A Trial to Evaluate Renal Artery Denervation in Addition to Catheter Ablation to Eliminate Atrial Fibrillation (ERADICATE-AF II)

评估除导管消融之外的肾动脉去神经术以消除心房颤动的试验 (ERADICATE-AF II)

• 批准号: 10212737
• 负责人: Jonathan S. Steinberg
• 金额: $ 23.37万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10212737
• 关键词: Ablation; Adverse effects; Ambulatory Blood Pressure Monitoring; Ambulatory Monitoring; Anti-Arrhythmia Agents; Arrhythmia; Atrial Fibrillation; Autonomic ganglion; Autonomic nervous system; Blood Pressure; Cardiac; Cardiac ablation; Cardiovascular system; Cessation of life; Clinical; Clinical Trials; Complication; Coupled; Denervation; Development; EFRAC; Emergency department visit; Enrollment; Event; Failure; Frequencies; Goals; Hospitalization; Hour; Hypertension; Lead; Measurement; Measures; Mediating; Medical; Muscle; Nerve; Norepinephrine; Outcome; Output; Patients; Pharmaceutical Preparations; Posture; Pre-Clinical Model; Procedures; Publishing; Pulmonary veins; Quality of life; Randomized; Randomized Clinical Trials; Recurrence; Resistance; Resistant Hypertension; Safety; Single-Blind Study; Sympathetic Nervous System; Techniques; Testing; Therapeutic; Thick; Time; cardiovascular emergency; follow-up; indexing; pilot trial; predict clinical outcome; pressure; programs; randomized trial; renal artery; success; symptomatic improvement

ABSTRACT Pulmonary vein isolation (PVI) is the cornerstone of ablation strategies for atrial fibrillation (AF) and has been consistently effective in reducing arrhythmia recurrence. Nonetheless, PVI has a recognized and not insignificant rate of short- and long-term failure, often requires multiple procedures and is less effective for persistent AF. The mechanisms of AF are diverse, but increased efferent cardiac sympathetic nerve stimulation can contribute to the development and perpetuation of AF. Reduction in cardiac sympathetic input has been proposed as a logical adjunctive approach to PVI but its technical application via cardiac ablation has had only mixed or modest results. The therapeutic objective of reduced cardiac sympathetic stimulation can be potentially accomplished by renal artery denervation (RDN), a technique originally developed for the treatment of resistant hypertension. RDN’s potential for antiarrhythmic effect may be mediated by reduced central nervous sympathetic output and is exemplified by a decrease in whole-body norepinephrine spillover and muscle-sympathetic nerve activity. The recently completed randomized, multicenter, single-blind clinical trial, ERADICATE-AF, was published in JAMA and convincingly demonstrated that RDN plus PVI resulted in a relative 43% reduction (absolute change, 15%; P < 0.001) in recurrent incident AF during one year of follow-up. The trial enrolled > 300 patients with paroxysmal AF referred for ablation, all with poorly controlled hypertension despite medication. There was no difference in complications between the 2 groups. The trial results suggested that a strategy of reducing cardiac autonomic input is an effective antiarrhythmic approach. Until now, this approach has only been tested in patients with resistant and/or poorly controlled hypertension. We propose a multicenter, single-blinded, randomized clinical trial to Evaluate Renal Artery Denervation In Addition to Catheter Ablation to Eliminate Atrial Fibrillation (ERADICATE-AF II), to test the hypothesis that RDN in addition to PVI enhances long-term antiarrhythmic efficacy in comparison to PVI alone for patients with persistent AF with controlled hypertension or without hypertension. The trial will be advantaged by performing implantable loop recordings (ILR) in all patients, which will facilitate the calculation of AF burden, now recognized as a powerful predictor of clinical outcome. With successful completion of this pilot program, we hope to launch a large-scale trial with cardiovascular and death events as endpoints. The principal goal of this trial is to determine if adjunctive RDN results in reduced AF burden over time in comparison to patients who undergo only PVI. The secondary goals are to examine: procedural complication, postural blood pressure, and pressure control as assessed by 24-hour ambulatory monitors; autonomic nervous system effects; frequency of cardiovascular hospitalizations; return to persistent AF; need for repeat ablation procedures; and quality of life.

摘要 肺静脉隔离（PVI）是房颤（AF）消融策略的基石， 持续有效地减少心律失常复发。尽管如此，PVI具有公认的且并非微不足道的 短期和长期失败率，通常需要多次手术，对持续性AF效果较差。 AF的机制是多种多样的，但是增加的传出心脏交感神经刺激可以有助于AF的发生。 心脏交感神经输入的减少已被提出作为一个逻辑的 肺静脉隔离的成功方法，但其通过心脏消融术的技术应用只有混合或适度的结果。 减少心脏交感神经刺激的治疗目标可以通过肾移植潜在地实现。 动脉去神经支配（RDN），一种最初为治疗顽固性高血压而开发的技术。RDN's 潜在的抗癫痫作用可能是通过减少中枢神经交感神经输出来介导的， 例如全身去甲肾上腺素溢出和肌肉交感神经活动的减少。 最近完成的随机、多中心、单盲临床试验ERADICATE-AF发表在 JAMA并令人信服地证明RDN加PVI导致相对减少43%（绝对变化， 15%; P < 0.001）。该试验招募了> 300名患者， 阵发性房颤转介消融，尽管使用药物，但高血压控制不佳。没有 两组之间的并发症差异。试验结果表明，减少心脏病的策略 自主神经输入是一种有效的抗抑郁方法。到目前为止，这种方法只在患者身上进行过测试 患有顽固性和/或控制不佳的高血压。 我们提出了一个多中心，单盲，随机临床试验，以评估肾动脉去神经， 增加导管消融消除房颤（ERADICATE-AF II），以检验RDN 与单纯肺静脉隔离相比，肺静脉隔离还可增强患者的长期抗肿瘤疗效， 持续性房颤伴控制性高血压或不伴高血压。试验将通过表演 所有患者的植入式线圈记录（ILR），这将有助于计算AF负担，现在已被认可 作为临床结果的有力预测器。随着这项试点计划的成功完成，我们希望推出 一项以心血管和死亡事件为终点的大规模试验。 本试验的主要目的是确定连续性RDN是否会随着时间的推移减少AF负担， 与仅接受肺静脉隔离的患者相比。次要目标是检查：手术并发症， 通过24小时动态监测仪评估体位血压和压力控制;自主神经 系统效应;心血管住院频率;复发持续性AF;需要重复消融 程序;和生活质量。