Development and Pre-Clinical Testing of a Smart Defibrillator Algorithm for Treatment of Cardiac Arrhythmias

用于治疗心律失常的智能除颤器算法的开发和临床前测试

• 批准号: 10260027
• 负责人: MARTIN L. MAYSE
• 金额: $ 25.17万
• 依托单位: ARRHYTHMIA DYNAMICS, LLC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-15 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10260027
• 关键词: Algorithms; Animal Model; Arrhythmia; Atrial Fibrillation; Benign; Cardiac; Cell Death; Computer Models; Coupling; Data; Defibrillators; Development; Devices; Electric Countershock; Electroporation; Energy Therapy; Entropy; Goals; Grant; Health Care Costs; Heart; Heart Atrium; Injury; Learning; Life; Maps; Measures; Modeling; Myocardial Stunning; Optics; Pain; Pain Threshold; Palate; Patients; Pattern; Performance; Phase; Preclinical Testing; Predictive Value; Probability; Randomized Controlled Trials; Rattus; Resolution; Risk; Savings; Shock; Sinus; Stimulus; Time; Tissues; United States; Ventricular; Ventricular Arrhythmia; Ventricular Fibrillation; Work; base; clinically relevant; density; experience; feasibility testing; improved; innovation; mortality; myocardial injury; prospective test; sensor; spatiotemporal; sudden cardiac death; voltage

Project Summary / Abstract: Significance: Each year 300,000 to 400,000 patients experience sudden cardiac death in the United States. For patients at risk, implantable cardiac defibrillators (ICDs) improve survival, largely through the delivery of high energy shocks to restore sinus rhythm. While high energy shocks are clearly life-saving, they are not necessarily benign. Patients receiving high energy shocks have increased mortality and programming the device to reduce the number of shocks delivered can improve mortality. High energy shocks are associated with myocardial stunning, injury, and cell death. In addition, they are painful to the patient, are associated with significant healthcare costs, and result in more rapid battery depletion. Innovation: Arrhythmia Dynamics, LLC is developing the IntelliSync ICD control algorithm which enable ICDs to save lives while minimizing the use of harmful and damaging high energy shocks. IntelliSync will do this in two ways: 1) recognizing ventricular arrhythmia episodes which have high probability of terminating on their own without therapy; and 2) making the delivery of low energy defibrillation more likely to terminate the arrhythmia by optimally timing it to a period of high baseline synchronization in the ventricular chambers. Approach: In this grant we propose testing the feasibility of these algorithms in computational and rat models of ventricular fibrillation. In order to be clinically relevant, the algorithms must function and guide the defibrillator’s decision quickly. The goal of our IntelliSync algorithm are 2-fold: 1) Analyze the first 6-8 seconds of an arrythmia within 2 seconds, recognize patterns of regional coupling within the heart that herald imminent arrhythmia termination. If identified, the algorithm would trigger the ICD to wait for VF to terminate on its own, and only deliver therapy after a time-out period has occurred. 2) Measure patterns of coupling within the heart and time low energy therapy (if appropriate) to a period of high synchronization when it is more likely to succeed. IntelliSync may also work for atrial fibrillation (AF) and could make an atrial defibrillator palatable if shocks above the pain threshold could be avoided. Aim 1 (months 1-6): Optimize algorithm performance in computational models of ventricular fibrillation Sub-aim 1A: Determine minimum spatiotemporal resolution needed to represent high density intracellular voltage maps. Sub aim 1B: Identify threshold of change in the RQA variable Entropy which predicts imminent termination. Sub-aim 1C: Demonstrate that low energy therapies can be effectively timed to periods of greater tissue synchronization. Aim 2 (months 3-9): Demonstrate feasibility of delivering low energy therapy timed to period of high synchronization based on real-time calculations in a small animal model of VF Sub aim 2A: Demonstrate that synchrony measured from limited epicardial sensors are representative of full optical maps Sub-aim 2B: Establish threshold values for the RQA variable Entropy which identify episodes likely to self-terminate Sub-aim 2C: Prospectively test threshold value of Entropy from Aim 2B. Sub-Aim 2D: Demonstrate feasibility of performing real-time RQA calculations to guide delivery of low energy therapy.

项目概要/摘要： 重要性：在美国，每年有30万至40万患者发生心脏性猝死。患者 植入式心脏除颤器（ICD）主要通过向患者提供高能量电击来提高生存率， 恢复窦性心律虽然高能量冲击显然可以挽救生命，但它们不一定是良性的。患者接受 高能量电击增加了死亡率， 降低死亡率。高能电击与心肌顿抑、损伤和细胞死亡有关。此外他们 对患者来说是痛苦的，与显著的医疗保健成本相关，并且导致更快的电池耗尽。 创新：Arrhythmia Dynamics，LLC正在开发IntelliSync ICD控制算法，使ICD能够挽救生命 同时最小化有害和破坏性高能量冲击的使用。IntelliSync将通过两种方式实现这一点：1） 识别在没有治疗的情况下自行终止的概率很高的室性心律失常发作; 以及2）通过将低能量除颤的递送最佳地定时到 心室腔中的高基线同步期。 方法：在这项资助中，我们提出在计算和大鼠模型中测试这些算法的可行性。 心室颤动为了与临床相关，算法必须起作用并指导除颤器的 迅速决定。我们的智能同步算法的目标是2倍：1）分析前6-8秒的心律失常在2 几秒钟，识别心脏内区域耦合的模式，预示着即将到来的心律失常终止。如果 识别后，算法将触发ICD等待VF自行终止，并且仅在 超时时间已发生。2)测量心脏内的耦合模式并定时低能量治疗（如果 适当的）到更有可能成功的高度同步的时期。IntelliSync也可用于心房 心房纤颤（AF），如果可以避免高于疼痛阈值的电击，则可以使心房除颤器变得可口。 目标1（1-6个月）：优化心室颤动计算模型中的算法性能 子目标1A：确定表示高密度细胞内电压图所需的最小时空分辨率。 子目标1B：确定预测即将终止的RQA变量熵的变化阈值。 子目标1C：证明低能量治疗可以有效地定时到更大的组织同步周期。 目标2（3-9个月）：证明将低能量治疗定时到高同步期的可行性 基于VF小动物模型的实时计算， 子目标2A：证明从有限心外膜传感器测量的同步性可代表完整光学标测图 子目标2B：确定RQA变量熵的阈值，以识别可能自我终止的发作 子目标2C：目标2B的熵的概率测试阈值。 子目标2D：证明执行实时RQA计算以指导低能量治疗输送的可行性。