New generation of catheters for treatment of atrial fibrillation

 描述（由申请人提供）心房颤动（AF）仍然是最常见的心律失常。它与较低的生活质量和较高的发病率和死亡率相关，主要是由于血液动力学不良和经常中风。治疗房颤的主要选择之一是使用经皮射频（RF）导管消融异常电活动源。射频损伤隔离了心脏中不同部位（包括肺静脉）异常电活动的传播。因此，AF消融术治疗的基础是电隔离具有RF损伤的肺静脉（PV），基本上在PV内的致瘤病灶和心脏其余部分之间形成电屏障。通常，心脏病专家过度消融或消融不足，留下间隙，这些间隙仍然可以将异常电活动传输到心脏的其余部分。到 迄今为止，用于在RF消融过程期间实时监测组织损伤的手段有限，并且没有直接可视化消融的心脏组织以将其与存活的传导组织区分开的手段。在这里，我们建议创建新一代的成像导管，以区分正常的心脏组织从消融的心脏组织在真实的时间。它们基于由热损伤引起的组织自发荧光的光谱变化而工作。具体而言，在第二阶段，我们将扩展我们目前的第一代导管的设计，该导管依赖于从单个光谱带采集发射，以包括从380- 600 nm自发荧光范围内的多个发射带采集，并使用采集后分析来揭示对内皮胶原蛋白层和底层心房肌的热损伤。然后将使用UV多光谱导管检查和可视化活体大型动物（如猪）的经皮射频消融损伤。我们还对新鲜切除的人类心房组织进行了测试。导管将接受大量的文件记录、验证和确认，以便批准用于人体研究。制造过程说明将由制造合作伙伴制定和审查，制造合作伙伴将对各种导管组件进行构造、包装和灭菌。我们将与我们的临床合作伙伴共同制定人体研究方案，并将制定知情同意书、使用说明书和伦理审查和FDA批准所需的其他文件。在第二阶段结束时，我们的目标是拥有一个功能齐全、经过统计学测试的12 Fr多光谱成像导管，该导管已获得批准并准备用于首次人体研究。我们的最终长期目标是开发新一代消融导管，实现消融心脏组织的实时可视化。这项技术将 通过让心脏病专家真实的时间查看病变是否完整或是否有需要填补的缺口，为更简单、更快速、更安全、更具成本效益、更可靠和微创的房颤消融手术铺平道路。在消融后复发的患者的情况下，如果存在间隙，则导管将用于快速且有效地识别差距在哪里。

 DESCRIPTION (provided by applicant) Atrial fibrillation (AF) remains the most commonly occurring cardiac arrhythmia. It is associated with a lower quality of life and a higher rate of morbidity & mortality primarily due to poor hemodynamics and often stroke. One of the main options to treat atrial fibrillation is to ablate abnormal sources of electrical activity using percutaneous radiofrequency (RF) catheters. RF lesions isolate the spread of abnormal electrical activity from various sites in the heart including the pulmonary veins. As a result, a cornerstone of therapy in AF ablation procedures is to electrically isolate the pulmonary veins (PVs) with RF lesions, essentially creating an electrical barrier between the arrhythmogenic foci inside the PVs and the rest of the heart. Often the cardiologist over- ablates or under-ablates leaving gaps which can still transmit the abnormal electrical activity to the rest of the heart. To date, there are limited means for real-time monitoring of tissue injury during RF ablation procedures and there are no means of directly visualizing ablated cardiac tissue to distinguish it from viable conducting tissue. Here we propose to create a new generation of imaging catheters to distinguish normal cardiac tissue from ablated cardiac tissue in real time. They operate based on spectral changes in tissue autofluorescence caused by thermal damage. Specifically, in Phase II we will expand the design of our current, 1st generation catheter, that relied on acquiring emission from a single spectral band, to include acquisition from multiple emission bands within an autofluorescence range of 380-600nm and to use post-acquisition analysis to reveal thermal damage to layers of endocardial collagen and underlying atrial muscle. The UV multispectral catheter will be then used to examine and visualize percutaneous RF ablation lesions in live large animals such as pigs. We also test on freshly excised donated human atrial tissue. The catheter will undergo extensive documentation, verification, and validation in order to be approved for use in a human study. Manufacturing process instructions will be developed and reviewed by the manufacturing partners who will construct, package, and sterilize the various catheter components. We will work with our clinical partners to develop a human study protocol, and will develop informed consent documentation, instructions for use, and other documentation necessary for ethics review and FDA approval. At the end of Phase II we aim to have a fully functional, statistically tested 12 Fr multispectral imaging catheter, approved and ready for first-in-man studies. Our ultimate long term goal is to develop a new generation of ablation catheters enabling real-time visualization of ablated cardiac tissue. This technology will pave the way for easier, faster, safer, more cost- effective, more reliable and minimally invasive AF ablation procedures by allowing cardiologists to see in real time if lesions are complete or if there are gaps that need to be filled in. in the case of a patient who has a recurrence post-ablation, the catheter will be used to quickly and efficiently identify where the gap is if one exists.