic Valve Replacement [SENTINEL]; NCT02214277).
The rest period for coronary arteries in the cardiac cycle varies substantially from patient to patient, which may cause quality to be inconsistent in current coronary MR angiography. A cardiac motion image prior to coronary data acquisition (preimage) may be used to estimate the optimal duration and timing in the cardiac cycle for coronary MR angiography.
Background
—Therapeutic angiogenesis, a new experimental strategy for the treatment of vascular insufficiency, uses the administration of mediators known to induce vascular development in embryogenesis to induce neovascularization of ischemic adult tissues. This report summarizes a phase I clinical experience with a gene-therapy strategy that used an E1
−
E3
−
adenovirus (Ad) gene-transfer vector expressing human vascular endothelial growth factor (VEGF) 121 cDNA (Ad
GV
VEGF121.10) to induce therapeutic angiogenesis in the myocardium of individuals with clinically significant coronary artery disease.
Methods and Results
—Ad
GV
VEGF121.10 was administered to 21 individuals by direct myocardial injection into an area of reversible ischemia either as an adjunct to conventional coronary artery bypass grafting (group A, n=15) or as sole therapy via a minithoracotomy (group B, n=6). There was no evidence of systemic or cardiac-related adverse events related to vector administration. In both groups, coronary angiography and stress sestamibi scan assessment of wall motion 30 days after therapy suggested improvement in the area of vector administration. All patients reported improvement in angina class after therapy. In group B, in which gene transfer was the only therapy, treadmill exercise assessment suggested improvement in most individuals.
Conclusions
—The data are consistent with the concept that direct myocardial administration of Ad
GV
VEGF121.10 to individuals with clinically significant coronary artery disease appears to be well tolerated, and initiation of phase II evaluation of this therapy is warranted.
Cells proliferating from human atherosclerotic lesions are resistant to the antiproliferative effect of TGF- 1, a key factor in wound repair. DNA from human atherosclerotic and restenotic lesions was used to test the hypothesis that microsatellite instability leads to specific loss of the Type II receptor for TGF- 1 (T  R-II), causing acquired resistance to TGF- 1. High fidelity PCR and restriction analysis was adapted to analyze deletions in an A 10 microsatellite within T  R-II. DNA from lesions, and cells grown from lesions, showed acquired 1 and 2 bp deletions in T  R-II, while microsatellites in the hMSH3 and hMSH6 genes, and hypermutable regions of p53 were unaffected. Sequencing confirmed that these deletions occurred principally in the replication error-prone A 10 microsatellite region, though nonmicrosatellite mutations were observed. The mutations could be identified within specific patches of the lesion, while the surrounding tissue, or unaffected arteries, exhibited the wild-type genotype. This microsatellite deletion causes frameshift loss of receptor function, and thus, resistance to the antiproliferative and apoptotic effects of TGF- 1. We propose that microsatellite instability in T  R-II disables growth inhibitory pathways, allowing monoclonal selection of a disease-prone cell type within some vascular lesions. ( J. Clin. Invest. 1997.
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