ANCILLARY STUDY OF SUBSTRATE AND INTERVENTION MECHANISMS FOR MALIGNANT ARRHYTHMIA

描述(申请人提供)：危及生命的室性心动过速(VT)仍然是心肌梗死的主要并发症。室性心动过速的底物是病变的心肌，使局部传导减慢，从而使电路折返永久化。这项建议旨在加强我们对室速底物的解剖细节及其对抗心律失常药物治疗和导管消融患者反应的影响的了解，导管消融是一种旨在破坏室速底物的替代治疗模式。目前，消融是通过局部的、逐点获取的心内电信号来进行的，它可以替代每个患者独特的VT底物。这一策略受到抽样密度低和缺乏特异性的限制。最近，通过计算机断层扫描(CT)等成像技术，直接评估解剖VT底物已成为可能。我们建议对“结构性心脏病的室性心动过速消融与增强药物治疗”(VINISH)和“早期消融治疗植入心脏复律除颤器患者的缺血性室性心动过速”(ASPIRE)多中心随机临床试验进行一项时间敏感的辅助研究。我们将在随机化前和一年的随机化时对200名失踪者和ASPIRE受试者进行静息心肌CT灌注和延迟增强CT心肌梗死成像。这些数据将被用来a)定义预测VT治疗最佳模式的解剖特征，从而允许正确选择消融和抗心律失常药物；b)确定慢传导VT底物的解剖细节；c)确定VT抑制所需的底物变化；以及d)表征消融和药物治疗所导致的心脏重构。我们已经组建了一支CT图像采集和分析、流行病学、生物统计学和VT管理方面的专家团队。本研究结果将对优化心肌梗死后室性心动过速患者的治疗策略具有广泛的适用性。

DESCRIPTION (provided by applicant): Life-threatening ventricular tachycardia (VT) remains a major complication of myocardial infarction. The VT substrate is diseased myocardium that slows local conduction sufficiently to perpetuate circuit reentry. This proposal aims to enhance our understanding of the anatomic details of the VT substrate and its effects upon patient response to antiarrhythmic drug therapy and catheter ablation, an alternative mode of therapy that aims to destroy the VT substrate. Currently, ablation is performed by use of local, point-by-point acquired, intra- cardiac electrograms, which serve as surrogates for each patient's unique VT substrate. This strategy is limited by low sampling density and lack of specificity. Direct evaluation of the anatomic VT substrate has recently become feasible with imaging techniques such as computed tomography (CT). We propose a time-sensitive ancillary study to the "Ventricular Tachycardia Ablation vs. Enhanced Drug Therapy In Structural Heart Disease" (VANISH) and the "Early Ablation Therapy for the Treatment of Ischemic Ventricular Tachycardia in Patients with Implantable Cardioverter Defibrillators" (ASPIRE) multicenter randomized clinical trials. We will acquire resting myocardial CT perfusion and delayed contrast-enhanced CT infarct imaging in 200 VANISH and ASPIRE participants prior to randomization, and at 1-year follow-up. The data will be used to a) define anatomic features that predict the optimal mode of VT therapy thereby allowing proper selection of ablation versus antiarrhythmic drugs, b) define the anatomic details of slow conduction VT substrates, c) determine the substrate changes necessary for VT suppression, and d) characterize the resultant cardiac remodeling from ablation versus drug therapy. We have assembled a team of experts in CT image acquisition and analysis, epidemiology, biostatistics, and VT management. The findings of this study will have wide applicability to optimization of management strategies for patients with post-infarct VT.