3-year follow-up of 100 consecutive coronary bifurcation lesions treated with Taxus stents and the crush technique.

OBJECTIVES: To determine the 3 year safety and efficacy of crush-stenting with paclitaxel-eluting stents. BACKGROUND: The optimum two-stent strategy for treatment of coronary bifurcation lesions is undetermined. Crush-stenting is advocated to minimize restenosis through complete circumferential stent coverage; long-term follow-up data are lacking. METHODS AND RESULTS: In a single center prospective registry, 100 consecutive patients with bifurcation lesions were treated with the Crush technique. The vast majority (93%) were true bifurcations, predominantly involving the left anterior descending and diagonal arteries. Technical success was 98%. Final kissing balloon dilatation, which became standard practice during the study, was attempted in 68 patients and successful in 51. Abciximab was used in all cases. There were no peri-procedural stent thromboses. Follow-up was 100% at 3 years. Symptom-driven target lesion revascularisation was 8% at 3 years. Cumulative 3-year major adverse cardiac events was 28% (7 cardiac deaths, 15 myocardial infarctions, 11 target vessel revascularisations). Absence of a final kissing inflation predicted repeat revascularisation but not death, infarction or stent thrombosis. Three probable stent thromboses occurred, of which two were very late. CONCLUSION: Where a two-stent bifurcation strategy is required, Crush-stenting with paclitaxel-eluting stents is safe and effective in the long-term. Failure to perform a final kissing dilatation increases the likelihood of revascularisation but not other adverse events.

Genetic analysis of pathways regulated by the von Hippel-Lindau tumor suppressor in Caenorhabditis elegans.

The von Hippel-Lindau (VHL) tumor suppressor functions as a ubiquitin ligase that mediates proteolytic inactivation of hydroxylated alpha subunits of hypoxia-inducible factor (HIF). Although studies of VHL-defective renal carcinoma cells suggest the existence of other VHL tumor suppressor pathways, dysregulation of the HIF transcriptional cascade has extensive effects that make it difficult to distinguish whether, and to what extent, observed abnormalities in these cells represent effects on pathways that are distinct from HIF. Here, we report on a genetic analysis of HIF-dependent and -independent effects of VHL inactivation by studying gene expression patterns in Caenorhabditis elegans. We show tight conservation of the HIF-1/VHL-1/EGL-9 hydroxylase pathway. However, persisting differential gene expression in hif-1 versus hif-1; vhl-1 double mutant worms clearly distinguished HIF-1-independent effects of VHL-1 inactivation. Genomic clustering, predicted functional similarities, and a common pattern of dysregulation in both vhl-1 worms and a set of mutants (dpy-18, let-268, gon-1, mig-17, and unc-6), with different defects in extracellular matrix formation, suggest that dysregulation of these genes reflects a discrete HIF-1-independent function of VHL-1 that is connected with extracellular matrix function.