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，已被 在减少心律失常复发方面一贯有效。尽管如此，PVI有一个公认的但并不是微不足道的 短期和长期失败率，通常需要多次手术，对持续性房颤效果较差。这个 房颤的机制多种多样，但增加心脏交感神经的传出刺激可能有助于房颤的发生。 房颤的发展和永续。减少心脏交感神经输入被认为是一种合乎逻辑的 PVI的辅助入路，但其通过心脏消融的技术应用只取得了好坏参半的结果。 减少心脏交感神经刺激的治疗目标可能通过肾脏来实现。 动脉失神经(RDN)，最初是为治疗顽固性高血压而开发的一种技术。RDN%s 抗心律失常的潜在作用可能是通过减少中枢神经交感神经输出和IS介导的 表现为全身去甲肾上腺素外溢和肌肉交感神经活动减少。 最近完成的随机、多中心、单盲临床试验--根除房颤，发表在 JAMA和令人信服地证明，RDN加PVI导致相对减少43%(绝对变化， 15%；P&lt；0.001)在一年随访中复发的房颤。这项试验招募了300名患有 阵发性房颤进行消融，尽管有药物治疗，但高血压控制都很差。根本没有 两组并发症发生率差异有统计学意义。试验结果表明，减少心脏疾病的策略 自主神经输入是一种有效的抗心律失常方法。到目前为止，这种方法只在患者身上进行了测试。 患有顽固性和/或控制不良的高血压。 我们提出了一项多中心、单盲、随机的临床试验，以评估肾动脉失神经在 除导管消融以消除心房颤动外(消除房颤II)，以验证RDN的假设 与单用PVI相比，PVI还能增强长期抗心律失常的疗效 持续性房颤伴控制性高血压或无高血压。审判将是有利的，通过执行 所有患者的植入式循环记录(ILR)，这将有助于计算房颤负荷，现在已被认识到 作为临床结果的有力预测指标。随着这一试点计划的圆满完成，我们希望推出 一项以心血管事件和死亡事件为终点的大规模试验。 这项试验的主要目标是确定随着时间的推移，辅助性RDN是否会导致房颤负荷的降低 与仅接受PVI的患者进行比较。次要目标是检查：程序复杂性， 体位血压和由24小时动态监护仪评估的压力控制；自主神经 系统影响；心血管住院频率；返回持续性房颤；需要重复消融 程序；和生活质量。