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\begin{document}

\title{Thrombus formation on the ablation line after pulmonary vein isolation
with a cryoballoon}



\author[1]{Yoshiki Kitazumi}%
\author[1]{Daisuke Yuji}%
\author[1]{Kouichi Nagashima}%
\author[2]{Akira Sezai}%
\author[1]{Masashi Tanaka}%
\affil[1]{Nihon Daigaku Igakubu Fuzoku Itabashi Byoin}%
\affil[2]{Nihon University}%


\vspace{-1em}



  
  \date{May 27, 2024}


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\selectlanguage{english}
\begin{abstract}
Catheter ablation is a widely accepted therapy for atrial fibrillation
(AF), of which stroke is a major complication. A stroke after catheter
ablation has been reported in numerous studies not only in the acute
phase but also in the chronic phase. A 66-year-old man with drug
refractory paroxysmal AF underwent catheter ablation. Fourteen months
later, the patient was diagnosed with cerebral infarction.
Transesophageal echocardiography detected an ovoid mass on the anterior
aspect of the right superior pulmonary vein atrium, where the previous
ablation was performed. We report a very rare case of left atrial
thrombus formation required surgical treatment 14 months after
cryoballoon ablation.Careful follow up with multimodalities is necessary
for the detection and diagnosis of chronic phrase thrombus formation.%
\end{abstract}%



\sloppy


Thrombus formation on the ablation line after pulmonary vein isolation
with a cryoballoon.

Yoshiki Kitazumi, MD, Daisuke Yuji, MD, PhD, Kouichi Nagashima, MD, PhD,
Akira Sezai, MD, PhD, Masashi Tanaka, MD, PhD

Department of Cardiovascular Surgery

Nihon University School of Medicine, Tokyo, Japan

Short running title: Ablation area thrombus formation

Address for correspondence: Kitazumi Yoshiki

Department of Cardiovascular surgery, Nihon University School of
Medicine

30-1 Ohyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan

Tel: +81-3-3972-8111

Fax: +81-3-3972-1098

E-mail: kitazumi.yoshiki@nihon-u.ac.jp

The authors declare no conflicts of interest associated with this
manuscript.

Abstract

Catheter ablation is a widely accepted therapy for atrial fibrillation
(AF), of which stroke is a major complication. A stroke after catheter
ablation has been reported in numerous studies not only in the acute
phase but also in the chronic phase. A 66-year-old man with drug
refractory paroxysmal AF underwent catheter ablation. Fourteen months
later, the patient was diagnosed with cerebral infarction.
Transesophageal echocardiography detected an ovoid mass on the anterior
aspect of the right superior pulmonary vein atrium, where the previous
ablation was performed. We report a very rare case of left atrial
thrombus formation required surgical treatment 14 months after
cryoballoon ablation.Careful follow up with multimodalities is necessary
for the detection and diagnosis of chronic phrase thrombus formation.

Keywords: Left Atrial Thrombus, Atrial Fibrillation, Cryoballoon,
Catheter Ablation

Introduction

Catheter ablation by means of radiofrequency (RF) energy or cryoballoon
is a widely accepted, non-pharmacological therapy for atrial
fibrillation (AF). However procedure-related stroke is a serious
complication. Stroke is primarily caused by thromboembolism during the
ablation and further appropriate anticoagulant therapy is
crucial.\textsuperscript{1} Despite appropriate anticoagulation, the
stroke may be due to late left atrial (LA) thrombus formation in chronic
phase. Only two previous cases of LA thrombus post pulmonary vein
isolation (PVI) in the chronic phase have been reported.
\textsuperscript{2,3} We encountered a rare case of late detected LA
thrombus, following cryoballoon ablation.

Case presentation

A 66-year-old man with drug-refractory paroxysmal AF was referred to our
institution for initial catheter ablation. The patient posed a low risk
for stroke as he was without any concomitant diseases such as
hypertension or hyperlipidemia, only slight high body mass index of 27
kg/m2. (CHA2DS2-Vasc score: 1 point). Transthoracic echocardiography
(TTE) revealed slight LA dilation that was 39mm in diameter, and
transesophageal echocardiography (TEE) detected no LA thrombus. PVI was
performed with a 28 mm cryoballoon (ARC-Adv-CB, Arctic Front Advance;
Medtronic Inc., Minneapolis, MN9 guided by Ensite NavX Velocity mapping
(Abbott Laboratories, Abbott Park, IL). Intravenous heparin was
administered to maintain an activated clotting time of \textgreater{}
300s during the procedure. Although sustained AF remained inducible
after PVI, no additional LA ablation was performed. The patient was
managed with oral dose of 100 mg bepridil, 20 mg aprindine, and 5 mg
apixaban twice daily. Electrocardiogram (ECG) and Holter monitoring
detected no AF recurrence throughout follow-up.

Fourteen months after PVI, the patient arrived at our emergency
department with left arm paralysis. Brain computed tomography (CT) and
magnetic resonance imaging (MRI) revealed cerebral infarctions of the
subcortical regions of bilateral temporal lobes, suggestive of embolic
shower. ECG monitoring revealed no AF recurrence during hospitalization.
The patient continued to take bepridil and apixaban until admission. TEE
detected no thrombus in the LA appendage (LAA), but an ovoid mass 15 mm
in diameter was observed on the anterior aspect of the right superior PV
antrum (Fig 1A,B). Contrasted-enhanced CT revealed that the location of
the mass matched the previous ablation area (Fig 1C). Due to the episode
of embolic shower, surgical resection was performed to prevent further
cerebral infarction. Resection of the LA mass followed by Cox Maze
procedure and LAA resection was performed. The mass was 12 mm in
diameter above the ablation line, consisted of smoothly marginated soft
tissue, and was excised easily (Fig 2A,B). Histologic examination
revealed that the thrombus adhered to the LA endocardium. Layers of
organized thrombus were formed on endocardium and fibrin thrombi were
above them. Part of endocardium was replaced with necrotic tissue and
structure of muscle layer was collapsed. Epicardium consists loose
collagen fibers with inflammatory cells and neocapillaries are formed
(Fig 3). The patient was discharged given the favorable clinical course
after surgery. At his several follow up visit, the patient was managed
with 100 mg flecainide and 5 mg apixaban twice a day orally, and no
recurrence of stroke or AF ensued for 20 months.

Discussion

Cryoballoom ablation-related stroke in the acute phase occurs rarely,
with a reported incidence of 0.2\%\textsuperscript{4}. However, its
occurrence in the chronic phase has been unknown. Based on the data, its
incidence of LA thrombus formation associated with cryoballoon ablation
is estimated to be even lower. In the patient considered here, the
mechanism of LA thrombus formation appeared to differ from that of AF,
because the patient was at low risk for stroke and symptoms were managed
with apixaban. Also, TEE revealed no thrombus of the LAA. Histological
findings of thrombus adhesion to the LA endocardium, which had been
replaced with necrotic tissue, might also support our hypothesis. Based
on these findings, LA endothelium damage due to the cryo-thermal energy
might be a main cause of thrombus formation, although cryoballoon
ablation was likely less damaging to LA endothelium or endocardium than
ablation\textsuperscript{5}. Therefore, adding antithrombotic therapy to
anticoagulant therapy might be warranted in these patients. TEE is a
useful modality for detecting LA thrombus, most of which occur in the
LAA as a result of decreased outflow velocity. However, uncommon
thrombus locations such as the septum and previous PVI have been
reported\textsuperscript{2,3,6}. In these cases, differentiation of the
thrombus from the myxoma is crucial for determining a treatment
strategy. Determination of a narrow stroke between a thrombus and myxoma
is not always straightforward\textsuperscript{6,7}. Use of multiple
modalities, such as CT or MRI, might facilitate a correct diagnosis.

Conclusion

We encountered a rare case with late LA thrombus within a previous
cryo-ablation area. When monitoring the AF patients post-ablation,
clinicians should be aware of the possibility of late LA thrombus
formation despite appropriate anticoagulant therapy. Careful examination
with multiple modalities is often necessary for detecting and correctly
diagnosing an LA thrombus.

\textbf{Author Contributions}

Y. Kitazumi, MD: Drafting article

D. Yuji, MD: Critical revision of article

K. Nagashima: Critical revision of article

A. Sezai, MD, PhD: Critical revision of article

M. Tanaka, MD, PhD: Critical revision of article, Approval of article

\textbf{References}

\begin{enumerate}
\tightlist
\item
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\item
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\item
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\item
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\item
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\item
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\end{enumerate}

Figure Legend

Fig1 A,B,C

A,B A transesophageal echocardiography image of an ovoid mass 15 mm in
diameter (arrows) at the anterior aspect of the right superior pulmonary
vein antrum is shown.

C Contrast-enhanced computed tomography of location of the mass (red
arrow) revealed that it occurred at the previous ablation site.

Fig2 A,B

A A red, soft mass was observed at the cranial aspect of the right upper
pulmonary vein orifice, as seen in the preopereative examination.

B The mass had adhered to the previous ablation site and was easily
removed. Its size was 15 \selectlanguage{ngerman}× 12 mm.

Fig3

Hematoxylin Eosin statin of specimen from surgery is shown. Scale bar is
shown right above in the picture.

Layers of organized thrombus were formed on endocardium and fibrin
thrombi were above them. Part of endocardium was replaced with necrotic
tissue and structure of muscle layer was collapsed. Epicardium consists
loose collagen fibers with inflammatory cells and neocapillaries are
formed.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Fig-1A,B/Fig-1A,B}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Fig-1C/Fig-1C}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Fig-2A/Fig-2A}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Fig-2B/Fig-2B}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Fig-3/Fig-3}

\end{center}
\end{figure}

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