PROPHYLACTIC CARDICA SYMPATHETIC DENERVATION FOR PREVENTION OF VENTRICULAR TACHYARRHYTHMIAS (PREVENT VT)

预防性贲门交感神经去神经术预防室性快速心律失常（预防室性心动过速）

基本信息

批准号：
10043765
负责人：
David Elashoff
金额：
$ 24.03万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-10 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10043765
关键词：
Ablation Acute Adverse event Affect Amiodarone Angiotensin-Converting Enzyme Inhibitors Anti-Arrhythmia Agents Arrhythmia Bilateral Cardiac Cardiac ablation Cardiomyopathies Case Series Cause of Death Cessation of life Chronic Clinical Data Defibrillators Dose EFRAC Enrollment Fiber Goals Heart Heart Diseases Heart Transplantation Heart failure Hospitalization Implant Interruption Left Life Maintenance Medical Morbidity - disease rate Multicenter Trials Myocardium Neurons Observational Study Operative Surgical Procedures Participant Pathologic Patient Care Patient Recruitments Patients Pharmaceutical Preparations Pharmacotherapy Pilot Projects Play Prevention Procedures Quality of life Randomized Randomized Clinical Trials Recurrence Refractory Reporting Resources Retrospective Studies Risk Role Safety Savings Shock Structure Sudden Death Sympathectomy Sympathetic Ganglia Sympathetic Nervous System Tachyarrhythmias Testing Therapeutic Time Ventricular Ventricular Arrhythmia Ventricular Fibrillation Ventricular Tachycardia adverse event risk arm beta-adrenergic receptor cost design experience hospital readmission implantation improved outcome mortality myocardial injury novel strategies power analysis primary endpoint prophylactic randomized trial routine care side effect standard of care structural heart disease sudden cardiac death treatment arm treatment strategy ventricular assist device

项目摘要

ABSTRACT Ventricular tacharrhythmias (VT/VF) are a common cause of mortality in patients with structural heart disease, resulting in implantation of ICDs to reduce risk of sudden cardiac death. Over 150,000 ICDs are implanted in the U.S. each year. Although a life-saving therapy, many patients experience recurrent ICD shocks despite optimal medical therapy, resulting in decreased quality of life and increased morbidity. Furthermore, recurrent VT and ICD shocks are associated with increased mortality over time. Therefore, catheter ablation of VT has become standard-of-care for patients with recurrent shocks. Yet, up to 30-50% of patients experience recurrent VT/VF and shocks within 12 months of their procedure, despite medical and anti-arrhythmic therapy, resulting in multiple attempts at ablation, repeat hospitalizations, and referral for ventricular assist device placement or heart transplantation. The sympathetic nervous system is known to play a critical role in the genesis and maintenance of VT/VF, and neuraxial modulation represents a new course-altering avenue for treatment of these arrhythmias in patients with structural heart disease. Medications that target the sympathetic nervous system, including β- adrenergic receptor blockers, have been shown to reduce the risk of sudden cardiac death and improve outcomes of heart failure patients. Bilateral cardiac sympathetic denervation (CSD), by interrupting sympathetic efferent and afferent fibers, can have a similar potential impact, and has been reported to significantly reduce the burden of ICD shocks in retrospective observational studies of patients with structural heart disease and VT. However, the value of this potentially important therapy is unknown and needs to be tested in a randomized fashion. We propose a clinical pilot study of 40 patients randomized to CSD plus routine care or routine care alone. The goal of this pilot study is to obtain important feasibility, efficacy, and safety data to allow for the design of a large-scale multi-center trial that can then determine whether bilateral CSD can increase the time to ICD shock/VT/VF and decrease burden of ICD shocks as compared to routine care alone. The proposed pilot study will provide essential data on patient recruitment, power, and analysis of side-effects and complications related to the procedure. Bilateral CSD is an approach that has the potential for a global impact, given the prohibitive high cost and resources needed for catheter ablation procedures, ventricular assist device implantation, and heart transplantion. The results of this pilot study will allow for the design of a proper randomized trial to test the value of this potentially life-saving therapy.

抽象的室性快速心律失常（VT/VF）是结构性心脏病患者死亡的常见原因，植入 ICD 以降低心源性猝死的风险超过 150,000 个 ICD 被植入。尽管这是一种挽救生命的疗法，但许多患者每年都会经历反复的 ICD 电击。最佳的药物治疗，导致生活质量下降和发病率增加。 VT 和 ICD 电击与死亡率随着时间的推移而增加有关，因此，VT 导管消融已成为现实。成为复发性休克患者的标准治疗方法，然而，高达 30-50% 的患者会出现复发性休克。尽管进行了药物和抗心律失常治疗，但在手术后 12 个月内出现 VT/VF 和休克，导致多次尝试消融、重复住院以及转诊心室辅助装置放置或心脏移植。众所周知，交感神经系统在神经系统的发生和维持中发挥着关键作用。 VT/VF 和椎管内调制代表了治疗这些心律失常的新途径针对结构性心脏病的患者服用针对交感神经系统的药物，包括β- 肾上腺素能受体阻滞剂，已被证明可以降低心源性猝死的风险并改善通过中断双侧心脏交感神经支配（CSD）来评估心力衰竭患者的结果。交感传出纤维和传入纤维，可以产生类似的潜在影响，并且有报道称在对结构性心脏病患者的回顾性观察研究中，显着减轻了 ICD 电击的负担然而，这种潜在重要疗法的价值尚不清楚，需要进一步研究。我们建议对 40 名随机接受 CSD plus 治疗的患者进行一项临床试点研究。这项试点研究的目标是获得重要的可行性、有效性和有效性。安全数据允许设计大规模多中心试验，然后确定双边是否与常规电击相比，CSD 可以延长 ICD 电击/VT/VF 的时间并减轻 ICD 电击的负担拟议的试点研究将提供有关患者招募、权力和分析的重要数据。与手术相关的副作用和并发症。双边 CSD 是一种有潜力的方法。鉴于导管消融手术所需的高昂成本和资源，将产生全球影响，该试点研究的结果将允许心室辅助装置植入和心脏移植。设计适当的随机试验来测试这种可能挽救生命的疗法的价值。