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

基本信息

批准号：
8105062
负责人：
Miguel Valderrabano
金额：
$ 19.25万
依托单位：
METHODIST HOSPITAL RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-06 至 2014-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8105062
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

项目摘要

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、长期目标是探索马歇尔静脉（VOM）输注乙醇在治疗心房颤动（AF）中的潜在作用。 AF 是成人中最常见的持续性心律失常，影响超过 250 万美国人，并与中风和死亡率显着增加相关。房颤导管消融包括肺静脉窦隔离 (PVAI)，是治疗房颤最有效的治疗策略，约 80% 的患者可实现正常心律。 PVAI 的机制基础、最佳导管技术以及并发症风险的重要细节尚不完整或存在争议。 VOM 是冠状窦的左心房静脉分支，是左上腔静脉的胚胎残余物，包含重要的交感神经和副交感神经，与 AF 的发生有关。源自 VOM 的异常异位搏动已被证明可引发 AF。 VOM 位于 LA 中的某个位置，该位置通常是 PVAI 中目标组织的一部分，并且由于其厚度（侧脊）而难以以常规方式消融。值得注意的是，它也位于冠状窦和左肺静脉之间，该区域通常被消融以避免左心房扑动。它还可以靠近左心房和食道之间的接触点。开发了一种逆行插入 VOM 的新技术，并在狗和人类身上进行了验证。一旦插管，乙醇输注即可实现快速组织消融，而不会产生附带损伤的风险。潜在的优势包括：消融促进 AF 的交感神经和副交感神经支配、消融 AF 的 VOM 触发因素、从心外膜侧消融侧脊，以及从右侧手术快速消融组织。我们建议研究该技术的机制基础的细节，并确定其在人类 AF 治疗中的作用。具体目标#1 是确定 VOM 乙醇输注对狗的电生理影响。我们假设 VOM 乙醇输注会导致 LA 发生明显的直接和间接电生理变化，从而影响其维持 AF 的能力。直接影响将包括新的乙醇消除的不可兴奋的洛杉矶区域。间接影响包括消除 VOM 所具有的迷走神经和交感神经影响。将进行实验来描述这些影响。具体目标#2 是确定 VOM 乙醇输注作为人类 AF 导管消融的有用辅助手段的作用。 VOM 乙醇输注的可行性、安全性、消融效果和手术影响将在接受传统 AF 导管消融的患者中进行测试。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 VOM 乙醇输注在采用 PVAI 的从头 AF 导管消融术中以及在既往 PVAI 后复发 AF 的情况下的价值。公共卫生相关性：心房颤动是一个严重的健康问题，会导致中风并增加死亡率。导管消融对其治疗有效，但还可以改进。我们开发了一种机械上合理的新技术，可以改善基于导管的 AF 治疗。

项目成果

期刊论文数量（17）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Deciphering the electrogram in ventricular fibrillation to extract physiological information.

破译心室颤动的电图以提取生理信息。

DOI：
发表时间：
2011-05
期刊：
影响因子：
5.5
作者：
Valderrábano; Miguel
通讯作者：
Miguel

Pulmonary Vein Isolation Using the Visually Guided Laser Balloon: Results of the U.S. Feasibility Study.

使用视觉引导激光球囊进行肺静脉隔离：美国可行性研究的结果。

DOI：
发表时间：
2015-09
期刊：
影响因子：
2.7
作者：
Dukkipati, Srinivas R;Woollett, Ian;McELDERRY, H Thomas;Böhmer, Marie;Doshi, Shephal K;Gerstenfeld, Edward P;Horton, Rodney;D'Avila, Andre;Haines, David E;Valderrabano, Miguel;Mangrum, J Michael;Ruskin, Jeremy N;Natale, Andrea;Reddy
通讯作者：
Reddy

Strategies for phrenic nerve preservation during ablation of inappropriate sinus tachycardia.

不适当窦性心动过速消融期间保留膈神经的策略。

DOI：
发表时间：
2016-06
期刊：
影响因子：
5.5
作者：
Ibarra;Rodríguez;Kreidieh, Bahij;Schurmann, Paul;Dave, Amish S;Valderrábano, Miguel
通讯作者：
Valderrábano, Miguel

Ligament and vein of Marshall: A therapeutic opportunity in atrial fibrillation.

马歇尔韧带和静脉：心房颤动的治疗机会。

DOI：
10.1016/j.hrthm.2015.10.018
发表时间：
2016-02
期刊：
Heart rhythm
影响因子：
5.5
作者：
Rodríguez-Mañero M;Schurmann P;Valderrábano M
通讯作者：
Valderrábano M

Incidence, Risk Factors, Prognosis, and Electrophysiological Mechanisms of Atrial Arrhythmias after Lung Transplantation.

肺移植术后房性心律失常的发生率、危险因素、预后和电生理机制。

DOI：
发表时间：
2015-08-01
期刊：
影响因子：
0
作者：
Chaikriangkrai, Kongkiat;Jyothula, Soma;Jhun, Hye Yeon;Chang, Su Min;Graviss, Edward A;Shuraih, Mossaab;Rami, Tapan G;Dave, Amish S;Valderrábano, Miguel
通讯作者：
Valderrábano, Miguel