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.

补充奖项目摘要 项目总结：心房颤动（AF）是最常见的持续性心律失常： 每年有8万人死亡，影响大约340万美国人，预计将增加到1000万人。 未来30到40年。终止房颤的主要电疗法--直流电复律有明显的副作用 包括电穿孔和组织损伤，以及可能导致胃吸入的镇静风险 内容物、肺炎和其他问题。对于阵发性心脏病，射频消融的成功率仅高达60%。 房颤，但不到30%的持续性房颤。方法来管理房颤并不都是成功的，需要改进。 在本补充中，我们建议进一步研究和优化我们开发的低能量电治疗AF 低能量抗纤颤起搏（LEAP）。这包括一系列5个电脉冲， 心律失常的主导频率来自两个场电极，而不是来自点源。我们已经证明 LEAP的成功率超过94%，使用的能量不到心脏复律的10%。LEAP通过以下方式抑制AF： 在组织内的异质性处创建虚拟电极，这允许AF的加速或欠驱动起搏。 假设同步是AF通过LEAP终止的机制，因此可以应用于任何 动物物种，并优化用于人类，并最终用作需要非常小能量的治疗。 在本补充中，我们将LEAP的实施扩展为通过旋转场而不是 静态场这是我们研究的一个自然延伸，它源于小组在表演时的讨论， 分析LEAP实验。这是一个完美的扩展项目的研究生采取和完成在剩余的 由于许多所需的计划和实验设置已经到位，因此父母补助金的时间已经结束。研究生 一名学生（Giraldo Pino）将扩展数值模拟，以研究由旋转电动机提供的LEAP效应 场，而不是一个固定的，他还将扩大LEAP实验在猪心房实施旋转 现场的实验设置，并进行实验。这个项目的假设是，除颤已经 显示出当沿着心脏纤维的轴沿着施加场时需要较低的能量。由于中庭有一个复杂的 在解剖结构中，纤维以不同程度旋转通过右心房和左心房，预期旋转场将 能够以较低能量激励壁内虚拟电极。本项目采用综合优化的方法， LEAP同时在猪心房进行模拟和实验，因此该项目将培训皮诺先生 不同的领域，并产生许多新的技能。 Pino先生将在猪心房中反复进行数值模拟和离体AF实验，以测试 假设，并使用它来优化旋转场的电极配置，以使用最低能量抑制AF 可能（低于疼痛阈值），从而为使用LEAP作为另一种植入式设备的开发铺平了道路。 管理患者房颤的方法。