To “isolate” or “not to isolate,” the left atrial appendage, “that is the question”
To Bisolate^ or Bnot to isolate,^ the left atrial appendage, Bthat is the question^
Luigi Di Biase 0 1 2 4 5 6 7 8
Andrea Natale 0 1 2 4 5 6 7 8
0 Department of Biomedical Engineering, University of Texas , Austin, TX , USA
1 Texas Cardiac Arrhythmia Institute at St. David's Medical Center , Austin, TX , USA
2 Montefiore-Einstein Center for Heart and Vascular Care, Montefiore Medical Center, Albert Einstein College of Medicine , 111 East 210th Street, Silver Zone, Bronx, NY 10467-2400 , USA
3 Luigi Di Biase
4 California Pacific Medical Center , San Francisco, CA , USA
5 Dell Medical School , Austin, TX , USA
6 Scripps Clinic , San Diego, CA , USA
7 Case Western Reserve University , Cleveland, OH , USA
8 Department of Cardiology, University of Foggia , Foggia , Italy
The left atrial appendage (LAA) has a trabecular shape, various morphologies, and derives from the embryonic left atrium as an outgrowth of the pulmonary veins (PV). The LAA plays a role in volume homeostasis secreting ANP and in autonomic innervation due to the presence of ganglia along the groove between the left superior PV and the LAA [1-9]. PVs isolation is the cornerstone of ablation of atrial fibrillation (AF) [10, 11]. Despite a permanent PVs isolation, patients may experience AF recurrences due to the presence of non-PV triggers responsible of AF [12, 13]. The relevance of non-PV triggers ablation in addition to PV isolation is extremely important for the treatment of persistent and longstanding persistent AF . The most common and reported non-PV trigger sites are the superior vena cava, the coronary sinus, the atrial septum, and the ligament of Marshall.
Recently, the LAA has been reported as an unrecognized
trigger site of AF in all subtype of AF and especially in patients
with non-paroxysmal AF [
]. For many years,
electrophysiologists have concentrated their effort to achieve durable PVs
isolation, considering PVs reconnection the only cause of
ablation failure. There is now evidence that despite isolated PVs
patients may experience AF recurrence. In 2010, we reported
a series of 266 patients undergoing redo AF ablation
procedures with demonstrated silent PVs. In 27 % of these patients,
a firing from the LAA was documented, and in 8 % of the
patients, the LAA was the only site responsible for AF. In our
series, we also showed that focal ablation of the LAA was not
as efficacious as complete electrical isolation to achieve
freedom from AF at follow-up [
]. After our initial report,
many case reports and series have shown the relevance of the
LAA for triggering and the maintenance of AF [
Hocini et al.  reported patients with localized re-entrant
arrhythmias originating within the LAA after failed standard
AF ablation and supported the hypothesis of LAA as a main
trigger for the maintenance of AF. Chan et al. [
suggested that LAA isolation may be caused by disruption of
Bachmann’s bundle, which runs along the LA anterior wall
and surrounds the LAA. Recently, the LAALA registry has
shown a lower AF burden by mechanically inducing electrical
isolation with the LARIAT closure device [
]. The aMAZE
] will enroll patient with persistent AF undergoing
LARIAT LAA closure and mechanical electrical isolation
and then PV isolation with radiofrequency. Although other
non-PV triggers such as the coronary sinus and posterior wall
will not be ablated, which might jeopardize the results, the
study will probably support the relevance of the LAA as an
In this issue of the journal, Hwan-Cheol Park [
] et al.
from Korea present a series of 846 consecutive patients
undergoing PVI plus extensive left atrial wall ablation guided by
CFAEs, cavo tricuspid isthmus bidirectional block and a clear
pre- and post-LAA angiogram in sinus rhythm during right
ventricular pacing. Of these, 89 patients (14 paroxysmal AF
and 75 non-paroxysmal) met all the pre-identified inclusion
criteria. These 89 patients were divided into three groups
according to the LAA delay or LAA electrical isolation during
ablation. Group 1 was composed by 24 patients where no
LAA delay or electrical isolation was present; group 2, where
LAA delay without electrical isolation was present (n = 47),
and group 3 was composed by patient with LAA electrical
isolation (n = 18). The LAA potential injury was evaluated
by the ejection fraction of the LA and of the LAA measured
by LA angiograms. No statistical differences in the patient
demographic and procedural characteristic among groups
were noted. Interestingly, at the 21 months follow-up, only 3
patients (17 %) in group 3 ( LAA electrical isolation) had
recurrence when compared to 11 (23 %) in group 2 (LAA
delay but no isolation), and 12 (50 %) in group 1 (no LAA
delay or isolation) (P = 0.028). In multivariate analysis, only
diabetes mellitus and LAA potential delay were independent
predictors of AF recurrence (P = 0.021, P = 0.008,
respectively). Although this data shows that LAA delay is associated
with decreased recurrence, one must recognize that LAA
isolation and LAA delay share common physiology; hence, as
the authors appropriately addressed in the discussion, the
insufficient number of patients in the LAA isolation group may
be the reason for non-significance in terms of recurrence (47
vs. 18 patients, respectively). Of note, despite the immediate
post-ablation LA angiography showing severely decreased
LAA contractility in the LAA isolation cases compared to
the other patients, the values of LA ejection fraction (EF)
did not statistically differ among groups. The changes from
LAA EF1 (pre-ablation) to LAA EF2 (post-ablation) in each
of the three groups were significantly reduced (P < 0.001 for
groups 1, 2, 3, respectively). At the post-ablation
transesophageal echocardiogram (TEE), 16 patients in group 3 (LAA
isolation) underwent TEE 1 month after ablation to evaluate
LAA systolic function, detect thrombus formation, LAA flow
velocity, and transmitral E/A ratio. Only one of the 16 patients
lacked any detectable emptying velocity of the LAA. LAA
contractility was well preserved or mildly decreased in eight
patients (50 %), and the remaining patients had poor
contractility. No spontaneous echo contrast or thrombus was
observed in the LA or LAA. The authors data [
] are consistent
with our 2010 [
] series and demonstrate the relevance and
efficacy of LAA isolation to achieve freedom from AF at
follow-up without increasing the thromboembolic risk. The
BELIEF randomized trial [NCT01362738] has been recently
presented at the late breaking trial of the ESC 2015 [
clearly showed that the empirical electrical isolation of the
LAA improves the ablation outcome at follow-up of long
standing persistent (LSP) AF patients without increasing
complications. There is common BBELIEF^ that LAA does not
play a role in the initiation and maintenance of AF and that
LAA isolation could be dangerous. However, this was not
shown in the trial. Additionally, more recently, we presented
at HRS 2016 data from 1854 consecutive AF patients (84 %
non-paroxysmal AF) receiving LAA isolation along with PV
]. TEE at 6 months post-ablation follow-up
showed impaired LAA mechanics in 58 % of the patients. The
overall thromboembolic event rate was 0.08 and 2.26 % in on
and off oral anticoagulation (OAC) populations, respectively
(P < 0.001). Of the 14 patients with stroke, 12 (85.7 %) had
sub-therapeutic INR or discontinued their OACs for >5 days.
These results provide more evidence that LAA isolation is not
associated with higher risk of thromboembolic events even in
the presence of impaired LAA function as long as optimal
anticoagulation is maintained. For many years, several
treatment strategies have Bmade sense^ in the electrophysiology
field before we could realize they were actually wrong.
Dsotalol post-myocardial infarction, cardiac pacing for the
treatment of vasovagal syncope, class IC antiarrhythmic drug to
suppress PVCs, ventricular stimulation for hyperthrophic
cardiomyopathy, and amiodarone use to reduce mortality in
patients with left ventricular dysfunction represent all examples
of negative evidence based medicine, but Bcommon belief^
for clinicians. In the field of catheter ablation for AF, for a long
period of time, many assumed that only the PV triggering AF
had to be isolated. Only years after, clinical experience as the
guidelines and the consensus documents have agreed that all
PVs should be Bempirically^ isolated in patients undergoing
ablation for AF to increase success rate at follow-up. The final
results of the BELIEF randomized  trial will probably
answer the question of whether or not the LAA should be
always empirically isolated in patients with LSP AF to
improve clinical outcomes. The current paper by Hwan-Cheol
Park et al. [
] clearly shows the efficacy of LAA isolation.
Furthermore, the notion that Cox-Maze III surgery data have
demonstrated a 90 % success rate at maintaining sinus rhythm
and a low incidence of thromboembolic events with
successful LAA exclusion/excision over long-term follow-up is of
]. The present study reinforces the relevance of
the LAA as an important structure to be isolated irrespective
of the firing in persistent and LSP AF.
The main criticism against LAA electrical isolation is
its potential added thromboembolic risk. Our results,
including data from the BELIEF trial [
], and the
current paper by Hwan-Cheol Park et al.  demonstrate
that around 50 % of patients have a flow velocity within
normal range after LAA isolation and that with proper AC
no added stroke risk exists. Importantly, many of the
patients requiring LAA electrical isolation need long-term
AC due to their CHADS-VASc score >2 irrespective of
the LAA electrical status. In patients with abnormal flow
velocity, long-term AC or LAA closure device can be
In conclusion, we believe this is the price to pay to maintain
sinus rhythm. The question about love in Shakespeare’s play
Hamlet translates into LAA electrical isolation: to be isolated
or not to be isolated it is an easy answer in this author’s
Compliance with ethical standards
Conflicts of interest Dr. Di Biase is a consultant for Biosense Webster,
Stereotaxis, and St. Jude Medical, and has received speaker honoraria/
travel from Boston Scientific, Medtronic, Janssen, EPiEP, Biotronik, and
Pfizer. Dr Natale received speaker honorariums from Boston Scientific,
Biosense Webster, St. Jude Medical, Biotronik, and Medtronic, and is a
consultant for Biosense Webster St. Jude Medical and Janssen.
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