Treatment of severe aortic valve stenosis in high-risk patients with percutaneous implantation of the CoreValve prosthesis is feasible and associated with a lower mortality rate than predicted by risk algorithms.

Background— The morbidity and mortality of surgical aortic valve replacement are increased in elderly patients with multiple high-risk comorbid conditions. Therefore, a prospective, single-center, nonrandomized study was performed in high-risk patients with aortic valve disease to evaluate the feasibility and safety of percutaneous implantation of a novel self-expanding aortic valve bioprosthesis (CoreValve). Methods and Results— Symptomatic high-risk patients with an aortic valve area <1 cm 2 were considered for enrollment. CoreValve implantation was performed under general anesthesia with extracorporeal support using the retrograde approach. Clinical follow-up and transthoracic echocardiography were performed after the procedure and at days 15 and 30 after device implantation to evaluate short-term patient and device outcomes. A total of 25 patients with symptomatic aortic valve stenosis (mean gradient before implantation, 44.2±10.8 mm Hg) and multiple comorbidities (median logistic EuroScore, 11.0%) were enrolled. Device success and procedural success were achieved in 22 (88%) and 21 (84%) patients, respectively. Successful device implantation resulted in a marked reduction in the aortic valve gradients (mean gradient after implantation, 12.4±3.0 mm Hg; P <0.0001). The mean aortic regurgitation grade was unchanged. Major in-hospital cardiovascular and cerebral events occurred in 8 patients (32%), including mortality in 5 patients (20%). Among 18 patients with device success surviving to discharge, no adverse events occurred within 30 days after leaving the hospital. Conclusions— Percutaneous implantation of the self-expanding CoreValve aortic valve prosthesis in high-risk patients with aortic stenosis with or without aortic regurgitation is feasible and, when successful, results in marked hemodynamic and clinical improvement.

Background-The need for prolonged aspirin and thienopyridine therapy and the risk of stent thrombosis (ST) remain as drawbacks associated with drug-eluting stents. Methods and Results-A prospective observational cohort study was conducted between June 2002 and January 2004 on 3021 patients consecutively and successfully treated in 5389 lesions with drug-eluting stents. Detailed patient information was collected on antiplatelet therapy. We analyzed the incidence of ST throughout the 18-month follow-up period and its relationship with thienopyridine therapy. ST occurred in 58 patients (1.9%) at 18 months. Forty-two patients (1.4%) experienced the event within 6 months of stent implantation. Acute myocardial infarction (fatal or nonfatal) occurred in 46 patients (79%) and death in 23 patients (39%) with ST. The median interval from discontinuation of thienopyridine therapy to ST was 13.5 days (interquartile range 5.2 to 25.7 days) for the first 6 months and 90 days (interquartile range 30 to 365 days) between 6 and 18 months. On multivariable analysis, the strongest predictor for ST within 6 months of stenting was discontinuation of thienopyridine therapy (hazard ratio, 13.74; 95% CI, 4.04 to 46.68; PϽ0.001). Thienopyridine discontinuation after 6 months did not predict the occurrence of ST (hazard ratio, 0.94; 95% CI, 0.30 to 2.98; Pϭ0.92). Conclusions-Discontinuation of thienopyridine therapy was the major determinant of ST within the first 6 months, but insufficient information is available to determine whether there is benefit in continuing a thienopyridine beyond 6 months. (Circulation. 2007;116:745-754.)

Background— Percutaneous aortic valve replacement is a new emerging technology for interventional treatment of severe aortic valve stenosis in surgical high-risk patients. This study was intended to provide a summary of the development and current safety and efficacy status of the self-expanding CoreValve Revalving prosthesis. Method and Results— Between 2005 and 2008, we have enrolled 136 consecutive patients with percutaneous aortic valve replacement using the CoreValve prosthesis. In this prospective nonrandomized, single-center trial, we analyzed procedural outcome, complications and clinical status up to 1 year. First, second, and third generation of the CoreValve prosthesis were implanted in 10, 24, and 102 consecutive high-risk patients (logistic EuroScore: 23.1�15.0%) with severe symptomatic aortic valve stenosis. Mean transvalvular pressure gradient was 41.5�16.7 mm Hg. The procedural success rate increased from generation 1/2 to 3 from 70.0%/70.8% to 91.2% ( P =0.003). The 30-day combined rate of death/stroke/myocardial infarction was 40.0%/20.8%/14.7% ( P =0.11) for generation 1, 2, and 3, with no procedural death in generation 3. Pressure gradients improved significantly with a final mean gradient of 8.1�3.8 mm Hg. Overall functional status assessed by New York Heart Association class improved from 3.3�0.5 (pre) to 1.7�0.7 (post) ( P <0.001) and remained stable in the follow-up. Conclusion— In experienced hands, percutaneous aortic valve replacement with the CoreValve system for selected patients with severe aortic valve stenosis has a high acute success rate associated with a low periprocedural mortality/stroke rate as well as remarkable clinical and hemodynamic improvements, which persist over time. Additional studies are now required to confirm these findings, particularly head-to-head comparisons with surgical valve replacement in different risk populations.

P ulmonary hypertension (PH) frequently coexists with severe aortic stenosis (AS) and confers a worse prognosis.1,2 Transcatheter aortic valve implantation (TAVI) is an alternative therapeutic modality to surgical aortic valve replacement (SAVR) for patients with symptomatic severe AS who are either inoperable or high risk for conventional SAVR.3-5 Patient selection for TAVI relies on clinical and anatomic factors, and risk assessment is a critical component of the procedural planning. 6 Previous studies have shown PH to be a predictor of mortality after TAVI. [7][8][9][10][11] However, studies to date have focused mainly on PH severity rather than hemodynamic presentation and used noninvasive measurements of pulmonary artery systolic pressure (PASP), which correlate only modestly with invasive measurements.12 According toBackground-Pulmonary hypertension (PH) frequently coexists with severe aortic stenosis, and PH severity has been shown to predict outcomes after transcatheter aortic valve implantation (TAVI). The effect of PH hemodynamic presentation on clinical outcomes after TAVI is unknown. Methods and Results-Of 606 consecutive patients undergoing TAVI, 433 (71.4%) patients with severe aortic stenosis and a preprocedural right heart catheterization were assessed. Patients were dichotomized according to whether PH was present (mean pulmonary artery pressure, ≥25 mm Hg; n=325) or not (n=108). Patients with PH were further dichotomized by left ventricular end-diastolic pressure into postcapillary (left ventricular end-diastolic pressure, >15 mm Hg; n=269) and precapillary groups (left ventricular end-diastolic pressure, ≤15 mm Hg; n=56). Finally, patients with postcapillary PH were divided into isolated (n=220) and combined (n=49) subgroups according to whether the diastolic pressure difference (diastolic pulmonary artery pressure−left ventricular end-diastolic pressure) was normal (<7 mm Hg) or elevated (≥7 mm Hg). Primary end point was mortality at 1 year. PH was present in 325 of 433 (75%) patients and was predominantly postcapillary (n=269/325; 82%

Transcatheter aortic valve implantation without balloon pre-dilation is feasible and safe, resulting in similar acute safety and efficacy as the current standard approach of TAVI with pre-dilation.

The Jostent coronary stent graft (CSG) is composed of a PTFE layer sandwiched between two stainless steel stents, initially introduced for the treatment of coronary perforations and aneurysms with excellent results. By providing a mechanical barrier, this stent design also may be beneficial in the treatment of complex ulcerated lesions and in-stent restenosis by preventing debris protrusion and neointimal proliferation through the stent struts. To evaluate the safety and efficacy of this stent graft, we implanted 78 CSGs in 70 patients for a broad range of indications, including coronary perforations, aneurysms, degenerated saphenous vein grafts, complex lesions, and in-stent restenosis. The primary angiographic success rate (95.9%) was high, and using intravascular ultrasound (IVUS) guidance during stent implantation and high inflation pressures (19.3 +/- 3.2 atm), stent expansion with optimal symmetry was achieved in 94.7%. One limitation of the Jostent CSG was the side-branch occlusion rate (18.6%) and the resulting non-Q-wave infarction rate in seven cases (mean CK elevation, 238 U/l), acute Q-wave MI in two cases, and transient ventricular fibrillation in one patient after occlusion of the proximal RCA side branch without further complications. Subacute stent thrombosis occurred in four cases (5.7%) 7 to 70 days after stent implantation, despite using combined antiplatelet therapy with aspirin (ASA), ticlopidine, and/or clopidogrel for 30 days. Angiographic follow-up was available in 56 patients (80.0%) after a mean of 159 +/- 49 days, and follow-up IVUS was available in 38 cases. The overall restenosis rate (> 50% diameter stenosis) was 31.6% manifest primarily as edge restenosis (29.8% stent edge vs. 8.8% stent center; P < 0.001). IVUS examinations showed a minimal late lumen loss of 0.4 +/- 2.2 mm(2) within the center of the stent graft vs. 3.2 +/- 2.3 mm(2) at the stent edges (P < 0.001). The restenosis rate in the prespecified subgroups was 33.3% for saphenous vein grafts (2/6 lesions), 30.0% in complex lesions (6/20 lesions), and 38.5% (10/26 lesions) for the treatment of in-stent restenosis. Implantation of the Jostent CSG is feasible and safe, even in complex lesion subsets, and is associated with high primary success rates provided major side branches are avoided. The use of this stent may require an extended time course of antiplatelet therapy. Frequent focal stent edge renarrowing influences the overall restenosis rate. However, in treatment of complex in-stent restenosis and vein graft lesions, stent grafts may offer benefit over conventional therapies. Covered stents such as the JoMed coronary stent graft may become essential for bailout treatment of coronary perforations.

Background-The molecular pathophysiology of coronary artery disease (CAD) includes cytokine release and a localized inflammatory response within the vessel wall. The extent to which CAD and its severity is reflected by gene expression in circulating cells is unknown. Key Words: gene expression Ⅲ coronary disease Ⅲ blood, peripheral Ⅲ atherosclerosis Ⅲ leukocytes Ⅲ polymerase chain reaction Ⅲ stenosis C oronary artery disease (CAD) and sequelae of atherosclerotic disease such as stroke and myocardial infarction are the largest source of morbidity and mortality in the developed world. The risk of developing CAD events over time can be estimated with clinical factors and family history, as in the Framingham Risk Score. 1 For patients with suspicious clinical histories, extant coronary disease may be diagnosed by indirect methods, including nuclear perfusion imaging and computed tomography angiography, but coronary angiography remains the "gold standard." These tests have drawbacks, including radiation exposure, contrast agent allergy, nephrotoxicity, and, in the case of coronary angiography, invasiveness of the procedure. Therefore, the development of a blood test that reliably identified patients with CAD would have diagnostic utility. Methods and Results-From Editorial see p 7 Clinical Perspective see p 38The cellular and molecular basis of atherosclerotic plaque development has a systemic inflammatory component involving primarily monocytes/macrophages and CD4 ϩ T cells. 2,3 Oxidized lipids initiate the process with subsequent responses by endothelial, vascular smooth muscle cells, and circulating cells. Peripheral-blood studies have identified gene expression signatures that are correlated with the presence of systemic inflammatory and immune-mediated disorders, as well as cardiovascular diseases, 4 suggesting that such an approach might be useful for CAD. However, although investigators have identified profiles for atherosclerosis directly from arterial wall samples in murine models and human atheroma samples, 5-9 it is unclear whether such localized processes are detectable or their severity reflected in the peripheral circulation. As a first step, we sought to identify genes for which expression levels distinguished patients with and without significant coronary artery stenosis. We approached this problem by microarray analysis on an angiographically defined patient cohort to identify a set of discriminatory genes. We then replicated these results using real-time polymerase chain reaction (RT-PCR) on 2 addi-