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

术后心房颤动节律控制和心率控制的非药物方法。

• 批准号: 10625696
• 负责人: Seungyup Lee
• 金额: $ 40.25万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10625696
• 关键词: Affect; Algorithms; Anatomy; Arrhythmia; Atrial Fibrillation; Behavior; Canis familiaris; Cardiac Surgery procedures; Characteristics; Clinical; Clinical Trials; Complication; Connexin 43; Data; Electric Countershock; Electrodes; Electrophysiology (science); Epicardium; Event; Fatty acid glycerol esters; Health Care Costs; Heart Atrium; Heart failure; Hypotension; Incidence; Inflammation; Left; Length; Length of Stay; Maintenance; Maps; Modality; Modeling; Morbidity - disease rate; Muscle Cells; Myocarditis; Outcome; Patients; Pericarditis; Pharmaceutical Preparations; Play; Postoperative Period; Prevention; Proliferating; Pulmonary veins; Recurrence; Research Proposals; Risk; Role; Secure; Sinus; Site; Sterility; Stroke; Surgeon; Testing; Therapeutic; Time; Ventricular; atrioventricular node; canine model; connexin 40; density; epicardial mapping; hemodynamics; improved; insight; mortality; treatment strategy

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.

项目摘要/摘要 术后心房颤动（POAF）是心脏手术后最​​常见的并发症， 发病率高达50％。它与明显的发病率有关，包括中风，心力衰竭和 血液动力学妥协。为了治疗POAF，有两种策略，要么节奏控制（还原 并保持窦性心律）或速率控制（控制心室速率）。用于维持窦的药物 节奏在很大程度上是无效的，而在POAF期间用于控制心室率的节奏通常会引起低血压。 因此，为了改善POAF的管理，可以实施一种非药物治疗策略。 POAF的当前非药物治疗是直流电（DC）心脏version，通常需要 治疗血液动力学不稳定的患者。但是，DC心脏反应通常是无效的，因为POAF 通常很快返回。尽管最近的临床试验表明节奏控制和速率控制是等效的 就死亡率，住院时间长度和并发症率而言，POAF的持续时间更长 长期生存和AF复发风险恶化。 POAF缺乏令人满意的治疗 我们对其机制的理解不足的一部分。在我们的犬无菌心包炎模型中（实验 与POAF相对），我们证明了心外膜炎症的激活和增殖发生在 心房会产生心外膜心肌细胞的损失，并改变了连接蛋白40和43的分布。 变化与不均匀的传导减速有关，从而为 POAF的自发启动和维护。我们在该模型中的心外膜映射研究证明了 POAF是由围绕肺静脉循环的重进入电路引起的。我们最近对患者的研究 心脏开放手术后的POAF显示，从选定的左心房记录的POAF期间的心房电图 （LA）位点显示了常规周期长度，与类似于我们犬模型的LA重新进入电路一致。 因此，像其他重入心律失常一样，POAF节奏有可能终止（节奏） 控制）。当有另一种维护POAF的机制时，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。我们提议的核心假设是 POAF是由于重进入机制，可以通过非药物节奏控制策略终止 （超速起搏）；当POAF是由于其他机制引起的时，可以通过非药物率对其进行管理 控制方法（心室节点脂肪垫刺激）。要测试的假设具有三个具体目标： 目的1是在我们的犬类模型中开发非药物方法。目标2是检验以下假设 POAF是由于心脏病手术后患者的解剖学再入学回路。使用夹带起搏 在POAF期间，我们将验证重入电路的存在。目标3是检验POAF可以是的假设 通过特定于患者的非药物方法管理。我们提议的研究的见解将改变 用于治疗POAF的范式，并有助于改善这些患者的临床结果。