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着深刻的差异，但只有两种主要的治疗方法：电疗法和消融疗法。药物治疗大多无效或因副作用而受阻。消融治疗心房性心动过速越来越被接受。然而，消融过程是复杂的，耗时的，并有许多副作用。几种电疗方式在预防室性心动过速和房颤（VT/VF）引起的心源性猝死以及阻止房性心动过速和房颤（AT/AF）方面是有效的。然而，目前的生物电治疗模式有许多局限性。抗心动过速起搏（ATP）由于其低能量需求是最理想的方法，但ATP的有效性是有限的。在过去的70年里，高压双相电击除颤已经发展成为治疗房颤和房颤的主要和高效的电疗方法。然而，房颤的能量需求不是最理想的：高能电击是痛苦的，并可能导致心肌损伤。在我们的项目中，我们的目标是解决当前电疗的局限性，并提出一个新的假设：多阶段生物电疗法将使心房纤颤的DFT显著降低。基于我们实验室之前nih资助的研究，我们已经开发了一种基于几种低阶段（即逐步减少）能量水平和频率的多重脉冲电疗法来终止房性心动过速的方法：(1)远场低能量多次冲击，(2)远场超低能量牵引刺激，(3)近场牵引起搏。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)最先进的铅基植入式装置和(2)由伊利诺伊大学厄巴纳-香槟分校罗杰斯实验室开发的柔性电子设备。该项目的成功完成将通过(1)减少高压电击引起的心肌损伤和继发于这种损伤的休克后传导异常，(2)减少与快速心律失常终止相关的疼痛，(3)减少可植入装置的能量消耗来推进心律失常的植入式生物电治疗。将DFT降至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. Rogers开发的新型可拉伸电子技术可能会改变基于高解剖分辨率局部传感和多阶段异常节律治疗的心律失常电疗。

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.