Biomechanical Approaches and Technologies for Enhancing TAVR Outcomes

提高 TAVR 效果的生物力学方法和技术

基本信息

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
项目类别：
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

项目摘要

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（TAVR）已成为无法手术的救生解决方案钙化主动脉瓣疾病（CAVD）和严重主动脉狭窄（AS）的老年患者。但是，最近年份某些局限性和严重的不良事件出现了：由于曲折主动脉几何形状而导致交付失败以及严重的瓣膜计算，瓣膜迁移，传导异常和旁腔泄漏（PVL）领先以增加中风风险的栓塞，增加了TAVR后的总体发病率和死亡率。当前的 TAVR技术基于适合TAVR的组织阀，但不是专门设计的。那些可以在压接和部署期间维持损害，导致耐用性有限和功能受损。在最新一代的TAVR设备临时解决方案减少PVL已与更高的事件有关心脏传导异常（CCA），通常导致需要并发永久起搏器植入。这可能会限制TAVR公用事业及其预期扩展到年轻，较低的风险患者，包括 BAV（双刺主动脉瓣）患者，其中标签不使用TAVR的患者正在迅速出现。考虑到美国老化预计到本世纪中叶的人口段高风险，这将是至关重要的优化程序并开发长期TAVR技术 - 优化以减少并发症比率同时获得更好的临床结果。我们的翻译项目旨在发展下一代TAVR 技术。在精致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量身定制的TAVR程序，以更好地实现患者的结果并减少随之而来的并发症。我们还旨在提供一项破坏性技术：下一代专门针对TAVR优化的阀。使用我们的设计优化开发了多元诺娃聚合物阀 U01量子项目和当前STTR奖项下的DTE方法论。它包含了一个小说的XSIBS 偏向性聚合物，对压接和部署胁迫的耐受性更好，血液动力学改善性能和动力孔，并扩展耐用性。其TAVR原型将经过严格测试，并且进一步优化。这些目标将通过采用创新的反向钙化技术（RCT）来预测 cavd进程。我们将使用来自大型CAVD患者数据库的患者特定的重建几何形状作为精制数值模拟的输入。我们将扩展现有的CAVD患者的大型CT扫描数据库（目前n = 750），以及从两个其他医疗中心（n = 293和94）中使用TAVR数据库），分类疾病的进展以进一步阐明，计划和预测介入结果。使用RCT作为前瞻性钙化生长的预测模型的基础 - 均在三尖（TAV）和双刺CAVD患者，我们将采用一种合并的硅和体外生物力学分析，将包括详细和精制的结构，FSI（流体结构相互作用）和CFD（计算流体动力学）模拟在患者特定的几何形状中从CT扫描重建。异质组织通过对手术CAVD标本的生物力学测试，将获得AVC组件的性能患者。多尺度组织和计算建模将利用从微CT测量到的输入到微调模型。基于RCT模型，各种CAVD阶段将使用FSI进行研究，并验证在左心模拟器（LHS）和制造的3D印刷模型中进行血液动力学测量血管模拟中CAVD患者的复制品复制器系统，具有后续血栓形成性由柏林左心室辅助装置和Syncardia供电的流动环的测量值总人工心脏。我们将使用上面的Polynova聚合物TAVR阀的体外血液动力学和耐用性微调方法以及Vivitro Hi-Cycle系统，并为BAV患者开发专门的设计部署和阀门偏心问题。在活心人类模型（LHHM）中使用硅型建模，我们将评估可预测CCA和与TAVR相关的房室阻塞的组织菌株部署，并将成功的TAVR病例与CCA和起搏器植入的案例进行比较。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效率降低偏心率和密封PVL。

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

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.