Biomechanical Approaches and Technologies for Enhancing TAVR Outcomes

提高 TAVR 效果的生物力学方法和技术

• 批准号: 10449331
• 负责人: DANNY BLUESTEIN
• 金额: $ 76.39万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-15 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10449331
• 关键词: 3D Print; Address; Age; Aging; Anatomy; Aortic Valve Stenosis; Award; Berlin; Bicuspid; Biocompatible Materials; Biological Assay; Biomechanics; Blood Platelets; Blood Vessels; Cardiac; Catalogs; Clinical; Control Groups; Coupled; Data; Databases; Devices; Disease; Disease Progression; Enhancement Technology; Extravasation; Gender; Generations; Geometry; Goals; Growth; Health; Heart; Heart failure; Human; Image; Impairment; In Vitro; Incidence; Intervention; Lead; Left; Life; Liquid substance; Measurement; Mechanics; Medical center; Methodology; Modeling; Morbidity - disease rate; Morphology; Nodule; Operative Surgical Procedures; Outcome; Pacemakers; Patient-Focused Outcomes; Patients; Pattern; Performance; Physiological; Plant Roots; Polymers; Population; Procedures; Property; Protocols documentation; Risk; Savings; Scanning; Serious Adverse Event; Silicones; Site; Small Business Technology Transfer Research; Specimen; Stents; Stress; Structure; Subgroup; Surface; Surgical Valves; System; Techniques; Technology; Testing; Therapeutic Embolization; Tissues; X-Ray Computed Tomography; advanced simulation; aortic valve disorder; aortic valve replacement; base; bicuspid aortic valve; biomechanical model; biomechanical test; calcification; case control; design; effective therapy; follow-up; hemodynamics; high risk; human model; implantation; improved; in silico; innovation; left ventricular assist device; microCT; migration; minimally invasive; mortality; next generation; novel; off-label use; older patient; patient subsets; performance tests; predictive modeling; prospective; prototype; quantum; replacement tissue; replicator; seal; simulation; stroke risk; thrombogenesis; tool; total artificial heart; validation studies; valve replacement

Project Summary Transcatheter Aortic Valve Replacement (TAVR) has emerged as a life-saving solution for inoperable elderly patients with calcific aortic valve disease (CAVD) and severe Aortic Stenosis (AS). However, in recent years certain limitations and serious adverse events emerged: failed delivery due to tortuous aortic geometry and severe valvular calcification, valve migration, conduction abnormalities, and paravalvular leaks (PVL) leading to embolization with increased stroke risk, increasing the overall morbidity and mortality post-TAVR. Current TAVR technology is based on tissue valves adapted to, but not specifically designed for TAVR. Those may sustain damage during crimping and deployment, resulting in limited durability and impaired functionality. In latest-generation TAVR devices ad hoc solutions to reduce PVL have been associated with higher incidence of cardiac conduction abnormalities (CCAs), often leading to the need for concurrent permanent pacemaker implantation. This may limit TAVR utility and its anticipated expansion into younger, lower risk patients, including a BAV (bicuspid aortic valve) patients, in which off-label use of TAVR is rapidly emerging. Given the aging U.S. population segment at high risk for AS that is expected to double by mid-century, there is a critical need for optimizing the procedure and developing long-term TAVR technology – optimized to reduce the complications rates while achieving better clinical outcomes. Our translational project aims to develop next generation TAVR technology. Combining imaging, computational, and in vitro tools in a refined biomechanical analysis methodology, an optimization approach will guide the pre-planning and tailor TAVR procedures for achieving significantly better patient outcomes and reduce ensuing complications. We also aim to offer a disruptive technology: next generation valves specifically optimized for TAVR. The Polynova polymeric valve was developed using our design optimization DTE methodology under a U01 Quantum project and a current STTR award. It incorporates a novel xSIBS hemcompatible polymer with better tolerance to crimping and deployment stresses, improved hemodynamic performance and thromboresistance, and extended durability. Its TAVR prototypes will be rigorously tested and further optimized. These goals will be achieved by employing an innovative Reverse Calcification Technique (RCT) to predict CAVD Progression. We will use patient specific reconstructed geometries from a large CAVD patient’s database as input for refined numerical simulations. We will expand our existing large CT scans database of CAVD patients (currently n=750), as well as utilize TAVR databases from two additional medical centers (n=293 and 94, respectively), to catalog the disease progression to further serve to elucidate, plan and predict interventional outcomes. Using RCT as a base for predictive models of prospective calcification growth – both in tricuspid (TAV) and bicuspid CAVD patients, we will employ a combined in silico and in vitro biomechanical analysis that will include detailed and refined structural, FSI (Fluid Structure Interaction) and CFD (Computational Fluid Dynamics) simulations in the patient specific geometries reconstructed from CT scans. Heterogeneous tissue and AVC components properties will be obtained by biomechanical testing of specimens from surgical CAVD patients. Multiscale tissue and calcification modeling will utilize input derived from micro-CT measurements to fine tune the models. Various CAVD stages will be studied with FSI based on the RCT models, and validated with hemodynamics measurements in a ViVitro left heart simulator (LHS) and in fabricated 3D printed model replicas of CAVD patients in the Vascular Simulations Replicator® system, with follow-up thrombogenicity measurements in flow loops powered by a Berlin left ventricular assist device and SynCardia total artificial heart. We will fine-tune the in vitro hemodynamic and durability of the Polynova polymeric TAVR valve using the above approaches, as well a ViVitro Hi-Cycle system, and develop a dedicated design for BAV patients addressing deployment and valve eccentricity issues. Using in silico modeling with the Living Heart Human Model (LHHM), we will evaluate tissue strains that is predictive of CCAs and atrioventricular blockage associated with TAVR deployment, and compare successful TAVR cases to those with CCAs and pacemaker implantation. Finally, we will study the in vitro and in silico efficacy of pre-adherent polymeric biomaterials applied to TAVR stents in reducing eccentricity and sealing PVL.

项目概要 经导管主动脉瓣置换术 (TAVR) 已成为无法手术患者的救生解决方案 患有钙化性主动脉瓣疾病（CAVD）和严重主动脉瓣狭窄（AS）的老年患者。然而，最近 多年来出现了某些限制和严重的不良事件：由于主动脉几何形状曲折而导致分娩失败 严重的瓣膜钙化、瓣膜移位、传导异常和瓣周漏 (PVL) 导致 栓塞治疗会增加中风风险，增加 TAVR 后的总体发病率和死亡率。当前的 TAVR 技术基于适应 TAVR 的组织瓣膜，但并非专门为 TAVR 设计。那些可能 在压接和展开过程中遭受损坏，导致耐用性有限和功能受损。在 最新一代 TAVR 设备减少 PVL 的临时解决方案与较高的发生率相关 心脏传导异常（CCA），通常导致需要同时安装永久起搏器 植入。这可能会限制 TAVR 的实用性及其预期扩展到年轻、风险较低的患者，包括 BAV（二叶式主动脉瓣）患者，其中 TAVR 的超说明书使用正在迅速出现。鉴于美国的老龄化 AS 高危人群预计到本世纪中叶将增加一倍，因此迫切需要 优化手术并开发长期 TAVR 技术 – 优化以减少并发症 率，同时实现更好的临床结果。我们的转化项目旨在开发下一代 TAVR 技术。将成像、计算和体外工具结合到精细的生物力学分析方法中， 优化方法将指导预先规划和定制 TAVR 程序，以实现更好的效果 患者的治疗效果并减少随之而来的并发症。我们还致力于提供颠覆性技术：下一代 专为 TAVR 优化的阀门。 Polynova 聚合物阀门是使用我们的设计优化开发的 U01 Quantum 项目和当前 STTR 奖项下的 DTE 方法。它采用了一种新颖的 xSIBS 血液相容性聚合物具有更好的抗卷曲和展开应力能力，改善血液动力学 性能和抗血栓性，以及延长的耐用性。其 TAVR 原型将经过严格测试并 进一步优化。 这些目标将通过采用创新的反向钙化技术（RCT）来预测来实现 CAVD 进展。我们将使用来自大型 CAVD 患者数据库的患者特定重建几何形状 作为精细数值模拟的输入。我们将扩展现有的 CAVD 患者大型 CT 扫描数据库 （目前 n=750），以及利用另外两个医疗中心的 TAVR 数据库（n=293 和 94， 分别），对疾病进展进行分类，以进一步阐明、计划和预测介入治疗 结果。使用随机对照试验作为三尖瓣预期钙化生长预测模型的基础 (TAV) 和二尖瓣 CAVD 患者，我们将采用计算机模拟和体外生物力学分析相结合的方法 将包括详细和细化的结构、FSI（流体结构相互作用）和 CFD（计算流体 动力学）模拟根据 CT 扫描重建的患者特定几何形状。异质组织 AVC 组件特性将通过对手术 CAVD 标本进行生物力学测试来获得 患者。多尺度组织和钙化建模将利用微 CT 测量得出的输入来 微调模型。将基于 RCT 模型使用 FSI 研究各个 CAVD 阶段，并进行验证 在 ViVitro 左心模拟器 (LHS) 和制造的 3D 打印模型中进行血流动力学测量 血管模拟 Replicator® 系统中的 CAVD 患者复制品，具有后续血栓形成情况 由柏林左心室辅助装置和 SynCardia 全人工心脏驱动的流动回路中的测量。 我们将使用上述方法微调 Polynova 聚合物 TAVR 瓣膜的体外血流动力学和耐用性 方法以及 ViVitro Hi-Cycle 系统，并为 BAV 患者开发专用设计，解决 部署和阀门偏心问题。使用活体心脏人体模型 (LHHM) 进行计算机建模， 我们将评估可预测 CCA 和与 TAVR 相关的房室传导阻滞的组织应变 部署，并将成功的 TAVR 病例与 CCA 和起搏器植入病例进行比较。最后， 我们将研究应用于 TAVR 支架的预粘附聚合物生物材料的体外和计算机功效 减少偏心并密封PVL。

项目成果

Structural Responses of Integrated Parametric Aortic Valve in an Electro-Mechanical Full Heart Model.

• DOI: 10.1007/s10439-020-02575-0
• 发表时间: 2021-01
• 期刊: Annals of biomedical engineering
• 影响因子: 3.8
• 作者: Morany A;Lavon K;Bluestein D;Hamdan A;Haj-Ali R
• 通讯作者: Haj-Ali R

Fragmentation of Different Calcification Growth Patterns in Bicuspid Valves During Balloon Valvuloplasty Procedure.

球囊瓣膜成形术过程中二尖瓣不同钙化生长模式的破碎。

• DOI: 10.1007/s10439-022-03115-8
• 发表时间: 2023
• 期刊: Annals of biomedical engineering
• 影响因子: 3.8
• 作者: Morany,Adi;Lavon,Karin;Halevi,Rotem;Haj-Ali,Nora;Bluestein,Danny;Raanani,Ehud;Hamdan,Ashraf;Haj-Ali,Rami
• 通讯作者: Haj-Ali,Rami

Assessment of Paravalvular Leak Severity and Thrombogenic Potential in Transcatheter Bicuspid Aortic Valve Replacements Using Patient-Specific Computational Modeling.

使用患者特定计算模型评估经导管二尖瓣主动脉瓣置换术中的瓣周漏严重程度和血栓形成可能性。

• DOI: 10.1007/s12265-021-10191-z
• 发表时间: 2022-08
• 期刊: JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH
• 影响因子: 3.4
• 作者: Anam, Salwa B.;Kovarovic, Brandon J.;Ghosh, Ram P.;Bianchi, Matteo;Hamdan, Ashraf;Haj-Ali, Rami;Bluestein, Danny
• 通讯作者: Bluestein, Danny

Progressive Calcification in Bicuspid Valves: A Coupled Hemodynamics and Multiscale Structural Computations.

• DOI: 10.1007/s10439-021-02877-x
• 发表时间: 2021-12
• 期刊: Annals of biomedical engineering
• 影响因子: 3.8
• 作者: Lavon K;Morany A;Halevi R;Hamdan A;Raanani E;Bluestein D;Haj-Ali R
• 通讯作者: Haj-Ali R

A computational framework for post-TAVR cardiac conduction abnormality (CCA) risk assessment in patient-specific anatomy.

• DOI: 10.1111/aor.14189
• 发表时间: 2022-07
• 期刊: Artificial organs
• 影响因子: 2.4