Integrative Experimental and Multiscale High Resolution ModeIntegrative Experimental and Multiscale High Resolution Modling of Atrial Arrhythmias to Optimize Low Energy Anti-fibrillation Pacing (LEAP)

综合实验和多尺度高分辨率模式房性心律失常的综合实验和多尺度高分辨率建模以优化低能量抗颤起搏 (LEAP)

• 批准号: 10250771
• 负责人: Flavio H Fenton
• 金额: $ 1.92万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10250771
• 关键词: 3-Dimensional; Address; Adopted; Affect; American; Anatomy; Animals; Area; Arrhythmia; Atrial Fibrillation; Award; Cardiac; Cessation of life; Code; Complex; Development; Devices; Differential Equation; Disease; Electric Countershock; Electrodes; Electroporation; Family suidae; Fiber; Frequencies; Heart; Heart Atrium; Heterogeneity; Human; In Vitro; Language; Left atrial structure; Life; Methods; Modeling; Optics; Pain; Pain Threshold; Patients; Peer Review; Physiologic pulse; Pneumonia; Positioning Attribute; Protocols documentation; Radiofrequency Interstitial Ablation; Research; Resolution; Right atrial structure; Risk; Rotation; Sedation procedure; Shock; Source; Stomach Content; Structure; Testing; Time; Tissues; Training; United States; disabling symptom; effective therapy; electric field; experimental study; graduate student; heart rhythm; implantable device; in silico; parent grant; programs; side effect; simulation; skills; success; virtual; voltage

Project Summary for the supplement award PROJECT SUMMARY: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia: it contributes to 80,000 deaths annually and affects approximately 3.4 million Americans, with a projected increase to 10 million over the next 30 to 40 years. The primary electrical therapy for termination of AF, DC cardioversion, has significant side effects including electroporation and tissue damage, in addition to risks from sedation that can result in aspiration of stomach contents, pneumonia, and other problems. Radiofrequency ablation has a success rate of only up to 60% for paroxysmal AF, but less than 30% for persistent AF. Approaches to manage AF are not all successful and improvements are needed. In this supplement, we propose to further study and optimize our developed low-energy electrical therapy for AF suppression, low-energy antifibrillation pacing (LEAP). This consists of a train of 5 electrical pulses delivered at or near the dominant frequency of the arrhythmia from two field electrodes, rather than from a point source. We have shown that LEAP has a success rate of more than 94% and uses less than 10% the energy of cardioversion. LEAP suppresses AF by virtual electrodes created at heterogeneities within the tissue, which permits overdrive or underdrive pacing of AF. We hypothesize that synchronization is the mechanism by which AF is terminated via LEAP and thus, can be applied to any animal species and be optimized to be used in humans and eventually to be used as treatment requiring very small energies. In this supplement we are extending our implementation of LEAP to be delivered by a rotating field instead of a static field. This is a natural extension to our study, that grew out of discussions by the group team while performing and analyzing LEAP experiments. This is a perfect extension project for a graduate student to take and complete in the remaining time of the parent grant, as many of the required programs and experimental setups are already in place. The graduate student (Giraldo Pino) will extend the numerical simulations to study the effect of LEAP delivered by a rotating electric field, rather than a stationary one, he will also extend the LEAP experiments in porcine atria by implementing a rotating field in the experimental setup and also perform experiments. The hypothesis for this project, is that defibrillation has been shown to require lower energies when the field is applied along the axis of the cardiac fibers. Since the atrium has a complex anatomy with fibers rotating in various degrees through the right and left atria, it is expected that a rotating field would be able to excite intramural virtual electrodes with lower energies. This project adopts an integrative approach to optimize LEAP suing simultaneously simulations and experiments in porcine atria, therefore this project will train Mr. Pino in different areas and generate many new skills. Mr. Pino will iteratively perform numerical simulations and ex-vivo AF experiments in pig atria to test the hypothesis and use it to optimize electrode configurations for a rotating field to suppress AF using the lowest energies possible (below the pain threshold), Thereby paving the way for development of implantable devices using LEAP as another methods for managing AF in patients.

补充奖的项目摘要 项目简介：房颤(房颤)是最常见的持续性心律失常 到每年8万人死亡，影响到大约340万美国人，预计比 接下来的30到40年。终止房颤的主要电疗法是直流电复律，副作用显著 包括电穿孔和组织损伤，以及可能导致胃吸入的镇静风险 内容、肺炎等问题。射频消融治疗阵发性心脏病的成功率只有60%。 房颤，但持续性房颤不到30%。房颤的管理方法并不都是成功的，需要改进。 在这一补充中，我们建议进一步研究和优化我们开发的治疗房颤的低能量电疗法 抑制，低能量抗纤颤起搏(LEAP)。这包括在或附近传递5个电脉冲的序列 心律失常的主要频率来自两个场电极，而不是来自点源。我们已经证明了 Leap的成功率超过94%，而使用的复律能量不到10%。LEAP通过以下方式抑制房颤 在组织内的异质性处创建的虚拟电极，允许过驱动或欠驱动的房颤起搏。我们 假设同步是通过LEAP终止AF的机制，因此可以应用于任何 它是动物物种的一种，经过优化后可用于人类，并最终用于只需很小能量的治疗。 在本补充资料中，我们将扩展实施LEAP，使其通过旋转磁场而不是 静态场。这是我们研究的自然延伸，这是团队在表演和 分析LEAP实验。对于研究生来说，这是一个完美的延伸项目，可以在剩下的时间里完成。 家长拨款的时间，因为许多必要的计划和实验设置已经到位。这位毕业生 学生吉拉尔多·皮诺将扩展数值模拟，以研究旋转电子传递的跳跃效应。 而不是静止的，他还将在猪的心房上实施旋转的跳跃实验 在实验设置中的场，并执行实验。这个项目的假设是除颤已经被 当沿着心脏纤维的轴线施加磁场时，显示需要较低的能量。因为中庭有一个综合体 解剖时，纤维在左右心房不同程度地旋转，预计旋转场将是 能够以较低的能量激发壁内虚拟电极。该项目采用了综合优化的方法 Leap在猪心房同时进行模拟和实验，因此这个项目将培训Pino先生 不同的领域并产生许多新的技能。 皮诺先生将反复在猪心房进行数值模拟和体外房颤实验，以测试 假设，并使用它来优化旋转磁场的电极配置，以使用最低能量抑制房颤 有可能(低于疼痛阈值)，从而为使用LEAP作为另一种可植入设备的开发铺平道路 房颤患者的处理方法。