- Email: [email protected]
Clinical impact of ethanol infusion into the vein of Marshall on the mitral isthmus area evaluated by atrial electrograms recorded inside the coronary sinus
Accepted Manuscript Clinical Impact of an Ethanol Infusion into the Vein of Marshall on the Mitral Isthmus Area evaluated by Atrial Electrograms recorded inside the Coronary Sinus Naohiko Kawaguchi, MD, Kaoru Okishige, MD, FHRS, FACC, FJCS, Yasuteru Yamauchi, MD, Manabu Kurabayashi, MD, Tomofumi Nakamura, MD, Takehiko Keida, MD, Tetsuo Sasano, MD, Kenzo Hirao, MD, FJCS, Miguel Valderrábano, MD, FACC PII:
S1547-5271(19)30103-1
DOI:
https://doi.org/10.1016/j.hrthm.2019.01.031
Reference:
HRTHM 7896
To appear in:
Heart Rhythm
Received Date: 11 August 2018
Please cite this article as: Kawaguchi N, Okishige K, Yamauchi Y, Kurabayashi M, Nakamura T, Keida T, Sasano T, Hirao K, Valderrábano M, Clinical Impact of an Ethanol Infusion into the Vein of Marshall on the Mitral Isthmus Area evaluated by Atrial Electrograms recorded inside the Coronary Sinus, Heart Rhythm (2019), doi: https://doi.org/10.1016/j.hrthm.2019.01.031. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Clinical Impact of an Ethanol Infusion into the Vein of Marshall on the Mitral Isthmus Area
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evaluated by Atrial Electrograms recorded inside the Coronary Sinus.
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Short title: Impact of chemical ablation on the mitral isthmus
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Naohiko Kawaguchi, MD†, Kaoru Okishige, MD, FHRS, FACC, FJCS†, Yasuteru Yamauchi, MD†,
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Manabu Kurabayashi, MD†, Tomofumi Nakamura, MD†, Takehiko Keida, MD‡, Tetsuo Sasano, MD§,
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Kenzo Hirao, MD, FJCS§, Miguel Valderrábano, MD¶, FACC
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1-12-3 Shin-yamashita, Naka-ward, Yokohama, Japan, 231-8682
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‡
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2-24-18 Higashikoiwa, Edogawa-ward, Tokyo, Japan 133-0052
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Department of Cardiology, Edogawa Hospital
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Heart Center, Japan Red Cross Yokohama City Bay Hospital
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Heart Rhythm Center, Tokyo Medical and Dental University
1-5-45 Yushima, Bunkyo-ward, Tokyo, Japan 113-8519
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¶
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Methodist DeBakey Heart and Vascular Center and Methodist Hospital Research Institute
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6560 Fannin St, Suite 1144, Houston, TX 77030
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Address for correspondence: Kaoru Okishige, MD
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1-12-3 Shin-yamashita, Naka-ward, Yokohama, Japan, 231-8682
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Telephone: +81-45-628-6100
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E-mail: [email protected]
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Total words; 4999
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Conflicts of interest; none
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This research did not receive any specific grant from funding agencies in the public, commercial, or
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not-for-profit sectors.
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Abstract
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Background
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The left atrial myocardium (LAM) and coronary sinus (CS) musculature (CSM) generate atrial
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electrograms recorded inside the CS (AECSs). The vein of Marshall (VOM) courses the mitral isthmus
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(MI) and VOM ethanol infusion (EI-VOM) is useful to ablate it. Its detailed effect on the MI, which
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contains LAM, CSM and those connections, is unknown.
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Objective
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To investigate the impact of EI-VOM on the MI by assessing the AECS.
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Eighty-four consecutive patients with atrial fibrillation undergoing MI ablation with successful
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EI-VOM were included. After the EI-VOM, radiofrequency (RF) catheter touch-up ablation was
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performed at MI gap sites or inside the CS (RFCS), as needed, to achieve bi-directional conduction block
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(BCB). Ablation effects on the AECSs were evaluated during MI ablation procedure.
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Results
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The AECSs demonstrated double potentials consisting of low amplitude LAM components and high
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amplitude CSM components in 31 (37%) patients. Of those, 21/31 had a distal-to-proximal activation
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sequence of the LAM along with a proximal-to-distal activation sequence of the CSM during left atrial
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appendage pacing, suggesting a CSM isolation from the LAM due to electrical LAM-CSM disconnection,
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and only 2/21 required RFCS. The remaining 10 patients with a distal-to-proximal activation in both
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CSM and LAM, suggesting an incomplete CSM isolation and persistent LAM-CSM conduction, required
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RFCS. Overall, combined EI-VOM with RF created BCB at the MI in 78 (93%) patients.
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Conclusions
assessment of the AECSs can predict a requirement for RFCS.
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Key words: ethanol, vein of Marshall, mitral isthmus, catheter ablation, atrial electrogram
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An EI-VOM can ablate the LAM and myocardial connections between the LAM and CSM. Careful
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Introduction
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Creation of bi-directional conduction block (BCB) at the mitral isthmus (MI) is critical for the
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successful treatment of perimitral flutter, but can be technically challenging.1-2 Radiofrequency (RF)
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catheter ablation (RFCA) has been the standard therapeutic tool for MI ablation, but it is often difficult to
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achieve a successful BCB at the MI. Human hearts have epicardial myocardial connections between the
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left atrial myocardium (LAM) and coronary sinus (CS) musculature (CSM) with varying anatomical
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characteristics, some of which are wide and consist of multiple components.3 This complex anatomy
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makes endocardial ablation prone to failure, leading to the necessity for an RF application inside the CS
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(RFCS).1-2
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The vein of Marshall (VOM) has muscle bundles connecting the LAM and CSM, the so called
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Marshall bundles, which often harbor epicardial myocardial connections that can bypass endocardial MI
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ablation lesions.4-7 The VOM also has been proved to play an important role for the genesis, maintenance,
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triggering AF by ectopic foci, and a source of parasympathetic and sympathetic innervations regardless of
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paroxysmal or persistent AF.8-10 Ethanol infusion (EI) into the VOM (EI-VOM) produces chemical injury
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around the MI and has been reported to contribute to elimination of focal ectopy from the VOM,
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abolishment of local vagal responses, and facilitation in the achievement of MI conduction block.9-11
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Generally, atrial electrograms recorded inside the CS (AECSs) consist of a complex of far-field LAM
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potential and near-field CSM potential.12-15 During MI ablation, the AECSs sometimes split into the LAM
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and CSM components and demonstrate double potentials, suggesting a change in the excitation pattern at
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the MI.13-15 Therefore, a detailed assessment of the AECSs after the EI-VOM may give us novel
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information about the clinical efficacy of the EI-VOM for the MI ablation.
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AECSs.
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The aim of this study was to evaluate the clinical impact of the EI-VOM on the MI by assessing the
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Methods
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Inclusion and exclusion criteria
Consecutive patients undergoing the MI ablation concomitant with a successful EI-VOM were enrolled.
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Exclusion criteria included severe valvular disease, severe coronary artery disease, a left atrial diameter
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>55mm, and the existence of a thrombus in the left atrium (LA). Written informed consent was obtained
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from all patients prior to the ablation procedure. This study protocol was approved by the institutional
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review board and conformed to the ethical guidelines of the 1975 Declaration of Helsinki.
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From April 2017 to February 2018, de novo AF ablation was performed in patients with drug refractory
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AF. CS venography was performed in all patients as the first step of the procedure. If the VOM was
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identified by CS venography, EI-VOM was attempted prior to a pulmonary vein isolation (PVI). Then, a
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PVI using irrigated RF energy with a “point-by-point” ablation catheter or cryothermal energy with a
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cryoballoon catheter was performed. After successful PVI, a supplemental MI ablation using RF was
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undertaken.
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Procedural management
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The patients received conscious sedation with propofol combined with dexmedetomidine
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hydrochloride. A total of 5000 units of Heparin was administered immediately after a single transseptal
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puncture prior to the EI-VOM, and additionally given to maintain an activated clotting time between 300
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and 350 seconds during the ablation procedure. The surface ECG and bipolar endocardial
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electrocardiograms were filtered from 0.5 to 100 Hz and 30 to 150 Hz, respectively, and continuously
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recorded on a digital recording system (Prucka CardioLab XT recording systems, GE Healthcare,
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Chicago, IL).
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EI-VOM Procedure
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A 9Fr outer guiding sheath (CPS Aim SL, Abbott, Minneapolis, MN) was engaged into the CS via the
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right internal jugular vein. An occlusive CS venography was performed using a wedge balloon infusion
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catheter (Figure 1A). When the VOM was identified and considered to be suitable for an infusion of
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ethanol, a 7Fr inner guiding sheath (CPS Direct SL
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sheath and engaged at the VOM ostium. An angioplasty wire (0.014”) was advanced into the VOM,
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followed by a coronary angioplasty balloon catheter (1.5 to 2.0 mm diameter and 8.0 to 10 mm length,
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depending on the VOM size), and advanced in a “over-the-wire” fashion as deep as possible into the
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VOM. Selective, occlusive VOM angiography through the angioplasty balloon central lumen revealed the
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anatomical characteristics of the VOM (Figure 1B), and then 98% ethanol was slowly injected into the
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VOM for 90 seconds. Ethanol was infused starting from the most distal part of the VOM, then, the
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angioplasty balloon was slightly pulled back proximally, and a subsequent EI was performed (Figure 1C,
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1D). This procedure was carried on until the angioplasty balloon was finally positioned at the VOM
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ostium. The application number of EIs was 1 to 3 according to the VOM length. The amount of injected
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ethanol was 1.5 to 2.0 ml per infusion.
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, Abbott) was inserted through the outer guiding
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PVI procedure Both methods of the PVI by RFCA or a cryoballoon have been described previously.16-17 Briefly, in the
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case of the PVI by RFCA, two circular mapping catheters were placed in the superior and inferior PVs
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and the left and right ipsilateral PVs were circumferentially ablated by an externally irrigated catheter
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(FlexAbility, Abbott or Smart touch, Biosense Webster, Diamond Bar, CA).
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In the case of cryoballoon ablation, a 14Fr sheath (Flexcath Advance, Medtronic, Minneapolis, MN)
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and second-generation 28mm cryoballoon (Arctic Front Advance, Medtronic) were inserted to the LA.
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The inflated balloon was advanced against the orifice of the targeted PVs, and the freezing cycle was
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started for 3 minutes. No bonus freezing was performed.
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Supplemental MI ablation after the EI-VOM
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During left atrial appendage (LAA) pacing at a cycle length of 600ms, an endocardial bipolar voltage
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map around the MI after the EI-VOM and PVI was created utilizing a 3-dimensional mapping system
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(NavX, Abbott or CARTO3, Biosense Webster). A scar area was defined as bipolar endocardial voltage
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amplitudes of <0.1mV. Touch-up endocardial RF ablation was carried out at conduction gap sites along
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the VOM, where local LAM potential was still recorded. A decapolar mapping catheter was inserted into
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the CS and the distal tip of the electrode was located just septal to the endocardial MI ablation site. When
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endocardial ablation could not achieve successful MI conduction block in spite of abolishment of local
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LAM potential along the VOM, additional RFCS was subsequently performed targeting near-field CSM
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potentials which was inscribed earlier than any AECSs. An irrigated catheter (FlexAbility or Smart touch)
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was used for the touch-up MI ablation, and delivered with a maximum power of 35W for 30seconds
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during the endocardial RF application and 25W for 30seconds during the RFCS with a saline irrigation
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rate of 17-30 ml/min. The BCB at the MI was confirmed by differential pacing.18
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Methods of the AECS evaluation
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The AECSs recorded by a decapolar mapping catheter were continuously evaluated during the MI
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ablation procedure. If the AECSs split and demonstrated double potentials, the detailed characteristics of
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the double potential component were evaluated, and classified into the two types as follows according to
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previously described reports.12-15 Double potentials were defined as two discrete electrograms separated
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by an isoelectric line.
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Pattern 1: far-field LAM potentials with a low amplitude and low frequency preceded the near-field
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CSM potentials which had high amplitude and high frequency. LAA pacing demonstrated a
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distal-to-proximal activation sequence of the LAM followed by a proximal-to-distal activation sequence
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of the CSM (Figure 2A). The distal-mid portion of the CSM was isolated from the LAM due to electrical
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LAM-CSM disconnection (Figure 2B).
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Pattern 2: LAA pacing revealed a distal-to-proximal activation sequence of the CSM along with that
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of LAM activation (Figure 2C). The distal-mid portion of the CSM was not electrically isolated and
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connection between the LAM and CSM were still preserved (Figure 2D).
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Results
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Study population
One-hundred-fifteen consecutive patients (64.3±9.7 years-old, 83 male, 70 paroxysmal AF) underwent
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catheter ablation to treat AF. CS venography was performed in all patients. Of those 115 patients, a
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successful EI-VOM was performed in 84 (73.4%). In the remaining 31 patients, the EI-VOM could not be
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performed because of the absence, small size, or tortuosity of the VOM. A total of 84 patients undergoing
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the MI ablation with the EI-VOM were enrolled. The patient characteristics are shown in Table 1.
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Results of the PVI
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A successful PVI by an RFCA procedure or cryoballoon system was obtained in all patients. Of 11
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patients undergoing the PVI by RFCA, complete left inferior PV (LIPV) isolation was observed in one
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patient just after the EI-VOM, and RF applications at anterior LIPV aspect could be spared in three for
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LIPV isolation due to scar created by the EI-VOM.
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Results of the EI-VOM and supplemental MI ablation
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The length and ostial diameter of the VOM measured on the fluoroscopic images was 3.9±1.2 cm and
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2.1±0.6 mm, respectively. The total amount of infused ethanol was 4.1±1.0 ml. Voltage maps after the
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EI-VOM demonstrated scar areas along the VOM in all 84 patients, and viable LAM areas were mainly
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observed at mitral annular side (Figure 3). Therefore, majority of conduction gaps of the LAM was also
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located near the mitral annulus. The total time of the RF application at the MI was 4.8±4.6 minutes.
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Thirty-eight (45.2%) patients required additional 2.0±1.5 minutes of RFCSs. Eventually, a successful
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BCB at the MI was accomplished in 78 (92.9%) patients. There was no significant difference about a
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success rate of BCB at the MI between patients with the PVI by RFCA and by cryoballoon ablation
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(11/11 vs. 67/73, p=1.0). There were no significant differences between patients with paroxysmal and
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persistent AF about the VOM length (4.0±1.2 vs. 3.8±1.1 cm; p=0.63) and the diameter of the VOM
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ostium (2.1±0.4 vs. 2.2±0.6 mm; p=0.57).Ⅱ
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AECS evaluation
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Baseline LAA pacing prior to the EI-VOM was performed in the initial 11 patients, and it demonstrated
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just a single AECS component with a distal-to-proximal activation sequence, suggesting that both the
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LAM and CSM were activated simultaneously. Taking that observation into account, no baseline LAA
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pacing was performed in the following 73 patients.
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In 31 (36.9%) out of 84 patients, the AECSs demonstrated double potentials during MI ablation after the
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EI-VOM. Of those 31 patients, the double potentials were recognized solely after the EI-VOM without an
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RF application in 13 (41.9%) and during the 1st RF application in six (19.4%). An average of 0.8±2.2
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minutes of an RF application was needed for the double potentials to become apparent. The details of
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those 31 patients with double potentials were evaluated (Figure 4A). Pattern 1 and 2 type double
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potentials were recorded in 21 (67.7%) and 10 (32.3%) patients, respectively. In 19 of 21 patients with
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pattern 1, a BCB could be obtained at the MI with a 2.6±1.6 minute endocardial ablation without any
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RFCSs (Figure 5). All of the other 10 patients with pattern 2 required 1.7±1.5 minute additional RFCSs
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after the endocardial ablation (Figure 6). In two patients who required an RFCS in spite of pattern 1,
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subsequent RFCSs failed to obtain MI conduction block. Finally, repeated endocardial ablation could
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obtain it. All 31 patients with double potentials achieved a successful MI conduction block as a result.
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Of the patients with pattern 1, three initially had double potentials in the AECSs thought to be a
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preliminary step of pattern 1 (Figure 7A). The CSM potentials following the LAM occurred at the
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middle portion of the CS and propagated proximally and distally. Endocardial RF applications changed
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these AECSs to pattern 1 type double potentials (Figure 7B). The distal LAM-CSM myocardial
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connections were already electrically disconnected, however, those of the middle portion were still
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preserved (Figure 7C).12
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Additionally 53 patients out of the entire cohort did not have distinct double potentials during the MI
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ablation. Of those 53 patients, split AECSs were observed in 25 (47.2%), but did not satisfy the definition
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of double potentials. A successful MI conduction block was obtained in 47 (88.7%) patients.
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Follow-up data
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After the 1st procedure, 22/84 patients (9 with paroxysmal, 13 with persistent AF) had a recurrence of
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atrial tachyarrhythmia. Of those, 17 underwent a re-do procedure, and 9/17 had a persistent MI
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conduction block. Given that 2/17 patients failed to obtain successful MI conduction block at the 1st
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procedure, persistent MI conduction block was maintained in 9/15 (60%). Peri-mitral flutter was observed
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in two persistent AF patients. All eight patients with MI re-conduction, including those with peri-mitral
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flutter, underwent RF touch-up ablation in the MI area. Three patients required only an endocardial
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ablation, whereas the remaining five required additional RFCS. As a result, MI conduction block could be
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created in all these patients. The length and ostial diameter of the VOM was not related to the location of
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the conduction gaps. At the end of the re-do procedure, the non-inducibility of peri-mitral flutter was
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confirmed by atrial programmed stimulation.
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The detailed follow-up data in patients with double potentials was shown in Figure 4B.
Complications
Of a total of 84 enrolled patients, a pericardial effusion was observed in two and groin hematoma in
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three. A pericardiocentesis or blood transfusion was not required because their hemodynamic status was
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stable. Of the other 31 patients in whom the EI-VOM was abandoned, a dissection of the VOM was
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provoked by an angioplasty wire insertion into a tortuous VOM in two. In both patients, an EI-VOM was
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not performed, and no pericardial effusion was observed by transthoracic echocardiography.
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Discussion
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The major findings of the present study were: (1) an MI ablation with the EI-VOM could create BCB at
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the MI in approximately 93% of patients with an average of a 4.8 minute RF application, (2) double
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potentials in the AECSs were observed in 37% of patients, (3) of the patients with double potentials,
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approximately two-thirds had pattern 1 and the other one-third had pattern 2 type double potentials, and
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(4) pattern 1 required no RFCS in any except for two patients, whereas pattern 2 required an RFCS in
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all cases.
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Both the VOM and LAM-CSM myocardial connections including the Marshall bundles exist in the
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epicardial MI area. Therefore, the influence of the EI-VOM is supposed to involve not only the LAM
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around the MI, but also the LAM-CSM myocardial connections. Although several studies have reported
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cases of MI conduction using epicardial LAM-CSM myocardial connections,6-7,19 to the best of our
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knowledge, this is the first clinical study that systematically revealed the detailed influence of the
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EI-VOM on the myocardial structures around the MI.
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Comparison with previous studies
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A comparable or higher success rate of the MI ablation with a much shorter RF application duration
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was recognized in comparison with the previous studies that reported acute and chronic success rate of
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the MI ablation with some adjunctive procedures.20-22 Baez-Escudero, et al. reported a successful MI
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ablation in all patients by an approximately two minute RF application following the EI-VOM.11 The
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patient population of that study included 50 of 71 enrolled patients with a previous PVI and 30 with a
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previous MI ablation, whereas all patients in the present study underwent a de novo AF ablation. The
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difference in the patient characteristics between these two clinical studies might lead to the difference in
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the results of the success rate of the MI ablation and RF application time.
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Although the results about persistent maintenance of MI conduction block at re-do procedures in the
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present study was encouraging, follow up periods were relatively short and only patients undergoing
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re-do procedures could be investigated. Further prospective study which enrolls larger number of patients
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and investigates long-term outcome of the EI-VOM is required.
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Assessment of double potentials in the AECSs during the MI ablation
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Successful distal-mid CSM isolation from the LAM by the RFCA is difficult because electrical
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disconnection of epicardial LAM-CSM myocardium is required, and this anatomical feature is certainly
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associated with an incomplete MI conduction block even with multiple RF applications. We could prove a
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successful electrical disconnection of the myocardium between the LAM and CSM in 21 patients with
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pattern 1 type double potentials. Of those 21 patients, 19 could obtain a BCB at the MI by mean of only
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a 2.6 minute endocardial RF application. It suggested the electrical distal-mid CSM isolation effectively
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facilitated the MI ablation. It might be associated with persistent maintenance of the MI conduction block
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and prevention from a peri-mitral flutter, further evaluation of long-term outcome in large number of
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patients undergoing the EI-VOM is expected to prove that.
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Localization of conduction gaps
Considering the mechanisms of pattern 1 and 2 type double potentials, the critical conduction gap
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could be predicted. In patients with pattern 1, the conduction gaps were considered to exist at the LAM.
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In fact, all except for two patients did not require any RFCSs. In the case of pattern 2, an electrical
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isolation of the CSM was incomplete, thus all patients inevitably required additional RFCS. This concept
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could be applicable not only to the MI ablation following the EI-VOM but also to the conventional linear
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MI ablation connecting the LIPV and mitral annulus. However, the EI-VOM might provoke a separation
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of the LAM and CSM potentials more easily because of its potent ability to ablate the LAM and
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LAM-CSM myocardial connections at the same time.
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Clinical implications
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The present study revealed the ability of the EI-VOM to ablate the LAM and LAM-CSM myocardial
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connections. This ability will surely contribute to a creation of successful MI conduction block, especially
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in tough cases. Furthermore, the assessment of double potentials in the AECSs during the MI ablation
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informed us of the location of conduction gaps with a quite high accuracy. It could help us to avoid
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unnecessary RFCSs.
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Study limitations
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This study was a retrospective study, and study population was relatively small. The enrolled patients
were limited to those with successful EI-VOM.
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Voltage map was not performed at baseline, and it was undertaken following the EI-VOM and PVI.
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Therefore, low voltage area around the MI might include scars caused by the LA remodeling, especially
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in patients with persistent AF. Similarly, a comparison of the AECSs between before and after the
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EI-VOM could not be performed in all patients. Those factors might overestimate an efficacy of the
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EI-VOM alone.
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In the present study, touch up MI ablation was finally performed following the EI-VOM and PVI.
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Although the MI was ablated mainly by the EI-VOM and RF ablation, the PVI also might influence the
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MI conduction, especially near the LIPV.
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The clinical impact of the EI-VOM on the MI in patients without double potentials could not be
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investigated. Satisfactory results of the MI ablation were provided even in those patients. These facts
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might mean that the electrophysiological effects of the EI-VOM on the MI could not be observed
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presumably due to the anatomical characteristics in each case.
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Conclusions
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The EI-VOM could provide a high success rate in creating a BCB at the MI. The EI-VOM had an
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influence not only on the LAM, but also on the LAM-CSM myocardial connections. Careful assessment
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of the AECS could predict the localization of conduction gaps and the requirement for an RFCS.
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References
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myocardial extension and autonomic innervation on ligament of Marshall in humans. J Cardiovasc
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Marshall: A structual analysis in human heart with implications for atrial arrhythmias. J Am Coll
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conduction across the mitral isthmus via the vein of Marshall with High-density activation mapping.
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Importance of the vein of Marshall. J Cardiovasc Electrophysiol. 2015;26:352-3.
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Yoshitani K, Miyamoto T, Sato Y, Takatsu Y. Another gate keeper to protect the mitral isthmus?
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Kurotobi T, Ito H, Inoue K, Iwakura K, Kawano S, Okamura A, Date M, Fujii K. Marshall vein as
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arrhythmogenic source in patients with atrial fibrillation: correlation between its anatomy and
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electrophysiological findings. J Cardiovasc Electrophysiol. 2006;17:1062-7.
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Keida T, Fujita M, Okishige K, Takami M. Elimination of non-pulmonary vein ectopy by ethanol
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infusion in the vein of Marshall. Heart Rhythm. 2013;10:1354-6.
10. Valderrabano M, Chen HR, Sidhu J, Rao L, Ling Y, Khoury DS. Retrograde ethanol infusion in the
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vein of Marshall: regional left atrial ablation, vagal denervation and feasibility in humans. Circ
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12. Antz M, Otomo K, Arruda M, Scherlag BJ, Pitha J, Tondo C, Lazzara R, Jackman WM. Electrical
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conduction between the right atrium and the left atrium via the musculature of the coronary sinus.
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13. Shah AJ, Pascale P, Miyazaki S, et al. Prevalence and types of pitfall in the assessment of mitral
isthmus linear conduction block. Circ Arrhythm Electrophysiol. 2012;5:957-67.
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14. Takatsuki S, Extramiana F, Hayashi M, Leenhardt A. Conduction through the lateral mitral isthmus:
block or pseudoblock. J Cardiovasc Electrophysiol. 2008;19:98-9.
15. Matsuo S, Yamane T, Hioki M, Narui R, Tanigawa S, Date T, Yoshimura M. Double potentials of
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coronary sinus during the mitral isthmus ablation. J Cardiovasc Electrophysiol. 2012;23:1037-9.
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16. Okishige K, Aoyagi H, Ihara K, Iwai S, Nakamura T, Yamashita M, Katoh N, Hasegawa T,
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Kawaguchi N, Keida T, Sasano T, Hirao K. Reappraisal of the clinical implications of adenosine
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triphosphate in terms of the prediction of reconnection sites in cases with electrical isolation of the
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pulmonary veins. J Interv Card Electrophysiol. 2015;44:171-8.
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17. Okishige K, Aoyagi H, Kawaguchi N, et al. Novel Method for Earlier Detection of Phrenic Nerve
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Injury during Cryoballoon Applications for Electrical Isolation of Pulmonary Veins in Patients with
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Atrial Fibrillation. Heart Rhythm. 2016;13:1810-1816
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18. Shah D, Haissaguerre M, Takahashi A, Jais P, Hocini M, Clementy J. Differential pacing for
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distinguishing block from persistent conduction through an ablation line. Circulation.
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2000;102:1517-1522.
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19. Miyazaki S, Shah AJ, Haissaguerre M. Recurrent perimitral tachycardia using epicardial coronary
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sinus connection to bypass endocardial conduction block at the mitral isthmus. Circ Arrhythm
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Electrophysiol. 2011;4:e39-41.
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20. Huemer M, Wutzler A, Parwani AS, Attanasio P, Matsuda H, Blaschke F, Boldt LH, Haverkamp W.
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Comparison of the anterior and posterior mitral isthmus ablation lines in patients with perimitral
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annulus flutter or persistent atrial fibrillation. J Interv Card Electrophysiol. 2015;44:119-29.
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21. Hocini M, Shah AJ, Nault I, et al. Mitral isthmus ablation with and without temporary spot occlusion
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of the coronary sinus: a randomized clinical comparison of acute outcomes. J Cardiovasc
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Electrophysiol. 2012;23:489-96.
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22. Okubo K, Kuwahara T, Takigawa M, et al. Impact of anteroinferior transseptal puncture on creation
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of a complete block at the mitral isthmus in patients with atrial fibrillation. J Interv Card
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Electrophysiol. 2017;48:317-325.
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Table 1: Clinical characteristics of the study population
Age, years
64.8±10.2
62 (74)
Paroxysmal AF† (%)
50 (60)
AF duration, months
37.6±45.5
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PVI‡ by cryoballoon (%)
73 (87)
CHADS2 score
0.9±0.8
LA§ diameter, mm
§
LA: left atrium
LVEF: left ventricular ejection fraction
‡
359
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AF: atrial fibrillation
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62.4±11.5
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41.4±6.6
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Number of patients, n
PVI: pulmonary vein isolation
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Figure legends
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Figure 1: Fluoroscopic images of the procedure regarding the EI-VOM.
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(A): CS venography. (B): selective VOM venography, ethanol infusion in the distal (C) and proximal (D)
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portion of the VOM.
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CS, coronary sinus; EI-VOM, ethanol infusion into the vein of Marshall; VOM, vein of Marshall
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Figure 2: Electrocardiograms and schemes of the double potentials in the AECSs.
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(A), (B) are about pattern 1, (C), (D) are about pattern 2.
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(A): The activation sequence of the LAM and CSM was oriented in opposite directions, respectively.
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(B): The activation pattern was directed from lateral to septal across the LAM endocardially and
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subsequently from septal to lateral through the CSM epicardially. The activation of the CSM potential
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takes a detour due to an electrical disconnection between the LAM and CSM.
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(C): The CSM potentials were recorded with a distal-to-proximal sequence followed by the LAM
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potentials.
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(D): The activation pattern was directed from lateral to septal through the CSM epicardially and
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subsequently propagated to the LAM via the LAM-CSM myocardial connections.
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The activation of the LAM and CSM propagates along with the red and blue arrows, respectively.
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AECSs, atrial electrograms recorded inside the coronary sinus; CS, coronary sinus; CSM, coronary sinus
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musculature; LAA, left atrial appendage; LAM, left atrial myocardium; LIPV, left inferior pulmonary
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vein; MI, mitral isthmus
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Figure 3: (A), (B): Fluoroscopic images during the EI-VOM. (C), (D): Bipolar voltage maps after the
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EI-VOM and PVI.
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EI-VOM, ethanol infusion into the vein of Marshall; LAA, left atrial appendage; LIPV, left inferior
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pulmonary vein; MV, mitral valve; PVI, pulmonary vein isolation; VOM, vein of Marshall
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Figure 4: Flow chart of the patients with double potentials during the MI ablation regarding requirement
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for an RFCS (A) and the outcome (B).
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MI, mitral isthmus; RFCS, radiofrequency application inside the coronary sinus
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Figure 5: Representative case of pattern 1 type double potentials.
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(A): Pattern 1 type double potentials were recognized after the EI-VOM.
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(B): Endocardial ablation could create conduction block at the MI.
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(C),(D): Differential pacing from two different sites (CS1-2 and CS4-5) demonstrated the completion of
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the bi-directional conduction block at the MI. The interval from the pacing stimulus to the electrogram
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recorded by the ablation catheter (ABL1-2) located just on the lateral side of the block line during pacing
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from the distal bipole of the CS catheter (CS1-2) was longer than that during pacing from the proximal
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bipole of the CS catheter (CS4-5).
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(E): Fluoroscopic image during the endocardial MI ablation.
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ABL, ablation catheter; CS, coronary sinus; EI-VOM, ethanol infusion into the vein of Marshall; LAA,
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left atrial appendage; MI, mitral isthmus
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Figure 6: Representative case of pattern 2 type double potentials.
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(A): Before the MI ablation, the activation pattern of the LAM and CSM was mutually directed from
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lateral to septal
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(B): Pattern 2 type double potentials were recognized during the 2nd endocardial ablation, however,
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conduction block could not be created.
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(C): The local atrial activation time recorded in ablation catheter (ABL1-2) inside the CS was inscribed
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earlier than any bipole of the CS catheter.
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(D): A single radiofrequency application at that site inside the CS created MI conduction block.
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(E): Fluoroscopic image during ablation inside the CS.
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ABL, ablation catheter; CS, coronary sinus; CSM, coronary sinus musculature; LAA, left atrial
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appendage; LAM, left atrial myocardium; MI, mitral isthmus
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Figure 7: The preliminary stage of the pattern 1 type double potentials.
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(A): The LAM activation sequence was distal-to-proximal, and the following activation sequence of the
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CSM began close to the CS4-5 bipole.
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(B): The AECSs changed to pattern 1 type double potentials during endocardial ablation.
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(C): The activation pattern was directed from lateral to septal across the LAM endocardially and
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subsequently propagated to the CSM via the middle LAM-CSM myocardial connections. Further
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endocardial ablation disconnected the residual LAM-CSM myocardial connections close to the CS4-5
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bipole and then pattern 1 type double potentials could be observed.
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ABL, ablation catheter; AECSs, atrial electrograms recorded inside the coronary sinus; CS, coronary
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sinus; CSM, coronary sinus musculature; LAA, left atrial appendage; LAM, left atrial myocardium
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S1547-5271(19)30103-1
DOI:
https://doi.org/10.1016/j.hrthm.2019.01.031
Reference:
HRTHM 7896
To appear in:
Heart Rhythm
Received Date: 11 August 2018
Please cite this article as: Kawaguchi N, Okishige K, Yamauchi Y, Kurabayashi M, Nakamura T, Keida T, Sasano T, Hirao K, Valderrábano M, Clinical Impact of an Ethanol Infusion into the Vein of Marshall on the Mitral Isthmus Area evaluated by Atrial Electrograms recorded inside the Coronary Sinus, Heart Rhythm (2019), doi: https://doi.org/10.1016/j.hrthm.2019.01.031. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Clinical Impact of an Ethanol Infusion into the Vein of Marshall on the Mitral Isthmus Area
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evaluated by Atrial Electrograms recorded inside the Coronary Sinus.
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Short title: Impact of chemical ablation on the mitral isthmus
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Naohiko Kawaguchi, MD†, Kaoru Okishige, MD, FHRS, FACC, FJCS†, Yasuteru Yamauchi, MD†,
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Manabu Kurabayashi, MD†, Tomofumi Nakamura, MD†, Takehiko Keida, MD‡, Tetsuo Sasano, MD§,
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Kenzo Hirao, MD, FJCS§, Miguel Valderrábano, MD¶, FACC
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†
1-12-3 Shin-yamashita, Naka-ward, Yokohama, Japan, 231-8682
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‡
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2-24-18 Higashikoiwa, Edogawa-ward, Tokyo, Japan 133-0052
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§
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Department of Cardiology, Edogawa Hospital
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Heart Center, Japan Red Cross Yokohama City Bay Hospital
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Heart Rhythm Center, Tokyo Medical and Dental University
1-5-45 Yushima, Bunkyo-ward, Tokyo, Japan 113-8519
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¶
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Methodist DeBakey Heart and Vascular Center and Methodist Hospital Research Institute
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6560 Fannin St, Suite 1144, Houston, TX 77030
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Address for correspondence: Kaoru Okishige, MD
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1-12-3 Shin-yamashita, Naka-ward, Yokohama, Japan, 231-8682
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Telephone: +81-45-628-6100
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E-mail: [email protected]
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Total words; 4999
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Conflicts of interest; none
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This research did not receive any specific grant from funding agencies in the public, commercial, or
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not-for-profit sectors.
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Abstract
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Background
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The left atrial myocardium (LAM) and coronary sinus (CS) musculature (CSM) generate atrial
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electrograms recorded inside the CS (AECSs). The vein of Marshall (VOM) courses the mitral isthmus
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(MI) and VOM ethanol infusion (EI-VOM) is useful to ablate it. Its detailed effect on the MI, which
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contains LAM, CSM and those connections, is unknown.
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Objective
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To investigate the impact of EI-VOM on the MI by assessing the AECS.
Methods
Eighty-four consecutive patients with atrial fibrillation undergoing MI ablation with successful
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EI-VOM were included. After the EI-VOM, radiofrequency (RF) catheter touch-up ablation was
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performed at MI gap sites or inside the CS (RFCS), as needed, to achieve bi-directional conduction block
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(BCB). Ablation effects on the AECSs were evaluated during MI ablation procedure.
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Results
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The AECSs demonstrated double potentials consisting of low amplitude LAM components and high
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amplitude CSM components in 31 (37%) patients. Of those, 21/31 had a distal-to-proximal activation
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sequence of the LAM along with a proximal-to-distal activation sequence of the CSM during left atrial
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appendage pacing, suggesting a CSM isolation from the LAM due to electrical LAM-CSM disconnection,
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and only 2/21 required RFCS. The remaining 10 patients with a distal-to-proximal activation in both
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CSM and LAM, suggesting an incomplete CSM isolation and persistent LAM-CSM conduction, required
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RFCS. Overall, combined EI-VOM with RF created BCB at the MI in 78 (93%) patients.
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Conclusions
assessment of the AECSs can predict a requirement for RFCS.
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Key words: ethanol, vein of Marshall, mitral isthmus, catheter ablation, atrial electrogram
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An EI-VOM can ablate the LAM and myocardial connections between the LAM and CSM. Careful
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Introduction
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Creation of bi-directional conduction block (BCB) at the mitral isthmus (MI) is critical for the
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successful treatment of perimitral flutter, but can be technically challenging.1-2 Radiofrequency (RF)
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catheter ablation (RFCA) has been the standard therapeutic tool for MI ablation, but it is often difficult to
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achieve a successful BCB at the MI. Human hearts have epicardial myocardial connections between the
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left atrial myocardium (LAM) and coronary sinus (CS) musculature (CSM) with varying anatomical
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characteristics, some of which are wide and consist of multiple components.3 This complex anatomy
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makes endocardial ablation prone to failure, leading to the necessity for an RF application inside the CS
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(RFCS).1-2
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The vein of Marshall (VOM) has muscle bundles connecting the LAM and CSM, the so called
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Marshall bundles, which often harbor epicardial myocardial connections that can bypass endocardial MI
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ablation lesions.4-7 The VOM also has been proved to play an important role for the genesis, maintenance,
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triggering AF by ectopic foci, and a source of parasympathetic and sympathetic innervations regardless of
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paroxysmal or persistent AF.8-10 Ethanol infusion (EI) into the VOM (EI-VOM) produces chemical injury
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around the MI and has been reported to contribute to elimination of focal ectopy from the VOM,
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abolishment of local vagal responses, and facilitation in the achievement of MI conduction block.9-11
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Generally, atrial electrograms recorded inside the CS (AECSs) consist of a complex of far-field LAM
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potential and near-field CSM potential.12-15 During MI ablation, the AECSs sometimes split into the LAM
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and CSM components and demonstrate double potentials, suggesting a change in the excitation pattern at
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the MI.13-15 Therefore, a detailed assessment of the AECSs after the EI-VOM may give us novel
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information about the clinical efficacy of the EI-VOM for the MI ablation.
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The aim of this study was to evaluate the clinical impact of the EI-VOM on the MI by assessing the
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Methods
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Inclusion and exclusion criteria
Consecutive patients undergoing the MI ablation concomitant with a successful EI-VOM were enrolled.
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Exclusion criteria included severe valvular disease, severe coronary artery disease, a left atrial diameter
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>55mm, and the existence of a thrombus in the left atrium (LA). Written informed consent was obtained
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from all patients prior to the ablation procedure. This study protocol was approved by the institutional
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review board and conformed to the ethical guidelines of the 1975 Declaration of Helsinki.
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From April 2017 to February 2018, de novo AF ablation was performed in patients with drug refractory
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AF. CS venography was performed in all patients as the first step of the procedure. If the VOM was
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identified by CS venography, EI-VOM was attempted prior to a pulmonary vein isolation (PVI). Then, a
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PVI using irrigated RF energy with a “point-by-point” ablation catheter or cryothermal energy with a
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cryoballoon catheter was performed. After successful PVI, a supplemental MI ablation using RF was
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undertaken.
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Procedural management
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The patients received conscious sedation with propofol combined with dexmedetomidine
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hydrochloride. A total of 5000 units of Heparin was administered immediately after a single transseptal
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puncture prior to the EI-VOM, and additionally given to maintain an activated clotting time between 300
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and 350 seconds during the ablation procedure. The surface ECG and bipolar endocardial
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electrocardiograms were filtered from 0.5 to 100 Hz and 30 to 150 Hz, respectively, and continuously
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recorded on a digital recording system (Prucka CardioLab XT recording systems, GE Healthcare,
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Chicago, IL).
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EI-VOM Procedure
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A 9Fr outer guiding sheath (CPS Aim SL, Abbott, Minneapolis, MN) was engaged into the CS via the
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right internal jugular vein. An occlusive CS venography was performed using a wedge balloon infusion
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catheter (Figure 1A). When the VOM was identified and considered to be suitable for an infusion of
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ethanol, a 7Fr inner guiding sheath (CPS Direct SL
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sheath and engaged at the VOM ostium. An angioplasty wire (0.014”) was advanced into the VOM,
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followed by a coronary angioplasty balloon catheter (1.5 to 2.0 mm diameter and 8.0 to 10 mm length,
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depending on the VOM size), and advanced in a “over-the-wire” fashion as deep as possible into the
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VOM. Selective, occlusive VOM angiography through the angioplasty balloon central lumen revealed the
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anatomical characteristics of the VOM (Figure 1B), and then 98% ethanol was slowly injected into the
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VOM for 90 seconds. Ethanol was infused starting from the most distal part of the VOM, then, the
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angioplasty balloon was slightly pulled back proximally, and a subsequent EI was performed (Figure 1C,
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1D). This procedure was carried on until the angioplasty balloon was finally positioned at the VOM
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ostium. The application number of EIs was 1 to 3 according to the VOM length. The amount of injected
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ethanol was 1.5 to 2.0 ml per infusion.
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PVI procedure Both methods of the PVI by RFCA or a cryoballoon have been described previously.16-17 Briefly, in the
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case of the PVI by RFCA, two circular mapping catheters were placed in the superior and inferior PVs
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and the left and right ipsilateral PVs were circumferentially ablated by an externally irrigated catheter
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(FlexAbility, Abbott or Smart touch, Biosense Webster, Diamond Bar, CA).
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In the case of cryoballoon ablation, a 14Fr sheath (Flexcath Advance, Medtronic, Minneapolis, MN)
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and second-generation 28mm cryoballoon (Arctic Front Advance, Medtronic) were inserted to the LA.
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The inflated balloon was advanced against the orifice of the targeted PVs, and the freezing cycle was
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started for 3 minutes. No bonus freezing was performed.
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Supplemental MI ablation after the EI-VOM
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During left atrial appendage (LAA) pacing at a cycle length of 600ms, an endocardial bipolar voltage
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map around the MI after the EI-VOM and PVI was created utilizing a 3-dimensional mapping system
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(NavX, Abbott or CARTO3, Biosense Webster). A scar area was defined as bipolar endocardial voltage
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amplitudes of <0.1mV. Touch-up endocardial RF ablation was carried out at conduction gap sites along
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the VOM, where local LAM potential was still recorded. A decapolar mapping catheter was inserted into
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the CS and the distal tip of the electrode was located just septal to the endocardial MI ablation site. When
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endocardial ablation could not achieve successful MI conduction block in spite of abolishment of local
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LAM potential along the VOM, additional RFCS was subsequently performed targeting near-field CSM
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potentials which was inscribed earlier than any AECSs. An irrigated catheter (FlexAbility or Smart touch)
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was used for the touch-up MI ablation, and delivered with a maximum power of 35W for 30seconds
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during the endocardial RF application and 25W for 30seconds during the RFCS with a saline irrigation
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rate of 17-30 ml/min. The BCB at the MI was confirmed by differential pacing.18
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Methods of the AECS evaluation
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The AECSs recorded by a decapolar mapping catheter were continuously evaluated during the MI
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ablation procedure. If the AECSs split and demonstrated double potentials, the detailed characteristics of
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the double potential component were evaluated, and classified into the two types as follows according to
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previously described reports.12-15 Double potentials were defined as two discrete electrograms separated
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by an isoelectric line.
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Pattern 1: far-field LAM potentials with a low amplitude and low frequency preceded the near-field
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CSM potentials which had high amplitude and high frequency. LAA pacing demonstrated a
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distal-to-proximal activation sequence of the LAM followed by a proximal-to-distal activation sequence
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of the CSM (Figure 2A). The distal-mid portion of the CSM was isolated from the LAM due to electrical
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LAM-CSM disconnection (Figure 2B).
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Pattern 2: LAA pacing revealed a distal-to-proximal activation sequence of the CSM along with that
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of LAM activation (Figure 2C). The distal-mid portion of the CSM was not electrically isolated and
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connection between the LAM and CSM were still preserved (Figure 2D).
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Results
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Study population
One-hundred-fifteen consecutive patients (64.3±9.7 years-old, 83 male, 70 paroxysmal AF) underwent
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catheter ablation to treat AF. CS venography was performed in all patients. Of those 115 patients, a
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successful EI-VOM was performed in 84 (73.4%). In the remaining 31 patients, the EI-VOM could not be
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performed because of the absence, small size, or tortuosity of the VOM. A total of 84 patients undergoing
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the MI ablation with the EI-VOM were enrolled. The patient characteristics are shown in Table 1.
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Results of the PVI
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A successful PVI by an RFCA procedure or cryoballoon system was obtained in all patients. Of 11
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patients undergoing the PVI by RFCA, complete left inferior PV (LIPV) isolation was observed in one
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patient just after the EI-VOM, and RF applications at anterior LIPV aspect could be spared in three for
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LIPV isolation due to scar created by the EI-VOM.
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Results of the EI-VOM and supplemental MI ablation
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The length and ostial diameter of the VOM measured on the fluoroscopic images was 3.9±1.2 cm and
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2.1±0.6 mm, respectively. The total amount of infused ethanol was 4.1±1.0 ml. Voltage maps after the
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EI-VOM demonstrated scar areas along the VOM in all 84 patients, and viable LAM areas were mainly
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observed at mitral annular side (Figure 3). Therefore, majority of conduction gaps of the LAM was also
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located near the mitral annulus. The total time of the RF application at the MI was 4.8±4.6 minutes.
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Thirty-eight (45.2%) patients required additional 2.0±1.5 minutes of RFCSs. Eventually, a successful
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BCB at the MI was accomplished in 78 (92.9%) patients. There was no significant difference about a
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success rate of BCB at the MI between patients with the PVI by RFCA and by cryoballoon ablation
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(11/11 vs. 67/73, p=1.0). There were no significant differences between patients with paroxysmal and
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persistent AF about the VOM length (4.0±1.2 vs. 3.8±1.1 cm; p=0.63) and the diameter of the VOM
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ostium (2.1±0.4 vs. 2.2±0.6 mm; p=0.57).Ⅱ
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AECS evaluation
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Baseline LAA pacing prior to the EI-VOM was performed in the initial 11 patients, and it demonstrated
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just a single AECS component with a distal-to-proximal activation sequence, suggesting that both the
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LAM and CSM were activated simultaneously. Taking that observation into account, no baseline LAA
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pacing was performed in the following 73 patients.
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In 31 (36.9%) out of 84 patients, the AECSs demonstrated double potentials during MI ablation after the
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EI-VOM. Of those 31 patients, the double potentials were recognized solely after the EI-VOM without an
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RF application in 13 (41.9%) and during the 1st RF application in six (19.4%). An average of 0.8±2.2
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minutes of an RF application was needed for the double potentials to become apparent. The details of
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those 31 patients with double potentials were evaluated (Figure 4A). Pattern 1 and 2 type double
189
potentials were recorded in 21 (67.7%) and 10 (32.3%) patients, respectively. In 19 of 21 patients with
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pattern 1, a BCB could be obtained at the MI with a 2.6±1.6 minute endocardial ablation without any
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RFCSs (Figure 5). All of the other 10 patients with pattern 2 required 1.7±1.5 minute additional RFCSs
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after the endocardial ablation (Figure 6). In two patients who required an RFCS in spite of pattern 1,
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subsequent RFCSs failed to obtain MI conduction block. Finally, repeated endocardial ablation could
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obtain it. All 31 patients with double potentials achieved a successful MI conduction block as a result.
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Of the patients with pattern 1, three initially had double potentials in the AECSs thought to be a
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preliminary step of pattern 1 (Figure 7A). The CSM potentials following the LAM occurred at the
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middle portion of the CS and propagated proximally and distally. Endocardial RF applications changed
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these AECSs to pattern 1 type double potentials (Figure 7B). The distal LAM-CSM myocardial
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connections were already electrically disconnected, however, those of the middle portion were still
200
preserved (Figure 7C).12
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Additionally 53 patients out of the entire cohort did not have distinct double potentials during the MI
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ablation. Of those 53 patients, split AECSs were observed in 25 (47.2%), but did not satisfy the definition
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of double potentials. A successful MI conduction block was obtained in 47 (88.7%) patients.
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Follow-up data
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After the 1st procedure, 22/84 patients (9 with paroxysmal, 13 with persistent AF) had a recurrence of
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atrial tachyarrhythmia. Of those, 17 underwent a re-do procedure, and 9/17 had a persistent MI
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conduction block. Given that 2/17 patients failed to obtain successful MI conduction block at the 1st
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procedure, persistent MI conduction block was maintained in 9/15 (60%). Peri-mitral flutter was observed
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in two persistent AF patients. All eight patients with MI re-conduction, including those with peri-mitral
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flutter, underwent RF touch-up ablation in the MI area. Three patients required only an endocardial
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ablation, whereas the remaining five required additional RFCS. As a result, MI conduction block could be
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created in all these patients. The length and ostial diameter of the VOM was not related to the location of
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the conduction gaps. At the end of the re-do procedure, the non-inducibility of peri-mitral flutter was
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confirmed by atrial programmed stimulation.
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The detailed follow-up data in patients with double potentials was shown in Figure 4B.
Complications
Of a total of 84 enrolled patients, a pericardial effusion was observed in two and groin hematoma in
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three. A pericardiocentesis or blood transfusion was not required because their hemodynamic status was
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stable. Of the other 31 patients in whom the EI-VOM was abandoned, a dissection of the VOM was
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provoked by an angioplasty wire insertion into a tortuous VOM in two. In both patients, an EI-VOM was
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not performed, and no pericardial effusion was observed by transthoracic echocardiography.
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Discussion
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The major findings of the present study were: (1) an MI ablation with the EI-VOM could create BCB at
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the MI in approximately 93% of patients with an average of a 4.8 minute RF application, (2) double
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potentials in the AECSs were observed in 37% of patients, (3) of the patients with double potentials,
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approximately two-thirds had pattern 1 and the other one-third had pattern 2 type double potentials, and
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(4) pattern 1 required no RFCS in any except for two patients, whereas pattern 2 required an RFCS in
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all cases.
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Both the VOM and LAM-CSM myocardial connections including the Marshall bundles exist in the
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epicardial MI area. Therefore, the influence of the EI-VOM is supposed to involve not only the LAM
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around the MI, but also the LAM-CSM myocardial connections. Although several studies have reported
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cases of MI conduction using epicardial LAM-CSM myocardial connections,6-7,19 to the best of our
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knowledge, this is the first clinical study that systematically revealed the detailed influence of the
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EI-VOM on the myocardial structures around the MI.
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Comparison with previous studies
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A comparable or higher success rate of the MI ablation with a much shorter RF application duration
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was recognized in comparison with the previous studies that reported acute and chronic success rate of
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the MI ablation with some adjunctive procedures.20-22 Baez-Escudero, et al. reported a successful MI
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ablation in all patients by an approximately two minute RF application following the EI-VOM.11 The
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patient population of that study included 50 of 71 enrolled patients with a previous PVI and 30 with a
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previous MI ablation, whereas all patients in the present study underwent a de novo AF ablation. The
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difference in the patient characteristics between these two clinical studies might lead to the difference in
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the results of the success rate of the MI ablation and RF application time.
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Although the results about persistent maintenance of MI conduction block at re-do procedures in the
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present study was encouraging, follow up periods were relatively short and only patients undergoing
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re-do procedures could be investigated. Further prospective study which enrolls larger number of patients
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and investigates long-term outcome of the EI-VOM is required.
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Assessment of double potentials in the AECSs during the MI ablation
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Successful distal-mid CSM isolation from the LAM by the RFCA is difficult because electrical
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disconnection of epicardial LAM-CSM myocardium is required, and this anatomical feature is certainly
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associated with an incomplete MI conduction block even with multiple RF applications. We could prove a
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successful electrical disconnection of the myocardium between the LAM and CSM in 21 patients with
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pattern 1 type double potentials. Of those 21 patients, 19 could obtain a BCB at the MI by mean of only
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a 2.6 minute endocardial RF application. It suggested the electrical distal-mid CSM isolation effectively
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facilitated the MI ablation. It might be associated with persistent maintenance of the MI conduction block
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and prevention from a peri-mitral flutter, further evaluation of long-term outcome in large number of
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patients undergoing the EI-VOM is expected to prove that.
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Localization of conduction gaps
Considering the mechanisms of pattern 1 and 2 type double potentials, the critical conduction gap
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could be predicted. In patients with pattern 1, the conduction gaps were considered to exist at the LAM.
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In fact, all except for two patients did not require any RFCSs. In the case of pattern 2, an electrical
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isolation of the CSM was incomplete, thus all patients inevitably required additional RFCS. This concept
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could be applicable not only to the MI ablation following the EI-VOM but also to the conventional linear
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MI ablation connecting the LIPV and mitral annulus. However, the EI-VOM might provoke a separation
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of the LAM and CSM potentials more easily because of its potent ability to ablate the LAM and
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LAM-CSM myocardial connections at the same time.
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Clinical implications
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The present study revealed the ability of the EI-VOM to ablate the LAM and LAM-CSM myocardial
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connections. This ability will surely contribute to a creation of successful MI conduction block, especially
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in tough cases. Furthermore, the assessment of double potentials in the AECSs during the MI ablation
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informed us of the location of conduction gaps with a quite high accuracy. It could help us to avoid
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unnecessary RFCSs.
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Study limitations
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This study was a retrospective study, and study population was relatively small. The enrolled patients
were limited to those with successful EI-VOM.
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Voltage map was not performed at baseline, and it was undertaken following the EI-VOM and PVI.
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Therefore, low voltage area around the MI might include scars caused by the LA remodeling, especially
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in patients with persistent AF. Similarly, a comparison of the AECSs between before and after the
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EI-VOM could not be performed in all patients. Those factors might overestimate an efficacy of the
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EI-VOM alone.
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In the present study, touch up MI ablation was finally performed following the EI-VOM and PVI.
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Although the MI was ablated mainly by the EI-VOM and RF ablation, the PVI also might influence the
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MI conduction, especially near the LIPV.
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The clinical impact of the EI-VOM on the MI in patients without double potentials could not be
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investigated. Satisfactory results of the MI ablation were provided even in those patients. These facts
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might mean that the electrophysiological effects of the EI-VOM on the MI could not be observed
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presumably due to the anatomical characteristics in each case.
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Conclusions
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The EI-VOM could provide a high success rate in creating a BCB at the MI. The EI-VOM had an
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influence not only on the LAM, but also on the LAM-CSM myocardial connections. Careful assessment
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of the AECS could predict the localization of conduction gaps and the requirement for an RFCS.
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References
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Jais P, Hocini M, Hsu LF, et al. Technique and results of linear ablation at the mitral isthmus.
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Importance of the vein of Marshall. J Cardiovasc Electrophysiol. 2015;26:352-3.
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Yoshitani K, Miyamoto T, Sato Y, Takatsu Y. Another gate keeper to protect the mitral isthmus?
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Kurotobi T, Ito H, Inoue K, Iwakura K, Kawano S, Okamura A, Date M, Fujii K. Marshall vein as
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arrhythmogenic source in patients with atrial fibrillation: correlation between its anatomy and
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Keida T, Fujita M, Okishige K, Takami M. Elimination of non-pulmonary vein ectopy by ethanol
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10. Valderrabano M, Chen HR, Sidhu J, Rao L, Ling Y, Khoury DS. Retrograde ethanol infusion in the
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11. Baez-Escudero JL, Morales PF, Dave AS, Sasaridis CM, Kim YH, Okishige K, Valderrabano M.
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Ethanol infusion in the vein of Marshall facilitates mitral isthmus ablation. Heart Rhythm.
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12. Antz M, Otomo K, Arruda M, Scherlag BJ, Pitha J, Tondo C, Lazzara R, Jackman WM. Electrical
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16. Okishige K, Aoyagi H, Ihara K, Iwai S, Nakamura T, Yamashita M, Katoh N, Hasegawa T,
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Kawaguchi N, Keida T, Sasano T, Hirao K. Reappraisal of the clinical implications of adenosine
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19. Miyazaki S, Shah AJ, Haissaguerre M. Recurrent perimitral tachycardia using epicardial coronary
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20. Huemer M, Wutzler A, Parwani AS, Attanasio P, Matsuda H, Blaschke F, Boldt LH, Haverkamp W.
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Comparison of the anterior and posterior mitral isthmus ablation lines in patients with perimitral
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annulus flutter or persistent atrial fibrillation. J Interv Card Electrophysiol. 2015;44:119-29.
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21. Hocini M, Shah AJ, Nault I, et al. Mitral isthmus ablation with and without temporary spot occlusion
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of the coronary sinus: a randomized clinical comparison of acute outcomes. J Cardiovasc
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22. Okubo K, Kuwahara T, Takigawa M, et al. Impact of anteroinferior transseptal puncture on creation
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Electrophysiol. 2017;48:317-325.
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Table 1: Clinical characteristics of the study population
Age, years
64.8±10.2
62 (74)
Paroxysmal AF† (%)
50 (60)
AF duration, months
37.6±45.5
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PVI‡ by cryoballoon (%)
73 (87)
CHADS2 score
0.9±0.8
LA§ diameter, mm
§
LA: left atrium
LVEF: left ventricular ejection fraction
‡
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62.4±11.5
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41.4±6.6
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Number of patients, n
PVI: pulmonary vein isolation
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Figure legends
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Figure 1: Fluoroscopic images of the procedure regarding the EI-VOM.
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(A): CS venography. (B): selective VOM venography, ethanol infusion in the distal (C) and proximal (D)
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portion of the VOM.
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CS, coronary sinus; EI-VOM, ethanol infusion into the vein of Marshall; VOM, vein of Marshall
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Figure 2: Electrocardiograms and schemes of the double potentials in the AECSs.
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(A), (B) are about pattern 1, (C), (D) are about pattern 2.
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(A): The activation sequence of the LAM and CSM was oriented in opposite directions, respectively.
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(B): The activation pattern was directed from lateral to septal across the LAM endocardially and
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subsequently from septal to lateral through the CSM epicardially. The activation of the CSM potential
374
takes a detour due to an electrical disconnection between the LAM and CSM.
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(C): The CSM potentials were recorded with a distal-to-proximal sequence followed by the LAM
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potentials.
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(D): The activation pattern was directed from lateral to septal through the CSM epicardially and
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subsequently propagated to the LAM via the LAM-CSM myocardial connections.
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The activation of the LAM and CSM propagates along with the red and blue arrows, respectively.
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AECSs, atrial electrograms recorded inside the coronary sinus; CS, coronary sinus; CSM, coronary sinus
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musculature; LAA, left atrial appendage; LAM, left atrial myocardium; LIPV, left inferior pulmonary
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vein; MI, mitral isthmus
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Figure 3: (A), (B): Fluoroscopic images during the EI-VOM. (C), (D): Bipolar voltage maps after the
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EI-VOM and PVI.
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EI-VOM, ethanol infusion into the vein of Marshall; LAA, left atrial appendage; LIPV, left inferior
392
pulmonary vein; MV, mitral valve; PVI, pulmonary vein isolation; VOM, vein of Marshall
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Figure 4: Flow chart of the patients with double potentials during the MI ablation regarding requirement
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for an RFCS (A) and the outcome (B).
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MI, mitral isthmus; RFCS, radiofrequency application inside the coronary sinus
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Figure 5: Representative case of pattern 1 type double potentials.
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(A): Pattern 1 type double potentials were recognized after the EI-VOM.
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(B): Endocardial ablation could create conduction block at the MI.
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(C),(D): Differential pacing from two different sites (CS1-2 and CS4-5) demonstrated the completion of
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the bi-directional conduction block at the MI. The interval from the pacing stimulus to the electrogram
408
recorded by the ablation catheter (ABL1-2) located just on the lateral side of the block line during pacing
409
from the distal bipole of the CS catheter (CS1-2) was longer than that during pacing from the proximal
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bipole of the CS catheter (CS4-5).
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(E): Fluoroscopic image during the endocardial MI ablation.
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ABL, ablation catheter; CS, coronary sinus; EI-VOM, ethanol infusion into the vein of Marshall; LAA,
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left atrial appendage; MI, mitral isthmus
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Figure 6: Representative case of pattern 2 type double potentials.
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(A): Before the MI ablation, the activation pattern of the LAM and CSM was mutually directed from
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lateral to septal
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(B): Pattern 2 type double potentials were recognized during the 2nd endocardial ablation, however,
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conduction block could not be created.
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(C): The local atrial activation time recorded in ablation catheter (ABL1-2) inside the CS was inscribed
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earlier than any bipole of the CS catheter.
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(D): A single radiofrequency application at that site inside the CS created MI conduction block.
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(E): Fluoroscopic image during ablation inside the CS.
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ABL, ablation catheter; CS, coronary sinus; CSM, coronary sinus musculature; LAA, left atrial
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appendage; LAM, left atrial myocardium; MI, mitral isthmus
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Figure 7: The preliminary stage of the pattern 1 type double potentials.
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(A): The LAM activation sequence was distal-to-proximal, and the following activation sequence of the
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CSM began close to the CS4-5 bipole.
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(B): The AECSs changed to pattern 1 type double potentials during endocardial ablation.
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(C): The activation pattern was directed from lateral to septal across the LAM endocardially and
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subsequently propagated to the CSM via the middle LAM-CSM myocardial connections. Further
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endocardial ablation disconnected the residual LAM-CSM myocardial connections close to the CS4-5
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bipole and then pattern 1 type double potentials could be observed.
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ABL, ablation catheter; AECSs, atrial electrograms recorded inside the coronary sinus; CS, coronary
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sinus; CSM, coronary sinus musculature; LAA, left atrial appendage; LAM, left atrial myocardium
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