Percutaneous valve replacement may be an alternative to conventional open heart surgery in selected high-risk patients with severe symptomatic aortic stenosis.

R educed plasma levels of high-density lipoprotein (HDL) cholesterol are associated with an increased risk of coronary artery disease (CAD).1 Moreover, in patients with CAD that are treated with statin and have low levels of low-density lipoprotein (LDL) cholesterol, reduced HDL cholesterol levels were predictive of major cardiovascular events.2 Besides promoting reverse cholesterol transport, 3,4 HDL has been demonstrated to exert antiatherosclerotic effects, including antiinflammatory properties and stimulation of endothelial nitric oxide (NO) production. [5][6][7][8][9] However, these effects of HDL have been observed to be highly heterogenous in patients with CAD or diabetes mellitus. 10-12 Editorial see p 868 Clinical Perspective on p 904Endothelial dysfunction and injury are thought to contribute importantly to the progression of CAD. [13][14][15] Experimental studies have indicated that atherosclerotic lesion-prone vascular regions are characterized by a high endothelial cell turnover, 16 which has been attributed to an increased rate of endothelial cell apoptosis. Moreover, superficial atherosclerotic plaque erosion with the loss of an intact endothelial cell monolayer is observed quite frequently in patients with an acute coronary syndrome (ACS) based on pathological studies, 17,18 and on Background-Endothelial dysfunction and injury are thought to play an important role in the progression of coronary artery disease (CAD). High-density lipoprotein from healthy subjects (HDL Healthy ) has been proposed to exert endothelial antiapoptotic effects that may represent an important antiatherogenic property of the lipoprotein. The present study therefore aimed to compare effects of HDL CAD and HDL Healthy on the activation of endothelial anti-and proapoptotic pathways and to determine which changes of the lipoprotein are relevant for these processes. Methods and Results-HDL was isolated from patients with stable CAD (HDL sCAD ), an acute coronary syndrome (HDL ACS ), and healthy subjects. HDL Healthy induced expression of the endothelial antiapoptotic Bcl-2 protein Bcl-xL and reduced endothelial cell apoptosis in vitro and in apolipoprotein E-deficient mice in vivo. In contrast, HDL sCAD and HDL ACS did not inhibit endothelial apoptosis, failed to activate endothelial Bcl-xL, and stimulated endothelial proapoptotic pathways, in particular, p38-mitogen-activated protein kinase-mediated activation of the proapoptotic Bcl-2 protein tBid. Endothelial antiapoptotic effects of HDL Healthy were observed after inhibition of endothelial nitric oxide synthase and after delipidation, but not completely mimicked by apolipoprotein A-I or reconstituted HDL, suggesting an important role of the HDL proteome. HDL proteomics analyses and subsequent validations and functional characterizations suggested a reduced clusterin and increased apolipoprotein C-III content of HDL sCAD and HDL ACS as mechanisms leading to altered effects on endothelial apoptosis. Conclusions-The present study demonstrates for the first time that HDL CAD d...

PAVI provided superior hemodynamic performance compared with the surgical bioprostheses in terms of transprosthetic gradient and prevention of severe prosthesis-patient mismatch, but was associated with a higher incidence of AR.