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\begin{document}

\title{Mechanism of successful cryoballoon ablation of focal atrial tachycardia
originating from the left inferior pulmonary vein: a case report}



\author[1]{Atsushi Doi}%
\author[1]{Wataru Nakano}%
\author[1]{Tasuku Ashida}%
\author[1]{Takayuki Yamada}%
\affil[1]{Otemae Byoin}%


\vspace{-1em}



  
  \date{June 09, 2024}


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\selectlanguage{english}
\begin{abstract}
Atrial fibrillation (AF) is mainly initiated by arrhythmogenic triggers
originating from the pulmonary veins, and ganglion plexus often plays a
crucial role in the induction and maintenance of AF. In this report, we
describe a case of successful cryoballoon ablation of focal atrial
tachycardia originating from the left inferior pulmonary, in which vagal
response was observed, and discuss its tachycardia mechanism.%
\end{abstract}%



\sloppy


Mechanism of successful cryoballoon ablation of focal atrial tachycardia
originating from the left inferior pulmonary vein: a case report

Atsushi Doi, MD, PhD; Wataru Nakano, MD; Tasuku Ashida, MD; Takayuki
Yamada, MD.

Department of Cardiovascular Medicine, Otemae Hospital, 1-5-34 Otemae,
Chuo-ku, Osaka, 540-0008, Japan.

Correspondence to Atsushi Doi, MD, PhD.

Department of Cardiovascular Medicine, Otemae Hospital, 1-5-34 Otemae,
Chuo-ku, Osaka, 540-0008, Japan.

E-mail; adoi7abl@gmail.com

\textbf{Short title:} cryoballoon ablation of focal atrial tachycardia
originating from the left inferior pulmonary

\textbf{Keywords:} atrial tachycardia, cryoballoon ablation,
ganglionated plexus, left pulmonary vein

The authors have no funding sources to disclose.

The authors have no conflicts of interest to disclose.

\textbf{ABSTRACT}

Atrial fibrillation (AF) is mainly initiated by arrhythmogenic triggers
originating from the pulmonary veins, and ganglion plexus often plays a
crucial role in the induction and maintenance of AF. In this report, we
describe a case of successful cryoballoon ablation of focal atrial
tachycardia originating from the left inferior pulmonary, in which vagal
response was observed, and discuss its tachycardia mechanism.

\textbf{CASE REPORTS}

\textbf{Case presentation}

A 40 year-old woman who had undergone a left mastectomy and breast
reconstruction for breast cancer was admitted to our hospital because of
palpitations and dyspnea on exertion. A 12-lead electrocardiogram showed
atrial tachycardia (AT) with a positive notched P wave in leads I, II,
III, aV\textsubscript{F}, V1, and V2 (Figure 1A). A Holter electrogram
revealed incessant AT and transient atrial fibrillation (AF). A thoracic
echocardiogram indicated reduced contractility, with an ejection
fraction (EF) of 35\%. A radiofrequency ablation for AT was performed
due to severe discomfort caused by palpitations after obtaining informed
consent. AT with a constant atrial activation sequence constantly
appeared, and the cycle length during tachycardia varied between 260 and
310 ms (Figure 1B). Activation mapping of the AT was performed in the
left atrium (LA) using a three-dimensional mapping system (NavX, St.
Jude Medical, St. Paul, Minnesota, USA). The earliest AT activation site
was observed at the bottom of the left inferior pulmonary vein (LIPV)
ostium (Figures 2A and 2B). Because AF and AT were identified prior to
the procedure, we attempted PV isolation using a 28-mm cryoballoon (CB)
(Arctic Front, Medtronic, Minneapolis, Minnesota, USA). First, CB
ablation of the left superior PV (LSPV) orifice and antrum resulted in
the termination of AT 51 seconds after the temperature measured at the
balloon's base dropped below freezing (Figures 2C and 3A). Thereafter, a
single atrial extrastimulus with the same atrial activation sequence was
observed; however, AT was no longer induced. Subsequently, after the CB
ablation of the LIPV (Figure 3A), the atrial extrastimulus also
disappeared. In this case, CB ablation of the LSPV resulted in
termination and no induction of AT originating from the bottom of the
LIPV ostium. Hence, this study aimed to identify the mechanism of AT.

\textbf{Discussion}

AF is primarily initiated by arrhythmogenic triggers originating from
the PV. PV isolation is the cornerstone of AF ablation, and PVI with CB
ablation has been proven to be non-inferior to radiofrequency ablation
with regard to safety and clinical outcomes.\textsuperscript{1} In this
case, the AT was a focal tachycardia originating from the LIPV ostium.
Kistler et al. demonstrated that in the vast majority of AT originating
from the PVs, the tachycardia focus originated from the ostium of the PV
rather than from further distal PVs, in contrast to
AF.\textsuperscript{2} Wei et al. showed that CB ablation was an
effective and safe tool to treat AT originating from the
PVs.\textsuperscript{3} In this case, CB ablation of the LSPV resulted
in termination and no induction of the AT originating from the bottom of
the LIPV ostium. We hypothesized that the mechanism of AT initiation and
maintenance might be related to ganglion plexus (GP) hyperactivity near
the vicinity of the PV-LA junction.

Previous studies have shown that the intrinsic cardiac autonomic nervous
system (ANS), an epicardial neural system composed of GPs and a complex
network of interconnecting neurons, plays a crucial role in the
induction and maintenance of AF through both sympathetic and
parasympathetic nervous system stimulation.\textsuperscript{4} The GPs
act as an integration and interconnection system between the extrinsic
cardiac ANS nerves, originating from the central ANS and reaching the
heart through the mediastinum, and the rest of the intrinsic cardiac
ANS. The function of GPs is not only to modulate the autonomic interplay
between the extrinsic and intrinsic cardiac ANS, but also to
independently regulate cardiac electrical and mechanical functions
through the transduction of local signals. In LA, the major GPs are
located close to the PV-LA junction. GPs contain both sympathetic and
parasympathetic components. GPs activation creates intracellular calcium
overload and shortening of action potential duration, which in turn
results in early after depolarization and triggers firing in surrounding
atrial tissue or neighboring PVs, thereby causing initiation and
maintenance of AF.\textsuperscript{4} Vagal reactions manifesting as
bradycardia and hypotension have been reported as markers of GPs
modification during PVI.\textsuperscript{5} Vagal reactions during
CB-based PVI were reported to be frequent from 36 \% to 50 \%. PVI with
the 28-mm CB catheter is associated with a broad antral ablation area
that extends from the PV ostium toward the LA, thus increasing the
possibility of concomitant and extended GP
ablation.\textsuperscript{6}Yorgun et al. demonstrated that the patients
with vagal response during CB ablation had a lower incidence of AF
recurrence, suggesting modulation of the cardiac ANS through GP
modification.\textsuperscript{5} Other studies have suggested that
adding GP ablation to PV isolation may achieve better clinical outcomes
in patients with AF.\textsuperscript{7} These findings indicate that both
larger areas of transmural lesion formation and GP modification may
contribute to the efficacy of CB ablation. In this case, one minute
after CB ablation of the LSPV was completed, transient sinus arrest and
atrioventricular block due to the vagal response were also observed
(Figure 3B). Histological examination of the human heart has
demonstrated that the Marshall tract GP is located within the fat pad
anterior to the LSPV and LIPV, and the superior left GP is located on
the roof of the LA, medial to the LSPV.\textsuperscript{4} The
interruption of axons from these hyperactive GP to the LIPV by CB
ablation of the LSPV may have contributed to eliminating the initiation
and maintenance of this AT.

The present case highlighted termination and no induction of AT
originating from the LIPV and the vagal response was observed with CB
ablation of the LSPV. It could also be deduced that the mechanism of the
AT strongly involved the GPs hyperactivity.

\textbf{Acknowledgements}

We would like to thank Honyaku Center Inc. for English language editing.

\textbf{References}

\begin{enumerate}
\tightlist
\item
  Kuck KH, Brugada J, F\selectlanguage{ngerman}ürnkranz A, Metzner A, Ouyang F, Chun KR, Elvan
  A, Arentz T, Bestehorn K, Pocock SJ, Albenque JP, Tondo C; FIRE AND
  ICE Investigators. Cryoballoon or Radiofrequency Ablation for
  Paroxysmal Atrial Fibrillation. N Engl J 2016;374:2235-2245.
\item
  Kistler PM, Sanders P, Fynn SP, Stevenson IH, Hussin A, Vohra JK,
  Sparks PB, Kalman JM. Electrophysiological and electrocardiographic
  characteristics of focal atrial tachycardia originating from the
  pulmonary veins: acute and long-term outcomes of radiofrequency
  ablation. Circulation 2003;108:1968-1975.
\item
  Wei HQ, Guo XG, Zhou GB, Sun Q, Liu X, Luo B, Yang JD, Zhang S, Ma J.
  Long-term outcome of cryoballoon ablation versus radiofrequency
  ablation for focal atrial tachycardias originating from the pulmonary
  veins. J Interv Card Electrophysiol 2019;56:271-278.
\item
  Nakagawa H, Scherlag BJ, Patterson E, Ikeda A, Lockwood D, Jackman WM.
  Pathophysiologic basis of autonomic ganglionated plexus ablation in
  patients with atrial fibrillation. Heart Rhythm 2009;6:S26-34.
\item
  Yorgun H, Aytemir K, Canpolat U, \selectlanguage{polish}Ş\selectlanguage{english}ahiner L, Kaya EB, Oto A. Additional
  benefit of cryoballoon-based atrial fibrillation ablation beyond
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  Europace. 2014;16:645-651.
\item
  Su W, Kowal R, Kowalski M, Metzner A, Svinarich JT, Wheelan K, Wang P.
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  Scherlag BJ, Nakagawa H, Patterson E, Jackman WM, Lazzara R, Po SS.
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\end{enumerate}

\textbf{FIGURE LEGENDS}

\textbf{Figure 1}

Twelve-lead electrocardiogram during the atrial tachycardia of 105 bpm
with a positive notched P wave in leads I, II, III, aV\textsubscript{F},
V1, and V2.

Intracardiac electrograms during the atrial tachycardia with an unstable
cycle length of 260 to 310 ms.

I, aV\textsubscript{F}, V1 = surface electrogram; CS = coronary sinus;
RA = right atrium. The arrow marker indicates the initiation of atrial
tachycardia.\textbf{Figure 2}

Intracardiac electrograms of atrial tachycardia with catheter placement
in the left inferior pulmonary vein.

Activation map in left atrium during atrial tachycardia.

The earliest activation site of atrial tachycardia was observed at the
bottom of the left inferior pulmonary vein ostium.

Cryoballoon ablation of the left superior pulmonary vein orifice and
antrum resulted in termination of atrial tachycardia.

AT = atrial tachycardia; LAO = left anterior oblique view; LIPV = left
inferior pulmonary vein; LSPV = left superior pulmonary vein; PA =
postero-anterior view. The other abbreviations are as in Figure 1. The
arrow marker indicates the earliest activation site of atrial
tachycardia.\textbf{Figure 3}

Left panel: Fluoroscopic image of a circular mapping catheter placed at
the left inferior pulmonary vein ostium at the earliest activation site
of atrial tachycardia. Middle panel: Fluoroscopic image during
cryoballoon ablation of the left superior pulmonary vein. Right panel:
Fluoroscopic image during cryoballoon ablation of the left inferior
pulmonary vein.

The dotted line corresponds to the bottom of the left inferior pulmonary
vein.

Vagal response observed after the completion of cryoballoon ablation of
the left superior pulmonary vein. Transient atrioventricular block was
observed during left atrial appendage pacing due to the appearance of
sinus arrest.

The other abbreviations are as in Figure 1.\selectlanguage{english}
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