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

配备 IVUS 引导输送系统的小叶保留经导管主动脉瓣膜。

• 批准号: 10385414
• 负责人: Ronald J Hosmer
• 金额: $ 34.93万
• 依托单位: VALVENTION, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10385414
• 关键词: Address; Adoption; Aortic Valve Stenosis; Bioprosthesis device; Calcium; Case Study; Chronic; Clinical; Collagen Fiber; Complication; Crystallization; Data; Defect; Deterioration; Devices; Elderly; Evaluation; Extravasation; Failure; Fluoroscopy; Freedom; Generations; Hemorrhage; Implant; Incidence; Institutes; Life Expectancy; Microscopic; Operative Surgical Procedures; Paris, France; Patients; Perforation; Performance; Pericardial effusion; Phase; Physicians; Procedures; Radiation; Recommendation; Research Personnel; Retrieval; Risk; Stenosis; Stents; Stress; Structure; Surface; System; Technology; Testing; Thinness; Thrombosis; Traumatic injury; Uncertainty; aortic valve; aortic valve replacement; calcification; cost; high risk; implantation; improved; mortality; next generation; novel; older patient; protective effect; sheep model; survivorship; ultrasound; vascular injury

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.

项目摘要/摘要 经导管主动脉瓣置换（TAVR）是手术主动脉瓣置换的必不可少的替代方法 （Safr）在老病瓣狭窄的老患者中。在当前空间，TAVR程序有望 从2020年的〜163,000增加到2025年的〜289,000，而患有严重主动脉的患者人数 预计到2050年，狭窄预计将增加到350万。 鉴于中级和高风险TAVR组中主要是老年患者，血管损伤与 出血仍然是主要的并发症（发生率为6％至8％），并且必须避免使用未满足的临床需求 通过具有较低配置文件的下一代设备。但是，降低当前TAVR交付的轮廓 具有较小鞘尺寸的系统以更具侵略性的支架碎屑为代价。支架引起的创伤 经导管实施后的叶子受伤已在科学上和临床上建立。 考虑到每个细支架的支撑杆施加的压力等于压缩力除以支撑杆 表面压在叶子上，支架 - 折叠应力的大小将是巨大的，因为支柱 表面很小。由于当前的支架压接的练习引起了钙 导致钙晶核钙和胶原蛋白纤维破坏的涌入，易于传单 脱位和早期瓣膜破坏，如小叶增厚，僵硬和明显的钙化所示。 foldavalve™技术，一种新颖的可自我膨胀的14-FR transforal Tavr系统，使用 Kheradvar Lab已开发了与支架折痕的备用传单的根本不同的概念，以 通过减少交付剖面，同时避免侵略性支架刺痛来解决TAVR临床未满足的需求 叶子。由于其独特的折叠机制，Foldavalve™达到了最小的14-FR的交付尺寸， 使用15-FR鞘植入。除了其较小的交付配置文件外，鉴于侵略性的支架criming是 被认为是早期结构确定和亚临床小叶血栓形成的触发因素 研究人员，Foldavalve应促进TAVR耐用性。此外，foldavalve™是唯一等效的 具有血管内超声（IVUS）指导的输送系统（Ingenuity™），这减少了对 植入过程中的透视镜检查，并最大程度地减少对患者和实物的辐射。 Ingenuity™唯一 即使阀门完全植入并允许完整 经术内瓣膜的检索，在其他TAVR系统中尚未实行。 该阶段I项目将首先检验以下假设，即在鞘下方的foldavalve的反折叠机制 与当前的TAVR一代相比，保护阀的结构完整性并提高其耐用性 支架crimping，然后根据ISO 5840-3：2021评估Foldavalve的长期性能： 特定目标1：建立富特瓦尔夫的反折叠机构在鞘下的受保护效果 与其他TAVR系统所实施的传统支架式冰箱进行比较。 特定目标2：评估Foldavalve的慢性表现（20周） 根据ISO 5840-3：2021，旁腔泄漏，小叶血栓形成和钙化。