Transcatheter Strategies for Leaflet Extension to Treat Mitral Regurgitation

经导管小叶延伸治疗二尖瓣关闭不全的策略

基本信息

批准号：
10001587
负责人：
Sai Muralidhar Padala
金额：
$ 38.49万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-01 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10001587
关键词：
Acute Address American Animal Model Anterior Biomedical Engineering Blood Cardiac Cardiac Surgery procedures Catheters Chronic Clinical Clip Complex Complication Congestive Heart Failure Data Development Device Designs Devices Echocardiography Endothelium Engineering Enhancers Environment FDA approved Failure Family suidae Future Geometry Heart Heart Research Heart Valves Heart failure Height Implant Left Left Ventricular Remodeling Length Lesion Liquid substance Measurement Measures Mechanics Medical Mitral Valve Mitral Valve Insufficiency Modeling Myocardial Infarction Myocardial Ischemia Operative Surgical Procedures Outcome Patients Pharmaceutical Preparations Physiological Polytetrafluoroethylene Procedures Public Health Recording of previous events Recurrence Reflux Research Project Grants Residual state Risk Safety Sarin Site Sudden Death Surface Surgeon System Techniques Technology Testing The Sun Therapeutic Thrombosis Time Tissues Translational Research Translations Ventricular Ventricular Remodeling Work animal imaging base biomechanical engineering clinical practice clinical translation design engineering design experience feasibility trial flexibility healing heart function hospitalization rates image guided improved innovation insight member mortality multidisciplinary new technology nitinol novel parallelization preservation prototype repaired safety and feasibility sound success surgical research tissue stress

项目摘要

ABSTRACT/PROJECT SUMMARY Ischemic mitral regurgitation (IMR) is reflux of blood through the mitral valve, developing in patients surviving a myocardial infarction or chronic ischemic heart disease. 2.7 million Americans suffer from this condition and progressively develop congestive heart failure. Their hospitalization rates are higher and they present with significant risk of sudden death. Timely correction of IMR can halt adverse ventricular remodeling, but current techniques to repair IMR require open-heart surgery, a risky procedure in these patients. Several transcatheter strategies are in development, but all of them have demonstrated poor outcomes with significant remnant regurgitation or repair failure due to procedural complexity. We hypothesized that the most effective and durable technique to correct IMR is by extending the native leaflet lengths at the site of the regurgitation, restoring systolic leaflet edge parallelization, so that coaptation is restored and regurgitation is effectively eliminated. We developed a novel, flexible;; nitinol implant covered with expanded polytetrafluoroethylene, which when deployed on the anterior or posterior mitral valve leaflet extends the leaflet shelf and restores leaflet coaptation. The device integrates into the native leaflet with tissue encapsulation over 4-6 weeks, and the endothelialized tissue permanently adds to the native leaflet length for IMR correction. Strong preliminary data supporting the feasibility and safety of this concept have been generated in ex vivo and swine models. In this R01 application, we propose to advance this concept further, with a focus on optimizing the device design to best restore valve function and preserve valve mechanics. Three aims are proposed - (Aim 1) Optimize the device features to achieve best IMR reduction and highest leaflet coaptation, while preserving the native valve mechanics and fluid dynamics;; (Aim 2) investigate the durability of the device in correcting IMR in a progressively remodeling LV, investigate chronic device healing and tissue remodeling, and measure the thrombotic potential of the device in swine;; and (Aim 3) develop a trans-septal delivery catheter for image guided deployment of the device on the mitral valve, and assess the safety and efficacy of this procedure in swine. We have assembled a collaborative, multidisciplinary team with experience in biomedical device design & engineering, computational tissue and fluid mechanics, animal models and imaging, and clinical experience in transcatheter valve therapies, in an environment with a history of innovative cardiac research. There is high potential for clinical translation of this technology, and the proposed work will optimize the technology and mitigate the failure modes & risks. Completion of the proposed aims will result in a significantly better therapeutic option to repair ischemic mitral regurgitation, which is a highly translational end-point and will address a significant unmet clinical need.

摘要/项目摘要缺血性二尖瓣反流 (IMR) 是指血液通过二尖瓣反流，发生于存活下来的患者。 270 万美国人患有心肌梗塞或慢性缺血性心脏病。他们的住院率较高，并出现充血性心力衰竭。及时纠正 IMR 可以阻止不良的心室重构，但目前存在显着的猝死风险。修复 IMR 的技术需要进行心脏直视手术，这对这些患者来说是一种危险的手术。战略正在制定中，但所有战略都显示出效果不佳，并存在大量残留由于程序复杂而导致的反流或修复失败，我们提供了最有效和最有效的帮助。纠正 IMR 的持久技术是延长反流部位的原生小叶长度，恢复收缩期小叶边缘平行化，从而恢复接合并有效地进行反流我们开发了一种新型、灵活的；；覆盖有膨胀聚四氟乙烯，当部署在前二尖瓣或后二尖瓣小叶上时，其会延伸小叶架并恢复小叶接合在 4-6 周内通过组织封装整合到天然小叶中，并且内皮化组织永久性地增加了原始小叶长度，以进行强初步校正。支持这一概念可行性和安全性的数据已经在离体和猪模型中产生。在此 R01 应用程序中，我们建议进一步推进这一概念，重点是优化设备设计。为了最好地恢复瓣膜功能并保持瓣膜力学，提出了三个目标 - （目标 1）优化瓣膜。设备的特点是实现最佳的 IMR 减少和最高的小叶接合，同时保留原生瓣膜力学和流体动力学；（目标 2）研究该装置在校正 IMR 方面的耐用性逐步重塑左心室，研究慢性装置愈合和组织重塑，并测量该装置在猪体内的血栓形成潜力；以及（目标 3）开发用于成像的经房间隔输送导管引导装置在二尖瓣上的部署，并评估该程序的安全性和有效性我们组建了一支具有生物医学设备设计经验的协作型多学科团队。与工程、计算组织和流体力学、动物模型和成像以及临床经验在经导管瓣膜治疗中，在具有创新心脏研究历史的环境中。该技术具有临床转化的潜力，拟议的工作将优化该技术并减轻故障模式和风险完成拟议的目标将带来显着改善。修复缺血性二尖瓣反流的治疗选择，这是一个高度转化的终点，将解决重大的未满足的临床需求。