Center for Quantitative Electrocardiography and Cardiac Safety

描述（由申请人提供）： 心脏安全仍然是一个主要的公共卫生问题。例如，心脏性猝死（SCD）占所有心脏病死亡的一半，是美国自然死亡的最大原因（每年约有325，000名成年人）。尽管通过早期高级护理来减少这一数字，但显然需要改进风险分层技术，以优化预防性治疗（如植入式乳房植入体和药物治疗）的使用。同时，心脏安全性也是开发新分子实体的最具挑战性的障碍之一。据估计，在药物开发中检测的所有药物中，多达86%显示出钾离子动力学的特异性抑制活性，在某些情况下可导致尖端扭转型室性心动过速并可能导致SCD。据美国食品药品监督管理局（FDA）介绍，目前制药无法有效筛选出潜在有害药物的主要原因是缺乏更好的标志物来提高新化合物的可预测性和疗效。体表心电图（ECG）作为评估药物心脏毒性、预测心血管事件以及对心脏病和非心脏病患者进行风险分层的非侵入性方法的作用至关重要。我们建议NHLBI通过支持其围绕以下方面的初始活动来创建“定量心电图和心脏安全中心”（CES）：1）计算机资源（数据存储和计算中心）的开发和维护，2）医疗信息的部署和3）科学网络的形成。CES将主办遥测和霍尔特心电图仓库，这是一项目前由FDA、罗切斯特大学及其医疗中心工作人员组成的工作组实施的倡议。CES将向国际科学界分发这些资源，分享独特的临床和ECG信息，以设计和验证技术，改善定量心电图和心脏安全性。

DESCRIPTION (provided by applicant): Cardiac safety remains a major public health concern. Sudden cardiac death (SCD) for instance, is responsible for half of all heart disease deaths and is the largest cause of natural death in the U.S. (representing about 325,000 adults each year). Despite the effort implemented to reduce this number by early advanced care, there is a clear need for the improvement of risk stratification techniques to optimize the use of prophylactic therapies such as implantable defibrillators and drug therapies. Meanwhile cardiac safety is also one of the most challenging hurdles in the development of new molecular entities. It has been estimated that as many as 86% of all drugs tested in pharmaceutical development show specific inhibitory activity of potassium ion kinetics which in some cases can lead to torsades de pointes and potentially to SCD. According to the US Food and Drug Administration (FDA), the main reason for the inability of the current pharmaceutical to effectively screen out potentially harmful drugs is the lack of better markers to improve predictability and efficacy of new compounds. The roles of the surface electrocardiograms (ECGs) as a noninvasive approach to assess drug cardiotoxicity, to predict arrhythmic events, and to risk stratify cardiac and non-cardiac patients represent a matter of paramount importance. We propose to the NHLBI to enable the creation of a "Center for Quantitative Electrocardiography and Cardiac Safety" (CES) by supporting its inceptive activities around 1) the development and maintenance of computer resources (data storage and computing center), 2) the deployment of medical information and 3) the formation of a scientific network. The CES will host the Telemetric and Holter ECG Warehouse, an initiative currently implemented by a working group consisting of staff members from the FDA, the University of Rochester and its Medical Center. The CES will distribute these resources to the International scientific community, sharing unique clinical and ECG information for the design and validation of technologies to improve quantitative electrocardiography and cardiac safety.