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.