Modifiable Determinants of Ventricular Arrythmias

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DESCRIPTION (provided by applicant): Since ventricular tachycardia (VT) and/or ventricular fibrillation (VF) underlie approximately 80% of the 400,000 SCDs that occur in the United states annually, the identification of risk factors for VT/VF is of public health importance. We are submitting this application in response to PA-03-015, which uses the R21 mechanism. This program requires the utilization of existing human data, does not require preliminary results, and limits the Research Plan to only 10 pages. In this application, we propose to utilize existing data assembled during the Triggers of Ventricular Arrhythmias (TOVA) study to identify predictors of ventricular arrhythmias in a population known to be at high risk. TOVA is a multi-center prospective cohort study that enrolled 1188 ICD patients at 31 centers in the United States and was designed to identify triggers of VT/VF among susceptible patients. The extensive information collected on clinical characteristics, lifestyle habits, psychosocial factors, and medications along with the collection and validation of electrograms from 500 instances of ICD firings over the course of the study provides a unique opportunity to examine the impact of lifestyle factors and medications on subsequent shocks for life-threatening ventricular arrhythmias. Specific hypotheses that will be examined in this population include the impact of psychosocial factors such as anger and anxiety; lifestyle factors such as smoking, alcohol, and physical activity; and non-traditional antiarrhythmic medications such as statins and angiotensin converting enzyme inhibitors on the risk of VT/VF. Multivariable Cox proportional hazards models will be used to evaluate associations between exposures and time to first ICD discharge for a confirmed episode of VT/VF, and Anderson-Gill proportional hazards models will be used to incorporate recurrent ICD discharges. By identifying risk factors specific for VT/VF in this high risk population, new understanding regarding the pathophysiology of ventricular arrhythmias may be gained, which may aid in the development of new preventive modalities for ventricular arrhythmias and SCO in the general population as well as in high risk patients. As a secondary goal, the identification of potentially modifiable lifestyle habits and medications that may influence risk of painful ICD shocks may significantly impact the clinical management and the subsequent quality of life of ICD patients.