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.

项目摘要 经导管主动脉瓣置换术（TAVR）已成为无法手术的患者的救生解决方案。 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。但近几 年，出现了某些局限性和严重不良事件：由于迂曲的主动脉几何结构导致输送失败 严重瓣膜钙化、瓣膜移位、传导异常和瓣周漏（PVL）导致 栓塞导致卒中风险增加，增加TAVR术后的总体发病率和死亡率。电流 TAVR技术基于适应TAVR的组织瓣膜，但不是专门为TAVR设计的。这些可能 在卷曲和展开过程中遭受损坏，导致有限的耐久性和受损的功能。在 减少PVL的最新一代TAVR器械特别解决方案与较高的 心脏传导异常（CCA），通常导致需要同时植入永久性起搏器 置入这可能会限制TAVR的实用性及其预期扩展到年轻、低风险患者，包括 a BAV（二叶式主动脉瓣）患者，其中TAVR的标签外使用正在迅速出现。鉴于美国人口老龄化， 预计到本世纪中叶，AS高风险人群将翻一番，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 同时获得更好的临床结果。我们的转化项目旨在开发下一代TAVR 技术.在精细的生物力学分析方法中结合成像、计算和体外工具， 优化方法将指导预先计划和定制TAVR手术， 患者的治疗效果并减少并发症。我们还致力于提供颠覆性技术：下一代 专门为TAVR优化的瓣膜。Polynova聚合物阀是使用我们的设计优化开发的 U 01 Quantum项目下的DTE方法和当前的STTR奖。它采用了一种新颖的xSIBS 血液相容性聚合物，具有更好的压握和展开应力耐受性，改善血液动力学 性能和抗血栓性以及延长的耐久性。其TAVR原型将经过严格测试， 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 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结构 作为精细数值模拟的输入。我们将扩大我们现有的CAVD患者的大型CT扫描数据库 （目前n=750），以及利用来自另外两个医疗中心的TAVR数据库（n=293和94， 分类疾病进展，以进一步用于阐明、计划和预测介入治疗。 结果。使用RCT作为前瞻性钙化生长预测模型的基础-三尖瓣 (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， 将包括详细和完善的结构，FSI（流体结构相互作用）和CFD（计算流体 动力学）模拟。异质组织 将通过外科CAVD样本的生物力学测试获得AVC组件特性 患者多尺度组织和钙化建模将利用来自微CT测量的输入， 微调模型。将基于RCT模型使用FSI研究不同的CAVD分期，并进行验证 在ViVitro左心模拟器（LHS）和3D打印模型中进行血液动力学测量 在Vascular Simulations Replicator®系统中的CAVD患者的复制品，随访血栓形成 在由柏林左心室辅助装置和SynCardia全人工心脏提供动力的流动回路中进行测量。 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久性 方法以及ViVitro Hi-Cycle系统，并为BAV患者开发专用设计， 展开和阀门偏心问题。使用活体心脏人体模型（LHHM）的计算机建模， 我们将评估预测与TAVR相关的CCA和房室阻滞的组织应变 展开，并将成功的TAVR病例与CCA和起搏器植入病例进行比较。最后， 我们将研究预粘附聚合物生物材料应用于TAVR支架的体外和计算机模拟有效性， 减小偏心和密封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

Patient-Specific Bicuspid Aortic Valve Biomechanics: A Magnetic Resonance Imaging Integrated Fluid-Structure Interaction Approach.

• DOI: 10.1007/s10439-020-02571-4
• 发表时间: 2021-03
• 期刊: Annals of biomedical engineering
• 影响因子: 3.8
• 作者: Emendi M;Sturla F;Ghosh RP;Bianchi M;Piatti F;Pluchinotta FR;Giese D;Lombardi M;Redaelli A;Bluestein D
• 通讯作者: Bluestein D