PRE-DETERMINE: Biologic Markers and MRI SCD Cohort Study

描述（由申请人提供）：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，对于左心室射血分数（LVEF）小于35%和充血性心力衰竭的患者，植入式心律转复除颤器（ICD）治疗具有令人信服的生存益处，但绝大多数心脏骤停患者的LVEF将达到0.35。这项资助申请，“预先确定：生物标志物和MRI SCD队列研究”，旨在确定左心室射血分数（LVEF>35%）保留的冠心病患者中存在明显较高的心律失常死亡风险的患者。该应用程序利用了一项计划中的随机试验，即由St. Jude Medical赞助的通过磁共振成像评估（decision）来降低风险的除颤器试验，该试验汇集了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的ICD治疗指征。来自NHLBI的额外支持将提供一个独特而及时的机会，利用为试验筛选的患者集合，他们将进行对比增强磁共振成像（CE-MRI）扫描，以创建一个宝贵的5300名保存lvef的患者队列，其中MRI成像明确了潜在的心脏底物，并且临床信息，生活习惯，心电图，在基线时采集血样在随访期间记录突发心律失常事件。在第4-5年，有希望的蛋白质、遗传和代谢生物标志物结合先进的底物成像对心律失常事件风险的预测价值将在6850名患者中进行检查，这些患者分别参加了观察性pre - decide队列和父母的随机试验。目的是获得一系列标志物，单独或联合特异性地预测冠心病高危人群中与其他死亡原因相比的心律失常死亡风险。如果生物标记物或遗传标记物被确定可以特别预测室性心律失常的风险，那么这些标记物可以作为相对廉价的方法来识别那些有风险的人。

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.