Therapeutic Microlesioning by Contrast Echocardiography for Myocardial Reduction

通过对比超声心动图进行微损伤治疗以减少心肌

• 批准号: 8341386
• 负责人: Oliver D Kripfgans
• 金额: $ 36.68万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-17 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8341386
• 关键词: Ablation; Alcohols; Anterior; Area; Arrhythmia; Automobile Driving; Cardiac; Cardiac Myocytes; Cardiac Surgery procedures; Cardiovascular Diseases; Cicatrix; Complex; Contrast Media; Contrast echocardiography procedure; Development; Diagnostic; Diagnostic Imaging; Echocardiography; Effectiveness; Electrocardiogram; Family suidae; Feedback; Genetic; Gold; Healed; Heart Block; Histology; Hypertrophic Cardiomyopathy; Hypertrophy; Image; Imagery; In Situ; Incidence; Infusion procedures; Intervention; Left; Left Ventricular Outflow Obstruction; Life; Mechanics; Medical; Methods; Microbubbles; Modeling; Monitor; Myocardial; Myocardial perfusion; Myocardial tissue; Myocardium; Obstruction; Outcome; Pacemakers; Paint; Palpitations; Patients; Physiologic pulse; Positioning Attribute; Procedures; Protocols documentation; Public Health; Quality of life; Rattus; Reporting; Research; Right Ventricular Hypertrophy; Safety; Shortness of Breath; Signal Transduction; Sudden Death; System; Systems Development; Testing; Therapeutic; Time; Tissues; Treatment Efficacy; Treatment Protocols; Tumor Debulking; Ultrasonics; Ultrasonography; Ventricular; attenuation; diagnosis standard; experience; follow-up; healing; improved; indexing; injured; innovation; innovative technologies; minimally invasive; new technology; outcome forecast; premature; prophylactic; research clinical testing; tool

DESCRIPTION (provided by applicant): Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disease, occurring in 1 in 500 people. For some young patients, the first sign is sudden death. Septal hypertrophy leads to obstruction of the left ventricular outflow path and about one-third of patients with obstruction remain symptomatic after pharmacological therapy. Presently available treatments to reduce obstruction are open heart surgery for septal myectomy and transcatheter septal ablation with alcohol. The less invasive alcohol ablation procedure unfortunately has a high incidence of serious complications and is not widely applied. A completely new non-invasive option for tissue reduction is sorely needed for HCM and potentially other myocardial hypertrophies. The objective of this project is to create a safer, gentler method of myocardial reduction for HCM. Myocardial contrast echocardiography (MCE) has enabled visualization of myocardial perfusion by imaging strong echos from contrast-agent microbubbles. For high amplitude MCE, intermittent destruction of contrast microbubbles has been shown to lethally injure cardiomyocytes by the cavitation mechanism, which leads to randomly scattered microlesions seen in histology. The central hypothesis driving this project is that the microlesioning effect seen in diagnostic MCE can be enhanced to achieve therapeutically efficacious cardiac reduction. Echocardiography together with electrocardiography is the gold standard for diagnosis and treatment follow-up for HCM. The potential breakthrough resulting from fusion of enhanced diagnostic MCE with controlled microlesioning, for therapeutic MCE (TMCE), creates a compelling rationale for this project. Our research strategy has three specific aims: (1) enhance microlesioning by MCE for efficacious myocardial reduction with monitoring of cavitation emissions, (2) develop an ultrasonic system with TMCE capability and treatment feedback and (3) demonstrate the safety and efficacy of therapeutic myocardial reduction by TMCE in a realistic porcine model. Although the possibility of MCE for HCM therapy was conceivable in 2005, three developments have coalesced to make the idea practical: the development of integrated cavitation emissions as a monitoring method for accumulated bioeffects, the realization that premature complexes in the ECG report the microlesion threshold regardless of in situ attenuation, and the availability of new platforms for ultrasound system development. The outcomes expected from achieving our aims are a safe and efficacious protocol for TMCE, an ultrasonic machine fusing imaging with therapeutic treatment, and the proof of principle for this breakthrough therapy. The overall impact of this project will be the advent of a minimally invasive new tool for myocardial reduction therapy. This innovative technology will advance medical ultrasonics and improve significantly the prognosis for patients living with life-threatening myocardial hypertrophy. PUBLIC HEALTH RELEVANCE: Myocardial hypertrophies are life threatening conditions which require myocardial reduction in many patients. A noninvasive alternative to open heart surgery would be a significant advance for public health. This project will enhance microlesioning by contrast echocardiography for efficacious myocardial reduction, develop an ultrasonic imaging system with therapeutic capability and demonstrate the safety and efficacy of this innovative new technology for myocardial reduction therapy.

描述（由申请人提供）：肥厚型心肌病 (HCM) 是最常见的遗传性心血管疾病，每 500 人中就有 1 人发生这种疾病。对于一些年轻患者来说，第一个征兆就是猝死。室间隔肥厚导致左心室流出道梗阻，约三分之一的梗阻患者在药物治疗后仍存在症状。目前可用的减少阻塞的治疗方法是心脏直视手术进行室间隔肌切除术和经导管酒精室间隔消融术。不幸的是，侵入性较小的酒精消融手术严重并发症的发生率很高，并且没有得到广泛应用。 HCM 和潜在的其他心肌肥厚迫切需要一种全新的非侵入性组织缩小选择。该项目的目标是为 HCM 创造一种更安全、更温和的心肌复位方法。心肌造影超声心动图（MCE）通过对造影剂微泡的强回声进行成像，实现了心肌灌注的可视化。对于高振幅 MCE，对比微泡的间歇性破坏已被证明会通过空化机制致命地损伤心肌细胞，从而导致在组织学中看到随机分散的微损伤。推动该项目的中心假设是，可以增强诊断性 MCE 中观察到的微损伤效应，以实现治疗有效的心脏复位。超声心动图与心电图一起是 HCM 诊断和治疗随访的金标准。增强型诊断性 MCE 与控制性微损伤融合带来的潜在突破，用于治疗性 MCE (TMCE)，为该项目创造了令人信服的理由。我们的研究策略有三个具体目标：（1）通过监测空化发射来增强 MCE 的微损伤，以实现有效的心肌缩小，（2）开发具有 TMCE 功能和治疗反馈的超声系统，（3）在现实的猪模型中证明 TMCE 治疗性心肌缩小的安全性和有效性。虽然 MCE 用于 HCM 治疗的可能性在 2005 年就已经可以想象，但三项进展已经结合起来使这一想法变得可行：开发集成空化发射作为累积生物效应的监测方法，实现心电图中的过早复合体报告微病变阈值，而不管原位衰减如何，以及用于超声系统开发的新平台的可用性。实现我们目标的预期结果是安全有效的 TMCE 协议，这是一种将成像与治疗相融合的超声波机器，以及这一突破性疗法的原理证明。该项目的总体影响将是心肌减少治疗的微创新工具的出现。这项创新技术将推动医疗超声技术的发展，并显着改善患有危及生命的心肌肥厚患者的预后。 公众健康相关性：心肌肥大是危及生命的病症，许多患者需要进行心肌缩小术。心脏直视手术的无创替代方案将是公共卫生的重大进步。该项目将通过对比超声心动图增强微损伤，以实现有效的心肌复位，开发具有治疗能力的超声成像系统，并证明这种创新的心肌复位治疗新技术的安全性和有效性。