Biomechanical Optimization of Mitral Valve Repair Operations and Annuloplasty Rings for Primary Mitral Valve Regurgitation

项目摘要 二尖瓣返流是世界范围内最常见的心脏瓣膜病之一，是一个重要的心脏瓣膜疾病。 全球发病率和死亡率的原因。尽管二尖瓣修复手术在几十年前就被首次描述， 近年来，已经开发了许多新的修复技术。然而，这些技术 主要基于解剖学原理描述，并以瓣膜外观和功能为指导，主要通过 视觉评估和超声心动图生物力学工程原理与基础 基本的各种二尖瓣修复技术很少被研究，修复策略仍然存在。 主要取决于外科医生的偏好。随着不断发展的指导方针倡导更早，更积极的干预 在可能的情况下进行二尖瓣修复，特别是对于易发性病变，本提案的目标是 建立对原发性二尖瓣返流二尖瓣修复生物力学的坚实理解。这是 对于优化这些复杂的二尖瓣修复手术以增强瓣膜可修复性、扩张瓣膜 修复工艺适应性强，提高修复耐久性。目标1将表征和优化我们的新型3D- 具有选择性柔性的打印二尖瓣成形环原型。使用健康人心脏MRI标记物 跟踪和疲劳试验结果，瓣膜成形环设计将得到完善，以促进自体二尖瓣 环形运动，增强耐用性。接下来，建立伴有瓣叶脱垂的原发性二尖瓣返流模型， 将产生并评估环形扩张。目前临床上采用的修复手术，即三角 使用我们的新型设计和其他瓣环成形术环进行切除、新腱索重建和瓣环成形术 具有不同的灵活性，将在这些原发性二尖瓣返流模型上进行测试。创新的生物力学 传感器和先进的心脏成像技术将有助于详细分析工程 这些手术的基本原理和瓣环成形术环设计。目标2将验证来自前 临床前绵羊模型中的体内实验。瓣膜成形环弹性对天然二尖瓣环的影响 将在健康绵羊模型中研究瓣环成形术后的运动和左心室涡流模式 没有二尖瓣返流二尖瓣修复手术将在具有慢性炎症的绵羊模型上进行评价。 后叶腱索横断引起的原发性二尖瓣返流。结果将与 离体研究。本文提出的实验具有很大的临床实用性。从这个研究结果 可以帮助外科医生获得二尖瓣修复生物力学的实质性理解，从而直接将 手术室里的病人护理

PROJECT SUMMARY Mitral valve regurgitation is one of the most prevalent valvular heart diseases worldwide and is a significant cause of global morbidity and mortality. Although mitral repair operations were first described several decades ago, numerous new repair techniques have been developed in recent years. However, these techniques were described primarily based on anatomic principles and guided by valvular appearance and function, mostly via visual assessment and echocardiography. The biomechanical engineering principles and fundamentals underlying various mitral valve repair techniques have rarely been investigated, and repair strategy remains largely based on surgeon’s preference. With evolving guidelines advocating earlier, more aggressive intervention with mitral valve repair whenever possible, especially for regurgitant lesions, the goal of this proposal is to establish a solid understanding of mitral valve repair biomechanics for primary mitral regurgitation. This is essential for optimizing these complex mitral valve repair operations to enhance valve repairability, expand valve repair technique adoptability, and improve repair durability. Aim 1 will characterize and optimize our novel 3D- printed mitral annuloplasty ring prototype with selective flexibility. Using healthy human cardiac MRI marker tracking and fatigue testing results, the annuloplasty ring design will be perfected to facilitate the native mitral annular motion and enhance durability. Next, primary mitral regurgitation models with leaflet prolapse and annular dilation will be created and assessed. Current clinically employed repair operations, namely triangular resection, neochordal reconstruction, and ring annuloplasty using our novel design and other annuloplasty rings with varying flexibility, will be tested on these primary mitral regurgitation models. Innovative biomechanical sensors and advanced cardiac imaging technologies will facilitate the detailed analysis of the engineering principles underlying these operations and annuloplasty ring designs. Aim 2 will validate findings from the ex vivo experiments in pre-clinical ovine models. The effect of annuloplasty rings’ flexibility on natural mitral annular motion and left ventricular vortex flow pattern after ring annuloplasty will be investigated in healthy ovine models without mitral regurgitation. The mitral valve repair operations will be evaluated on the ovine models with chronic primary mitral regurgitation generated by posterior leaflet chordal transection. The results will be compared to the ex vivo studies. The experiments proposed herein have great clinical applicability. Findings from this study can help surgeons gain substantial understanding of mitral valve repair biomechanics thereby translating directly to patient care in the operating room.