Adenosine administration during hybrid atrial fibrillation ablation to test dormant pulmonary vein conduction
J Interv Card Electrophysiol
Adenosine administration during hybrid atrial f ibrillation ablation to test dormant pulmonary vein conduction
Mindy Vroomen 0 1 2 3
Laurent Pison 0 1 2 3
Mark La Meir 0 1 2 3
Jos G. Maessen 0 1 2 3
Harry J. Crijns 0 1 2 3
0 Department of Cardiac Surgery and Cardiovascular Research Institute Maastricht, Maastricht University Medical Center , Maastricht , The Netherlands
1 Department of Cardiology, Maastricht University Medical Center , PO Box 5800, Maastricht , The Netherlands
2 Mindy Vroomen
3 Department of Cardiac Surgery, University Hospital Brussels , Brussels , Belgium
Background Adenosine administration after initial pulmonary vein isolation (PVI) reveals dormant conduction and predicts atrial fibrillation (AF) recurrence. Elimination of dormant conduction when present may increase a long-term success rate of AF ablation procedures. There are no studies till date using adenosine to reveal acute reconduction of pulmonary veins (PVs) after epicardial PVI during a hybrid AF ablation procedure. Methods We included 24 patients (21 male, 55 ± 9 years) undergoing hybrid ablation for symptomatic paroxysmal (n = 12) and persistent (n = 12) AF, using an epicardial bipolar radiofrequency clamp to perform PVI. All antiarrhythmic medications were discontinued 5 days prior to the procedure, except for patients on amiodarone. Thirty minutes after PVI and once sinus rhythm was obtained, a bolus of adenosine (12 to 36 mg) was administered intravenously. The subsequent response was assessed for each PV (n = 96) using an in situ circular mapping catheter. Results Dormant conduction (i.e., the reappearance of PV potentials during at least one beat) was seen in 1 out of 96 PVs (1%). If reconduction was seen, further endocardial ablation using a 3.5-mm irrigated tip catheter was performed until no more reconduction occurred after repeating the adenosine bolus. Conclusions Adenosine administration after PVI with the use of an epicardial bipolar radiofrequency clamp in the setting of hybrid AF ablation reveals acute reconduction in 1% of the PVs.
Atrial fibrillation; Pulmonary vein isolation; Ablation; Hybrid; Adenosine
The cornerstone of endocardial catheter ablation procedures
for atrial fibrillation (AF) is ablation at the ostium or antrum of
the pulmonary veins (PVs), with the endpoint of electrical
isolation of these veins from the left atrium (LA). The
rationale for this is the seminal observation by
Haissaguerre et al.
that AF was almost always triggered by ectopic beats
arising from the muscle sleeves of the PVs . The success
rate of PV isolation (PVI) in patients with paroxysmal AF is
greater than 80%. One of the most frequent reasons for AF
recurrence is PV reconduction [2, 3]. Adenosine may be used
following initial PVI to unmask dormant PV conduction .
Additional ablation at sites with acute reconnection may
improve single-procedure success rates [5, 6].
Although being a common practice during endocardial
catheter ablation procedures, there is no data about the safety,
feasibility, and efficacy of adenosine administration as a
strategy to assess for transient PV reconnection during hybrid
thoracoscopic surgical and transvenous catheter ablation
procedures for AF.
2.1 Patient characteristics
Twenty-four consecutive patients with symptomatic AF
underwent hybrid thoracoscopic surgical and transvenous
catheter ablation between September 2012 and January
2014. In this period, no stand-alone epicardial ablations, and
258 catheter ablations were performed in the same center.
Patients were eligible for a hybrid AF ablation based on one
or more of the following criteria: (1) previously failed catheter
ablation, (2) failure of at least one antiarrhythmic drug (AAD)
class I or III, (3) LA volume ≥29 ml/m2, (4) persistent or
longstanding persistent AF, or (5) patient preference for a hybrid
procedure instead of a percutaneous approach. All patients
underwent a transthoracic echocardiography, a cardiac
computed tomography, and a pulmonary function test
preoperatively. Definitions of paroxysmal, persistent, and
longstanding persistent AF; success and failure of ablation; and
follow-up monitoring were based on the Heart Rhythm
Society, European Heart Rhythm Association, and European
Cardiac Arrhythmia Society consensus statement .
2.2 Hybrid ablation procedure
The hybrid ablation procedure was undertaken in a manner as
described in detail elsewhere . Briefly, one working port
and two camera ports were inserted on both sides of the thorax
in order to open the pericardium and the transverse and
oblique sinuses during selective lung ventilation. Via the
femoral venous approach, a His bundle (St. Jude Medical, St.
Paul, Minnesota) and a coronary sinus catheter (Medtronic,
Minneapolis, Minnesota) were placed under fluoroscopy, and
transseptal puncture was performed with a long 8-F sheath
(SL0, St. Jude Medical) into the LA, followed by full
heparinization. The PVs were mapped and checked with a
circular mapping catheter (Lasso, Biosense Webster,
Diamond Bar, California). Antral isolation of the right and left
PVs as a pair was performed with a bipolar radiofrequency
(RF) clamp (AtriCure, West Chester, Ohio). Each application
had a duration of about 15 s, with a median output of 10 to
15 W. The endpoint for PV ablation was entrance and exit
block, documented by the circular mapping catheter. In case
of sinus rhythm after PVI, reinduction of AF was attempted
five times by pacing in the coronary sinus for 10 s at the
shortest cycle length resulting in 1:1 atrial capture. AF was
considered inducible if it lasted more than 1 min. If AF
became noninducible, isoproterenol was infused at rates of 10 to
30 μg/min. If AF had not terminated or still was inducible,
linear lesions were deployed. A roof line (connecting both
superior PVs) and an inferior line (connecting both inferior
PVs) were made epicardially using a bipolar RF pen or linear
pen device (Isolator Coolrail pen; AtriCure). These two linear
lesions, in combination with bilateral antral PVI, result in
complete electrical isolation of the posterior LA (box lesion).
Any conduction gap in these epicardial linear lesions was
ablated endocardially with a 3.5-mm cooled tip RF catheter
(Thermo Cool; Biosense Webster). If the patient was known to
have typical atrial flutter (AFL) or if this arrhythmia occurred
during the procedure, the cavotricuspid isthmus (CTI) was
ablated endocardially. If the right atrium was dilated
(>64 mL), two additional epicardial ablation lines were
placed: one encircling the superior caval vein and the other
connecting both caval veins. Patients still in AF after PVI and
deployment of linear lesions underwent electrical
cardioversion. The left atrial appendage (LAA) was excluded using a
clipping device (AtriClip; AtriCure). The indication for LAA
exclusion was a CHA2DS2-VASc score ≥2. The pericardium
was approximated with a stitch, and a chest tube was placed in
both pleural cavities.
2.3 Adenosine administration
At least 30 min after epicardial PVI and once sinus rhythm
was obtained with other ablation lesions and electrical
cardioversion if necessary, a Lasso catheter was placed sequentially
at the ostium of each PV and in the area of the box. If
bidirectional block was still present, a bolus of adenosine (12 mg at
least) was given intravenously for each PV. If necessary, this
bolus was repeated with a higher dose until at least one
blocked P wave occurred or a pause ≥3 s. Dormant conduction
was defined as the reappearance of PV potentials in a PV or in
the box during at least one beat. The PVs and box were also
checked for exit block after adenosine administration. In the
event of dormant conduction, selective endocardial ablation at
sites of reconduction was performed. After additional
endocardial ablation, adenosine administration was repeated.
2.4 Postablation care and follow-up
Low molecular weight heparin was started 6 h after the
procedure, and on the second postoperative day, acenocoumarol
was reinitiated. Patients restarted as soon as possible their
preoperative AAD regimens. Any symptomatic patient not
in sinus rhythm was cardioverted before the 3-month
followup visit. One patient had a pacemaker, which was used for
monitoring. The remaining patients underwent 7-day
continuous Holter monitoring at 3, 6, 9, and 12 months. If a 7-day
Holter monitoring was not available, patients underwent at
least 48- or 24-h Holter monitoring. According to the current
guidelines , success was defined as no episode of AF, AFL,
or any atrial tachycardia (AT) lasting more than 30 s off AAD
c l a s s I o r I I I a f t e r t h e 3 - m o n t h b l a n k i n g p e r i o d .
Acenocoumarol and AADs were discontinued if the
6month monitoring visit confirmed the absence of atrial
2.5 Statistical analysis
Data were prospectively entered into a database. Statistical
analysis was performed using SPSS version 22.0 (SPSS, Inc.,
Chicago, Illinois). Continuous variables are summarized with
means and standard deviations. Any episode of AF, AFL, or AT
lasting mor e than 30 s detected after the 3-month
postprocedural period by electrocardiography, pacemaker
interrogation, or 7-day, 48-h, or 24-h continuous Holter monitoring
performed at 3, 6, 9, and 12 months was considered failure.
3.1 Perioperative results
Twenty-four patients underwent a
hybrid procedure between
and October 2014. Twelve patients (50%)
underwent a prior PVI for AF (at a mean time of 2 years before
the hybrid ablation) and four patients (17%) an ablation for
AFL. At the beginning of each hybrid procedure, all PVs were
tested for exit and entrance block. In case of AF, the PVs were
only tested for entrance block. Only one of all 48 PVs was
isolated at an antral level in the patients who had a prior PVI
for AF. All AADs were stopped 5 days prior to the procedure
except for patients on amiodarone. Patients’ baseline
characteristics are shown in Table 1. Eleven patients had persistent AF
and one long-standing persistent AF. Eleven patients were in
AF at the start of the procedure. In all patients, we achieved a
bidirectional block of all the PVs with epicardial ablation (at
antral level) only. No endocardial touch-up was needed for
PVI. For the left-sided PVs, a mean of 7 ± 2 RF applications
was performed with a mean duration of 10 ± 4 s. For the
rightsided PVs, a mean of 7 ± 1 RF applications was performed with
a mean duration of 9 ± 4 s. In one patient, we did not deploy
any other lesion because no arrhythmia was inducible. A box
lesion was created epicardially in 23 patients. In 14 patients
(61%), we were able to demonstrate endocardial entrance and
exit block in the box during sinus rhythm. After endocardial
touch-up in nine patients (39%), we completed the box lesion.
Five patients needed an endocardial touch-up at the roof line
and four at both the roof and inferior line. In seven patients, we
created a bicaval line epicardially and isolated the superior
caval vein. The cavotricuspid isthmus was ablated
endocardially in four patients. The LAA was excluded in 12
patients. Four patients (patients #2, #5, #15, and #21) needed
electrical cardioversion at the end of the procedure to restore
sinus rhythm. All the other patients were in sinus rhythm.
3.2 Acute reconnection after adenosine administration
At the time the Lasso catheter was placed at the ostium of the
PV, all the PVs (n = 96) (24 left superior PVs, 24 left inferior
PVs, 24 right superior PVs, and 24 right inferior PVs), and
also the area of the box (n = 23), still displayed entrance and
exit block. In Table 2, the injected doses of adenosine are
outlined. Dormant conduction induced by adenosine
administration (i.e., the reappearance of PV potentials during at least
one beat) was seen in 1 out of 96 PVs (1%) (Fig. 1). It
occurred in patient #14 at the junction of the left superior PV
ostium with the roof of the LA. Additional endocardial
ablations were performed at this site (Fig. 2). Repeating the
administration of adenosine did not result anymore in acute
In one case (#13), no entrance block could be verified in the
box after the administration of adenosine. The endocardial
voltage map showed an incomplete roof and inferior line.
After endocardial touch-up, a bidirectional block was
All patients (100%) reached 1-year follow-up. At 1 year, 23
out of 24 patients (96%) were in sinus rhythm, with no
episodes of AF, AFL, or AT lasting longer than 30 s on office
(electrocardiogram) follow-up and Holter monitoring
(Table 1). Three patients (12.5%) were still on AADs, of
which one had AF, one experienced palpitations which later
appeared not to be AF, and one patient suffered AF in the
blanking period and wanted to use AAD a few months longer.
No deaths or conversion to cardiopulmonary bypass was
encountered. No patient demonstrated paralysis of the phrenic
nerve. One patient suffered from basilar artery thrombosis
after the procedure. The administration of adenosine did not
result in any significant hemodynamic instability nor
This study aimed to test the feasibility and efficacy of
administration of adenosine after epicardial ablation in the setting of
a hybrid AF ablation. The major findings were as follows:
The use of adenosine during hybrid ablation for AF is an
effective tool to check for dormant PV conduction at the
antral level after epicardial PVI
Adenosine reveals dormant conduction at the antral level
in only 1% of the PVs after epicardial PVI.
Pulmonary vein reconnection after initial PVI remains
the most important reason for AF recurrence in
paroxysmal AF . It is present in more than 80% of patients
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who undergo a repeat procedure [9, 10]. This
phenomenon still remains one of the BAchilles heels^ of modern
invasive electrophysiology. New energy sources and
balloon-based devices have been developed to improve
long-term results of PVI, but it is too early to draw
definitive conclusions [11, 12]. Contact catheter technology is
also promising and may provide more long-lasting
lesions, but there is no long-term data available yet .
Dormant conduction is the phenomenon of transiently
restored conduction through a previously isolated PV,
induced by an intravenous purinergic agonist such as
adenosine. The use of adenosine as a provocative measure to
unmask the presence of dormant conduction after PVI was
first studied by Arentz et al. in 2004 . They showed that
after successful ostial PVI, 25% of the studied PVs regained
electrical activity after the administration of adenosine. Since
this observation, the use of this drug during PVI procedures
became a common clinical practice. Datino et al. described
the mechanisms by which adenosine restores dormant PV
conduction by recording action potentials from canine LA
and PV cells . The restoration of conduction in damaged
but viable PVs is based on selective activation of the IKAdo
inward rectifier current, resulting in hyperpolarization of the
resting membrane potential. As PVs with dormant
conduction are characterized by less resting membrane
depolarization than veins without dormant conduction, the
adenosineinduced hyperpolarization will selectively restore excitability
in PVs with dormant conduction by removing
voltagedependent INa inactivation.
McLellan et al. published a systematic review on the use of
adenosine after PVI . Several interesting observations from
this paper are worth highlighting. Data from nonrandomized
and retrospective studies showed that patients undergoing
adenosine testing and ablation of reconnections had better
outcomes than patients in whom adenosine testing was not
used. However, in patients with acute reconnection after
adenosine and additional ablation at these sites, the occurrence of
recurrent AF tended to be higher than in patients without acute
reconnection. The reason for this finding remains unclear. A
possible explanation could be that acute reconnection is a
surrogate marker of the impossibility to create completely
transmural circular lesions, e.g., because of anatomic reasons
. The ADVICE trial is a prospective and randomized
study designed to analyze the effects of additional ablation
in PVs, showing acute reconnection after adenosine
administration in patients with paroxysmal AF. The recently published
results of this trial showed that this strategy unmasked
dormant PV conduction in 21% of the tested PVs and that
additional adenosine-guided ablation did improve arrhythmia-free
Fig. 1 Circular mapping
of PV potentials. a The
administration of 21 mg of
adenosine in patient #14 induced
transient AV block and the
transient reappearance of PV
potentials (black arrow) on the
circular mapping catheter (Lasso)
at the first blocked P wave. b
Twelve seconds later the PV
potentials disappeared (white
survival (69.4 vs. 42.3%) . However, these results could
not be confirmed in two also recently published trials in which
no significant reduction of recurrence in the adenosine-guided
ablation group could be found [17, 18].
Transient reconnection after successful endocardial PVI has
been described to occur in up to 35% of the PVs after the use of
adenosine . To the best of our knowledge, no study has
assessed the effects of adenosine administration after epicardial
PVI in a hybrid AF ablation setting, neither in an epicardial
setting. In our series of patients, only one single PV (1%)
showed dormant conduction. In this particular patient, it was
very difficult to guide the bipolar RF clamp completely around
the left PVs. The very upper part of the antrum of the left
superior PV (junction with the LA roof) never got in between
the jaws of the clamp. This might explain the fact why it was
not possible to create a completely transmural lesion
epicardially at this specific spot and the apparent entrance block
of this PV when checking with the endocardial Lasso catheter
as a result of incomplete injury. The fact that epicardial PVI
seems to result in significantly less dormant conduction might
be explained by the greater ability to create completely
transmural lesions compared to endocardial energy sources.
The epicardial application of bipolar and bilateral RF energy,
as used in this series, overcomes the heat sink by clamping the
tissue and excluding the effect of the circulating blood on
ablation, which seems to result in more persistent lesions [20, 21].
This means that the use of adenosine to reveal dormant
conduction might be questioned in epicardial AF ablations.
4.1 Study limitations
The small number of patients in this single-center study
prevents definitive conclusions. It remains unclear whether
additional endocardial application of RF at sites showing
acute reconnection improves long-term results. Prolonging
the waiting time after initial epicardial PVI may increase the
number of PVs with acute reconnection after adenosine.
Although only one of the PVs was isolated in the patients with
a previous catheter ablation procedure (tested at the beginning
of the hybrid procedure), it cannot be excluded that previous
catheter ablation f avorably influenced the results.
Furthermore, the creation of additional linear lesions (roof
and inferior line) connecting with antral PVI may influence
the occurrence of acute PV reconnection. The adenosine
testing thus must be interpreted in the light of these entire lesion
sets, which may have reduced finding dormant conduction.
Also, the role of general anesthesia may have played a role
in the low prevalence of PV reconnection.
Adenosine administration after PVI with the use of an
epicardial bipolar RF clamp in the setting of hybrid AF ablation
unmasks dormant conduction in 1% of the PVs.
Compliance with ethical standards
Conflict of interest
Mark La Meir and Laurent Pison are consultant for
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