Pre-DETERMINE: Biologic Markers and MRI SCD Cohort Study

据估计，美国每年有250，000例心脏性猝死（SCD）， 大约50%的心源性死亡虽然临床试验已经证明了令人信服的生存 植入式心律转复除颤器（ICD）治疗对选定的左心室患者带来的益处 心室射血分数（LVEF）小于35%和充血性心力衰竭，绝大多数 遭受心脏骤停的患者将具有LVEF> 0.35。在这场竞争的延续中， 确定：生物标志物和MRI SCD队列研究，我们建议确定生物标志物是否 在LVEF>30-35%的CHD患者中，可利用标记物和ECG来提前预测SCD风险 缺乏SCD风险预测的方法。在第一个资助周期，5764例冠心病患者和 LVEF>30-35%入组多中心前瞻性队列研究，PREDETERMINE和血液样本 和心电图被收集，储存，和一组生物标志物，脂肪酸，和大量的心电图参数， 已经/将要被测量。此外，大量的人口统计学、临床和生活方式信息 特征和心脏测试结果已被收集和存储。在一部分患者中，对比- 收集增强心脏MRI（CE-MRI）并分析梗死面积和其他形态学特征。 该队列已通过邮件和电话集中随访3年，失访率较低， 并且正在对死因特异性死亡率和中毒事件进行裁定。主要终点是 猝死和/或猝死（SAD）和院外VF骤停（VF）的联合终点。在 竞争延续，我们将利用这一丰富和独特的资源，在第一个赠款周期， 在这一未充分研究的人群中实现以下关于SCD风险预测的目标。1）.评估 生物标志物和ECG特征是否可用于识别高风险的存在 CE-MRI上的致瘤性心肌瘢痕。2）.以确定是否这些和其他生物和心电图 一般人群中与SCD相关的标记物与该人群中的SAD/VF相关。3）.至 基于生物标志物、ECG特征和 与其他死亡原因相比，预测SAD/VF风险的传统风险因素 无严重收缩功能障碍的CHD患者。4）.测试遗传风险评分是否可以增加SAD/VF 无严重收缩功能障碍的CHD患者的风险重新分类。如果生物标志物、ECG或 与其他原因相比，识别出可以更大程度地预测SAD/VF发生的遗传标记 的死亡率，那么这些标记物可以作为相对便宜的方法来识别 可能受益于ICD的CHD和LVEF>30-35%的患者。这些发现也可能提高我们的 在CHD背景下对SAD的机制理解，这可能导致新的预防方法， 一般人群，其中CHD是大多数SCD的基础。

There are an estimated 250,000 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. In this competing continuation of the PRE- DETERMINE: Biologic Markers and MRI SCD Cohort Study, we propose to determine whether biologic markers and ECGs can be utilized to advance SCD risk prediction in patients with CHD and LVEF>30-35% where methods for SCD risk prediction are lacking. In the first grant cycle, 5764 patients with CHD and LVEF>30-35% were enrolled in multicenter prospective cohort study, PREDETERMINE, and blood samples and ECGs were collected, stored, and a panel of biomarkers, fatty acids, and a multitude of ECG parameters have been/will be measured. In addition, a wealth of information on demographics, clinical and lifestyle characteristics, and cardiac test results has been collected and stored. In a subset of patients, contrast- enhanced cardiac MRIs (CE-MRI) were collected and analyzed for infarct size and other morphologic features. The cohort has been closely followed centrally by mail and phone for 3 years with low rates of lost to follow-up, and adjudication of cause specific mortality and arrhythmic events is ongoing. The primary endpoint is a combined endpoint of sudden and/or arrhythmic death (SAD) and out-of-hospital VF arrest (VF). In the Competing Continuation, we will leverage this rich and unique resource created during the first grant cycle to address the following aims regarding SCD risk prediction in this understudied population. 1).To evaluate whether biomarkers and ECG characteristics can be utilized to identify the presence of high risk arrhythmogenic myocardial scar on CE-MRI. 2).To determine whether these and other biologic and ECG markers associated with SCD in the general population are associated with SAD/VF in this population. 3).To develop clinically useful predictive models based on combinations of biomarkers, ECG characteristics and conventional risk factors that predict risk of SAD/VF as opposed to other causes of mortality in patients with CHD who do not have severe systolic dysfunction. 4).To test whether genetic risk scores can add to SAD/VF risk reclassification in CHD patients who do not have severe systolic dysfunction. If biomarkers, ECG, or genetic markers are identified that can predict the occurrence of SAD/VF to a greater extent than other causes of mortality in this population, then these markers may serve as relatively inexpensive methods to identify patients with CHD and LVEF>30-35% who might benefit from the ICD. The findings may also enhance our mechanistic understanding of SAD in the setting of CHD, which could lead to novel preventive approaches in the general population, where CHD underlies the majority of SCD.