Transmural Electrophysiological Imaging to Guide Catheter Ablation of Arrhythmias

描述（由申请人提供）：在美国，室性心动过速（VT）每年导致约40万院外心脏性猝死。一个重要的治疗策略是通过导管消融罪魁祸首组织来中断心律失常回路。VT消融的现状与导管测绘程序紧密交织在一起，该程序在心脏表面逐点组装电压和/或激活图。这种测绘过程是侵入性的，耗时的，缺乏完整的心脏表面下的三维数据，并且空间分辨率有限。在这种实践中，医生需要进行长时间的临床操作，仅在放置导管尖端的有限位置获取信息。这些基本的限制导致了高复发率和高并发症发生率的VT消融。该研究的长期目标是开发一种无创的经壁电生理成像（TEPI）系统来绘制室性心律失常，并为VT消融提供术前规划。基于我们强有力的初步数据，本提案的总体目标是优化和确定TEPI在两个关键的术前手术中的临床价值。首先，我们将确定TEPI在电解剖疤痕成像中的表现，并预测TEPI的诱导性。我们的假设是，与有创电解剖电压定位相比，无创TEPI与延迟对比增强成像在疤痕描绘方面更一致，其疤痕指标更能预测VT诱发性。其次，我们将确定TEPI绘制室性心律失常和预测消融目标的能力。我们的假设是TEPI可以用来绘制室性心律失常和确定成功的消融部位。这些研究将在使用梗死后猪心脏的详细动物模型中进行，涉及计算、实验和临床科学家的跨学科团队的合作。在本项目完成后，我们将能够确定TEPI在VT消融中的临床应用，并为设计R01临床研究提供重要的先导数据，具有更高的统计能力。我们将获得一种无创、跨壁、高分辨率的成像工具来表征室性心律失常的基础和动态，通过提供更好的术前计划和靶向，有望改善室速消融的临床结果。从长远来看，这项研究将有助于临床电生理研究从侵入性、表面性和逐点性向无创性、跨壁性和高分辨率的转变。它将提高电生理研究的有效性和安全性，同时减少其在更广泛的心律失常常规临床实践中的持续时间和成本。

DESCRIPTION (provided by applicant): Ventricular tachycardia (VT) causes about 400,000 out-of-hospital sudden cardiac deaths each year in the United States. An important therapeutic strategy is to interrupt the arrhythmic circuit by catheter ablation of the culprit tissue. The staus quo of VT ablation is tightly interwoven with a catheter mapping procedure that assembles voltage and/or activation maps point-by-point on the heart surface. This mapping procedure is invasive, time-consuming, lacking complete 3D data beneath the heart surface, and limited in spatial resolution. With this practice, physicians are engaged in a prolonged clinical procedure to acquire information at only limited sites where the catheter tip is placed. These fundamental limitations have contributed to high recurrence and high complication rates of VT ablation. The long-term goal of the proposed research is to develop a noninvasive transmural electrophysiological imaging (TEPI) system to map ventricular arrhythmia and to provide pre-procedural planning of VT ablation. Based on our strong preliminary data, the overall objective of this proposal is to optimize and determine the clinical value of TEPI in two critical pre-ablatin utilities. First, we will determine the performance of TEPI in electroanatomical scar imaging and in predicting the inducibility of TEPI. Our hypothesis is that, in comparison to invasive electroanatomical voltage mapping, noninvasive TEPI is more consistent with delayed contrast-enhanced imaging in scar delineation and its scar metrics are more predictive of VT inducibility. Second, we will determine the ability of TEPI to map ventricular arrhythmia and to predict ablation targets. Our hypothesis is that TEPI can be used to map ventricular arrhythmia and identify successful ablation sites. These investigations will be carried out in detailed animal models using post-infarction porcine hearts, involving collaborations between an interdisciplinary team of computational, experimental, and clinical scientists. At the completion of this project, we will be able to determine the clinical utility of TEPI in VT ablation, and to generate important pilot data for designing a R01 clinical study with increased statistical power. We will obtain a noninvasive, transmural, and high-resolution imaging tool to characterize both the substrate and dynamics of ventricular arrhythmia, which is expected to improve the clinical outcome of VT ablation by providing better pre-procedural planning and targeting. In the long term, this research will contribute to the fundamental change of clinical electrophysiological studies from being invasive, surface-based, and point-by-point to being noninvasive, transmural, and high-resolution. It will improve the efficacy and safety of electrophysiological study while reducing its duration and cost in routine clinical practice for a broader spectrum of heart rhythm disorders.