TRIGGERS OF VENTRICULAR ARRHYTHMIAS (TOVA) STUDY

这是一个申请竞争性更新我们以前的NHLBI补助金，其特征是触发非致命性心肌梗死（MI）。 我们建议应用我们的MI研究的方法和结果来表征植入式心脏复律除颤器（ICD）的放电触发。室性心律失常触发（TOVA）研究的长期目的是深入了解触发对预防一般人群中原发性心律失常所致心脏性猝死（SCD）有用;作为次要目的，我们将获得对预防ICD放电有用的信息。现有的证据，主要是轶事，表明与交感神经系统激活相关的活动触发SCD和ICD放电。 我们将研究植入ICD的患者，因为1）SCD患者无法提供历史触发数据，2）事件发生率高的ICD患者可以进行前瞻性研究，3）ICD的电描记图是ICD放电前心率和心律信息的新来源。TOVA研究将采用队列设计和嵌套病例交叉分析，这允许在我们先前的研究中识别超过17%的非致死性MI的触发因素。 一项对164名植入ICD的患者进行的初步研究表明，39例出院患者中有23%可能触发ICD。 我们将在全国44个中心接受治疗的3,000名患者中描述4年内2,000次ICD放电事件的触发特征。工业界已认捐部分资金。本研究的具体目的是：1）确定触发ICD放电的活动，如剧烈运动; 2）确定改变触发敏感性的因素，如β受体阻滞剂; 3）确定ICD放电是否在觉醒后3小时内、周一和冬季更频繁地发生;以及4）利用ICD放电之前记录的电描记图来识别触发期间的交感神经激活。ICD放电触发的特征将为预防普通人群中原发性心律失常导致的猝死提供有价值的见解。

This is an application for competitive renewal of our prior NHLBI grant that characterized triggering of non-fatal myocardial infarction (MI). We propose to apply the methods and findings of our MI study to characterize triggering of discharge of implantable cardioverter-defibrillators (ICDs). The long-term objective of the Triggers of Ventricular Arrhythmias (TOVA) Study is to gain insights into triggering useful for prevention of sudden cardiac death (SCD) due to primary arrhythmia in the general population; as a secondary objective we will obtain information useful for prevention of ICD discharge. Available evidence, largely anecdotal, indicates that activities associated with activation of the sympathetic nervous system trigger both SCD and ICD discharge. We will study patients with ICDs because 1) SCD victims cannot give historical triggering data, 2) ICD patients, who have a high rate of events, can be studied prospectively, and 3) electrograms from ICDs are a novel source for information about rate and rhythm prior to ICD discharge. TOVA study will utilize a cohort design with a nested case-crossover analysis, which permitted identification of triggering in over 17 percent of non-fatal MIs in our prior study. A pilot study of 164 patients with ICDs has demonstrated possible triggering in 23 percent of 39 discharges. We will characterize triggering in 2,000 episodes of ICD discharge in 3,000 patients treated in 44 centers nationwide over 4 years. Partial funding has been pledged by industry. The specific aims of this study are: 1) To identify activities, such as heavy exertion, that trigger ICD discharge; 2) To determine factors, such as beta-blockade, that modify the susceptibility to triggering; 3) To determine if ICD discharges occur more frequently in the 3 hours after awakening, on Monday, and in winter; and, 4) To utilize electrograms recorded prior to ICD discharge to identify sympathetic activation during triggering. Characterization of triggering of ICD discharge will provide insights valuable for prevention of sudden death due to primary arrhythmias in the general population.