The prevalence of atrial fibrillation (AF) is increasing with the development of an aging society. At present, for catheter ablation of persistent atrial fibrillation, substrate modifications beyond pulmonary vein isolation is still lacking in evidence for further reducing the long-term recurrence. Some researchers believe that the long-term recurrence rate of persistent AF is related to mitral valve block rate (1).

Vein of Marshall ethanol infusion (VOM-Et) has become a popular topic in recent years. The block rate of the mitral isthmus (MI) can be improved by injecting absolute ethanol into the Marshall vein. In addition, VOM-Et can also play a role in intervening the autonomic nerve and AF triggers originating from the vein of Marshall, so as to reduce the recurrence rate of catheter ablation for persistent AF. However, few study has focus on the effect of VOM-Et on mitral isthmus ablation. The present study aims to investigate the impact of VOM-Et on MI ablation, as well as potential factors associated with the effect size.

The main findings of the present study, indicate that VOM ethanol infusion facilitates MI conduction block. Furthermore, in the subgroup analysis, our data support that male sex, age >60 years, LA diameter <55 mm and AF duration <3 years were independently associated with the benefits of VOM-Et for AF patients.

The success rates for achieving MI block using RF range from 42% to 92% for the posterior MI line (2–8), 85%–88% for the anterior MI line (9, 10), and 98.2% for the superolateral MI line (11). Acute and long-term success may be impacted by MI thickness and duration. A growing body of research has shown that VOM is significantly associated with arrhythmias, and the main potential pathophysiological mechanisms are proximal VOM autonomic nervous system imbalance, VOM-related AT, VOM-related reentrant activities triggering AF, and focal activities perpetuating AF (12). According to preliminary clinical studies, ethanol effusion into VOM can result in a complete linear lesion along the MI and successfully block the MI (13, 14), making it a viable treatment option for peri-mitral AT. In contrast to catheter ablation alone, catheter ablation with VOM-Et enhanced the likelihood of independence from AF/AT for PeAF with one-year follow-up, according to a recent randomized, multi-center experiment (VENUS trial) (1).

The difficulties in MI ablation and the low block rate is the major consideration that preclude application of MI ablation in clinical practice. Complete MI block may be difficult to achieve due to several physical restrictions, including a thicker and longer MI (15), the heat-sink effect of blood flow in the CS and circumflex arteries, and epicardial fibers like the CS myocardial sleeve and ligament of Marshall (16–18). These factors often result in longer ablation time and higher procedural risk. In our study, we found that the size of LA and the application of VOM-Et are key factors affecting the success rate of MI Block. Atrial structural remodeling is a common phenomenon in patients with atrial fibrillation (AF), usually manifested as increased atrial volume and atrial wall fibrosis, which will increase the success rate of catheter ablation to achieve MI block. Left atrial enlargement is closely related to the severity of atrial fibrillation, especially in persistent atrial fibrillation, which increases the success rate of both PVI isolation and MI block (19).With VOM-Et, MI ablation is much facilitated. Particularly, less RF applications are required in the mid to distal part of MI including the LAA base, which has more trabeculated and creviced structures susceptible to perforation. Although VOM rupture and leaking of ethanol may occur during VOM-Et and cause pericardial effusion or pericarditis, most of these complications could be manage with medical observation and appropriate medications.

It's also critical to understand VOM-Et's own limitations. The VOM is not always available, and the accessibility rate ranges from 71.4% to 96% (13, 20, 21). The difference in techniques, limited sample size of the reports could be the potential explanations that require further research. Of special note, the annulus side of MI is not covered by the VOM-Et lesion. As previously stated and anticipated due to anatomical factors, VOM-Et mostly affects the pulmonary venous side of the mitral isthmus while sparing the annular aspect (22). For mitral isthmus ablation, epicardial ablation via the CS is frequently necessary. Epicardial ablation often targets the annular side of the mitral isthmus due to the path of the CS, paying particular attention to the CS and GCV (23).

Although VOM-Et has a great help in improving the success rate of MI Block, there are some factors that can affect its effectiveness. Our study is the first to analyze individual factors that influence the clinical outcome of VOM-Et, including the sex, age, left atrial size, and duration of atrial fibrillation, as well as hypertension, diabetes, smoking, and alcohol consumption. These factors are also important for the success rate of radiofrequency catheter ablation for atrial fibrillation. In previous reports, it has been found that the success rate of catheter ablation of MI block is affected by the thickness of the isthmus, anatomic isomerism, and connection to the epicardium. It is well known that patients with atrial fibrillation will expand the atrium because of the long duration of AF and age, which will aggravate the degree of myocardial fibrosis. These conditions can lead to a thickening of the isthmus, resulting in a low success rate of MI block for traditional catheter ablation and the need for further VOM for complementary ablation. High blood pressure, diabetes, smoking and alcohol consumption are also risk factors for exacerbating the progression of atrial fibrillation, so it is not difficult to understand their influence on the effect of VOM-Et. Sex differences have been recognized in many aspects of AF management, including epidemiology, clinical presentation, and response to treatment (24). Although current studies reported trivial sex differences in sinus rhythm maintenance after ablation (25–27), there are clues indicating sex differences in the pathophysiology of AF, such as the prevalence of non-PV triggers, atrial fibrosis, PV reconnection rate, and thickness of epicardial adipose tissue (28–31). In the present study, we further suggested a lower MI block rate in male patients who tended to benefit more from VOM-Et.

Other clinically relevant outcomes, such as the AF burden rate of repeat surgeries, showed the benefits of Marshall ethanol as well technique complications were not increased by the VOM-Et technique. The overall aggressive ablation strategy adopted in both groups was consistent with adverse outcomes. These findings further confirm the safety and efficacy of VOM-Et in improving the success rate of MI block and optimizing AF catheter ablation

This study has several limitations. First, the study was a single-center, exploratory cross-sectional study, and the end point was immediate intraoperative MI block rate, mainly limited by the lack of follow-up and analysis of redo procedures, not possible to evaluate the long-term injury effect of VOM-Et and its contribution to the success rate of ablation of atrial fibrillation. Subgroup analysis should be interpreted with caution. Although we tried to enroll as many patients as possible, we still do not have adequate power to illustrate the effectiveness of VOM-Et in every subgroup. Therefore, a larger cohort with a longer follow-up period is warranted in the future.

The present study provided further evidence for the effect of VOM-Et on MI ablation in the general population and different subgroups. VOM-Et is recommended to those more refractory to radiofrequency ablation, like younger, male patients.