TRIGGERS OF VENTRICULAR ARRHYTHMIAS (TOVA) STUDY

这是我们之前的NHLBI授权的竞争性续签申请，该授权以非致命性心肌梗死(MI)的触发为特征。我们建议应用我们MI研究的方法和结果来表征植入型心律转复除颤器(ICD)的放电触发。室性心律失常触发因素(TOVA)研究的长期目标是深入了解触发因素对预防普通人群中由原发性心律失常引起的心脏性猝死(SCD)有帮助；作为次要目标，我们将获得有助于预防ICD放电的信息。现有的证据，大部分是轶事，表明与交感神经系统激活相关的活动同时触发SCD和ICD放电。我们将对ICD患者进行研究，因为1)SCD患者不能提供历史触发数据，2)事件发生率高的ICD患者可以进行前瞻性研究，3)ICD的心电图是ICD出院前有关心率和节律信息的新来源。TOVA研究将利用具有嵌套病例交叉分析的队列设计，在我们先前的研究中，允许在超过17%的非致命性失误中识别触发。一项对164名ICD患者的初步研究表明，39例出院患者中有23%可能触发。我们将在4年内在全国44个中心治疗的3000名患者中描述触发ICD出院的2000次发作的特征。工业界已承诺提供部分资金。这项研究的具体目的是：1)确定引发ICD放电的活动，如过度劳累；2)确定改变触发敏感性的因素，如β-受体阻滞剂；3)确定ICD放电是否更频繁地发生在觉醒后3小时、周一和冬季；以及4)利用ICD放电之前记录的电信号来确定触发过程中的交感神经激活。ICD放电触发的特征将为预防普通人群中由原发性心律失常引起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.