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.

摘要 缺血性心肌病室性心动过速（VT）的射频消融充满了 由于次优疗效、并发症风险和频繁需要重复手术而导致的局限性。缺血性 室性心动过速是由于梗死心肌瘢痕内或周围的折返性回路引起的。的共定位 心室动脉、静脉和神经的起源是一个解剖学事实，由冠状动脉的胚胎学决定。 船舶.正如心肌梗死有一个“罪魁祸首”或“梗死相关动脉”， “梗死相关静脉”或VT基质中的静脉。此外，众所周知，自主神经支配-- 解剖学上接近静脉-在MI后血管生成中起重要作用。我们已经开发了一个 通过在提供静脉回流的冠状静脉中输送乙醇靶向消融难治性VT的方法 来自致炎部位（静脉乙醇，VE）。除了最初的一组病例报告外，我们还验证了 在一项大型多国登记研究中，我们确定了VE在RF难治性患者中的安全性和有效性 佛蒙特州考虑到心外膜动脉、静脉和神经的共同定位，VE可能特别适合于撞击 梗死神经支配因此，该提议的中心目标是利用冠状静脉的存在， 心外膜方面的心肌疤痕作为一个独特的机制治疗的机会。我们假设 在常规导管消融中加入VE可改善VT消融的结果。我们提出一个单一的网站， 制药商发起的VE临床试验。 在Aim 1-R61阶段-，我们建议完成随机临床试验的设计，以评估临床疗效， 与单独射频消融相比，VE与射频消融联合使用时的安全性-静脉乙醇 左心室缺血性室性心动过速-VELVET临床试验。审判将包括一个 FDA的研究性新药（IND）授权。缺血性VT患者将随机分配至 在梗死相关静脉中，单独进行常规腔内消融vs联合VE。 在Aim 2 -R33阶段-我们将招募总共156例患者，并收集以下方面的疗效、安全性和手术数据： VE对导管消融的影响。这项试验将允许收集大量新的成像数据 这将表征VE前后心肌瘢痕和神经支配的程度-与内皮细胞相比， RF单独在Aim 3 -R33阶段-我们将收集表征VT基质的多模态成像数据， 消融后-单独导管消融vs联合VE。心脏磁共振，静脉CT 血管造影和局部肾上腺素能神经分布图与正电子发射断层扫描（PET）扫描， 神经支配示踪剂（11 C羟麻黄碱，11 C-HED）将提供VT的完整结构评估 基板，烧蚀之前和之后。 如果完成，该项目将验证一个新的程序战略，并将提供关键的新见解， 室性心动过速消融成功的结构决定因素。