- Email: [email protected]
Pulmonary Vein Nonconduction
JACC: CLINICAL ELECTROPHYSIOLOGY
VOL. 2, NO. 1, 2016
ª 2016 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY ELSEVIER
ISSN 2405-500X/$36.00 http://dx.doi.org/10.1016/j.jacep.2015.10.001
EDITORIAL COMMENT
Pulmonary Vein Nonconduction A False Indicator of Durable Pulmonary Vein Isolation* André d’Avila, MD, PHD,a Arash Aryana, MS, MDb
D
urable isolation following pulmonary vein
examined the same phenomenon in a live canine
(PV) ablation may not be necessary for
model by intentionally creating transmural RF abla-
effective suppression of atrial fibrillation
tion lines with anatomic gap. The gap length was pro-
(AF) in certain patients with AF. However, most pa-
gressively decreased until there was conduction
tients are thought to benefit from durable PV isola-
block. The ablation line was then analyzed using
tion, because PV reconnection seems to by and large
magnetic resonance imaging and correlated with
underlie the mechanism of AF following catheter
histology. The authors similarly found that gaps
ablation (1). A recent study found that among
ranging between 1.8 and 5.5 mm (median of 4.1 mm)
patients undergoing $3 radiofrequency (RF) catheter
could exist while displaying acute conduction block.
ablations for AF, presence of durable isolation in
More recently, Miller et al. (5) showed that although
all PVs was only noted in w8% (2). It has been shown
electrical PV isolation could be achieved frequently
that in most cases, PV conduction recovery occurs
without completion of a circumferential RF ablation
rapidly, with as many as one-third of targeted PVs
line, more than one-fourth of these “isolated” PVs
and four-fifths of those that recover electrical
exhibited dormant conduction via the unablated
conduction reconnecting in as little as 30 min (3).
visible gaps in the ablation lesion set. These findings
Moreover, there still remains the possibility that
support the notion that reversible tissue injury may
conduction block may be observed despite presence
contribute to acute PV isolation that may not be
of a conduction gap. Ranjan et al. (4) created a
necessarily durable.
2-dimensional model of the cardiac syncytium simulating RF ablation lines with gaps of varying lengths,
SEE PAGE 14
conductivity, and orientation. The simulation model
In this issue of JACC: Clinical Electrophysiology,
showed that with normal conductivity in the gaps
Baldinger et al. (6) report on the findings of a similar
and RF ablation lines oriented parallel to the direc-
study conducted to characterize the relationship
tion of the conducting fibers, a maximum gap of
between PV excitability and acute entrance block in
1.4 mm could exist while exhibiting conduction block.
patients undergoing PV isolation as treatment for AF.
As the conductivity was decreased, the maximum
This study provides several important insights. First,
gap length with conduction block increased exponen-
the findings reaffirm that entrance block can be ach-
tially, such that at 67% of normal tissue conductivity,
ieved in w60% of PVs despite a visible anatomic gap
the maximum gap length exhibiting conduction block
measuring >10 mm within the RF ablation circum-
increased to 4 mm. Subsequently, the authors
ferential lesion set, once again demonstrating that an anatomically continuous line of RF applications is not necessary to achieve conduction block. Second, they
*Editorials published in JACC: Clinical Electrophysiology reflect the views
found that the initial loss of conduction commonly
of the authors and do not necessarily represent the views of JACC:
occurred when areas remote from the RF ablation line
Clinical Electrophysiology or the American College of Cardiology. From the aDepartment of Cardiology, Instituto de Pesquisa em Arritmia Cardiaca, Hospital Cardiologico, Florianopolis, SC, Brazil; and the bDepartment of Cardiology, Dignity Health Heart and Vascular Institute,
in the PVs lose excitability. That is, only approximately one-third of PVs remained excitable to pacing while exhibiting exit block despite the incomplete-
Sacramento, California. Both authors have reported that they have no
ness of the ablation line, whereas approximately two-
relationships relevant to the contents of this paper to disclose.
thirds showed loss of excitability even at sites remote
d’Avila and Aryana
JACC: CLINICAL ELECTROPHYSIOLOGY VOL. 2, NO. 1, 2016 FEBRUARY 2016:24–6
Pulmonary Vein Nonconduction?
from the ablation line despite the presence of a visible
consideration may be to pharmacologically challenge
gap. Hence, the latter may suggest an interconnection
patients intraprocedurally with an agent such as
between the PVs and the left atrial tissue. Third, the
adenosine in an attempt to uncover presence of
majority of PVs (83%) that required an anatomically
dormant conduction. In the recently published
complete RF ablation line to yield entrance block
ADVICE
remained excitable to pacing, suggesting that perhaps
Isolation to Target Dormant Conduction Elimination)
nonexcitability may contribute to the phenomenon of
trial (11), administration of adenosine successfully
conduction block. Lastly, loss of excitability to pacing
unmasked dormant PV conduction in 53% of patients
in PVs was more likely to occur if the anatomic gap
undergoing RF catheter ablation, which in turn was
was larger in the RF ablation line. The latter suggests
retargeted. Using such an approach, the authors
tissue edema or stunning as a potential mechanism
demonstrated a greater incidence of freedom from
leading to acute PV isolation in such a scenario. The
atrial arrhythmias during long-term follow-up with
finding that the tissue within the visible ablation gap
an absolute risk reduction of 27% (hazard ratio: 0.44).
was in fact excitable indicates that such a gap will fail
But to the contrary, the outcomes from the UNDER-
to serve as a permanent barrier to electrical conduc-
ATP (UNmasking Dormant Electrical Reconduction
(ADenosine
Following
Pulmonary
Vein
tion once the PV muscular sleeves regain conduction
by Adenosine TriPhosphate) trial (12) have in fact
recovery. These observations unequivocally suggest
disputed these findings. That is, although adminis-
that presence of acute PV entrance and exit block by
tration of adenosine in the latter study provided
itself is an insufficient endpoint of catheter ablation
further identification of dormant PV conduction in
of AF. Furthermore, these findings also offer an
approximately 28% of patients, nearly all of which
explanation for the high rate of PV conduction re-
(98%) were then retargeted, this did not translate into
covery commonly observed despite achieving the
long-term improvements in freedom from atrial
acute endpoints of entrance and exit block at the time
arrhythmias.
of PV isolation. As such, they are entirely consistent
In
summary,
entrance
and
exit
block
can
with the clinical experience and the published liter-
frequently occur in the presence of visible anatomic
ature on the long-term outcomes of PV isolation and
gaps within the RF ablation lesion set prior to
AF ablation. For instance, in the GAP-AF study (7), of
completion of a circumferential PV ablation line. As
those who underwent a “complete” PV isolation, up
such, conduction block alone should not be used as a
to 70% of patients and 57% of PVs exhibited PV
steadfast indicator of durable PV isolation. Other
reconnection at 3 months. Willems et al. (8) also
confirmatory techniques such as administration of
discovered evidence of PV conduction recovery in
adenosine or pacing along the PV isolation lines may
77% of patients and 43% of all PVs at 3 months
prove helpful in improving the procedural efficacy.
post-ablation. Similarly, in the more contemporary
Lastly, additional research is needed to enhance our
EFFICAS I study (9), only 51% of PVs and 35% of
understanding of durable PV isolation and optimal
patients exhibited complete PV isolation at 3 months
lesion formation to improve the long-term outcomes
post-catheter ablation by operators blinded to RF
of catheter ablation of AF. The paper by Baldinger
force sensing data. These findings further emphasize
et al. (6) represents a great starting point.
the role for improving the quality of RF applications delivered through novel technologies such
REPRINT REQUESTS AND CORRESPONDENCE: Dr.
as force sensing (9). Alternatively, strategies such
André d’Avila, Cardiac Arrhythmia Service, Instituto
as pacing along the PV isolation line to ensure
de Pesquisa em Arritmia Cardiaca, Hospital Car-
nonexcitability
diologico,
seems
necessary
to
maximize
the long-term procedural efficacy (10). Another
Florianopolis,
SC
88030-000,
Brazil.
E-mail: [email protected].
REFERENCES 1. Anter E, Contreras-Valdes FM, Shvilkin A, Tschabrunn CM, Josephson ME. Acute pulmonary vein reconnection is a predictor of atrial fibrillation recurrence following pulmonary vein isolation.
3. Wang XH, Liu X, Sun YM, et al. Early identification and treatment of PV re-connections: role of observation time and impact on clinical results of atrial fibrillation ablation. Europace 2007;9:
J Interv Card Electrophysiol 2014;39:225–32.
481–6.
2012;14:653–60.
2. Lin D, Santangeli P, Zado ES, et al. Electro-
4. Ranjan R, Kato R, Zviman MM, et al. Gaps in
6. Baldinger SH, Kumar S, Barbhaiya CR, et al. The
physiologic findings and long-term outcomes in patients undergoing third or more catheter ablation procedures for atrial fibrillation. J Cardiovasc Electrophysiol 2015;26:371–7.
the ablation line as a potential cause of recovery from electrical isolation and their visualization using MRI. Circ Arrhythm Electrophysiol 2011;4: 279–86.
timing and frequency of pulmonary veins unexcitability relative to completion of a wide area circumferential ablation line for pulmonary vein isolation. J Am Coll Cardiol EP 2016;2:14–23.
5. Miller MA, d’Avila A, Dukkipati SR, et al. Acute electrical isolation is a necessary but insufficient endpoint for achieving durable PV isolation: the importance of closing the visual gap. Europace
25
26
d’Avila and Aryana
JACC: CLINICAL ELECTROPHYSIOLOGY VOL. 2, NO. 1, 2016 FEBRUARY 2016:24–6
Pulmonary Vein Nonconduction?
7. Kuck KH. Gap-AF—AFNET 1 trial. Paper presented at the European Heart Rhythm Association Europace 2013 Annual Scientific Sessions; May 16, 2013; Athens, Greece. 8. Willems S, Steven D, Servatius H, et al. Persistence of pulmonary vein isolation after robotic remote-navigated ablation for atrial fibrillation and its relation to clinical outcome. J Cardiovasc Electrophysiol 2010;21:1079–84. 9. Neuzil P, Reddy VY, Kautzner J, et al. Electrical reconnection after pulmonary vein isolation is contingent on contact force during initial
treatment: results from the EFFICAS I study. Circ Arrhythm Electrophysiol 2013;6:327–33. 10. Steven D, Sultan A, Reddy V, et al. Benefit of pulmonary vein isolation guided by loss of pace capture on the ablation line: results from a prospective 2-center randomized trial. J Am Coll Cardiol 2013;62:44–50. 11. Macle L, Khairy P, Weerasooriya R, et al., ADVICE Trial Investigators. Adenosine-guided pulmonary vein isolation for the treatment of paroxysmal atrial fibrillation: an international, multicentre, randomised superiority trial. Lancet 2015;386:672–9.
12. Kobori A, Shizuta S, Inoue K, et al., UNDER-ATP Trial Investigators. Adenosine triphosphate-guided pulmonary vein isolation for atrial fibrillation: the UNmasking Dormant Electrical Reconduction by Adenosine TriPhosphate (UNDER-ATP) trial. Eur Heart J 2015;36: 3276–87.
KEY WORDS atrial fibrillation, conduction block, pulmonary vein conduction, pulmonary vein isolation, pulmonary vein reconnection
VOL. 2, NO. 1, 2016
ª 2016 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY ELSEVIER
ISSN 2405-500X/$36.00 http://dx.doi.org/10.1016/j.jacep.2015.10.001
EDITORIAL COMMENT
Pulmonary Vein Nonconduction A False Indicator of Durable Pulmonary Vein Isolation* André d’Avila, MD, PHD,a Arash Aryana, MS, MDb
D
urable isolation following pulmonary vein
examined the same phenomenon in a live canine
(PV) ablation may not be necessary for
model by intentionally creating transmural RF abla-
effective suppression of atrial fibrillation
tion lines with anatomic gap. The gap length was pro-
(AF) in certain patients with AF. However, most pa-
gressively decreased until there was conduction
tients are thought to benefit from durable PV isola-
block. The ablation line was then analyzed using
tion, because PV reconnection seems to by and large
magnetic resonance imaging and correlated with
underlie the mechanism of AF following catheter
histology. The authors similarly found that gaps
ablation (1). A recent study found that among
ranging between 1.8 and 5.5 mm (median of 4.1 mm)
patients undergoing $3 radiofrequency (RF) catheter
could exist while displaying acute conduction block.
ablations for AF, presence of durable isolation in
More recently, Miller et al. (5) showed that although
all PVs was only noted in w8% (2). It has been shown
electrical PV isolation could be achieved frequently
that in most cases, PV conduction recovery occurs
without completion of a circumferential RF ablation
rapidly, with as many as one-third of targeted PVs
line, more than one-fourth of these “isolated” PVs
and four-fifths of those that recover electrical
exhibited dormant conduction via the unablated
conduction reconnecting in as little as 30 min (3).
visible gaps in the ablation lesion set. These findings
Moreover, there still remains the possibility that
support the notion that reversible tissue injury may
conduction block may be observed despite presence
contribute to acute PV isolation that may not be
of a conduction gap. Ranjan et al. (4) created a
necessarily durable.
2-dimensional model of the cardiac syncytium simulating RF ablation lines with gaps of varying lengths,
SEE PAGE 14
conductivity, and orientation. The simulation model
In this issue of JACC: Clinical Electrophysiology,
showed that with normal conductivity in the gaps
Baldinger et al. (6) report on the findings of a similar
and RF ablation lines oriented parallel to the direc-
study conducted to characterize the relationship
tion of the conducting fibers, a maximum gap of
between PV excitability and acute entrance block in
1.4 mm could exist while exhibiting conduction block.
patients undergoing PV isolation as treatment for AF.
As the conductivity was decreased, the maximum
This study provides several important insights. First,
gap length with conduction block increased exponen-
the findings reaffirm that entrance block can be ach-
tially, such that at 67% of normal tissue conductivity,
ieved in w60% of PVs despite a visible anatomic gap
the maximum gap length exhibiting conduction block
measuring >10 mm within the RF ablation circum-
increased to 4 mm. Subsequently, the authors
ferential lesion set, once again demonstrating that an anatomically continuous line of RF applications is not necessary to achieve conduction block. Second, they
*Editorials published in JACC: Clinical Electrophysiology reflect the views
found that the initial loss of conduction commonly
of the authors and do not necessarily represent the views of JACC:
occurred when areas remote from the RF ablation line
Clinical Electrophysiology or the American College of Cardiology. From the aDepartment of Cardiology, Instituto de Pesquisa em Arritmia Cardiaca, Hospital Cardiologico, Florianopolis, SC, Brazil; and the bDepartment of Cardiology, Dignity Health Heart and Vascular Institute,
in the PVs lose excitability. That is, only approximately one-third of PVs remained excitable to pacing while exhibiting exit block despite the incomplete-
Sacramento, California. Both authors have reported that they have no
ness of the ablation line, whereas approximately two-
relationships relevant to the contents of this paper to disclose.
thirds showed loss of excitability even at sites remote
d’Avila and Aryana
JACC: CLINICAL ELECTROPHYSIOLOGY VOL. 2, NO. 1, 2016 FEBRUARY 2016:24–6
Pulmonary Vein Nonconduction?
from the ablation line despite the presence of a visible
consideration may be to pharmacologically challenge
gap. Hence, the latter may suggest an interconnection
patients intraprocedurally with an agent such as
between the PVs and the left atrial tissue. Third, the
adenosine in an attempt to uncover presence of
majority of PVs (83%) that required an anatomically
dormant conduction. In the recently published
complete RF ablation line to yield entrance block
ADVICE
remained excitable to pacing, suggesting that perhaps
Isolation to Target Dormant Conduction Elimination)
nonexcitability may contribute to the phenomenon of
trial (11), administration of adenosine successfully
conduction block. Lastly, loss of excitability to pacing
unmasked dormant PV conduction in 53% of patients
in PVs was more likely to occur if the anatomic gap
undergoing RF catheter ablation, which in turn was
was larger in the RF ablation line. The latter suggests
retargeted. Using such an approach, the authors
tissue edema or stunning as a potential mechanism
demonstrated a greater incidence of freedom from
leading to acute PV isolation in such a scenario. The
atrial arrhythmias during long-term follow-up with
finding that the tissue within the visible ablation gap
an absolute risk reduction of 27% (hazard ratio: 0.44).
was in fact excitable indicates that such a gap will fail
But to the contrary, the outcomes from the UNDER-
to serve as a permanent barrier to electrical conduc-
ATP (UNmasking Dormant Electrical Reconduction
(ADenosine
Following
Pulmonary
Vein
tion once the PV muscular sleeves regain conduction
by Adenosine TriPhosphate) trial (12) have in fact
recovery. These observations unequivocally suggest
disputed these findings. That is, although adminis-
that presence of acute PV entrance and exit block by
tration of adenosine in the latter study provided
itself is an insufficient endpoint of catheter ablation
further identification of dormant PV conduction in
of AF. Furthermore, these findings also offer an
approximately 28% of patients, nearly all of which
explanation for the high rate of PV conduction re-
(98%) were then retargeted, this did not translate into
covery commonly observed despite achieving the
long-term improvements in freedom from atrial
acute endpoints of entrance and exit block at the time
arrhythmias.
of PV isolation. As such, they are entirely consistent
In
summary,
entrance
and
exit
block
can
with the clinical experience and the published liter-
frequently occur in the presence of visible anatomic
ature on the long-term outcomes of PV isolation and
gaps within the RF ablation lesion set prior to
AF ablation. For instance, in the GAP-AF study (7), of
completion of a circumferential PV ablation line. As
those who underwent a “complete” PV isolation, up
such, conduction block alone should not be used as a
to 70% of patients and 57% of PVs exhibited PV
steadfast indicator of durable PV isolation. Other
reconnection at 3 months. Willems et al. (8) also
confirmatory techniques such as administration of
discovered evidence of PV conduction recovery in
adenosine or pacing along the PV isolation lines may
77% of patients and 43% of all PVs at 3 months
prove helpful in improving the procedural efficacy.
post-ablation. Similarly, in the more contemporary
Lastly, additional research is needed to enhance our
EFFICAS I study (9), only 51% of PVs and 35% of
understanding of durable PV isolation and optimal
patients exhibited complete PV isolation at 3 months
lesion formation to improve the long-term outcomes
post-catheter ablation by operators blinded to RF
of catheter ablation of AF. The paper by Baldinger
force sensing data. These findings further emphasize
et al. (6) represents a great starting point.
the role for improving the quality of RF applications delivered through novel technologies such
REPRINT REQUESTS AND CORRESPONDENCE: Dr.
as force sensing (9). Alternatively, strategies such
André d’Avila, Cardiac Arrhythmia Service, Instituto
as pacing along the PV isolation line to ensure
de Pesquisa em Arritmia Cardiaca, Hospital Car-
nonexcitability
diologico,
seems
necessary
to
maximize
the long-term procedural efficacy (10). Another
Florianopolis,
SC
88030-000,
Brazil.
E-mail: [email protected].
REFERENCES 1. Anter E, Contreras-Valdes FM, Shvilkin A, Tschabrunn CM, Josephson ME. Acute pulmonary vein reconnection is a predictor of atrial fibrillation recurrence following pulmonary vein isolation.
3. Wang XH, Liu X, Sun YM, et al. Early identification and treatment of PV re-connections: role of observation time and impact on clinical results of atrial fibrillation ablation. Europace 2007;9:
J Interv Card Electrophysiol 2014;39:225–32.
481–6.
2012;14:653–60.
2. Lin D, Santangeli P, Zado ES, et al. Electro-
4. Ranjan R, Kato R, Zviman MM, et al. Gaps in
6. Baldinger SH, Kumar S, Barbhaiya CR, et al. The
physiologic findings and long-term outcomes in patients undergoing third or more catheter ablation procedures for atrial fibrillation. J Cardiovasc Electrophysiol 2015;26:371–7.
the ablation line as a potential cause of recovery from electrical isolation and their visualization using MRI. Circ Arrhythm Electrophysiol 2011;4: 279–86.
timing and frequency of pulmonary veins unexcitability relative to completion of a wide area circumferential ablation line for pulmonary vein isolation. J Am Coll Cardiol EP 2016;2:14–23.
5. Miller MA, d’Avila A, Dukkipati SR, et al. Acute electrical isolation is a necessary but insufficient endpoint for achieving durable PV isolation: the importance of closing the visual gap. Europace
25
26
d’Avila and Aryana
JACC: CLINICAL ELECTROPHYSIOLOGY VOL. 2, NO. 1, 2016 FEBRUARY 2016:24–6
Pulmonary Vein Nonconduction?
7. Kuck KH. Gap-AF—AFNET 1 trial. Paper presented at the European Heart Rhythm Association Europace 2013 Annual Scientific Sessions; May 16, 2013; Athens, Greece. 8. Willems S, Steven D, Servatius H, et al. Persistence of pulmonary vein isolation after robotic remote-navigated ablation for atrial fibrillation and its relation to clinical outcome. J Cardiovasc Electrophysiol 2010;21:1079–84. 9. Neuzil P, Reddy VY, Kautzner J, et al. Electrical reconnection after pulmonary vein isolation is contingent on contact force during initial
treatment: results from the EFFICAS I study. Circ Arrhythm Electrophysiol 2013;6:327–33. 10. Steven D, Sultan A, Reddy V, et al. Benefit of pulmonary vein isolation guided by loss of pace capture on the ablation line: results from a prospective 2-center randomized trial. J Am Coll Cardiol 2013;62:44–50. 11. Macle L, Khairy P, Weerasooriya R, et al., ADVICE Trial Investigators. Adenosine-guided pulmonary vein isolation for the treatment of paroxysmal atrial fibrillation: an international, multicentre, randomised superiority trial. Lancet 2015;386:672–9.
12. Kobori A, Shizuta S, Inoue K, et al., UNDER-ATP Trial Investigators. Adenosine triphosphate-guided pulmonary vein isolation for atrial fibrillation: the UNmasking Dormant Electrical Reconduction by Adenosine TriPhosphate (UNDER-ATP) trial. Eur Heart J 2015;36: 3276–87.
KEY WORDS atrial fibrillation, conduction block, pulmonary vein conduction, pulmonary vein isolation, pulmonary vein reconnection