Stroke & cognition in surgical aortic stenosis

描述(申请人提供)：背景：钙化性主动脉狭窄(AS)是美国主要的瓣膜疾病。随着人口老龄化，确诊需要主动脉瓣置换术(AVR)的患者数量迅速增加。栓子与大多数中风和心脏手术后认知功能障碍(POCD)有关。表现为AS的AVR的患者被定义为术后中风的“特殊”风险亚组(10%)，40%的患者遭受多个脑血栓事件。这些患者在短期内还面临POCD和/或继发于这些多发性脑梗塞的血管认知障碍的风险，并可能面临加速发展为长期血管性痴呆的风险。这是一个关键人群，不仅需要研究中风和POCD的发病机制，而且还可以有效地证明神经保护干预的成败。目的：1)研究老年AS患者AVR术后卒中和短暂性脑缺血事件的发生率及转归；2)采用弥散加权磁共振成像(DWI)技术，确定AVR术后脑缺血事件的替代成像生物标志物的有效性；AIM-3)研究老年AS患者AVR术后认知功能的变化，并与年龄/疾病匹配的对照组进行比较。相关性：手术后中风预示着早期死亡率增加5-10倍，而69%的患者遭受严重残疾。在普通中风人群中，早期诊断和有组织的早期干预方法对预后产生了深远的影响，在治疗方面取得了进展。奇怪的是，在一个中风发生不仅频繁而且可预测的“被俘”人群中，很少存在有组织的方法来监测心脏手术后的中风。(AVR后报告的中风发病率的5倍差异非常能说明问题。)相反，有了密切监测的机会，可以合理地预期快速干预/神经保护的益处将超过普通人群的益处。由于设计不当，神经保护试验以惊人的速度失败。设计适当动力研究的一个关键因素是准确地知道要研究的结果的频率。准确计算两个重要的缺血性终点--卒中和POCD的风险，将为未来的试验奠定基础。验证AVR、DWI-MRI损伤后卒中的潜在成像替代物，可能允许在小得多的人群中有效地进行“概念验证”研究。先进的成像方法结合详细的认知分析可能会加深我们对POCD发病机制的理解。最后，研究数据库将使我们能够仔细检查心脏手术期间栓塞过程中认知障碍和痴呆症的长期风险。

DESCRIPTION (provided by applicant): Background: Calcific aortic stenosis(AS) is the leading valvular disease in the United States. The number of patients with this diagnosis and requiring aortic valve replacement(AVR) is growing rapidly with the aging of our population. Emboli are implicated in most strokes and in postopertive cognitive dysfunction(POCD) after heart surgery. Patients presenting for AVR for AS define a subgroup at "extraordinary" risk(10%) for postoperative stroke, and 40% suffer multiple cerebral embolic events. These patients also are at risk for POCD and or vascular cognitive impairment secondary to these multiple cerebral infarctions in the short- term, and may be at risk for an acceleration toward long-term vascular dementia. This is a key population in which to study not only the pathogenesis of stroke and POCD, but also one in which the success or failure of neuroprotective interventions may be efficiently demonstrable. Aims: Aim-1) To determine the incidence the outcomes of stroke and cerebral transient ischemic events in an aged population, after AVR for AS; Aim-2) To determine the validity of a surrogate imaging biomarkertor postoperative cerebral ischemic events after AVR, using pre and postoperative Diffusion-Weighted MRI(DWI); Aim-3)Jo determine the change in cognitive performance in the aged patient after AVR for AS as compared to age/disease matched controls over time. Relevance:Post-surgical stroke portends a 5-10-fold increase in early mortality, while 69% suffer severe disability. Advances in the treatment of patients in the general stroke population, where early diagnosis, and an organized approach to early intervention has profoundly impacted outcome. Oddly, an organized approach to stroke surveillance after heart surgery, in a "captured" population, where the occurrence of stroke is not only frequent but predictable, rarely exists. (The 5-fold variance in the reported incidence of stroke after AVR is very telling.) Conversely, with the opportunity for close surveillance, benefits of rapid intervention/neuroprotection could reasonably be expected to surpass those seen in the general population. Neuroprotection trials have failed at an alarming rate due to inadequate design. A key element in designing properly powered studies is knowing accurately the frequency of the outcome to be studied. An accurate accounting of the risk of two important ischemic endpoints, stroke and POCD, will serve as a foundation for future trials. Validation of a potential imaging surrogate for stroke after AVR, DWI-MRI lesions, may allow for the efficient conduct of "proof of concept" studies in much smaller populations. Advanced imaging approaches paired with detailed cognitive analyses may allow us to deepen our understanding of the pathogenesis of POCD. Finally, the study database will allow us to closely examine the long-term risks for cognitive impairment & dementia from embolic processes during heart surgery..