PRIMARY ECG - MRI RISK STRATIFICATION

描述(由申请人提供)： 这项建议的目标是在心力衰竭进展和心脏性猝死(SCD)的个性化风险评估中实施新的策略，使用包括心电图和心脏MRI分析的顺序算法，结合传统和新出现的风险分层方法。虽然在风险不确定的患者中预防心力衰竭进展和SCD是当代心脏病学最具挑战性的问题之一，但在降低心力衰竭发生率和SCD死亡率方面进展甚微。此外，目前的风险分层方法侧重于左心功能障碍和电生理指标，缺乏个性化护理所需的敏感性和特异性。在这里，我们通过应用新的基于自动心电图的QRS评分结合对比增强MRI对心肌结构和存活的异质性的检测来评估心肌损伤。我们已经验证了心电图QRS评分算法与MRI高分辨率SCAR量化的对比，从而证明了它在识别需要接受MRI详细的梗塞异质性研究以进行进一步风险分层的个体方面的潜在价值。因此，在第一阶段，我们将两种模式顺序地与现有的标记相结合，以完善算法的开发，然后在第二阶段期间，该算法将用于在大型(n&>；2,000)多中心分析中解决该方法的可行性和准确性，其中，在第一阶段中精炼的技术、后勤和智力进步将在另外4个机构实施。标记物关联、心脏事件和统计结果将通过我们机构的NIH心血管研究网格资源(CVRG)提供的中央计算机系统进行分析。根据初步数据，我们预计这种新的联合诊断方法将区分那些以前没有检测到的心力衰竭进展的高风险患者以及使用当前策略无法检测到的SCD死亡易感性。第二阶段对辅助遗传和生物标记物的评估将提供对个体化风险评估有用的额外预后信息。相关性(参见说明书)：这项建议解决了心脏病学中的两个主要公共卫生挑战：1)心脏性猝死和2)心力衰竭进展和死亡患者的改进识别和风险分层。重点放在与评估特定个人相关的非侵入性方法上，以利用新的和现有的疗法改善药物和设备的靶向性。

DESCRIPTION (provided by applicant): The goal of this proposal is to implement new strategies in personalized risk assessment for heart failure progression and sudden cardiac death (SCD) using a sequential algorithm involving ECG and cardiac MRI analyses in combination with conventional and newly emerging risk-stratification methods. While prevention of heart failure progression and SCD in patients of indeterminate risk represents one of the most challenging issues in contemporary cardiology, there has been little progress in reducing the incidence of heart failure and SCD mortality. Furthermore, current risk-stratification methods that focus on LV dysfunction and electrophysiological metrics lack the sensitivity and specificity needed for individualized care. Here we assess myocardial damage by applying novel automated ECG based QRS scoring combined with the detection of heterogeneity in myocardial structure and viability with contrast-enhanced MRI. We have validated the ECG QRS-scoring algorithm against high resolution scar quantification by MRI, thus demonstrating its potential utility in identifying individuals who should undergo detailed infarct heterogeneity studies by MRI for further risk stratification. Thus, in Phase I we apply the two modalities sequentially in combination with existing markers to refine development of an algorithm that will then be used to address feasibility and accuracy of the approach in a large (n>2,000) multi-center analysis during Phase II, where technological, logistical and intellectual advances refined in Phase I will be implemented at 4 additional institutions. Marker associations, cardiac events and statistical outcomes will be analyzed via the centralized computer system provided by the NIH Cardiovascular Research GRID resource (CVRG) at our institution. Based on preliminary data, we anticipate that this new combined diagnostic approach will discriminate patients who harbor previously undetected high risk for heart failure progression as well as SCD mortality susceptibility that is not detectable using current strategies. Evaluation of ancillary genetic- and bio-markers during Phase II will provide additional prognostic information useful for individualized risk assessment. RELEVANCE (See instructions): This proposal addresses two major public health challenges in cardiology: improved identification and risk stratification of patients for 1) sudden cardiac death and 2) heart failure progression and mortality. Focus is placed on non-invasive approaches relevant to evaluation of specific individuals to improve drug and device targeting using new and existing therapies.