Virtual cardiac electrophysiologic testing for sudden death risk stratification

描述（由申请人提供）：心源性猝死是美国死亡的主要原因。尽管已证明植入式心律转复除颤器（ICD）可有效预防室性心律失常患者的心源性猝死，但目前用于确定谁将受益于ICD或不受益于ICD的风险分层方法尚不理想。在本应用中，提出了一种新的风险分层工具的开发和评估，以预测心肌梗死（即心脏病发作）患者的心源性猝死。这种方法是基于电生理测试；一种风险分层方法，其中通过放置在心室的导管进行程序化刺激，用于测试潜在危及生命的室性心动过速的诱导性。我们假设计算机模拟可以用于无创测试这些室性心动过速的诱导性。研究表明，由梗死引起的疤痕和部分活组织为这些室性心律失常的发生提供了基础。对比增强磁共振成像（MRI）可以有效区分存活心肌、部分存活心肌和梗死疤痕。通过将真实的电生理特征和传导特性分配到输入工作站的三维MRI图像，假设使用该模型模拟的程序化刺激将识别患有诱发性室性心动过速的患者，从而从ICD中受益。除了猝死风险分层，电生理计算机建模和心脏MRI的整合可能还有其他潜在的临床应用，包括双心室起搏治疗候选人的电非同步化评估，记录室性心动过速患者的导管消融术前规划，以及作为培训医生和医疗专业人员的教育软件工具。在本研究的第一阶段，我们计划利用健康志愿者和接受电生理测试的患者的MRI数据来开发和实施该工具，以调整模型参数。在第二阶段，我们将重点比较“虚拟”电生理测试与实际电生理测试的结果，在更大的患者队列中，评估其预测室性心律失常风险的能力。有效的心源性猝死风险分层是及时、适当治疗的必要条件。一种检测患者是否具有心律失常的必要底物的非侵入性方法可以显著提高对心源性猝死的预防，心源性猝死是美国死亡的主要原因。

DESCRIPTION (provided by applicant): Sudden cardiac death is a leading cause of death in the United States. Although implanted cardioverter defibrillators (ICD) have been shown to be effective in preventing sudden cardiac death in patients who experience ventricular arrhythmias, current risk stratification methods in determining who will or will not benefit from an ICD have been suboptimal. In this application, the development and evaluation of a novel risk stratification tool to predict sudden cardiac death in patients who have had a myocardial infarction (i.e. heart attack) is proposed. This method is based on electrophysiologic testing; a risk stratification approach in which programmed stimulation via catheters placed in the ventricle is used to test for inducibility of potentially life threatening ventricular tachyarrhythmias. We hypothesize that computer simulations could be used to non- invasively test for inducibility of these ventricular tachyarrhythmias. It has been shown that the scars and partially viable tissue resulting from an infarction provide the substrate for these ventricular arrhythmias to occur. Contrast-enhanced magnetic resonance imaging (MRI) can effectively differentiate between viable myocardium, partially viable myocardium, and infarction scar. By assigning realistic electrophysiologic characteristics and conduction properties to the three-dimensional MRI image that is imported to the workstation, it is hypothesized that simulated programmed stimulation using this model will identify the patients who have inducible ventricular tachyarrhythmias and thus would benefit from an ICD. The integration of electrophysiologic computer modeling and cardiac MRI may have other potential clinical applications beyond sudden death risk stratification, including the evaluation of electrical dyssynchrony in candidates for bi- ventricular pacing therapy, pre-procedure planning for catheter ablation of patients with documented ventricular tachycardias, and as an educational software tool for training doctors and medical professionals. In the first stage of this study we plan to develop and implement of the tool using MRI data from healthy volunteers and patients undergoing electrophysiology testing to adjust model parameters. In the second stage, we will focus on comparing the results of "virtual" electrophysiologic testing to actual electrophysiologic testing in a larger cohort of patients and evaluating its ability to predict risk for ventricular arrhythmias. PUBLIC HEALTH RELEVANCE Effective risk stratification for sudden cardiac death is necessary for timely and appropriate therapy. A non- invasive approach to detect whether a patient has the necessary substrate for arrhythmias could significantly improve the prevention of sudden cardiac death, a leading cause of mortality in the United States.