Temporal and spatial variability of cardiac repolarization

心脏复极的时间和空间变异性

• 批准号: 6430513
• 负责人: Ronald D Berger
• 金额: $ 20.97万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-01-01 至 2001-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6430513
• 关键词: action potentials; arrhythmia; arrhythmic agent; bioimaging /biomedical imaging; clinical research; electrocardiography; heart electrical activity; heart failure; heart innervation; human subject; hypertrophic myocardiopathy; myocardial ischemia /hypoxia; prognosis; sudden cardiac death

Heart disease remains the number one killer in the United States. The majority of these deaths occur suddenly as the result of lethal ventricular tachyarrhythmias. There is growing evidence that malignant arrhythmias in these patients are a consequence of altered ventricular repolarization. The central hypothesis of this research program is that lability in ventricular repolarization duration, or the electrocardiographic QT interval, provides a non-invasive measure of electrical instability. This proposal includes one set of aims to study mechanisms of repolarization lability, and another set of aims testing the clinical utility of beat-to-beat QT interval variability measurements. We will determine the role of autonomic regulation in the genesis of repolarization changes by studying the effects of selective autonomic blockade on QT interval variability in patients undergoing clinical electrophysiologic study. In some patients, we will also record monophasic action potentials from multiple endocardial sites to establish whether repolarization lability is a focal or diffuse phenomenon. These measurements will be repeated in a subset of patients who will receive intravenous ibutilid3e to provoke early after-depolarizations and ventricular pro-arrhythmia. The long-term predictive value of QT variability measurement will be tested prospectively in a large cohort of patients with ischemic and non- ischemic dilated cardiomyopathy. In addition, we will test the short-term predictive significance of increased QT variability in hospitalized patients in the Cardiac Care Unit and in ambulatory patients with implantable cardioverter defribllators (ICDs) who experience malignant ventricular arrhythmias. Finally, patients undergoing coronary angioplasty will be studied to determine the effects of acute myocardial ischemia on QT interval variability. This work should enhance our understand of arrhythmia mechanisms that cause sudden cardiac death and our ability to predict its occurrence.

心脏病仍然是美国的头号杀手。这些死亡大多数是由于致命性室性快速性心律失常而突然发生的。越来越多的证据表明，这些患者的恶性心律失常是心室复极改变的结果。本研究项目的中心假设是心室复极持续时间或心电图QT间期的不稳定性提供了电不稳定性的非侵入性测量。该提案包括一组研究复极不稳定性机制的目标，以及另一组测试逐搏QT间期变异性测量的临床实用性的目标。我们将通过研究选择性自主神经阻滞对接受临床电生理学研究的患者QT间期变异性的影响，确定自主神经调节在复极变化发生中的作用。在某些患者中，我们还将记录多个内分泌部位的单相动作电位，以确定复极不稳定是局灶性还是弥漫性现象。这些测量将在接受静脉注射伊布利特3e以引起早期后除极和室性致心律失常的患者亚组中重复进行。将在一个大型缺血性和非缺血性扩张型心肌病患者队列中前瞻性检验QT变异性测量的长期预测价值。此外，我们还将在心脏监护室住院患者和植入心律转复除颤器（ICD）并发生恶性室性心律失常的非卧床患者中检测QT变异性增加的短期预测意义。最后，将对接受冠状动脉成形术的患者进行研究，以确定急性心肌缺血对QT间期变异性的影响。这项工作应该提高我们对导致心脏性猝死的心律失常机制的理解，以及我们预测其发生的能力。