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: 10603460
• 负责人: Howard Levin
• 金额: $ 78.45万
• 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/10603460
• 关键词: Ablation; Acceleration; Acoustics; Acute; Adverse effects; Alcohols; Anatomy; Animal Model; Animals; Brain; Cardiac Electrophysiologic Techniques; Cardiac conduction system; Catheters; Certification; Characteristics; Chest Pain; Chronic; Clinical; Clinical Pathology; Clinical Trials; Coronary artery; Critical Illness; Dangerousness; Data; Defibrillators; Development; Devices; Disease; Dyspnea; Elements; Endothelium; Equilibrium; Equipment; Femur; Frequencies; Future; Gel; Geometry; Grant; Health; Heart Block; Heart Diseases; Histopathology; Human; Hypertrophic Cardiomyopathy; Hypertrophy; Industry Standard; Inflammation; Inherited; Injury; International; Irrigation; Laboratories; Left; Lesion; Life; Lung; Medical; Methods; Modality; Nature; Obstruction; Operative Surgical Procedures; Organ; Output; Pacemakers; Pathology; Patients; Performance; Persons; Phase; Physics; Pre-Clinical Model; Preparation; Procedures; Process; Prognosis; Radiation; Refractory; Reporting; Resistance; Resolution; Right ventricular structure; Risk; Risk Reduction; Safety; Small Business Innovation Research Grant; Source; Sterility; System; Techniques; Technology; Testing; Therapeutic; Thick; Thinness; Thrombus; Tissues; Transducers; Ultrasonic Transducer; Venous; Ventricular; Ventricular septum; Work; animal data; atrioventricular node; behavior observation; cardiac magnetic resonance imaging; commercialization; comorbidity; design; design verification; dosimetry; healing; heart rhythm; implantation; improved; manufacturability; manufacture; meetings; minimally invasive; mortality; novel; patient subsets; pre-clinical; preservation; prototype; public health relevance; research clinical testing; response; side effect; tool; ultrasound; ultrasound ablation; verification and validation

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 阻塞性肥厚性心肌病（OHCM）是一种常见的遗传性心脏病，可能引起主要局限性 日常生活行为，预后不良和死亡率。仅在美国，就有多达1.5 m的HCM患者，2/3 患有该疾病的阻塞性形式，对医疗管理的难治程度超过50k，并且是 候选分子还原疗法（SRT）。尽管如此，目前指示的50K每年只有约1200名患者 接受SRT，使绝大多数最严重的患者未经治疗。原因是高度侵入性的性质 导致频率心律异常的现有SRT需要植入起搏器或心脏扭曲器 除颤器（ICD）具有不可接受的围场和术后死亡率（最高10％）。此外，许多 由于现有的合并症和/或解剖学局限性，患者不适合现有的SRT程序。 这一II期SBIR提议通过精确针对阻塞来源来开发OHCM的新型治疗方法 使用新型的高强度热超声（HITU）导管在介入隔膜（IVS）上。我们的方法 使用现有的送货工具并了解相对安全，股静脉静脉的方法（RV） 在心脏电生理中。治疗的重点是将HITU的交付以选择性地消除整个宫心个性中心 在子心心脏（His-Purkinje）上保留心脏传导系统时，IVS的ivs的风险降低了 需要起搏器或ICD插入的心脏块。 该提议建立在声学物理学的第一阶段等效工作，并具有原型的临时概念证明 导管表明，通过在山脉中产生深层病变，可以减小IVS的厚度 约为30％。基于导管灌溉特征和烈馆的自然聚焦特征，该特征很少 即使在该地区大量消融的情况下，也可以避免心内心脏块。 该提案的目的将集中于导管设计元素和制造方法的成熟，以使 适用于临床评估的原型设备，验证系统对相关国际的功能和安全性 安全标准（部分IEC 60601-2-62标准），并验证此疗法的安全性，效率和耐用性 急性和慢性（3个月）临床前模型通过临床接受方式（心脏MRI，TTE，临床病理学， 严重的病理学和组织病理学）。 本赠款中获得的信息将用于直接支持与FDA提交的早期可行性IDE提交 赠款未来阶段的一部分。我们系统的商业化将使救生疗法对成千上万的批判性疗法带来 每年患病的患者，有时会扩展到在疾病的早期治疗HCM患者之前的治疗 站立的阻塞性肥大会导致不可逆转的健康后果。