Leaflet sparing transcatheter aortic valve equipped with IVUS-guided delivery system.

项目总结/摘要 经导管主动脉瓣置换术（TAVR）是外科主动脉瓣置换术的重要替代方案 （SAVR）在老年主动脉瓣狭窄患者中的应用。按照目前的速度，TAVR手术预计将 从2020年的约163，000人增加两倍至2025年的约289，000人，严重主动脉瓣狭窄患者的数量 预计到2050年，狭窄将上升到350万。 考虑到中度和高风险TAVR组中主要是老年患者， 出血仍然是一种主要并发症（发生率为6%至8%），是一种未满足的临床需求，必须避免 下一代更低配置的设备。然而，降低当前TAVR输送的外径 具有较小鞘尺寸的系统以更积极的支架压接为代价。支架致创伤 经导管瓣膜植入后对瓣叶的损伤已在科学和临床上得到证实。 考虑到每个薄支架支柱施加的应力等于压接力除以支柱的压接力， 在瓣叶上的表面挤压，支架压握应力的大小将是巨大的，因为支柱 表面非常小。由于当前支架压握实践导致TAVR中瓣叶损伤， 内流导致钙晶体成核和胶原纤维破坏，易导致小叶 退化和早期瓣膜失效，表现为瓣叶增厚、硬化和明显钙化。 FoldaValve™技术是一种新型自膨式14 Fr经股动脉TAVR系统， Kheradvar实验室开发了一种从根本上不同的概念，使瓣叶免于支架压握， 通过减小输送外径同时避免过度的支架压握，解决TAVR临床未满足的需求 传单由于其独特的折叠机制，FoldaValve™在真正的14 Fr时达到了最小的输送尺寸， 使用15 Fr鞘管植入。除了其小的输送轮廓之外，考虑到积极的支架压握是 许多人认为这是早期结构退化和亚临床瓣叶血栓形成的触发因素 研究者认为，FoldaValve应有助于TAVR耐久性。此外，FoldaValve™配备了独特的 使用血管内超声（IVUS）引导输送系统（Incidity ™），可减少 植入过程中的荧光透视，最大限度地减少对患者和医生的辐射。Incidence ™独一无二 允许在六个自由度中重新定位，即使瓣膜完全植入， 在其他TAVR系统中尚未实施的术中瓣膜回收。 该I期项目将首先测试FoldaValve在鞘管下的反向折叠机制 保护瓣膜的结构完整性，并与当前TAVR产品相比提高其耐用性 支架压握，然后根据ISO 5840-3：2021评估FoldaValve的长期性能： 具体目标1：确定鞘管下FoldaValve反向折叠机制的保护作用， 与其他TAVR系统实践的传统支架预置相比。 具体目标2：评估FoldaValve在标准绵羊模型中的长期性能（20周）， 根据ISO 5840-3：2021，瓣周漏、瓣叶血栓形成和钙化。

PROJECT SUMMARY/ABSTRACT Transcatheter aortic valve replacement (TAVR) is an essential alternative to surgical aortic valve replacement (SAVR) in elderly patients with aortic valve stenosis. At the current pace, TAVR procedures are expected to increase twofold from ~163,000 in 2020 to ~289,000 in 2025, and the number of patients with severe aortic stenosis is anticipated to rise to 3.5M by 2050. Given the predominately older patients in the intermediate and high-risk TAVR groups, vascular injury with bleeding is still a major complication (6% to 8% incidence), and an unmet clinical need, which must be avoided by next-generation devices with lower profiles. However, lowering the profile of the current TAVR delivery systems with smaller sheath size comes at the cost of a more aggressive stent-crimp. Stent-induced traumatic injury to the leaflets after transcatheter valve implantation has been scientifically and clinically established. Considering that the stress exerted by each thin stent's strut is equal to the crimping force divided by strut's surface pressing over the leaflets, the magnitude of stent-crimping stress will be enormous since the strut surface is very small. Leaflet damage in TAVR due to current practice of stent crimping provokes a calcium influx that leads to calcium crystal nucleation and collagen fiber disruption, which predispose to leaflet degeneration, and early valve failure, as presented by leaflet thickening, stiffening and apparent calcification. FoldaValve™ Technology, a novel self-expandable 14-Fr transfemoral TAVR system which uses a fundamentally different concept to spare leaflets from stent-crimping, has been developed by Kheradvar Lab to address TAVR clinical unmet needs by reducing the delivery profile while avoiding aggressive stent-crimp of the leaflets. Due to its unique folding mechanism, FoldaValve™ attains the smallest delivery size at true 14-Fr, implantable using a 15-Fr sheath. In addition to its small delivery profile, given that aggressive stent-crimping is considered a triggering factor for early structural deterioration and subclinical leaflet thrombosis by many investigators, FoldaValve should contribute to TAVR durability. Moreover, FoldaValve™ is uniquely equipped with an intravascular ultrasound (IVUS)-guided delivery system (Ingenuity™), which reduces the need for Fluoroscopy during implantation and minimizes radiation to both patient and physician. Ingenuity™ uniquely allows repositioning in six degrees-of-freedom even when the valve is fully implanted and allows complete intraprocedural valve retrieval, which has not yet practiced in other TAVR systems. This Phase I project will first test the hypothesis that FoldaValve's inverse folding mechanism under the sheath protects the valve's structural integrity and improve its durability compared to the current TAVR generation's stent-crimping, and then will assess FoldaValve's chronic performance according to ISO 5840-3:2021: Specific Aim 1: Establish the protective effects of FoldaValve's inverse folding mechanism under the sheath in comparison with the traditional stent-crimping as practiced by other TAVR systems. Specific Aim 2: Assess FoldaValve's chronic performance (20 weeks) in standard ovine model considering paravalvular leakage, leaflet thrombosis, and calcification according to ISO 5840-3:2021.