Implications of Intra-Myocardial Fat Deposition upon Propensity for Malignant Arrhythmia

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。导管 消融的目的是破坏室性心动过速基质，即病变心肌，它会减缓局部传导，足以 使巡回再入永久化。目前对VT衬底的理解围绕着相互作用 存活的心肌束主要位于梗死疤痕的外围。然而，我们的初步数据显示， 提示关键的室性心动过速回路部位是位于疤痕核心的有活力的心肌链，并且通常 周围是心肌内脂肪沉积。心肌内脂肪不是一个简单的旁观者；它是代谢的 活性和血管，导电纤维的有效绝缘体，并调节局部导电性能。这 提案将研究脉冲作用下心肌内脂肪沉积的机制后果 既往有心肌梗死的成年人的传导和维持室速的倾向。我们建议使用核磁共振 心肌梗死后室性心动过速患者的CT图像以1)来确定心肌脂肪的患病率和分布 既往有心肌梗死和室性心动过速患者的沉积，2)传导和复极的特征 基于与心肌脂肪的接近程度的瘢痕内存活通道的特性，3)检查其相关性 4)分析心肌脂肪对室速的影响。 事件使用特定于患者的模型，并评估模型预测的最佳诊断性能 消融部位包含和不包含心肌脂肪。我们的团队在核磁共振安全方面拥有丰富的经验 以及除颤器接受者的图像优化。此外，我们还组建了一支图像专家团队 获取和分析、流行病学、生物统计学、模拟和VT管理。这项研究的发现 这项研究将对我们从机制上理解和处理梗死后室性心动过速具有广泛的适用性。

Life-threatening ventricular tachycardia (VT) remains a major complication of myocardial infarction. Catheter ablation aims to destroy the VT substrate, diseased myocardium that slows local conduction sufficiently to perpetuate circuit reentry. The current understanding of the VT substrate revolves around the interaction of surviving strands of viable myocardium primarily at the periphery of infarct scar. Our preliminary data, however, suggests that critical VT circuit sites are viable myocardial strands that reside in the scar core, and are often surrounded by intra-myocardial fat deposition. Intra-myocardial fat is not a simple bystander; it is metabolically active and vascular, an effective insulator of conductive fibers, and modulates local conduction properties. This proposal will investigate the mechanistic consequence of intra-myocardial fat deposition upon impulse conduction and the propensity to sustain VT in adults with prior myocardial infarction. We propose to use MRI and CT images of patients with post-infarct VT to 1) to define the prevalence and distribution of myocardial fat deposition in patients with prior infarction and VT, 2) to characterize the conduction and repolarization properties of viable channels within scar based upon proximity to myocardial fat, 3) to examine the association of VT circuit sites with proximity to myocardial fat, and 4) to dissect the contribution of myocardial fat to VT events using patient-specific models, and to evaluate the diagnostic performance of model-predicted optimal ablation sites with and without inclusion of myocardial fat. Our group has extensive experience with MRI safety and image optimization in defibrillator recipients. Additionally, we have assembled a team of experts in image acquisition and analysis, epidemiology, biostatistics, simulations, and VT management. The findings of this study will have wide applicability to our mechanistic understanding and management of post-infarct VT.