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

马歇尔静脉作为治疗心房颤动的治疗剂

• 批准号: 7990712
• 负责人: Miguel Valderrabano
• 金额: $ 23.1万
• 依托单位: METHODIST HOSPITAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-06 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7990712
• 关键词: Ablation; Adult; Affect; American; Animals; Anterior; Antral; Area; Arrhythmia; Atrial Fibrillation; Atrial Flutter; Autonomic ganglion; Canis familiaris; Cardiac ablation; Catheters; Clinical; Complex; Coronary sinus structure; Death Rate; Disease; Ectopic beats; Embryo; Esophageal; Esophageal Fistula; Esophagus; Ethanol; Generations; Health; Heart Atrium; Human; Inferior; Infusion procedures; Lateral; Lead; Left; Left atrial structure; Location; Marshal; Methods; Morbidity - disease rate; Muscle; Nerve; Pathway interactions; Patient Selection; Patients; Physiology; Procedures; Pulmonary veins; Randomized Clinical Trials; Recurrence; Reporting; Reproducibility; Risk; Role; Running; Safety; Side; Stroke; Superior vena cava structure; Techniques; Testing; Therapeutic; Therapeutic Agents; Thick; Tissues; Veins; Work; appendage; auricular appendage; base; improved; mortality; nerve supply; neuromechanism; public health relevance; research study; response; sound; success; therapeutic target

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.

描述（由申请人提供）：该项目的广泛长期目标是探索乙醇输液在马歇尔（Marshall）静脉（VOM）中的潜在作用，在治疗房颤（AF）中。 AF是成年人中最常见的持续节奏障碍，影响超过250万美国人，并且与中风和死亡率的显着增加有关。 AF的导管消融，由肺静脉分离（PVAI）组成，是治疗AF的最强大的治疗策略，在约80％的患者中达到了正常的节奏。 PVAI机械基础，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是冠状窦的左心静脉分支，它是左上静脉腔的胚胎残留物，并包含重要的交感神经和副交感神经，这些神经与AF的发生有关。源自VOM的异常异位节拍已显示出启动AF。 VOM位于LA中通常是PVAI靶向组织的一部分的位置，由于其厚度（侧脊），通常很难消融。值得注意的是，它也位于冠状窦和左肺静脉之间，该区域通常消融以避免左心颤动。它也可以接近左心房和食道之间的接触点。在狗和人类中开发和验证了一种逆行插入VOM的新技术。一旦插管，乙醇输液就会实现快速组织消融，而没有附带损害的风险。潜在的优势包括：促进AF的交感神经和副交感神经的消融，呕吐物触发AF的触发器，从其心外膜侧消融侧脊以及从右侧手术中的快速组织消融。我们建议研究该技术的机理基础的细节，并确定其在人类中AF治疗中的作用。具体目的1是在狗中建立呕吐物输注的电生理作用。我们假设VOM乙醇输注会导致LA中显着直接和间接的电生理变化，从而影响其维持AF的能力。直接效果将包括新的乙醇融合了不可剥夺的洛杉矶区域。间接影响将包括废除VOM携带的迷走神经和交感性影响。将进行实验以描绘这些效果。具体目的＃2是确定VOM乙醇输注作为人类AF导管消融的有用辅助作用。在经常发生AF导管消融的患者中，将测试可行性，安全性，消融效果和呕吐物输注的程序影响。一旦确定了可行性和安全性，我们将在一项随机临床试验中评估辅助性呕吐物在从头向AF导管在PVAI中消融中的辅助性VOM乙醇的价值，以及在上一次PVAI后反复发生的AF的情况下。 公共卫生相关性：心房颤动是导致中风并提高死亡率的重大健康问题。导管消融在其治疗方面起作用，但可以改善。我们已经开发了一种新技术，该技术在机械上是合理的，可以改善基于导管的AF处理。