A Size Adjustable Pulmonary Valve Implant for Pediatric Applications

适合儿科应用的尺寸可调肺动脉瓣植入物

基本信息

批准号：
9397069
负责人：
Sophie-Charlotte Hofferberth
金额：
$ 6.31万
依托单位：
BOSTON CHILDREN'S HOSPITAL
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：
2017-08-01 至 2019-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9397069
关键词：
Achievement Address Adolescence Adopted Adverse event Advocate Affect Allografting Awareness Balloon Dilatation Biocompatible Materials Biological Preservation Caliber Cardiac Cardiac Surgery procedures Caring Child Childhood Chronic Clinical Clinical Management Communities Competence Computer Simulation Congenital Heart Defects Consensus Coupled Data Defect Development Devices Early Intervention Equilibrium Exhibits Face Failure Functional disorder Goals Growth Heart Heart Abnormalities Heart Atrium Heart failure Implant Incidence Institution Laboratories Lesion Life Live Birth Lung Modeling Morbidity - disease rate Myocardial dysfunction Obstruction Operative Surgical Procedures Outcome Patients Perioperative Positioning Attribute Procedures Prosthesis Prosthesis Implantation Pulmonary Valve Insufficiency Pulmonary Valve Stenosis Pulmonary valve structure Risk Stents Surgeon Surgical Management Symptoms Tachycardia Techniques Technology Tetralogy of Fallot Time Uncertainty Venous Ventricular Ventricular Arrhythmia Work base congenital heart disorder design exercise intolerance hemodynamics high risk implantation improved in vivo infancy innovation mortality pulmonary valve replacement reconstruction repaired restoration semilunar valve simulation success sudden cardiac death valve replacement

项目摘要

Abstract Tetralogy of Fallot (ToF) is the most common cyanotic congenital heart defect, occurring in 1 in every 3600 live births and affecting almost 10% of all children born with congenital heart disease. Contemporary management of ToF has evolved to elective complete surgical repair in early infancy, with perioperative mortality rates of <2%. Despite these advances, surgical augmentation of the right ventricular outflow tract remains a significant challenge. To date, transannular patch reconstruction, which involves disruption and enlargement of the pulmonary valve annulus, has been the most widely used repair strategy. However, a critical deficiency of this technique is the loss of structural integrity of the valvar apparatus, leading to chronic severe pulmonary insufficiency. Longitudinal data demonstrates severe pulmonary insufficiency often leads to progressive right ventricular dilation and biventricular dysfunction, leaving repaired ToF patients at significant risk of late adverse events, including development of ventricular arrhythmias, biventricular heart failure, and sudden cardiac death. To avoid these deleterious late outcomes, the majority of repaired ToF patients undergo eventual pulmonary valve replacement. The clinical pendulum is now shifting towards earlier valve replacement as it becomes increasingly evident that repaired ToF patients often develop significant right heart dysfunction several years before the onset of clinical symptoms. However, the unfortunate reality is that valve replacement options for small children are extremely limited. Existing prostheses often fail early, and, are universally unable to accommodate somatic growth of the child. Surgeons have attempted to address this urgent problem by implementing pulmonary valve-sparing repair strategies in children with ToF. Yet, emerging data from our institution demonstrates that most ToF patients who undergo valve-sparing repair develop early and progressive pulmonary insufficiency. Early loss of valve competency in ToF remains the Achilles heel of contemporary surgical management, and, critically, this unsolved problem leaves thousands of patients at ongoing risk of serious late adverse events. To address this urgent clinical problem, we propose to leverage promising simulation-based work from our group demonstrating venous-like valves remain competent across a wide range of vessel sizes, along with advances in stent technology and emerging biomaterials, to develop a growth-accommodating pulmonary valve replacement device to be implanted at the time of primary ToF repair. We propose two Specific Aims: Aim 1: Design an expandable, stent-mounted two-leaflet pulmonary valve replacement device that is capable of maintaining function across a wide range of diameters. Aim 2. Evaluate the feasibility of in vivo device expansion to accommodate somatic growth of the native pulmonary valve annulus in a growing ovine model. Achievement of this goal would represent a paradigm-shifting advance in the care of ToF patients, and, ultimately, would benefit any child who requires valve replacement early in life.

抽象的法洛四联症 (ToF) 是最常见的紫绀型先天性心脏病，每 3600 人中就有 1 人发生活产，影响近 10% 患有先天性心脏病的儿童。当代的 ToF 的管理已发展为婴儿早期选择性完全手术修复，围手术期死亡率<2%。尽管取得了这些进展，右心室流出道的手术增强仍然是一个重大挑战。迄今为止，跨环补片重建涉及破坏和肺动脉瓣环扩大，一直是应用最广泛的修复策略。然而，一个该技术的关键缺陷是瓣膜装置结构完整性的丧失，导致慢性严重肺功能不全。纵向数据表明严重的肺功能不全常常导致进行性右心室扩张和双心室功能障碍，使修复后的 ToF 患者处于晚期不良事件的重大风险，包括室性心律失常、双心室心脏的发展衰竭和心源性猝死。为了避免这些有害的后期结果，大多数修复的 ToF 患者最终接受肺动脉瓣置换术。临床钟摆现在正转向更早进行瓣膜置换，因为越来越明显的是，修复后的 ToF 患者经常会出现在临床症状出现前数年出现明显的右心功能障碍。然而，不幸的现实是，针对幼儿的瓣膜更换选择极其有限。现存的假肢通常会过早失效，并且普遍无法适应儿童的躯体生长。外科医生试图通过实施肺动脉瓣保留修复术来解决这一紧迫问题 ToF 儿童的治疗策略。然而，我们机构的新数据表明，大多数 ToF 患者接受保留瓣膜修复术的患者会出现早期进行性肺功能不全。瓣膜早期丧失 ToF 能力仍然是当代外科管理的致命弱点，而且至关重要的是，未解决的问题使数千名患者面临严重的晚期不良事件的持续风险。为了解决这一紧迫的临床问题，我们建议利用我们的有前途的基于模拟的工作小组展示了静脉样瓣膜在各种血管尺寸上仍然具有能力，以及支架技术和新兴生物材料的进步，开发适应生长的肺在初次 ToF 修复时植入瓣膜置换装置。我们提出两个具体目标：目标 1：设计一种可扩张、支架式二叶肺动脉瓣置换装置能够在各种直径范围内保持功能。目标 2. 评估可行性体内装置扩张以适应天然肺动脉瓣环的体细胞生长正在生长的绵羊模型。这一目标的实现将代表护理领域的范式转变进步的 ToF 患者，最终将使任何在生命早期需要更换瓣膜的儿童受益。