Delayed bipolar voltage changes in the left atrium after vein of Marshall ethanol infusion

Ethanol infusion into the Vein of Marshall (EIVOM) is a promising adjunctive ablation strategy and improves sinus rhythm (SR) maintenance among patients undergoing catheter ablation (CA) of persistent atrial fibrillation (AF).1 EIVOM is believed to enhance AF suppression by several mechanisms, including facilitation of left-sided pulmonary vein isolation (PVI) and mitral isthmus block, elimination of epicardial arrhythmogenic substrates, and vagal nerve modulation. Optimal techniques for EIVOM, understanding of the durability of EIVOM-induced low voltage area (LVA), and delineation of the complex epicardial left atrial (LA) venous system are still evolving.2 This study sought to evaluate the intraprocedural temporal changes in the extent of EIVOM-induced LVA as assessed by bipolar voltage mapping of atrial electrograms in SR during AFCA. This retrospective study included consecutive patients who underwent AFCA incorporating EIVOM between April and October 2022 at The Ohio State University Wexner Medical Center. This study was approved by the Institutional Review Board, required informed consent, and adhered to the Helsinki Declaration. Techniques for EIVOM were previously described.3 Briefly, a baseline LA voltage map (“Baseline map”) was created in SR using a multi-spline catheter (Pentaray, Biosense Webster or Advisor HD Grid, Abbott). Peak-to-peak bipolar voltage < 0.5 mV and < 0.1 mV were defined as LVA and scar, respectively. In order to ensure adequate catheter contact during point acquisition, a proprietary impedance-based algorithm (“Tissue Proximity Indicator”) was always enabled for Pentaray/Carto whereas flexion of the grid splines in relation to the catheter shaft visualized on the electroanatomical mapping system was primarily used as an indicator for sufficient tissue contact for HD grid/Ensite, in conjunction with fluoroscopy and intracardiac echocardiography, if necessary.4 After selective VOM cannulation with a coronary angioplasty wire and balloon occlusion via a femoral approach, contrast was injected through the inner lumen of the coronary dilatation balloon catheter to ensure no apparent proximal contrast leak. Further balloon inflation and/or balloon re-positioning distally in the VOM was performed if necessary. Then 3 mL of 98% ethanol was progressively injected up to 10 mL. Repeat high-density LA voltage maps were acquired immediately after (“Post-map 1″”) and 20 min after EIVOM (“Post-map 2″”) with particular attention paid to delineate bipolar voltage changes around the left PVs, the posterior mitral annular region, and the posterior wall. No radiofrequency ablation (RFA) was performed around the left PVs or posterior mitral isthmus area during the 20-min window. All patients subsequently received standard RFA lesion sets per operator discretion. Successful EIVOM was defined as injection of ≥ 3 mL ethanol into the VOM. Two electrophysiologists reviewed sequential bipolar voltage maps in each patient to evaluate for (1) development of the EIVOM-induced LVA and (2) delayed changes in the extent of LVA/scar from Post-map 1 to Post-map 2. EIVOM-induced LVA was defined as characteristic voltage loss in the posterior mitral isthmus and/or the anteroinferior quarter of the left inferior PV antrum.5 Delayed change was defined as substantial progression or regression of voltage loss in the characteristic areas after 20 min. During the study period, EIVOM was attempted in 77 patients (21 (27%) females, age 64.4 ± 10.2 years, CHA2DS2-VASc 2.7 ± 1.7, 31 (40%) with paroxysmal AF, and 32 (42%) with prior AFCA). Among the 77 patients, EIVOM was successful in 59 (77%) patients (mean ethanol 9.5 ± 0.6 mL). Among these 59 patients, 44 patients had complete serial LA maps in SR, of which 37 (84%) patients demonstrated characteristic EIVOM-induced LVA on Post-map 1. On Post-map 2, the extent of LVA further expanded, remained unchanged, or regressed in 4 (11%), 32 (86%) and 1 (3%) patient, respectively (Figure 1). Despite apparently successful VOM balloon occlusion and EIVOM, 7 (16%) patients demonstrated no new LVA on Post-map 1 or Post-map 2. One patient experienced a coronary sinus (CS) dissection (without pericardial effusion) during difficult CS cannulation, and EIVOM was then successfully completed from the internal jugular approach. No other intraprocedural complications were noted. Although the majority of the successful EIVOM cases demonstrated sustained LVA in the characteristic location, five patients demonstrated delayed LVA changes. Gradual infiltration of ethanol into capillaries within the complex atrial venous network may account for further LVA expansion. A mechanism for delayed voltage recovery is unclear. No apparent proximal contrast leakage or drainage through anastomoses with other coronary veins was noted on fluoroscopy before ethanol injection for this case. Similarly, the lack of any new LVA development in seven patients after apparently successful EIVOM remains unexplained, although inadvertent cannulation of a non-VOM atrial branch cannot be definitively excluded. This study has important limitations and should be considered hypothesis-generating. First, the patchy distribution of EIVOM-induced LVA was only visually assessed for the current study. Automatic quantification of voltage metrics through an advanced electrophysiology analysis platform would be an ideal tool for future studies.6 Second, a 20-min window was arbitrarily chosen to preserve clinical workflow. Third, whether delayed changes in LVA impact the clinical benefit of EIVOM remains unknown. Fourth, detailed morphologic assessment of VOM anatomy in different fluoroscopic angulations was not performed. Such an investigation may aid in understanding the correlation between specific VOM anatomy and temporal LVA changes. Finally, and most critically, sequential mapping with differing numbers of acquired points may have exposed limitations of bipolar voltage mapping such as wavefront directionality, catheter orientation, and mapping point density.7 In conclusion, delayed changes in LVA were observed in a subset of patients undergoing EIVOM during AF ablation. Further studies are needed to explore the relationship between the anatomical characteristics of the VOM and the extent/temporal changes of LVA induced by EIVOM. Concept/design: Toshimasa Okabe, Data collection: Toshimasa Okabe, Sapan Bhuta, Data analysis/interpretation: Toshimasa Okabe, John D. Hummel, Drafting article: Toshimasa Okabe, Sapan Bhuta, John D. Hummel. The authors have nothing to report. The authors have no relationships relevant to the contents of this paper to disclose. This study was approved by The Ohio State University Wexner Medical Center Institutional Review Board and patient consent was obtained. The data that support the findings of this study are available from the corresponding author upon reasonable request.