This project is a clinical study of repolarization factors that predict arrhythmia risk. It consists of two related subprojects that both focus on quantitative measures of repolarization that will lead to clinically useful assessment of arrhythmia risk. The techniques used to measure repolarization will be derived from those developed in the animal experimental studies in Project 4 and they will then be applied to studies that evaluate therapeutic interventions in arrhythmia prone patients. Hence this project plays a pivotal role in linking the technical developments in experimental studies to the direct clinical application of monitoring and will prospectively evaluate repolarization abnormalities in over 2000 post-myocardial infarction patients using multi-read electrocardiography. Project 5.2 will study the role of the autonomic nervous system on repolarization in a group of patients with documented ventricular tachycardia. One study will measure repolarization changes leading up to arrhythmic events by means of QT interval, ARIs, and T- wave amplitudes measured from Holter ECGs. The second wave will induce repolarization changes by means of head-up tilt and compare the ECGs. The second study will induce repolarization changes by means of head-up tilt and compare the resulting repolarization change to those observed prior to spontaneous episodes of ventricular tachycardia. Success in these studies would provide robust electrocardiographic screening methods for arrhythmic sudden cardiac death.
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