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.

抽象的 肺静脉隔离 (PVI) 是房颤 (AF) 消融策略的基石，已被广泛应用。 然而，PVI 在减少心律失常复发方面始终有效。 短期和长期失败率较高，通常需要多次手术，并且对于持续性 AF 效果较差。 AF 的机制多种多样，但增加心脏传出交感神经刺激可能有助于 心脏交感神经输入的减少已被认为是 AF 的发展和持续。 PVI 的辅助方法，但其通过心脏消融的技术应用仅取得了好坏参半或适度的结果。 减少心脏交感神经刺激的治疗目标可以通过肾脏调节来实现 动脉去神经术（RDN），最初是为治疗顽固性高血压而开发的技术。 抗心律失常作用的潜力可能是通过减少中枢神经交感神经输出来介导的，并且是 全身去甲肾上腺素溢出和肌肉交感神经活动的减少就是例证。 最近完成的随机、多中心、单盲临床试验ERADICATE-AF发表在 JAMA 令人信服地证明，RDN 加上 PVI 导致相对减少 43%（绝对变化， 15%；P < 0.001) 在一年的随访期间复发性 AF 患者。 阵发性房颤需要消融治疗，尽管接受了药物治疗，但高血压仍控制不佳。 两组之间并发症的差异表明，减少心脏病的策略。 自主输入是一种有效的抗心律失常方法，到目前为止，这种方法仅在患者身上进行了测试。 患有难治性和/或控制不佳的高血压。 我们提出一项多中心、单盲、随机临床试验来评估肾动脉去神经术 除导管消融消除心房颤动 (ERADICATE-AF II) 之外，以检验 RDN 的假设 对于患有以下疾病的患者，与单独使用 PVI 相比，除 PVI 之外，还可以增强长期抗心律失常疗效 持续性房颤伴高血压或无高血压的患者进行该试验将受益匪浅。 对所有患者进行植入式循环记录（ILR），这将有助于计算 AF 负担，目前已得到认可 作为临床结果的有力预测指标，随着该试点计划的成功完成，我们希望启动该计划。 以心血管和死亡事件为终点的大规模试验。 该试验的主要目标是确定辅助 RDN 是否会随着时间的推移减少 AF 负担 与仅接受 PVI 的患者进行比较 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； 系统影响；心血管住院频率；恢复持续性房颤的需要； 程序；和生活质量。