Rapid High-Resolution Electroanatomical Cardiac Mapping System for the Treatment

描述(由申请人提供)：该项目的长期目标是开发、验证和商业化一种新的快速高分辨率心脏电活动3D测绘系统。在对大型动物和人类进行性能和安全测试后，该系统预计将用于心脏电生理学实验室，以生成患者特定的心腔3D地图，描绘解剖和电信息。这种地形图被用来指导消融能量的输送，以消除临床心律失常(S)。这项第一阶段赠款申请特别需要建造一个原型系统，并在台式环境中对其进行初步验证。在过去的几十年里，心律失常的发病率和流行率出现了爆炸性增长，反映出所有已知促进节律异常的心脏病的数量都有惊人的增长。仅房颤一项就已达到流行程度，估计目前约有230万美国人受到影响，到2050年将有约560万人受到影响。传统的治疗方式，即药物治疗和心内直视手术，已经被发现不能满足越来越多的患者，要么是因为疗效差，要么是因为副作用，或者仅仅是因为外科手术的侵入性。专门的经皮导管的出现和其他使能技术的发展共同提高了微创治疗程序的安全性和有效性。在过去的十年里，基于经皮导管的治疗方法已经增长了10倍以上，已经成为有症状患者的首选干预模式。心律异常是一项重大的治疗挑战，因为它们往往是由心脏的特定区域选择性地触发和永久存在的，这些区域往往在患者之间高度可变。由于大多数经皮手术采用心内膜入路，有效的治疗依赖于复杂心内膜表面异常组织的可靠定位和准确地将消融能量输送到罪犯部位。为了响应这种新出现的需求，已经开发了几个系统来提供心腔的3D解剖和电测绘。不幸的是，所有可用的系统都受到重大限制的困扰，特别是在测绘持续时间(有时超过一小时)和分辨率方面。缓慢和/或不准确的标测的潜在后果包括无法标测一过性和血流动力学不稳定的心律失常，不必要地消融电正常的心脏组织，重复复发的程序，以及增加程序和X射线曝光时间。因此，毫无疑问，在改善基于导管的根治性手术的结果方面，快速高分辨率标测仍然是一个重要的未得到满足的需求。该系统将使用一种新的可定向多电极阵列导管跨多个心搏和导管位置采集心脏内信号。然后，这些数据将被输入到一个复杂的计算算法中，以准确地重建解剖信息。节律系统构成了下一代技术，其独特的架构旨在优化映射速度和分辨率之间的平衡。拟议的方法将允许在不到60秒的时间内完全覆盖一个典型的心腔，产生前所未有的1-2 mm分辨率的电子地图。这些特征的结合将支持对几乎所有致心律失常机制的标测，包括室速(通常以间歇性跑动和血流动力学不稳定为特征)和房颤(用于验证肺静脉隔离和标测潜在的非典型扑动)。通过大幅缩短手术时间和提高标测分辨率，节律系统可以对患者护理质量产生深远影响，并成功地与目前可用的3D标测系统竞争。在之前进行的可行性研究之后，拟议项目的第一阶段将包括开发一个原型系统，该原型系统由运行在基于PC的工作站上的专有计算引擎、标测导管和相关硬件(放大器和过滤器)组成。一旦投入使用，该系统将使用模拟血液和心脏周围结构的电特性的台式体模模型进行测试和改进。具体地说，第一阶段将有以下目标：(1)开发一个原型系统，能够在体外试验室内快速定位和可视化多个注入电流源。(2)通过定位单个注入电流源来量化体外测绘的空间分辨率。(3)通过对由多个注入电流源的顺序触发模拟的激活序列进行定位和定时，来量化体外整体标测分辨率。随着具体目标#3的完成，当系统在定位注入电流源方面的误差小于5 mm，在确定激活时间时误差小于5毫秒时，将实现可行性。在成功完成工作台验证后，第二阶段将开始包括大型动物研究。公共卫生相关性：心律失常困扰着越来越多的患者，仅在美国估计就有600万到1000万人。微创手术，如导管消融，已经成为消除心律失常和恢复正常心跳的首选方法。这项拟议的项目旨在开发下一代技术，以便更快、更准确地定位心脏内的罪犯组织。超高的标测速度和准确性将使治疗性消融能量能够更有针对性地输送，从而提高介入治疗的安全性和有效性。

DESCRIPTION (provided by applicant): The long-term objective of this project is to develop, validate, and commercialize a novel rapid high-resolution 3D mapping system of the heart's electrical activity. Following performance and safety testing in large animals and humans, the system is envisioned to be used in the cardiac electrophysiology laboratory to generate patient-specific 3D maps of the heart's chambers that delineate both anatomical and electrical information. Such maps are used to guide the delivery of ablative energy with the goal of abolishing the clinical arrhythmia(s). This Phase I grant application specifically entails the construction of a prototype system and its initial validation in a bench-top setting. The incidence and prevalence of cardiac arrhythmias has seen explosive growth in the last few decades, mirroring an alarming increase in all forms of heart disease known to promote rhythm abnormalities. Atrial fibrillation alone has reached epidemic proportions, estimated to currently afflict ~2.3 million Americans and ~5.6 million by 2050. Traditional treatment modalities, namely drug therapy and open heart surgery, have been found to be inadequate for a growing number of patients, either because of poor efficacy, side effects, or the mere invasiveness of surgical procedures. The advent of specialized percutaneous catheters and the development of other enabling technologies have collectively led to an improvement in the safety and efficacy of minimally-invasive curative procedures. Having grown more than 10-fold in the last decade, percutaneous catheter-based procedures have become the preferred mode of intervention in symptomatic patients. Cardiac rhythm abnormalities present a major treatment challenge, as they are often selectively triggered and perpetuated by specific areas of the heart that tend to be highly variable between patients. Since most percutaneous procedures utilize an endocardial approach, effective therapy depends on reliable localization of the aberrant tissue on the complex endocardial surface and accurate delivery of ablative energy to culprit sites. In response to this emerging need, several systems have been developed to provide 3D anatomical and electrical mapping of cardiac chambers. Unfortunately, all available systems are plagued by significant limitations, particularly as they relate to mapping duration (sometimes exceeding an hour) and resolution. The potential consequences of slow and/or inaccurate mapping include the inability to map transient and hemodynamically unstable arrhythmias, unnecessary ablation of electrically normal cardiac tissue, repeat procedures for recurrence, and increased procedure and x-ray exposure times. Therefore, there is no doubt that rapid high-resolution mapping remains a significant unmet need in improving the outcome of curative catheter-based procedures. The proposed system would acquire intra-cardiac signals with a novel steerable multi-electrode array catheter across multiple beats and catheter locations. These data would then feed into a sophisticated computational algorithm to accurately reconstruct electro-anatomical information. The Rhythmia system constitutes next- generation technology uniquely architected to optimize the balance between mapping speed and resolution. The proposed methodology would allow complete coverage of a typical cardiac chamber in less than 60 seconds, producing electrical maps with the unprecedented resolution of 1-2mm. This combination of features would support the mapping of virtually all arrhythmogenic mechanisms, including VT (often characterized by intermittent runs and hemodynamic instability) and AF (for the validation of pulmonary vein isolation and mapping of underlying atypical flutters). By substantially shortening procedure times and enhancing mapping resolution, the Rhythmia system could have a profound impact on the quality of patient care and successfully compete with currently available 3D mapping systems. On the heels of previously performed feasibility studies, Phase I of the proposed project will include the development of a prototype system comprised of a proprietary computational engine running on a PC-based workstation, mapping catheter, and relevant hardware (amplifiers and filters). Once operational, the system would be tested and improved using a bench-top phantom model mimicking the electrical properties of blood and structures surrounding the heart. Specifically, Phase I will have the following aims: (1) Develop a prototype system that would be able to rapidly localize and visualize multiple sources of injected current within an ex vivo test chamber. (2) Quantify mapping spatial resolution ex vivo by localizing a single source of injected current. (3) Quantify overall mapping resolution ex vivo by localizing and timing an activation sequence simulated by sequential triggering of multiple sources of injected current. Feasibility will have been attained with the completion of Specific Aim #3, when the system demonstrates sub- 5mm error in localizing sources of injected current and sub-5ms error in determining activation times. Upon successful completion of bench-top validation, Phase II would be commenced comprising of large animal studies. PUBLIC HEALTH RELEVANCE: Cardiac rhythm abnormalities afflict a growing number of patients, with estimates ranging from 6 to 10 million people in the US alone. Minimally invasive procedures, such as catheter ablation, have established themselves as the preferred approach to eliminating cardiac arrhythmias and restoring normal heart beat. The proposed project looks to develop next-generation technology that would more rapidly and accurately localize the culprit tissue inside the heart. Superior mapping speed and accuracy would enable more targeted delivery of therapeutic ablative energy, thus improving both the safety and effectiveness of interventional procedures.