Mapping and Targeting Focal Sources Before and After Surgical Ablation of Atrial Fibrillation

项目总结/摘要 心房颤动（AF）是最常见的快速性心律失常， 估计超过六百万。它与中风、心力衰竭和各种原因的风险增加有关。 mortality.在阵发性房颤患者中，最常见的是由肺静脉触发引发 (PVs)，肺静脉隔离（PVI）治疗AF相对有效。 持续性和长期持续性（LSP）房颤，房颤的消融治疗，包括肺静脉隔离， 由于缺乏要消融的患者特异性“机械”靶点，结果导致 消融过程在很大程度上是一种经验性的“一刀切”方法。为了强调这一事实，最近的临床试验 在持续性房颤和LSP房颤患者中， 单独接受肺静脉隔离的患者之间无房颤的比率没有显著差异 以及接受肺静脉隔离加其他经验性消融损伤组的患者。此外，消融损伤 肺静脉隔离后，植入永久性起搏器的需求显著增加。所有这些都支持了 需要1）通过激活模式识别维持AF的机制; 2）了解 每个消融损伤对负责维持AF的心房激动模式的影响，以便我们能够 确定消融损伤产生的激动模式的哪些变化对于终止AF至关重要， 防止其复发。因此，持续性和LSP AF的消融治疗可以从很大程度上改变 从经验性方法到患者特异性靶向方法。我们最近的研究使用同时，双心房，高 持续性房颤和LSP房颤患者的心外膜接触标测（510 - 512个电极） 心内直视手术发现，从焦点源和突破点发出的波前保持 AF.此外，我们对持续性房颤和LSP房颤患者的初步研究表明，房颤仍然存在 在手术消融后立即发生，并与上述持续激活模式相关。 该建议的中心假设是，手术消融后持续性房颤是由于持续的 基线局灶源维持AF，中断其激活将终止AF。 测试有三个具体的目的：目的1是识别持续性房颤和LSP房颤患者的局灶性源。 目的2是检验手术后从局灶源发出的波前的延续 消融（肺静脉隔离±附加线性消融线）维持房颤。我们将研究每次消融的效果 病灶组的激活行为的基线局灶源和突破网站。目标3是测试 假设局灶源的靶向消融将可靠地终止AF。我们将开发一种有效的 靶向局灶源的消融策略，通过减少组织数量来提高患者安全性 永久消融从我们拟议的研究数据提供的见解应该有助于重要的 消融方法，改善持续性和LSP AF患者的护理和临床结局。

Project Summary/Abstract Atrial fibrillation (AF) is the most common tachyarrhythmia, with the number of Americans diagnosed estimated at more than six million. It is associated with an increased risk of stroke, heart failure, and all-cause mortality. In patients with paroxysmal AF, which most often is initiated by triggers from the pulmonary veins (PVs), pulmonary vein isolation (PVI) has been relatively effective in treating AF. However, in patients with persistent and long-standing persistent (LSP) AF, ablation treatment of AF, which includes PVI, has been only modestly effective because of the lack of patient-specific “mechanistic” targets to ablate. As a result, the ablation procedure is largely an empiric “one size fits all” approach. To emphasize that fact, recent clinical trials in patients with persistent and LSP AF involving endocardial catheter ablation or surgical ablation showed that there was no significant difference in the rate of freedom from AF between patients who underwent PVI alone and those who underwent PVI plus additional empiric ablation lesion sets. Furthermore, ablation lesions beyond the PVI significantly increased the need for implantation of a permanent pacemaker. All this supports the need for 1) identifying the mechanism(s) that maintain AF by activation pattern; 2) understanding the effects of each ablation lesion set on atrial activation patterns responsible for maintaining AF so that we can determine what changes in activation patterns created by the ablation lesion are critical for terminating AF and preventing its recurrence. Thereby, ablation therapy of persistent and LSP AF could change from a largely empiric approach to a patient-specific targeted approach. Our recent studies using simultaneous, biatrial, high density (510 - 512 electrodes), epicardial contact mapping in patients with persistent and LSP AF undergoing open heart surgery found that wave fronts emanating from focal sources and breakthrough sites maintained AF. Also, our preliminary studies in patients with persistent and LSP AF showed that AF was still present immediately after surgical ablation, and was associated with continued activation patterns described above. The central hypothesis of this proposal is that persistent AF after surgical ablation is due to the continuation of baseline focal sources maintaining AF, and that interrupting their activation will terminate AF. The hypothesis to be tested has three specific aims: Aim 1 is to identify focal sources in patients with persistent and LSP AF. Aim 2 is to test the hypothesis that a continuation of wave fronts emanating from focal sources after surgical ablation (PVI ± additional linear ablation lines) maintains AF. We will investigate the effects of each ablation lesion set on the activation behavior of baseline focal sources and breakthrough sites. Aim 3 is to test the hypothesis that targeted ablation of focal sources will reliably terminate AF. We will develop an efficient ablation strategy for targeting focal sources to improve patient safety by decreasing the amount of tissue ablated permanently. Insights provided by data from our proposed study should contribute importantly to the ablative approach, the improvement of both care and clinical outcomes in patients with persistent and LSP AF.