QTRR Dynamic Coupling in Patients with the Long QT Syndrome

长 QT 综合征患者的 QTRR 动态耦合

基本信息

批准号：
9095430
负责人：
JEAN-PHILIPPE Y COUDERC
金额：
$ 41.13万
依托单位：
UNIVERSITY OF ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-01 至 2017-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9095430
关键词：
11p15.5 Acoustic Stimulation Adrenergic Agents Affect Age American Arousal Arrhythmia Cardiac Cessation of life Child Clinical Clinical Protocols Clinical Research Complement Coupling Cytogenetics Data Defect Dependency Diagnosis Electrocardiogram Emotions Enrollment Epinephrine Equipment Event Exercise Exogenous Factors France Frequencies Functional disorder Gender General Population Genes Genetic screening method Genotype Health Heart Heart Arrest Heart Rate Hour Impairment Implant Individual Inherited Ion Channel Ions Italy Life Location Long QT Syndrome Measurement Measures Medical Genetics Methods Molecular Molecular Biology Mutation Patients Percussion Phenotype Play Potassium Predisposition Process Prospective Studies Recording of previous events Registries Reporting Reproducibility Rest Resuscitation Retrospective Studies Risk Risk Marker Role Safety Scientist Severities Sleep Stimulus Stratification Stress Surface Syncope Syndrome Tachycardia Techniques Testing United States Ventricular Work base clinical risk cohort computerized digital genotyped patients imprint improved insight novel outcome forecast prospective rate of change response sudden cardiac death tool trafficking voltage young adult

项目摘要

DESCRIPTION (provided by applicant): While molecular biology has evidenced gene-specific ion-channel dysfunctions in patients with the Long QT syndrome (LQTS), the clinical studies have described a large spectrum of arrhythmogenic mechanisms involved in the triggering of life-threatening arrhythmias between and within specific gene. Genotyping is considered the most reliable tool to identify the presence of the LQTS, but genetic testing captures only 75% of phenotypically affected LQTS individuals, and negative test in a phenotype-positive patient does not rule out the presence of the syndrome. Importantly, these tests do not fully capture an individual risk to life-threatening arrhythmias that is modulated by exogenous factors. The surface electrocardiogram (ECG) is an investigational tool that could provide insights into the integrated functional defects associated with LQTS mutations. Therefore, we propose to conduct a project to identify ECG features associated with risk in LQTS patients. We will investigate ECG parameters beyond QTc prolongation focusing on capturing dynamic features of the QT and RR intervals coupling. More specifically, we propose to evaluate a method describing the instantaneous components of the QT response to changes in heart rate as a genetically-determined imprint of cardiac repolarization profile in LQTS patients. The proposal relies on a unique set of Holter ECGs recorded from ~1,210 genotyped LQTS patients gathered from three registries (American, Italian and French). We will study the reproducibility of the proposed ECG markers and their association with patients' events based on data from a retrospective and a prospective study. Several methods will be developed to risk stratify LQTS patients for cardiac events, and to estimate their susceptibility to specific triggers such as arousal, sleep/rest, and physical stress. Ultimately, we aim to improve the prognosis and management of LQTS patients.

描述（由申请人提供）：虽然分子生物学已经证明了长长QT综合征（LQT）患者的基因特异性离子通道功能障碍，但临床研究描述了与特定基因内部和特定基因内生命性心动不振的触发性危及的心律失常机制相关的大量心律失常机制。基因分型被认为是识别LQT存在的最可靠的工具，但是基因检测仅捕获75％的表型受影响的LQTS个体，而表型阳性患者中的阴性测试并不排除综合征的存在。重要的是，这些测试并不能完全捕获由外源性因素调节的威胁生命的心律不齐的个人风险。表面心电图（ECG）是一种研究工具，可以提供有关与LQTS突变相关的综合功能缺陷的见解。因此，我们建议进行一个项目，以识别LQTS患者风险相关的ECG特征。我们将研究ECG参数以外的QTC延长，重点是捕获QT和RR间隔耦合的动态特征。更具体地说，我们建议评估一种描述QT对心率变化的瞬时组成部分的方法，因为LQTS患者中心脏复极化的遗传确定烙印。该提案依赖于从三个注册表（美国，意大利语和法语）中收集的约1,210例基因型LQTS患者中记录的一组独特的Holter ECG。我们将根据回顾性和前瞻性研究的数据研究拟议的心电图标记的可重复性及其与患者事件的关联。将开发几种方法来冒险将LQTS患者分层为心脏事件，并估计其对特定触发因素（例如唤醒，睡眠/休息和身体压力）的敏感性。最终，我们旨在改善LQTS患者的预后和管理。