Strategies for Transcatheter Mitral Valve Replacement

描述（由申请人提供）：心脏瓣膜置换治疗正处于重大范式转变之中。影像学、导管技术和支架设计的改进使经导管置换主动脉瓣和肺动脉瓣成为临床现实。二尖瓣置换术（TMVR）的经导管方法将代表治疗的重大进步，因为约有240万美国人患有中度至重度缺血性二尖瓣返流（IMR），其中绝大多数被认为过于虚弱或虚弱，无法耐受心内直视手术。成功的TMVR需要：1）无缝线锚定机制~ 2）瓣周密封策略和3）可折叠性。作为广泛的前期工作的结果，我们已经开发出一种新的TMVR锚定和密封机制。目前的原型是一种自膨式瓣膜支架，由聚四氟乙烯覆盖的镍钛合金金属丝框架构成。从器械心室端伸出的臂有助于扩张，这些臂设计成无损伤地环绕腱索和瓣叶。我们的密封机制依赖于支架设计的灵活性，允许器械尺寸略微过大，从而允许器械紧贴瓣环和瓣叶圆锥体。在初步工作中，我们已经证明了我们的TMVR概念可以在大型动物模型中稳固地锚和密封。本项目的目标是优化当前原型的设计，以最大限度地提高器械的可折叠性和输送能力，同时不影响瓣膜的固定和密封。开发过程将遵循分级方法。具体目标1是使用开放手术技术进一步开发锚定和密封技术，以评价设计迭代。该开发阶段的结果将是无缝线二尖瓣置换术。具体目标2A将是开发一种微创手术输送系统，该系统最终将通过小型右胸切开术促进非体外循环二尖瓣置换术， 人类具体目标2B是进一步增强输送系统，以允许通过外周静脉和经房间隔入路进行二尖瓣置换。

DESCRIPTION (provided by applicant): Heart valve replacement therapy is in the midst of a major paradigm shift. Improvements in imaging, catheter technology and stent design have made transcatheter replacement of the aortic and pulmonic valves clinical realities. A transcatheter approach to mitral valve replacement (TMVR) would represent a major advance in treatment since approximately 2.4 million Americans suffer from moderate to severe ischemic mitral regurgitation (IMR) with the vast majority being deemed too sick or debilitated to tolerate open-heart surgery. Successful TMVR requires: 1) a sutureless anchoring mechanism~ 2) a perivalvular sealing strategy and 3) foldability. As the result of extensive preliminary work we have developed a novel anchoring and sealing mechanism for TMVR. The current prototype is a self-expanding valved stent constructed from a polytetrafluoroethylene covered nitinol wire frame. Anchoring is facilitated by arms emanating from the ventricular end of the device which are designed to atraumatically insinuate themselves around chordae and leaflets. Our sealing mechanism relies on the flexibility of the stent design which allows the device to be slightly oversized thereby permitting the device to conform snuggly to the annulus and leaflet cone. In preliminary work we have demonstrated that our TMVR concept can anchor and seal robustly in large animal models. The goal of the proposed project is to optimize the design of the current prototype to maximize device foldability and delivery without compromising valve fixation and seal. The development process will follow a graded approach. Specific Aim 1 is to further develop the anchoring and sealing technology using open surgical techniques to evaluate design iterations. The result of this development stage will be a sutureless mitral valve replacement. Specific Aim 2A will be to develop a minimally invasive surgical delivery system which will ultimately facilitate off pump mitral valve replacement via a small right thoracotomy in humans. Specific Aim 2B is to further enhance the delivery system to allow mitral valve replacement via peripheral vein and transatrial septal approach.