Discussion
The present study evaluated the effectiveness of a fixed, reproducible ‘upgraded 2C3L’ ablation strategy that combines the EI-VOM and RF ablation targeting bilateral PVAI and bidirectional linear block of MI, CTI, and LA roofline. This strategy is associated with higher sinus rhythm maintenance compared with the conventional ’2C3L’ approach during the 12-month follow-up.
Current guidelines have indicated that PVI alone is insufficient for maintaining sinus rhythm in patients with PeAF[1], and varieties of substrate modification strategies, including anatomical ablation (linear ablation) and electrogram guided ablation(ablation of rotors, fractionated electrograms, et al), have been widely adopted by electrophysiologists in recent decades. In surgical ablation, linear lesions have been proven to be effective in rhythm control[9]. Theoretically, linear ablation helps to achieve LA compartmentation, stop the rotors roaming around the left atrium, and therefore preventing the maintenance of AF[10]. But the conclusion is quite different for catheter ablation. The main reason for this inconsistency lies in the fact that transmural lesions cannot always be achieved by radiofrequency catheter ablation. As is reported in the STAR AF II trial[3], where LA linear ablation involving the roofline and mitral isthmus failed to bring about higher SR maintenance compared with PVI alone, the overall linear block rate was only 74%.
With the advancement of ablation technology, complete block of the roofline and CTI can now be achieved in most cases. But the ablation of the MI line remains challenging. In the ALINE study, even by using an AI-guided, point-by-point optimized RF ablation, MI bidirectional block can only be achieved in 80% of patients, while in most cases roofline can be easily blocked.[11] Meanwhile, conduction recovery across the MI line can occur in 38 of 52 patients with recurrent AF/AT[12]. Besides the atrial wall thickness and heat-sinking effect of epicardial vessels, one important cause is epicardial conduction through the ligament of Marshall[13]. In our previous study of the ’2C3L’ approach, perimitral atrial flutter accounts for 10 of 24 recurrent AF/ATs after ablation for PeAF [2]. Moreover, it is reported that the Marshall bundle (MB) participates in 30.2% of reentrant ATs after AF ablation. Only 81.6% of these MB-related ATs could be terminated using RF ablation, and the recurrence rate was as high as 41.3% during 18-months follow up[14].
EI-VOM may provide a solution to achieve MI bidirectional block. Through the VOM and its collateral flow, the ethanol can infiltrate into the atrial myocardium and rapidly cause transmural lesions that mainly involve the posterolateral LA free wall and anterior part of the left pulmonary antrum[15]. More importantly, lesions resulting from ethanol infusion has been proved to have higher durability, which prevents future reconnection across the blocked MI line[16]. For persistent atrial fibrillation, data revealing the value of EI-VOM on substrate modification is still limited. In the recently published VENUS trial, EI-VOM before RF ablation significantly improved long-term AF free survival and reduced AF burden compared with RF ablation alone[5]. However, as is reported in its post-hoc analysis, patients could benefit from EI-VOM only if MI was blocked[6]. Meanwhile, a prospective, single-arm study has demonstrated that EI-VOM in conjunction with a fixed strategy of LA linear ablation has ideal short- and long-term effectiveness [17]. In view of current studies, an anatomical ablation strategy targeting atrial compartmentation seems to better take advantage of EI-VOM, compared with empirical substrate modification.
Herein, we conducted a comparative study to further elucidate the value of a fixed ablation strategy that combines EI-VOM and the well-established ‘2C3L’ approach. At the very beginning of the procedure, both the proximal and distal parts of the VOM were ablated with ethanol infusion. With EI-VOM, anatomical structures refractory to RF energy, like the Marshall bundle, left lateral ridge, and LA myocardium near epicardial vessels can be easily injured transmurally. Theoretically, it is promising in reducing the recurrence of perimitral ATs. Meanwhile, facilitated LPV antrum ablation and better atrial compartmentation by linear lesions further prevent the recurrence of atrial fibrillation. Patients with AF triggers originating from the LOM can also benefit from EI-VOM[18]. Moreover, as is observed in the present study, in this fixed, less progressive ’upgraded 2C3L’ approach, ablation is mostly performed at sites with the latest atrial activation and is less likely to result in left atrial appendage conduction delay, preventing the physiology of atria. As for safety concerns, the incidence of the adverse event during EI-VOM is reasonably low in the present study, as is also reported previously[19].
It is also important to realize the limitation of EI-VOM itself. The VOM is not always accessible, and the accessible rate varies from 71.4%-96[5, 16, 17, 20]. 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 EI-VOM lesion. In the present study, ablation in the coronary sinus is equally required in both groups, and MI conduction gap near the annular side is the cause of recurrent perimitral flutters in group 1.