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.
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