Comparison of Mitral Isthmus Ablation Strategies after Ethanol Infusion into the Vein of Marshall: Voltage Map-Guided versus Conventional Mitral Isthmus Line Placement

Comparison of Mitral Isthmus Ablation Strategies after Ethanol Infusion into the Vein of Marshall: Voltage Map-Guided versus Conventional Mitral Isthmus Line Placement | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 3 September 2025 V1 Latest version Share on Comparison of Mitral Isthmus Ablation Strategies after Ethanol Infusion into the Vein of Marshall: Voltage Map-Guided versus Conventional Mitral Isthmus Line Placement Authors : Shingo Yoshimura 0000-0003-2744-0738 [email protected] , Kenichi Kaseno , Kojiro Hattori , Akiko Kodama 0009-0009-4253-1217 , Taiki Masuyama , Takehito Sasaki , Suguru Nishiuchi 0000-0002-3117-9985 , Kohki Nakamura 0000-0002-9777-4592 , and Shigeto Naito Authors Info & Affiliations https://doi.org/10.22541/au.175692266.61341048/v1 314 views 205 downloads Contents Abstract Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Introduction: Ethanol infusion into the vein of Marshall (VOM-Et) has been introduced as an adjunctive strategy to facilitate mitral isthmus (MI) block. However, the optimal placement of the MI line following VOM-Et remains uncertain, and the clinical efficacy of a voltage map-guided MI line has not been fully assessed. Objective: This study aimed to compare procedural and clinical outcomes between patients who underwent a voltage map-guided MI line after VOM-Et (Group A) and those who received a conventional MI line after VOM-Et (Group B). Methods: A total of 60 patients (mean age 69.1 ± 8.1 years; 37 men) with atrial fibrillation (AF) and/or atrial tachycardia (AT) were retrospectively analyzed. All patients underwent MI ablation following VOM-Et. In Group A (n = 39), the MI line was positioned along low-voltage areas identified post-VOM-Et. In Group B (n = 21), the MI line was placed from the 2–3 o’clock position of the mitral annulus to the left inferior pulmonary vein, irrespective of voltage mapping. Results: The overall acute success rate of MI block was 96.7%, with no significant difference between Groups A and B (94.9% vs. 100%, p = 0.30). Coronary sinus (CS) ablation was necessary in 38.3% of patients, with no difference between groups (38.5% vs. 38.1%, p = 0.98). However, Group A had significantly longer MI lines (41.3 ± 9.7 cm vs. 32.7 ± 7.4 cm, p < 0.01) and required more radiofrequency (RF) lesions (15.9 ± 5.7 vs. 12.6 ± 5.7, p = 0.03). No significant difference was observed in AT/AF recurrence rates between the groups (23.0% vs. 42.0%, p = 0.12). Conclusions: Regarding MI ablation after VOM-Et, the voltage map-guided MI line showed no significant differences compared with the conventional MI line in terms of MI block success, the need for CS ablation, or AT/AF recurrence . However, it was associated with significantly longer MI lines and a greater number of RF lesions, suggesting no clear procedural advantage. 1. INTRODUCTION The Marshall bundle (MB) is recognized as a potential non-pulmonary vein trigger and an epicardial conduction pathway for atrial tachycardia (AT), contributing to atrial arrhythmias. 1–4 Therefore, ethanol infusion into the vein of Marshall (VOM-Et) has been introduced to directly ablate the MB and suppress the occurrence of these arrhythmias. 5 Recently, adding VOM-Et to radiofrequency (RF) ablation in patients with persistent atrial fibrillation (AF) has demonstrated improved outcomes by modifying the AF substrate. 6,7 When creating the lateral mitral isthmus (MI) line, the acute success rate and long-term durability of MI block achieved with endocardial RF ablation alone are relatively low, reported at 64–80% and 32.6%, respectively. In contrast, performing VOM-Et before RF ablation has been shown to increase the likelihood of MI block, shorten RF ablation duration, and reduce the reconnection rate. 8–11 Although VOM-Et facilitates MI block, no standardized guidelines have been established regarding the optimal approach for subsequent lateral MI line creation. Previous studies focused exclusively on endocardial RF ablation for MI block have reported procedural outcomes—including MI block success rates and the need for epicardial ablation from within the coronary sinus (CS)—that vary depending on the MI line placement site. 12,13 In most cases, the MI line after VOM-Et is drawn from the mitral valve annulus toward the left inferior pulmonary vein (PV). 14 However, the strategy for MI line creation following VOM-Et remains inadequately studied. VOM-Et predominantly affects epicardial muscular tissue, and its impact can be assessed through voltage mapping performed after VOM-Et. 15 A commonly employed approach involves constructing the MI line along the low-voltage areas identified on a post-VOM-Et voltage map (voltage map-guided MI line). This technique may enhance transmural lesion formation by targeting both endocardial and epicardial aspects of the left atrium (LA), potentially improving block line durability. Nonetheless, prior studies have found no significant difference in acute MI block success between patients who underwent RF ablation before VOM-Et and those who received VOM-Et first. 8,11 As the MI lines were created conventionally in patients who underwent RF ablation first, regardless of VOM-Et-induced low-voltage areas, these findings raise questions about the clinical efficacy of voltage map-guided MI lines following VOM-Et. Accordingly, this study aims to investigate the efficacy of constructing the MI line based on voltage mapping after VOM-Et. 2. METHODS 2.1 Study Population This retrospective study included patients with AF and/or AT who underwent both MI ablation and VOM-Et using the CARTO system (Biosense Webster Inc., Diamond Bar, CA, USA) at Gunma Prefectural Cardiovascular Center between August 2021 and July 2024. The exclusion criteria were as follows: (1) patients in whom VOM-Et could not be performed because the VOM was not visualized on CS angiography or could not be accessed by a catheter or guidewire, and (2) patients in whom VOM-Et was performed after endocardial MI ablation. The local Ethics Committee of Gunma Prefectural Cardiovascular Center approved this study. Informed consent was obtained using an opt-out approach. 2.2 Ablation Protocol Before the procedure, left atrial anatomy was assessed using contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI). Deep sedation was induced with propofol and/or dexmedetomidine. A multipolar electrode catheter was positioned in the CS via a femoral vein, and transseptal puncture was performed. A three-dimensional (3D) electroanatomic map was created using the CARTO system and merged with CT or MRI images. In the initial procedure for AF, PV isolation and cavotricuspid isthmus linear ablation were routinely performed. The decision to perform additional ablation beyond VOM-Et and MI ablation was left to the operator’s discretion. For RF ablation, a 3.5-mm irrigated-tip catheter (Thermocool Smart Touch SF or QDOT Micro; Biosense Webster Inc., Diamond Bar, CA, USA) was used. RF applications were delivered at a power of 35–40 W, targeting an ablation index of 550. Esophageal temperature was continuously monitored using a temperature probe, and RF delivery was halted when the temperature reached 41°C. In the posterior wall adjacent to the esophagus, RF power was reduced to 20–30 W, or a high-power short-duration setting was used. 2.3 Ethanol Infusion into the Vein of Marshall A steerable long sheath (Agilis NXT; Abbott, St. Paul, MN, USA) was advanced via the femoral vein into the CS. CS angiography was performed using a wedge pressure catheter (Arrow Balloon Wedge-Pressure Catheters; Teleflex, Wayne, PA, USA) or a 4Fr Judkins Right (JR) catheter (OptiFlash; Terumo, Tokyo, Japan) to confirm the presence of the VOM. After the JR catheter was engaged at the VOM ostium, an angioplasty guidewire (Runthrough Ph; Terumo, Tokyo, Japan) was advanced distally into the VOM, followed by a 1.5–2.5 mm × 8 mm over-the-wire balloon (Emerge; Boston CV/IC, Marlborough, MA, USA). The balloon was positioned as close as possible to the VOM ostium and inflated to occlude the vein. Selective VOM angiography was performed through the balloon tip to confirm occlusion and evaluate the course and arborization of the VOM. Ethanol (2.5 mL per injection) was administered over a minimum of 1 min for a total of four injections. Following ethanol administration, repeat VOM angiography was performed to confirm myocardial staining, which reflected the ethanol-affected region. 16 2.4 MI Ablation Two methods were used for MI ablation (Figure 1). From August 2021 through June 2023, a voltage map-guided approach (Group A) was employed, whereas from July 2023 onward, a conventional approach (Group B) was adopted: Group A (voltage map-guided MI line): After VOM-Et, a voltage map was created using a multipolar mapping catheter (PENTARAY or OCTARAY; Biosense Webster Inc.). Low-voltage areas were defined as bipolar potentials <0.5 mV for sinus rhythm or <0.2 mV for AF. If a continuous low-voltage region extended from the mitral annulus to the ridge, the MI line was created along this low-voltage area from the mitral annulus to the left inferior PV. If the low-voltage area was discontinuous, the MI line was positioned at the narrowest segment of residual electrical activity between the mitral annulus and the ridge. Group B (conventional MI line): A voltage map was not necessarily created after VOM-Et. The operator placed the MI line from the 2–3 o’clock position of the mitral annulus to the left inferior PV, irrespective of low-voltage distribution. The bidirectional block of the MI line was confirmed using differential pacing and a 3D electroanatomic map. If the MI block was incomplete, additional endocardial ablations guided by the 3D electroanatomic map or epicardial ablations from within the CS (25 W for 30 s) were performed. For CS ablation, RF energy was initially delivered to the anchored wall facing the LA. If the MI block remained incomplete, CS ablation was subsequently applied to the free wall. 2.5 Analysis of Low-voltage Areas and MI Line on a Three-dimensional Image Low-voltage areas and the MI line were analyzed using the CARTO3 system. The low-voltage areas were delineated manually, with surface area quantification performed automatically by the system. As illustrated in Figure 2, the LA was segmented to evaluate the extent of low-voltage areas induced by VOM-Et. The MI line length was determined based on the tags of RF lesions. The approximate ”clock-face” position of the MI line was evaluated by observing the mitral annulus from the left anterior oblique view (Figure 2). 2.6 Follow-Up Recurrence was defined as any documented AT/AF episode lasting more than 30 s, detected after a 3-month blanking period. Following discharge, patients were followed in the outpatient clinic every 1–3 months. A 12-lead electrocardiogram (ECG) was obtained at each visit, and any symptoms suggestive of arrhythmia were thoroughly assessed. If an arrhythmic event was suspected, a 24-h Holter ECG was performed. Patients whose arrhythmia was not captured on initial evaluation were instructed to return when they experienced arrhythmic symptoms. The decision to discontinue antiarrhythmic drugs (AADs) was made by the attending physician. 2.7 Statistical Analysis Data were summarized as mean ± standard deviation for normally distributed variables and median (25th–75th percentile) for skewed distributions. Differences between continuous variables were evaluated using the Student’s t-test or the Mann–Whitney U-test, as appropriate. Categorical variables were presented as counts and percentages and compared using the chi-square test. One-way analysis of variance (ANOVA) was used to compare subgroups based on the distribution of low-voltage areas induced by VOM-Et. AT/AF recurrence rates between Groups A and B were compared using the log-rank test. A p-value < 0.05 was considered statistically significant. All statistical analyses were performed using SPSS Statistics version 25.0 (IBM Corp, Armonk, NY, USA). 3. RESULTS 3.1 Patient Characteristics This study initially enrolled 71 patients, 11 of whom were excluded. Consequently, 60 patients were included in the final analysis. The mean age was 69.1 ± 8.1 years, and 37 (61.7%) were male. Among these, 15 patients (25.0%) had paroxysmal AF, 30 (50.0%) had persistent AF, eight (13.3%) had long-standing persistent AF, and 18 (30.0%) had atrial tachycardia. A total of 39 patients were assigned to Group A, while 21 patients were assigned to Group B. No significant differences were observed in baseline characteristics between the two groups, except for the left ventricular ejection fraction (Table 1). 3.2 Procedural Data Table 2 summarizes the procedural data. The overall acute success rate of MI block was 96.7%, with no significant difference between Groups A and B (37 [94.9%] vs. 21 [100%], p = 0.30). Epicardial ablation from within the CS was performed in 23 patients (38.3%), including RF ablation on the anchored wall in 22 patients (36.7%) and on the free wall in six patients (10.0%); neither parameter differed significantly between the groups. The MI line was significantly longer in Group A than in Group B (41.3 ± 9.7 cm vs. 32.7 ± 7.4 cm, p < 0.01). Additionally, MI lines in Group A were positioned at the 2.8 ± 0.8 o’clock position of the mitral annulus, compared to the 2.3 ± 0.5 o’clock position in Group B (p < 0.01), indicating that Group A had a more inferiorly located MI line. No significant difference was observed between the groups in the mean duration of RF ablation required to achieve MI block (15.9 ± 9.7 vs. 16.1 ± 11.3 minutes, p = 0.93). However, Group A required significantly more RF lesions than Group B (15.9 ± 5.7 vs. 12.6 ± 5.7, p = 0.03). No complications, including pericardial effusion or stroke, were observed in either group. 3.3 Voltage Map Data In Group A, a post-VOM-Et voltage map was created for all patients. The mean area of low-voltage regions induced by VOM-Et was 7.4 ± 4.4 cm². Low-voltage involvement following VOM-Et was confined to the ridge in 5 patients (12.8%), extended to both the ridge and lateral wall in 20 patients (51.2%), and further extended to the ridge, lateral wall, and inferior wall in 14 patients (35.9%) (Table 3). No significant differences were noted in MI block success among these subgroups (5 [100%] for ridge only, 19 [95.0%] for ridge and lateral wall, and 13 [92.9%] for ridge, lateral wall, and inferior wall; p = 0.84). However, MI line length increased proportionally with the extent of low-voltage involvement (5.0 ± 3.1 cm vs. 6.4 ± 4.5 cm vs. 9.6 ± 4.0 cm; p = 0.04) (Figure 3). 3.4 Follow-up Data During a median follow-up period of 8.5 months (4.4, 12.8), 18 patients (30.0%) experienced AT/AF recurrence. Among these, 15 were AF recurrences, while three were AT recurrences. Postoperative use of Class I/III AADs was continued in eight patients (20.5%) in Group A and seven patients (33.3%) in Group B, with no significant difference (p = 0.28). AT/AF recurrence rates did not differ significantly between Groups A and B (AT/AF, 9 [23.1%] vs. 9 [42.8%], p = 0.12; AF, 7 [17.9%] vs. 8 [38.1%], p = 0.09; AT, 2 [5.1%] vs. 1 [4.7%], p = 0.95). 4. DISCUSSION 4.1 Main Findings This study revealed three key findings: (1) the voltage map-guided MI line after VOM-Et demonstrated no significant difference in the acute success rate of MI block or the need for CS ablation compared to the conventional MI line; (2) the voltage map-guided MI line was longer and required more RF lesions; and (3) no significant difference was observed in AT/AF recurrence between the two groups. These findings do not support the superiority of the voltage map-guided MI line. 4.2 MI Block The lateral MI comprises three structural components: the LA lateral wall, VOM, and great cardiac vein (GCV). When VOM-Et is performed without endocardial MI ablation, the MI block success rate remains low at approximately 6%, necessitating additional endocardial ablation in most patients. 8,9 Furthermore, even with VOM-Et adjunctive to endocardial MI ablation, 47% of patients still require epicardial ablation within the GCV. 17 These findings suggest that three key factors are required to achieve a complete MI block: (1) endocardial conduction block, (2) epicardial conduction block via the MB, and (3) epicardial conduction block via the GCV. As VOM-Et primarily affects the ridge area, which contains a thick myocardial substrate, gaps in MI conduction persist in the relatively thinner myocardial regions near the mitral annulus. 9,18 Consequently, achieving endocardial conduction block becomes more feasible following VOM-Et. In this study, the acute success rate of MI block was 96.7%, and the two unsuccessful cases exhibited persistent epicardial conduction through the GCV. Once conduction via the MB was eliminated by VOM-Et, the success of MI block depended primarily on RF ablation within the GCV rather than endocardial RF ablation. The number of patients requiring CS ablation did not differ significantly between the voltage map-guided MI line and the conventional MI line groups, which may explain why voltage map-guided MI ablation did not improve MI block outcomes. This finding also suggests that the necessity for CS ablation is not contingent on the MI line placement strategy. Myocardial tissue injured by VOM-Et remains stable in the chronic phase. 19,20 Additionally, MI line reconduction in the chronic phase typically occurs at the annular aspect of the MI, particularly within the GCV, an area not directly targeted by VOM-Et. 19,21 These findings suggest that MI line placement may not be a critical determinant of long-term MI reconduction. 4.3 Length of MI Line Performing MI ablation along low-voltage areas resulted in longer MI lines and an increased number of RF lesions. This outcome can be attributed to the broader low-voltage area induced by VOM-Et, which extended from the ridge to the lateral and inferior walls. As a result, the MI lines were positioned in a more inferior region, where the distance from the LIPV to the mitral annulus was greater (Figure 4). Shorter MI lines are associated with higher MI block success rates when only endocardial MI ablation is performed. 22 Although no significant difference in MI block success was observed in this study, a conventional MI line may be preferable to minimize the number of RF applications. 4.4 AT/AF Recurrence No significant difference in AT/AF recurrence was observed between the two groups. A previous study found no significant difference in recurrence rates between patients who underwent MI ablation before VOM-Et and those who underwent VOM-Et before MI ablation (21.4% vs. 25.0%). 11 When MI ablation was performed before VOM-Et, the MI line was created without consideration of low-voltage areas induced by ethanol. Therefore, the MI line location may not significantly influence long-term outcomes when VOM-Et is adjunctive to MI ablation, aligning with the findings of this study. 4.5 Limitations This study has several limitations. First, it was conducted at a single center using a retrospective design and included a relatively small sample size. Second, MI line durability was not evaluated; although no significant difference in AT/AF recurrence was found between the groups, it remains unclear whether MI reconduction contributed to arrhythmia recurrence. Third, this study did not sufficiently investigate whether RF ablation was necessary within the low-voltage area induced by VOM-Et. It was assumed that VOM-Et primarily affected epicardial muscular tissue, allowing endocardial conduction to persist despite the presence of low-voltage areas. However, some studies suggest that ethanol-affected myocardial tissue may be transmural, 20 implying that endocardial RF ablation and epicardial CS ablation confined to the MI annular aspect (an area unaffected by VOM-Et) may be sufficient. Further prospective studies are warranted to clarify this issue. 5. CONCLUSION Regarding the MI ablation after VOM-Et, the voltage map-guided MI line demonstrated no significant differences compared to the conventional MI line in terms of MI block success, the need for CS ablation, or AT/AF recurrence rates. However, the voltage map-guided ablation resulted in significantly longer MI lines and a greater number of RF lesions. These findings suggest that the voltage map-guided MI line does not confer a procedural or clinical advantage over the conventional MI line. REFERENCES 1. Lin WS, Tai CT, Hsieh MH, Tsai CF, Lin YK, Tsao HM, et al. Catheter ablation of paroxysmal atrial fibrillation initiated by non-pulmonary vein ectopy. Circulation 2003;107:3176-3183. 2. Santangeli P, Marchlinski FE. Techniques for the provocation, localization, and ablation of non–pulmonary vein triggers for atrial fibrillation. Heart Rhythm 2017;14:1087-1096. 3. Chugh A, Gurm HS, Krishnasamy K, Saeed M, Lohawijarn W, Hornsby K, et al. Spectrum of atrial arrhythmias using the ligament of Marshall in patients with atrial fibrillation. Heart Rhythm 2018;15:17-24. 4. Vlachos K, Denis A, Takigawa M, Kitamura T, Martin CA, Frontera A, et al. The role of Marshall bundle epicardial connections in atrial tachycardias after atrial fibrillation ablation. Heart Rhythm 2019;16:1341-1347. 5. Valderrábano M, Chen HR, Sidhu J, Rao L, Yuesheng L, Khoury DS. Retrograde ethanol infusion in the vein of Marshall: regional left atrial ablation, vagal denervation, and feasibility in humans. Circ Arrhythm Electrophysiol 2009;2:50-56. 6. Valderrábano M, Peterson LE, Swarup V, Schurmann PA, Makkar A, Doshi RN, et al. Effect of catheter ablation with vein of Marshall ethanol infusion vs catheter ablation alone on persistent atrial fibrillation: the VENUS randomized clinical trial. JAMA 2020;324:1620-1628. 7. Derval N, Duchateau J, Denis A, Ramirez FD, Mahida S, André C, et al. Marshall bundle elimination, pulmonary vein isolation, and line completion for anatomical ablation of persistent atrial fibrillation (Marshall-PLAN): prospective, single-center study. Heart Rhythm 2021;18:529-537. 8. Gillis K, O’Neill L, Wielandts JY, Hilfiker G, Almorad A, Lycke M, et al. Vein of Marshall ethanol infusion as first step for mitral isthmus linear ablation. JACC Clin Electrophysiol 2022;8:367-376. 9. Nakashima T, Pambrun T, Vlachos K, Goujeau C, André C, Krisai P, et al. Impact of vein of Marshall ethanol infusion on mitral isthmus block: efficacy and durability. Circ Arrhythm Electrophysiol 2020;13:e008884. 10. Zuo S, Sang C, Long D, Bo X, Lai Y, Guo Q, et al. Efficiency and durability of EIVOM on acute reconnection after mitral isthmus bidirectional block. JACC Clin Electrophysiol 2024;10:685-694. 11. Gao MY, Sang CH, Huang LH, Lai YW, Guo Q, Liu XX, et al. Vein of Marshall ethanol infusion: first-step or adjunctive choice for perimitral atrial tachycardia? Pacing Clin Electrophysiol 2023;46:20-30. 12. Maurer T, Metzner A, Ho SY, Wohlmuth P, Reißmann B, Heeger C, et al. Catheter ablation of the superolateral mitral isthmus line: a novel approach to reduce the need for epicardial ablation. Circ Arrhythm Electrophysiol 2017;10. 13. Maheshwari A, Shirai Y, Hyman MC, Arkles JS, Santangeli P, Schaller RD, et al. Septal versus lateral mitral isthmus ablation for treatment of mitral annular flutter. JACC Clin Electrophysiol 2019;5:1292-1299. 14. Krisai P, Pambrun T, Nakatani Y, Nakashima T, Takagi T, Kamakura T, et al. How to perform ethanol ablation of the vein of Marshall for treatment of atrial fibrillation. Heart Rhythm 2021;18:1083-1087. 15. Kamakura T, André C, Duchateau J, Nakashima T, Nakatani Y, Takagi T, et al. Distribution of atrial low voltage induced by vein of Marshall ethanol infusion. J Cardiovasc Electrophysiol 2022;33:1687-1693. 16. Landra F, Nesti M, Garibaldi S, Mirizzi G, Startari U, Panchetti L, et al. A proposed index of myocardial staining for vein of Marshall ethanol infusion: an Italian single-center experience. J Interv Card Electrophysiol 2024;67:1267-1277. 17. Pambrun T, Derval N, Duchateau J, Denis A, Chauvel R, Tixier R, et al. Epicardial course of the musculature related to the great cardiac vein: anatomical considerations and clinical implications for mitral isthmus block after vein of Marshall ethanol infusion. Heart Rhythm 2021;18:1951-1958. 18. Becker AE. Left atrial isthmus: anatomic aspects relevant for linear catheter ablation procedures in humans. J Cardiovasc Electrophysiol 2004;15:809-812. 19. Laredo M, Ferchaud V, Thomas O, Moubarak G, Cauchemez B, Zhao A. Durability of left atrial lesions after ethanol infusion in the vein of Marshall. JACC Clin Electrophysiol 2022;8:41-48. 20. Aranyó J, Juncà G, Sarrias A, Bazan V, Cea D, Villuendas R, et al. Left atrial structure and function following ethanol infusion into vein of Marshall (MR-SHALL Study). J Cardiovasc Electrophysiol 2025;36:157-167 21. Schurmann P, Da-Wariboko A, Kocharian A, Lador A, Patel A, Mathuria N, et al. Mechanisms of mitral isthmus reconnection after ablation with and without vein of Marshall ethanol infusion. JACC Clin Electrophysiol 2024;10:2420-2430. 22. Scherr D, Derval N, Sohal M, Pascale P, Wright M, Jadidi A, et al. Length of the mitral isthmus but not anatomical location of ablation line predicts bidirectional mitral isthmus block in patients undergoing catheter ablation of persistent atrial fibrillation: a randomized controlled trial. J Cardiovasc Electrophysiol 2015;26:629-634. Table 1. Patient characteristics Age, year 69.1±8.1 68.4±8.5 70.3±7.4 0.58 Men, n (%) 37 (61.7) 26 (66.6) 11 (52.4) 0.29 Body mass index, kg/m 2 24.2±4.4 24.1±4.4 24.4±4.3 0.80 Comorbidities Hypertension, n (%) 33 (55.0) 20 (51.2) 13 (61.9) 0.44 Diabetes mellitus, n (%) 8 (13.3) 4 (10.2) 4 (19.0) 0.34 Heart failure, n (%) 13 (21.7) 8 (20.5) 5 (23.8) 0.77 Stroke, n (%) 5 (8.3) 4(10.2) 1 (4.7) 0.47 Underlying heart disease, n (%) 12 (20.0) 6 (15.3) 6 (28.5) 0.23 History of arrhythmia Paroxysmal AF, n (%) 15 (25.0) 7 (17.9) 8 (38.1) 0.09 Persistent AF, n (%) 30 (50.0) 22 (56.4) 8 (38.1) 0.18 Long-standing persistent AF, n (%) 8 (13.3) 7 (17.9) 1 (4.8) 0.16 AT, n (%) 18 (30.0) 12 (30.8) 6 (28.5) 0.86 Medications before ablation Antiarrhythmic drug, n (%) 33 (55.0) 22 (56.4) 11 (52.3) 0.77 Beta blocker, n (%) 35 (58.3) 22 (56.4) 13 (61.9) 0.69 Ablation history Previous atrial ablation, n (%) 50 (83.3) 33 (84.6) 17 (80.9) 0.72 Number of previous atrial ablation 1.0±0.5 0.9±0.5 1.0±0.6 0.98 PV isolation, n (%) 50 (83.3) 33 (84.6) 17 (80.9) 0.72 Cavotricuspid isthmus line, n (%) 48 (80.0) 32 (82.1) 16 (76.2) 0.59 Posterior wall isolation, n (%) 11 (18.3) 9 (23.1) 2 (9.5) 0.20 Roofline, n (%) 5 (8.3) 4 (10.2) 1 (4.8) 0.47 Superior vena cava isolation, n (%) 9 (15.0) 8 (20.5) 1 (4.8) 0.11 Complex fractionated atrial electrograms ablation, n (%) 4 (6.7) 3 (7.7) 1 (4.8) 0.67 Non-PV triggers ablation, n (%) 2 (3.3) 1 (2.6) 1 (4.8) 0.65 Echocardiographic measurements Left atrial diameter, mm 42.2±6.5 43.0±5.5 40.9±7.8 0.23 Left ventricular ejection fraction, % 56.7±10.0 59.3±7.3 51.8±14.6 0.01 Table 2. Procedural data Additional ablation First PV isolation, n (%) 10 (16.7) 7 (17.9) 3 (14.2) 0.72 PV re-isolation, n (%) 21 (35.0) 14 (35.9) 7 (33.3) 0.84 Cavotricuspid isthmus line, n (%) 13 (21.7) 7 (17.9) 6 (28.6) 0.35 Posterior wall isolation, n (%) 41 (68.3) 30 (76.9) 11 (52.4) 0.05 Roofline, n (%) 8 (13.3) 1 (2.6) 7 (33.3) <0.01 Superior vena cava isolation, n (%) 31 (51.7) 21 (53.8) 10 (47.6) 0.65 Complex fractionated atrial electrograms ablation, n (%) 0 (0) 0 (0) 0 (0) 1.0 Non-PV triggers ablation, n (%) 4 (6.7) 3 (7.7) 1 (4.8) 0.67 Induced peri-mitral AT, n (%) 25 (41.7) 18 (46.1) 7(33.3) 0.35 MI ablation MI block acute success 58 (96.7) 37 (94.9) 21 (100) 0.30 Length of MI line, mm 38.3±9.9 41.3±9.7 32.7±7.4 <0.01 Direction of MI line, o’clock 2.7±0.8 2.8±0.8 2.3±0.5 <0.01 CS ablation, n (%) 23 (38.3) 15 (38.5) 8 (38.1) 0.98 CS anchored wall ablation, n (%) 22 (36.7) 14 (35.9) 8(38.1) 0.87 CS free wall ablation, n (%) 6 (10.0) 5 (12.8) 1 (4.8) 0.33 RF duration to achieve MI block, min 15.9±10.3 15.9±9.7 16.1±11.3 0.93 RF lesions to achieve MI block 14.8±5.9 15.9±5.7 12.6±5.7 0.03 Adverse event Pericardial effusion, n (%) 0 (0) 0 (0) 0 (0) 1.0 Stroke, n (%) 0 (0) 0 (0) 0 (0) 1.0 MI, mitral isthmus; CS, coronary sinus; RF radiofrequency Table 3. Voltage map data Low voltage area around VOM before VOM-Et, cm 2 1.4±2.9 Low voltage area induced by VOM-Et, cm 2 7.4±4.4 Distribution of low voltage area induced by VOM-Et Ridge only, n (%) 5 (12.8) Ridge and lateral wall, n (%) 20 (51.2) Ridge, lateral and inferior wall, n (%) 14 (35.9) VOM, vein of Marshall; VOM-Et, Ethanol infusion into the vein of Marshall FIGURE LEGENDS Figure 1 Illustration of the two strategies for MI ablation. Group A (voltage map-guided MI line creation after VOM-Et): The ablation line (blue dots) is drawn from the mitral annulus along the low-voltage areas (red shading) toward the LIPV. Group B (conventional MI line creation): The ablation line is placed from the 2–3 o’clock position of the mitral annulus to the LIPV, irrespective of low-voltage areas. Abbreviations: MI, mitral isthmus; VOM-Et, Ethanol infusion into the vein of Marshall; LIPV, left inferior PV Figure 2 Segmented LA for evaluating the extent of VOM-Et-induced low-voltage areas. The ”clock-face” positions indicate the directional orientation for MI line creation. Abbreviations: LA, left atrium; MI mitral isthmus; VOM-Et, Ethanol infusion into the vein of Marshall Figure 3 Box-and-whisker plots comparing MI line length among subgroups within Group A. Each subgroup was categorized based on the extent of the low-voltage area induced by VOM-Et: confined to the ridge only (n = 5), involving both the ridge and lateral wall (n = 20), or extending to the ridge, lateral wall, and inferior wall (n = 14). Abbreviations: MI, mitral isthmus; VOM-Et, Ethanol infusion into the vein of Marshall Figure 4 Voltage maps before (left) and after VOM-Et (right) for Group A (top two rows) and Group B (bottom row). In the first row, VOM-Et resulted in low-voltage areas involving the ridge and lateral wall. In the second row, VOM-Et affected the ridge, lateral wall, and inferior wall. Notably, MI lines in Group A (top two rows) tended to be positioned more inferiorly compared to those in Group B (bottom low). Abbreviations: LSPV, left superior PV; LIPV, left inferior PV; RSPV, right superior PV; RIPV, right inferior PV; MI, mitral isthmus; VOM-Et, Ethanol infusion into the vein of Marshall Information & Authors Information Version history V1 Version 1 03 September 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords clinical: cardiac mapping – 3-dimensional systems clinical: cardiac mapping – voltage clinical: catheter ablation – atrial fibrillation clinical: catheter ablation – atrial flutter clinical: catheter ablation – atrial tachycardia Authors Affiliations Shingo Yoshimura 0000-0003-2744-0738 [email protected] Gunma Kenritsu Shinzo Kekkan Center View all articles by this author Kenichi Kaseno Gunma Kenritsu Shinzo Kekkan Center View all articles by this author Kojiro Hattori Gunma Kenritsu Shinzo Kekkan Center View all articles by this author Akiko Kodama 0009-0009-4253-1217 Gunma Kenritsu Shinzo Kekkan Center View all articles by this author Taiki Masuyama Gunma Kenritsu Shinzo Kekkan Center View all articles by this author Takehito Sasaki Gunma Kenritsu Shinzo Kekkan Center View all articles by this author Suguru Nishiuchi 0000-0002-3117-9985 Gunma Kenritsu Shinzo Kekkan Center View all articles by this author Kohki Nakamura 0000-0002-9777-4592 Gunma Kenritsu Shinzo Kekkan Center View all articles by this author Shigeto Naito Gunma Kenritsu Shinzo Kekkan Center View all articles by this author Metrics & Citations Metrics Article Usage 314 views 205 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Shingo Yoshimura, Kenichi Kaseno, Kojiro Hattori, et al. Comparison of Mitral Isthmus Ablation Strategies after Ethanol Infusion into the Vein of Marshall: Voltage Map-Guided versus Conventional Mitral Isthmus Line Placement. Authorea . 03 September 2025. DOI: https://doi.org/10.22541/au.175692266.61341048/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . 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