Novel ECG Measures and Risk of Sudden Cardiac Death

新的心电图测量方法和心源性猝死的风险

• 批准号: 8595389
• 负责人: Larisa Gennadievna Tereshchenko
• 金额: $ 40.55万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2013-12-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8595389
• 关键词: Accounting; Adult; Age; Atherosclerosis; Autopsy; Biometry; Bundle-Branch Block; Cardiac; Cardiology; Cardiovascular system; Cause of Death; Cells; Cessation of life; Cicatrix; Classification; Clinical; Cohort Studies; Communities; Computer software; Coronary heart disease; Coupling; Depressed mood; Development; Echocardiography; Electrocardiogram; Electrophysiology (science); Epidemiology; Frequencies; Functional disorder; Funding; Future; Gender; General Population; Genes; Genetic; Health; Heart; Heart Diseases; Heart Rate; Human Genetics; Intervention; Laboratories; Lead; Left; Left Ventricular Hypertrophy; Measures; Metric; Molecular; Natural History; Pathologic; Patients; Persons; Phenotype; Physiological; Population; Populations at Risk; Prevention; Property; Public Health; Race; Rest; Risk; Risk Estimate; Risk Factors; Risk Marker; Source; Stratification; Techniques; Testing; United States National Institutes of Health; Variant; Ventricular; Ventricular Arrhythmia; Ventricular Fibrillation; Visit; base; case control; cohort; digital; follow-up; genome wide association study; heart cell; heart disease risk; high risk; improved; mortality; notch protein; novel; prevent; prospective; public health relevance; repository; sudden cardiac death; tool; trait

DESCRIPTION (provided by applicant): Sudden cardiac death (SCD) is a major public health concern, accounting for 400,000 deaths in the US each year. Clinical and autopsy studies have consistently demonstrated a predominant, common pathophysiology in Western populations, showing that the most common electro-physiologic mechanism for SCD is ventricular fibrillation (VF) and the most common pathologic substrate is coronary heart disease (CHD). In about half of SCD cases, death is the first clinical manifestation of CHD. Yet risk factors of SCD early in the natural history of conditions predisposing SCD have not been fully identified, and SCD risk stratification strategy in general population has not been developed. ECG is easy available, non-expensive and non- invasive tool, which carries valuable information on electrophysiological properties of the heart. However, traditional analysis of ECG includes very limited assessment of the arrhythmogenic substrate. Recently we developed novel 12-lead ECG SCD risk score, composed of parameters that measure (1) slow discontinued conduction, (2) temporal repolarization lability, and (3) adverse electrical remodeling. Preliminary gender-, race-, and age-matched case-control analysis of the Atherosclerosis In Community (ARIC) study showed a total continuous net reclassification improvement of 86.0% as compared to the Framingham risk score alone. We hypothesize that (1) the "SCD ECG risk score", comprised of the mechanistic ECG markers of arrhythmogenic substrate derived in the resting 12-lead ECG analysis accurately stratify persons into high-, intermediate- and low-risk groups and improve classification in comparison to the risk stratification on the basis of traditional CHD risk factor; (2) heritable factors of the novel ECG phenotype are associated with the increased SCD risk. This application bridges a critical gap between understanding of the SCD mechanisms and SCD risk stratification in a general population. We will leverage 2 unique large NIH-funded prospective community-dwelling GWAS cohorts with an available digital 12-lead ECG repository: ARIC and CHS. Baseline digital 12-lead ECG will be analyzed by customized Matlab software in PI's laboratory. The SCD ECG risk score will be developed in ARIC and validated in the CHS cohort. Net reclassification improvement will be assessed. Longitudinal changes in studied ECG parameters over 20 years of follow-up will be evaluated as predictors of cardiac structural and functional phenotype, assessed by echocardiography at the 5th ARIC visit. Our study will identify genes, associated with specific ECG traits, which will lead to novel targets fo treatments and in the future will enable SCD prevention.

描述(申请人提供)：心脏性猝死(SCD)是一个主要的公共卫生问题，在美国每年有40万人死亡。临床和尸检研究一直表明，在西方人群中，SCD最常见的电生理机制是室颤(VF)，最常见的病理基础是冠心病(CHD)。在大约一半的SCD病例中，死亡是CHD的首发临床表现。然而，在诱发SCD的条件的自然历史早期，SCD的危险因素还没有完全被识别，并且SCD在普通人群中的风险分层策略也没有被制定。心电是一种易于获得、价格低廉、非侵入性的工具，它携带着关于心脏电生理特性的有价值的信息。然而，传统的心电分析包括非常有限的评估心律失常的底物。最近，我们开发了新的12导联心电图SCD风险评分，由测量(1)缓慢传导中断，(2)短暂复极不稳定，(3)逆电重构的参数组成。对社区动脉粥样硬化(ARIC)研究的初步性别、种族和年龄匹配病例对照分析显示，与单独的Framingham风险评分相比，总的持续净重新分类改善了86.0%。我们假设(1)由12导联静息心电分析中得出的致心律失常底物的机械心电标记物组成的“SCD心电风险评分”准确地将患者分为高、中、低三个风险组，并在传统的冠心病风险因素的基础上改进了风险分层；(2)新的心电表型的遗传因素与SCD风险的增加有关。这项应用弥合了对SCD机制的理解和普通人群中SCD风险分层之间的关键差距。我们将利用两个独特的大型NIH资助的潜在社区居住的GWA群，以及可用的数字12导联心电图库：ARIC和CHS。基线数字12导联心电将在Pi的实验室使用定制的MatLab软件进行分析。SCD心电风险评分将在ARIC中开发，并在CHS队列中进行验证。将对改叙净改进进行评估。经过20年的随访，研究的心电图参数的纵向变化将被评估为心脏结构和功能表型的预测因子，在第五次ARIC会诊时通过超声心动图进行评估。我们的研究将确定与特定心电特征相关的基因，这将导致治疗的新靶点，并将在未来实现SCD的预防。