Yale University School of Medicine and Yale Cardiovascular Research Group, 1 Church Street Suite #330, PO Box 208017, New Haven, CT 06510, USA.
BMC Med. 2013 Dec 11;11:257. doi: 10.1186/1741-7015-11-257.
Neurological events associated with transcatheter aortic valve implantation are major contributors to morbidity and mortality. Choosing an appropriate endpoint to determine neuroprotection device efficacy is a key difficulty inhibiting the translation of the innovation from the laboratory to the bedside. Cost and sample size limitations inhibit the feasibility of using the rate of clinical (such as stroke or other cerebral) events as the primary efficacy endpoint. This paper focuses on consensus opinions from the 2013 Yale-University College London (UCL) Device Innovation Summit.
Neuroimaging, specifically diffusion-weighted magnetic resonance imaging (DW MRI), may serve as a surrogate endpoint for clinical studies detecting cerebral events in which cost and sample-size limitations prohibit the use of clinical outcomes. A major limitation of using imaging to prove efficacy in cardiac device studies is that no standardized endpoint exists. Ongoing trials investigating cerebral protection devices for transcatheter aortic valve implantation are utilizing and reporting various qualitative and quantitative DW MRI values; however, single lesion volume, number of new lesions, and total lesion volume have been found to be the most reproducible and prognostically important imaging measures.
DW MRI may be a useful surrogate endpoint for clinical studies detecting cerebral events to determine the device's success in neurological protection. Consensus from the 2013 Yale-UCL Device Innovation Summit specifically recommends the reporting of mean single lesion volume, number of new lesions, and total volume, and encourages European Union (EU)-US regulatory consensus in the guidance of implementing this endpoint.
与经导管主动脉瓣植入术相关的神经系统事件是发病率和死亡率的主要原因。选择适当的终点来确定神经保护装置的疗效是将创新从实验室转化到临床的关键难点之一。成本和样本量的限制抑制了使用临床（如中风或其他脑部）事件发生率作为主要疗效终点的可行性。本文重点介绍了 2013 年耶鲁大学-伦敦大学学院（UCL）设备创新峰会的共识意见。
神经影像学，特别是弥散加权磁共振成像（DW MRI），可以作为替代终点，用于检测临床研究中的脑部事件，而这些研究因成本和样本量的限制而无法使用临床结局。在心脏设备研究中使用影像学来证明疗效的一个主要限制是没有标准化的终点。正在进行的经导管主动脉瓣植入术的脑保护装置研究正在使用和报告各种定性和定量的 DW MRI 值；然而，已发现单病灶体积、新病灶数量和总病灶体积是最可重复和预后最重要的影像学指标。
DW MRI 可能是一种有用的替代终点，用于检测临床研究中的脑部事件，以确定该装置在神经保护方面的成功。2013 年耶鲁-UCL 设备创新峰会的共识特别建议报告平均单病灶体积、新病灶数量和总体积，并鼓励欧盟（EU）-美国监管机构在实施这一终点的指导方面达成共识。
