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\begin{document}

\title{Pulmonary vein isolation with ``ablation index'' via single trans-septal
crossing: Critical role of carina isolation.}



\author[1]{Raphael Rosso}%
\author[1]{Ehud Chorin }%
\author[1]{Arie Schwartz}%
\author[1]{Yuval  Levi}%
\author[1]{Aviram Hochstadt}%
\author[1]{Sami Viskin}%
\affil[1]{Tel Aviv Sourasky Medical Center}%


\vspace{-1em}



  
  \date{May 24, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Background. Pulmonary veins (PV) reconnection is the most common reason
for atrial fibrillation (AF) recurrence. The ablation-index is a marker
of ablation lesion quality which use achieves high percentages of first
pass isolation and improved results of AF ablation. Most operators use a
double trans-septal approach with confirmation of PV isolation with a
circular mapping catheter. In the present study we aimed to show that an
ablation-index guided procedure using a single trans-septal approach and
ablation catheter only would achieve adequate PV isolation while
demonstrating the critical role of the carina in PV isolation. Methods.
76 consecutive patients with paroxysmal AF: 34 patients underwent WACA,
32 patients underwent WACA+ (including empiric carina isolation) and 10
patients underwent a staged procedure of WACA followed by WACA+ in case
of lack of first pass isolation. All procedures were performed via
single trans-septal. Results. Compared to WACA-only, WACA+ increased the
odds of PV isolation from 65\% to 91\%, p=0.012. In WACA-only, ablation
of the carina was needed to achieve PV isolation. The role of the carina
was confirmed in 10 patients with sequential ablation. PV isolation was
confirmed by inserting a circular mapping catheter through the single
trans-septal sheath. At 18 months of follow-up {[}IQR 15.2-20.8
months{]}, freedom from AF was 84\% for the entire cohort. Conclusion.
Our study confirms the high success rate of PV isolation using ablation
index and shows that this can be achieved via single trans-septal
crossing. Our study confirms the role of the carina in PV isolation.%
\end{abstract}%



\sloppy


\textbf{Abstract.}

\textbf{Background.} Pulmonary veins (PV) reconnection is the most
common reason for atrial fibrillation (AF) recurrence. The
ablation-index is a marker of ablation lesion quality which use achieves
high percentages of first pass isolation and improved results of AF
ablation. Most operators use a double trans-septal approach with
confirmation of PV isolation with a circular mapping catheter. In the
present study we aimed to show that an ablation-index guided
procedure\emph{using a single trans-septal approach} and ablation
catheter only would achieve adequate PV isolation while demonstrating
the critical role of the carina in PV isolation.

\textbf{Methods.} 76 consecutive patients with paroxysmal AF: 34
patients underwent WACA, 32 patients underwent WACA+ (including empiric
carina isolation) and 10 patients underwent a staged procedure of WACA
followed by WACA+ in case of lack of first pass isolation. All
procedures were performed via single trans-septal.

\textbf{Results.} Compared to WACA-only, WACA+ increased the odds of PV
isolation from 65\% to 91\%, p=0.012. In WACA-only, ablation of the
carina was needed to achieve PV isolation. The role of the carina was
confirmed in 10 patients with sequential ablation. PV isolation was
confirmed by inserting a circular mapping catheter through the single
trans-septal sheath. At 18 months of follow-up {[}IQR 15.2-20.8
months{]}, freedom from AF was 84\% for the entire cohort.

\textbf{Conclusion.} Our study confirms the high success rate of PV
isolation using ablation index and shows that this can be achieved via
single trans-septal crossing. Our study confirms the role of the carina
in PV isolation.

\textbf{Introduction} :

Radiofrequency (RF) catheter ablation is an accepted therapy for
patients with symptomatic, drug-refractory, paroxysmal atrial
fibrillation (AF). A fundamental step during this ablation procedure,
involves performing electrical isolation of the pulmonary veins (PVs) by
creation of a set of circular lesions around the pulmonary veins antrum
(WACA).\textsuperscript{1-10} However, permanent and complete isolation
of all pulmonary veins is challenging. In fact, electrical reconnection
of the pulmonary veins is the most frequent finding when a second
ablation procedure is performed following recurrence of atrial
fibrillation.\textsuperscript{11-16} Therefore, technological
innovations that will improve the thoroughness of ablation during WACA
are continuously developed.

The Visitag module with ablation-index was recently integrated in the
Carto 3V4 mapping system (Biosense Webster, Inc, Diamond Bar, CA,USA) as
an indicator of ablation lesion quality. The ablation-index formula
incorporates contact force (CF), power and ablation-delivery time into a
single value that also takes into account catheter stability at the time
of RF delivery. In a prospective study, Das et. al showed that lack of
achievement of minimum values of ablation-index, at any given pulmonary
vein segments, was predictive of pulmonary vein reconnection at a
repeated electrophysiology study performed two months
later.\textsuperscript{17} More recently, Hussein et al. reported a 97\%
isolation of the pulmonary veins following a first pass of WACA when an
ablation index of 500 and 400 were used at the roof-ridge and the
posterior-inferior quadrants, respectively.\textsuperscript{18} In the
remaining 3\% of WACA with lack of first pass isolation, additional RF
delivery was needed and this was invariably at the carina
level.\textsuperscript{18} In these studies, a double trans-septal
technique was performed to allow for the introduction of a circular
mapping catheter along the ablation catheter in the left atrium, to
monitor and confirm PV isolation during WACA. Continuous recording of
the PV electrograms during WACA may represent a potential bias since the
operator could instinctively ablate longer of more diffusely in area of
WACA associated with changes in activation on the circular mapping
catheter or leading to PV isolation.

Limiting the number of trans-septal crossings during an ablation
procedure is important, particularly for safety reasons but also for an
economic perspective. We therefore performed the present study to show
that: 1) An ablation-index guided procedure \emph{using a single
trans-septal approach} would succeed in achieving complete acute PV
isolation while obviating the need for a double transeptal. 2) RF
ablation of the carina area is crucial for achieving complete PV
isolation. Accordingly, we tested the following new strategy: 1) WACA
based on the new ablatio-index was performed with a single trans-septal
puncture. 2) The completeness of pulmonary vein isolation was confirmed
with the ablation catheter. As part of the study protocol, at the end of
the procedure the ablation catheter was replaced by a standard circular
mapping catheter to confirm that the assessment of PV isolation made
with the ablation catheter is indeed correct. 3) We tested the
contribution of carina ablation to achieve acute complete PV isolation
by comparing the acute success rate (defined as first pass complete PV
isolation) among patients undergoing a standard WACA vs. patients
undergoing WACA plus carina isolation (WACA+).

\textbf{Methods} .

\textbf{Study patients.} The study included consecutive patients with
symptomatic, drug-refractory paroxysmal AF, referred for a first
ablation. All the procedures were performed by a single operator (R.R.)
experienced with atrial fibrillation ablation procedure, including the
use of contact-force sensing ablation-catheters and the use of Visitag
and ablation-index. The AF ablations were performed between December
2017 and April 2019. Outcome data were extracted from an institutional
review board-approved registry.

\textbf{Atrial fibrillation ablation technique.} The procedure was
performed under uninterrupted warfarin therapy (aiming for an INR of 2
on the day of the procedure) or after skipping a single dose of new oral
anticoagulants (NOAC). All antiarrhythmic agents, except amiodarone,
were discontinued before the procedure. A computerized tomography
angiogram (CTA) of the left atrium was performed before the ablation to
assess the left atrial size, PV anatomy and to exclude the presence of
left atrial appendage thrombi. Patients in whom the CTA could not
definitively exclude the presence of left atrial appendage thrombi
underwent a trans-esophageal echocardiogram (TEE) before or during the
procedure. The ablation procedure was conducted under general
anesthesia.

One decapolar and 1 quadripolar catheter were positioned in the coronary
sinus and the His bundle position through the right femoral vein. One
8.5F long sheath (SL1, St. Jude Medical, Minneapolis, USA) was
introduced into the left atrium with a single trans-septal puncture.
Intravenous bolus of heparin was injected intravenously just prior to
the trans-septal puncture and repeated as needed to maintain an
activated clotting time (ACT) of \textgreater{}350 seconds throughout
the procedure. All PVs were visualized by selective angiography. The PV
antrum was defined with angiography and the segmented left atrial CTA
imported in the Carto 3 mapping system (Biosense Webster). A Lasso
circular mapping catheter (Biosense Webster) was introduced through the
SL1 sheath into the left atrium for electrical mapping of the PVs and
then retrieved. At this point, an irrigated ablation catheter3.5-mm D-F
curve ablation catheter with smart-touch technology (Navistar
Thermocool, Biosense Webster) was introduced through the original SL1
sheath into the left atrium for ablation. In case of difficulties in
positioning the ablation catheter in the left atrium, the SL-1 sheath
was replaced with a steerable sheath (Agilis 8.5F, t. Jude Medical,
Minneapolis, USA). The ablation catheter was used to create a
fast-anatomic map (FAM) of the left atrium, to set landmarks (PV
drop-off points into the left atrium) necessary to merge the CTA scan of
the left atrium to the FAM (Carto Merge, Biosense Webster, Inc).
Ablation was performed with a ``point by point'' technique. Settings
were: catheter irrigation-flow rate of 18 mL/min, target temperature 45\selectlanguage{ngerman}°
and maximal energy of 25 W for the posterior atrial wall and 30 W for
the ridge and carina areas. During the ablation we aimed to achieve a
contact force of 10 to 50 grams at all times. RF energy was applied at
each ablation site using the automated lesion tagging ablation-index to
mark the location and efficacy of each lesion. The ablation-index
settings were: catheter stability position minimum-time of 5 seconds,
and maximum range 3-4 mm, minimum force 3 g, (the blue and yellow marks
give two different contact force values) and lesion tag of 2 mm. The
maximal RF time at each ablation site was 60 seconds. We aimed for a
minimum ablation-index value of 415 for the back wall and posterior half
of the carinas, 515 for the anterior ridge, roof, inferior quadrants and
anterior half of the carinas. We aimed for ablation dots that overlap
each other along the WACA. The exclusion of gaps in between the dots was
also evaluated with the use of the grid function on the mapping system.
The grid function identifies all areas where radiofrequency energy was
delivered including those were Visitag did not tag the ablation due to
poor catheter stability. This feature allows for better identification
of potential gaps hiding in between the Visitag dots.

\textbf{Ablation groups.} The first 34 patients underwent two WACA
ablation lesions, each one encircling the antrum of two ipsilateral
pulmonary veins (WACA group). A second group of 32 patients underwent,
in addition to the WACA ablation, also ablation along the carinas (WACA+
group) (fig.1). After realizing that the WACA+ plus had better results
in terms of PV isolation, we added a small third group of 10 patients
who underwent a staged procedure. For these 10 patients, we first
performed a standard WACA step. Upon completion of the WACA, the
presence of PV isolation was evaluated by placing the ablation catheter
at the carina, proximal to the WACA line. Isolation was assumed to be
present if pulmonary vein potentials were not recorded distal to the
WACA and exit block was demonstrated. In case of residual electrograms
recorded with the ablation catheter distal to the WACA, the location of
earliest activation was tagged on the mapping system. As for the
original 2 groups (WACA and WACA+ groups), the isolation was then
confirmed with the circular mapping catheter.

\emph{Ablation endpoint.} Upon completion of the ablation set, the
ablation catheter was withdrawn from the left atrium and replaced by a
lasso circular mapping catheter. The acute end-point of the procedure
was first pass electrical isolation of the PVs demonstrated by
disappearance of local PV electrograms and confirmed by standard pacing
maneuvers, to confirm entrance and exit block, with a lasso circular
mapping catheter. In case of lack of isolation, the conduction gaps were
tagged on the mapping system and additional RF ablation with the same
ablation index targets was delivered in the identified gap areas. At
this point the ablation catheter was once again exchanged for the
circular mapping catheter and PV isolation was checked again. In case of
lack of isolation, the same maneuver was repeated until the vein was
isolated. After a waiting period of 20 minutes from the last ablation,
each pulmonary vein was assessed for entrance and exit block. Each vein
was also assessed for the presence of dormant pulmonary vein-left atrium
connection with intravenous adenosine 18 mg injection. Patients with
evidence of dormant connections revealed by adenosine challenge,
received additional ablations according to the mapping catheter until
the connections were completely abolished.

\textbf{Post-procedure Care.} After the ablation procedure, patients on
warfarin received low molecular weight heparin until an INR of 2.0--3.0
was achieved. Warfarin was administered for at least 3 months in
patients with CHA2DS2VASc 0--1 score or indefinitely in patients with
CHA2DS2VASc of 2 or more. Patients previously treated with NOACs,
underwent the ablation after skipping one dose. The NOAC therapy was
restarted between 3-5 hours post procedure and continued for at least 3
months in patients with CHA2DS2VASc 0--1 score or indefinitely in
patients with CHA2DS2VASc of 2 or more. Antiarrhythmic therapy was
restarted immediately after the procedure and continued for 1 month.

\textbf{Follow-Up.} Clinical and electrocardiographic follow-up was
performed at 3, 6, 9, and 12 months, respectively, and every 6 months
thereafter. Holter monitoring was performed at 2- and 3-months post
procedure and then twice every 6 months. Holter recordings and
trans-telephonic monitoring were also performed when symptoms suggested
recurrence. Episodes of atrial tachycardia on Holter (number of
episodes, number of beats and heart rate) lasting less then 30 seconds
were analyzed for the prediction of atrial fibrillation recurrence. AF
recurrence was defined by the presence of symptoms suggestive of AF
and/or electrocardiographic documentation of\textgreater{} 30 seconds of
AF/atrial flutter/atrial tachycardia beyond the first 3 months after the
procedure off antiarrhythmic drugs AADs.

\textbf{Statistical methods.}

Continuous variables are shown as Mean ± SD or as Median {[}IQR{]} as
appropriate, while discrete variable as n(\%). Comparison of continuous
variables was preformed using Mann-Whitney U test, while comparison of
discrete variables using Fisher's exact test. Event free survival was
assed using Kaplan-Mayer curves, statistical significance of the
difference between curves was assessed using a log-rank test. Results
were considered significant when p\textless{}0.05. All calculations were
done using R version 3.5.0, R Foundation for Statistical Computing,
Vienna, Austria.

\textbf{Results.}

A total of 76 consecutive patients with symptomatic, drug refractory
paroxysmal AF were enrolled. The study group included 34 patients
undergoing WACA and 32 patients undergoing WACA+. Finally, 10 patients
underwent a staged procedure of WACA that was followed by WACA+ in case
of lack of first pass isolation with WACA only (Table 1). Procedural
time, dwell time, fluoroscopy time and radiofrequency time were not
different between the study (WACA and WACA+) groups (Table 2).

In contrast to a WACA only approach, the WACA+ approach (of
systematically performing ablation of the carina in addition to WACA)
increased the odds of achieving PV isolation from 65\% (22 of 34 in the
WACA group) to 91\% (29 of 32 in the WACA+ group, p=0.012). Analysis of
patients not achieving first pass PV isolation further demonstrated the
crucial role of the carina. In the WACA-only group, first pass isolation
was not achieved in 12 patients: in 7 patients (representing 20\% of the
WACA group and 58\% of the WACA not achieving first pass PV isolation),
the right carina had to be ablated to achieve right sided veins
isolation; in 3 patients, the left carina had to be ablated to achieve
left sided veins isolation; finally, in 2 (6.7 \%) patients both carinas
had to be ablated to achieve pulmonary veins isolation.

In the WACA+ group, first pass isolation confirmed with circular mapping
catheter was achieved in 29 (91\%) of patients. Two patients (9\%)
required additional ablations to achieve isolation. In the first, this
was delivered at the anterior ridge where the previous ablation reached
an ablation index value of 480, while in the second additional ablation
was required at the anterior carina.

Based on the results of the study group (WACA and WACA+ groups) pointing
out at the carina as a critical site that needs to be ablated to achieve
complete PV isolation, we added a small third group of 10 patients who
underwent a step-by-step ablation of WACA and carina. In group 3, before
the carina was ablated, first pass isolation was achieved in 2 patients
(20\%) patients only. In all patients the lack of isolation and its
location demonstrated with the ablation catheter was confirmed with the
circular mapping catheter. In the remaining 8 patients, the left carina,
the right carina and both carina areas, had to be ablated to achieve PV
isolation in 4 (40\%), 2 (20\%) and 2 (20\%) patients, respectively.

Adenosine challenge revealed dormant PV-LA connections in 5/34 (14.7\%)
in the WACA group, 4/32 (12.5\%) in the WACA+ patients and 1/10 (10\%)
in group 3 (p=NS). In 4 of 5 patients with dormant PV-LA connection
revealed by adenosine in group 1, the dormant connection was detected in
the 3 at the left carina, in 1 in the right carina and in 1 at the
anterior ridge. In group 2, the dormant connections were detected at the
left carina and the right carina in 2 patients each. In group 3 dormant
connection was detected at the left carina.

At the procedure termination, acute pulmonary vein isolation was
achieved in 100\% of pulmonary veins ablated in the three groups.

No major complications occurred in any of the patients enrolled.

At a mean follow up of 18 months {[}IQR 15.2-20.8{]}, freedom from
atrial fibrillation was 84\% for the entire cohort. In group 1 the
success rate was 76.5\% (26/34). In group 2 the success rate was 87.5\%
(28/32), (p=0.342). In group 3 the success rate was 90\% (9/10). In view
of the small number of patients, the success rate of group 3 was not
compared to that of group 1 and 2.

\textbf{Discussion.}

The present study confirms the high success rate of pulmonary vein
isolation using ablation index: Our long-term results, with freedom from
atrial fibrillation in 84\% of patients, are similar to those achieved
by other groups using ablation index.\textsuperscript{18-21}

Previous studies have shown a higher rate of first pass isolation using
ablation index compared to conventional ablation settings and force time
integral (FTI) and the need for ablation of the carina in case of lack
of first pass isolation.\textsuperscript{18 20 22} In all these studies,
the ablation was conducted with a circular mapping catheter positioned
at the pulmonary vein to confirm isolation during the ablation through
as double trans-septal approach. In contrast, in the present study we
demonstrate that a strategy of ablation solely based on the use of the
ablation catheter through \emph{a single trans-septal
puncture}consisting of \emph{WACA plus empiric carina ablation guided by
ablation index} , can reliably achieve high percentages of first pass
isolation. Moreover, the confirmation of pulmonary vein isolation can be
effectively performed with the use of the ablation catheter only by the
identification of residual electrograms distal to the WACA and by pacing
maneuvers demonstrating exit block. A strategy solely based on the use
of the ablation catheter via single trans-septal crossing, has several
potential advantages. Every trans-septal puncture potentially involves
important risk of complications in particular pericardial effusion and
tamponade, inadvertent puncture of the aorta or air
embolism.\textsuperscript{23-25} A single trans-septal puncture would
intuitively results in a lower incidence of complications. Also, use of
only an ablation catheter would results in reduction in procedural
costs. Finally, having only one (as opposed to two catheters) in the
left atrium, simplifies catheter manipulation during the ablation
procedure, particularly in small atria.

The role of carina ablation to achieve pulmonary vein isolation has been
previously reported\textsuperscript{26-29} and is here confirmed. In our
study first pass isolation was significantly higher in patients when the
strategy of WACA was complemented by carina ablation. This is probably
due to the presence of pulmonary vein muscular fibers connecting
ipsilateral veins at the carina.\textsuperscript{30 31} Indeed first
pass isolation was achieved in all but two patients in whom empiric
carina ablation was added to the WACA and in one of the two patients
with residual PV electrograms the residual connection was located at a
site on the anterior ridge where the AI didn't reach the target value of
515. Moreover, dormant PV-LA connections, revealed by adenosine
challenge, were mapped at the carina in all but one case. The presence
of dormant PV-LA connections at the carinas despite RF ablation this
area an ablation index between 415 and 515, and the need for additional
RF applications at this area, might be related to the epicardial nature
of the muscular sleeves connecting the ipsilateral PVs at the
carina\textsuperscript{30 31}.

\textbf{Limitations:}

Our study has potential limitations. The study is single center and was
non-randomized and therefore bias related to the strategy of ablation
applied for each patient cannot be excluded. Nevertheless, the findings
of the present study are important. A strategy of ablation based solely
on the use of ablation catheter with single trans-septal, ablation
guided by AI based on WACA and additional carina ablation can achieve
high rate of first pass isolation safely and with high long-term success
rate. Randomized, larger studies are needed to confirm the feasibility
of this approach.

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\textbf{Hosted file}

\verb`Table 1. Clinical  Characteristics.docx`  available at \url{https://authorea.com/users/357822/articles/480221-pulmonary-vein-isolation-with-ablation-index-via-single-trans-septal-crossing-critical-role-of-carina-isolation}

\textbf{Hosted file}

\verb`Table 2.Procedural data.docx`  available at \url{https://authorea.com/users/357822/articles/480221-pulmonary-vein-isolation-with-ablation-index-via-single-trans-septal-crossing-critical-role-of-carina-isolation}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Fig1-JCE2/Fig1-JCE2}

\end{center}
\end{figure}

\selectlanguage{english}
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