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）是检测和治疗室性心动过速（VT）或室性颤动（VF）等心律失常的最有效手段。然而，尽管ICD技术被迅速接受，但目前ICD技术的主要局限性在于它的目的是在心律失常开始后才终止心律失常。鉴于检测VT/VF的失败、延迟或错误检测是危及生命的问题，下一代ICD技术必须能够预防心律失常的开始，而不是在心律失常发生后终止心律失常。电交替是在每隔一次心跳的基础上出现的心电图波形形状变化的模式。心室复极交替，即复极交替（RA），与心力衰竭患者VT/VF易感性增加和心源性猝死（SCD）相关。因此，在这项R21拨款申请中，我们提出了一项假设，即在心律异常发生之前应用ICD治疗不仅可以预防SCD，还可以提高患者对ICD治疗的接受程度和生活质量。我们开发了一种系统，既可以从心内电图实时估计RA，又可以及时传递与心电活动耦合的电脉冲。在本研究中，我们将在慢性心肌梗死动物模型中研究RA触发的临床合适的电疗法在抑制/终止RA和预防VT/VF发展中的适用性。为了实现本提案的目标，我们将(i)建立在猪动物模型中检测具有统计学意义的RA的标准，（ii）开发有效的算法来触发电治疗，并研究电治疗在降低/抑制RA水平方面的有效性。

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.