Non-Pharmacologic Approach to Rhythm Control and Rate Control of Postoperative Atrial Fibrillation.

项目概要/摘要 术后房颤（POAF）是心脏直视手术后最常见的并发症， 发病率高达50%。它与显著的发病率相关，包括中风、心力衰竭和 血流动力学受损对于POAF的治疗，有两种策略，或者节律控制（恢复）， 和维持窦性心律）或速率控制（控制心室率）。用于维持鼻窦的药物 在POAF期间，用于控制心室率的心律在很大程度上是无效的，并且这些心律经常引起低血压。 因此，为了改善POAF的管理，可以实施非药物治疗策略。 目前POAF的非药物治疗是直流电复律，这是经常需要的 来治疗血流动力学不稳定的病人然而，直流电复律通常是无效的，因为POAF 通常会很快回来。尽管最近的一项临床试验表明，节律控制和心率控制是等效的， 就死亡率、住院时间和并发症发生率而言，POAF持续时间较长与 长期生存率和房颤复发风险恶化。POAF缺乏令人满意的治疗主要是由于 部分原因是我们对它的机制认识不足。在我们的犬无菌心包炎模型（实验性 与POAF相对应），我们证明了发生在POAF中的心外膜炎症的激活和增殖， 心房产生心外膜肌细胞的损失和连接蛋白40和43的改变的分布。这些 变化与传导的不均匀减慢有关，从而为 POAF的自发启动和维持。我们在该模型中的心外膜标测研究表明， POAF是由肺静脉周围的折返性循环引起的。我们最近对患有 心脏直视手术后POAF显示，POAF期间记录的心房电图来自选定的左房， (LA)部位表现出规则的周期长度，与我们的犬模型相似的左心房折返性回路一致。 因此，与其他折返性心律失常一样，POAF心律有可能被起搏终止（心律失常）。 对照）。当有另一种机制维持POAF时，使用脂肪垫刺激的速率控制方法 可用于控制POAF期间的心室率。我们建议的核心假设是，当 POAF是由折返机制引起的，可以通过非药物节律控制策略终止 （起搏）;当POAF是由于其他机制，它可以通过非药物率管理 对照方法（房室结脂肪垫刺激）。待检验的假设有三个具体目标： 目的1是在我们的犬模型中开发非药物方法。目的2是检验假设， POAF是由于心脏直视手术后患者的解剖学折返回路所致。使用夹带起搏 在POAF期间，我们将验证折返回路的存在。目的3是检验POAF可以 通过患者特异性非药物方法进行管理。我们提出的研究的见解将改变 POAF的治疗范例，并有助于改善这些患者的临床结局。

Project Summary/Abstract Postoperative atrial fibrillation (POAF) is the most common complication following open heart surgery, with an incidence of up to 50%. It is associated with significant morbidity, including stroke, heart failure, and hemodynamic compromise. For the treatment of POAF, there are two strategies, either rhythm control (restoring and maintaining sinus rhythm) or rate control (controlling ventricular rate). Medications used to maintain sinus rhythm are largely ineffective, and those used to control ventricular rates during POAF often cause hypotension. Therefore, to improve management of POAF, a non-pharmacologic treatment strategy could be implemented. The current non-pharmacologic treatment of POAF is direct current (DC) cardioversion, which is often needed to treat patients who are hemodynamically unstable. However, DC cardioversion is often ineffective, as the POAF usually returns quickly. Although a recent clinical trial showed that rhythm control and rate control are equivalent in terms of mortality, length of hospital stay, and complication rates, a longer duration of POAF is associated with worsened long-term survival and risk of AF recurrence. The lack of satisfactory treatment of POAF is due in large part to our insufficient understanding of its mechanism. In our canine sterile pericarditis model (an experimental counterpart to POAF), we demonstrated that activation and proliferation of epicardial inflammation occurring in the atria produces a loss of epicardial myocytes and an altered distribution of connexins 40 and 43. These changes are associated with non-uniform slowing of conduction, thus creating the vulnerable substrate for the spontaneous initiation and maintenance of POAF. Our epicardial mapping studies in this model demonstrated that POAF is caused by a reentrant circuit circulating around pulmonary veins. Our recent study in patients with POAF after open heart surgery showed that atrial electrograms during POAF recorded from selected left atrial (LA) sites demonstrated regular cycle lengths, consistent with a LA reentrant circuit similar to our canine model. Therefore, like other reentrant arrhythmias, the POAF rhythm has the potential to be pace terminated (rhythm control). When there is another mechanism maintaining POAF, a rate control approach using fat pad stimulation could be used to control the ventricular rate during POAF. The central hypothesis of our proposal is that when POAF is due to a reentrant mechanism, it can be terminated by a non-pharmacologic rhythm control strategy (overdrive pacing); when POAF is due to other mechanisms, it can be managed by a non-pharmacologic rate control approach (atrioventricular node fat pad stimulation). The hypothesis to be tested has three specific aims: Aim 1 is to develop non-pharmacologic approaches in our canine model. Aim 2 is to test the hypothesis that POAF is due to an anatomical reentrant circuit in patients after open heart surgery. Using entrainment pacing during POAF, we will verify the existence of a reentrant circuit. Aim 3 is to test the hypothesis that POAF can be managed by a patient-specific non-pharmacologic approach. Insights from our proposed studies will change the paradigm for the treatment of POAF, and contribute to improved clinical outcomes in these patients.