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

• 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
• 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

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.

项目摘要 梗阻性肥厚型心肌病(OHCM)是一种常见的遗传性心脏病，可导致严重的 日常生活行为，预后差，死亡率高。仅在美国就有多达150万人患有HCM，占全球人口的三分之二 有阻塞性疾病，但仍有超过50000人无法进行医疗管理，并且 间隔缩小治疗(SRT)的候选对象。尽管如此，目前显示的50000名患者中，每年只有1200名左右 接受SRT，使绝大多数最严重的患者得不到治疗。原因是具有高度侵入性的 现有的SRT导致频率心律异常，需要植入起搏器或心律转复器 使用除颤器(ICD)的患者，围手术期和术后死亡率高得令人无法接受(高达10%)。此外，许多 由于存在并发症和/或解剖学限制，患者不适合进行现有的SRT手术。 这项第二阶段的SBIR建议开发一种新的治疗方法，通过精确定位梗阻的来源来治疗oHCM 使用一种新型的高强度治疗性超声(HITU)导管对室间隔(IVS)进行治疗。我们的方法 采用相对安全的股静脉途径进入右室(RV)，使用现有的分娩工具和技术 心脏电生理学。治疗重点是应用HITU选择性消融整个中层心肌 同时避免心脏传导系统位于心内膜下(希氏-浦肯野)，从而降低 需植入起搏器或ICD的心脏传导阻滞。 这项建议建立在第一阶段--声学物理中的等效工作，以及用原型进行的临床前概念验证的基础上 导管显示，通过HITU在中隔产生深部病变，IVS厚度可以减少 增加了大约30%。基于导管冲洗的特点和HITU的自然聚焦特性，节省了亚 即使在该区域广泛消融的情况下，也可以避免心内膜、心脏传导阻滞。 这项提案的目标将集中在导管设计元素和制造方法的成熟上，以使 适用于临床评估的样机装置，向相关国际机构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、有效性和持久性 通过临床接受的方式(心脏MRI、TTE、临床病理学、 大体病理学和组织病理学)。 在这笔赠款中获得的信息将用于直接支持尽早向FDA提交可行性集成开发环境，如 这是赠款未来阶段的一部分。我们系统的商业化将为数以千计的危重患者带来救命治疗 每年都有病人患病，并最终在不久的将来扩大到治疗疾病早期的肥厚型心肌炎患者- 直立性梗阻性肥厚导致了不可逆转的健康后果。