His-Purkinje Pacing for Low Energy Implantable Cardioverter Defibrillators

用于低能量植入式心脏复律除颤器的希氏浦肯野起搏

• 批准号: 8944632
• 负责人: Derek J Dosdall
• 金额: $ 48.72万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8944632
• 关键词: Algorithms; American; Animal Model; Animals; Anxiety; Arrhythmia; Atrial Fibrillation; Canis familiaris; Cardiac; Cardiac conduction system; Catheters; Cause of Death; Cessation of life; Chronic; Clinical; Conscious; Dilated Cardiomyopathy; Effectiveness; Electric Countershock; Electrodes; Electroporation; Failure; Goals; Heart; Heart failure; Implant; Implantable Defibrillators; Lead; Legal patent; Length; Maintenance; Maps; Measures; Microelectrodes; Modeling; Morbidity - disease rate; Myocardial; Myocardial Ischemia; Myocardium; Optics; Oryctolagus cuniculus; Pain; Patients; Physiologic pulse; Play; Quality of life; Risk; Role; Series; Shock; Sinus; Structure of purkinje fibers; System; Techniques; Technology; Testing; Time; Tissues; Training; Ventricular; Ventricular Fibrillation; Work; clinically relevant; effective therapy; high risk; implantable device; implantation; improved; mortality; public health relevance; simulation; sudden cardiac death; theories; virtual

 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.

 描述（由申请人提供）：室颤（VF）是工业化国家的主要死亡原因。VF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VF高风险患者接受植入式心律转复除颤器（ICD）。ICD提供的大电击可能导致患者的心脏损伤和焦虑。除颤电击能量的显著降低可导致ICD患者死亡率降低和生活质量改善。 本提案的总体目标是开发一种临床相关的除颤策略，该策略将电击能量显著降低到传统除颤电击的疼痛和损伤阈值以下。该提案的主要假设是，直接输送到浦肯野系统的关键定时起搏电平脉冲将捕获临界质量的心脏组织并终止VF。这项工作建立在最近的理解，浦肯野系统在维持VF中发挥积极作用，最近复苏的低能量除颤技术的工作，并出现了临床可用的电极导线系统，直接接口的希氏浦肯野系统。本提案的具体目的是：1）证明VF中His-Purkinje系统中存在可兴奋间隙，在此期间起搏脉冲捕获大面积消融组织，2）确定哪种低能量除颤算法以最少能量终止VF，以及3）证明这些技术在可集成到当前ICD技术中的临床相关模型中的实施。 这些目标的完成将导致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，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，则仅在小动物心脏中有效的低能量除颤技术和模拟在较大心脏中有效。这些技术将在正常和心力衰竭动物模型中进行开发和测试。这个项目的最终结果将是一个临床上可翻译的技术和算法终止VF 其脉冲如此之小，以至于使用ICD进行除颤治疗的损伤和疼痛将完全消除。