Innovative Image-Guided Device for Beating Heart Mitral Valve Repair

 描述（由申请人提供）：二尖瓣疾病是美国最常见的心脏瓣膜功能障碍，约占总人口的0.7%和75岁以上人口的3.5%。随着人口老龄化，预计到2020年，美国和欧洲重度二尖瓣返流（MR）的发生率将超过500万，并将带来日益沉重的经济负担。问题：二尖瓣返流导致左心室容量超负荷，进而发展为心室扩张、射血性能下降、肺动脉高压、症状性充血性心力衰竭、房颤、右心室功能障碍和死亡。 虽然常规二尖瓣手术是安全有效的，但它仍然非常具有侵入性和病态性，并且明显未得到充分利用。解决方案：Harpoon Medical开发了微创、图像引导、心脏跳动二尖瓣修复技术，通过肋骨之间的锁孔切口进行。该创新器械允许术者通过使用大体积结锚将人工腱索（新腱索）固定到脱垂的二尖瓣瓣叶上，并将瓣叶重新悬挂在其正常位置，从而消除二尖瓣返流。鱼叉装置消除了需要打开胸部，把病人放在心肺机和停止心脏。这将使传统的二尖瓣手术从复杂的3-6小时手术转变为60分钟的手术，并允许患者在一周内恢复正常的日常活动。初步数据：一项正在进行的早期可行性研究证实，Harpoon器械成功地将2例退行性二尖瓣疾病患者的重度二尖瓣返流减少至微量。具体目标：该项目需要进行必要的开发工作和临床前测试，以创建一个用于美国人体试验的自动输送系统，并加速Harpoon微创心脏跳动二尖瓣修复设备的商业化。在特定目标1中，我们将开发一种带有单个按钮致动器的自动输送系统，并在实验室和急性猪研究中对其进行验证。在特定目标2中，我们将开发一种方法，用于在超声心动图引导下滴定多个新腱索的长度，并将其固定到心脏的心外膜表面。将在特定目标3中对目标1中开发的自动输送系统和目标2中开发的用于滴定腱索长度的方法进行评价，作为退行性二尖瓣疾病犬临床研究的一部分，以确认该器械在自然发生疾病模型中的安全性、性能和有效性。预期结果：在这项直接进入第二阶段SBIR赠款结束时，Harpoon将拥有一种微创、跳动的心脏二尖瓣修复装置，该装置已在急性和慢性动物研究中得到验证，并准备在美国进行临床试验，以支持FDA的批准。

 DESCRIPTION (provided by applicant): Mitral valve disease is the most prevalent heart valve dysfunction in the U.S., affecting approximately 0.7% of the total population and 3.5% of the population over age 75. With the aging population, the occurrence of severe mitral regurgitation (MR) in the U.S. and Europe is projected to exceed 5M by 2020 and will present an increasing economic burden. The Problem: MR causes a volume overload on the left ventricle which in turn progresses to ventricular dilation, decreased ejection performance, pulmonary hypertension, symptomatic congestive heart failure, atrial fibrillation, right ventricular dysfunction and death. While conventional mitral valve surgery is safe and effective, it remains very invasive and morbid and is significantly underutilized. The Solution: Harpoon Medical has developed technology for minimally invasive, image-guided, beating-heart mitral valve repair, performed via a keyhole incision between the ribs. The innovative device allows an operator to eliminate MR by securing artificial chordae tendineae (neochords) to a prolapsed mitral valve leaflet with a bulky knot anchor and resuspending the leaflet in its normal position. The Harpoon device eliminates the need crack the chest, put the patient on a heart-lung machine and stop the heart. This will transform conventional mitral valve surgery from a complex 3-6 hour operation to a sixty minute procedure and allow patients to return to normal daily activities within a week. Preliminary Data: An ongoing early feasibility study has confirmed that the Harpoon device successfully reduced severe MR to trace in two patients suffering from degenerative mitral valve disease. Specific Aims: This project entails the development work and preclinical testing necessary to create an automated delivery system for human trials in the U.S and accelerate the commercialization of Harpoon's minimally invasive, beating heart mitral valve repair device. In Specific Aim 1 we will develop an automated delivery system with a single button actuator and validate it at the bench and in acute pig studies. In Specific Aim 2 we will develop a method for titrating the length of multiple neochords under echocardiographic guidance and securing them to the epicardial surface of the heart. The automated delivery system developed in Aim 1 and the method for titrating the length of the neochords developed in Aim 2 will be evaluated as part of a clinical study in dogs with degenerative mitral valve disease in Specific Aim 3 to validate the safety, performance and efficacy of the device in a naturally occurring disease model. Expected Outcomes: At the end of this Direct to Phase II SBIR Grant, Harpoon will have a minimally invasive, beating heart mitral valve repair device that has been validated in acute and chronic animal studies and is ready for clinical testing in the U.S. to support FDA approval.