Minimally Invasive High Intensity Therapeutic Ultrasound for the Treatment of Obstructive Hypertrophic Cardiomyopathy

微创高强度超声治疗梗阻性肥厚型心肌病

基本信息

批准号：
10851470
负责人：
Howard Levin
金额：
$ 12.27万
依托单位：
CORIDEA, LLC
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-05-01 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10851470
关键词：
Ablation Acoustics Acute Anatomy Cardiac Electrophysiologic Techniques Cardiac conduction system Catheters Characteristics Chronic Clinical Clinical Pathology Critical Illness Defibrillators Development Devices Disease Elements Femur Frequencies Future Grant Health Heart Block Heart Diseases Histopathology Hypertrophic Cardiomyopathy Hypertrophy Inherited International Irrigation Lesion Life Medical Methods Modality Nature Obstruction Operative Surgical Procedures Pacemakers Pathology Patients Persons Phase Physics Pre-Clinical Model Procedures Prognosis Refractory Right ventricular structure Risk Reduction Safety Small Business Innovation Research Grant Source System Therapeutic Thick Venous Ventricular septum Work cardiac magnetic resonance imaging commercialization comorbidity design heart rhythm implantation manufacture minimally invasive mortality novel pre-clinical prototype public health relevance research clinical testing side effect tool ultrasound

项目摘要

Project Summary Obstructive hypertrophic cardiomyopathy (oHCM) is a common inherited heart disease that can cause major limitations to daily acts of living, poor prognosis, and mortality. There are as many as 1.5 M people with HCM in the US alone, 2/3 of whom have the obstructive form of the disease with over 50k remaining refractory to medical management and are candidates for septal reduction therapy (SRT). Despite this, only ~1,200 patients per year of the 50k currently indicated receive SRT, leaving the vast majority of the most severe patients untreated. The reason for is the highly invasive nature of existing SRTs that cause frequency cardiac rhythm abnormalities requiring implantation of a pacemaker or cardioverter defibrillator (ICD) and have unacceptably high rates of peri- and post- procedural mortality (up to 10%). Additionally, many patients are unsuitable for existing SRT procedures due to existing co-morbidities and/or anatomical limitations. This Phase II SBIR proposes development of a novel treatment for oHCM by precisely targeting the source of the obstruction on the interventricular septum (IVS) using a novel high-intensity therapeutic ultrasound (HITU) catheter. Our approach takes a relatively safe, femoral venous approach to the right ventricle (RV) using existing delivery tools and knowhow within cardiac electrophysiology. Treatment focuses on delivery of HITU to selectively ablate the entire mid-myocardium of the IVS while sparing the cardiac conduction system on the sub-endocardium (His-Purkinje), thereby reducing risk of heart block requiring pacemaker or ICD insertion. This proposal builds upon the Phase I-equivalent work in acoustic physics, and pre-clinical proof of concept with a prototype catheter demonstrating that, by generating deep lesions in the mid-septum with a HITU, the IVS thickness can be reduced by approximately 30%. Based on catheter irrigation features and HITU’s natural focusing characteristics sparing the sub- endocardium, heart block can be avoided even in the setting of extensive ablation in this region. The aims of this proposal will focus on maturation of catheter design elements and manufacturing methods to make the prototype device suitable for clinical evaluation, verify the functionality and safety of the system to relevant international safety standards (particularly IEC 60601-2-62 standards), and validate the safety, efficacy, and durability of this therapy in acute and chronic (3-month) preclinical models via clinically accepted modalities (cardiac MRI, TTE, clinical pathology, gross pathology and histopathology). The information obtained in this grant will be used in direct support of early feasibility IDE submission with the FDA as part of a future phase of the grant. Commercialization of our system will bring lifesaving therapy to thousands of critically ill patients every year and eventually expand to treatment of HCM patients in earlier stages of the disease before long- standing obstructive hypertrophy resulted in irreversible health consequences.

项目概要梗阻性肥厚型心肌病 (oHCM) 是一种常见的遗传性心脏病，可导致严重限制仅在美国就有 150 万人患有 HCM，占全国的 2/3。患有阻塞性疾病的人，其中超过 50,000 人仍难以接受医疗管理，并且正在尽管如此，目前在 50,000 名患者中，每年只有约 1,200 名患者需要接受间隔复位治疗 (SRT)。接受 SRT，导致绝大多数最严重的患者得不到治疗，原因是其高度侵入性。现有的 SRT 会导致频率心律异常，需要植入起搏器或心脏复律器除颤器 (ICD) 的围术期和术后死亡率高得令人无法接受（高达 10%）。由于现有的共病和/或解剖学限制，患者不适合现有的 SRT 手术。该 II 期 SBIR 提议通过精确瞄准阻塞源来开发一种新的 oHCM 治疗方法使用新型高强度治疗超声 (HITU) 导管对室间隔 (IVS) 进行治疗。使用现有的输送工具和专业知识，采用相对安全的股静脉途径进入右心室 (RV) 心脏电生理学领域的治疗重点是 HITU 选择性消融整个中层心肌。 IVS 的同时保留心内膜下 (His-Purkinje) 上的心脏传导系统，从而降低了风险需要插入起搏器或 ICD 的心脏传导阻滞。该提案建立在声学物理学中的第一阶段等效工作以及带有原型的临床前概念验证的基础上导管证明，通过使用 HITU 在中隔中产生深层病变，可以减少 IVS 厚度基于导管冲洗功能和 HITU 的自然聚焦特性，可减少约 30%。即使在该区域进行广泛消融的情况下，也可以避免心内膜、心脏传导阻滞。该提案的目标将侧重于导管设计元素和制造方法的成熟，以使适合临床评估的原型设备，向相关国际验证系统的功能和安全性安全标准（特别是 IEC 60601-2-62 标准），并验证该疗法的安全性、有效性和耐久性通过临床可接受的方式（心脏 MRI、TTE、临床病理学、大体病理学和组织病理学）。在此拨款中获得的信息将用于直接支持向 FDA 提交早期可行性 IDE 我们的系统商业化的未来阶段的一部分将为数千名重症患者提供挽救生命的治疗。每年都有患者患病，不久之后最终扩展到疾病早期阶段的 HCM 患者的治疗长期阻塞性肥大会导致不可逆转的健康后果。