His-Purkinje Pacing for Low Energy Implantable Cardioverter Defibrillators

 描述(由申请人提供)：室颤(VF)是工业化世界的主要死亡原因。室颤的唯一有效治疗方法是电除颤。仅在美国，每年就有大约150,000名室颤高危患者接受植入式心律转复除颤器(ICD)治疗。ICD传递的大电击可能会导致患者的心脏损伤和焦虑。除颤冲击能量的显著减少可能导致ICD患者死亡率的降低和生活质量的提高。这项建议的总体目标是开发一种具有临床意义的除颤策略，显著降低电击能量，使之低于传统除颤电击的疼痛和损害阈值。这一建议的主要假设是，直接发送到Purkinje系统的关键时间的起搏水平脉冲将捕获临界质量的心脏组织并终止VF。这项工作建立在对Purkinje系统在维持VF中发挥的积极作用的最新理解、低能量除颤技术最近的复兴以及临床上可用的直接连接His-Purkinje系统的导联系统的出现的基础上。这项建议的具体目的是：1)证明在室颤患者的His-Purkinje系统中存在可兴奋的间隙，在此期间起搏脉冲捕捉大片纤颤组织；2)确定哪种低能量除颤算法以最少的能量终止VF；3)展示这些技术在临床相关模型中的实施，该模型可能集成到当前的ICD技术中。这些目标的完成将使人们进一步了解浦肯野系统在心律失常中的作用和重要性。它将证明，只有在小动物心脏和模拟中被证明有效的低能量除颤技术，如果使用专门的传导系统在整个工作心肌中分配起搏脉冲，在较大的心脏中也是有效的。这些技术将在正常动物模型和心力衰竭动物模型中进行开发和测试。该项目的最终结果将是临床上可翻译的终止室颤的技术和算法 脉搏如此之小，以至于ICD除颤治疗的损伤和痛苦将被完全消除。

 DESCRIPTION (provided by applicant): Ventricular fibrillation (VF) is a leading cause of death in the industrialized world. The only effective treatment for VF is electrical defibrillation. In te US alone, approximately 150,000 patients at high risk of VF receive implantable cardioverter defibrillators (ICDs) each year. The large shocks delivered by ICDs may lead to cardiac damage and anxiety in patients. Significant reductions in defibrillation shock energy may lead to reduced mortality and improved quality of life for ICD patients. The overall goal of this proposal is to develop a clinically relevant defibrillation strategy that significantly lowers the shock energy below the pain and damage thresholds of conventional defibrillation shocks. The main hypothesis of this proposal is that critically timed pacing-level pulses delivered directly to the Purkinje system will capture a critical mass of cardiac tissue and terminate VF. This work builds on recent understanding that the Purkinje system plays and active role in the maintenance of VF, a recent resurgence of work in low-energy defibrillation techniques, and the emergence of clinically available lead systems that directly interface the His-Purkinje system. The specific aims of this proposal are to: 1) demonstrate that there is an excitable gap in the His-Purkinje system in VF during which pacing pulses capture large regions of fibrillating tissue, 2) determine which low-energy defibrillation algorithm terminates VF with the least amount of energy, and 3) demonstrate the implementation of these techniques in a clinically relevant model that may be integrated into current ICD technology. Completion of these aims will lead to further understanding of the role and importance of the Purkinje system in cardiac arrhythmias. It will demonstrate that low energy defibrillation techniques which have only been demonstrated to be effective in small animal hearts and simulations are effective in larger hearts if the specialized conduction system is used to distribute pacing pulses throughout the working myocardium. The techniques will be developed and tested in normal and heart failure animal models. The end result of this project will be a clinically translatable technique and algorithm for terminating VF with pulse so small that damage and pain from defibrillation therapy with ICDs will be eliminated entirely.