Advanced Pacing Methods for Treating Heart Rhythm Disturbances

描述（由申请人提供）：植入式心律转复除颤器（ICD）是检测和治疗心律失常（如室性心动过速（VT）或室颤（VF））的最有效方法。然而，尽管其被迅速接受，但当前ICD技术的主要局限性在于其旨在仅在心律失常已经开始之后终止心律失常。鉴于VT/VF检测失败、延迟或错误检测是危及生命的问题，下一代ICD技术必须能够防止心律失常开始，而不是在开始后终止心律失常。电交替是心电图波形形状的一种变化模式，每隔一次搏动出现一次。心室复极交替，即复极交替（RA），与心力衰竭患者VT/VF和心源性猝死（SCD）的易感性增加有关。因此，在这项R21资助申请中，我们建议调查这样一种假设，即在心律异常发生之前应用ICD进行治疗不仅可以显著改善SCD的预防，而且可以显著改善患者对ICD治疗的接受程度和生活质量。我们已经开发了一个系统，既可以估计RA在真实的时间从心内电描记图和提供电脉冲，及时耦合到心脏电活动。在本提案中，我们将研究RA触发的临床适当的电治疗的适用性，以抑制/终止RA，并防止VT/VF的发展在慢性心肌梗死的动物模型。为了实现本提案的目标，我们将（i）建立猪动物模型中快速性心律失常事件发生前检测统计学显着RA的标准，（ii）开发有效的算法来触发电疗并研究电疗的功效减少/抑制快速性心律失常事件发生前的RA水平。 公共卫生相关性：植入式心律转复除颤器（ICD）是一种检测心律失常（如VT或VF）并通过向心脏输送一个或多个电脉冲终止心律失常的器械。然而，在检测VT或VF中的故障、延迟或错误检测是非常令人关注的。本研究计划调查在心律异常发生之前应用ICD治疗，从而不仅在预防心脏性猝死方面，而且在患者接受ICD治疗和生活质量方面提供显着改善。

DESCRIPTION (provided by applicant): The implantable cardioverter defibrillator (ICD) is the most effective means of detecting and treating arrhythmias, such as ventricular tachycardia (VT) or ventricular fibrillation (VF). However, despite its rapid acceptance, the main limitation of the current ICD technology is that it aims to terminate an arrhythmia only after the arrhythmia has started. Given that failure, delay or false detection in detecting VT/VF is a life- threatening concern, it is imperative that the next generation of ICD technology is able to prevent arrhythmias from starting rather than terminating them after their initiation. Electrical alternans is a pattern of variation in the shape of electrocardiographic waveform that appears on an every other beat basis. Alternation in ventricular repolarization, namely repolarization alternans (RA), has been associated with increased vulnerability to VT/VF and sudden cardiac death (SCD) in patients with heart failure. Thus, in this R21 grant application, we propose to investigate the hypothesis that therapy application by an ICD before the abnormal heart rhythm develops will provide a significant improvement not only in preventing SCD but also in patient acceptance of ICD therapy and quality of life. We have developed a system that can both estimate RA in real- time from intracardiac electrograms and deliver electrical pulses that are timely coupled to the cardiac electrical activity. In this proposal we will investigate the applicability of RA-triggered delivery of clinically appropriate electrical therapy to suppress/terminate RA and prevent the development of VT/VF in an animal model of chronic myocardial infarction. To achieve the aims of this proposal we will (i) establish criteria for the detection of statistically significant RA preceding the onset of a tachyarrhythmic event in a swine animal model, (ii) develop effective algorithms to trigger electrical therapy and investigate the efficacy of electrical therapy in reducing/suppressing the level of RA preceding the onset of a tachyarrhythmic event. PUBLIC HEALTH RELEVANCE: The implantable cardioverter defibrillator (ICD) is a device that detects arrhythmias, such as VT or VF, and terminates them by delivery of one or more electrical impulses to the heart. However, failure, delay or false detection in detecting VT or VF are of great concern. This research proposal investigates the application of therapy by an ICD before the abnormal heart rhythm develops, thus providing a significant improvement not only in preventing sudden cardiac death but also in patient acceptance of ICD therapy and quality of life.