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: 10685356
• 负责人: Jonathan S. Steinberg
• 金额: $ 23.68万
• 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/10685356
• 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; Echocardiography; Emergency department visit; Event; Failure; Frequencies; Goals; Hospitalization; Hour; Hypertension; Implant; Measurement; Measures; Mediating; Medical; Muscle; Nerve; Norepinephrine; Outcome; Output; Patients; Pharmaceutical Preparations; Posture; Pre-Clinical Model; Procedures; Publishing; Pulmonary veins; Quality of life; Randomized; Recurrence; Resistance; Resistant Hypertension; Single-Blind Study; Sympathetic Nervous System; Techniques; Testing; Therapeutic; Thick; Time; cardiovascular emergency; follow-up; hypertensives; indexing; pilot trial; predict clinical outcome; pressure; programs; randomized trial; randomized, clinical trials; renal artery; safety assessment; success; symptomatic improvement; trial enrollment

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）是房颤消融策略的基石（AF），已经是 一贯有效减少心律不齐的复发。尽管如此，PVI还是公认的且不显着的 短期和长期失败的速率通常需要多个程序，并且对持续的AF效果较差。 AF的机制是潜水员，但有效的心脏交感神经刺激增加会有助于 AF的开发和延续。已经提出了减少心脏交感的输入作为逻辑 PVI的辅助方法，但其通过心脏消融的技术应用仅具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脏来实现 动脉神经（RDN），这是一种最初用于治疗耐药性高血压的技术。 RDN的 抗心律失常效应的潜力可能是通过降低中枢神经交感输出来介导的，并且 全身去甲肾上腺素和肌肉交感神经活动的降低体现了体现。 最近完成的随机，多中心，单盲临床试验Eradicate-AF发表在 JAMA和令人信服地表明，RDN Plus PVI导致相对降低43％（绝对变化， 15％； p <0.001）在随访的一年中，反复事件AF。该试验注册> 300例患者 阵发性AF被引用进行消融，所有这些都受到控制不良的高血压目的地药物治疗。没有 两组之间并发症的差异。试验结果表明，减少心脏的策略 自主输入是一种有效的抗心律失常方法。到目前为止，这种方法仅在患者中进行了测试 耐药性和/或控制不良的高血压。 我们提出了一项多中心，单盲，随机临床试验，以评估肾动脉神经 除了导管消融以消除房颤（Eradicate-AF II），以检验RDN的假设 除PVI外，与单独的PVI相比 持久性AF具有控制性高血压或无高血压。通过执行试验将是有利的 所有患者的植入循环记录（ILR），这将有助于AF Burnen的计算，现在已识别 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 一项大规模试验，其中心血管和死亡事件是终点。 该试验的主要目的是确定辅助RDN是否会导致AF燃烧随着时间的推移减少 与仅接受PVI的患者进行比较。次要目标是检查：程序上的并发症， 由24小时卧床监测器评估的姿势血压和压力控制；自主神经 系统效应；心血管住院的频率；返回持续的AF；需要重复消融 程序；和生活质量。

项目成果

The Emerging Therapeutic Potential of Botulinum Toxin in Cardiology.

• DOI: 10.1016/j.hrthm.2022.08.032
• 发表时间: 2022-09
• 期刊: Heart rhythm
• 影响因子: 5.5
• 作者: J. Steinberg;Alexander Romanov

Ready to deploy prophylactics?

准备好部署预防措施了吗？

• DOI: 10.1111/jce.15482
• 发表时间: 2022
• 期刊: Journal of cardiovascular electrophysiology
• 影响因子: 2.7
• 作者: Aktas,MehmetK;Steinberg,JonathanS
• 通讯作者: Steinberg,JonathanS