- Email: [email protected]
Spectrum of atrial arrhythmias using the ligament of Marshall in patients with atrial fibrillation
Accepted Manuscript Spectrum of Atrial Arrhythmias Utilizing the Ligament of Marshall in Patients with Atrial Fibrillation Aman Chugh, MD, Hitinder S. Gurm, MD, Kavita Krishnasamy, MD, Mohammed Saeed, MD, Watchara Lohawijarn, MD, Kyle Hornsby, MD, Ryan Cunnane, MD, Hamid Ghanbari, MD, Rakesh Latchamsetty, MD, Thomas Crawford, MD, Krit Jongnarangsin, MD, Frank Bogun, MD, Hakan Oral, MD, Fred Morady, MD PII:
S1547-5271(17)30957-8
DOI:
10.1016/j.hrthm.2017.07.033
Reference:
HRTHM 7260
To appear in:
Heart Rhythm
Received Date: 15 April 2017 Revised Date:
1547-5271 1547-5271
Accepted Date: 1547-5271 1547-5271
Please cite this article as: Chugh A, Gurm HS, Krishnasamy K, Saeed M, Lohawijarn W, Hornsby K, Cunnane R, Ghanbari H, Latchamsetty R, Crawford T, Jongnarangsin K, Bogun F, Oral H, Morady F, Spectrum of Atrial Arrhythmias Utilizing the Ligament of Marshall in Patients with Atrial Fibrillation, Heart Rhythm (2017), doi: 10.1016/j.hrthm.2017.07.033. 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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Spectrum of Atrial Arrhythmias Utilizing the Ligament of Marshall in Patients with Atrial Fibrillation
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Aman Chugh, MD, Hitinder S. Gurm, MD, Kavita Krishnasamy, MD, Mohammed Saeed, MD, Watchara Lohawijarn, MD, Kyle Hornsby, MD, Ryan Cunnane, MD, Hamid Ghanbari, MD, Rakesh Latchamsetty, MD, Thomas Crawford, MD, Krit Jongnarangsin, MD, Frank Bogun, MD, Hakan Oral, MD, Fred Morady, MD
Running title: Ligament of Marshall in AF
Conflict of interest: None Address for Correspondence:
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Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI.
Aman Chugh, MD.
Jean and Samuel Frankel Cardiovascular Center 1500 E. Medical Center Dr. SPC 5853
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Ann Arbor, MI 48109-5853 Tel:
734 936 6858
Fax:
734 936 7026
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Email: [email protected]
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ABSTRACT Background: The role of the ligament of Marshall (LOM) in patients with atrial
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fibrillation (AF) has not been well defined.
Objective: To describe the role of the LOM in patients with AF and related arrhythmias.
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Methods: Fifty-six patients (age=63±11 years, persistent AF in 48 [86%], ejection
arrhythmias were included.
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fraction=0.49±0.13, left atrial [LA] diameter=4.7±0.6 cm) with LOM-mediated
Results: A LOM-pulmonary vein (PV) connection was present in 18 patients (32%), and was eliminated with radiofrequency (RF) ablation at the left lateral ridge or crux (n=12),
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the mitral annulus (n=3), or with alcohol (EtOH) ablation of the vein of Marshall (VOM; n=3). A LOM-mediated atrial tachycardia (AT) was present in 13 patients (23%). Thirtyone patients were referred for potential EtOH ablation refractory mitral isthmus
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conduction. In the 6 patients in whom VOM was injected during perimitral reentry, EtOH resulted in slowing in 3, and termination in 1 patient. In others, EtOH infusion resulted in
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complete isolation of the left-sided PVs, and the LA appendage. Repeat RF and adjunctive EtOH ablation of the VOM tended may be more effective in creating conduction block across the mitral isthmus compared to RF ablation alone (p=0.057).
Conclusion: The LOM is responsible for a variety of arrhythmia mechanisms in patients with AF and AT. It may be ablated at any point along its course, at the mitral annulus,
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lateral ridge/PV antrum, and epicardially in the CS and the VOM itself. EtOH ablation of the VOM may be an adjunctive strategy in patients with refractory perimitral reentry.
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Key words: ligament of Marshall; vein of Marshall; atrial fibrillation, atrial flutter; catheter ablation; coronary sinus
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The ligament of Marshall (LOM) has been implicated as an arrhythmogenic source in patients with atrial fibrillation (AF). Prior studies in humans have primarily described the connections of the LOM to the coronary sinus (CS) and the left atrium
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(LA)/pulmonary veins (PVs) in patients with and without LOM-mediated atrial
arrhythmias.1-4 More recently, the LOM has been targeted in patients with refractory
isthmus conduction despite radiofrequency ablation of perimitral atrial flutter.5 The goal
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of the current study is to describe the role of the LOM in a series of patients undergoing
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catheter ablation of AF or post-ablation atrial tachycardia (AT).
Methods
The study was approved by the institutional review board of the University of Michigan, School of Medicine. Fifty-six consecutive patients who underwent an ablation
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procedure for AF and or related arrhythmias from 2010-2016, and in whom there was evidence of LOM-mediated arrhythmias were included. Specifically, patients in whom a PV connection was shown to be mediated by the LOM (by pacing techniques described
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below) or was eliminated by ethanol (EtOH) injection into the vein of Marshall (VOM), atrial tachycardia from the LOM (diagnostic criteria described below), and refractory
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perimitral tachycardia requiring EtOH injection were included in this series. Patient characteristics are shown in Table 1. Most patients had persistent AF (48, 86%), and 53 (95%) had had previously undergone at least 1 prior ablation procedure (mean, 2.2±1.0). Structural heart disease was present in 37 patients (66%): cardiomyopathy and/or heart failure in 19, valve repair, replacement or mitral valvuloplasty in 7, pacemaker or
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defibrillator in 8, coronary artery disease in 7, and hypertrophic cardiomyopathy in 5 patients.
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Electrophysiologic Study
The indication for the procedure was AF in 12 patients (21%), post-ablation AT in 37 (66%), and AF and AT in 7 patients (13%). The electrophysiologic study was
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performed in the fasting state under conscious sedation. The procedure was performed
from a femoral vein. In patients who were being considered for alcohol/ethanol (EtOH)
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ablation of the vein of Marshall (VOM), internal jugular venous access was also obtained. Oral anticoagulation with warfarin was not interrupted. Novel oral anticoagulants were discontinued 36 hours before the procedure. After the transseptal puncture, systemic anticoagulation was achieved with intravenous heparin, and the
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activated clotting time was maintained at about 350 s throughout the procedure. In patients with persistent AF, the ablation protocol consisted of PV isolation (or re-isolation in patients presenting for a repeat session), ablation of complex electrograms,
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linear ablation at the LA roof, and right atrial ablation (RA) if a right-to-left gradient in frequency or complexity was documented. In patients with paroxysmal AF, only PV
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isolation was performed using a 3-D mapping system (CARTO 3, Biosense Webster, Diamond-Bar, California), and 3.5 mm irrigated-tip ablation (25 W) catheter (Thermocool). In patients presenting to the laboratory in AT, an activation map was performed using the 3-D mapping system. Findings on activation mapping were verified with entrainment mapping. The endpoints of the AT procedure were tachycardia termination, PV re-isolation as needed, linear block at all relevant isthmi, and
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noninducibility with rapid atrial pacing to 160 ms ensuring 1:1 capture and programmed atrial stimulation during isoproterenol infusion (10-20 mcg/minute).
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Mapping and Ablation of the LOM
If the left PVs could not be electrically isolated during antral ablation, the earliest breakthrough on the ring catheter was then targeted. This entailed RF energy delivery at
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the crux between ipsilateral veins and, then at the ostia of the PVs, as required for
complete isolation. If the PVs remained connected thereafter, differential pacing was
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performed from the distal CS and the LA appendage. In the setting of a conventional LAPV connection, pacing from the distal CS would be expected to accentuate the delay between LA and PV potentials (LA activation followed by PV activation). In the context of a LOM-PV connection, CS pacing would be expected to advance the LOM potential,
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resulting in a reversal of activation (i.e., LOM activation followed by atrial activation). Such a connection can be considered a “bypass tract”3 by which the Marshall bundle connects directly to the PV myocardium without intervening LA myocardium.
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Radiofrequency energy was delivered at appropriate sites along the course of the LOM, i.e., the left lateral ridge, myocardium outside the anterior aspect of the left-sided PVs,
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the lateral or posterolateral mitral isthmus. A diagnosis of a reentrant AT involving the LOM was considered after excluding
the conventional macro-reentrant LA ATs, as has been previously described.6 Briefly, a roof dependent macro-reentrant AT was excluded if the anterior and posterior walls of the LA were not involved as shown by entrainment mapping. Likewise, lack of participation of both septal and lateral aspects of the mitral annulus excluded the presence
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of perimitral flutter. Other criteria included either distal-to-proximal CS activation or mid CS activation preceding proximal and distal CS activation. In addition, a difference between the post-pacing interval and the tachycardia cycle length ≤20 ms at the left-
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lateral ridge, posterior base of the LA appendage, inferolateral LA (overlying the CS), and/or the mid-to-distal CS region confirmed the participation of the LOM. These
tachycardias were distinguished from clockwise mitral isthmus dependent flutter by
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documenting long return cycles during entrainment mapping from the septal annulus. A focal AT or AF was considered to be originating from the Marshall bundle if the earliest
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activation (with respect to the p-wave) was found along the endocardial course of the LOM or epicardially at the mid-to-distal CS, that is, at the origin of the VOM as confirmed on venography.
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CS Venography and EtOH Ablation
Patients who had failed a prior procedure for either mitral isthmus dependent flutter or suspected LOM mediated tachycardia were offered a repeat procedure using
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EtOH ablation of the VOM as described by Valderrabano, et al.5 A selective, balloonocclusion venogram was performed from the right internal jugular vein. The VOM was
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defined as a branch originating near junction of the CS and the great cardiac vein, and which coursed superiorly and posteriorly (toward a catheter placed in the left inferior PV in the anteroposterior/right anterior oblique view). An angioplasty wire (Asahi Soft, Abbott Vascular) supported by an over-the-wire
balloon catheter was advanced as distally as possible into the VOM and also used to record unipolar electrograms. An appropriately sized balloon (1.5-2.5 mm diameter and
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12-15 mm length was used depending on the size of the VOM identified on the venogram. The balloon was inflated at low pressure (1-2 atmospheres) in the distal part of the vein and the guidewire was removed. A selective venogram of the VOM was
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performed by injecting 0.5-1 ml of contrast medium through the wire port of the balloon. After confirming balloon occlusion, 0.5-1 ml of alcohol was slowly injected over 1
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minute, and a selective venogram of the VOM was repeated.
Follow-up
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Patients were observed for overnight following the ablation procedure. Patients were discharged on an oral anticoagulant, and rate controlling medications. They were instructed to call a clinical care coordinator in case of recurrence or change in clinical status. The patients were seen in the office at 3 and 6 months, and 12 months, and as
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needed thereafter. In patients without an obvious recurrence, a 30-day, auto-trigger (Lifestar AF Express, Life Watch Inc., Buffalo Grove, IL, USA) was prescribed at 12 months after the ablation procedure. Recurrence was defined as sustained (>1 minute),
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symptomatic or asymptomatic AF or AT after the 3-month blinding period.
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Statistical analysis
Continuous variables, expressed as mean±SD, were compared by Student’s t-test
or paired t-test, as appropriate. Categorical variables were compared using the Fisher’s exact test. P<0.05 indicated statistical significance.
Results
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PV-LOM Connections A PV connection mediated by the LOM was observed in 18 of the 56 study patients (32%) (Figure 1). Fifteen of the 18 patients (83%) had previously undergone
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complete antral PV isolation in a conventional fashion, with no evidence of a LOM-
mediated PV connection during the prior procedure. In 2 of the 3 remaining patients, a LOM connection was responsible for acute reconnection during the index ablation
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procedure. The LOM connection was eliminated during RF energy delivery outside the
anterior aspect of the left-sided PVs (left lateral ridge, myocardium outside the PV ostia,
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or crux) in 12 of the 18 patients (67%) (Figure 1). In 3 patients (16%), the LOM-PV connection was eliminated during RF energy application at the ventricular aspect of the lateral or posterolateral mitral annulus (Figure 2). In the remaining 3 patients (17%), the left inferior pulmonary vein was completely isolated after EtOH injection into the VOM
AT and AF
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without any RF energy delivery (see below).
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A LOM-mediated tachycardia was present in 13 patients (23%). In 9 cases, the mechanism was reentry and in the other 4, the mechanism was focal activity. In these
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latter 4 patients, AT was also found to be triggering episodes of AF. In the 13 patients with reentry, the AT terminated during RF application at the ridge in 5, distal CS in 1, and the lateral mitral annulus in 1 patient (Figure 3). After restoration of sinus rhythm during RF energy application in the latter patient, that tachycardia persisted at the anterolateral mitral annulus despite sinus rhythm, i.e., complete exit block to the remaining atrial mass (Figure 3). In 2 others, RF ablation was unsuccessful in terminating
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the reentrant AT. One of these patients presented for a repeat procedure for possible EtOH ablation but venography revealed no VOM. In the 4 patients with focal AT/AF, RF
patients, and the lateral mitral annulus in 1 patient.
VOM Venography for Perimitral Reentry or AT
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ablation eliminated the arrhythmia during RF energy delivery in the distal CS in 3
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In the remaining 31 patients of the 56 study patients, the Marshall bundle was
targeted in patients with perimitral reentry (n=29) or in whom a suspected epicardial AT
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from the LOM could not be eliminated with RF ablation in the CS during a prior procedure (n=2). In the former 29 patients, either perimitral reentry (or mitral isthmus conduction) could not be eliminated during a prior procedure, or AT recurred during follow-up despite successful mitral isthmus ablation during a prior procedure. Balloon
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occlusion venography revealed a VOM branch in 23 of the 31 patients (74%) (Figure 4A and 4B). Unipolar atrial electrograms from the VOM were recorded before and after EtOH infusion (Figure 5). EtOH was infused into the VOM in 16 of the 23 patients
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(70%). EtOH was not infused in 7 patients because of very small caliber of the VOM (n=4), complete lack of atrial electrograms in the VOM (n=2), or extensive
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collateralization (n=1, Figure 4C). In the last patient, there was already evidence of severe LA scarring, and it was felt that EtOH infusion may exacerbate atrial uncoupling, which would be widespread owing to the extensive venous communication with the VOM.
Acute Effects of EtOH Ablation
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EtOH ablation of the VOM resulted in linear block across the mitral isthmus (n=2) (Figure 6A), complete isolation of the left inferior PV (n=3) (Figure 6B), and complete isolation of the lateral LA and the LA appendage (n=1) (Figure 6C), without
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any RF energy delivery. In the 6 patients who underwent alcohol ablation of the VOM
during mitral isthmus dependent flutter, EtOH resulted in termination (Figure 7) of the
tachycardia in one patient, slowing (10-30 milliseconds) in 3 patients; in 2 others, there
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Mitral Isthmus Conduction
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was no change in the cycle length.
Among the 31 patients with who were referred for potential alcohol ablation, venography revealed a suitable VOM in 23, and EtOH was infused into the vein in 16 patients (70%). Mitral isthmus block was achieved in 15/16 patients (94%). The average
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conduction delay was 193±32 ms during pacing. EtOH infusion alone yielded block in 3 of these patients (i.e., without any RF energy), and RF energy was required endocardially and/or epicardially in the CS in the remaining 12 patients. In a patient with hypertrophic
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cardiomyopathy who received alcohol but in whom isthmus block could not be achieved, the maximal bipolar voltage at the lateral LA was 13 mv. In 12 patients in whom there
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was evidence of isthmus conduction who did not undergo EtOH infusion into the VOM (either because of its absence or small caliber), conduction block was achieved in 7 (58%) with endocardial and/or epicardial ablation in the CS, compared to 15/16 (94%) patients who were treated with an EtOH infusion (p=0.057). In 3 patients, further intervention at the mitral isthmus was not required owing to presence of pre-existing conduction block.
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Outcomes The endpoint of AT/AF termination and noninducibility was met in 48 patients
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(86%). Despite deep sedation, 2 (13%) patients experienced fleeting chest discomfort with EtOH infusion, without changes in the electrocardiogram. There were no other
complications attributable to alcohol infusion or vascular complications related to internal
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jugular vein cannulation. Transient ischemic attack was noted in one patient. Fifty-two patients (93%) remained in sinus rhythm over a follow-up of 23±22 months, with 14
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(25%) of these patients taking antiarrhythmic medications.
Discussion Main Findings
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The ligament of Marshall may be responsible for PV reconnection, focal tachycardias that can trigger AF, and reentrant ATs. The LOM also mediates epicardial conduction in patients with mitral isthmus-dependent atrial flutter. The LOM can be
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ablated anywhere along its course, from its insertion into the main body of the CS, endocardial aspect of the mitral annulus, the left lateral ridge/base of LA appendage, or
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the crux between the left-sided PVs. The VOM itself is too small to be targeted by a conventional ablation catheter but the atrial tissue drained by the vein maybe ablated by EtOH infusion. In patients with recurrent perimitral flutter, EtOH ablation of the VOM, along with supplemental RF energy, seems to be more effective in eliminating isthmus conduction than RF ablation alone.
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Anatomic Considerations The LOM, via the Marshall bundle, has variable connections to the adjacent
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myocardium. A majority of patients have 2 or more connections between the Marshall bundle and the myocardium of the CS, LA or the PV’s.3 Han, et al conjectured that
patients with 2 connections (i.e., CS and PVs) may be able to generate macro-reentry
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utilizing the LOM.3 Macro-reentry utilizing the Marshall bundle was recently reported,7 and is further confirmed in this study as shown in Figure 7. In another case of LOM-
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mediated reentrant AT (Figure 3), RF ablation at the mitral annulus eliminated a connection between the Marshall bundle and the LA, resulting in sinus rhythm despite ongoing tachycardia along the LOM. This observation is in keeping with the LOM
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serving as the “inferior interatrial pathway” as originally described by Scherlag.8
LOM and the Pulmonary Veins
In the context of a conventional LA-PV connection, CS pacing results first in
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atrial followed by PV activation, and also accentuates the delay between the two. When there is a direct connection between the Marshall bundle and the left PVs,9 the latter may
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be activated directly without antecedent LA activation, in essence, constituting a bypass tract between the CS and PVs. In this setting, pacing from the CS would be expected to advance the LOM electrogram, i.e., LOM activation precedes atrial activation. It is important to make a distinction between the disparate mechanisms of PV connections as the ablation strategy may be different. For PV connections attributable to the LOM, RF
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ablation may be required at sites not typically targeted during conventional antral ablation, e.g., the left lateral ridge, mitral annulus, CS, or even the VOM itself.
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LOM in Latent PV Conduction
In nearly all patients with a LOM-mediated PV connection in this series, the PVs had been isolated during conventional antral ablation, either during the initial or current
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procedure. However, recurrent PV conduction was not mediated by the typical
connections between the LA myocardium and the PVs, but instead by the LOM. These
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observations suggest that there may be a hierarchy of PV connections, with those between LA and PV muscle sleeve superseding the LOM-PV connections. It is not clear why LOM connections do not manifest themselves acutely after elimination of the conventional LA-PV connections in most cases.
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It is likely that LOM-mediated PV connections are frequently ablated during the course of PV isolation, specifically at the crux, left lateral ridge (where the LOM is <3 mm from the endocardial surface), and the atrial myocardium inferolateral to the left
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inferior PV.10 In this series, RF ablation of conventional target sites failed to abolish PV conduction, and pacing maneuvers elucidated the presence of LOM connections.
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Although a prior study found that the Marshall bundle was not found to be the major contributor to reconnection of the left PVs,4 latent LOM-mediated PV connections may be responsible for arrhythmia recurrence in some patients.11
Mitral Isthmus Conduction
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Mitral isthmus-dependent tachycardia is among the most common macroreentrant tachycardias that occurs in patients undergoing a substrate-based ablation procedure for AF. Anatomic factors such as endocardial pouches, presence of coronary
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arteries that exert a heat-sink effect,12 myocardial thickness, and others, can make it
difficult to achieve permanent conduction block in some patients. Also, isthmus block requires RF energy delivery in the CS in the majority of patients, which itself may be
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challenging owing to tortuosity, and is associated with a risk of injury to the coronary arteries.13
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In the current study, EtOH infusion per se resulted in slowing (n=3) or termination (n=1) in the 6 patients in whom alcohol ablation was performed during perimitral flutter. The extent of response, of course, depends on the size and location (i.e., endo- versus epi-cardial) of the conduction gap. Even after extensive ablation during
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multiple procedures and infusion of alcohol into the VOM, perimitral tachycardia may persist in some difficult cases. For example, the maximal bipolar voltage at the lateral LA in one patient in whom the tachycardia could not be eliminated was 13 mv. Myocardial
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thickness in this case probably helps explain why a combination of endocardial and epicardial ablation plus EtOH infusion into the VOM did not terminate perimitral
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tachycardia.
Thus, EtOH ablation should not be considered a panacea for patients with
recurrent arrhythmias after prior radiofrequency ablation attempts. Some anatomic limitations cannot be overcome despite multiple approaches. Furthermore, EtOH ablation only targets a very specific and small portion of the lateral LA. The adjunctive role of
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EtOH ablation of the VOM in patients with AF is currently being evaluated in randomized studies (NCT01898221).
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LOM and the LA Appendage
EtOH infusion of the VOM also resulted in complete electrical isolation of the LA appendage in one of the patients in this series. The LOM not only connects to the PV
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myocardium, but apparently also may connect to atrial myocardial fibers around the LA appendage. The patient in question had undergone multiple prior procedures for AF and
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AT. The LA appendage is an attractive target in patients with persistent AF,14 and it can be difficult to isolate by circumferential ablation along its base. We have previously shown that the LA appendage may be isolated from relatively remote areas such as Bachmann’s bundle, endocardial mitral isthmus and the distal CS.15 If an arrhythmia
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source cannot be completely eliminated from the LA appendage, for example due to an epicardial source, despite extensive endocardial ablation, EtOH infusion of the VOM
Conclusions
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may be an option prior to attempting a formal epicardial ablation procedure.16, 17
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The LOM is responsible for both focal and reentrant arrhythmias in patients with
AF. It also serves as a connection to the PVs, which may then serve as triggers and/or drivers of AF and related arrhythmias. The ligament may be ablated at any point along its course from the mid-to-distal CS to the LA appendage. If necessary, the VOM may be directly ablated utilizing EtOH infusion to eliminate PV contribution, effect conduction block across the mitral isthmus, and others. EtOH ablation of the VOM, supplemented
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with RF ablation, may be more effective in yielding conduction block at the mitral
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isthmus as compared to repeat radiofrequency ablation alone.
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Table 1.
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56 63±11 44/12 8/48 0.49±0.13 (0.17-0.65) 4.7±0.6 (3.3-6.0) 2.2±1.0 (0-4) 12/37/7 37 (66%) 19 7 8 7 5
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No. of patients Age (years) Gender (M/F) AF type (PAF/PsAF) Ejection fraction Left atrial diameter (cm) Prior procedures Indication (AF/AT, AF and AT) Structural heart disease Cardiomyopathy/CHF Valve repair/replacement/valvuloplasty Pacemaker/defibrillator Coronary artery disease Hypertrophic cardiomyopathy
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M=males. F=females. PAF=paroxysmal AF. Ps=persistent. AT=atrial tachycardia. CHF=congestive heart failure.
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References
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15. Chan CP, Wong WS, Pumprueg S, et al. Inadvertent electrical isolation of the left atrial appendage during catheter ablation of persistent atrial fibrillation. Heart Rhythm. 2010;7:173-80. 16. Phillips KP, Natale A, Sterba R, Saliba WI, Burkhardt JD, Wazni O, Liberman L and Schweikert RA. Percutaneous pericardial instrumentation for catheter ablation of focal atrial tachycardias arising from the left atrial appendage. J Cardiovasc Electrophysiol. 2008;19:430-3. 17. Yamada T, McElderry HT, Allison JS and Kay GN. Focal atrial tachycardia originating from the epicardial left atrial appendage. Heart Rhythm. 2008;5:766-7.
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Figure Legends
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1. An example of ligament of Marshall (LOM)-pulmonary vein (PV) connection. During sinus rhythm, the ring catheter placed in the left superior PV (LSPV) records 2 potentials, a far-field left atrial (LA) potential, followed by the LOM. Pacing from the distal coronary sinus (CS), advances the 2nd potential and results in reversal of activation, confirming the presence of a LOM-PV connection. The LOM is activated immediately after CS activation. Pacing from the LA appendage (LAA) further accentuates the delay between LA and the LOM. After elimination of the LOM connection with radiofrequency ablation, delay is longer (130 ms to 160 ms) suggesting that the LOM’s role in mitral isthmus conduction. (Mitral isthmus block could not be achieved in this patient due to presence of a large pouch at the lateral isthmus). 2.
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A. An example of a LOM-PV connection that was eliminated during radiofrequency ablation at the lateral mitral annulus (MA). B. Fluoroscopic image showing the position of the ablation catheter and the ring catheter in the LSPV. 3.
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A. Termination of a reentrant atrial tachycardia involving the LOM during radiofrequency (RF) ablation at the lateral mitral annulus. This patient had previously undergone excision of the LA appendage as part of a surgical maze procedure. B. Further mapping actually revealed that tachycardia persisted at the anterior mitral annulus during sinus rhythm, suggesting that LOM and the subjacent atrial myocardium responsible for maintaining the tachycardia were insulated from the endocardium which was activated by the sinus rhythm wavefront. C. A schematic showing the likely mechanism of the tachycardia (red arrows) and proposed route of activation of the atrial mass. Conduction block across Bachmann’s bundle (BB) was caused by RF ablation of another tachycardia that was ablated at the anterior LA (not shown). D. Schema showing ongoing tachycardia with conduction block to the CS and the atria during sinus rhythm. RA=right atrium. VOM=vein of Marshall. GCV=great cardiac vein. LIPV=left inferior PV. SA=sinoatrial node.
4.
A. Balloon-occlusion of the CS showing the vein of Marshall (VOM). LI=left inferior. B. After inflation of a 1.5 mm balloon in the VOM, contrast injection shows dye “hang up.” C. Another selective venogram of the VOM shows extensive venous-venous communication over the left atrium. Alcohol instillation into the VOM in
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such a case would not only affect the lateral LA myocardium but also numerous other areas drained by the various intercommunicating veins. 5.
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A. Unipolar electrograms recorded by a catheter inserted into the vein of Marshall. B. Instillation of 1 cc of EtOH into the VOM leads to complete abolition of the atrial electrograms. (EtOH ablation of the VOM had no effect on AFEtOH infusion in this case was performed for mitral isthmus conduction.)
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6. Pleiotropic effects of EtOH ablation of the VOM. A. Without any RF energy delivery, infusion of 1 cc of EtOH yielded complete bidirectional block across of the mitral isthmus in this patient with prior LAA isolation. LLR=left lateral ridge. B. Complete isolation of the LIPV. C. Complete isolation of the LAA. A bipolar voltage map after EtOH infusion of the VOM showing absence of electrical conduction into the LAA. 7. A. An example of dual loop macro-reentrant tachycardia utilizing the LOM. The dashed arrows over the lateral mitral isthmus denotes epicardial conduction overlying the area of endocardial scar. RF energy (delivered at sites denoted by white tags between the LSPV and LAA) slowed the tachycardia (not shown). Gold tags=sites where the post pacing interval approximated the tachycardia cycle length. B. However, tachycardia termination required EtOH infusion into the vein of Marshall.
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Figure 1 Distal CS pacing
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Figure 2 A
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Figure 4
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S1547-5271(17)30957-8
DOI:
10.1016/j.hrthm.2017.07.033
Reference:
HRTHM 7260
To appear in:
Heart Rhythm
Received Date: 15 April 2017 Revised Date:
1547-5271 1547-5271
Accepted Date: 1547-5271 1547-5271
Please cite this article as: Chugh A, Gurm HS, Krishnasamy K, Saeed M, Lohawijarn W, Hornsby K, Cunnane R, Ghanbari H, Latchamsetty R, Crawford T, Jongnarangsin K, Bogun F, Oral H, Morady F, Spectrum of Atrial Arrhythmias Utilizing the Ligament of Marshall in Patients with Atrial Fibrillation, Heart Rhythm (2017), doi: 10.1016/j.hrthm.2017.07.033. 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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Spectrum of Atrial Arrhythmias Utilizing the Ligament of Marshall in Patients with Atrial Fibrillation
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Aman Chugh, MD, Hitinder S. Gurm, MD, Kavita Krishnasamy, MD, Mohammed Saeed, MD, Watchara Lohawijarn, MD, Kyle Hornsby, MD, Ryan Cunnane, MD, Hamid Ghanbari, MD, Rakesh Latchamsetty, MD, Thomas Crawford, MD, Krit Jongnarangsin, MD, Frank Bogun, MD, Hakan Oral, MD, Fred Morady, MD
Running title: Ligament of Marshall in AF
Conflict of interest: None Address for Correspondence:
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Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI.
Aman Chugh, MD.
Jean and Samuel Frankel Cardiovascular Center 1500 E. Medical Center Dr. SPC 5853
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Ann Arbor, MI 48109-5853 Tel:
734 936 6858
Fax:
734 936 7026
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Email: [email protected]
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ABSTRACT Background: The role of the ligament of Marshall (LOM) in patients with atrial
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fibrillation (AF) has not been well defined.
Objective: To describe the role of the LOM in patients with AF and related arrhythmias.
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Methods: Fifty-six patients (age=63±11 years, persistent AF in 48 [86%], ejection
arrhythmias were included.
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fraction=0.49±0.13, left atrial [LA] diameter=4.7±0.6 cm) with LOM-mediated
Results: A LOM-pulmonary vein (PV) connection was present in 18 patients (32%), and was eliminated with radiofrequency (RF) ablation at the left lateral ridge or crux (n=12),
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the mitral annulus (n=3), or with alcohol (EtOH) ablation of the vein of Marshall (VOM; n=3). A LOM-mediated atrial tachycardia (AT) was present in 13 patients (23%). Thirtyone patients were referred for potential EtOH ablation refractory mitral isthmus
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conduction. In the 6 patients in whom VOM was injected during perimitral reentry, EtOH resulted in slowing in 3, and termination in 1 patient. In others, EtOH infusion resulted in
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complete isolation of the left-sided PVs, and the LA appendage. Repeat RF and adjunctive EtOH ablation of the VOM tended may be more effective in creating conduction block across the mitral isthmus compared to RF ablation alone (p=0.057).
Conclusion: The LOM is responsible for a variety of arrhythmia mechanisms in patients with AF and AT. It may be ablated at any point along its course, at the mitral annulus,
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lateral ridge/PV antrum, and epicardially in the CS and the VOM itself. EtOH ablation of the VOM may be an adjunctive strategy in patients with refractory perimitral reentry.
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Key words: ligament of Marshall; vein of Marshall; atrial fibrillation, atrial flutter; catheter ablation; coronary sinus
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The ligament of Marshall (LOM) has been implicated as an arrhythmogenic source in patients with atrial fibrillation (AF). Prior studies in humans have primarily described the connections of the LOM to the coronary sinus (CS) and the left atrium
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(LA)/pulmonary veins (PVs) in patients with and without LOM-mediated atrial
arrhythmias.1-4 More recently, the LOM has been targeted in patients with refractory
isthmus conduction despite radiofrequency ablation of perimitral atrial flutter.5 The goal
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of the current study is to describe the role of the LOM in a series of patients undergoing
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catheter ablation of AF or post-ablation atrial tachycardia (AT).
Methods
The study was approved by the institutional review board of the University of Michigan, School of Medicine. Fifty-six consecutive patients who underwent an ablation
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procedure for AF and or related arrhythmias from 2010-2016, and in whom there was evidence of LOM-mediated arrhythmias were included. Specifically, patients in whom a PV connection was shown to be mediated by the LOM (by pacing techniques described
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below) or was eliminated by ethanol (EtOH) injection into the vein of Marshall (VOM), atrial tachycardia from the LOM (diagnostic criteria described below), and refractory
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perimitral tachycardia requiring EtOH injection were included in this series. Patient characteristics are shown in Table 1. Most patients had persistent AF (48, 86%), and 53 (95%) had had previously undergone at least 1 prior ablation procedure (mean, 2.2±1.0). Structural heart disease was present in 37 patients (66%): cardiomyopathy and/or heart failure in 19, valve repair, replacement or mitral valvuloplasty in 7, pacemaker or
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defibrillator in 8, coronary artery disease in 7, and hypertrophic cardiomyopathy in 5 patients.
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Electrophysiologic Study
The indication for the procedure was AF in 12 patients (21%), post-ablation AT in 37 (66%), and AF and AT in 7 patients (13%). The electrophysiologic study was
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performed in the fasting state under conscious sedation. The procedure was performed
from a femoral vein. In patients who were being considered for alcohol/ethanol (EtOH)
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ablation of the vein of Marshall (VOM), internal jugular venous access was also obtained. Oral anticoagulation with warfarin was not interrupted. Novel oral anticoagulants were discontinued 36 hours before the procedure. After the transseptal puncture, systemic anticoagulation was achieved with intravenous heparin, and the
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activated clotting time was maintained at about 350 s throughout the procedure. In patients with persistent AF, the ablation protocol consisted of PV isolation (or re-isolation in patients presenting for a repeat session), ablation of complex electrograms,
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linear ablation at the LA roof, and right atrial ablation (RA) if a right-to-left gradient in frequency or complexity was documented. In patients with paroxysmal AF, only PV
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isolation was performed using a 3-D mapping system (CARTO 3, Biosense Webster, Diamond-Bar, California), and 3.5 mm irrigated-tip ablation (25 W) catheter (Thermocool). In patients presenting to the laboratory in AT, an activation map was performed using the 3-D mapping system. Findings on activation mapping were verified with entrainment mapping. The endpoints of the AT procedure were tachycardia termination, PV re-isolation as needed, linear block at all relevant isthmi, and
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noninducibility with rapid atrial pacing to 160 ms ensuring 1:1 capture and programmed atrial stimulation during isoproterenol infusion (10-20 mcg/minute).
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Mapping and Ablation of the LOM
If the left PVs could not be electrically isolated during antral ablation, the earliest breakthrough on the ring catheter was then targeted. This entailed RF energy delivery at
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the crux between ipsilateral veins and, then at the ostia of the PVs, as required for
complete isolation. If the PVs remained connected thereafter, differential pacing was
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performed from the distal CS and the LA appendage. In the setting of a conventional LAPV connection, pacing from the distal CS would be expected to accentuate the delay between LA and PV potentials (LA activation followed by PV activation). In the context of a LOM-PV connection, CS pacing would be expected to advance the LOM potential,
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resulting in a reversal of activation (i.e., LOM activation followed by atrial activation). Such a connection can be considered a “bypass tract”3 by which the Marshall bundle connects directly to the PV myocardium without intervening LA myocardium.
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Radiofrequency energy was delivered at appropriate sites along the course of the LOM, i.e., the left lateral ridge, myocardium outside the anterior aspect of the left-sided PVs,
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the lateral or posterolateral mitral isthmus. A diagnosis of a reentrant AT involving the LOM was considered after excluding
the conventional macro-reentrant LA ATs, as has been previously described.6 Briefly, a roof dependent macro-reentrant AT was excluded if the anterior and posterior walls of the LA were not involved as shown by entrainment mapping. Likewise, lack of participation of both septal and lateral aspects of the mitral annulus excluded the presence
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of perimitral flutter. Other criteria included either distal-to-proximal CS activation or mid CS activation preceding proximal and distal CS activation. In addition, a difference between the post-pacing interval and the tachycardia cycle length ≤20 ms at the left-
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lateral ridge, posterior base of the LA appendage, inferolateral LA (overlying the CS), and/or the mid-to-distal CS region confirmed the participation of the LOM. These
tachycardias were distinguished from clockwise mitral isthmus dependent flutter by
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documenting long return cycles during entrainment mapping from the septal annulus. A focal AT or AF was considered to be originating from the Marshall bundle if the earliest
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activation (with respect to the p-wave) was found along the endocardial course of the LOM or epicardially at the mid-to-distal CS, that is, at the origin of the VOM as confirmed on venography.
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CS Venography and EtOH Ablation
Patients who had failed a prior procedure for either mitral isthmus dependent flutter or suspected LOM mediated tachycardia were offered a repeat procedure using
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EtOH ablation of the VOM as described by Valderrabano, et al.5 A selective, balloonocclusion venogram was performed from the right internal jugular vein. The VOM was
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defined as a branch originating near junction of the CS and the great cardiac vein, and which coursed superiorly and posteriorly (toward a catheter placed in the left inferior PV in the anteroposterior/right anterior oblique view). An angioplasty wire (Asahi Soft, Abbott Vascular) supported by an over-the-wire
balloon catheter was advanced as distally as possible into the VOM and also used to record unipolar electrograms. An appropriately sized balloon (1.5-2.5 mm diameter and
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12-15 mm length was used depending on the size of the VOM identified on the venogram. The balloon was inflated at low pressure (1-2 atmospheres) in the distal part of the vein and the guidewire was removed. A selective venogram of the VOM was
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performed by injecting 0.5-1 ml of contrast medium through the wire port of the balloon. After confirming balloon occlusion, 0.5-1 ml of alcohol was slowly injected over 1
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minute, and a selective venogram of the VOM was repeated.
Follow-up
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Patients were observed for overnight following the ablation procedure. Patients were discharged on an oral anticoagulant, and rate controlling medications. They were instructed to call a clinical care coordinator in case of recurrence or change in clinical status. The patients were seen in the office at 3 and 6 months, and 12 months, and as
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needed thereafter. In patients without an obvious recurrence, a 30-day, auto-trigger (Lifestar AF Express, Life Watch Inc., Buffalo Grove, IL, USA) was prescribed at 12 months after the ablation procedure. Recurrence was defined as sustained (>1 minute),
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symptomatic or asymptomatic AF or AT after the 3-month blinding period.
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Statistical analysis
Continuous variables, expressed as mean±SD, were compared by Student’s t-test
or paired t-test, as appropriate. Categorical variables were compared using the Fisher’s exact test. P<0.05 indicated statistical significance.
Results
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PV-LOM Connections A PV connection mediated by the LOM was observed in 18 of the 56 study patients (32%) (Figure 1). Fifteen of the 18 patients (83%) had previously undergone
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complete antral PV isolation in a conventional fashion, with no evidence of a LOM-
mediated PV connection during the prior procedure. In 2 of the 3 remaining patients, a LOM connection was responsible for acute reconnection during the index ablation
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procedure. The LOM connection was eliminated during RF energy delivery outside the
anterior aspect of the left-sided PVs (left lateral ridge, myocardium outside the PV ostia,
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or crux) in 12 of the 18 patients (67%) (Figure 1). In 3 patients (16%), the LOM-PV connection was eliminated during RF energy application at the ventricular aspect of the lateral or posterolateral mitral annulus (Figure 2). In the remaining 3 patients (17%), the left inferior pulmonary vein was completely isolated after EtOH injection into the VOM
AT and AF
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without any RF energy delivery (see below).
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A LOM-mediated tachycardia was present in 13 patients (23%). In 9 cases, the mechanism was reentry and in the other 4, the mechanism was focal activity. In these
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latter 4 patients, AT was also found to be triggering episodes of AF. In the 13 patients with reentry, the AT terminated during RF application at the ridge in 5, distal CS in 1, and the lateral mitral annulus in 1 patient (Figure 3). After restoration of sinus rhythm during RF energy application in the latter patient, that tachycardia persisted at the anterolateral mitral annulus despite sinus rhythm, i.e., complete exit block to the remaining atrial mass (Figure 3). In 2 others, RF ablation was unsuccessful in terminating
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the reentrant AT. One of these patients presented for a repeat procedure for possible EtOH ablation but venography revealed no VOM. In the 4 patients with focal AT/AF, RF
patients, and the lateral mitral annulus in 1 patient.
VOM Venography for Perimitral Reentry or AT
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ablation eliminated the arrhythmia during RF energy delivery in the distal CS in 3
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In the remaining 31 patients of the 56 study patients, the Marshall bundle was
targeted in patients with perimitral reentry (n=29) or in whom a suspected epicardial AT
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from the LOM could not be eliminated with RF ablation in the CS during a prior procedure (n=2). In the former 29 patients, either perimitral reentry (or mitral isthmus conduction) could not be eliminated during a prior procedure, or AT recurred during follow-up despite successful mitral isthmus ablation during a prior procedure. Balloon
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occlusion venography revealed a VOM branch in 23 of the 31 patients (74%) (Figure 4A and 4B). Unipolar atrial electrograms from the VOM were recorded before and after EtOH infusion (Figure 5). EtOH was infused into the VOM in 16 of the 23 patients
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(70%). EtOH was not infused in 7 patients because of very small caliber of the VOM (n=4), complete lack of atrial electrograms in the VOM (n=2), or extensive
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collateralization (n=1, Figure 4C). In the last patient, there was already evidence of severe LA scarring, and it was felt that EtOH infusion may exacerbate atrial uncoupling, which would be widespread owing to the extensive venous communication with the VOM.
Acute Effects of EtOH Ablation
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EtOH ablation of the VOM resulted in linear block across the mitral isthmus (n=2) (Figure 6A), complete isolation of the left inferior PV (n=3) (Figure 6B), and complete isolation of the lateral LA and the LA appendage (n=1) (Figure 6C), without
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any RF energy delivery. In the 6 patients who underwent alcohol ablation of the VOM
during mitral isthmus dependent flutter, EtOH resulted in termination (Figure 7) of the
tachycardia in one patient, slowing (10-30 milliseconds) in 3 patients; in 2 others, there
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Mitral Isthmus Conduction
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was no change in the cycle length.
Among the 31 patients with who were referred for potential alcohol ablation, venography revealed a suitable VOM in 23, and EtOH was infused into the vein in 16 patients (70%). Mitral isthmus block was achieved in 15/16 patients (94%). The average
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conduction delay was 193±32 ms during pacing. EtOH infusion alone yielded block in 3 of these patients (i.e., without any RF energy), and RF energy was required endocardially and/or epicardially in the CS in the remaining 12 patients. In a patient with hypertrophic
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cardiomyopathy who received alcohol but in whom isthmus block could not be achieved, the maximal bipolar voltage at the lateral LA was 13 mv. In 12 patients in whom there
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was evidence of isthmus conduction who did not undergo EtOH infusion into the VOM (either because of its absence or small caliber), conduction block was achieved in 7 (58%) with endocardial and/or epicardial ablation in the CS, compared to 15/16 (94%) patients who were treated with an EtOH infusion (p=0.057). In 3 patients, further intervention at the mitral isthmus was not required owing to presence of pre-existing conduction block.
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Outcomes The endpoint of AT/AF termination and noninducibility was met in 48 patients
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(86%). Despite deep sedation, 2 (13%) patients experienced fleeting chest discomfort with EtOH infusion, without changes in the electrocardiogram. There were no other
complications attributable to alcohol infusion or vascular complications related to internal
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jugular vein cannulation. Transient ischemic attack was noted in one patient. Fifty-two patients (93%) remained in sinus rhythm over a follow-up of 23±22 months, with 14
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(25%) of these patients taking antiarrhythmic medications.
Discussion Main Findings
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The ligament of Marshall may be responsible for PV reconnection, focal tachycardias that can trigger AF, and reentrant ATs. The LOM also mediates epicardial conduction in patients with mitral isthmus-dependent atrial flutter. The LOM can be
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ablated anywhere along its course, from its insertion into the main body of the CS, endocardial aspect of the mitral annulus, the left lateral ridge/base of LA appendage, or
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the crux between the left-sided PVs. The VOM itself is too small to be targeted by a conventional ablation catheter but the atrial tissue drained by the vein maybe ablated by EtOH infusion. In patients with recurrent perimitral flutter, EtOH ablation of the VOM, along with supplemental RF energy, seems to be more effective in eliminating isthmus conduction than RF ablation alone.
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Anatomic Considerations The LOM, via the Marshall bundle, has variable connections to the adjacent
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myocardium. A majority of patients have 2 or more connections between the Marshall bundle and the myocardium of the CS, LA or the PV’s.3 Han, et al conjectured that
patients with 2 connections (i.e., CS and PVs) may be able to generate macro-reentry
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utilizing the LOM.3 Macro-reentry utilizing the Marshall bundle was recently reported,7 and is further confirmed in this study as shown in Figure 7. In another case of LOM-
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mediated reentrant AT (Figure 3), RF ablation at the mitral annulus eliminated a connection between the Marshall bundle and the LA, resulting in sinus rhythm despite ongoing tachycardia along the LOM. This observation is in keeping with the LOM
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serving as the “inferior interatrial pathway” as originally described by Scherlag.8
LOM and the Pulmonary Veins
In the context of a conventional LA-PV connection, CS pacing results first in
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atrial followed by PV activation, and also accentuates the delay between the two. When there is a direct connection between the Marshall bundle and the left PVs,9 the latter may
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be activated directly without antecedent LA activation, in essence, constituting a bypass tract between the CS and PVs. In this setting, pacing from the CS would be expected to advance the LOM electrogram, i.e., LOM activation precedes atrial activation. It is important to make a distinction between the disparate mechanisms of PV connections as the ablation strategy may be different. For PV connections attributable to the LOM, RF
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ablation may be required at sites not typically targeted during conventional antral ablation, e.g., the left lateral ridge, mitral annulus, CS, or even the VOM itself.
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LOM in Latent PV Conduction
In nearly all patients with a LOM-mediated PV connection in this series, the PVs had been isolated during conventional antral ablation, either during the initial or current
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procedure. However, recurrent PV conduction was not mediated by the typical
connections between the LA myocardium and the PVs, but instead by the LOM. These
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observations suggest that there may be a hierarchy of PV connections, with those between LA and PV muscle sleeve superseding the LOM-PV connections. It is not clear why LOM connections do not manifest themselves acutely after elimination of the conventional LA-PV connections in most cases.
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It is likely that LOM-mediated PV connections are frequently ablated during the course of PV isolation, specifically at the crux, left lateral ridge (where the LOM is <3 mm from the endocardial surface), and the atrial myocardium inferolateral to the left
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inferior PV.10 In this series, RF ablation of conventional target sites failed to abolish PV conduction, and pacing maneuvers elucidated the presence of LOM connections.
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Although a prior study found that the Marshall bundle was not found to be the major contributor to reconnection of the left PVs,4 latent LOM-mediated PV connections may be responsible for arrhythmia recurrence in some patients.11
Mitral Isthmus Conduction
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Mitral isthmus-dependent tachycardia is among the most common macroreentrant tachycardias that occurs in patients undergoing a substrate-based ablation procedure for AF. Anatomic factors such as endocardial pouches, presence of coronary
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arteries that exert a heat-sink effect,12 myocardial thickness, and others, can make it
difficult to achieve permanent conduction block in some patients. Also, isthmus block requires RF energy delivery in the CS in the majority of patients, which itself may be
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challenging owing to tortuosity, and is associated with a risk of injury to the coronary arteries.13
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In the current study, EtOH infusion per se resulted in slowing (n=3) or termination (n=1) in the 6 patients in whom alcohol ablation was performed during perimitral flutter. The extent of response, of course, depends on the size and location (i.e., endo- versus epi-cardial) of the conduction gap. Even after extensive ablation during
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multiple procedures and infusion of alcohol into the VOM, perimitral tachycardia may persist in some difficult cases. For example, the maximal bipolar voltage at the lateral LA in one patient in whom the tachycardia could not be eliminated was 13 mv. Myocardial
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thickness in this case probably helps explain why a combination of endocardial and epicardial ablation plus EtOH infusion into the VOM did not terminate perimitral
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tachycardia.
Thus, EtOH ablation should not be considered a panacea for patients with
recurrent arrhythmias after prior radiofrequency ablation attempts. Some anatomic limitations cannot be overcome despite multiple approaches. Furthermore, EtOH ablation only targets a very specific and small portion of the lateral LA. The adjunctive role of
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EtOH ablation of the VOM in patients with AF is currently being evaluated in randomized studies (NCT01898221).
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LOM and the LA Appendage
EtOH infusion of the VOM also resulted in complete electrical isolation of the LA appendage in one of the patients in this series. The LOM not only connects to the PV
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myocardium, but apparently also may connect to atrial myocardial fibers around the LA appendage. The patient in question had undergone multiple prior procedures for AF and
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AT. The LA appendage is an attractive target in patients with persistent AF,14 and it can be difficult to isolate by circumferential ablation along its base. We have previously shown that the LA appendage may be isolated from relatively remote areas such as Bachmann’s bundle, endocardial mitral isthmus and the distal CS.15 If an arrhythmia
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source cannot be completely eliminated from the LA appendage, for example due to an epicardial source, despite extensive endocardial ablation, EtOH infusion of the VOM
Conclusions
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may be an option prior to attempting a formal epicardial ablation procedure.16, 17
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The LOM is responsible for both focal and reentrant arrhythmias in patients with
AF. It also serves as a connection to the PVs, which may then serve as triggers and/or drivers of AF and related arrhythmias. The ligament may be ablated at any point along its course from the mid-to-distal CS to the LA appendage. If necessary, the VOM may be directly ablated utilizing EtOH infusion to eliminate PV contribution, effect conduction block across the mitral isthmus, and others. EtOH ablation of the VOM, supplemented
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with RF ablation, may be more effective in yielding conduction block at the mitral
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isthmus as compared to repeat radiofrequency ablation alone.
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Table 1.
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56 63±11 44/12 8/48 0.49±0.13 (0.17-0.65) 4.7±0.6 (3.3-6.0) 2.2±1.0 (0-4) 12/37/7 37 (66%) 19 7 8 7 5
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No. of patients Age (years) Gender (M/F) AF type (PAF/PsAF) Ejection fraction Left atrial diameter (cm) Prior procedures Indication (AF/AT, AF and AT) Structural heart disease Cardiomyopathy/CHF Valve repair/replacement/valvuloplasty Pacemaker/defibrillator Coronary artery disease Hypertrophic cardiomyopathy
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M=males. F=females. PAF=paroxysmal AF. Ps=persistent. AT=atrial tachycardia. CHF=congestive heart failure.
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References
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1. Lin W, Tai C, Hsieh M, et at a and asd d. Catheter ablation of paroxysmal atrial fibrillation initiated by non-pulmonary vein ectopy. Circulation. 2003;107:31763183. 2. Kamanu S, Tan AY, Peter CT, Hwang C and Chen PS. Vein of Marshall activity during sustained atrial fibrillation. J Cardiovasc Electrophysiol. 2006;17:839-46. 3. Han S, Joung B, Scanavacca M, Sosa E, Chen PS and Hwang C. Electrophysiological characteristics of the Marshall bundle in humans. Heart Rhythm. 2010;7:786-93. 4. Dave AS, Baez-Escudero JL, Sasaridis C, Hong TE, Rami T and Valderrabano M. Role of the vein of Marshall in atrial fibrillation recurrences after catheter ablation: therapeutic effect of ethanol infusion. J Cardiovasc Electrophysiol. 2012;23:583-91. 5. Baez-Escudero JL, Morales PF, Dave AS, Sasaridis CM, Kim YH, Okishige K and Valderrabano M. Ethanol infusion in the vein of Marshall facilitates mitral isthmus ablation. Heart Rhythm. 2012;9:1207-15. 6. Yokokawa M, Latchamsetty R, Ghanbari H, et al. Characteristics of atrial tachycardia due to small vs large reentrant circuits after ablation of persistent atrial fibrillation. Heart Rhythm. 2013;10:469-76. 7. Yamamoto T, Maruyama M, Seino Y and Shimizu W. Marshall bundle reentry: a novel type of macroreentrant atrial tachycardia. Heart Rhythm. 2014;11:1229-32. 8. Scherlag BJ, Yeh BK and Robinson MJ. Inferior interatrial pathway in the dog. Circ Res. 1972;31:18-35. 9. Tan AY, Chou CC, Zhou S, Nihei M, Hwang C, Peter CT, Fishbein MC and Chen PS. Electrical connections between left superior pulmonary vein, left atrium, and ligament of Marshall: implications for mechanisms of atrial fibrillation. Am J Physiol Heart Circ Physiol. 2006;290:H312-22. 10. Cabrera JA, Ho SY, Climent V and Sanchez-Quintana D. The architecture of the left lateral atrial wall: a particular anatomic region with implications for ablation of atrial fibrillation. Eur Heart J. 2008;29:356-62. 11. Matsuo S, Yamane T, Tokuda M, Kanzaki Y, Inada K, Shibayama K, Miyanaga S, Date T, Miyazaki H, Abe K, Sugimoto K and Yoshimura M. The dormant epicardial reconnection of pulmonary vein: an unusual cause of recurrent atrial fibrillation after pulmonary vein isolation. Pacing Clin Electrophysiol. 2008;31:920-4. 12. Yokokawa M, Sundaram B, Garg A, Stojanovska J, Oral H, Morady F and Chugh A. Impact of mitral isthmus anatomy on the likelihood of achieving linear block in patients undergoing catheter ablation of persistent atrial fibrillation. Heart Rhythm. 2011;8:1404-10. 13. Wong KC, Lim C, Sadarmin PP, Jones M, Qureshi N, De Bono J, Rajappan K, Bashir Y and Betts TR. High incidence of acute sub-clinical circumflex artery 'injury' following mitral isthmus ablation. Eur Heart J. 2011;32:1881-90. 14. Di Biase L, Burkhardt JD, Mohanty P, et al. Left Atrial Appendage Isolation in Patients With Longstanding Persistent AF Undergoing Catheter Ablation: BELIEF Trial. J Am Coll Cardiol. 2016;68:1929-1940. 19
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15. Chan CP, Wong WS, Pumprueg S, et al. Inadvertent electrical isolation of the left atrial appendage during catheter ablation of persistent atrial fibrillation. Heart Rhythm. 2010;7:173-80. 16. Phillips KP, Natale A, Sterba R, Saliba WI, Burkhardt JD, Wazni O, Liberman L and Schweikert RA. Percutaneous pericardial instrumentation for catheter ablation of focal atrial tachycardias arising from the left atrial appendage. J Cardiovasc Electrophysiol. 2008;19:430-3. 17. Yamada T, McElderry HT, Allison JS and Kay GN. Focal atrial tachycardia originating from the epicardial left atrial appendage. Heart Rhythm. 2008;5:766-7.
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Figure Legends
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1. An example of ligament of Marshall (LOM)-pulmonary vein (PV) connection. During sinus rhythm, the ring catheter placed in the left superior PV (LSPV) records 2 potentials, a far-field left atrial (LA) potential, followed by the LOM. Pacing from the distal coronary sinus (CS), advances the 2nd potential and results in reversal of activation, confirming the presence of a LOM-PV connection. The LOM is activated immediately after CS activation. Pacing from the LA appendage (LAA) further accentuates the delay between LA and the LOM. After elimination of the LOM connection with radiofrequency ablation, delay is longer (130 ms to 160 ms) suggesting that the LOM’s role in mitral isthmus conduction. (Mitral isthmus block could not be achieved in this patient due to presence of a large pouch at the lateral isthmus). 2.
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A. An example of a LOM-PV connection that was eliminated during radiofrequency ablation at the lateral mitral annulus (MA). B. Fluoroscopic image showing the position of the ablation catheter and the ring catheter in the LSPV. 3.
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A. Termination of a reentrant atrial tachycardia involving the LOM during radiofrequency (RF) ablation at the lateral mitral annulus. This patient had previously undergone excision of the LA appendage as part of a surgical maze procedure. B. Further mapping actually revealed that tachycardia persisted at the anterior mitral annulus during sinus rhythm, suggesting that LOM and the subjacent atrial myocardium responsible for maintaining the tachycardia were insulated from the endocardium which was activated by the sinus rhythm wavefront. C. A schematic showing the likely mechanism of the tachycardia (red arrows) and proposed route of activation of the atrial mass. Conduction block across Bachmann’s bundle (BB) was caused by RF ablation of another tachycardia that was ablated at the anterior LA (not shown). D. Schema showing ongoing tachycardia with conduction block to the CS and the atria during sinus rhythm. RA=right atrium. VOM=vein of Marshall. GCV=great cardiac vein. LIPV=left inferior PV. SA=sinoatrial node.
4.
A. Balloon-occlusion of the CS showing the vein of Marshall (VOM). LI=left inferior. B. After inflation of a 1.5 mm balloon in the VOM, contrast injection shows dye “hang up.” C. Another selective venogram of the VOM shows extensive venous-venous communication over the left atrium. Alcohol instillation into the VOM in
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such a case would not only affect the lateral LA myocardium but also numerous other areas drained by the various intercommunicating veins. 5.
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A. Unipolar electrograms recorded by a catheter inserted into the vein of Marshall. B. Instillation of 1 cc of EtOH into the VOM leads to complete abolition of the atrial electrograms. (EtOH ablation of the VOM had no effect on AFEtOH infusion in this case was performed for mitral isthmus conduction.)
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6. Pleiotropic effects of EtOH ablation of the VOM. A. Without any RF energy delivery, infusion of 1 cc of EtOH yielded complete bidirectional block across of the mitral isthmus in this patient with prior LAA isolation. LLR=left lateral ridge. B. Complete isolation of the LIPV. C. Complete isolation of the LAA. A bipolar voltage map after EtOH infusion of the VOM showing absence of electrical conduction into the LAA. 7. A. An example of dual loop macro-reentrant tachycardia utilizing the LOM. The dashed arrows over the lateral mitral isthmus denotes epicardial conduction overlying the area of endocardial scar. RF energy (delivered at sites denoted by white tags between the LSPV and LAA) slowed the tachycardia (not shown). Gold tags=sites where the post pacing interval approximated the tachycardia cycle length. B. However, tachycardia termination required EtOH infusion into the vein of Marshall.
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Figure 1 Distal CS pacing
V1 LAd
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LOM
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Sinus rhythm
LAA pacing – post isolation
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Figure 2 A
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B III
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Figure 3
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Figure 4
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VOM LIPV
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I 1 cc EtOH
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Figure 5
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Figure 6
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Figure 7