VENOUS ETHANOL ABLATION IN ISCHEMIC VENTRICULAR TACHYCARDIA- VELVET TRIAL

静脉乙醇消融治疗缺血性室性心动过速 - VELVET 试验

• 批准号: 10663024
• 负责人: Miguel Valderrabano
• 金额: $ 73.83万
• 依托单位: METHODIST HOSPITAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10663024
• 关键词: Ablation; Adhesions; Adrenergic Agents; Anatomy; Angiography; Area; Arteries; Atherosclerosis; Authorization documentation; Cannulations; Cardiac; Cardiac ablation; Cardiomyopathies; Case Study; Catheterization; Characteristics; Cicatrix; Circulation; Clinical; Clinical Trials; Collection; Contracts; Coronary; Coronary Vessels; Coronary artery; Coronary sinus structure; Data; Denervation; Embryology; Enrollment; Ethanol; Fatty acid glycerol esters; Future; Goals; Heart; Hypersensitivity; Image; Infarction; Infusion procedures; Investigational Drugs; Ischemia; Left; Lesion; Magnetic Resonance; Manuals; Maps; Multimodal Imaging; Myocardial; Myocardial Infarction; Myocardial Ischemia; Myocardium; Nerve; Outcome; Patients; Pericardial body location; Phase; Play; Positron-Emission Tomography; Procedures; Protocols documentation; Radiofrequency Interstitial Ablation; Randomized; Refractory; Registries; Research Personnel; Risk; Role; Route; Safety; Site; Structure; Structure of left gastric vein; Structure of phrenic nerve; Techniques; Testing; Therapeutic; Therapeutic Effect; Tracer; Veins; Venous; Ventricular; Ventricular Arrhythmia; Ventricular Premature Complexes; Ventricular Tachycardia; Work; authority; cardiac magnetic resonance imaging; clinical efficacy; clinical trial protocol; design; experience; improved; injured; insight; ischemic cardiomyopathy; nerve supply; operation; radio frequency; randomized trial; randomized, clinical trials; structural determinants; success

Abstract Radiofrequency (RF) ablation of ventricular tachycardia (VT) in ischemic cardiomyopathy is fraught with limitations due to suboptimal efficacy, risk of complications, and frequent need for repeat procedures. Ischemic VT arises as a result of reentrant circuits within or around the myocardial scar of an infarct. The co-localization of ventricular arteries, veins, and nerves, is an anatomical fact, determined by the embryology of coronary vessels. Just as myocardial infarctions have a “culprit” or “infarct-related artery”, there commonly exists an “infarct-related vein” or veins in VT substrate. Additionally, it is well known that autonomic innervation -in anatomical proximity to the veins- plays an important role in post-MI arrhythmogenesis. We have developed an approach to target ablation-refractory VTs via ethanol delivery in the coronary veins that provide venous return from arrhythmogenic sites (venous ethanol, VE). Beyond an initial set of case reports, we have validated the utility of VE in a large, multinational registry, in which we establish the safety and efficacy of VE in RF-refractory VT. Given the co-localization of epicardial arteries, veins and nerves, VE may be particularly suited to impact infarct innervation. Thus, a central goal of this proposal is to capitalize on the presence of coronary veins on the epicardial aspect of a myocardial scar as a therapeutic opportunity of unique mechanisms. We hypothesize that VE added to conventional catheter ablation improves the results of VT ablation. We propose a single-site, investigator-initiated clinical trial on VE. In Aim 1-R61 phase-, we propose to finalize the design of randomized clinical trial to assess the clinical efficacy, and safety of VE when used in combination with RF ablation compared with RF ablation alone -Venous Ethanol for Left Ventricular Ischemic VEntricular Tachycardia -VELVET clinical trial. The trial will include an investigational new drug (IND) authorization by the FDA. Patients with ischemic VT will be randomized to conventional endocardial ablation alone, vs combined with VE in the infarct-related vein. In Aim 2 -R33 phase- we will enroll a total of 156 patients, and collect efficacy, safety and procedural data on the impact of VE added to catheter ablation. This trial will allow for a wealth of new imaging data to be collected that will characterize the extent of myocardial scar and innervation before and after VE -compared to endocardial RF alone. In Aim 3 -R33 phase- we will collect multi-modality imaging data characterizing the VT substrate before and after ablation -with catheter ablation alone vs combined with VE. Cardiac magnetic resonance, venous CT angiograms and regional adrenergic innervation maps with positron emission tomography (PET) scans of innervation tracers (11C hydroxyephedrine, 11C-HED) will provide a complete structural assessment of the VT substrate, before and after ablation. If completed, the project will validate a new procedural strategy and will provide key new insights into the structural determinants of VT ablation success.

抽象的 缺血性心肌病中心室心动过速（VT）的射频（RF）消融 由于次优效率，并发症的风险以及经常需要重复程序引起的限制。缺血性 VT是由于基础设施的心肌疤痕内或周围的重进入电路而产生的。共定位 心室动脉，静脉和神经是一个解剖事实，取决于冠状动脉的胚胎学 船只。正如心肌梗死具有“罪魁祸首”或“梗塞相关的动脉”一样，通常也存在 VT底物中的“梗死相关静脉”或静脉。此外，众所周知，自主神经 - 与静脉的解剖学接近 - 在MI后心律失常发生中起重要作用。我们已经开发了 通过冠状静脉中乙醇递送靶向消融 - 侵产性VT的方法 来自心律失常部位（静脉乙醇，VE）。除了初始案例报告之外，我们还验证了 VE在大型跨国注册表中的效用，在该注册表中，我们确定了RF-弗里克里的VE的安全性和效率 VT。鉴于心外膜动脉，静脉和神经的共定位，VE可能特别适合影响 梗塞神经。这就是该提议的核心目标是利用冠状动脉静脉在 心心疤痕的心外神经方面是独特机制的治疗机会。我们假设这一点 在常规导管消融中增加的VE改善了VT消融的结果。我们提出了一个单位， 研究人员发动的VE临床试验。 在AIM 1-R61期中，我们建议最终确定随机临床试验的设计，以评估临床效率， 与单独的RF消融相比，与RF消融结合使用时VE的安全性 用于左心室缺血性心室心动过速临床试验。审判将包括一个 FDA的研究新药（IND）授权。缺血性VT患者将随机分为 仅常规的心内膜消融，与梗死相关的静脉中的VE相结合。 在AIM 2 -R33阶段 - 我们将总共注册156名患者，并收集有关效率，安全性和程序数据 VE的影响增加了导管消融。该试验将允许收集大量的新成像数据 这将表征在VE与心内膜之前和之后的心肌疤痕和神经的范围 独自一人。在AIM 3 -R33阶段 - 我们将收集表征VT基板的多模式成像数据 在消融之后 - 仅与导管消融与VE结合在一起。心脏磁共振，静脉CT 具有正电子发射断层扫描（PET）扫描的血管造影和区域肾上腺神经图图 神经示踪剂（11C羟基麻黄碱，11C-HED）将对VT提供完整的结构评估 底物，消融前后。 如果完成，该项目将验证一种新的程序策略，并将为此提供关键的新见解 VT消融成功的结构决定者。