Study of Ventricular Repolarization in Long QT Syndrome

描述(申请人提供)：长QT综合征(LQTS)，家族性 心肌钾钠离子编码基因突变引起的疾病 临床表现为ECO中QT间期延长。 以及有危及生命的室性心律失常的倾向。遗传形式的 LQT是由钠和钾通道基因突变引起的， 与心电图中不同的T波模式和不同的临床相关 随着时间的推移而产生的结果。然而，有大量重叠的心电模式和 由LQT1和LQT2基因突变引起的LQT1和LQT2的临床表现 不同的钾通道基因(分别为KVLQT1和HERG)。实验 数据和一些轶事临床观察表明，在LQT1和LQT2 在各种条件下，复极各种刺激的动态反应是 导致心律失常的关键因素。然而，有有限的 关于临床可应用的无创和有创检测的知识和 可靠地识别和量化震级动态的参数 LQTS患者的复极异常，尤其是LQT1和 LQT2类型占已知基因型别患者的大多数。 因此，本研究的主要目的是：1)提高临床疗效 无创性和有创性诊断LQTS的准确性 电生理测试；2)测定心室反应 LQTS患者对生理/药物刺激的复极 与对照非LQTS受试者进行比较；3)找出在 LQT1和LQT2的LQTS患者的心室复极参数 基因突变。这些目标将通过开展一系列 无创和有创电生理测试 50例LQT1携带者、50例LQT2携带者的生理/药理刺激 和50名健康对照的非LQTS受试者，以及 来自LQT1和LQT2家族的相当数量的非载波。第二个 本研究的目的是：1)开发和验证标准化的无创和 有创电生理学方法评价异常室壁 LQTS的复极；2)确定无创性的临床应用 QT间期临界性延长的有创检测 来自具有相似QTC间期的非载波的间期；3)确定 LQT1期心脏复极动力学对β受体阻滞剂治疗的反应 和LQT2患者之间的关系/联系；4)了解 LQTS与正常人的无创性和侵袭性电生理表现 研究对象。

DESCRIPTION (provided by applicant): The long QT syndrome (LQTS), a familial disorder caused by mutations of genes encoding myocardial potassium sodium ion channels, is manifest clinically by prolongation of the QT interval in the ECO and by a propensity life-threatening ventricular arrhythmias. Genetic forms of LQTS are caused by mutations of sodium and potassium channel genes and are associated with distinct T-wave patterns in the ECG and different clinical outcome over time. However, there is a substantial overlap of ECG patterns and clinical manifestation between LQT1 and LQT2 types caused by mutations of two different potassium channel genes (KVLQT1 and HERG, respectively). Experimental data and some anecdotal clinical observations indicate that in LQT1 and LQT2 conditions, the dynamic response of repolarization various stimuli is a critical factor contributing to arrhythmogenesis. However, there is limited knowledge regarding clinically applicable noninvasive and invasive tests and parameters that reliably identify and quantify the magnitude dynamic repolarization abnormalities in LQTS patients, especially those with LQT1 and LQT2 types that account for majority of patients with known genotype. Therefore, the primary aims of this study are: 1) to improve the clinical accuracy of diagnosing patients with LQTS using noninvasive and invasive electrophysiologic testing; 2) to determine response of ventricular repolarization to physiologic/pharmacologic stimuli in LQTS patients when compared to control non-LQTS subjects; 3) to identify differences in ventricular repolarization parameters between LQTS patients with LQT1 and LQT2 gene mutations. These goals will be accomplished by conducting a series of noninvasive and invasive electrophysiologic tests with physiological/pharmacological stimuli in 50 LQT1 carriers, 50 LQT2 carriers, and 50 healthy control non-LQTS subjects as well as noninvasive tests in equivalent numbers of non-carriers from LQT1 and LQT2 families. The secondary aims of this study are: 1) to develop and validate standardized noninvasive and invasive electrophysiologic protocols for evaluating abnormal ventricular repolarization in LQTS; 2) to determine the clinical usefulness of noninvasive and invasive testing to identify LQTS patients with borderline prolonged QTc intervals from non-carriers with similar QTc intervals; 3) to determine the response in ventricular repolarization dynamics to beta-blocker therapy in LQT1 and LQT2 patients; 4) to understand the relationship/association between noninvasive and invasive electrophysiologic findings in LQTS and normal subjects.