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 项目摘要：心房颤动（AF）是最常见的持续性心律不齐：它有助于 每年80,000人死亡，影响约340万美国人，预计将增加到1000万 接下来的30至40年。终止AF的主要电疗法DC心脏version具有显着的副作用 除了镇静的风险外，包括电穿孔和组织损伤，这可能导致胃抽吸 内容，肺炎和其他问题。阵发的射频消融率仅高达60％ AF，但持久性AF的不到30％。管理AF的方法并非全部成功，需要改进。 在这种补充剂中，我们建议进一步研究和优化我们开发的低能电疗法用于AF 抑制作用，低能反振动起搏（LEAP）。这是由在或附近传递的5次电脉冲的火车组成 心律不齐的主要频率来自两个场电极，而不是从点源。我们已经表明 LEAP的成功率超过94％，使用心脏扭转能量的10％。 LEP抑制AF 在组织内部的异质性产生的虚拟电极，该电极允许AF的超速驱动或降低起搏。我们 假设同步是通过飞跃终止AF的机制，因此可以应用于任何 动物物种并被优化以用于人类，并最终用作需要非常小能量的治疗方法。 在这种补充中，我们正在扩展我们的LEAP的实施 静态场。这是我们研究的自然扩展，这是由于小组团队在表演和 分析LEAP实验。这是一个完美的扩展项目，供研究生在其余的 父母赠款的时间，因为许多必需的程序和实验设置已经到位。毕业生 学生（Giraldo Pino）将扩展数值模拟，以研究旋转电动的LEAP的效果 他还将通过实施旋转来扩展猪心房中的LEAP实验，而不是固定的场 实验设置中的字段并执行实验。该项目的假设是除颤已经 当沿心脏纤维轴施加磁场时，表明需要较低的能量。由于中庭有一个复杂的 纤维的解剖结构在各个程度上旋转，穿过左右心房，预计旋转场将是 能够以较低的能量激发壁内虚拟电极。该项目采用一种综合方法来优化 LEAP同时在猪Atria中同时模拟和实验，因此该项目将训练Pino先生 不同的领域并产生许多新技能。 皮诺先生将在猪心房中进行数值模拟和前体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（在疼痛阈值之下），从而为使用LEAP作为另一个的植入设备开发铺平了道路 患者管理AF的方法。