Atrial fibrillation (AF) is the most common tachyarrhythmia in adults and is associated with high morbidity and mortality. Its estimated prevalence is between 2-4% and is expected to increase progressively in the coming years. The benefits of rhythm control in these patients include not only a significant improvement in quality of life but also reduced hospitalizations and mortality, particularly in patients with ventricular dysfunction. Ablation techniques generally focus on isolating the pulmonary veins (PVs), as they represent the most common arrhythmogenic substrate. The efficacy of endocardial ablation in patients with paroxysmal AF is approximately 70-80%; however, in persistent AF, this efficacy is more modest, reaching a success rate of 40-70%, with approximately 1 in 3 patients requiring a repeat procedure. Additionally, the complex pathophysiology of persistent AF necessitates exploring substrates beyond electrical isolation of the PVs.

To improve these outcomes and address new electroanatomic substrates, hybrid ablation was developed. This is a novel technique that combines a surgical epicardial approach with conventional endocardial catheter ablation. The epicardial surgical access can be achieved through thoracoscopy, subxiphoid approach, or minithoracotomy. Lesions are created (using various available radiofrequency devices) to isolate the posterior atrial wall through one of three methods: PV isolation and connecting lines between each pair of veins at the atrial roof and floor; posterior “box” isolation; or posterior wall ablation. In the first approach, a clamp device (e.g., Atricure® Isolator Synergy®) is applied around the PVs, followed by creation of roof and floor lines. The second approach is technically simpler, as two specific devices (Estech® COBRA Fusion® and Medtronic® Cardioblate Gemini-S®) jointly encircle the antrum of the four PVs. In the third approach, a single access is used to perform ablation with the Atricure® EPi-Sense® device, applying radiofrequency to the posterior atrial wall. Additionally, some groups perform accessory lesions at other levels, and epicardial left atrial appendage exclusion using a clip (AtriClip® Pro®, Pro-2®, and Pro-V®) is recommended as standard. Subsequently, endocardial ablation assesses the zones blocked through the epicardial approach, with any detected gaps being re-ablated. Procedures can be simultaneous or staged, beginning with epicardial application, followed by endocardial ablation after 1-3 months. No studies compare these two strategies; however, a staged approach allows for detection of reconnections following the formation of the definitive epicardial scar, making endocardial ablation a rescue step.

A significant limitation of hybrid ablation is lesion durability. Long-term data following both procedures is lacking, and the high heterogeneity of observational studies limits interpretation of their results. This is compounded by the variability in surgical approaches, technologies, and procedural intervals, resulting in a wide range of reconnection rates (7-80%) across studies. The carina between PVs and the atrial roof line are the most common sites of reconnection.

Regarding procedural efficacy, this article compiles results from various observational studies. The percentage of patients free of tachyarrhythmias at 1 year, depending on whether procedures were performed sequentially or simultaneously, is 83% (95% CI: 68%-94%) and 71% (95% CI: 68%-75%), respectively. However, these results should be interpreted cautiously due to several limitations. One limitation is the varying definition of tachyarrhythmia and its monitoring across studies. In most cases, the goal was to detect 30 seconds of any type of atrial arrhythmia, but detection methods varied, with some studies using a subcutaneous Holter monitor and others using serial ECGs, the latter of which have a lower detection capability and may overestimate procedural success. Another major limitation previously mentioned is the heterogeneity in lesion types, approaches, devices, and procedural intervals, preventing standardized action and outcome comparison. Moreover, the external validity of these studies is limited; although they included patients with persistent AF, they generally excluded patients with dilated atria (common in patients with longer AF duration due to atriopathy progression) or ventricular dysfunction (groups in which rhythm control has demonstrated mortality reduction).

In 2020, a meta-analysis of 34 observational studies demonstrated higher success rates with hybrid ablation (70%) compared to conventional ablation (50%). That same year, the CONVERGE study was published—the only randomized trial with 150 patients comparing hybrid and conventional ablation in patients with persistent and long-standing persistent AF (>12 months), including those with more advanced atrial pathology and an average AF duration of 4 years. After one year of follow-up, hybrid ablation increased the percentage of patients free from atrial arrhythmias (67% vs. 50%) and significantly reduced arrhythmic burden.

Despite these positive outcomes, it is known that hybrid ablation is a more invasive technique, inevitably increasing complication risks. To date, this risk is 3-7 times higher than with conventional interventional ablation, mainly due to the surgical procedure. Possibly, standardization of these techniques could optimize and reduce these figures.

COMMENTARY:

It is clear that new approaches are needed to address the complex pathophysiology of persistent AF. Hybrid ablation offers both benefits and challenges. Current evidence is limited and highly heterogeneous, but it points to the potential benefits of this technique, even in patients with more advanced disease stages, albeit with an increase in adverse effects.

The FAST study provides some information on one of the main gaps in this technique. This study found that exclusive epicardial ablation in AF patients was superior to conventional interventional ablation in maintaining sinus rhythm over 7 years of follow-up. Therefore, it might be expected that if a single procedure provides this durability, even better results could be achieved with both approaches. However, the reality is that we currently lack data beyond one year following the two procedures. Another relevant detail is that we are comparing a procedure that involves two ablations with a single endocardial procedure, which logically could overestimate the effect of hybrid ablation, and the ongoing incorporation of new technologies in endocardial approaches will likely enhance the performance of this technique in the future.

We should also note that, at present, there is insufficient evidence supporting ablation (at least endocardial) of substrates beyond the PVs. Posterior wall ablation has sparked interest in this patient group due to its embryologic origin shared with the PVs, heterogeneous fiber orientation that facilitates micro-reentry formation, and rich autonomic innervation— all possible pathophysiological mechanisms of persistent AF. Endocardial ablation at this level is technically complex with a risk of esophageal perforation of 0.5-0.6%, so epicardial ablation could facilitate more durable transmural lesions at this site. Based on this, could epicardial ablation demonstrate the need to ablate these extrapulmonary substrates? This is still an open question, and new clinical trials are needed to answer it.

In conclusion, many questions remain to be answered before standardizing this therapy. The 2020 European Society of Cardiology guidelines recommend (Class IIa) hybrid ablation for patients with symptomatic persistent AF following failed rhythm control with antiarrhythmic drugs and/or endocardial interventional ablation. Its application as first-line treatment for symptomatic persistent AF patients with risk factors for recurrence has yet to prove efficacy, with guidelines offering only a Class IIb recommendation based on expert opinion. Upcoming clinical trials will shed more light on this technique, potentially providing a new therapeutic option for these patients with a complex approach.

REFERENCE:

Bisleri G, Pandey AK, Verma S, Ali Hassan SM, Yanagawa B, Khandaker M, et al. Combined minimally invasive surgical and percutaneous catheter ablation of atrial fibrillation: JACC review topic of the week. J Am Coll Cardiol. 2023 Feb 14;81(6):606-619. doi: 10.1016/j.jacc.2022.11.039.