Spatial Resynchronization Therapy for AFib

AFib 空间再同步治疗

• 批准号: 10546248
• 负责人: Graydon Ernest Beatty
• 金额: $ 29.94万
• 依托单位: MAXWELL BIOMEDICAL INC
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2023-09-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10546248
• 关键词: Ablation; Acute; Address; Adopted; Adult; Affect; Algorithmic Analysis; Algorithms; Anesthesia procedures; Anti-Arrhythmia Agents; Arrhythmia; Atrial Fibrillation; Cardiac; Cardiac ablation; Cardiovascular system; Caring; Cessation of life; Chest; Cicatrix; Clinical; Clinical Research; Complex; Computer Simulation; Consumption; Data; Defibrillators; Development; Devices; Direct Costs; Disease; Economic Burden; Effectiveness; Electric Countershock; Electrodes; Epicardium; Event; Feedback; Freezing; Future; Harvest; Healthcare Systems; Heart Atrium; Heart failure; Hospitalization; Impaired cognition; Implant; Incidence; Infection; Institutes; Left; Left atrial structure; Legal patent; Location; Methods; National Heart, Lung, and Blood Institute; Pain; Pain Threshold; Pathway interactions; Patients; Pattern; Persons; Pharmaceutical Preparations; Pharmacology; Phase; Physiologic pulse; Physiological; Play; Positioning Attribute; Power Sources; Prevalence; Procedures; Process; Progressive Disease; Quality of life; Records; Refractory; Reporting; Risk; Role; Sedation procedure; Shock; Signal Transduction; Silicon; Site; Stroke; Survival Rate; System; Systems Theory; Technology; Testing; TimeLine; Tissues; United States National Institutes of Health; base; clinical application; commercialization; common treatment; cost; cost estimate; design; dynamic system; efficacy evaluation; efficacy validation; flexibility; functional status; hazard; heart rhythm; high risk; implantable device; in vivo; mortality; novel; patient population; phase 1 study; porcine model; relating to nervous system; response; sensor; spatiotemporal; standard of care; stroke risk; success; technology/technique; therapy design; treatment strategy; trend; voltage; wireless

ABSTRACT More than 450,000 hospitalizations each year in the US are due to atrial fibrillation (AF) which contributes to approximately 160,000 deaths. This trend has been increasing for more than two decades, with estimations that 12.1 million people in the US will have AF by 2030, placing a significant burden on the healthcare system. Complications of AF include stroke, heart failure, and increasing mortality. AF is a progressive disease with catheter ablation becoming increasingly common for the treatment of AF despite limited and highly variable success rates and complications, with arrhythmia-free survival rates < 29% at 5 years. The current acute standard of care is external cardioversion, with or without antiarrhythmic drugs. Unfortunately, high-voltage external shocks are extremely painful, can cause additional arrhythmias, and often require escalation of care at an annual cost of ~$26 billion. Efforts to address this unmet need have focused on internal atrial cardioversion which has not been widely adopted due to the invasiveness and intolerable pain suffered from shocks. Efforts to overcome these limitations have focused on wireless implantable devices which have been hindered by high power consumption attributable to power harvesting modules of the circuit design. The Maxwell Biomedical Spatial Resynchronization Therapy (SRT) System resolves the limitations of wireless implantable technologies and high energy cardioversion for treating AF by utilizing spatiotemporal identification and stimulation to globally advance refractoriness of complex reentry patterns enabling imperceptible pace-termination of AF. This is accomplished via the SATELLITETM epicardial implant device, which is a wirelessly powered flexible circuit with multiple paired electrodes that, when implanted, are distributed across the posterior wall of the left atrium. The system records cardiac electrograms from each of the electrodes and the algorithm analyzes these signals to determine electronic selection and pacing of paired electrodes using a state-of-the-art method from Dynamical System Theory. Importantly, it operates below 0.1 J, an order of magnitude below the threshold for pain. Evidence for the effectiveness of this approach has been shown in bench and in vivo studies, where the SATELLITETM silicon CMOS components and sensors demonstrated a power transfer efficiency of 68%, far exceeding current wirelessly powered devices. The ability of the algorithm to identify and pace-terminate AF has also been confirmed in an open chest swine model of AF, which supports the translatability of SRT. The Maxwell Biomedical SRT System is now ready for final refinement of the algorithm and implant hardware to achieve design freeze, which will be characterized first on the bench (Aim 1), followed by the assessment of efficacy and deliverability in vivo (Aim 2). Successful execution of Phase I studies will position SRT System for full development, clinical studies, regulatory approval (future Phase II), and commercialization of a highly disruptive technology to treat the growing population of patients with AF.

摘要 在美国，每年有超过450，000例住院治疗是由于房颤（AF）， 约16万人死亡。这一趋势已经持续了二十多年，估计 到2030年，美国将有1210万人患有AF，给医疗保健系统带来重大负担。 AF的并发症包括中风、心力衰竭和死亡率增加。AF是一种进行性疾病， 尽管有限且高度可变，但导管消融术在房颤治疗中越来越常见 成功率和并发症，5年无疟疾生存率< 29%。当前的严峻 标准治疗是体外心脏复律，使用或不使用抗心律失常药物。不幸的是，高压 外部电击非常痛苦，可能导致额外的心律失常，并且通常需要在 每年花费约260亿美元。解决这一未满足需求的努力集中在内部心房复律上 由于电击的侵入性和无法忍受的疼痛，其尚未被广泛采用。努力 为了克服这些限制，已经集中在无线可植入装置上， 归因于电路设计的功率收集模块的功率消耗。麦克斯韦生物医学 空间重建治疗（SRT）系统解决了无线植入技术的局限性 以及利用时空识别和刺激进行治疗AF的高能量心脏复律， 全面提高复杂折返模式的不应性，实现难以察觉的AF起搏终止。 这是通过SATELLITETM心外膜植入装置完成的，该装置是一种无线供电的柔性 带有多个成对电极的电路，当植入时，电极分布在左心室后壁 中庭系统记录每个电极的心电图，算法分析这些心电图 使用最先进的方法确定成对电极的电子选择和起搏的信号， 动力系统理论重要的是，它在0.1 J以下工作，比用于 痛苦实验室和体内研究已经证明了这种方法的有效性，其中 SATELLITETM硅CMOS元件和传感器的功率传输效率为68%， 超过目前的无线供电设备。算法识别和起搏终止AF的能力 在AF的开胸猪模型中也得到了证实，这支持了SRT的可平移性。的 麦克斯韦Biomedical SRT系统现已准备好进行算法和植入硬件的最终完善， 实现设计冻结，首先在试验台上进行表征（目标1），然后评估 在体内的功效和递送能力（目的2）。I期研究的成功执行将使SRT系统定位于 全面开发，临床研究，监管批准（未来的第二阶段），和商业化的高度 突破性技术来治疗不断增长的房颤患者。