Optically guided catheter ablation of atrial fibrillation

摘要：房颤(AF)影响约300万患者，其患病率预计将上升 随着人口老龄化。导管消融，对有症状的患者的首选治疗策略，创造了 心房局部组织坏死区域，称为病变，旨在消除异常电活动 这会导致房颤。然而，房颤的复发在这些患者中是显著的，主要是由于病变不充分。 通过消融或恢复异常的电活动而形成的。目前，标准护理技术可以 引导病变形成依赖于仅略微改善结果的病变形成的替代物。 此外，在一些房颤患者中，负责的异常活动不能被定位，从而 需要针对替代结构底物的辅助性损害，如纤维化和瘢痕形成。 然而，目前确定的替代AF基材是基于间接基材的基材代理，而不是 底物本身，这尚未被证明是有效的。因此，成功治疗的主要障碍是 房颤的继续是：a)造成完全和永久地阻断异常电活动的损伤， 以及b)准确识别已知引起房颤的底物。光学相干层析成像(OCT)是 一种可以实时监控病变形成的成像方法，并且近红外光谱(NIRS)可以 在射频消融过程中，根据测量的漫反射组织反射率来量化光学特性。当组合在一起时， OCT/NIRS可以提供有关病变形成、深度和组织成分的直接信息。基于我们的 之前的工作和初步数据我们假设，与标准护理方法相比， OCT/NIR可以更安全、更有效地创建完整且持久的损伤并用于测绘 AF结构基板。为了验证这一假设，我们的目标是：1.开发和验证实时光学制导 房颤消融病变的形成；2.建立和验证房颤结构的实时光学标测 底物。对于这两个目标，开发包括创新的OCT/NIRS软件和硬件 方法对正常猪、房颤猪及房颤猪的心房进行体内外验证。 来自有或没有房颤的人的组织。然后，在这些发展的基础上，我们的目标是：3.比较实时 光学引导的病变形成和对照标准护理方法的房颤结构底物的标测。 结果将在手术后立即在体内和体外进行尖锐的确定和验证 以确定病变的耐久性。为了实现这些目标，我们组建了一支唯一合格的 拥有OCT(罗林斯和亨登博士)、NIR(亨登博士)和Basic专业知识的多学科多PI团队 心脏电生理学(Laurita博士)，以及Co-I在临床房颤消融方面的专业知识(Ziv博士)和 心血管病理学(马尔博博士)。我们团队的长期目标是开发创新技术，以 改善房颤消融效果。

SUMMARY: Atrial fibrillation (AF) affects approximately 3 million patients and its prevalence is expected to rise as the population ages. Catheter ablation, the preferred treatment strategy for symptomatic patients, creates local regions of tissue necrosis in the atria called lesions that are meant to abolish abnormal electrical activity that causes AF. However, AF recurrence is significant in these patients mostly due to inadequate lesions formed by ablation or by recovery of abnormal electrical activity. Currently, standard-of-care technology to guide lesion formation relies on surrogates for lesion formation that only marginally improve outcomes. Additionally, in some patients with AF the abnormal activity responsible cannot be localized, which then requires adjunctive lesions targeting alternative structural substrates for AF such as fibrosis and scarring. However, alternative AF substrates are currently identified indirectly based substrate proxies rather than the substrate itself, which has yet to be proven effective. Therefore, the main barriers to the successful treatment of AF continue to be: a) creating lesions that completely and permanently block abnormal electrical activity, and b) accurately identifying substrates that are known to cause AF. Optical coherence tomography (OCT) is an imaging method that can monitor lesion formation in real-time, and near-infrared spectroscopy (NIRS) can quantify optical properties from measured diffuse tissue reflectance during RF ablation. When combined, OCT/NIRS can provide direct information on lesion formation, depth, and tissue composition. Based on our previous work and preliminary data we hypothesize that compared to standard-of-care methods, combined OCT/NIRS can be safe and more effective at creating lesions that are complete and durable and for mapping AF structural substrates. To test this hypothesis, we aim to: 1. Develop and validate real-time optically guided atrial ablation lesion formation, and 2. Develop and validate real-time optical mapping of AF structural substrates. For both of these aims, development includes innovative OCT/NIRS software and hardware methods along with validation in vivo and ex vivo in atria from normal pigs and pigs with AF as well as in atrial tissue from humans with or without AF. Then, based on these developments we aim to: 3. Compare real-time optically guided lesion formation and mapping of AF structural substrates against standard-of-care methods. Outcomes will be determined acutely in vivo and verified ex vivo immediately after the procedure and chronically to determine durability of lesions. To achieve these aims, we have assembled a uniquely qualified multi-disciplinary multi-PI team with expertise in OCT (Drs. Rollins and Hendon), NIRS (Dr. Hendon), and basic cardiac electrophysiology (Dr. Laurita), along with Co-I expertise in clinical AF ablation (Dr. Ziv) and cardiovascular pathology (Dr. Marboe). Our team's long-term goal is to develop innovative technologies to improve AF ablation outcomes.