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。导管消融术是有症状患者的首选治疗策略， 心房中的局部组织坏死区域，称为病变，旨在消除异常电活动 然而，在这些患者中，AF复发是显著的，主要是由于病变不充分 通过消融或通过恢复异常电活动形成。目前，标准护理技术 引导损伤形成依赖于损伤形成的替代物，其仅略微改善结果。 此外，在一些房颤患者中，无法定位导致房颤的异常活动，因此 需要针对AF的替代结构基质（如纤维化和瘢痕形成）的连续性损伤。 然而，替代的AF衬底目前是基于间接的衬底代理而不是基于间接的衬底代理来识别的。 这是一种尚未被证明有效的基质本身。因此，成功治疗的主要障碍 AF的主要原因仍然是：a）产生完全和永久阻断异常电活动的损伤， 和B）准确识别已知引起AF的基底。光学相干断层扫描（OCT） 一种可以实时监测病变形成的成像方法，近红外光谱（NIRS）可以 在射频消融期间，根据测量的组织漫反射率量化光学特性。当结合时， OCT/NIRS可提供关于病变形成、深度和组织组成的直接信息。基于我们 根据先前的工作和初步数据，我们假设与标准治疗方法相比， OCT/NIRS在创建完整和持久的病变以及标测方面安全且更有效 AF结构基质。为了验证这一假设，我们的目标是：1。开发并验证实时光学制导 心房消融损伤形成，和2.开发并验证AF结构的实时光学映射 印刷受体.为了实现这两个目标，开发包括创新的OCT/NIRS软件和硬件 方法沿着在正常猪和AF猪的心房以及心房中的体内和离体验证 然后，基于这些发展，我们的目标是：3.实时比较 光学引导的损伤形成和AF结构基质的标测相对于标准护理方法。 将在体内即刻确定结局，并在手术后立即进行体外验证， 以确定损伤的持久性。为了实现这些目标，我们组建了一个独特的合格的 多学科多PI团队，具有OCT（Rollins博士和亨登博士）、NIRS（亨登博士）和基本 心脏电生理学（Laurita博士），沿着Co-I在临床AF消融方面的专业知识（Ziv博士）， 心血管病理学（Marboe博士）。我们团队的长期目标是开发创新技术， 改善房颤消融结局。

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.