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

项目摘要/摘要 房颤(房颤)是最常见的快速性心律失常，被诊断为房颤的美国人 估计有600多万人。它与中风、心力衰竭和各种原因的风险增加有关。 死亡率。在阵发性房颤患者中，最常见的是肺静脉触发 肺静脉隔离(PVI)是治疗房颤的有效方法。然而，在患有 持续性和长期持续性(LSP)房颤，包括PVI在内的房颤的消融治疗一直只有 由于缺乏针对患者的“机械性”消融靶点，因此疗效不高。因此， 消融手术在很大程度上是一种经验性的“一刀切”的方法。为了强调这一事实，最近的临床试验 在持续性和LSP患者中，涉及心内膜导管消融或外科消融的房颤显示 单独接受PVI的患者中，房颤的自由率没有显著差异 接受PVI加额外经验性消融治疗的患者。此外，消融损伤 除PVI外，植入永久性起搏器的需求显著增加。所有这些都支持 需要1)通过激活模式识别维持房颤的机制(S)；2)理解 每组消融对维持房颤的心房激动模式的影响，以便我们能够 确定消融病变产生的激活模式中的哪些变化对于终止房颤和 防止其再次发生。因此，持续性房颤和LSP房颤的消融治疗可以从很大程度上改变 针对特定患者的有针对性的经验性方法。我们最近的研究使用同步、双心房、高位 持续性和LSP房颤患者的密度(510-512个电极)、心外膜接触标测 心内直视手术发现，从灶源和突破点发出的波锋保持不变 自动对焦。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 手术消融后即刻，并与上述持续激活模式相关。 这一建议的中心假设是外科消融后的持续性房颤是由于持续的 维持房颤的基线震源，中断其激活将终止房颤。假说 接受测试有三个具体目标：目标1是确定持续性和LSP房颤患者的病灶来源。 目标2是检验这样一种假设，即手术后从焦点来源发出的波前的延续 消融(PVI±附加线性消融线)维持房颤。我们将调查每一次消融的效果 病灶设置在基线震源和突破点的激活行为上。目标3是测试 假设靶向消融焦点源将可靠地终止房颤。我们将开发一种高效的 靶向焦源的消融策略，通过减少组织数量来提高患者的安全性 永久地消融了。我们拟议研究中的数据提供的见解应该对 消融方法，改善持续性和LSP房颤患者的护理和临床结果。

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.