持续性心房颤动消融策略的研究进展
Advances in Ablation Strategies for Persistent Atrial Fibrillation
DOI: 10.12677/acm.2025.1551567, PDF, HTML, XML,   
作者: 赵英竹:山东第一医科大学(山东省医学科学院)研究生部,山东 济南;山东第一医科大学第一附属医院心血管内科,山东 济南;闫素华*:山东第一医科大学第一附属医院心血管内科,山东 济南
关键词: 持续性房颤消融策略Marshall静脉无水乙醇消融Persistent Atrial Fibrillation Ablation Strategy Vein of Marshall Alcohol Ablation
摘要: 心房颤动(以下简称房颤)是临床上最常见的心律失常之一,持续性心房颤动(PsAF)的导管消融治疗一直是临床上的挑战。PsAF消融以肺静脉隔离为基石,但单纯肺静脉隔离治疗效果有限。近年来房颤消融策略不断优化,并在临床试验中取得良好的疗效,其中Marshall静脉(VOM)无水乙醇消融作为一种新兴技术,展现出独特的优势和应用前景,多项临床研究证实了其安全性和有效性。
Abstract: Atrial fibrillation is one of the most common arrhythmias in clinical practice, and catheter ablation therapy for persistent atrial fibrillation (PsAF) has been a clinical challenge. PsAF ablation therapy is based on pulmonary vein isolation as a cornerstone, but pulmonary vein isolation alone has limited efficacy. Atrial fibrillation ablation strategies have been optimised in recent years and have shown promising results in clinical trials. Among them, vein of Marshall (Vein of Marshall, VOM) alcohol ablation, as an emerging technology, shows unique advantages and application prospects.
文章引用:赵英竹, 闫素华. 持续性心房颤动消融策略的研究进展[J]. 临床医学进展, 2025, 15(5): 1859-1865. https://doi.org/10.12677/acm.2025.1551567

1. 引言

心房颤动(房颤),是目前最常见的心律失常之一,可表现为心悸、胸痛等症状。导管消融是控制症状、治疗房颤的一种既定手术方式。在最新的ESC指南[1]中,对心律失常药物治疗有抵抗或不耐受的阵发性或持续性房颤(persistent atrial fibrillation, PsAF)患者推荐导管消融作为I类治疗。PsAF相较于阵发性房颤,存在更严重的心房重构、纤维化,并且其触发还与其他非肺静脉触发灶有关,从而导致PsAF单纯肺静脉隔离治疗不够充分,不足以长期维持窦性心律。近几十年来,在肺静脉隔离基础上,联合解剖消融(线性消融)、低电压区域消融、转子消融、复杂碎裂电位消融及非肺静脉触发灶消融等多种手术策略已经被电生理学家所采用。本文系统介绍了目前应用于PsAF治疗的消融策略及其临床效果,为临床实践工作提供了参考依据。

2. 房颤发病机制

房颤的发生机制十分复杂,且尚未完全阐明,在电生理机制方面,既往研究发现其发生机制主要涉及两个方面,分别是房颤的触发和维持机制。

2.1. 房颤触发机制

1998年,Haïssaguerre等人研究发现引起房颤的异位搏动94%起源于肺静脉,提出肺静脉是诱发房颤频繁发作的异位搏动的重要来源,并可通过射频消融消除[2]。非肺静脉病灶的定位研究表明,异位触发通常聚集在离散的解剖区域,这些部位已被证明含有可表现出致心律失常活性的心肌细胞[3]。房颤的发生是由心房肌异常电活动引起,这可能是心房肌自律性增强、触发活动以及局部微折返回路的综合作用结果。离子通道异常也与房颤的触发机制密切相关。细胞内钙离子处理异常是房颤触发活动增强的重要原因,Ca2+超载会导致心房肌细胞中的肌浆网释放过多的Ca2+,一项临床研究中,Patterson等人发现犬肺静脉组织发生早期后去极化是由于Ca2+瞬态电流增加和Na-Ca交换电流增加所致[4]。另外,心脏自主神经系统在房颤的触发和维持中起着至关重要的作用。

2.2. 房颤维持机制

一是多子折返波理论,由Moe等人从实验研究和计算机实验中提出,认为房颤的维持依赖于心房内同时存在的多个子折返波,这些折返波在心房内不断碰撞、分裂和重组,形成复杂的电活动模式从而诱发房颤[5]。二是局灶激动,心房某处局灶激动表现为自律性极高的电活动,频率远高于周围心房组织,这种快速电活动通过电传导扩布,由于周围组织的传导不均一性,从而形成颤动样传导。三是转子学说,房颤转子是一种稳定的自旋波,是围绕高频核心的转动样激动,移动的转子可形成多发子波,转子相当于异位心房激动或子波可在心内膜或心外膜中传导[6]

3. PsAF导管消融策略

肺静脉隔离是房颤消融治疗的基石,肺静脉的局灶性触发是引发房颤最常见的机制,尤其是在阵发性房颤患者中,肺静脉隔离通过消除肺静脉内的异常电活动,能够有效预防房颤的复发。然而,与阵发性房颤相比,PsAF消融手术的有效性较差。一项Meta分析报道,纳入了14项研究,共956例PsAF患者,单次导管消融治疗PsAF的成功率为43%至67% [7]。在导管消融术后房颤复发患者中,多项研究表明,房颤患者再次消融过程中,80%的患者肺静脉存在电传导恢复[8] [9],这表明实现肺静脉隔离的持久性至关重要。目前各种不同的附加消融方法已经被提出,旨在提高PsAF患者消融手术的有效性。

3.1. 线性消融

房颤线性消融可以起到阻断折返回路、改善心房基质作用,心房通过消融被分割成独立区域,使房颤不能进行折返,导致其发作不能维持。从胚胎学、解剖学及电生理学角度来看,左心房后壁与肺静脉有关,被认为在维持PsAF中起作用[10],在肺静脉隔离后可以检测到来自左心房后壁的异位触发,具有致心律失常作用[3]。因此在肺静脉消融基础上,对左心房顶部和底部进行线性消融,形成盒状消融区域,达到左心房后壁隔离的消融策略已被临床应用,然而由于后壁位置和食管的距离较近,增加了意外伤害的风险,左房后壁消融成功具有一定的挑战性。一项临床试验表明,附加左房后壁消融组和单独肺静脉消融组的患者,术后12个月的房性心律失常复发率无显著差异,左房后壁联合肺静脉消融并不能改善房性心律失常的复发[10]。“2C3L”术式是临床上治疗PsAF最常用的消融策略,但其难点及挑战在于二尖瓣峡部实现完全传导阻滞,需要进一步通过心外膜消融或Marshall韧带消融达到二尖瓣峡部完全阻滞,进而降低二尖瓣峡部依赖的大折返性心房扑动的房颤复发。

3.2. 复杂碎裂电位消融

复杂碎裂电位消融是一种心房基质改良的房颤消融策略。Nademanee等[11]首先提出复杂碎裂电位,该区域具有明确的电生理基础,是通过消融消除房颤和维持正常窦性心律的靶点,研究对纳入的阵发性和PsAF患者行复杂碎裂电位消融,在一年的随访中,91%患者可维持窦性心律。荟萃分析表明,在单次或多次消融手术后,肺静脉隔离联合消融复杂碎裂电位并没有改善窦性心律的维持,但手术时间增加[12]。STAR AF II [8]是一项大型随机对照试验,结果发现在肺静脉隔离的基础上进行线性消融或复杂分割心电图消融均未降低PsAF患者术后复发率,其中,二尖瓣峡部未能完全阻滞是重要原因之一。

3.3. 低电压区域消融

低电压区域消融基于心房纤维化,通过标测和消融心房内的低电压区域,改善心房基质,从而减少房颤的维持和复发。Gang Yang等[13]研究,共纳入164例非阵发性房颤患者,Kaplan-Meier分析显示,随访24个月后低电压区域消融组与递进式消融组窦性心律维持率的分别为69.8%和51.3%,基于左房电压标测指导下的个体化消融组术后成功率明显高于递进式消融组,这主要是通过降低术后房性心动过速的发生率来实现的。针对心房内低电压区域进行消融,使该区域内的电活动趋于一致,消除局部组织的异质性,从而使心房的整体电传导得到改善。一项前瞻性观察队列研究[14]发现,在低电压区域广泛的非阵发性房颤患者中,以左房电压为基础的消融旨在均匀低电压区的疗效有限,低电压区的程度是低电压区均匀化后复发的独立预测因素。然而广泛低电压区消融可能增加心房穿孔、损伤食管等临近结构、僵硬左房综合征及医源性房速的并发症风险,因此把握消融范围及深度是低电压区域消融的主要挑战之一。

3.4. 转子消融

转子是一种特殊类型的功能性折返,被认为是快速且相对规则的微折返,以涡流形式传播。转子消融可以提高房颤导管消融成功率,在CONFIRM试验[15]中,首次证明在人类中房颤可以通过电转子和焦脉冲形式的局部源来维持,该试验前瞻性地将PsAF患者分为FIRM组(肺静脉隔离 + 转子消融)和对照组(单纯肺静脉隔离),结果发现FIRM组术中的房颤终止率明显高于对照组。然而转子消融的临床效果存在一定的争议。一项回顾性研究共纳入首次行消融治疗的PsAF患者,肺静脉隔离 + 转子消融组与单纯肺静脉隔离组相比,附加转子消融组的窦性心律维持率无明显提高[16]。因此还需要大型前瞻性研究来评价转子消融在PsAF术后的远期疗效。

3.5. 肺静脉外触发灶消融

肺静脉是PsAF主要的触发位点,11%的患者可引发非肺静脉触发器,PsAF患者左心房触发器的房颤患病率高于阵发性房颤[17]。肺静脉外触发灶常见于二尖瓣环、左心耳、房间隔(尤其是卵圆窝/边缘区)、冠状窦、上腔静脉及Marshal韧带等。上腔静脉是最常见的非肺静脉触发灶之一,在持续性及长程PsAF患者射频消融术后效果中发现未能明显提高房颤消融成功率,上腔静脉诱发的房颤与房颤进展无关[18]。冠状窦的触发因素很常见,特别是在非阵发性房颤[19]患者中,完全隔离应优于局灶消融,因其消除了与房性心动过速复发相关的所有潜在冠状窦触发因素[20]。Marshal韧带作为重要的肺静脉外触发灶,其消融既可以消除房颤异位触发,还有助于实现二尖瓣峡部完全阻滞,提高房颤导管消融手术成功率。目前Marshall韧带通过Marshall静脉(Vein of Marshall, VOM)无水乙醇消融已经广泛应用于临床,成为治疗PsAF的重要消融策略。

4. 房颤消融能量

房颤射频消融通过导管释放射频能量(高频电流),精准破坏导致房颤的异常电信号起源点(如肺静脉口部)。主要关键点在于1. 肺静脉电隔离:90%以上的阵发性房颤由肺静脉异常放电引起,消融其周围组织可阻断异常电传导。2. 基质改良(适用于持续性房颤):除PVI外,可能需消融左心房后壁、冠状窦、二尖瓣峡部等区域。冷冻消融作为房颤治疗的替代技术发展迅速,尤其在阵发性房颤治疗中已成为与射频消融并列的一线选择。冷冻消融通常采用球囊导管技术,球囊与肺静脉口部紧密贴靠后释放冷冻能量,形成连续且均匀的环形损伤带。这种设计相较于逐点射频消融更为高效,能够一次性完成肺静脉隔离。值得注意的是,冷冻能量对组织的损伤具有“选择性”特点,心肌细胞比周围组织结构(如食道、膈神经等)对低温更为敏感,这在一定程度上降低了手术相关并发症的风险。脉冲电场消融作为一种非热能源消融技术,凭借其组织选择性(优先损伤心肌而避免食管、膈神经等周围结构损伤)成为研究热点。脉冲电场消融在阵发性房颤中的单次消融成功率与传统射频相当,但手术时间更短,且并发症风险显著降低。MANIFEST-PF及EUPORIA等多中心、前瞻性研究表明在大样本人群中,脉冲电场消融治疗房颤具有高有效性及安全性。

5. Marshall韧带消融

5.1. Marshall韧带解剖结构

Marshall韧带常走行于二尖瓣峡部的心外膜面,包含VOM、肌束、交感神经及副交感神经等,其走行过程中形成多个肌束,由多个插入点插入心房肌,位于左心房后壁和游离壁,通过心外膜连接左房与左侧肺静脉,其中,VOM起自近左下肺静脉处,是左上腔静脉的退化残留,其解剖变异较大,最终汇入冠状静脉窦[21] [22]

5.2. VOM无水乙醇消融的作用

VOM注射无水乙醇能够渗入其周围心房肌,首先,Marshall韧带是诱导房颤发生的主要触发灶之一,其周围富含自主神经纤维,并且与肺静脉解剖位置相邻,肺静脉存在较多Marshall韧带的心外膜连接,通过化学消融可消除Marshall韧带的异位触发灶及周围神经丛,累及左房后外侧游离壁及左侧肺静脉前缘引起跨壁损伤,阻断左心房与左肺静脉之间的电传导,提高肺静脉隔离持久性;二尖瓣峡部解剖结构复杂、相邻血管散热效应[23]以及其存在个体解剖差异[24]降低消融效率,乙醇化学消融作用具有较高的持久性,能够实现透壁损伤,进而实现二尖瓣峡部双向阻滞,降低房颤复发率。此外,VOM无水乙醇消融还可使肺静脉充分损伤,进而减少肺静脉射频消融时间。对于VOM无水乙醇消融的有效性,已有多项大型临床研究,如VENUS [25]、Marshall-PLAN [26]及PROMPT-AF [27]研究,Marshall-PLAN研究显示PsAF患者单次Marshal1-PLAN术后12个月成功率达79%,其完整术式的可行性达90%以上,较传统PVI术式未增加手术并发症发生率,并不会影响左心房功能。PROMPT-AF研究结果表明,PsAF患者“改良2C3L”策略消融术后1年无房性心律失常复发率为70.7%,显著优于传统肺静脉隔离组(61.5%)。VOM无水乙醇消融联合导管消融显著改善PsAF患者术后12月内房性心律失常发生率,提高手术成功率。

5.3. VOM无水乙醇化学消融的安全性

辅助性VOM无水乙醇化学消融,注入到VOM的乙醇,渗入其周围心房肌,进而扩大消融面积,存在损害左房功能的可能性,因此VOM无水乙醇消融的安全性已成为电生理学家的关注重点之一。最近的多项荟萃分析显示,辅助VOM无水乙醇消融能够降低房颤/房速复发率并成功实现二尖瓣峡部双向阻断,但未增加不良事件的发生率,具有较高的有效性及安全性[28]-[30]

6. 结论

PsAF是一种机制复杂、难以治疗的心律失常疾病,其窦性心律维持受多种因素影响,在肺静脉隔离基础上各种附加消融策略“百花齐放”,每种消融术式皆有其优势及不足,未来仍需要更多临床试验进一步证实。PsAF治疗的发展方向将围绕技术优化、临床证据积累和个性化治疗展开。VOM无水乙醇消融为PsAF的治疗提供了新的思路和方法,目前已有临床试验对其有效性及安全性进行研究,随着临床研究的深入以及消融技术的不断进步,VOM无水乙醇消融有望成为PsAF消融治疗的重要组成部分,其临床应用前景广阔,为PsAF患者带来更优的治疗手段。

NOTES

*通讯作者。

参考文献

[1] Van Gelder, I.C., Rienstra, M., Bunting, K.V., Casado-Arroyo, R., Caso, V., Crijns, H.J.G.M., et al. (2024) 2024 ESC Guidelines for the Management of Atrial Fibrillation Developed in Collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). European Heart Journal, 45, 3314-3414.
https://doi.org/10.1093/eurheartj/ehae176
[2] Haïssaguerre, M., Jaïs, P., Shah, D.C., Takahashi, A., Hocini, M., Quiniou, G., et al. (1998) Spontaneous Initiation of Atrial Fibrillation by Ectopic Beats Originating in the Pulmonary Veins. New England Journal of Medicine, 339, 659-666.
https://doi.org/10.1056/nejm199809033391003
[3] Santangeli, P. and Marchlinski, F.E. (2017) Techniques for the Provocation, Localization, and Ablation of Non-Pulmonary Vein Triggers for Atrial Fibrillation. Heart Rhythm, 14, 1087-1096.
https://doi.org/10.1016/j.hrthm.2017.02.030
[4] Patterson, E., Lazzara, R., Szabo, B., Liu, H., Tang, D., Li, Y., et al. (2006) Sodium-Calcium Exchange Initiated by the Ca2+ Transient: An Arrhythmia Trigger Within Pulmonary Veins. Journal of the American College of Cardiology, 47, 1196-1206.
https://doi.org/10.1016/j.jacc.2005.12.023
[5] Moe, G.K. and Abildskov, J.A. (1959) Atrial Fibrillation as a Self-Sustaining Arrhythmia Independent of Focal Discharge. American Heart Journal, 58, 59-70.
https://doi.org/10.1016/0002-8703(59)90274-1
[6] Guillem, M.S., Climent, A.M., Rodrigo, M., Fernández-Avilés, F., Atienza, F. and Berenfeld, O. (2016) Presence and Stability of Rotors in Atrial Fibrillation: Evidence and Therapeutic Implications. Cardiovascular Research, 109, 480-492.
https://doi.org/10.1093/cvr/cvw011
[7] Voskoboinik, A., Moskovitch, J.T., Harel, N., Sanders, P., Kistler, P.M. and Kalman, J.M. (2017) Revisiting Pulmonary Vein Isolation Alone for Persistent Atrial Fibrillation: A Systematic Review and Meta-Analysis. Heart Rhythm, 14, 661-667.
https://doi.org/10.1016/j.hrthm.2017.01.003
[8] Verma, A., Jiang, C., Betts, T.R., Chen, J., Deisenhofer, I., Mantovan, R., et al. (2015) Approaches to Catheter Ablation for Persistent Atrial Fibrillation. New England Journal of Medicine, 372, 1812-1822.
https://doi.org/10.1056/nejmoa1408288
[9] Ouyang, F., Tilz, R., Chun, J., Schmidt, B., Wissner, E., Zerm, T., et al. (2010) Long-Term Results of Catheter Ablation in Paroxysmal Atrial Fibrillation: Lessons from a 5-Year Follow-Up. Circulation, 122, 2368-2377.
https://doi.org/10.1161/circulationaha.110.946806
[10] Kistler, P.M., Chieng, D., Sugumar, H., Ling, L., Segan, L., Azzopardi, S., et al. (2023) Effect of Catheter Ablation Using Pulmonary Vein Isolation with vs without Posterior Left Atrial Wall Isolation on Atrial Arrhythmia Recurrence in Patients with Persistent Atrial Fibrillation: The CAPLA Randomized Clinical Trial. JAMA, 329, 127-135.
https://doi.org/10.1001/jama.2022.23722
[11] Nademanee, K., McKenzie, J., Kosar, E., Schwab, M., Sunsaneewitayakul, B., Vasavakul, T., et al. (2004) A New Approach for Catheter Ablation of Atrial Fibrillation: Mapping of the Electrophysiologic Substrate. Journal of the American College of Cardiology, 43, 2044-2053.
https://doi.org/10.1016/j.jacc.2003.12.054
[12] Fadahunsi, O., Talabi, T., Olowoyeye, A., Iluyomade, A., Shogbesan, O. and Donato, A. (2016) Ablation of Complex Fractionated Atrial Electrograms for Atrial Fibrillation Rhythm Control: A Systematic Review and Meta-Analysis. Canadian Journal of Cardiology, 32, 791-802.
https://doi.org/10.1016/j.cjca.2015.07.008
[13] Yang, G., Yang, B., Wei, Y., Zhang, F., Ju, W., Chen, H., et al. (2016) Catheter Ablation of Nonparoxysmal Atrial Fibrillation Using Electrophysiologically Guided Substrate Modification during Sinus Rhythm after Pulmonary Vein Isolation. Circulation: Arrhythmia and Electrophysiology, 9, e003382.
https://doi.org/10.1161/circep.115.003382
[14] Yamaguchi, T., Tsuchiya, T., Fukui, A., Kawano, Y., Otsubo, T., Takahashi, Y., et al. (2018) Impact of the Extent of Low-Voltage Zone on Outcomes after Voltage-Based Catheter Ablation for Persistent Atrial Fibrillation. Journal of Cardiology, 72, 427-433.
https://doi.org/10.1016/j.jjcc.2018.04.010
[15] Narayan, S.M., Krummen, D.E., Shivkumar, K., Clopton, P., Rappel, W. and Miller, J.M. (2012) Treatment of Atrial Fibrillation by the Ablation of Localized Sources: CONFIRM (Conventional Ablation for Atrial Fibrillation with or Without Focal Impulse and Rotor Modulation) Trial. Journal of the American College of Cardiology, 60, 628-636.
https://doi.org/10.1016/j.jacc.2012.05.022
[16] Kirzner, J.M., Raelson, C.A., Liu, C.F., Thomas, G., Ip, J.E., Lerman, B.B., et al. (2019) Effects of Focal Impulse and Rotor Modulation‐Guided Ablation on Atrial Arrhythmia Termination and Inducibility: Impact on Outcomes after Treatment of Persistent Atrial Fibrillation. Journal of Cardiovascular Electrophysiology, 30, 2773-2781.
https://doi.org/10.1111/jce.14240
[17] Santangeli, P., Zado, E.S., Hutchinson, M.D., Riley, M.P., Lin, D., Frankel, D.S., et al. (2016) Prevalence and Distribution of Focal Triggers in Persistent and Long-Standing Persistent Atrial Fibrillation. Heart Rhythm, 13, 374-382.
https://doi.org/10.1016/j.hrthm.2015.10.023
[18] 张道良, 徐楷, 王泽呈, 等. 长程持续性房颤与上腔静脉的关系研究[J]. 国际心血管病杂志, 2019, 46(5): 301-304.
[19] Della Rocca, D.G., Mohanty, S., Mohanty, P., Trivedi, C., Gianni, C., Al‐Ahmad, A., et al. (2018) Long‐Term Outcomes of Catheter Ablation in Patients with Longstanding Persistent Atrial Fibrillation Lasting Less than 2 Years. Journal of Cardiovascular Electrophysiology, 29, 1607-1615.
https://doi.org/10.1111/jce.13721
[20] Della Rocca, D.G., Gianni, C., Gedikli, O., Chen, Q., Natale, A. and Al-Ahmad, A. (2020) Provocation and Ablation of Non-Pulmonary Vein Triggers in Nonparoxysmal Atrial Fibrillation: Role of the Coronary Sinus. HeartRhythm Case Reports, 6, 231-236.
https://doi.org/10.1016/j.hrcr.2019.10.010
[21] de Oliveira, I.M., Scanavacca, M.I., Correia, A.T., Sosa, E.A. and Aiello, V.D. (2007) Anatomic Relations of the Marshall Vein: Importance for Catheterization of the Coronary Sinus in Ablation Procedures. Europace, 9, 915-919.
https://doi.org/10.1093/europace/eum175
[22] Hwang, C., Wu, T., Doshi, R.N., Peter, C.T. and Chen, P. (2000) Vein of Marshall Cannulation for the Analysis of Electrical Activity in Patients with Focal Atrial Fibrillation. Circulation, 101, 1503-1505.
https://doi.org/10.1161/01.cir.101.13.1503
[23] Gillis, K., O’Neill, L., Wielandts, J., Hilfiker, G., Almorad, A., Lycke, M., et al. (2022) Vein of Marshall Ethanol Infusion as First Step for Mitral Isthmus Linear Ablation. JACC: Clinical Electrophysiology, 8, 367-376.
https://doi.org/10.1016/j.jacep.2021.11.019
[24] He, B., Zhao, F., Yu, W., Li, Y., Wu, X. and Lu, Z. (2022) Ethanol Infusion of Vein of Marshall for the Treatment of Persistent Atrial Fibrillation: The Basics and Clinical Practice. Journal of Cardiovascular Development and Disease, 9, 270.
https://doi.org/10.3390/jcdd9080270
[25] Lador, A., Peterson, L.E., Swarup, V., Schurmann, P.A., Makkar, A., Doshi, R.N., et al. (2021) Determinants of Outcome Impact of Vein of Marshall Ethanol Infusion When Added to Catheter Ablation of Persistent Atrial Fibrillation: A Secondary Analysis of the VENUS Randomized Clinical Trial. Heart Rhythm, 18, 1045-1054.
https://doi.org/10.1016/j.hrthm.2021.01.005
[26] Derval, N., Duchateau, J., Denis, A., Ramirez, F.D., Mahida, S., André, C., et al. (2021) Marshall Bundle Elimination, Pulmonary Vein Isolation, and Line Completion for Anatomical Ablation of Persistent Atrial Fibrillation (Marshall-Plan): Prospective, Single-Center Study. Heart Rhythm, 18, 529-537.
https://doi.org/10.1016/j.hrthm.2020.12.023
[27] Sang, C., Liu, Q., Lai, Y., Xia, S., Jiang, R., Li, S., et al. (2025) Pulmonary Vein Isolation with Optimized Linear Ablation vs Pulmonary Vein Isolation Alone for Persistent AF: The PROMPT-AF Randomized Clinical Trial. JAMA, 333, 381-389.
https://doi.org/10.1001/jama.2024.24438
[28] Ge, W., Li, T., Lu, Y., Jiang, J., Tung, T. and Yan, S. (2023) Efficacy and Feasibility of Vein of Marshall Ethanol Infusion during Persistent Atrial Fibrillation Ablation: A Systematic Review and Meta‐Analysis. Clinical Cardiology, 47, e24178.
https://doi.org/10.1002/clc.24178
[29] He, Z., Yang, L., Bai, M., Yao, Y. and Zhang, Z. (2021) Feasibility, Efficacy, and Safety of Ethanol Infusion into the Vein of Marshall for Atrial Fibrillation: A Meta‐Analysis. Pacing and Clinical Electrophysiology, 44, 1151-1162.
https://doi.org/10.1111/pace.14263
[30] Li, F., Sun, J., Wu, L., Zhang, L., Qu, Q., Wang, C., et al. (2022) The Long-Term Outcomes of Ablation with Vein of Marshall Ethanol Infusion vs. Ablation Alone in Patients with Atrial Fibrillation: A Meta-Analysis. Frontiers in Cardiovascular Medicine, 9, Article 871654.
https://doi.org/10.3389/fcvm.2022.871654