Genetic Predictors of QT Response During Exercise

项目概述：对运动压力的反应是心脏病预后的一个公认的预测因子。 这项K23提案的总体目标是建立在我以前在这一领域的经验基础上，以识别基因和 其他运动应激反应的预测指标，从而开始开发一个新的框架 接近心律失常导致猝死的风险。具体的目标将决定确定的作用 以及调节中间电生理表型的变异性的新的多态，包括 对运动压力和内在心率的反应。在具体目标1中，我将表现为Qt和Rr 正常受试者在运动和康复过程中的反应，并测试基因多态在 调节这些反应的可变性。在特定的目标2中，我将表现出内在的QT和RR反应 在正常受试者的运动和康复过程中，并测试基因多态在调节 这些反应的可变性。在特定的目标3，1将确定一种延长QT的药物对 固有心率和QT间期。让我进一步发展成为一名临床研究人员和 检验这些目标背后的假设是否到位。这个奖项将提高我作为临床医生的技能。 通过临床研究、明确的教育计划和正式的指导过程 高度支持和富有成效的研究和指导环境。在这种情况下，很可能是 最大限度地提高我作为一名独立调查员的发展目标，使其具有强大的研究计划 已实现。 相关性：每年有42万美国人死于心脏性猝死。这项研究有可能 允许识别有心源性猝死风险的个人，因此与 公共卫生。

Project Summary: Response to exercise stress is a well-recognized predictor of outcome in heart disease. The overall goal of this K23 proposal to is build on my previous experience in this area to identify genetic and other predictors of response to exercise stress, and thereby begin to develop a new framework for approaching risk of sudden death due to arrhythmias. The Specific Aims will determine the role of defined and new polymorphisms in modulating variability in intermediate electrophysiologic phenotypes, including responses to exercise stress and intrinsic heart rate. In Specific Aim 1, I will phenotype QT and RR responses during exercise and recovery in normal subjects, and test the role of genetic polymorphisms in mediating variability in these responses. In Specific Aim 2, I will phenotype intrinsic QT and RR response during exercise and recovery in normal subjects, and test the role of genetic polymorphisms in mediating variability in these responses. In Specific Aim 3,1 will determine the effect of a QT-prolonging drug on intrinsic heart rate and QT interval. The resources for me to develop further as a clinical investigator and to test the hypotheses underlying these aims are in place. This award will enhance my skills as a clinical investigator through clinical research, a defined educational program, and a formal mentoring process in a highly supportive and productive research and mentoring environment. In this way, the likelihood is maximized that my goal of developing as an independent investigator with a robust research program will be achieved. Relevance: Sudden cardiac death kills 420,000 Americans each year. This research has the potential to permit identification of individuals at risk for sudden cardiac death and therefore has significant relevance to public health.