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\begin{document}

\title{Notched P-wave related to a conduction disturbance in a thoracic vein as
a potential arrhythmogenic substrate of atrial fibrillation}



\author[1]{Noriyuki Kobayashi}%
\author[1]{Teppei Yamamoto}%
\author[1]{Yuhi Fujimoto}%
\author[1]{Kenji Yodogawa}%
\author[1]{Yu-ki Iwasaki}%
\author[1]{Wataru Shimizu}%
\affil[1]{Nippon Medical School}%


\vspace{-1em}



  
  \date{May 24, 2024}


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\selectlanguage{english}
\begin{abstract}
A 65-year-old male underwent a second ablation procedure for recurrent
paroxysmal atrial fibrillation (AF). Twelve-lead ECG during sinus rhythm
exhibited biphasic and split P-wave with a prolonged duration, which
called notched P-wave (NPW). Radio-frequency applica-tion in the
coronary sinus (CS) resulted AF termination and elimination of
triggering ectopy with NPW disappearance. The CS musculature which
played a principal role in triggering and maintaining AF formed the NPW.
In patients with repetitive recurrent AF after the estab-lishment of the
PV isolation who exhibit NPW during sinus rhythm, the CS might be one of
the arrhythmogenic sources of AF.%
\end{abstract}%



\sloppy


\textbf{Keywords}

atrial fibrillation, notched P-wave, coronary sinus musculature

\textbf{Case description}

A 65-year-old man with a history of a circumferential PV isolation for
paroxysmal atrial fibrillation (AF) and sick sinus syndrome underwent a
second ablation procedure for recurrent paroxysmal AF. Twelve-lead ECG
during sinus rhythm exhibited biphasic and split P-wave with a prolonged
duration, which called notched P-wave (NPW, Figure 1A). Echocardiography
revealed a normal LV systolic and diastolic function and an LA diameter
of 31 mm. Written informed consent was obtained before the procedure. An
electrophysiological study was conducted in the fasting state and under
deep conscious sedation. Although the first component of the NPW was
formed by the total atrial activation including that of the LA
appendage, the timing of the second component of the NPW was identical
to that of the coronary sinus (CS) activation (Figure 1B). Activation
mapping during distal CS pacing using an electroanatomical mapping
system (CARTO3, Biosense Webster Inc., Diamond Bar, CA, USA)
demonstrated 2 remote earliest activation sites in the LA near the
anterolateral mitral annulus and inferior mitral annulus, respectively
(Figure 2A). The shortest interval between the pacing stimulation spike
to the LA was 45 ms suggesting selective local capture of the CS
musculature (Figure 2B). Reconnections of the left superior PV and right
inferior PV were also noted. AF was spontaneously initiated by an
ectopic beat and repeated immediate recurrences occurred after
electrical defibrillation even after the achievement of the PV
isolation. Complex fractionated atrial electrograms were recorded at the
LA lateral wall, LA appendage, and CS. Therefore, additional ablation at
the mitral annulus and LA lateral wall was performed, however, it did
not terminate the AF. The second component of the NPW remained unchanged
after the ablation. Radio-frequency applications in distal portion of CS
terminated AF and eliminated the ectopic beats (Figure 3) along with the
disappearance of the second component of the P-wave (Figure 1B).
Eventually, sinus rhythm was maintained, and AF was no longer induced by
programmed stimulation with or without isoproterenol.

\textbf{Discussion}

Biphasic and split P-wave prolongation during sinus rhythm have been
considered as an independent predictor of the development of AF and the
recurrence of AF after PV isolation.\textsuperscript{1-3} The P-wave
prolongation is considered mainly to be a result of an electric
conduction disturbance in the inter- or intra-atrium, and the second
component of the P-wave is considered to be formed by delayed activation
in the LA.\textsuperscript{4} Yanagisawa et
al.\textsuperscript{1}reported that the disappearance of NPW after a
previous PV isolation was predictor of a durable PV isolation and that
the P-wave duration was shortened after the PV isolation in patients
with NPW. Another report\textsuperscript{5} suggested that a prolonged
conduction time from the right atrium to the CS predicted the recurrence
of AF after catheter ablation. Therefore, a prolonged P-wave duration
might suggest not only an inter- or intra-atrial conduction disturbance
but also the presence of a conduction delay at the structures that have
electrical connections to the LA, leading to the development of an
atrial arrhythmogenic substrate. On the other hand, CS musculature
possesses arrhythmogenicity for triggering AF as well as other thoracic
vein and forms an arrhythmogenic substrate due to multiple myocardial
connections to the LA for maintaining AF.\textsuperscript{6} Catheter
ablation targeting a CS region is significantly associated with AF
termination and a prolongation of AF cycle length.\textsuperscript{6} It
has been reported that the additional ablation strategies beyond the PV
isolation fail to reduce the AF recurrence rate.\textsuperscript{7}

From the anatomic and electrophysiologic viewpoint, the volume of
cardiomyocytes in the CS musculature is small in comparison to that of
the rest of atrium, and the electrical contribution of the CS
musculature excitation on body surface ECG is limited. An electrical
propagation from the proximal to distal CS during sinus rhythm is masked
or fused by the LA excitation. However, in patients with a persistent
left superior vena cava which has a substantial volume of
cardiomyocytes, that causes changes in the P wave morphology, especially
in the terminal portion of the positive/negative in lead III with
significant left axis deviation.\textsuperscript{8} In addition, a
significant conduction disturbance between the atrium and CS unmasks the
excitation of the CS and also leads to a change in the P wave
morphology. In our present case, the timing of the activation at LA
appendage and lateral LA was identical to that of the first component of
the P-wave, and the timing of the CS excitation was identical to that of
the second component of the NPW even after the PV isolation (Figure 1B).
The results of the termination and suppression of AF, and the
disappearance of the second component of the P-wave with the RF
application in the CS, strongly suggested that the second component of
the P-wave was formed by the CS musculature activation and that the CS
musculature played an important role in triggering AF.

To the best of our knowledge, this is the first report showing an NPW
that was formed by the activation in the CS musculature which played a
principal role in triggering and maintaining AF. In patients with
repetitive recurrent AF after the establishment of the PV isolation who
exhibit NPW during sinus rhythm, the CS might be one of the
arrhythmogenic sources of the AF.

\textbf{Acknowledgement}

The authors thank Mr. John Martin for his linguistic assistance.

\textbf{References}

\textbf{1.} Yanagisawa S, Inden Y, Okamoto H, et al. Electrocardiogram
characteristics of P wave associated with successful pulmonary vein
isolation in patients with paroxysmal atrial fibrillation: Significance
of changes in P-wave duration and notched P wave. Ann Noninvasive
Electrocardiol. 2020;25:e12712.

\textbf{2.} Caldwell J, Koppikar S, Barake W, et al. Prolonged P-wave
duration is associated with atrial fibrillation recurrence after
successful pulmonary vein isolation for paroxysmal atrial fibrillation.
J Interv Card Electrophysiol. 2014;39:131-138.

\textbf{3.} Hayashi H, Horie M. Biphasic P wave in inferior leads and
the development of atrial fibrillation. J Arrhythm. 2015;31:376-380.

\textbf{4.} Antz M, Otomo K, Arruda M, et al. Electrical conduction
between the right atrium and the left atrium via the musculature of the
coronary sinus. Circulation. 1998;98:1790-1795.

\textbf{5.} Kanemaru Y, Arima Y, Kaikita K, et al. Elongation of the
high right atrium to coronary sinus conduction time predicts the
recurrence of atrial fibrillation after radiofrequency catheter
ablation. Int J Cardiol. 2020;300:147-153.

\textbf{6.} Haissaguerre M, Hocini M, Takahashi Y, et al. Impact of
catheter ablation of the coronary sinus on paroxysmal or persistent
atrial fibrillation. J Cardiovasc Electrophysiol. 2007;18:378-386.

\textbf{7.} Verma A, Jiang CY, Betts TR, et al. Approaches to catheter
ablation for persistent atrial fibrillation. N Engl J Med.
2015;372:1812-1822.

\textbf{8.} Ito-Hagiwara K, Iwasaki YK, Hayashi M, et al.
Electrocardiographic characteristics in the patients with a persistent
left superior vena cava. Heart Vessels. 2019;34:650-657.

\textbf{Figure legends}

\textbf{Figure 1 A:} Surface 12-lead ECG showing sinus rhythm with
notched P-wave (left, pre-procedure) and without notched P-wave (right,
post-procedure). \textbf{B:} The delayed coronary sinus (CS) potentials
are identical only to the second component of the notched P wave
(arrow). \textbf{C:} The notched P-wave disappeared after radio
frequency applications in the CS. The amplitudes of the CS potentials
were lower in intra-CS electrograms of post ablation. LA = left atrium.

\textbf{Figure 2 A:} Left lateral view of the activation map.
The\emph{blue circular tags} indicate the earliest activation sites and
the\emph{blue star tag} indicates the site where pacing was
performed.\textbf{B:} Pacing from the distal pair of electrodes of the
catheter placed in the coronary sinus (CS) exhibiting a potential by 45
ms delay from the stimulation spike on the mapping catheter (Map) placed
on the anterolateral wall of the mitral annulus. ABL = ablation
catheter.

\textbf{Figure 3 A:} Recordings during the radiofrequency (RF) energy
application. The arrhythmia was terminated by an RF application at a
distal site in coronary sinus (CS). \textbf{B:} Fluoroscopic image
during the successful RF application. The CS catheter was pulled back in
order to allow the ablation catheter (ABL) to be cannulated into the
distal CS. Eso = esophagus; LAA = left atrial appendage.\selectlanguage{english}
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