Strategies for Transcatheter Mitral Valve Replacement

描述（由申请人提供）：心脏瓣膜替代疗法正处于一个重大的范式转变之中。影像学、导管技术和支架设计的改进使得经导管主动脉瓣和肺动脉瓣置换术成为临床现实。由于大约240万美国人患有中度至重度缺血性二尖瓣反流（IMR），其中绝大多数人被认为过于虚弱或无法忍受直视心脏手术，经导管方法进行二尖瓣置换术（TMVR）将代表着治疗的重大进步。成功的TMVR需要：1)无缝线锚定机制；2)瓣周密封策略；3)可折叠性。作为广泛的前期工作的结果，我们已经开发了一种新的TMVR锚定和密封机制。目前的原型是一个自膨胀的有阀支架，由聚四氟乙烯覆盖镍钛诺金属丝框架构成。锚定是由从装置的心室端发出的手臂促进的，这些手臂被设计成自动地在脊索和小叶周围暗示自己。我们的密封机制依赖于支架设计的灵活性，允许设备稍微过大，从而允许设备紧贴环和小叶锥。在初步工作中，我们已经证明我们的TMVR概念可以在大型动物模型中稳固地锚定和密封。该项目的目标是优化当前原型的设计，在不影响阀门固定和密封的情况下，最大限度地提高设备的可折叠性和交付性。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发展锚定和密封技术，以评估设计迭代。这个发展阶段的结果将是一个无缝合线的二尖瓣置换术。具体的目标2A将是开发一种微创手术输送系统，最终通过小的右开胸术实现体外二尖瓣置换术

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.