PRE-DETERMINE: Biologic Markers and MRI SCD Cohort Study

简介(申请人提供)：据估计，美国每年有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，植入型心脏复律除颤器(ICD)疗法在特定的左心室射血分数(LVEF)低于35%和充血性心力衰竭的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&GT；将为0.35。这项赠款申请名为“预先确定：生物标记物和核磁共振SCD队列研究”，旨在确定左心室射血分数(LVEF&GT；35%)未受影响的冠心病患者中心律失常死亡风险显著更高的患者。该应用程序利用了一项计划中的随机试验，即由圣裘德医疗赞助的核磁共振成像评估(DECHINE)试验，即除颤器以降低风险，以汇集目前没有基于左心功能的ICD治疗适应症的患者的独特预期队列。NHLBI的额外支持将提供一个独特和及时的机会，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，创建一个由5300名保留LVEF的患者组成的宝贵队列，其中潜在的心脏基质通过MRI成像得到明确定义，临床信息、生活习惯、心电图和血液样本将在基线收集，并将在后续时期记录突发心律失常事件。在第4-5年，将在6850名参加观察性预确定队列和父母确定随机试验的患者中检验有希望的蛋白质、遗传和代谢生物标记物与先进的底物成像相结合对心律失常事件风险的预测价值。我们的目标是得到一系列单独或联合使用的标记物，与冠心病高危人群中的其他死亡原因相比，这些标记物可以专门预测心律失常死亡的风险。如果识别出可以专门预测室性心律失常风险的生物标志物或遗传标志物，那么这些标志物可能会成为识别风险人群的相对廉价的方法。

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.