The Rho/rho-kinase (ROCK) pathway has an important role in the pathogenesis of several cardiovascular diseases. The activation of ROCK is involved in the regulation of vascular tone, endothelial dysfunction, inflammation and remodeling. The inhibition of ROCK has a beneficial effect in a variety of cardiovascular disorders. Evidence from animal models and from clinical use of ROCK inhibitors, such as Y-27632, fasudil and statins (i.e. pleiotropic effects), supports the hypothesis that ROCK is a potential therapeutic target. This review provides a current understanding of the role of ROCK pathway in the regulation of vascular function and the use of ROCK inhibitors in the treatment of cardiovascular disorders.

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Our preliminary data suggested LAA closure with ACP is safe, feasible with encouraging 1-yr clinical outcomes. Further large-scaled trials are needed to confirm the efficacy of this device.

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Background: Left atrial appendage (LAA) occlusion is an alternative to anticoagulation for stroke prevention in patients with atrial fibrillation. Accurate device sizing is crucial for optimal outcome. Patient-specific LAA models can be created using three-dimensional (3D) printing from 3D transesophageal echocardiographic (TEE) images, allowing in vitro model testing for device selection. The aims of this study were to assess the association of model-based device selection with procedural safety and efficacy and to determine if preprocedural model testing leads to superior outcomes. Methods: In 72 patients who underwent imaging-guided LAA occlusion, 3D models of the LAA were created from 3D TEE data sets retrospectively (retrospective cohort). The optimal device determined by in vitro model testing was compared with the actual device used. Associations of model-match and model-mismatch device sizing with outcomes were analyzed. In another 32 patients, device selection was prospectively guided by 3D models in adjunct to imaging (prospective cohort). The impact of model-based sizing on outcomes was assessed by comparing the two cohorts. Results: Patients in the retrospective cohort with model-mismatch sizing had longer procedure times, more implantation failures, more devices used per procedure, more procedural complications, more peridevice leak, more device thrombus, and higher cumulative incidence rates of ischemic stroke and cardiovascular or unexplained death (P < .05 for all) over 3.0 6 2.3 years after LAA occlusion. Compared with the retrospective imaging-guided cohort, the prospective model-guided patients achieved higher implantation success and shorter procedural times (P < .05) without complications. Clinical device compression (r = 0.92) and protrusion (r = 0.95) agreed highly with model testing (P < .0001). Predictors for sizing mismatch were nonwindsock morphology (odds ratio, 4.7) and prominent LAA trabeculations (odds ratio, 7.1). Conclusions: In patients undergoing LAA occlusion, device size selection in agreement with 3D-printed modelbased sizing is associated with improved safety and efficacy. Preprocedural device sizing with 3D models in adjunct to imaging guidance may lead to superior outcomes.

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It is postulated that the source of thromboembolism in 90% of patients with non-valvular atrial fibrillation (AF) arises from the left atrial appendage (LAA). Anticoagulation with warfarin is the standard medical therapy for stroke prevention in patients with AF. However, chronic warfarin therapy is contraindicated in 14 to 44% of patients with AF who are at risk for stroke. Mechanical exclusion of the LAA may prevent thrombus formation in the appendage and hence reduce the risk of stroke. Recently, several studies of percutaneous transcatheter delivery of dedicated LAA exclusion devices such as the PLAATO device, Watchman device and the Amplatzer cardiac plug, have shown encouraging results as an alternative to warfarin therapy for selected patients. This article aims to review the current evidence for LAA exclusion in patients with AF.

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