Transmural Electrophysiological Imaging to Guide Catheter Ablation of Arrhythmias

描述(申请人提供)：在美国，室性心动过速(VT)每年导致约40万例院外心脏性猝死。一个重要的治疗策略是通过导管消融罪犯组织来阻断心律失常回路。室速消融的现状与导管标测程序紧密交织在一起，导管标测程序在心脏表面逐点组装电压和/或激活图。这种标测过程是有创的，耗时，缺乏心脏表面下完整的3D数据，并且空间分辨率有限。在这种做法下，医生需要进行一项漫长的临床程序，以便仅在放置导管尖端的有限位置获取信息。这些基本的局限性导致了VT消融的高复发率和高并发症发生率。这项研究的长期目标是开发一种无创的跨壁电生理成像(TEPI)系统来标记室性心律失常，并提供VT消融的术前计划。基于我们强大的初步数据，这项建议的总体目标是优化和确定TEPI在两种关键的消融前工具中的临床价值。首先，我们将确定TEPI在电解剖瘢痕成像和预测TEPI诱发性方面的表现。我们的假设是，与有创电解剖电压标测相比，无创性TEPI在显示瘢痕方面与延迟对比增强成像更一致，其瘢痕指标更能预测室速的诱导性。其次，我们将确定TEPI标记室性心律失常和预测消融靶点的能力。我们的假设是，TEPI可以用来标记室性心律失常和识别成功的消融部位。这些研究将在详细的动物模型中进行，使用梗死后的猪心脏，涉及计算、实验和临床科学家的跨学科团队之间的合作。在这个项目完成后，我们将能够确定TEPI在VT消融中的临床应用，并为设计具有更强统计能力的R01临床研究产生重要的先导数据。我们将获得一种无创性、透壁性和高分辨率的成像工具来表征室性心律失常的基质和动力学，这有望通过提供更好的术前计划和靶向来改善VT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有创的、基于表面的、逐点的向无创的、跨壁的和高分辨率的转变。它将提高电生理研究的有效性和安全性，同时减少在更广泛范围的心律失常的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.