ANCILLARY STUDY OF SUBSTRATE AND INTERVENTION MECHANISMS FOR MALIGNANT ARRHYTHMIA

描述（由申请人提供）：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。室性心动过速的基质是病变的心肌，它使局部传导减慢，足以使回路折返永久化。该提案旨在增强我们对VT基质的解剖细节及其对抗心律失常药物治疗和导管消融（旨在破坏VT基质的替代治疗模式）的患者反应的影响的理解。目前，通过使用局部逐点采集的心内电描记图来执行消融，所述心内电描记图用作每个患者的独特VT基底的替代物。这一战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）等成像技术直接评价解剖VT基底已变得可行。我们建议对“结构性心脏病室性心动过速消融与增强药物治疗”（VANISH）和“植入式心律转复除颤器患者缺血性室性心动过速的早期消融治疗”（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1年随访时对200名VANISH和ASPIRE受试者进行静息心肌CT灌注和延迟对比增强CT梗死成像。数据将用于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与抗心律失常药物，B）定义慢传导VT基质的解剖细节，c）确定VT抑制所需的基质变化，以及d）表征消融与药物治疗的心脏重塑。我们已经组建了一个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。这项研究的结果将有广泛的适用性，以优化管理策略的患者梗死后室性心动过速。

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.