Visualizing the Substrate for Sudden Cardiac Death

描述（由申请人提供）：心源性猝死是美国一个重要的卫生保健问题，估计每年死亡人数在20万至40万人之间。在有心肌梗死（MI）病史的患者中，恶性室性心动过速（VTNF）至少占死亡的50%。这些心律失常是由于重新进入的电路主要位于健康组织和疤痕组织之间的边界地带。事实上，组织病理学研究表明，大多数致心律失常的疤痕是那些正常组织和异常组织之间含有最大程度交叉的疤痕。在这项研究中，我们提出验证假设，即心律失常性心室组织的结构特征可以通过磁共振成像（MRI）来识别。实验将结合体外和体内动物研究以及体内临床证实进行。我们假设这些方案将提供直接的实验证据，磁共振成像可以精确地识别心肌疤痕中心律失常“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，可以精确定位消除室速的导管消融手术，以识别和定位致心律失常的“热点”。其次，通过磁共振成像确定特定心肌梗死后患者的心肌疤痕是否包含任何这些致心律失常区，可以清楚地识别出那些需要治疗的心源性猝死风险最高的患者。该项目代表了学科（心脏电生理学、磁共振成像和图像处理）和新技术（基于基底的VT电解剖测绘、基于经皮导管的心外膜测绘、3D磁共振成像重建和电生理数据登记）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.