T Wave Alternans and Repolarization Abnormalities

T 波交替和复极异常

• 批准号: 6561810
• 负责人: DANIEL M BLOOMFIELD
• 金额: $ 2.54万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-01-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6561810
• 关键词: adrenergic agents; arrhythmia; autonomic nervous system; beta antiadrenergic agent; cardiovascular disorder risk; clinical research; diagnostic tests; electrocardiographic monitor; electrocardiography; electrophysiology; epinephrine; heart ventricle; isoproterenol; longitudinal human study; myocardium disorder; patient oriented research; prognosis; syncope

DESCRIPTION (provided by the applicant): Abnormalities in ventricular repolarization contribute importantly to the pathogenesis of life-threatening arrhythmias. This research program seeks to improve our understanding of the prognostic significance of and the autonomic mechanisms underlying repolarization abnormalities in patients with LV dysfunction.T wave alternans (TWA) is a 2:1 fluctuation in the amplitude or shape of T wave that has been linked to the genesis of ventricular arrhythmias. We have previously demonstrated that TWA is associated with spontaneous arrhythmic events in patients undergoing an EP study. Two large prospective epidemiologic studies are proposed in this grant designed and powered to definitively test the hypotheses that TWA is associated with an increased risk of having an arrhythmic event in patients with LV dysfunction (1) who have not yet had an arrhythmic event, and (2) who present with syncope. These epidemiologic studies will be combined with mechanistic studies designed to characterize autonomic modulation of repolarization in patients with LV dysfunction. We previously demonstrated in healthy subjects that isoproterenol was associated with longer QT intervals and greater U wave amplitude at a given heart rate compared to atropine. A series of studies are proposed to explore how sympathetic-parasympathetic interactions modulate repolarization, and to distinguish two aspects of the effects of 13-blockers on repolarization: direct effects and long-term effects on autonomic balance. Taken together, these studies will establish a new set of methods for evaluating the autonomic modulation of repolarization in different disease states and in response to drugs. The support from this K24 will enable the applicant to devote a substantial amount of effort towards developing this research as part of a comprehensive program to mentor clinical investigators. This program will include an intensive clinical research experience, didactic courses, training in data presentation and grant writing. A Critical Review Committee of experts will advise and monitor the progress of the research fellows in the program. Columbia University and its affiliated medical center represent one of the largest referral centers anywhere for patients with both heart failure and arrhythmias, and have active training programs in Epidemiology and Biostatistics which will be invaluable to the applicant in accomplishing the Aims of this proposal and in training junior investigators in patient-oriented research.

描述（申请人提供）： 心室复极异常对威胁生命的心律不齐的发病机理重要。该研究计划旨在提高我们对LV功能障碍患者的重极化异常的预后意义和自主神经机制的理解。T波替代品（TWA）是T波的幅度或形状的2：1波动，与c链息息相关，与c链息息相关。我们以前已经证明，在接受EP研究的患者中，TWA与自发性心律失常有关。在该赠款中提出了两项​​大型的前瞻性流行病学研究，旨在确定地测试TWA与尚未患有心律失常事件的LV功能障碍（1）患者发生心律不齐事件的风险增加有关的假设，并且（2）患有联合性。这些流行病学研究将与机械研究结合使用，旨在表征LV功能障碍患者复极化的自主神经调节。我们先前在健康受试者中证明，与阿托品相比，异丙肾上腺素与更长的QT间隔和更大的U波振幅相关。提出了一系列研究，以探讨交感神经相互作用如何调节复极化，并区分13个阻滞剂对复极化的影响的两个方面：直接影响和对自主平衡的长期影响。综上所述，这些研究将建立一组新的方法，用于评估不同疾病状态和对药物反应的复极化的自主神经调节。该K24的支持将使申请人能够大量的努力来开发这项研究，这是指导临床研究人员的综合计划的一部分。 该计划将包括密集的临床研究经验，教学课程，数据表现培训和赠款写作。一个批判性的专家审查委员会将建议和监控该计划研究研究员的进度。哥伦比亚大学及其附属医学中心代表着心力衰竭和心律不齐的患者的任何地方最大的推荐中心之一，并在流行病学和生物统计学方面进行了积极的培训计划，这对于申请人来说将是无价的，这将是实现这一建议的目标，并在以患者为方便的研究中培训初级研究员。