PeriPath: A Single Incision Delivery Tool for Epicardial Pacing and Defibrillation: Phase 2

项目摘要 每年，美国有近7200名婴儿出生时就患有复杂的先天性心脏病 在生命的第一年内需要手术干预的心脏病。适用于婴幼儿 有心律异常的儿童，介入治疗可能特别困难，因为 血管系统的大小和/或先天畸形通常排除了经静脉途径 植入心脏装置，如起搏器或除颤器的方法。因此，婴儿 必须接受胸骨切开或开胸手术才能进入心脏的心外膜表面。我们有 开发了一种新的微创心包切入工具来提供起搏和除颤 在内窥镜下直接观察到心脏的心外膜表面。利用 这个工具，我们假设我们可以安全有效地提供起搏和除颤治疗 通过一个单一的小港口。通过使用经皮途径，这应该可以减少疼痛和风险。 减少感染，减少手术时间，最大限度地减少手术并发症 手术方式。此外，程序的直接可视化使其比盲人更安全 心包穿孔。我们的团队使用了一种未成熟的猪心脏移植模型 设备，并证明经皮途径与开放手术一样安全和有效 外科技术。 此二期SBIR项目的具体目标是显示上心包 使用临床前动物模型与商用套管针进行心内膜起搏和心外膜起搏的比较 随着婴儿生长速度的加快，紧随其后的是人类(FIH)临床试验加速调控 PeriPath工具的批准和商业化。在这项工作中，我们将完成以下工作 3个具体目标： 目标1：展示商用套管针的卓越性能和可用性 通过设备性能和在纸巾板中的处理来衡量。我们将进行试点核查 PeriPath设备的制造符合FDA的规定。设备将受到 可用性、验证和验证测试和结果与EndoPath套管针进行比较 双面单侧检验。成功的定义是PeriPath获得卓越的性能和 在所有测试中，心包穿刺法与市售套管针进行比较。 目的2：在慢性起搏研究中证明稳定的起搏参数。我们会比较一下 植入PeriPath工具的电极慢性起搏性能的研究 EndoPath套管针。这项为期12周的研究将使用具有增长率的猪动物模型 相当于一个新生儿。我们将测量起搏结果以及设备的可用性和组织 治愈。我们将结合目标1的结果来申请调查设备豁免 (艾德)。成功的定义是卓越的可用性、稳定的起搏参数和更好的组织 PeriPath工具与EndoPath工具的修复得分比较。 目标3：首次使用PeriPath植入人工血管进行人体可行性临床研究 商业心脏起搏器领先。使用在目标2中获得的集成开发环境，我们将要求进行机构审查 儿童国家医院(CN)董事会(IRB)批准植入商业可获得的起搏导线 在一项五名患者的可行性研究中。这项研究将证明PeriPath的安全性和有效性 设备。将监测导线稳定性和起搏参数。成功是由完成决定的 人类可行性研究，并提交510(K)申请。 这项研究可能会对改变目前的临床实践产生革命性的影响 将开放的外科手术途径转变为微创的经皮手术。而当 研究设计关注患有先天性心脏病的婴儿和儿童的独特需求， 这些发现的推断可能会使数以千计的成年患者受益，这些患者有 心脏再同步化治疗，但由于缺乏 经静脉通路或足够的冠状静脉支流，以起搏关键部位 左心室，这可以用我们提出的工具和技术解决。

Project Summary Each year, nearly 7,200 infants in the United States are born with a complex congenital heart disease that requires surgical intervention within the first year of life. For infants and young children with heart rhythm abnormalities, interventional treatment can be especially difficult, as the size of their vasculature and/or congenital anomalies typically preclude a transvenous approach for implanting a cardiac device such as a pacemaker or defibrillator. As a result, infants must undergo a sternotomy or thoracotomy to access the epicardial surface of the heart. We have developed a novel minimally-invasive pericardial access tool to deliver pacing and defibrillation leads to the epicardial surface of the heart under direct visualization from an endoscope. Utilizing this tool, we hypothesize that we can safely and effectively deliver pacing and defibrillation therapy through a single small port. By using a percutaneous approach, this should reduce pain and risk of infection, decrease procedure times, and minimize operative complications from an open surgical approach. In addition, direct visualization of the procedure makes it safer than blind pericardial punctures. Our team has utilized an immature porcine model implantation of cardiac devices, and demonstrated the percutaneous approach was as safe and effective as an open surgical technique. The specific goal of this Phase II SBIR project is to demonstrate superior pericardial access and epicardial pacing compared to a commercial trocar using a preclinical animal model with infant growth rate, followed by first in human (FIH) clinical trials to accelerate regulatory approval and commercialization of the PeriPath tool. In this work, we will complete the following 3 specific aims: Aim 1: Demonstrate superior performance and usability to a commercial trocar as measured by device performance and handling in tissue plates. We will conduct a pilot verification build of the PeriPath device in compliance with FDA regulation. Devices will be subjected to usability, verification, and validation testing and results compared to an EndoPath trocar using a two-one-sided test. Success is defined as PeriPath achieving superior performance and pericardial access compared to the commercially available trocar in all tests. Aim 2: Demonstrate stable pacing parameters in a chronic pacing study. We will compare the chronic pacing performance of leads implanted with the PeriPath tool to leads implanted with the EndoPath trocar. The 12-week study will use a porcine animal model with a growth rate equivalent to a newborn. We will measure pacing outcomes as well as device usability and tissue healing. We will combine the results from Aim 1 to request an investigational device exemption (IDE). Success is defined as superior usability, stable pacing parameters, and better tissue healing scores for the PeriPath tool compared with EndoPath. Aim 3: Perform a first in human feasibility clinical study using PeriPath to implant a commercial pacemaker lead. Using the IDE obtained in Aim 2, we will request institutional review board (IRB) approval at Children’s National (CN) to implant a commercially available pacing lead in a five patient feasibility study. The study will demonstrate safety and efficacy of the PeriPath device. Lead stability and pacing parameters will be monitored. Success is defined by completion of the human feasibility study, and submission of a 510(k) application. This research could have a transformative impact in changing current clinical practice by converting an open surgical approach to a minimally invasive percutaneous procedure. While the study design focuses on the unique needs of infants and children with congenital heart disease, extrapolation of these findings may benefit thousands of adult patients who have indications for cardiac resynchronization therapy but do not achieve successful implantation due to lack of transvenous access or adequate coronary sinus venous tributaries to pace key locations in the left ventricle, which could be resolved with our proposed tools and techniques.