Discussion
In the present study, we described for the first time the feasibility and effectiveness of a novel stepwise endo-/epicardial approach for persistent/longstanding persistent AF ablation and one or more prior endocardial CA. The key messages are as follows: 1) a stepwise endo-/epicardial CA approach, by addressing endocardial as well as epicardial atrial arrhythmogenic substrates and ensuring lesion transmurality, could restore sinus rhythm in the vast majority of patients with persistent or longstanding persistent AF; 2) as previously hypothesized,6 epicardial ablation of the BB appeared to be a fundamental step of our comprehensive approach, resulting in conversion to sinus rhythm in a high proportion of cases; 3) during follow-up, most of these patients did not experience AF recurrences, allowing the discontinuation of antiarrhythmic drugs; 4) we observed a significant improvement in patients’ symptom status during follow-up, and the majority of patients were asymptomatic 9 months after the procedure; 5) our approach resulted in no mechanical complications and in a low risk of medical issues, usually managed with conservative measures; 6) although pericardial reflections and/or sinuses have been classically considered a hindrance to epicardial ablation of arrhythmogenic atrial structures,15 catheter manipulation into the transverse sinus was feasible in each patient, and allowed effective CA of the BB.
The optimal ablation approach for patients with persistent AF has yet to be determined.3-5 Recently, endo-epicardial dissociation has been proposed as a key mechanism underlying AF persistence in both animal models and human mapping studies, whereby conduction velocity and direction differ in the various atrial myocardial layers, acknowledging the transmural nature of the fibrillatory process in patients with longstanding AF episodes.16
Furthermore, the role of epicardial structures in the pathogenesis of AF is increasingly being recognized.6,7 A direct relationship between BB and AF is supported by epidemiological, animal, and clinical studies.17 Longitudinal dissociation of conduction along BB, by predisposing to reentrant circuits, is an important mechanistic link between BB and AF.6 Based on these observations, delivering ablation lesions on the BB during AF CA could eliminate a substrate for inhomogeneous conduction and AF perpetuation.18 Remarkably, given the epicardial location of BB’s body, its thickness (a median of 4 mm), and the presence of fatty tissue separating it from the limbus of the fossa ovalis,6 an endocardial CA approach aiming to eliminate such an arrhythmogenic substrate would only address distal extensions of the interatrial conduction system, leaving the BB’s body and its reentrant circuits substantially unchanged.
Our data support these hypotheses, since epicardial BB’s ablation resulted in restoration of sinus rhythm in 20% of cases, and the BB was also the most common site where atrial tachycardias appearing during the procedure could be mapped. Therefore, epicardial BB’s ablation appears to be a fundamental measure to incorporate in a stepwise CA procedure aiming to restore sinus rhythm. Although previous studies raised the concern that BB’s ablation could result in impairment of LA mechanical function and increase thromboembolic risk by delaying electrical activation of the LA appendage,19,20 it is worth reiterating that among patients with persistent/longstanding persistent AF, disrupted interatrial conduction is commonly present at baseline,17 confounding the assessment of the impact of CA. In our cohort, in which LA appendage was never electrically isolated, and all patients received long-term anticoagulant treatment as per CHA2DS2-VAsc score,1,2 no thromboembolic complication occurred. In addition, as a possible alternative to anticoagulation, LA appendage devices could potentially be used to mitigate stroke risk in these patients.21
Closure of a large set of anatomical isthmuses in LA and RA endocardium, as well as BB and LOM ablation in the epicardium resulted in a high rate of AF organization into atrial tachycardias, whose elimination led to AF termination in a high proportion of our cohort.22 This finding suggests that our stepwise approach results in emergence of important drivers sustaining arrhythmia recurrences in the form of atrial tachycardias in the individual patient, allowing a tailored approach aimed at eliminating these drivers.22,23 As compared to previous studies,9-11,23 we used for the first time an endo-/epicardial strategy in order to chase each emerging atrial tachycardia. By transmurally mapping and ablating these arrhythmias, we were able to obtain very high procedural and middle-term success. Furthermore, the addition of epicardial ablations allowed us to obtain lesion transmurality and bidirectional conduction block in the roof and anterior LA lines, thus eliminating potential substrates for atrial tachycardias during follow-up.9,23
Our stepwise endo-/epicardial approach differs in several ways from previously described hybrid techniques for AF CA.24,25Although we gained access to the pericardial space with a small subxiphoid pericardial window, we did not navigate the pericardium under direct vision, and all ablation lesions were delivered by the electrophysiologist using conventional ablation catheters, therefore limiting the need for assistance by the cardiac surgeon to the initial and terminal moments of the procedure. Furthermore, although every case was performed in cooperation with cardiac surgeons, the pericardial access was successfully performed by the electrophysiologist as first operator in the last 15 patients ablated, suggesting that a mini-invasive pericardial access is not surgically demanding. As compared to other hybrid techniques, the ability to deliver all ablation lesions during a single-stage procedure in a transmural fashion is an important advantage of our approach, which appears to be particularly appropriate for symptomatic patients strongly desiring to have their arrhythmia rapidly eliminated.
In patients with persistent AF, antiarrhythmic drugs are often prescribed to facilitate rhythm control.1,26 However, even amiodarone, the most effective drug, is inferior to CA in maintaining sinus rhythm1,27 and is plagued by adverse events, which can sometimes be life-threatening.1,26Endo-/epicardial CA may represent the ideal therapeutic strategy for younger patients, by allowing discontinuation of antiarrhythmic medications in the vast majority, thus avoiding long-term exposure to amiodarone.26
As a final remark, we found that each patient could be discharged in sinus rhythm irrespective of the presence of marked atrial dilation and longstanding AF duration, that most of these patients did not experience recurrences at follow-up, and that only one patient had a serious adverse medical event. These findings might support a more aggressive approach to rhythm control among patients with persistent/longstanding persistent AF and one or more prior endocardial CA, by incorporating the stepwise endo-/epicardial ablation protocol, which may represent a viable option when adverse atrial remodeling is present.