Vein of Marshall as a therapeutic agent in the treatment of atrial fibrillation

描述（由申请人提供）：本项目的广泛、长期目标是探索马歇尔静脉（VOM）乙醇输注在房颤（AF）治疗中的潜在作用。房颤是成年人中最常见的持续节律障碍，影响超过250万美国人，并与中风和死亡率的显著增加有关。房颤的导管消融包括肺静脉心房隔离（PVAI），是治疗房颤最有效的治疗策略，约80%的患者心律正常。PVAI的机制基础、最佳导管技术和并发症风险的重要细节是不完整或有争议的。VOM是左心室的冠状静脉窦静脉分支的胚胎残余左侧上腔静脉,并包含重要的交感和副交感神经参与房颤的起源,异常的异位比来自已被证明发起AF生效。VOM在于位置通常在洛杉矶PVAI目标组织的一部分,很难切除通常由于其厚度(侧脊)。值得注意的是，它也位于冠状窦和左肺静脉之间，这一区域通常被消融以避免左心房扑动。它也可以靠近左心房和食道之间的接触点。一种新的技术逆行插管的VOM被开发和验证在狗和人。一旦插管，乙醇输注实现快速组织消融，没有附带损伤的风险。潜在的优势包括：消融促进房颤的交感和副交感神经支配，消融房颤的VOM触发器，消融心外膜侧侧脊，以及右侧手术快速组织消融。我们建议研究该技术的机制基础细节，并确定其在治疗人类房颤中的作用。具体目的1是建立VOM乙醇输注对狗的电生理影响。我们假设，VOM乙醇输注导致LA明显的直接和间接电生理变化，影响其维持AF的能力。直接影响将包括一个新的乙醇消融的不可兴奋的LA区。间接影响包括消除迷走神经和交感神经对VOM的影响。将进行实验来描述这些影响。具体目的#2是确定VOM乙醇输注作为人类房颤导管消融的有用辅助手段的作用。在常规房颤导管消融患者中，研究VOM乙醇输注的可行性、安全性、消融效果和程序影响。一旦可行性和安全性得到确定，我们将在一项随机临床试验中评估辅助VOM乙醇输注在PVAI新发房颤导管消融和既往PVAI后房颤复发病例中的价值。

DESCRIPTION (provided by applicant): The broad, long-term objective of this project is to explore the potential role of ethanol infusion in the vein of Marshall (VOM) in the treatment of atrial fibrillation (AF). AF is the most common sustained rhythm disorder in adults, affects more than 2.5 million Americans, and is associated with significant increases in stroke and mortality. Catheter ablation of AF, consists of pulmonary vein antral isolation (PVAI) and is the most powerful therapeutic strategy to treat AF, achieving normal rhythm in ~80% of patients. Important details of the mechanistic basis of PVAI, the optimal catheter technique, and the risk of complications are incomplete or controversial. The VOM is a left atrial vein branch of the coronary sinus that is the embryonic remnant of the left superior vena cava, and contains important sympathetic and parasympathetic nerves that have been implicated in the genesis of AF. Abnormal ectopic beats originating from the VOM have been shown to initiate AF. The VOM lies in a location in the LA that is normally part of the targeted tissue in PVAI and can be difficult to ablate conventionally due to its thickness (lateral ridge). Of note, it is also between the coronary sinus and the left pulmonary veins, an area commonly ablated to avoid left atrial flutter. It can also run close to the point of contact between the left atrium and the esophagus. A new technique to retrogradely cannulate the VOM was developed and validated in dogs and humans. Once cannulated, ethanol infusion achieves rapid tissue ablation without risk of collateral damage. The potential advantages include: ablation of sympathetic and parasympathetic innervation that promotes AF, ablation of VOM triggers for AF, ablation the lateral ridge from its epicardial side, and rapid tissue ablation from a right-sided procedure. We propose to study details of the mechanistic basis of this technique and to establish its role in the treatment of AF in humans. Specific aim #1 is to establish in dogs the electrophysiological effects of VOM ethanol infusion. We hypothesize that VOM ethanol infusion leads to marked direct and indirect electrophysiological changes in the LA that affect its ability to sustain AF. Direct effects would include of a new ethanol- ablated unexcitable LA area. Indirect effects would include abolition of vagal and sympathetic influences carried by the VOM. Experiments will be performed to delineate these effects. Specific aim #2 is to establish the role of VOM ethanol infusion as a useful adjunct to catheter ablation of AF in humans. Feasibility, safety, ablative effects and procedural impact of VOM ethanol infusion will be tested in patients subjected to conventional AF catheter ablation. Once the feasibility and safety are established, we will assess, in a randomized clinical trial, the value of adjunctive VOM ethanol infusion in de novo AF catheter ablation with PVAI, and in cases of recurrent AF after previous PVAI. PUBLIC HEALTH RELEVANCE: Atrial fibrillation is a significant health problem that causes stroke and increases death rates. Catheter ablation works in its treatment but can be improved. We have developed a new technique that is mechanistically sound and may improve catheter-based treatment of AF.