Novel medical adjunctive therapy to catheter ablation for atrial fibrillation

心房颤动导管消融的新型医学辅助疗法

• 批准号: 10113417
• 负责人: JEFFREY J GOLDBERGER
• 金额: $ 71.99万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-15 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10113417
• 关键词: Ablation; Address; Adipose tissue; Affect; Anatomy; Anti-Arrhythmia Agents; Antral; Arrhythmia; Atrial Fibrillation; Biological Markers; Blood; Blood Pressure; Body Weight decreased; Body mass index; Calcium Signaling; Cardiac; Cardiac ablation; Cessation of life; Clinical; Clinical Research; Collagen; Coronary; Data; Development; Diabetes Mellitus; Diffuse; Disease; Drug or chemical Tissue Distribution; Echocardiography; Electric Countershock; Enrollment; Evaluation; Event; Fatty acid glycerol esters; Fibrosis; Foundations; Freedom; Gelatinase A; Genes; Goals; Guidelines; Health Expenditures; Heart; Heart Atrium; Image; Inflammation; Inflammatory; Interleukin-6; Left; Left atrial structure; Maintenance; Measurable; Measurement; Mediating; Mediator of activation protein; Medical; Metabolism; Methods; Monitor; Multi-Institutional Clinical Trial; Muscle Contraction; National Heart, Lung, and Blood Institute; Natriuretic Peptides; Organ; Outcome; Overweight; Oxidative Stress; Patient-Focused Outcomes; Patients; Peripheral; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology; Pharmacotherapy; Plasma; Plasminogen Activator Inhibitor 1; Play; Procedures; Process; Property; Pulmonary veins; Quality of life; Randomized; Recurrence; Reporting; Risk; Risk Factors; Role; Sinus; Specificity; Structure; Testing; Therapeutic; Thick; United States; Validation; adipokines; analog; base; cost; effective therapy; glucagon-like peptide 1; glycemic control; heart rhythm; improved; improved outcome; liraglutide; novel; novel strategies; obese patients; obesity treatment; open label; paracrine; primary endpoint; programs; success; targeted agent; transcriptome

Project Summary Atrial fibrillation (AF) is the most common arrhythmia affecting well over 2 million people in the US with projections that it will affect 8-12 million people by 2050. It is responsible for >$6 billion in annual health care expenditures in the US. Catheter ablation to achieve sinus rhythm is a growing therapeutic option due to its greater success rate compared to antiarrhythmic drug therapy. Yet, success rates for catheter ablation are suboptimal. For patients with persistent AF, catheter ablation has even lower success rates than for those with paroxysmal AF. The STAR AF II randomized multicenter clinical trial reported an average freedom from AF after one procedure of 50% for patients with persistent AF. Epicardial adipose tissue (EAT) may play an independent role in the progression, development and recurrence of AF after catheter ablation. Specifically, left atrial (LA) EAT due to its contiguity to the LA may directly influence LA substrate via inflammatory, profibrotic, and other adipocytokines. Liraglutide (a glucagon like peptide-1 analog), an effective therapy for obesity and diabetes, markedly reduces EAT. A combined medical approach for substrate stabilization with catheter ablation has not been evaluated. Thus, the overall goal of this project is to assess the novel approach of substrate stabilization as adjunctive therapy in patients with persistent AF undergoing catheter ablation. We hypothesize that Liraglutide treatment will significantly reduce LAEAT and consequently stabilize (and even perhaps ameliorate) AF substrate. Our specific aims are to: 1) Assess for serial changes in LAEAT, EAT, atrial size/function and biomarkers of inflammation in patients with persistent AF who opt for catheter ablation due to Liraglutide treatment; 2) Evaluate the correlation of LAEAT to LA biomarkers. We will enroll 60 patients with persistent AF who have elected to undergo catheter ablation. Pre-ablation therapy will include: 1) antiarrhythmic drug therapy and cardioversion (if needed) to promote reverse electrical remodeling; 2) Risk factor management; 3) Half will be randomized to receive Liraglutide. After pre-treatment for 3 months, catheter ablation will be performed using an antral pulmonary vein isolation based approach. The primary endpoint will be change in LAEAT at 3 months (prior to ablation). Substrate evaluation will include CT (EAT, LAEAT), echocardiography (strain, EAT thickness), and biomarkers at enrollment, pre-ablation, and at one year. We will assess freedom from AF at one year off antiarrhythmic drugs documented by long-term event monitoring and compare baseline LAEAT. Evaluating the broad array of imaging and blood biomarkers will help delineate parameters that can be used to track substrate stabilization therapy. Thus, this open label clinical study of Liraglutide in combination with catheter ablation for AF will provide foundational data that will be critical for the further testing and validation of this novel approach, one that could substantially improve outcomes for patients with AF.

项目摘要 心房颤动（AF）是最常见的心律失常，在美国影响超过200万人 预测到2050年将影响8-1200万人。它将有60亿美元的年度医疗保健 美国的支出。导管消融以实现鼻窦节奏是一种不断增长的治疗选择 与抗心律失常药物治疗相比，成功率更高。但是，导管消融的成功率是 次优。对于持续性AF的患者，导管消融的成功率甚至比患有 阵发性AF。 Star AF II随机多中心临床试验报告了AF的平均自由 经过50％的手术，持续性房颤患者。心外膜脂肪组织（EAT）可能会玩 在导管消融后AF的进展，发展和复发中独立作用。具体来说，左 由于与LA的连续性，房屋（LA）饮食可能直接通过炎症，纤维化，纤维化，饮食直接影响LA底物 和其他脂肪细胞因子。 liraglutide（像肽1类似物一样），一种有效的肥胖症治疗方法 糖尿病明显减少了进食。一种与导管底物稳定的联合医学方法 尚未评估消融。因此，该项目的总体目标是评估 底物稳定为持续AF的患者接受导管消融的辅助治疗。我们 假设Liraglutide治疗将显着降低承保并因此稳定（甚至 也许可以改善）AF基板。我们的具体目的是：1）评估承保，饮食的串行变化， 选择导管的患者的心房大小/功能和炎症的生物标志物 由于Liraglutide治疗而消融； 2）评估贴心与LA生物标志物的相关性。我们将 招募60例持久性自动房屋的患者选择进行导管消融。开放式疗法将 包括：1）抗心律失常的药物治疗和心脏version（如果需要）以促进反向电重塑； 2）风险因素管理； 3）一半将被随机接收Liraglutide。预处理3个月后， 导管消融将使用基于肺静脉隔离的方法进行。主要 终点将在3个月（消融之前）变化。底物评估将包括CT（EAT， 奖金），超声心动图（应变，饮食厚度）和注册，开放性的生物标志物和一个 年。我们将评估长期事件记录的抗心律失常药物一年的自由 监视和比较基线贴心。评估广泛的成像和血液生物标志物将 帮助描述可用于跟踪底物稳定疗法的参数。因此，这个开放的标签 利拉格林与导管消融的临床研究将提供基础数据 对于这种新颖方法的进一步测试和验证至关重要，这种方法可以大大改善 AF患者的结果。