PRE-DETERMINE: Biologic Markers and MRI SCD Cohort Study

预先确定：生物标志物和 MRI SCD 队列研究

• 批准号: 8536353
• 负责人: CHRISTINE M ALBERT
• 金额: $ 128.63万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-15 至 2017-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8536353
• 关键词: Adrenergic Agents; Applications Grants; Arrhythmia; Biological Markers; Blood; Blood specimen; Cardiac; Cardiac Death; Cessation of life; Cicatrix; Clinical; Clinical Trials; Code; Cohort Studies; Congestive Heart Failure; Coronary heart disease; Data; Defibrillators; Devices; Electrocardiogram; Eligibility Determination; Enrollment; Environmental Risk Factor; Event; Fibrosis; Functional disorder; Genes; Genetic; Genetic Markers; Goals; Habits; Health; Heart Arrest; Image; Image Analysis; Implantable Defibrillators; Incidence; Individual; Infarction; Inflammation; Inflammation Mediators; Ion Channel; Ischemia; Lead; Left Ventricular Ejection Fraction; Left Ventricular Function; Left Ventricular Mass; Life; Life Style; Magnetic Resonance Imaging; Measures; Medical; Membrane; Metabolic; Methods; Myocardial; Myocardial dysfunction; National Heart, Lung, and Blood Institute; Parents; Patients; Plasma; Population; Populations at Risk; Predictive Value; Prevention strategy; Prevention therapy; Process; Proteins; Public Health; Quality of life; Receptor Signaling; Research Infrastructure; Risk; Risk Factors; Saint Jude Children' s Research Hospital; Series; Stretching; Structural Protein; Testing; Time; United States; Variant; Ventricular; Ventricular Arrhythmia; Work; adrenergic; base; cohort; cost effective; follow-up; high risk; improved; mortality; novel; novel therapeutic intervention; predictive modeling; prospective; randomized trial; screening; sudden cardiac death; tool; trend

DESCRIPTION (provided by applicant): There are an estimated 250,000-400,000 sudden cardiac deaths (SCD) annually in the United States constituting approximately 50% of all cardiac deaths. Although clinical trials have demonstrated convincing survival benefits conferred by implantable cardioverter defibrillator (ICD) therapy in selected patients with left ventricular ejection fractions (LVEF) less than 35% and congestive heart failure, the overwhelming majority of patients who suffer a cardiac arrest will have an LVEF> 0.35. This grant application, "PRE-DETERMINE: Biologic Markers and MRI SCD Cohort Study," seeks to identify patients at a substantially higher risk of arrhythmic death among CHD patients with preserved left ventricular ejection fractions (LVEF>35%). The application takes advantage of a planned randomized trial, the Defibrillators To Reduce Risk by Magnetic Resonance Imaging Evaluation (DETERMINE) trial sponsored by St. Jude Medical to assemble a unique prospective cohort of patients who do not presently have an indication for ICD therapy based upon left ventricular function. The additional support from the NHLBI will provide a unique and timely opportunity to take advantage of the assembly of patients screened for the trial who will have contrast-enhanced magnetic resonance imaging (CE-MRI) scans to create an invaluable cohort of 5300 patients with preserved LVEFs where the underlying cardiac substrate is well-defined by MRI imaging and where clinical information, lifestyle habits, electrocardiograms, and blood samples will be collected at baseline and sudden arrhythmic events will be documented over the follow-up period. In years 4-5, the predictive value of promising protein, genetic, and metabolic biomarkers in combination with advanced substrate imaging on the risk of arrhythmic events will be examined in the 6850 patients enrolled in both the observational PRE-DETERMINE cohort and in the parent DETERMINE randomized trial. The goal is to arrive at a series of markers that alone or in combination specifically predict risk of arrhythmic death as compared to other causes of mortality among this at risk population of CHD patients. If biomarkers or genetic markers are identified that can specifically predict risk of ventricular arrhythmias, then these markers may serve as relatively inexpensive methods to identify those at risk.

描述（由申请人提供）：美国每年估计有250，000 - 400，000例心脏性猝死（SCD），约占所有心脏性死亡的50%。尽管临床试验已经证明植入式心律转复除颤器（ICD）治疗在选定的左心室射血分数（LVEF）小于35%和充血性心力衰竭患者中具有令人信服的生存益处，但绝大多数心脏骤停患者的LVEF> 0.35。这项资助申请，“PRE-DETERMINE：生物标志物和MRI SCD队列研究”，旨在确定左心室射血分数保留（LVEF>35%）的CHD患者中发生心肌梗死死亡风险显著较高的患者。该应用程序利用了一项计划的随机试验，即由圣犹达医疗用品有限公司申办的通过磁共振成像评价降低风险的除颤器（DETERMINE）试验，以汇集一个独特的前瞻性队列，这些患者目前没有基于左心室功能进行ICD治疗的适应症。来自NHLBI的额外支持将提供一个独特而及时的机会，以利用为试验筛选的患者集合，这些患者将进行对比增强磁共振成像（CE-MRI）扫描，以创建一个由5300名LVEF保留患者组成的宝贵队列，其中MRI成像明确定义了潜在的心脏基质，并且临床信息、生活习惯、心电图、并在基线时采集血样，并在随访期间记录突发性腹泻事件。在第4-5年，将在6850例入组PRE-DETERMINE观察性队列和母体DETERMINE随机试验的患者中检查有前景的蛋白质、遗传和代谢生物标志物联合先进底物成像对糖尿病事件风险的预测价值。目标是获得一系列标记物，其单独或组合特异性地预测CHD患者中与其他死亡原因相比的糖尿病死亡风险。如果生物标志物或遗传标志物被鉴定出可以特异性预测室性心律失常的风险，那么这些标志物可以作为相对便宜的方法来鉴定那些处于风险中的人。