Rapid High-Resolution Electroanatomical Cardiac Mapping System for the Treatment

用于治疗的快速高分辨率电解剖心脏标测系统

• 批准号: 7745680
• 负责人: Doron Harlev
• 金额: $ 22.14万
• 依托单位: RHYTHMIA MEDICAL, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-17 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7745680
• 关键词: Ablation; Adverse effects; Algorithms; American; Amplifiers; Anatomy; Animals; Applications Grants; Area; Arrhythmia; Atrial Fibrillation; Blood; Cardiac; Cardiac Surgery procedures; Cardiac ablation; Catheters; Choristoma; Clinical; Complex; Computational algorithm; Computer Systems Development; Computer software; Data; Development; Distal; Effectiveness; Electrodes; Electrophysiology (science); Elements; Ensure; Epidemic; Equilibrium; Family suidae; Feasibility Studies; Floor; Goals; Growth; Heart; Heart Diseases; Heel; Hour; Human; Incidence; Injection of therapeutic agent; Intervention; Laboratories; Location; Maps; Marketing; Measurement; Measures; Methodology; Modality; Modeling; Morphologic artifacts; Motion; Noise; Operative Surgical Procedures; Outcome; Patient Care; Patients; Performance; Pharmacotherapy; Phase; Physiological; Plague; Plant Roots; Play; Prevalence; Procedures; Pulmonary veins; Readiness; Recurrence; Resolution; Role; Running; Safety; Saline; Shapes; Signal Transduction; Simulate; Site; Source; Specific qualifier value; Speed; Structure; Surface; System; Technology; Testing; Therapeutic; Time; Tissues; Uncertainty; Validation; Visual; analog; base; data acquisition; design; digital; effective therapy; electrical property; feeding; heart electrical activity; heart rhythm; hemodynamics; improved; in vivo; minimally invasive; multidisciplinary; next generation; novel; novel strategies; phantom model; prototype; public health relevance; response; safety testing; success; targeted delivery

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.

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型的快速高分辨率心脏电活动3D标测系统。在大型动物和人类的性能和安全性测试之后，该系统被设想用于心脏电生理学实验室，以生成描绘解剖学和电学信息的心脏腔室的患者特定3D图。这种标测图用于引导消融能量的输送，目的是消除临床心律失常。这第一阶段的赠款申请特别需要一个原型系统的建设和它的初步验证在一个台式设置。在过去的几十年里，心律失常的发病率和患病率呈爆炸性增长，反映了已知会促进心律异常的所有形式的心脏病的惊人增长。仅心房纤颤就已达到流行病的程度，估计目前约有230万美国人患病，到2050年约有560万人患病。传统的治疗方式，即药物治疗和心脏直视手术，已被发现不适合越来越多的患者，无论是因为疗效差，副作用，或仅仅是侵入性的外科手术。专用经皮导管的出现和其他使能技术的发展共同导致微创治疗程序的安全性和有效性的改善。在过去的十年中，经皮导管手术已经增长了10倍以上，已经成为有症状患者的首选干预模式。心脏节律异常是一个主要的治疗挑战，因为它们通常是由心脏的特定区域选择性触发和持续的，这些区域往往在患者之间具有高度可变性。由于大多数经皮手术都采用心内膜方法，因此有效的治疗取决于复杂心内膜表面异常组织的可靠定位以及向罪魁祸首部位准确输送消融能量。为了响应这种新兴的需求，已经开发了几种系统来提供心腔的3D解剖和电标测。不幸的是，所有可用的系统都受到重大限制的困扰，特别是因为它们涉及映射时间（有时超过一小时）和分辨率。缓慢和/或不准确标测的潜在后果包括无法标测短暂和血流动力学不稳定的心律失常、电正常心脏组织的不必要消融、复发的重复手术以及手术和X射线暴露时间增加。因此，毫无疑问，快速高分辨率标测仍然是改善导管治疗手术结果的一个尚未满足的重大需求。所提出的系统将在多个心跳和导管位置上使用新型可操纵多电极阵列导管采集心内信号。然后，这些数据将输入复杂的计算算法，以准确地重建电解剖信息。Rhythmia系统构成了新一代技术，其独特的架构可优化标测速度和分辨率之间的平衡。所提出的方法将允许在不到60秒的时间内完全覆盖典型的心腔，产生具有前所未有的1- 2毫米分辨率的电子地图。这种功能组合将支持几乎所有致心律失常机制的标测，包括VT（通常以间歇性运行和血流动力学不稳定为特征）和AF（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，Rhythmia系统可能对患者护理质量产生深远影响，并成功与当前可用的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，该原型系统由在基于PC的工作站上运行的专有计算引擎、标测导管和相关硬件（放大器和滤波器）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电特性的台式体模模型进行测试和改进。具体来说，第一阶段将有以下目标：（1）开发一个原型系统，将能够快速定位和可视化的多个来源的注入电流在一个离体测试室。(2)通过定位单个注入电流源，体外量化标测空间分辨率。(3)通过定位和定时由多个注入电流源的顺序触发模拟的激活序列，体外量化总体标测分辨率。当系统在定位注入电流源时显示出低于5 mm的误差，在确定激活时间时显示出低于5 ms的误差时，完成特定目标#3将实现可行性。在成功完成实验室验证后，将开始第二阶段，包括大型动物研究。公共卫生相关性：心律异常困扰着越来越多的患者，仅在美国估计就有600万至1000万人。微创手术，如导管消融术，已成为消除心律失常和恢复正常心跳的首选方法。拟议中的项目旨在开发下一代技术，以更快速，更准确地定位心脏内的罪魁祸首组织。上级标测速度和准确性将使得能够更有针对性地输送治疗消融能量，从而提高介入手术的安全性和有效性。