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STATE-OF-THE-ART REVIEW Catheter Ablation of Arrhythmias Originating From the Left Ventricular Outow Tract Jim W. Cheung, MD, a Robert H. Anderson, MD, PHD, b Steven M. Markowitz, MD, a Bruce B. Lerman, MD a JACC: CLINICAL ELECTROPHYSIOLOGY CME/MOC/ECME This article has been selected as this months JACC: Clinical Electrophysiology CME/MOC/ECME activity, available online at http://www.acc.org/jacc-journals-cme by selecting the JACC Journals CME/MOC/ECME tab. Accreditation and Designation Statement The American College of Cardiology Foundation (ACCF) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) and the European Board for Accreditation in Cardiology (EBAC) to provide continuing medical education for physicians. The ACCF designates this Journal-based CME/MOC/ECME activity for a maximum of 1 AMAPRA Category 1 Credit or 1 EBAC Credit. Physicians should only claim credit commensurate with the extent of their partici- pation in the activity. Method of Participation and Receipt of CME/MOC/ECME Certicate To obtain credit for JACC: Clinical Electrophysiology CME/MOC/ECME, you must: 1. Be an ACC member or JACEP subscriber. 2. Carefully read the CME/MOC/ECME-designated article available online and in this issue of the journal. 3. Answer the post-test questions. A passing score of at least 70% must be achieved to obtain credit. 4. Complete a brief evaluation. 5. Claim your CME/MOC/ECME credit and receive your certicate electron- ically by following the instructions given at the conclusion of the activity. Catheter Ablation of Arrhythmias Originating From the Left Ventricular Outow Tract will be accredited by the European Board for Accreditation in Cardiology (EBAC) for 1 hour of External CME credits. Each participant should claim only those hours of credit that have actually been spent in the educational activity. The Accreditation Council for Continuing Med- ical Education (ACCME) and the European Board for Accreditation in Cardiology (EBAC) have recognized each others accreditation systems as substantially equivalent. Apply for credit through the post-course evaluation. CME/MOC/ECME Objective for This Article: Upon completion of this activity, the learner should be able to: 1) discuss the anatomic relationship between the aortic valvar leaets and the myocardial tissue at the aortic root and its implications for catheter ablation of arrhythmias arising from this region; 2) dene the juxtaposition of adjoining structures around the left ven- tricular outow and the role for targeting adjacent sites for successful ablation of arrhythmias arising from epicardial and intramural sites; and 3) recognize the potential limitations of electrocardiographic analysis for predicting the nal site of successful ablation of left ventricular outow tract arrhythmias. CME/MOC/ECME Editor Disclosure: CME/MOC/ECME Editor Smit Vasaiwala, MD, has reported that he has nothing to declare. Author Disclosures: Dr. Cheung has received consulting fees from Biosense Webster; and has received fellowship grant support from Abbott Medical, Biosense Webster, and Boston Scientic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Medium of Participation: Print (article only); online (article and quiz). CME/MOC/ECME Term of Approval Issue Date: January 2019 Expiration Date: December 31, 2019 ISSN 2405-500X/$36.00 https://doi.org/10.1016/j.jacep.2018.11.012 From the a Department of Medicine, Division of Cardiology, Weill Cornell MedicineNew York Presbyterian Hospital, New York, New York; and the b Institute of Genetic Medicine, Newcastle University, Newcastle Upon Tyne, United Kingdom. Dr. Cheung has received consulting fees from Biosense Webster; and has received fellowship grant support from Abbott Medical, Biosense Webster, and Boston Scientic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. All authors attest they are in compliance with human studies committees and animal welfare regulations of the authorsinstitutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page. Manuscript received October 22, 2018; revised manuscript received November 13, 2018, accepted November 21, 2018. JACC: CLINICAL ELECTROPHYSIOLOGY VOL. 5, NO. 1, 2019 ª 2019 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY ELSEVIER

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Page 1: Catheter Ablation of Arrhythmias Originating From the Left ... · APPROACH TO TARGETING AORTIC ROOT VA Aortic root VA account for up to 17% of idiopathic ventricular outflow tract

J A C C : C L I N I C A L E L E C T R O P H Y S I O L O G Y V O L . 5 , N O . 1 , 2 0 1 9

ª 2 0 1 9 B Y T H E AM E R I C A N C O L L E G E O F C A R D I O L O G Y F O UN DA T I O N

P U B L I S H E D B Y E L S E V I E R

STATE-OF-THE-ART REVIEW

Catheter Ablation ofArrhythmias Originating From theLeft Ventricular Outflow Tract

Jim W. Cheung, MD,a Robert H. Anderson, MD, PHD,b Steven M. Markowitz, MD,a Bruce B. Lerman, MDa

JACC: CLINICAL ELECTROPHYSIOLOGY CME/MOC/ECME

This article has been selected as this month’s JACC: Clinical

Electrophysiology CME/MOC/ECME activity, available online at

http://www.acc.org/jacc-journals-cme by selecting the JACC Journals

CME/MOC/ECME tab.

Accreditation and Designation Statement

The American College of Cardiology Foundation (ACCF) is accredited by

the Accreditation Council for Continuing Medical Education (ACCME)

and the European Board for Accreditation in Cardiology (EBAC) to

provide continuing medical education for physicians.

The ACCF designates this Journal-based CME/MOC/ECME activity for a

maximum of 1 AMAPRA Category 1 Credit or 1 EBAC Credit. Physicians

should only claim credit commensurate with the extent of their partici-

pation in the activity.

Method of Participation and Receipt of CME/MOC/ECME Certificate

To obtain credit for JACC: Clinical Electrophysiology CME/MOC/ECME,

you must:

1. Be an ACC member or JACEP subscriber.

2. Carefully read the CME/MOC/ECME-designated article available

online and in this issue of the journal.

3. Answer the post-test questions. A passing score of at least 70% must

be achieved to obtain credit.

4. Complete a brief evaluation.

5. Claim your CME/MOC/ECME credit and receive your certificate electron-

ically by following the instructions given at the conclusion of the activity.

Catheter Ablation of Arrhythmias Originating From the Left Ventricular

Outflow Tract will be accredited by the European Board for Accreditation

in Cardiology (EBAC) for 1 hour of External CME credits. Each participant

should claim only those hours of credit that have actually been spent in

ISSN 2405-500X/$36.00

From the aDepartment of Medicine, Division of Cardiology, Weill Cornell Me

New York; and the bInstitute of Genetic Medicine, Newcastle University, New

received consulting fees from Biosense Webster; and has received fellow

Webster, and Boston Scientific. All other authors have reported that they h

paper to disclose.

All authors attest they are in compliance with human studies committe

institutions and Food and Drug Administration guidelines, including patien

visit the JACC: Clinical Electrophysiology author instructions page.

Manuscript received October 22, 2018; revised manuscript received Novemb

the educational activity. The Accreditation Council for Continuing Med-

ical Education (ACCME) and the European Board for Accreditation in

Cardiology (EBAC) have recognized each other’s accreditation systems as

substantially equivalent. Apply for credit through the post-course

evaluation.

CME/MOC/ECME Objective for This Article: Upon completion of this activity,

the learner should be able to: 1) discuss the anatomic relationship between

the aortic valvar leaflets and the myocardial tissue at the aortic root and its

implications for catheter ablation of arrhythmias arising from this region;

2) define the juxtaposition of adjoining structures around the left ven-

tricular outflow and the role for targeting adjacent sites for successful

ablation of arrhythmias arising from epicardial and intramural sites; and

3) recognize the potential limitations of electrocardiographic analysis for

predicting the final site of successful ablation of left ventricular outflow

tract arrhythmias.

CME/MOC/ECME Editor Disclosure: CME/MOC/ECME Editor Smit

Vasaiwala, MD, has reported that he has nothing to declare.

Author Disclosures: Dr. Cheung has received consulting fees from

Biosense Webster; and has received fellowship grant support from Abbott

Medical, Biosense Webster, and Boston Scientific. All other authors have

reported that they have no relationships relevant to the contents of this

paper to disclose.

Medium of Participation: Print (article only); online (article and quiz).

CME/MOC/ECME Term of Approval

Issue Date: January 2019

Expiration Date: December 31, 2019

https://doi.org/10.1016/j.jacep.2018.11.012

dicine—New York Presbyterian Hospital, New York,

castle Upon Tyne, United Kingdom. Dr. Cheung has

ship grant support from Abbott Medical, Biosense

ave no relationships relevant to the contents of this

es and animal welfare regulations of the authors’

t consent where appropriate. For more information,

er 13, 2018, accepted November 21, 2018.

Page 2: Catheter Ablation of Arrhythmias Originating From the Left ... · APPROACH TO TARGETING AORTIC ROOT VA Aortic root VA account for up to 17% of idiopathic ventricular outflow tract

Cheung et al. J A C C : C L I N I C A L E L E C T R O P H Y S I O L O G Y V O L . 5 , N O . 1 , 2 0 1 9

Approach to LVOT Arrhythmias J A N U A R Y 2 0 1 9 : 1 – 1 2

2

Catheter Ablation of Arrhyt

hmias OriginatingFrom the Left Ventricular Outflow Tract Jim W. Cheung, MD,a Robert H. Anderson, MD, PHD,b Steven M. Markowitz, MD,a Bruce B. Lerman, MDa

ABSTRACT

The left ventricular outflow tract (LVOT) is a frequent source of arrhythmias in patients with and without structural heart

disease. An understanding of the anatomic relationship between the aortic valvar leaflets and their supporting sinuses,

coronary vessels, pulmonary arterial root, right ventricular outflow tract, and LVOT is essential for successful treatment of

arrhythmias arising from this region. The juxtaposition of aortic valvar leaflet insertion into the aortic root and the cres-

cents of myocardial tissue incorporated within the aortic sinuses of Valsalva has implications for mapping and ablation

above and below the aortic valve leaflets. The presence of epicardial fat, coronary arteries, and prominent myocardium in

the anteroseptal aspect of the LVOT can present unique challenges for targeting LV summit and intramural ventricular

arrhythmias. Advances in ablation techniques that achieve deeper transmural lesions, combined with the knowledge of the

complex LVOT anatomy and its adjoining structures, have increased success rates in targeting challenging LVOT

arrhythmias. (J Am Coll Cardiol EP 2019;5:1–12) © 2019 by the American College of Cardiology Foundation.

T he left ventricular outflow tract (LVOT) is animportant source of ventricular arrhythmias(VA) in patients with and without structural

heart disease. Up to one-third of all idiopathic VA inpatients without structural heart disease are thoughtto arise from the LVOT region (1–3). Furthermore, dueto the high prevalence of basal left ventricular (LV)and peri-aortic scar among patients with nonischemiccardiomyopathy (4,5), the LVOT is also a source ofarrhythmias in patients with structural heart disease.Arrhythmias arising from the aortic root and itssupporting ventricular structures, including the LVsummit, can all be targeted with catheter ablation. Adetailed understanding of the anatomy of the LVOTis central to successful ablation outcome. Herein, weprovide an overview of the ablation approaches fortargeting LVOT VA, with a focus on the uniqueaspects of the LVOT anatomy that determine the sitesof successful ablation.

OVERVIEW OF THE ANATOMY OF THE LVOT

The complex nature of LVOT anatomy and its rela-tionship with adjoining structures have implicationsfor mapping and ablating arrhythmias arising fromthe region. The anatomic ventriculo-arterial junction(VAJ) marks the interface of the LV myocardialaspect of the muscular septum and the fibroelasticwall of the aortic trunk (Figure 1). The hinge lines ofthe aortic valvar leaflets, supported by the coronarysinuses, extend proximally below the VAJ, thuscreating crescents of ventricular myocardial tissue at

the base of the sinuses (6). This tissue constitutesthe origin of aortic root VA. The right aortic valvarleaflet, supported by the right aortic sinus of Val-salva (ASV), forms the anterior attachment of theaorta to the LVOT, whereas the left aortic valvarleaflet, supported by the left ASV, forms the lateralattachment. The anterior aspect of the left aorticvalvar leaflet interfaces with LVOT myocardiumwhereas its posterior aspect abuts the left fibroustrigone and the region of the aortomitral continuity(AMC). Therefore, significantly less myocardial tis-sue is present within the left ASV than in the rightASV (7). The AMC is supported by a triangular regionof myocardial tissue that is a site for both idiopathicVA (8) and VA associated with myocardial scar (9).The noncoronary ASV lies adjacent to the paraseptalregion between the right and left atria. Its leafletforms the major component of the region of theAMC. The rightward border of this region is part ofthe central fibrous body, which incorporates themembranous septum (10). The membranous septumoccupies the base of the interleaflet triangle betweenthe hinges of the right and noncoronary valvarleaflets. The bundle of His penetrates through theatrioventricular component of the membranousseptum to reach the crest of the muscular ventricularseptum. Rarely, the noncoronary leaflet of the aorticvalve may have myocardial support. Therefore, inmost instances, only the septal, anterior, and ante-rolateral aspects of the endocardial LVOT below theattachment of the aortic valvar leaflets are made upof myocardium.

Page 3: Catheter Ablation of Arrhythmias Originating From the Left ... · APPROACH TO TARGETING AORTIC ROOT VA Aortic root VA account for up to 17% of idiopathic ventricular outflow tract

FIGURE 1 Anatomy of the Aortic Root

Gross dissection of the aortic valve with a sagittal cut made between the right (R) and non-

coronary (NC) aortic valvar leaflets. The noncoronary aortic sinus has been pulled to the

left (L) with the photograph taken from a left posterior oblique view with respect to the

heart position within chest. The aortic root is bounded superiorly by the sinotubular

junction (black dashed line) and inferiorly by the nadirs of the attachments of the semi-

lunar aortic valvar leaflets (blue line). The ventriculo-arterial junction (VAJ) is demarcated

with a thick black dotted line. Regions where ventricular myocardium may be identified

within the aortic sinus of Valsalva (ASV) are shown in red. The interleaflet spaces are

shown in green. AMC ¼ aortomitral continuity; LVOT ¼ left ventricular outflow tract.

AB BR E V I A T I O N S

AND ACRONYM S

AIV = anterior interventricular

vein

AMC = aortomitral continuity

ASV = aortic sinus of Valsalva

ECG = electrocardiography

GCV = great cardiac vein

LV = left ventricular

LVOT = left ventricular

outflow tract

R-L commissure =

commissure between right and

left aortic sinuses of Valsalva

RVOT = right ventricular

outflow tract

VA = ventricular arrhythmia

VAJ = ventriculo-arterial

ion

J A C C : C L I N I C A L E L E C T R O P H Y S I O L O G Y V O L . 5 , N O . 1 , 2 0 1 9 Cheung et al.J A N U A R Y 2 0 1 9 : 1 – 1 2 Approach to LVOT Arrhythmias

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The LV summit constitutes the superior-mostaspect of the LV ostium. Although the entire basalmyocardial aspect of this region could be consideredthe summit, we will restrict its anatomic definition forthe purposes of this review to its epicardial compo-nent, following the precedent of McAlpine (11). It isdefined as a triangular region, the apex of which isformed by the bifurcation of the left anteriordescending and left circumflex arteries, with its baseformed by the arc between the first septal perforatorof the left anterior descending artery and the leftcircumflex artery (Figure 2). The great cardiac vein(GCV) can bisect this space into medial and lateralregions, termed the basal and apical LV summit,respectively (12,13). The basal LV summit is charac-terized by its close proximity to the main stem of theleft coronary artery and the presence of epicardial fat.It should be noted, however, that the relationshipbetween the course of the GCV and the coronaryarteries can vary greatly (14). Communicating veinbranches of the GCV course epicardially over the LVsummit region (13,15), whereas septal perforatingbranches of the GCV drain the intramural LVOTmyocardium underneath the LV summit (16).

With regard to the anatomic relationships of thestructures surrounding the LV summit, it is impor-tant to appreciate the topological relationship be-tween the outflow tracts of the right and leftventricles. The right ventricular outflow tract (RVOT)wraps superiorly, anteriorly, and leftward above theaortic root. The left and right pulmonary sinuses,along with the posterior aspect of their supportingmuscular sleeve, lie in close apposition to the leftASV and the commissure between the right and leftASV (R-L commissure) (17) (Figure 3). The moreproximal aspect of the RVOT abuts the right coro-nary ASV. In some patients, the left-most aspect ofthe RVOT can be in close proximity (<10 mm) to theanterior interventricular vein (AIV) and the LVsummit (18). Therefore, based on the anatomicjuxtaposition of the endocardial LVOT, the aorticroot, the GCV with its communicating and septalbranches, and the RVOT, there are multiple ap-proaches to targeting a single site of arrhythmicorigin within the LVOT. This has implications notonly for successful catheter ablation outcome, butalso for adjudication of the sites of origin of ar-rhythmias, and their correlation with electrocardio-graphic (ECG) findings.

APPROACH TO TARGETING AORTIC ROOT VA

Aortic root VA account for up to 17% of idiopathicventricular outflow tract arrhythmias (19,20). Because

the arrhythmias arise at the region of the VAJ,they may be targeted from above or below thehinges of the aortic valvar leaflets. Whenapproaching the aortic valve from above witha retrograde approach, the pockets ofmyocardial tissue at the bases of the left andright ASV can be readily accessed withappropriate contact force. A transseptalapproach can also provide access to this tis-sue from a site below the leaflets, providedthat the extent of myocardial tissue above theleaflet hinges is limited (Figures 4A and 4B).Indeed, an autopsy series of 604 heartsshowed that the mean maximal extension ofventricular tissue above the attachment ofthe leaflets is 2.8 � 1.2 mm for the right cor-onary sinus and 1.5 � 0.5 mm for the leftcoronary sinus (7). These distances wouldgenerally fall within the range of an average

open irrigation radiofrequency ablation lesion(w7 mm depth with 30 W at 10 g contact force [21]). Itshould also be noted that the converse is also true—that is, VA arising just below the leaflet attachmentmay be successfully ablated using a retrograde,supravalvular approach, provided that the distancebetween the VA source and ablation catheter tip isrelatively small.

junct

Page 4: Catheter Ablation of Arrhythmias Originating From the Left ... · APPROACH TO TARGETING AORTIC ROOT VA Aortic root VA account for up to 17% of idiopathic ventricular outflow tract

FIGURE 2 Anatomic Definition of the LV Summit

The left ventricular (LV) summit (yellow dotted outline) is shown on a 3-dimensional

rendering of a cardiac computed tomography scan with coronary angiography and

venography in a cranial right anterior oblique view. It is defined as an epicardial triangular

structure whose apex is formed by the bifurcation of branches of the left coronary artery.

The basal extent of the triangle is formed by the arc drawn from the origin of the first

septal perforator of the left anterior descending artery (LAD) to the left circumflex artery

(LCX). The right and left ASV are outlined (light yellow dashed line). AIV ¼ anterior

interventricular vein; GCV ¼ great cardiac vein; LM ¼ left main coronary artery; R-L

comm ¼ commissure between right and left ASV; RVOT ¼ right ventricular outflow tract;

summit-CV ¼ communicating veins of the GCV; other abbreviations as in Figure 1.

Cheung et al. J A C C : C L I N I C A L E L E C T R O P H Y S I O L O G Y V O L . 5 , N O . 1 , 2 0 1 9

Approach to LVOT Arrhythmias J A N U A R Y 2 0 1 9 : 1 – 1 2

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In our experience, the distribution of sites of suc-cessful ablation of aortic root VA within the left ASV,right ASV, or the R-L commissure is largely dependenton whether a retrograde transaortic versus trans-septal mapping approach to the aortic root is used(Online Figure 1) (22). This is related to the semilunarinsertion of the aortic valvar leaflets within the aorticroot, which creates triangular interleaflet spaces(Figure 1). Arrhythmias appearing to arise from theR-L commissure likely originate from tissue at thelevel of the VAJ, just below the base of the interleaflettriangle. Hence, when approaching the aortic valvefrom below the leaflets with the transseptal approach,direct access to the interleaflet space below the R-Lcommissure is readily obtained. In the absence of theanatomic constraints posed by the insertion of theleaflets to the base of the LV ostium, a transseptalapproach is more likely to facilitate successful abla-tion in the region of the R-L commissure (Figure 5).Alternatively, if a retrograde approach is used, map-ping of the VAJ tissue is more readily performedwithin the valvar sinuses. However, direct access to

the interleaflet space of the R-L commissure is pre-cluded unless the catheter is advanced below thevalve. Therefore, the designation of the site of VAorigin with respect to the ASV can be arbitrary. It maybe more a function of the mapping approach(above-valve vs. below-valve), rather than a trueanatomic distinction. This highlights the potentiallimitations of ECG morphologic criteria to differen-tiate among VA arising from the left as opposed to theright ASV or the R-L commissure.

At our institution, we have adopted a first-linetransseptal approach to targeting VA arising fromthe aortic root and the LVOT for several reasons. First,a transseptal approach may facilitate construction ofa more comprehensive electroanatomic map of theLVOT. In a study of patients with VA arising from theanteroseptal region of the LVOT, Ouyang et al. (3)found that mapping via a transseptal approach facil-itated identification of the site of origin of VA. Incontrast, retrograde transaortic mapping led to gapsof up to 12 mm between the basal ring of the aorticroot and the LVOT, precluding access to sites of VAorigin that were approximately 5 mm below the aorticvalvar leaflets. Second, transseptal access to theLVOT may decrease the risks of complications asso-ciated with aortic instrumentation. Both coronaryarterial injury (23) and aortic dissection (24) havebeen described when ablating the aortic root using aretrograde approach. Furthermore, the retrogradeapproach to LV VA ablation may be associated with anincreased risk of brain emboli. In a study of patientswho underwent VA ablation followed by brain mag-netic resonance imaging, 63% of patients undergoinga retrograde approach to the LV had silent cerebralemboli (25). It should be acknowledged that manualcatheter manipulation to the LVOT via transseptalapproach can be challenging. This is because areversed S curve of the ablation catheter often has tobe created to reach the region (3). We have foundremote magnetic navigation to be useful in facili-tating catheter access to the LVOT and aortic rootwhile maintaining excellent catheter stability. In ourexperience, successful aortic root VA ablation can beachieved in 79% of patients using a first-line trans-septal approach by targeting the site of origin frombeneath the valve, without the need to switch toablation from above the valve (22).

APPROACH TO TARGETING INTRAMURAL

AND LV SUMMIT LVOT ARRHYTHMIAS

Although aortic root and endocardial LVOT VA can bereadily treated with endocardial ablation (26), intra-mural LVOT and LV summit VA can present specific

Page 5: Catheter Ablation of Arrhythmias Originating From the Left ... · APPROACH TO TARGETING AORTIC ROOT VA Aortic root VA account for up to 17% of idiopathic ventricular outflow tract

FIGURE 3 Anatomic Relationship Between the LVOT and RVOT at the Level of the Aortic and Pulmonary Arterial Roots

Histologic sagittal cuts were made between the LVOT, the RVOT, and the pulmonary and aortic roots. (A) Apposition between the infundibular

sleeve supporting the base of the right pulmonary sinus of Valsalva (PSV) and the commissure between the right and left ASV is shown.

(B) Apposition is shown between myocardium tissue at the bases of left ASV and left PSV. Red dots show the myocardial interface between the

ventricular outflow tracts at the crest of the ventricular septum. Modified from Sanchez-Quintana et al. (17). LCA ¼ left coronary artery; other

abbreviations as in Figures 1 and 2.

J A C C : C L I N I C A L E L E C T R O P H Y S I O L O G Y V O L . 5 , N O . 1 , 2 0 1 9 Cheung et al.J A N U A R Y 2 0 1 9 : 1 – 1 2 Approach to LVOT Arrhythmias

5

challenges for mapping and ablation. Intramural sitesof origin from the ventricular septal crest have beendescribed for idiopathic VA (16) as well as VA associ-ated with structural heart disease (27). LV summit VA,

FIGURE 4 Histology of the Aortic Root Region and Its Relevance to

(A) Histology of a sagittal section of the left aortic valvar leaflet is show

the leaflet (red dot) to the peak of the VAJ (black dotted line) is meas

valvar leaflet is shown with trichrome stain. The distance (black arrow) fr

VAJ (black dotted line) is measured here at 4.2 mm. Abbreviations as in

on the other hand, primarily occur in the absence ofstructural heart disease. Identification of an intra-mural septal VA origin requires meticulous mappingof the LVOT and all of its adjacent structures, which

Catheter Ablation of VA From Below the Aortic Valvar Leaflets

n with trichrome stain. The distance from a site below the insertion of

ured at 3.3 mm. (B) Histology of a sagittal section of the right aortic

om a site below the insertion of the leaflet (red dot) to the peak of the

Figures 1 and 2.

Page 6: Catheter Ablation of Arrhythmias Originating From the Left ... · APPROACH TO TARGETING AORTIC ROOT VA Aortic root VA account for up to 17% of idiopathic ventricular outflow tract

FIGURE 5 Illustrative Diagram Demonstrating Impact of Above-Valve Versus Below-Valve Approach to Aortic Root VA Ablation

(A)With a “below-valve” approach to targeting aortic root VA, the ablation catheter (blue) sits either below the interleaflet triangle beneath the right-left commissure or

directly below the hinges of the valvar leaflets. The sinotubular junction (dashed black line) and the VAJ (thick dotted black line) are shown. Interleaflet triangles are

shown in green, and the regions of myocardium with the ASV are shown in pink. The area of the VAJ that would be susceptible to ablation is outlined (blue hatching).

Note that portions of myocardium within the ASV may be present outside the zone of injury from ablation (gray). (B) With an “above-valve” approach to targeting aortic

root VA, the ablation catheter (blue) sits within the left or right ASV. The area of the VAJ that would be susceptible to ablation is marked by blue hatching. Note that all

of the myocardium within the ASV is accessible to the ablation catheter. A region at the VAJ at the commissure between the left and right ASV marked in gray would be

potentially inaccessible to a catheter placed above the valve leaflets. (C) Site of VA origin within the aortic root is marked with a red star. If a transseptal approach is

used, the VA would be successfully ablated from the right-left commissure. If a retrograde approach is used, the VA would be successfully ablated within the left ASV.

NC ¼ noncoronary; other abbreviations as in Figures 1 and 2.

Cheung et al. J A C C : C L I N I C A L E L E C T R O P H Y S I O L O G Y V O L . 5 , N O . 1 , 2 0 1 9

Approach to LVOT Arrhythmias J A N U A R Y 2 0 1 9 : 1 – 1 2

6

include the aortic root, the coronary venous system,and the RVOT. Endocardial LV and RV mappingshows broad early sites of activation on either side ofthe septum, suggestive of a mid-myocardial source.Additional mapping using the coronary venous sys-tem helps differentiate intramural from epicardial LVsummit sources. Activation of VA within the distalGCV and proximal AIV can be assessed using either anablation catheter or a small caliber multipolar cath-eter, such as a 4-F quadripolar catheter (Inquiry,Abbott, St. Paul, Minnesota). If activation in this re-gion is early (i.e., >25 ms pre-QRS onset with steep QSunipolar recording), then the site of origin is from theLV summit. On the other hand, if activation withinthe distal GCV and AIV region is late or broad, a se-lective venogram of the distal GCV and its branchesshould be performed. If epicardial communicating or

septal perforating branches are identified, then acti-vation mapping using an ablation catheter, a micro-catheter (e.g., 2-F EPstar Fix, Japan Lifeline, Tokyo,Japan) (15), or a coated guidewire (e.g., Visionwire,Biotronik, Berlin, Germany) should be performed(Figure 6). An early site in an epicardial communi-cating branch of the GCV would suggest an LV summitorigin whereas an early site in a septal perforatingvein would suggest an intramural source.

Once an intramural or LV summit VA site of originhas been established, the challenge is to deliveradequate ablation energy. If an early site is identifiedwithin the main body of the distal GCV and proximalAIV, irrigated radiofrequency ablation can beperformed safely as long as precautions are taken.Coronary angiography may be considered to ensurethat the target site is not within 5 mm of a major

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FIGURE 6 Mapping Branches of the GCV to Localize LV Summit VA

(A) Coronary sinus (CS) venography illustrates course of a communicating vein branch (summit-CV) (yellow arrows) of the GCV in right anterior oblique (RAO) (top) and

left anterior oblique (LAO) projection (bottom). (B) Positioning of a 2-F microcatheter placed in the summit-CV branch and an ablation catheter in posteroseptal aspect

of the RVOT. (C) Twelve-lead electrocardiographic and intracardiac recordings showing early premature ventricular contraction activation within the summit-CV branch

(44 ms pre-QRS interval) with a comparable but slightly later activation at the ablation catheter site in the RVOT. Ablation at the RVOT site eliminated the premature

ventricular contraction. Modified with permission from Komatsu et al. (15). ABL ¼ ablation catheter; AIVV ¼ anterior interventricular vein; HIS ¼ bundle of His; MC ¼microcatheter; SR ¼ sinus rhythm; other abbreviations as in Figures 1 and 2.

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arterial vessel. If sufficient distance is identified fromthe coronary arteries, then irrigated radiofrequencyenergy may be administered within the vein, using agradual titration of delivery of power, while payingclose attention to any rises in temperature orimpedance. Due to the low local blood flow within thevein, power delivery is often limited and higherirrigation flow rates may be required. These limita-tions, combined with the presence of epicardial fat inthe LV summit, can preclude successful radio-frequency ablation of LV summit VA from the coro-nary venous system. In such cases, alternativesshould be considered.

One approach for targeting intramural and LVsummit VA that are not accessible to ablation via thecoronary venous system is to ablate adjacent “nextbest” endocardial site(s), which include the ASV, theendocardial LVOT below the valvar leaflets, and theRVOT. The choice of the first adjacent endocardialsite to target should be guided by the comparison of

local VA activation times and the quality of pacemapping among these 3 regions. In cases whereearliest activation has been identified within a septalperforating vein or a communicating branch of theGCV, the position of the venous guidewire or diag-nostic catheter on fluoroscopy or 3-dimensionalelectroanatomic map can be used as a landmark todetermine the closest endocardial target. Separationof <1.35 cm between the site of VA origin and theadjacent site of endocardial ablation is associatedwith increased likelihood of successful ablation (28).To achieve sufficiently deep lesions, prolongedapplication of radiofrequency ablation may berequired with higher power and high contact force(29). In addition, sequential ablation at more than1 endocardial site may be required to achieve success.

Even with prolonged energy delivery, conven-tional unipolar radiofrequency ablation may notcreate sufficiently deep lesions in the thick myocar-dium of the anteroseptal LVOT to abolish LV summit

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CENTRAL ILLUSTRATION Overview of Approach to Targeting LVOT Arrhythmias

Cheung, J.W. et al. J Am Coll Cardiol EP. 2019;5(1):1–12.

*If an early site is identified within a branch of the great cardiac vein (GCV), then the guidewire or microcatheter position can be used as an

anatomic guide for adjacent ablation. **If ventricular arrhythmia activation within a GCV branch is not early or if access to communicating vein

or septal perforator branches of the GCV is not possible, then ablation of adjacent site(s) based on the earliest activation times achievable can

be performed in a sequential manner. AIV ¼ anterior interventricular vein; ASV ¼ aortic sinus of Valsalva; LVOT ¼ left ventricular outflow tract;

PSV ¼ pulmonary sinus of Valsalva; RVOT ¼ right ventricular outflow tract.

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FIGURE 7 Alteration of VA Exit Sites With Ablation in the RVOT and LVOT

(Left) Electroanatomic map of the right ventricle showing early activation in the septal aspect of the RVOT with onset of activation to QRS time of 30 ms and steep QS

unipolar (UNI) electrogram. Ablation at this site led to VA suppression for 5 min. (Middle) Twelve-lead electrocardiographic showing shift in QRS morphology of target

arrhythmia with precordial transition shifting from lead V4 to lead V3 (white ovals) following initial ablation in the RVOT. (Right) Repeat mapping of the GCV, LVOT, and

ASV showed earliest activation at a site under the left coronary cusp with a pre-potential preceding QRS onset by 38 ms. Ablation at this site led to VA elimination.

BI ¼ bipolar electrogram; other abbreviations as in Figures 1, 2, 5, and 6.

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and intramural VA. Alternative techniques such assimultaneous unipolar radiofrequency ablation,bipolar radiofrequency ablation, half-normal salineirrigation, retrograde ethanol ablation, and intra-mural needle ablation have been all been proposed.With simultaneous unipolar radiofrequency ablation,delivery of energy with 2 ablation catheters resultsin simultaneous resistive and conductive heating at2 sites. The convergence of 2 propagating thermalwave fronts toward a mid-myocardial site can thenlead to formation of a full transmural ablation lesion(30). In several patients, simultaneous unipolar radi-ofrequency ablation has been shown to be moreeffective than sequential ablation for targetingintramural VA, especially in cases where the inter-catheter distance is >8 mm (31).

Bipolar radiofrequency ablation, which uses2 ablation catheter tips, with one serving as the activepole and the other as the ground pole, has also beenshown to improve lesion transmurality. Instead ofusing a patch as the dispersive electrode, the use ofan ablation catheter tip as the ground allows moreefficient dissipation of current density to the tissuebetween the catheter tips (30). In ex vivo experimentsusing porcine ventricular tissue, use of bipolar

radiofrequency ablation yielded transmural lesionsup to 25 mm in depth (32). Variables such as cathetertip-to-tip distance and orientation, catheter electrodesize, contact force, and duration of energy deliverycan all influence the volume and depth of bipolarlesions. The parameters for monitoring bipolar abla-tion for the prevention of tissue overheating andsteam pops are less clear, and require further study.Recently, the use of half-normal saline irrigation hasbeen proposed as a method to increase radio-frequency ablation lesion depth (33). By decreasingthe ionic concentration, and thereby increasingthe impedance of the surrounding fluid around thetissue, increased current density is driven into thetissue during ablation, thus yielding deeper lesions.In ex vivo experiments, lesion sizes comparable tothose achieved with bipolar radiofrequency ablationwere achieved with half-normal saline irrigationunipolar ablation.

Needle ablation has also been investigated for thetreatment of intramural VA. Early studies using anovel deflectable catheter with an extendable andretractable nitinol needle that can record intramuralbipolar electrograms, as well as delivering irrigatedradiofrequency ablation, have been shown to be

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effective in the treatment of refractory intramuralVA (27). Nonradiofrequency ablation strategies suchas retrograde coronary venous ethanol ablation havealso been proposed, especially for targeting intra-mural septal and LV summit VA where coronaryvenous access to the VA site of origin has alreadybeen established. At high concentrations, ethanolsolubilizes cell membranes and leads to celldestruction. If a target vessel is identified, test dosesof ethanol can be administered with inflation of aproximal angioplasty balloon to assess for thera-peutic effect (34). Intracardiac echocardiographicvisualization of increased myocardial echogenicitycan further confirm the correct site of ethanolablation.

Should all of the above-mentioned approaches fail,an epicardial approach to the LV summit may beconsidered. Typically, given the presence of coronaryarteries, epicardial fat and the left atrial appendageoverlying the LV summit, a percutaneous trans-pericardial approach may not allow adequate accessto the VA site of origin. However, it is possible to use asurgical approach, where dissection of the epicardialfat and retraction of the left atrial appendage canallow access to the LV summit. Open surgical ap-proaches including the use of cryoablation have beendescribed, but they can be limited by arrhythmiasuppression with general anesthesia as well as riskof coronary injury (35). Mini-thoracotomy and endo-scopic surgical approaches for epicardial mappingand ablation of LV summit arrhythmias have alsobeen reported (36,37).

SPECIAL CONSIDERATIONS FOR TARGETING

LVOT ARRHYTHMIAS ASSOCIATED WITH

STRUCTURAL HEART DISEASE

The LVOT is a critical site for not only idiopathic VA,but also for VA associated with structural heart dis-ease. LVOT VA can arise from scar involving the basalLV septum and the peri-aortic region both in patientswith dilated nonischemic cardiomyopathy and inpatients with preserved LV ejection fraction (4,5).Some peri-aortic scar-associated LVOT VA may mimicidiopathic VA. LVOT VA due to structural heart dis-ease can be differentiated from idiopathic VA on thebasis of the presence of: 1) late gadolinium enhance-ment on cardiac magnetic resonance imaging; 2)abnormal bipolar or unipolar voltage in the peri-aorticregion; and 3) multiple inducible ventricular tachy-cardia morphologies, often with shorter cycle lengthsassociated with hemodynamic instability (4,5). Thepresence of abnormal septal LVOT unipolar voltage in

the setting of relatively normal epicardial and endo-cardial bipolar voltage in the region is suggestive ofabnormal intramural substrate (4). Adenosine testingcan also help distinguish scar-associated ventriculartachycardia from idiopathic ventricular tachycardia.Scar-associated ventricular tachycardia is usually dueto re-entry and is therefore adenosine-insensitive,whereas most idiopathic ventricular tachycardia aredue to triggered activity and hence are adenosine-sensitive (38). In general, due to the presence oflarger regions of arrhythmogenic substrate and thepropensity for these arrhythmias to arise from deepintramural sources, the risks of recurrence aftercatheter ablation of scar-associated LVOT VA arehigher than those of idiopathic VA. For intramuralscar-associated VA, the use of alternative ablationstrategies such as bipolar or ethanol ablation as wellas surgical ablation, as discussed, should beconsidered.

CAVEATS TO ECG ANALYSIS TO GUIDE

LVOT VA ABLATION

When planning for LVOT VA ablation, the ECG canhelp localize likely sites of origin. If ECG analysisstrongly favors an LV site of origin, mapping can startwith the ASV and endocardial LVOT region below thevalvar leaflets. An overview of our approach is sum-marized in the Central Illustration. Criteria based onQRS amplitudes and QRS morphology have beenproposed to differentiate LVOT from RVOT sites oforigin (39,40), as well as to localize sites to the indi-vidual aortic sinuses (19), the R-L commissure(20,41), the AMC region (8), and the LV summit(12,13). Whereas these ECG tools can be helpful inguiding initial mapping strategies, individualanatomic variations in the position of the heartwithin the chest cavity may limit their resolution.Furthermore, some VA can be approached fromdifferent sites with equal success. Indeed, 1 group hasshown that a significant number of VA localized tothe ASV on the basis of ECG criteria could be ablatedsuccessfully from within the left pulmonary sinus(42). The presence of preferential and multiple exitsof LVOT VA can further complicate their localizationbased on ECG criteria alone. In some cases, initialactivation mapping of VA may show early activationin the ASV. Following ablation, initial suppression isseen but recurrent premature ventricular contrac-tions then occur with an alteration in VA activationpattern suggestive of an RVOT origin. Alternatively,initial mapping of VA showing early activation in theRVOT followed by ablation can lead to a subsequent

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shift to an exit in the region of the ASV (Figure 7).This phenomenon has been shown to occur in 3% to4% of patients undergoing catheter ablation of idio-pathic outflow tract VA (43). These cases likelyrepresent sites of VA origin that lie at the interface ofthe RVOT and the LVOT with multiple preferentialexits.

CONCLUSIONS

The LVOT is a major source of arrhythmias in pa-tients with and without structural heart disease.The juxtaposition of the aortic valvar leaflets, thecoronary vessels, and the RVOT around the regionof the LVOT can present both multiple options, aswell as impediments, for successful treatment ofLVOT VA with catheter ablation. Whereas aorticroot VA can be readily ablated with success fromeither above or below the valvar leaflets due to thelimited extent of myocardial tissue incorporated at

the bases of the ASV, intramural LVOT and LVsummit arrhythmias are less readily accessed due tothe presence of thicker anteroseptal myocardiumand epicardial fat. Advances in techniques to ach-ieve deeper transmural ablation lesions, combinedwith the knowledge of the complex anatomy of theLVOT and its adjoining structures, are essential formeeting the challenges of targeting intramural andepicardial VA.

ACKNOWLEDGMENTS The authors thank Dr. Nav-neet Narula and Dr. Cathleen Matrai for providinganatomical and histological specimens for the figuresused in the work. The authors also thank Nicole Go forproviding technical assistance.

ADDRESS FOR CORRESPONDENCE: Dr. Jim W.Cheung, Division of Cardiology, Weill Cornell Medicine,520 East 70th Street, 4th Floor, New York, NewYork 10065. E-mail: [email protected].

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KEY WORDS aortic root, aortic sinuses ofValsalva, catheter ablation, left ventricularoutflow tract, left ventricular summit

APPENDIX For a supplemental figure, pleasesee the online version of this paper.

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