VENOUS ETHANOL ABLATION IN ISCHEMIC VENTRICULAR TACHYCARDIA- VELVET TRIAL

摘要 射频消融治疗缺血性心肌病的室性心动过速(VT) 由于疗效不佳、并发症风险和经常需要重复手术而造成的局限性。缺血型 室性心动过速是心肌梗死疤痕内或周围折返性循环的结果。共同本地化 是由冠状动脉的胚胎学决定的解剖学事实 船只。正如心肌梗死有“罪魁祸首”或“梗死相关动脉”一样，通常存在 “梗死相关静脉”或室速基质中的静脉。此外，众所周知，自主神经支配 解剖接近静脉-在心肌梗死后心律失常的发生中起着重要作用。我们已经开发出一种 靶向消融的方法--经提供静脉回流的冠状静脉注射乙醇治疗难治性室性心动过速 来自致心律失常部位(静脉注射无水乙醇，VE)。除了最初的一组案例报告外，我们还验证了 VE在大型跨国注册机构中的应用，在该注册中，我们确定了VE在射频耐火材料中的安全性和有效性 VT.鉴于心外膜动脉、静脉和神经的共同定位，VE可能特别适合于IMPACT 梗死性神经支配。因此，这项提议的一个中心目标是利用冠状动脉上存在的静脉 心外膜方面的心肌疤痕作为一种独特的治疗机制。我们假设 在常规导管消融的基础上加用VE可改善VT的消融效果。我们提出了一个单一的地点， 研究人员发起的关于VE的临床试验。 在目标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， 与单纯射频消融相比，VE与射频消融联合使用时的安全性-静脉无水乙醇 用于左室缺血性室性心动过速-天鹅绒临床试验。审判将包括一项 FDA批准的新药研究(IND)。缺血性室性心动过速患者将被随机分配到 单纯常规心内膜消融术，VS联合梗塞相关静脉VE。 在AIM 2-R33阶段-我们将招募总共156名患者，并收集以下方面的有效性、安全性和程序数据 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--与心内膜相比 只有射频。在AIM 3-R33阶段-我们将收集表征VT基板的多模式成像数据 消融后：单纯导管消融组与VE联合消融组。心脏磁共振、静脉CT 正电子发射断层扫描血管造影术和局部肾上腺素能神经支配图 神经示踪剂(11C羟麻黄碱，11C-Hed)将提供VT的完整结构评估 基片，消融前后。 如果完成，该项目将验证新的程序战略，并将提供对 室速消融成功的结构性决定因素。

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.