Quantitative Methods for Optimizing IMR Repair

优化 IMR 修复的定量方法

• 批准号: 10320967
• 负责人: Robert C Gorman
• 金额: $ 75.67万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-01-04 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10320967
• 关键词: Affect; Age; Agreement; American; Anatomy; Animal Model; Animals; Anterior; Calibration; Cells; Clinical; Clinical Research; Clinical Trials; Computer Models; Computer software; Consensus; Coronary Artery Bypass; Coupled; Data; Data Reporting; Development; Devices; Dilatation - action; Elements; Etiology; Evaluation; Geometry; Goals; Human; Image; Image Analysis; Image-Guided Surgery; Knowledge; Left Ventricular Function; Left Ventricular Remodeling; Measures; Mechanics; Methodology; Methods; Mitral Valve; Mitral Valve Insufficiency; Modeling; Myocardial Infarction; Pathogenesis; Pathology; Patients; Phase; Population; Postoperative Period; Procedures; Public Health; Recurrence; Registries; Resolution; Retrospective Studies; Secondary to; Sheep; Stress; Structure; Structure of chordae tendineae cordis; Techniques; Three-Dimensional Echocardiography; Time; Tissues; Validation; Work; base; clinical application; comparative efficacy; design; hemodynamics; imaging software; in silico; in vitro Model; in vivo; interest; novel; papillary muscle; patient subsets; prospective; randomized trial; repaired; sheep model; simulation; tool; translation to humans

Ischemic mitral regurgitation (IMR) occurs when a mitral valve (MV) is rendered incompetent by left ventricular (LV) remodeling induced by a myocardial infarction (MI). IMR is present in over 50% of patients with reduced LV function undergoing coronary artery bypass grafting (CABG) and affects at least 300,000 Americans. The magnitude of the problem is significant and is expected to grow substantially during the next 20 years as the population ages. MV repair with undersized ring annuloplasty is currently the preferred treatment for IMR. However, 1/3 of all patients treated this way develop significant recurrent IMR within 12 months. Using our real time 3D echocardiography (rt-3DE) image software we have demonstrated that IMR in humans is heterogeneous. In some patients the cause of IMR is annular dilatation and flattening. While in others leaflet tethering is the major pathology. In recent work we have demonstrated that it is in the latter group that undersized ring annuloplasty does not provide durable IMR repair. There is now agreement that adjunctive procedures are required to treat IMR caused by leaflet tethering. But there is no consensus regarding the best procedure. Despite significant interest in developing these procedures the reported data are from small, single center retrospective studies. Multi-center registries and randomized trials would be necessary to prove which procedure is superior. Given the number of proposed procedures and the complexity and duration of such studies it is highly unlikely that IMR procedure optimization could be effectively carried out this way. It is thus becoming clear that novel computational approaches directed towards optimized annuloplasty ring design and leaflet augmentation procedures can substantially reduce wasted time by minimizing trial-and-error approaches. We thus hypothesize that our state-of-the-art MV computational models, which can directly utilize rt-3DE imaging data coupled to novel effective MV leaflet and chordae tendonae (MVCT) structures, can be used in conjunction with clinically applicable large animal models to develop quantitatively optimize devices and procedures to treat IMR secondary to leaflet tethering. To prove this hypothesis the following specific aims will be achieved by leveraging our group's expertise in: 1) the pathogenesis of IMR, 2) IMR animal models, 3) rt-3DE MV imaging, 4) annuloplasty ring design, 4) MV cell-tissue coupled models, and 5) micro- and macro-anatomically accurate MV finite element models.

当二尖瓣 (MV) 因以下原因导致功能不全时，就会发生缺血性二尖瓣反流 (IMR) 心肌梗塞（MI）引起的左心室（LV）重构。 IMR 存在于超过 50% 左室功能下降的患者接受冠状动脉旁路移植术 (CABG) 并影响至少30万美国人。问题的严重性是重大的 随着人口老龄化，预计未来 20 年将大幅增长。 MV 修复 目前，小尺寸环瓣环成形术是 IMR 的首选治疗方法。然而，全部的1/3 以这种方式治疗的患者在 12 个月内出现明显的复发性 IMR。使用我们的实时时间 我们已经证明人类的 IMR 是通过 3D 超声心动图 (rt-3DE) 图像软件 异质。在一些患者中，IMR 的原因是环形扩张和变平。当在 其他传单束缚是主要的病理。在最近的工作中，我们已经证明它是在 后一组认为尺寸过小的环瓣环成形术不能提供持久的 IMR 修复。有 现在一致认为需要采取辅助程序来治疗由传单束缚引起的 IMR。 但对于最佳程序尚未达成共识。尽管人们对 开发这些程序所报告的数据来自小型、单中心回顾性数据 研究。需要多中心注册和随机试验来证明哪些 程序更优越。鉴于拟议程序的数量和复杂性 在此类研究的持续时间内，IMR 程序优化不太可能有效 是这样进行的。因此，很明显，新颖的计算方法指导 优化瓣环成形环设计和小叶增强手术可以 通过最大限度地减少试错方法，大大减少浪费的时间。我们因此 假设我们最先进的 MV 计算模型可以直接利用 rt-3DE 成像数据与新型有效 MV 瓣叶和腱索 (MVCT) 相结合 结构，可与临床适用的大型动物模型结合使用 开发定量优化设备和程序来治疗继发于传单的 IMR 网络共享。为了证明这一假设，将通过利用以下具体目标来实现 我们团队的专业知识包括：1) IMR 发病机制，2) IMR 动物模型，3) rt-3DE MV 成像，4) 瓣环成形环设计，4) MV 细胞-组织耦合模型，以及 5) 微和 宏观解剖学精确的 MV 有限元模型。

项目成果

Invited Commentary.

特邀评论。

• DOI: 10.1016/j.jvs.2008.11.103
• 发表时间: 2009
• 期刊: Journal of vascular surgery
• 影响因子: 4.3
• 作者: Dardik,Alan

Computational Investigation of Transmural Differences in Left Ventricular Contractility.

左心室收缩力跨壁差异的计算研究。

• DOI: 10.1115/1.4034558
• 发表时间: 2016
• 期刊: Journal of biomechanical engineering
• 作者: Wang,Hua;Zhang,Xiaoyan;Dorsey,ShaunaM;McGarvey,JeremyR;Campbell,KennethS;Burdick,JasonA;Gorman3rd,JosephH;Pilla,JamesJ;Gorman,RobertC;Wenk,JonathanF
• 通讯作者: Wenk,JonathanF

In-vivo transducer to measure dynamic mitral annular forces.

用于测量动态二尖瓣环力的体内传感器。

• DOI: 10.1016/j.jbiomech.2012.03.009
• 发表时间: 2012
• 期刊: Journal of biomechanics
• 影响因子: 2.4
• 作者: Siefert,AndrewW;Jimenez,JorgeH;West,DustinS;Koomalsingh,KevinJ;Gorman,RobertC;Gorman3rd,JosephH;Yoganathan,AjitP
• 通讯作者: Yoganathan,AjitP

An ovine model of pulmonary insufficiency and right ventricular outflow tract dilatation.

肺功能不全和右心室流出道扩张的绵羊模型。

• 发表时间: 2012
• 期刊: The Journal of heart valve disease
• 作者: Robb,JDaniel;Harris,MatthewA;Minakawa,Masahito;Rodriguez,Evelio;Koomalsingh,KevinJ;Shuto,Takashi;Dori,Yoav;Gorman,RobertC;Gorman3rd,JosephH;Gillespie,MatthewJ
• 通讯作者: Gillespie,MatthewJ

Isogeometric finite element-based simulation of the aortic heart valve: Integration of neural network structural material model and structural tensor fiber architecture representations.

• DOI: 10.1002/cnm.3438
• 发表时间: 2021-04
• 期刊: International journal for numerical methods in biomedical engineering
• 影响因子: 2.1
• 作者: Zhang W;Rossini G;Kamensky D;Bui-Thanh T;Sacks MS
• 通讯作者: Sacks MS