Low Energy Defibrillation

描述（由申请人提供）：心律失常是发达国家发病率和死亡率的主要原因。尽管各种心律失常的生理机制、解剖和遗传决定因素以及病因学存在深刻差异，但只有两种主要治疗方法：电治疗和消融治疗。药物治疗大多无效或受到副作用的阻碍。房性快速性心律失常的消融治疗越来越被接受。然而，消融手术复杂、耗时，并且具有许多副作用。几种电疗方法在预防室性心动过速和室颤（VT/VF）引起的心脏性猝死以及阻止房性心动过速和室颤（AT/AF）方面都是有效的。然而，目前的生物电治疗范例具有许多局限性。抗心动过速起搏（ATP）是最理想的方法，由于其低能量需求，但ATP的疗效有限。高压双相电击除颤在过去的70年里已经发展成为治疗AF和VF的主要和高效的电疗法。然而，AF的能量要求是次优的：高能量电击是痛苦的，并且可能导致心肌损伤。在我们的项目中，我们的目标是解决目前电疗的局限性，并提出一个新的假设：多阶段分阶段生物电治疗将允许显着减少DFT的心房颤动。基于我们实验室先前NIH资助的研究，我们开发了一种基于几种类型的多脉冲电疗法终止房性快速性心律失常的方法，这些电疗法具有低、阶段性（即逐渐降低）的能量水平和频率：（1）远场低能量多次电击，（2）远场超低能量夹带刺激，和（3）近场夹带起搏。我们将探索两个技术平台来实施和进一步研究我们的新方法：（1）最先进的基于铅的植入式设备和（2）伊利诺伊大学香槟分校罗杰斯实验室开发的柔性电子产品。本项目的成功完成将通过以下方式推进心律失常的植入式生物电治疗：（1）减少高压电击引起的心肌损伤和继发于该损伤的电击后传导异常，（2）减少与快速性心律失常终止相关的疼痛，以及（3）减少植入式器械的能耗。将DFT降低到0.2J以下可能使数百万AF患者的植入式心房除颤成为可能。由John A.罗杰斯可能会改变基于高解剖分辨率的局部感知和异常心律的多阶段治疗的心律失常的电疗法。

DESCRIPTION (provided by applicant): Heart rhythm disorders are the leading cause of morbidity and mortality in the developed world. Despite a profound difference in physiological mechanisms, anatomic and genetic determinants, and etiology of various arrhythmias, there are only two predominant treatments: electric and ablative therapies. Pharmacological therapy has been mostly ineffective or hampered by side effects. Ablative therapy for atrial tachyarrhythmias is growing in acceptance. However, the ablation procedure is complex, time-consuming, and has a number of side effects. Several modalities of electrotherapy have been effective in preventing sudden cardiac death due to ventricular tachycardia and fibrillation (VT/VF), and in arresting atrial tachycardia and fibrillation (AT/AF). However, the current bioelectric therapy paradigm has a number of limitations. Antitachycardia pacing (ATP) is the most desirable approach due to its low energy requirement, but the efficacy of ATP is limited. High- voltage biphasic shock defibrillation has evolved over the last 70 years as the dominant and highly effective electrotherapy against both AF and VF. However, the energy requirements for AF are suboptimal: high-energy shocks are painful and could cause myocardial damage. In our project we aim to address the limitations of current electrotherapy and present a novel hypothesis: multi-stage phased bioelectric therapy will allow significant reduction in DFT for atrial fibrillaton. Based on previous NIH-funded research from our laboratory we have developed an approach that terminates atrial tachyarrhythmia based on several types of multiple pulse electrotherapies with low, phased (i.e. progressively reducing) energy levels and frequencies: (1) far-field low energy multiple shocks, (2) far-field ultra-low energy entrainment stimulation, and (3) near-field entrainment pacing. We will explore two technological platforms to implement and further investigate our novel method: (1) state-of-the-art lead-based implantable device and (2) flexible electronics developed by the Rogers laboratory at the University of Illinois, Urbana-Champagne. Successful completion of this project will advance implantable bioelectric therapy of cardiac arrhythmias by (1) reducing high-voltage shock induced myocardial damage and post-shock conduction abnormalities secondary to this damage, (2) reducing pain associated with termination of tachyarrhythmias, and (3) reducing energy consumption in the implantable devices. Reduction of the DFT below 0.2J is likely to make implantable atrial defibrillation possible for millions of AF patients. Novel stretchable electronic technology developed by John A. Rogers is likely to transform electrotherapy of cardiac arrhythmias based on high anatomic resolution local sensing and multi-stage therapy of aberrant rhythms.