PRIMARY ECG - MRI RISK STRATIFICATION

描述（由申请人提供）： 本提案的目标是使用包括ECG和心脏MRI分析的序贯算法结合传统和新兴的风险分层方法，在心力衰竭进展和心源性猝死（SCD）的个性化风险评估中实施新策略。虽然预防不确定风险患者的心力衰竭进展和SCD是当代心脏病学中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，重点是左心室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检测心肌结构和存活率的异质性来评估心肌损伤。我们已经验证了ECG QRS评分算法对MRI高分辨率疤痕量化，从而证明了其潜在的效用，在识别个人谁应该接受详细的梗死异质性研究，MRI进一步的风险分层。因此，在第一阶段，我们将这两种模式与现有的标志物相结合，依次应用于改进算法的开发，然后在第二阶段的大型（n> 2，000）多中心分析中用于解决该方法的可行性和准确性，其中在第一阶段改进的技术，后勤和智力进步将在另外4个机构实施。将通过我们机构的NIH心血管研究网格资源（CVRG）提供的集中计算机系统分析标志物相关性、心脏事件和统计结局。根据初步数据，我们预计这种新的联合诊断方法将区分以前未检测到的心力衰竭进展高风险以及使用当前策略无法检测到的SCD死亡易感性的患者。在II期研究中对辅助遗传和生物标志物的评估将为个体化风险评估提供额外的预后信息。相关性（参见说明）：该提案解决了心脏病学的两个主要公共卫生挑战：改善患者的识别和风险分层，1）心源性猝死和2）心力衰竭进展和死亡率。重点放在与特定个体评价相关的非侵入性方法上，以使用新的和现有的治疗方法改善药物和器械的靶向。

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.