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\begin{document}

\title{Ablation in Atrial Fibrillation with Ventricular Pacing Results in
Similar Catheter Stability and Arrhythmia Recurrence Compared to
Ablation in Sinus Rhythm with Atrial Pacing}



\author[1]{Matthew Dai}%
\author[1]{Chirag Barbhaiya}%
\author[2]{Anthony Aizer}%
\author[2]{Douglas Holmes}%
\author[3]{Scott Bernstein}%
\author[4]{David Park}%
\author[1]{Edward Kogan}%
\author[1]{Jonathan Hyde}%
\author[1]{Michael Spinelli}%
\author[3]{Larry Chinitz}%
\author[1]{Lior Jankelson}%
\affil[1]{NYU Langone Health}%
\affil[2]{New York University Medical Center}%
\affil[3]{New York University School of Medicine}%
\affil[4]{NYU Langone Medical Center}%


\vspace{-1em}



  
  \date{May 18, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Background: Improved catheter stability is associated with decreased
arrhythmia recurrence after atrial fibrillation (AF) ablation. Recently,
atrial voltage mapping in AF was demonstrated to correlate better with
scar as compared to mapping in sinus rhythm (SR). However, it is unknown
whether ablation of persistent AF in sinus rhythm with atrial pacing or
in atrial fibrillation with ventricular pacing results in differences in
catheter stability or arrhythmia recurrence. Methods: We analyzed 53
consecutive patients undergoing first-time persistent AF ablation with
pulmonary vein and posterior wall isolation: 27 were cardioverted,
mapped, and ablated in sinus rhythm with atrial pacing, and 26 were
mapped and ablated in AF with ventricular pacing. Ablation data was
extracted from the mapping system and analyzed using custom MATLAB
software to determine high-frequency (60Hz) catheter excursion as a
novel metric for catheter spatial stability. Results: There was no
difference in catheter stability as assessed by maximal catheter
excursion, mean catheter excursion, or contact force variability between
the atrial-paced and ventricular-paced patients. Ventricular-paced
patients did have significantly greater mean contact forces compared to
atrial-paced patients. One year arrhythmia-free survival was similar
between the atrial paced and ventricular paced patients (78\% vs 67\%, p
= 0.31). Conclusion: For patients with persistent AF, ablation in AF
with ventricular pacing results in similar catheter stability and
arrhythmia recurrence as compared to cardioversion and ablation in sinus
rhythm with atrial pacing. Given the improved fidelity of mapping in AF,
mapping and ablating during AF with ventricular pacing may be preferred.%
\end{abstract}%



\sloppy


\textbf{Background}

Radiofrequency (RF) ablation is a widely accepted and effective therapy
in the management of atrial fibrillation (AF)\textsuperscript{1--3}.
However, ablation of persistent atrial fibrillation remains a
therapeutic challenge, with recurrence rates of 30-60\% at one year, and
a frequent need for repeat ablation.\textsuperscript{4--7} Improved
catheter stability results in more consistent catheter-tissue contact,
both allowing for more effective transmural lesion formation and
preventing excessive force that could result in cardiac perforation.
Furthermore, improved catheter stability has been shown to be associated
with decreased arrhythmia recurrence following AF
ablation.\textsuperscript{8} Multiple strategies and techniques exist
for improving catheter stability, including high frequency jet
ventilation\textsuperscript{9--11}, steerable catheter
sheaths\textsuperscript{11--13}, and rapid atrial
pacing\textsuperscript{14}. However, catheter stability may be affected
by the underlying atrial rhythm. In patients with persistent AF,
achieving stable sinus rhythm and reliable atrial pacing may be
challenging prior to ablation, and pacing can only be performed in the
ventricle. It is unknown whether ablation in AF with ventricular pacing
versus in sinus rhythm (SR) with atrial pacing has any effects on
catheter stability, lesion quality, or clinical outcomes. In the present
study, we sought to compare the ablation characteristics and clinical
outcomes between patients with persistent AF who were mapped and ablated
in sinus rhythm with atrial pacing compared to atrial fibrillation with
ventricular pacing.

\textbf{Methods}

\textbf{Patient population}

We identified 53 consecutive patients at a single experienced
electrophysiology center who underwent first time RF ablation for
persistent AF. Of these, 27 were cardioverted then mapped and ablated in
sinus rhythm with atrial pacing, and 26 were mapped and ablated in AF
with ventricular pacing. Pacing was performed at a cycle length of
500-600ms, regardless of pacing site. All procedures were performed
under general anesthesia with high frequency jet ventilation.
Electroanatomical mapping was performed using either the circular
Lasso\selectlanguage{ngerman}\textsuperscript{®} or five-spine
PentaRay\textsuperscript{®}mapping catheter and the
CARTO3\textsuperscript{®} mapping system, version 4 (Biosense Webster
Inc., USA). Radiofrequency ablation was performed using the ThermoCool
SmartTouch\textsuperscript{®}force-sensing catheter (Biosense Webster
Inc., USA) using point-by-point ablation at a power of 50W. All patients
underwent pulmonary vein isolation (PVI) via wide antral circumferential
ablation of the left and right pulmonary veins, as well as posterior
wall isolation (PWI) via superior and inferior posterior wall lines
connecting the PVI lesion sets. Additional ablation of the left and
right carinas and/or residual electro-active areas within the posterior
wall were performed at the discretion of the operator. VisiTag lesion
stability settings were set to 2mm and 5s. Electrical isolation,
including entrance and exit block, was confirmed using differential
pacing and adenosine administration.

\textbf{Ablation analysis and catheter spatial stability}

Our group had recently described a method for precise analysis of
catheter-tip spatial stability, utilizing custom developed MATLAB script
applied on X-Y-Z axis tip position data acquired at
60Hz\textsuperscript{8}. Briefly, ablation data was extracted from
CARTO\textsuperscript{®} and analyzed using custom MATLAB script
(Mathworks, USA). For each ablation lesion, the mean 3-dimensional (3-D)
catheter position was calculated, and catheter excursion was defined as
the distance between the position of the catheter tip, sampled at 60Hz,
to the mean 3-D catheter position for the lesion. The mean and maximal
catheter excursion were then calculated for each lesion (see Figure 1).
Contact force variability was defined as the standard deviation of the
contact force for the lesion.

\textbf{Ablation and clinical endpoints}

The primary ablation endpoint was catheter stability, defined by mean
and maximal catheter excursion. The secondary clinical endpoint was one
year freedom from AF recurrence, following a 3-month blanking period.
Recurrence was defined as an atrial arrhythmia lasting longer than 30
seconds on ambulatory monitoring, or an atrial arrhythmia documented on
a standard 12 lead electrocardiogram. Recurrences within 3 months were
included if they necessitated a repeat ablation.

\textbf{Statistics}

All statistical analysis was performed using SPSS Statistics 26 (IBM
Corp., USA) and graphs were constructed using Prism 8 (GraphPad Software
Inc., USA). Continuous variables are expressed as mean ± standard
deviation, and categorical variables are expressed as percentages.
Normality of data samples was assessed using Shapiro-Wilk test. Two
sample hypothesis testing was performed using either Student's\emph{t}
-test if samples had normal distributions or Mann-Whitney\emph{U} test
if samples did not have normal distributions. Hypothesis testing for
categorical variables was performed using Fisher's exact test. For
Kaplan-Meier survival analysis, significance testing between groups was
performed using log-rank test.

All patients provided written informed consent for their procedures, and
all data collection and analysis was approved by the NYU Langone Medical
Center Institutional Review Board.

\textbf{Results}

\textbf{Catheter stability and ablation characteristics}

Baseline patient characteristics are provided in Table 1.
Ventricular-paced patients had significantly larger left atrial
diameters (4.9 ± 0.6cm vs 4.4 ± 0.8cm, p = 0.02), but similar left
atrial volume indices (41 ± 15mL/m\textsuperscript{2} vs 33 ±
8mL/m\textsuperscript{2}, p = 0.14), as well as greater time since
initial diagnosis of AF (4.4 ± 4.7yrs vs 2.5 ± 4.2yrs, p = 0.02),
compared to atrial-paced patients. Otherwise, there were no significant
clinical or echocardiographic differences between the two groups. With
respect to ablation characteristics (Table 2), there were no significant
differences in measures of catheter stability between the atrial-paced
and ventricular-paced patients. Atrial-paced patients had similar mean
catheter excursions (0.79 ± 0.15mm vs 0.77 ± 0.10mm, p = 0.62), maximal
catheter excursions (2.14 ± 0.45mm vs 2.15 ± 0.35mm, p = 0.94), and
contact force variability (4.2 ± 1.0g vs 4.1 ± 0.9g, p = 0.58), compared
to ventricular-paced patients (Figure 2). In addition, the two groups
had similar mean absolute impedance declines (7.7 ± 1.5ohms vs 7.1 ±
1.7ohms, p = 0.15) and percentage impedance declines (6.3 ± 1.2\% vs 5.8
± 1.2\%, p = 0.12). Ventricular-paced patients had greater average
contact forces than atrial-paced patients (14.5 ± 2.4g vs 13.0 ± 1.7g, p
= 0.02) as well as greater force-time-integrals (FTIs, 107 ± 20gs vs 95
± 15gs, = 0.02), which was driven by the greater contact forces.

\textbf{Procedure characteristics}

Compared to atrial-paced patients, ventricular-paced patients had a
nonsignificant trend towards increased total procedure time (169 ± 34min
vs 151 ± 36min, p = 0.08). There was no significant difference in RF
time (43 ± 13min vs 41 ± 13min, p = 0.64) (Table 3). There no procedural
complications.

\textbf{Arrhythmia recurrence}

48 of 53 (91\%) patients completed 1 year follow up, with an average
follow up length of 11.5 ± 1.9 months. Follow up length was similar
between the two groups. Overall 6 patients (11\%) had long term
continuous monitoring with an implantable device (PPM, ICD, or ILR),
equally distributed between groups. The remaining patients underwent 1
or 2-week ambulatory event monitoring at 3, 6, and 12 months
post-procedure (average 2.3 ± 1.1 monitors). 87\% of patients were
maintained on an anti-arrhythmic medication (Amiodarone, Dronedarone, or
Flecainide) for one month post-procedure, and 85\% of patients were
continued on long term beta-blocker and/or calcium channel blocker
therapy (Table 1). One year arrhythmia-free survival was similar between
the atrial-paced and ventricular-paced patients (78\% vs 67\%, p = 0.31)
(Figure 3).

\textbf{Discussion}

In this study, we aimed to determine if pacing site and the rhythm
during AF ablation affect procedural characteristics, and most
importantly catheter stability. We have recently demonstrated that
improved spatial catheter stability is associated with lower rates of
arrhythmia recurrence after AF ablation\textsuperscript{8}. Therefore,
it is important to understand the interaction of the atrial rhythm
during AF ablation and catheter spatial stability.

Our data suggests that catheter ablation during atrial fibrillation with
ventricular pacing, compared to sinus rhythm with atrial pacing, does
not result in significant differences in high-resolution catheter
spatial stability and lesion quality. Despite the difference in the
underlying atrial rhythm, measures of catheter stability were similar
between the two groups. In fact, ventricular-paced patients had
significantly greater average contact forces (and subsequently greater
FTIs), suggesting maintaining adequate catheter-tissue contact may be
easier during atrial fibrillation, when there is less myocardial motion.
There were also no differences in impedance decline between atrial paced
and ventricular paced patients.

Ventricular-paced patients had longer procedure times and trended
towards a greater number of electrical cardioversions. This can be
explained by the fact that some patients in this group had unsuccessful
cardioversion attempts at the beginning of the procedure, which led to
the decision to perform ablation in AF with ventricular pacing instead.
All ventricular-paced patients in our study were successfully
cardioverted to sinus rhythm by procedure end.

Catheter ablation of persistent atrial fibrillation remains a
therapeutic challenge, with high recurrence rates and frequent need for
repeat ablations. The arrhythmogenic substrate in persistent atrial
fibrillation is complex and incompletely elucidated, and although the
pulmonary veins and posterior wall are frequently implicated, there is
no consensus regarding optimal ablation targets or
strategy\textsuperscript{15--19}. Whereas the majority of ectopic foci
in paroxysmal AF reside within the pulmonary vein-left atrial
interface\textsuperscript{20,21}, the mechanisms behind persistent AF
are more complex and often the result of long-standing atrial
remodeling\textsuperscript{22,23}. Underlying atrial myopathy and
fibrosis, particularly within the posterior wall of the left atrium, can
serve as additional triggers and propagators of persistent AF. Voltage
mapping can be performed to identify areas of scar and fibrosis,
although previous data has shown that voltage amplitudes are affected by
the underlying atrial rhythm\textsuperscript{24--26}. A recent study by
Qureshi et al. found that mapping during atrial fibrillation, compared
to sinus rhythm, may actually be more sensitive and specific in
identifying low voltage regions that correlate with atrial fibrosis on
cardiac MRI\textsuperscript{27}. More accurate intra-procedural voltage
mapping would provide invaluable information regarding identifying
arrhythmogenic substrate and refining ablation strategy.

Overall one year arrhythmia-free survival was 73\%, which is in line
with previous data for persistent AF ablation\textsuperscript{4,6,7} and
there was no significant difference in recurrence between the
atrial-paced and ventricular-paced patients. The ventricular-paced
patients had significantly greater LA diameters, time since AF
diagnosis, as well as trend toward greater LA volume indices and lower
LV ejection fraction. These measures have been shown to be associated
with increased arrhythmia recurrence\textsuperscript{28--31} thus sample
size may have confounded recurrence outcomes.

\textbf{Limitations}

This was a retrospective study of a consecutive cohort with a follow up
time of 1 year. The small sample size was insufficient for logistic
regression analysis to assess for predictors of arrhythmia recurrence.
Patients ablated in AF with ventricular pacing may represent a subset
with more complex substrate, evident by resistance to DCCV.

\textbf{Conclusions}

Ablation of persistent atrial fibrillation in atrial fibrillation with
ventricular pacing, compared to sinus rhythm with atrial pacing, results
in similar catheter stability and lesion quality as assessed by
impedance decline and ablation parameters. Given the recent evidence
suggesting voltage mapping during atrial fibrillation may provide more
accurate assessment of atrial fibrosis, it may be preferable, at least
in patients presenting in AF, to ablate during atrial fibrillation with
ventricular pacing, and defer cardioversion until after procedure
completion.

\textbf{Acknowledgements}

The authors would like to thank Mr. Morris Ziv-Ari (Biosense Webster
Inc., USA) for his assistance with MATLAB scripting.

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\textbf{Tables and Figures}

Table 1. Baseline Clinical Characteristics\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
& Overall (n = 53) & A-paced (n = 27) & V-paced (n = 26) &
\emph{p}\tabularnewline
\midrule
\endhead
Sex (\% male) & 74\% (39/53) & 74\% (20/27) & 73\% (19/26) &
1\tabularnewline
Age (yrs) & 63 \selectlanguage{ngerman}± 12 & 64 \selectlanguage{ngerman}± 10 & 62 \selectlanguage{ngerman}± 14 & 0.92\tabularnewline
BMI (kg/m\textsuperscript{2}) & 30.7 \selectlanguage{ngerman}± 6.5 & 29.3 \selectlanguage{ngerman}± 4.6 & 32.1 \selectlanguage{ngerman}± 7.8 &
0.12\tabularnewline
LVEF (\%) & 55 \selectlanguage{ngerman}± 12 & 57 \selectlanguage{ngerman}± 12 & 53 \selectlanguage{ngerman}± 13 & 0.11\tabularnewline
LA Diameter (cm) & 4.6 \selectlanguage{ngerman}± 0.7 & 4.4 \selectlanguage{ngerman}± 0.8 & 4.9 \selectlanguage{ngerman}± 0.6 &
0.02\tabularnewline
LA Volume Index (mL/m\textsuperscript{2}) & 37 \selectlanguage{ngerman}± 13 & 33 \selectlanguage{ngerman}± 8 & 41 \selectlanguage{ngerman}± 15 &
0.14\tabularnewline
Years Since AF Diagnosis & 3.4 \selectlanguage{ngerman}± 4.5 & 2.5 \selectlanguage{ngerman}± 4.2 & 4.4 \selectlanguage{ngerman}± 4.7 &
0.02\tabularnewline
CHA\textsubscript{2}DS\textsubscript{2}-VASc & 2.1 \selectlanguage{ngerman}± 1.7 & 2.0 \selectlanguage{ngerman}± 1.6 &
2.2 \selectlanguage{ngerman}± 1.7 & 0.78\tabularnewline
HTN & 62\% (33/53) & 59\% (16/27) & 65\% (17/26) & 0.78\tabularnewline
DM & 15\% (8/53) & 19\% (5/27) & 12\% (3/26) & 0.7\tabularnewline
CHF & 21\% (11/53) & 22\% (6/27) & 19\% (5/26) & 1\tabularnewline
CVA & 6\% (3/53) & 4\% (1/27) & 8\% (2/26) & 0.61\tabularnewline
Vascular Disease & 4\% (2/53) & 7\% (2/27) & 0\% (0/26) &
0.49\tabularnewline
OSA & 36\% (19/53) & 37\% (10/27) & 35\% (9/26) & 1\tabularnewline
Post-Ablation Medications & & & &\tabularnewline
Anti-arrhythmic & 87\% (46/53) & 81\% (22/27) & 92\% (24/26) &
0.42\tabularnewline
BB or CCB & 85\% (45/53) & 78\% (21/27) & 92\% (24/26) &
0.25\tabularnewline
Post-Ablation Monitoring & & & &\tabularnewline
ILR, PPM, or ICD & 11\% (6/53) & 11\% (3/27) & 12\% (3/26) &
1\tabularnewline
Number of Monitors & 2.3 \selectlanguage{ngerman}± 1.1 & 2.4 \selectlanguage{ngerman}± 1.0 & 2.1 \selectlanguage{ngerman}± 1.2 &
0.41\tabularnewline
\bottomrule
\end{longtable}

BMI = body mass index, LVEF = left ventricular ejection fraction, LA =
left atrium, AF = atrial fibrillation, HTN = hypertension, DM = diabetes
mellitus, CHF = congestive heart failure, CVA = cerebrovascular
accident, OSA = obstructive sleep apnea, BB = beta-blocker, CCB =
calcium channel blocker, ILR = implantable loop recorder, PPM =
permanent pacemaker, ICD = implantable cardioverter-defibrillator

Table 2. Ablation Characteristics\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
& Overall (n = 53) & A-paced (n = 27) & V-paced (n = 26) &
\emph{p}\tabularnewline
\midrule
\endhead
Count & 146 \selectlanguage{ngerman}± 44 & 136 \selectlanguage{ngerman}± 37 & 156 \selectlanguage{ngerman}± 49 & 0.10\tabularnewline
Lesion Duration (s) & 7.4 \selectlanguage{ngerman}± 0.8 & 7.4 \selectlanguage{ngerman}± 0.7 & 7.4 \selectlanguage{ngerman}± 0.8 &
0.53\tabularnewline
Average Force (g) & 13.7 \selectlanguage{ngerman}± 2.2 & 13.0 \selectlanguage{ngerman}± 1.7 & 14.5 \selectlanguage{ngerman}± 2.4 &
0.02\tabularnewline
Contact Force Variability (g) & 4.1 \selectlanguage{ngerman}± 0.9 & 4.2 \selectlanguage{ngerman}± 1.0 & 4.1 \selectlanguage{ngerman}± 0.9 &
0.58\tabularnewline
Max Power (W) & 51.1 \selectlanguage{ngerman}± 1.0 & 51.2 \selectlanguage{ngerman}± .4 & 50.9 \selectlanguage{ngerman}± 1.4 &
0.22\tabularnewline
Base Impedance (ohms) & 120 \selectlanguage{ngerman}± 14 & 120 \selectlanguage{ngerman}± 12 & 120 \selectlanguage{ngerman}± 16 &
0.90\tabularnewline
Impedance Decline (ohms) & 7.4 \selectlanguage{ngerman}± 1.6 & 7.7 \selectlanguage{ngerman}± 1.5 & 7.1 \selectlanguage{ngerman}± 1.7 &
0.15\tabularnewline
Percent Impedance Decline & 6.0 \selectlanguage{ngerman}± 1.2\% & 6.3 \selectlanguage{ngerman}± 1.2\% & 5.8 \selectlanguage{ngerman}± 1.2\% &
0.12\tabularnewline
FTI (gs) & 101 \selectlanguage{ngerman}± 19 & 95 \selectlanguage{ngerman}± 15 & 107 \selectlanguage{ngerman}± 20 & 0.02\tabularnewline
Mean Excursion (mm) & 0.78 \selectlanguage{ngerman}± 0.12 & 0.79 \selectlanguage{ngerman}± 0.15 & 0.77 \selectlanguage{ngerman}± 0.10 &
0.62\tabularnewline
Max Excursion (mm) & 2.15 \selectlanguage{ngerman}± 0.40 & 2.14 \selectlanguage{ngerman}± 0.45 & 2.15 \selectlanguage{ngerman}± 0.35 &
0.94\tabularnewline
\bottomrule
\end{longtable}

Contact force variability was defined as the standard deviation of the
contact force. FTI = force time integral

Table 3. Procedure Characteristics\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
& Overall (n = 53) & A-paced (n = 27) & V-paced (n = 26) &
\emph{p}\tabularnewline
\midrule
\endhead
RF Time (min) & 42 \selectlanguage{ngerman}± 13 & 41 \selectlanguage{ngerman}± 13 & 43 \selectlanguage{ngerman}± 13 & 0.64\tabularnewline
Total Procedure Time (min) & 160 \selectlanguage{ngerman}± 36 & 151 \selectlanguage{ngerman}± 36 & 169 \selectlanguage{ngerman}± 34 &
0.08\tabularnewline
Number of DCCVs & 1.0 \selectlanguage{ngerman}± 0.7 & 0.8 \selectlanguage{ngerman}± 0.6 & 1.2 \selectlanguage{ngerman}± 0.7 &
0.09\tabularnewline
[?]2 DCCVs (\%) & 19\% (10/53) & 11\% (3/27) & 27\% (7/26) &
0.18\tabularnewline
\bottomrule
\end{longtable}

RF = radiofrequency, DCCV = direct current cardioversion

Figure 1. Figure 1. Example ablation lesion set with excursion measures.
A) For each ablation lesion, catheter position was sampled at 60Hz. The
orange dotted trail represents all sampled positions during a single RF
lesion. Mean and maximal catheter excursion were calculated for each
ablation lesion, and the radius of each sphere represents the mean
catheter excursion for that lesion.

B) All patients underwent pulmonary vein isolation and posterior wall
isolation. Full lesion set is projected with the left atrium removed.

Figure 2. Measures of catheter stability in atrial-paced and
ventricular-paced patients. There was no significant difference in mean
excursion (A), maximal excursion (B), or standard deviation of contact
force (C) between the two groups. Ventricular paced patients had
significantly greater average contact force, compared to atrial paced
patients (\emph{p} = 0.02) (D).

Figure 3. One year arrhythmia free survival. There was no significant
difference in one year arrhythmia free survival between the atrial-paced
and ventricular-paced patients (78\% vs 67\%, \emph{p} = 0.31).

\textbf{Hosted file}

\verb`RFX.AV2 figures 5-8-2020.pptx`  available at \url{https://authorea.com/users/321186/articles/450487-ablation-in-atrial-fibrillation-with-ventricular-pacing-results-in-similar-catheter-stability-and-arrhythmia-recurrence-compared-to-ablation-in-sinus-rhythm-with-atrial-pacing}

\selectlanguage{english}
\FloatBarrier
\end{document}

