Development of a Hypertrophic Cardiomyopathy Consortium

描述（由申请人提供）：肥厚性心肌病 (HCM) 是最常见的遗传性心血管疾病，全世界每 500 人中就有 1 人发生这种疾病。它也是年轻人猝死的最常见原因，并与心力衰竭、心律失常和死亡有关。常规捕获与疾病的主要或次要特征相关的临床信息（表现为心脏结构和/或功能的变化）可能有助于识别面临这些不良结果风险的患者。我们的总体目标是利用世界各地现有研究团体中大量特征明确的 HCM 人群的力量，研究 HCM 临床重要结果的潜在新预测因素。因此，我们的具体目标是： 1) 确定不同步在预测 HCM 心力衰竭中的作用； 2) 确定心房颤动的预测因子；3) 确定晕厥和心源性猝死的电生理预测因子。对这些问题的综合评估理想情况下需要大量、特征明确、系统积累、最好是多种族的 HCM 患者群体，并以明确的方案方式进行纵向随访。尽管此类研究群体在组织和地理上分散，具有不同的科学目标，但几乎所有研究群体都收集了有助于解决我们的假设的关键临床和影像信息。将这些实体聚集在一起面临的挑战是多方面的，但主要与信息的数量和复杂性不利于轻松集成和分析这一事实有关。合并来自多个研究项目的数据需要复杂而强大的计算和信息学工具，以便收集、存储和分析不同形式的信息。该提案旨在将几个大型、独特的研究社区与 HCM 患者群体合作合并，利用 CVRG 提供的独特架构和工具来测试我们的假设。我们计划利用 CVRG 的专业知识和资源建立一个数据共享基础设施，参与调查的人员将在其中以符合 HIPAA 的方式安全地将大量信息上传到一个通用平台。随后，我们将应用现有的定制 CVRG 工具来管理和分析电生理学和成像数据。我们将使用现有的横断面和纵向数据来确定电生理学、心脏结构和功能的参数（无论是单独还是组合）是否可以预测 HCM 患者的临床相关结果。 公共卫生相关性： 该项目旨在利用心血管研究网格与来自美国、欧洲和亚洲的多个参与中心建立一个肥厚型心肌病临床联盟。该联盟是此类联盟中的首创，它将允许汇集临床和影像信息，从而创建一个大型数据库，能够回答有关肥厚性心肌病（一种常见遗传性疾病）管理的关键临床问题，而这在较小的单一机构规模中是不可能实现的。

DESCRIPTION (provided by applicant): Hypertrophic cardiomyopathy (HCM) is the commonest inherited cardiovascular disorder occurring in 1 in 500 persons worldwide. It is also the commonest cause of sudden death in the young and is associated with heart failure, cardiac arrhythmias and death. It is likely that routinely captured clinical information pertaining to primary or secondary features of the disease, manifesting as changes in cardiac structure and/or function, may allow identification of patients at risk for these adverse outcomes. Our overall goal is to examine potential novel predictors of clinically important outcomes of HCM by leveraging the power of large numbers of well-characterized HCM population available in a conglomeration of existing research communities across the world. Accordingly, our specific aims are: 1) To determine the role of dyssynchrony in predicting heart failure in HCM; 2) To ascertain the predictors of atrial fibrillation and 3) To determine the electrophysiologic predictors of syncope and sudden cardiac death. A comprehensive evaluation of these issues would ideally require large, well- characterized, systematically accrued, and preferably multi-ethnic populations of patients with HCM that have been followed longitudinally in a well-defined protocolized fashion. Although such research populations are organizationally and geographically dispersed with dissimilar scientific goals, almost all collect key clinical and imaging information that could help address our hypothesis. The challenges in bringing such entities together are manifold but primarily related to the fact that the volume and complexity of information does not lend itself to easy integration and analyses. Merging data from multiple research programs requires sophisticated and powerful computational and informatics tools that will allow collection, storage and analyses of disparate forms of information. This proposal seeks to collaboratively amalgamate several large, distinct research communities with populations of HCM patients to test our hypotheses exploiting the unique architecture and tools offered by the CVRG. We plan to use the CVRG expertise and resources to establish a data sharing infrastructure wherein participating investigators will securely, and in a HIPAA compliant fashion, upload large volumes of information on to a common platform. Subsequently, we will apply existing custom CVRG tools for management and analyses of electrophysiology and imaging data. We will use existing cross-sectional and longitudinal data to ascertain if parameters of electrophysiology, cardiac structure and function, either singly or in combination, predict clinically relevant outcomes in HCM patients. PUBLIC HEALTH RELEVANCE: This project seeks to develop a clinical consortium of hypertrophic cardiomyopathy using the cardiovascular research grid with several participating centers from the United States, Europe and Asia. This consortium, a first of its kind, would allow pooling of clinical and imaging information thus creating a large database capable of answering critical clinical questions concerning the management of hypertrophic cardiomyopathy, a common genetic disorder, not otherwise possible with smaller, single institution volumes.