New generation of catheters for treatment of atrial fibrillation

摘要 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，主要是由于血流动力学性能差， 经常中风。治疗房颤的主要选择之一是心脏消融术，医生在消融术中应用射频消融技术， 能量通过经皮导管形成一系列损伤，直接破坏或隔离异常源 电活动。针对房颤消融，会创建一系列环绕肺静脉的损伤 形成电屏障，将静脉内的致瘤病灶与心脏的其余部分隔离。 然而，在试图形成损伤集时，医生无意中留下了可能被破坏的可行间隙。 这是非常难以检测的，特别是当组织被电击但仍保持代谢活性时。 当这种情况发生时，这些间隙会随着时间的推移而愈合，并将异常的电活动重新传导到其他部位。 心脏，导致术后复发率高。因此，有强烈的临床需要来识别这些 差距。不幸的是，迄今为止，用于实时监测组织损伤和间隙检测的手段有限 并且没有直接检测永久性损伤的心脏组织的手段。 在这里，我们建议将新一代经皮导管商业化， 通过真实的时间感测组织自体荧光轮廓中的光谱变化来消融心脏组织， 热损伤在第二阶段，我们生产并在活体动物中测试了两种版本的导管， 从导管尖端接触组织的点处的单根光纤获取光学特征， 复杂的版本能够高光谱成像。这一IIB期提案寻求NIH资助，以帮助 在商品名OmniView™下商业化第一个光学使能的治疗消融导管。的 该提案的第一个主要任务是制造270个导管和20个仪器，用于 V&V测试和随后的临床试验。这些导管和器械将接受广泛的V&V 根据提案中概述的标准进行安全测试。GLP活体动物测试将在 大动物猪模型。成功进行V&V测试后，我们将准备试验用器械 为获得开始临床试验的许可而向FDA提交的豁免文件集。我们 已经确定了五家医院，这些医院都有高度重视的电生理学家，他们渴望参与。我们有 还与FDA举行了初步会议，以获得对临床策略的反馈，并确定了一个CRO， 临床试验监督。然后，我们将进行临床试验，作为迈向商业化的关键一步。在 总之，对于能够实时区分健康与非健康的系统， 以高分辨率消融心肌组织，以便识别和消融病变之间的间隙。我们的新 经皮导管和仪器的产生能够获取组织自体荧光分布 在消融过程中，因此帮助医生提供更好的护理。

ABSTRACT 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 and mortality primarily due to poor hemodynamic performance and often stroke. One of the primary options to treat AF is cardiac ablation where the physician applies radiofrequency energy via percutaneous catheters to form a series of lesions that directly destroys or isolates abnormal sources of electrical activity. Specific to AF ablation, a series of lesions are created to encircle the pulmonary veins forming an electrical barrier that isolates the arrhythmogenic foci inside the vein from the rest of the heart. However, while attempting to form lesion sets, the physician inadvertently leaves viable gaps that can be extremely difficult to detect, especially when the tissue is electrically stunned but remains metabolically viable. When this happens, these gaps will heal over time and reconduct the abnormal electrical activity to the rest of the heart, causing high post-procedural recurrence rates. As such, there is a strong clinical need to identify these gaps. Unfortunately, to date there are limited means for real-time monitoring of tissue injury and gap detection during ablation procedures and there are no means of directly detecting permanently damaged cardiac tissue. Here we propose to commercialize a new generation of percutaneous catheters that can distinguish viable from ablated cardiac tissue by sensing, in real time, spectral changes in tissue autofluorescence profiles caused by thermal damage. During the Phase II we produced and tested in live animals two versions of catheters, one that acquires an optical signature from a single fiber at the point where catheter tip touches the tissue, and a more complex version capable of hyperspectral imaging. This Phase IIB proposal seeks NIH funding to help commercialize the first optically enabled therapeutic ablation catheters under the trade name OmniView™. The first major task of the proposal to do so will be to manufacture 270 catheters and 20 instruments to be used for V&V testing and the subsequent clinical trial. These catheters and the instruments will undergo extensive V&V safety testing based upon standards outlined in the proposal. GLP live animal testing will be conducted in the large-animal porcine model. Following successful V&V testing, we will prepare an Investigational Device Exemption document set for submission to the FDA in order to receive permission to begin the clinical trial. We have identified five hospital sites with highly regarded electrophysiologists who are eager to participate. We have also held initial meetings with the FDA to obtain feedback on clinical strategy and have identified a CRO for clinical trial oversight. We will then perform the clinical trial as the key step towards commercialization. In summary, there remains an unmet clinical need for a system that can distinguish, in real-time, healthy versus ablated myocardial tissue with high resolution in order to identify and ablate gaps between lesions. Our new generation of percutaneous catheters and instruments is capable of acquiring tissue autofluorescence profiles during the ablation procedure therefore assisting physicians in providing better care.