High-Intensity Ultrasound Ablation for Septal Reduction Therapy of Hypertrophic Cardiomyopathy

高强度超声消融室间隔缩小术治疗肥厚型心肌病

• 批准号: 10339776
• 负责人: Babak Nazer
• 金额: $ 60.29万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-15 至 2022-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10339776
• 关键词: 3-Dimensional; Ablation; Acoustics; Alcohols; Anatomy; Animal Experimentation; Animals; Arrhythmia; Arteries; Award; Bundle-Branch Block; Cardiac ablation; Catheters; Chest Pain; Cicatrix; Clinical; Complication; Coronary artery; Custom; Development; Devices; Disease; Documentation; Due Process; Dyspnea; Echocardiography; Electrophysiology (science); Endocardium; Ensure; Feasibility Studies; Fibrosis; Frequencies; Genetic Diseases; Gold; Health Services Accessibility; Heart Septum; Heart failure; Histology; Hypertrophic Cardiomyopathy; Hypertrophy; Image; Incidence; Investigation; Laboratories; Left; Lesion; Location; Mechanics; Methods; Modeling; Morbidity - disease rate; Myocardial; Myocardium; Obstruction; Operative Surgical Procedures; Pacemakers; Pathology; Patients; Perioperative; Physics; Physiologic pulse; Positioning Attribute; Procedures; Process; Radial; Research; Research Methodology; Research Personnel; Resolution; Right ventricular structure; Risk; Safety; Signal Transduction; Sonication; Statistical Study; Sudden Death; Symptoms; System; Testing; Therapeutic; Thick; Time; Tissues; Transducers; Translating; Translations; Ultrasonic Therapy; Ultrasonic Transducer; Validation; Venous; Ventricular; Ventricular septum; Work; animal data; cardiac magnetic resonance imaging; coronary fibrosis; design; first-in-human; follow-up; heart imaging; high risk; image processing; implantation; improved; in vivo; indexing; mortality; mortality risk; multidisciplinary; novel; novel strategies; porcine model; preclinical safety; prototype; real time monitoring; reduce symptoms; simulation; simulation software; ultrasound; ultrasound ablation

PROJECT SUMMARY Obstructive hypertrophic cardiomyopathy (HCM) causes significant symptoms and morbidity due to left ventricular outflow tract obstruction (LVOTO). Interventricular septal (IVS) reduction procedures for LVOTO such as alcohol septal ablation and surgical myectomy relieve symptoms and reduce sudden death risk, but are often initiated late in the disease process due to their peri-operative risk, anatomic constrains, complications (particularly atrio-ventricular (AV) block) and limited efficacy. Our laboratory has developed an attractive approach to IVS reduction therapy (SRT) and obtained preliminary large animal data using a high- intensity ultrasound (HIU) catheter system for the treatment of oHCM, severe LVOTO and its consequences. HIU has distinct benefits over existing SRT methods in that it: 1) is less invasive (delivered via a femoral venous approach to the right ventricle (RV)). 2) selectively ablates the mid-myocardium while sparing the sub-endocardium (which contains the His- Purkinje system), thereby reducing risk of AV block. 3) does not rely on unpredictable anatomic availability of septal perforator coronary artery branches. This proposal will further develop HIU IVS reduction by optimizing lesion size and depth, avoiding the near-field subendocardium, tracking catheter location/orientation/contact, confirming effective formation non- invasively, and initiating regulatory work to position us for first-in-human studies with a subsequent award. In Aim 1, we will use acoustic simulations to design, fabricate and validate optimal HIU transducers and catheters in ex-vivo models. Aim 2 will develop and test several advanced catheter design features that will confirm transducer-tissue contact, track catheter location in real time, and confirm effective IVS ablation after HIU sonication is performed. Aim 3 will study fully-developed HIU catheters in-vivo to determine ability to reduce IVS thickness (and local myocardial mechanics) over 30 day survival. The assembled team includes exerts in therapeutic ultrasound, acoustic physics, echocardiography, cardiac MRI, large animal research methods, research sonographer, and an HCM clinical researcher who will help with eventual translation of this work to first-in-man studies. Regulatory consultants will ensure that animal studies are performed in a Good Labor and Practices (GLP)-compliant manner, positioning our group for an Investigational Device Exemption for an Early Feasibility Study with subsequent awards.

项目摘要 阻塞性肥厚性心肌病（HCM）引起左侧的明显症状和发病率 心室流出道阻塞（LVOTO）。 LVOTO的介入间隔（IVS）还原程序 例如酒精中的消融和手术肌切除术缓解症状并降低猝死风险，但 由于其围手术期风险，解剖学的约束，通常在疾病过程后期开始。 并发症（尤其是心脏室里（AV）块）和有限的功效。我们的实验室已经开发了 有吸引力的IVS还原疗法（SRT）的方法，并使用高级动物数据获得了初步的大型动物数据 强度超声（HIU）导管系统用于治疗OHCM，严重的LVOTO及其后果。 HIU比现有SRT方法具有明显的好处： 1）侵入性较小（通过股心静脉静脉输送到右心室（RV））。 2）选择性地浸入肌心室中的中心时，请放在子心脏中（其中包含his-- Purkinje系统），从而降低了AV块的风险。 3）不依赖间隔穿孔冠状动脉分支的不可预测的解剖学可用性。 该建议将通过优化病变的大小和深度来进一步发展HIU IVS，避免 近场亚心脏，跟踪导管位置/方向/接触，确认有效的形成非 - 令人震惊的，并发起监管工作，以将我们定位为首次人类研究，并随后的奖励。在 AIM 1，我们将使用声学模拟设计，制造和验证最佳HIU传感器和导管 在前体模型中。 AIM 2将开发和测试几个先进的导管设计功能，以确认 传感器组织接触，实时轨道导管位置，并确认HIU后有效的IVS烧蚀 进行超声处理。 AIM 3将在体内研究完全发达的HIU导管，以确定降低的能力 在30天的生存中，IVS厚度（和局部心肌力学）。 组装团队包括在治疗性超声，声学物理学，超声心动图， 心脏MRI，大型动物研究方法，研究超声波检查员和HCM临床研究人员将 最终将这项工作翻译成第一名研究。监管顾问将确保动物 研究是以良好的劳动和实践（GLP）的方式进行的，将我们的小组定位为 对早期可行性研究的调查设备豁免，并随后的奖项。