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.

项目概要/摘要 术后心房颤动（POAF）是心脏直视手术后最常见的并发症， 发生率高达50%。它与显着的发病率相关，包括中风、心力衰竭和 血流动力学妥协。对于POAF的治疗，有两种策略，要么节律控制（恢复节律） 并维持窦性心律）或心率控制（控制心室率）。用于维持鼻窦的药物 节律在很大程度上是无效的，而在 POAF 期间用于控制心室率的药物通常会导致低血压。 因此，为了改善 POAF 的治疗，可以实施非药物治疗策略。 目前 POAF 的非药物治疗是直流电 (DC) 电复律，这通常是需要的 治疗血流动力学不稳定的患者。然而，DC 电复律通常无效，因为 POAF 通常很快就会返回。尽管最近的一项临床试验表明节律控制和速率控制是等效的 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 缺乏满意的治疗有很大原因 部分原因是我们对其机制了解不够。在我们的犬无菌性心包炎模型中（实验性 POAF 的对应物），我们证明了心外膜炎症的激活和增殖发生在 心房产生心外膜肌细胞的损失以及连接蛋白 40 和 43 的分布改变。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。我们在此模型中的心外膜标测研究表明 POAF 是由肺静脉周围循环的折返回路引起的。我们最近对患者进行的研究 心脏直视手术后的 POAF 显示，POAF 期间从选定的左心房记录的心房电图 (LA) 站点表现出规则的周期长度，与类似于我们的犬模型的 LA 可重入回路一致。 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 控制）。当存在另一种机制维持 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。我们提案的中心假设是，当 POAF是由于可重入机制引起的，可以通过非药物节律控制策略来终止 （超速节奏）；当 POAF 是由其他机制引起时，可以通过非药物治疗来控制 控制方法（房室结脂肪垫刺激）。要检验的假设有三个具体目标： 目标 1 是在我们的犬模型中开发非药物方法。目标 2 是检验以下假设： POAF 是由心脏直视手术后患者的解剖学折返回路引起的。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 可以被 通过针对患者的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果。