Visualizing the Substrate for Sudden Cardiac Death

描述（由申请人提供）：心源性猝死是美国的一个重要卫生保健问题，估计每年的死亡发生率为20万至40万。恶性室性快速性心律失常（VTNF）至少占有心肌梗死（MI）病史患者死亡的50%。这些心律失常是由主要位于健康和瘢痕组织之间的边界区域的折返回路引起的。实际上，组织病理学研究已经揭示，最易致瘤的瘢痕是那些在正常和异常组织之间包含最大程度的交错的瘢痕。在这项研究中，我们提出了一个假设，即可以通过磁共振成像（MRI）来识别致心律失常的心室组织的结构特征。将使用离体和体内动物研究以及体内临床确证的组合进行实验。我们假设，这些协议将提供直接的实验证据表明，磁共振成像可以精确地识别心肌瘢痕中致炎性“热点”的存在和位置。这将对恶性室性心律失常的管理和预防的两个重要方面产生直接影响。首先，通过术前MR成像和3D重建可以精确定位导管消融术以消除室性心动过速，从而识别和定位致心律失常的“热点”。其次，通过MR成像确定特定MI后患者的心肌瘢痕是否包含任何这些致瘤区，可以清楚地识别需要治疗的心脏性猝死风险最高的患者。该项目代表了学科（心脏电生理学、MR成像和图像处理）和新技术（基于基质的VT电解剖标测、基于经皮导管的心外膜标测和3D MR成像重建以及与电生理数据配准）的独特融合，以解决美国的主要死亡原因。

DESCRIPTION (provided by applicant): Sudden cardiac death is a significant health care problem in the United States, with estimates of annual incidence ranging from 200,000 to 400,000 deaths. Malignant ventricular tachyarrhythmias (VTNF) account for at least 50% of death in patients with a history of myocardial infarction (MI). These arrhythmias result from re-entrant circuits residing predominantly at the border zone between healthy and scarred tissue. Indeed, histopathological studies have revealed that the most arrhythmogenic scars are those containing the greatest degree of interdigitation between normal and abnormal tissue. In this study, we propose to test the hypothesis that structural characteristics of arrhythmogenic ventricular tissue can be identified by magnetic resonance imaging (MRI). Experiments will be performed using a combination of ex vivo and in vivo animal studies, as well as in vivo clinical corroboration. We hypothesize that these protocols will provide direct experimental evidence that MR imaging can precisely identify the presence and location of arrhythmogenic "hotspots" in a myocardial scar. This would have a direct impact on two important aspects of the management and prevention of malignant ventricular arrhythmias. First, catheter ablation procedures to eliminate VT could be precisely targeted by pre-procedural MR imaging and 3D reconstruction to identify and localize the arrhythmogenic "hot spots". Second, by determining whether the myocardial scar in a particular post-MI patient contains any of these arrhythmogenic zones by MR imaging, one may be able to clearly identify those patients at highest risk for sudden cardiac death requiring treatment. This project represents a unique confluence of disciplines (Cardiac Electrophysiology, MR Imaging, and Image Processing)and novel techniques (substrate-based electroanatomical mapping of VT, percutaneous catheter-based epicardial mapping, and 3D MR imaging reconstruction and registration with electrophysiological data) to address the leading cause of death in the United States.