Suction Device for Control and Accuracy of Transseptal Access

摘要 左心手术经间隔(TS)入路是诊断的一个重要且迅速增长的领域 并提供治疗服务，预计美国患者总数将超过1000万。在美国和欧洲，TS 房颤消融、左心耳闭塞和未闭的介入治疗 卵圆孔关闭以及二尖瓣关闭不全的治疗。导管 即使对于最有经验的人来说，MC的定位和设备放置也是具有挑战性的 干预主义的心脏病专家(IC)和导致长时间的手术时间和大量的X射线暴露。这 新兴的治疗方法需要更高水平的导管稳定性和在穿刺术过程中对准确性的控制 卵圆窝(FO)。如果最初的穿刺术不准确，治疗几乎是不可能的，这通常是 需要拆卸、重新接合和设备重新推进。因此，初始局部化和稳定化 对于MC程序来说，在FO上限制分娩时间和X光曝光至关重要。此外，存在的 动脉瘤性或纤维性FO和心脏的持续运动使标准TS穿刺术 不可预测，并增加了心房或主动脉穿孔的风险。为了克服这些限制，我们 已经开发并验证了一种新型跨间隔通路导管(TSAC)的性能和用途，该导管 利用真空抽吸技术提供改进的导管定位和FO的稳定性。这个 我们的临床前研究结果非常成功，并通过稳定FO(4倍)支持这一点 减少穿刺力)，TSAC减少了帐篷(2.5倍)，以提高穿刺率(1.5倍) 在二尖瓣关闭不全的临床相关动物模型中与标准的TS介入装置进行比较。在这 第二阶段应用，我们建议使用研究设备豁免(IDE)来进行人体先导研究 它将被用来主要评估装置的安全性和辅助装置的可行性。 用于MC交付的TS访问权限。为实现这些第二阶段目标，提出了以下具体目标： 1)最终动物验证：在一组实验良好的动物身上评估TSAC的安全性 用于向FDA和机构审查委员会(IRBs)提交数据的实践(GLP)条件； 2)人的有效性：在一小群人中评估人的因素对可行性的贡献 一项双臂多中心研究中的人类(36名患者)。这项第二阶段研究涉及一项非常重要的 国家和世界范围内的临床需求不仅可以影响NHLBI，而且可以影响NIH的许多其他任务区。 成功完成这些拟议的目标将使我们能够将我们的研究成果转化为 商用设备，可显著改善TS接入程序，从而使患者 结果。

ABSTRACT Transseptal (TS) access for left heart procedures is an important and rapidly growing area for diagnostics and therapy delivery with an expected total of over 10 million U.S. patients. In the U.S. and Europe, TS access procedures are used for atrial fibrillation ablation, left atrial appendage occlusion and patent foramen ovale closure as well as treatment of mitral valve regurgitation with the MitraClip (MC). Catheter positioning and device placement for MC has been challenging even for the most experienced interventionalist cardiologists (ICs) and has led to long procedure times with significant x-ray exposure. This emerging therapy necessitates a higher level of catheter stability and control over accuracy during puncture of the fossa ovalis (FO). If the initial puncture is inaccurate, delivery of therapy is virtually impossible which often requires removal, re-engagement and device re-advancement. Thus, initial localization and stabilization on the FO is critical for MC procedures to limit delivery times and x-ray exposure. Additionally, the presence of aneurysmal or fibrotic FO and the constant movement of the heart makes standard TS access puncture unpredictable and contributes to increased risk for atrial or aortic perforation. To overcome these limitations, we have developed and validated the performance and utility of a novel transseptal access catheter (TSAC) that utilizes vacuum suction technology to provide improved catheter localization and stabilization of the FO. The results of our preclinical studies were highly successful and support that through stabilization of the FO (4-fold reduction in puncture force), the TSAC reduces tenting (2.5-fold) to improve puncture accuracy (1.5-fold) compared to standard TS access devices in a clinically relevant animal model of mitral regurgitation. In this Phase II application, we propose an investigational device exemption (IDE) to conduct a human pilot study which will be used to assess primarily device safety and secondarily device feasibility in patients undergoing TS access for MC delivery. To accomplish these Phase II objectives, the following specific aims are proposed: 1) Final Animal Validation: To assess the safety of the TSAC in a set of animals under good-laboratory practice (GLP) conditions to be used for data submission to the FDA and institutional review boards (IRBs); and 2) Human Validation: To assess the contribution of human factors to feasibility in a small group of humans (36 patients) in a double-arm multi-center study. This Phase II study addresses a highly significant national and worldwide clinical need that can impact not just NHLBI, but many other mission areas of NIH. Successful completion of these proposed Aims will allow us to translate our research findings to a commercially available device that could drastically improve TS access procedures and hence, patient outcomes.