Advanced Pacing Methods for Treating Heart Rhythm Disturbances

描述(申请人提供)：植入式心律转复除颤器(ICD)是检测和治疗室性心动过速(VT)或室颤(VF)等心律失常的最有效手段。然而，尽管它被迅速接受，但当前ICD技术的主要局限性是，它的目标是只有在心律失常开始后才能终止心律失常。鉴于VT/VF检测的失败、延迟或错误检测是一个危及生命的问题，下一代ICD技术必须能够防止心律失常的开始，而不是在心律失常开始后终止心律失常。电交替是每隔一个节拍出现的心电波形形状的一种变化模式。在心力衰竭患者中，心室复极交替，即复极交替(RA)，与VT/VF和心脏性猝死(SCD)的易感性增加有关。因此，在这项R21拨款申请中，我们建议调查这样一种假设，即在异常心律发展之前应用ICD治疗将不仅在预防SCD方面提供显著改善，而且还在患者对ICD治疗的接受度和生活质量方面提供显著改善。我们已经开发出一种系统，既可以根据心内电信号实时估计RA，又可以提供与心脏电活动及时耦合的电脉冲。在这项提案中，我们将研究在慢性心肌梗死动物模型中，RA触发的电疗法是否适用于抑制/终止RA和预防VT/VF的发展。为了实现这项建议的目的，我们将(I)建立在猪动物模型中在快速性心律失常事件发生之前检测到具有统计学意义的RA的标准，(Ii)开发有效的算法来触发电疗法，并研究电疗法在降低/抑制快速性心律失常事件发生前RA水平方面的有效性。 公共卫生相关性：植入式心律转复除颤器(ICD)是一种设备，可以检测室速或室颤等心律失常，并通过向心脏传递一个或多个电脉冲来终止心律失常。然而，在检测VT或VF时的失败、延迟或错误检测是非常令人担忧的。这项研究计划调查ICD在异常心律发展之前的治疗应用，从而不仅在预防心脏性猝死方面提供了显著的改善，而且在患者对ICD治疗的接受度和生活质量方面也有了显著的改善。

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.