Modifiable Determinants of Ventricular Arrythmias

描述（由申请人提供）：由于室性心动过速（VT）和/或心室颤动（VF）是美国每年发生的400,000例scd中约80%的基础，因此确定VT/VF的危险因素具有公共卫生重要性。我们提交这个申请是为了响应PA-03-015，它使用了R21机制。该计划要求利用现有的人类数据，不需要初步结果，并将研究计划限制在只有10页。在本应用中，我们建议利用室性心律失常触发器（TOVA）研究期间收集的现有数据来确定高危人群中室性心律失常的预测因子。TOVA是一项多中心前瞻性队列研究，在美国31个中心招募了1188名ICD患者，旨在确定易感患者中VT/VF的触发因素。在研究过程中收集了关于临床特征、生活习惯、社会心理因素和药物的广泛信息，并收集和验证了500例ICD触发的心电图，为检查生活方式因素和药物对危及生命的室性心律失常后续电击的影响提供了独特的机会。将在这一人群中检验的具体假设包括：愤怒和焦虑等社会心理因素的影响；生活方式因素，如吸烟、饮酒和体育活动；非传统抗心律失常药物，如他汀类药物和血管紧张素转换酶抑制剂，对VT/VF风险的影响。多变量Cox比例风险模型将用于评估确诊室性室间隔/室性室间隔的暴露与首次ICD放电时间之间的关系，Anderson-Gill比例风险模型将用于纳入反复ICD放电。通过识别这一高危人群中VT/VF的特定危险因素，可能会获得关于室性心律失常病理生理学的新认识，这可能有助于在普通人群和高危患者中开发新的室性心律失常和SCO预防模式。作为次要目标，确定可能影响痛苦ICD冲击风险的潜在可改变的生活习惯和药物可能会显著影响ICD患者的临床管理和随后的生活质量。

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.