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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

Localization of AccessoryPathways in Pediatric Patients WithWolff-Parkinson-White SyndromeUsing 3D-Rendered ElectromechanicalWave Imaging

Lea Melki, MSC, MPHIL,a,* Christopher S. Grubb, BS,b,* Rachel Weber, BA, RDCS, RVT,a Pierre Nauleau, PHD,a

Hasan Garan, MD,b Elaine Wan, MD,b Eric S. Silver, MD,c Leonardo Liberman, MD,c,y Elisa E. Konofagou, PHDa,d,y

ABSTRACT

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OBJECTIVES This study sought to demonstrate the feasibility of electromechanical wave imaging (EWI) for localization

of accessory pathways (AP) prior to catheter ablation in a pediatric population.

BACKGROUND Prediction of AP locations in patients with Wolff-Parkinson-White syndrome is currently based on

analysis of 12-lead electrocardiography (ECG). In the pediatric population, specific algorithms have been developed to aid

in localization, but these can be unreliable. EWI is a noninvasive imaging modality relying on a high frame rate ultrasound

sequence capable of visualizing cardiac electromechanical activation.

METHODS Pediatric patients with ventricular pre-excitation presenting for catheter ablation were imaged with EWI

immediately prior to the start of the procedure. Two clinical pediatric electrophysiologists predicted the location of

the AP based on ECG. Both EWI and ECG predictions were blinded to the results of catheter ablation. EWI and ECG

localizations were subsequently compared with the site of successful ablation.

RESULTS Fifteen patients were imaged with EWI. One patient was excluded for poor echocardiographic windows and

the inability to image the entire ventricular myocardium. EWI correctly predicted the location of the AP in all 14 patients.

ECG analysis correctly predicted 11 of 14 (78.6%) of the AP locations.

CONCLUSIONS EWI was shown to be capable of consistently localizing accessory pathways. EWI predicted the site of

successful ablation more frequently than analysis of 12-lead ECG. EWI isochrones also provide anatomical visualization of

ventricular pre-excitation. These findings suggest that EWI can predict AP locations, and EWI may have the potential to

better inform clinical electrophysiologists prior to catheter ablation procedures. (J Am Coll Cardiol EP 2019;5:427–37)

© 2019 by the American College of Cardiology Foundation.

A ccessory pathways (AP) in Wolff-Parkinson-White (WPW) syndrome are commonlytreated with catheter ablation (1–3). Localiza-

tion of the AP prior to catheter ablation is important

N 2405-500X/$36.00

m the aUltrasound Elasticity Imaging Laboratory, Department of Biomedic

rk; bDivision of Cardiology, Department of Medicine, Columbia Universi

ctrophysiology, Division of Pediatric Cardiology, Department of Pediatri

w York; and the dDepartment of Radiology, Columbia University Medica

ubb contributed equally to this work and are joint first authors. yDrs. Liberm

d are joint senior authors. Supported in part by the National Institutes of He

1 EB006042. All authors have reported that they have no relationships re

authors attest they are in compliance with human studies committees

tutions and Food and Drug Administration guidelines, including patient co

JACC: Clinical Electrophysiology author instructions page.

nuscript received August 15, 2018; revised manuscript received Decembe

for pre-procedure planning. The current standardfor locating the AP is the clinician’s interpretation of12-lead ECG. However, this method is limited andlocalization may differ among clinicians. Many

https://doi.org/10.1016/j.jacep.2018.12.001

al Engineering, Columbia University, New York, New

ty Medical Center, New York, New York; cPediatric

cs, Columbia University Medical Center, New York,

l Center, New York, New York. *Mrs. Melki and Mr.

an and Konofagou contributed equally to this work

alth grant nos. R01 HL114358, R01 HL140646-01, and

levant to the contents of this paper to disclose.

and animal welfare regulations of the authors’ in-

nsent where appropriate. For more information, visit

r 2, 2018, accepted December 4, 2018.

ABBR EV I A T I ON S

AND ACRONYMS

2D = 2-dimensional

3D = 3-dimensional

AP = accessory pathway

ECG = electrocardiography

EWI = electromechanical wave

imaging

IQR = interquartile range

WPW = Wolff-Parkinson-W

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algorithms have been proposed with varyingdegrees of success. Specific algorithms havebeen developed in the pediatric population,but there is still significant room for improve-ment (4–9). Moreover, the reported algo-rithms have been less accurate than thoseused in adult patients, and frequently theaccuracy of these algorithms in clinical prac-tice is lower than in the originating author’shands (9–11).

Noninvasive, more precise, and less time-

consuming localization of AP could be of clinicalbenefit to operating electrophysiologists. Previously,there have been multiple noninvasive methodsproposed for localization of AP, such as from Botvi-nick et al. (12). Modern electrical mapping approachessuch as ECG imaging have emerged in specializedclinical settings (13). However, ECG imaging is anexpensive technique that requires patient-specificmodels of cardiac geometry derived by computedtomography or cardiac magnetic resonance scan,potentially exposing patients to ionizing radiation oranesthesia. More recently, echocardiography strain-based methods have been explored as potentialtools for the noninvasive identification of AP (14,15).

Electromechanical wave imaging (EWI) is a nonin-vasive and nonionizing ultrasound-based modalitythat maps the electromechanical activation in allcardiac chambers at a very high frame rate (16,17).Moreover, EWI has been shown capable of accuratelydetermining the origin of activation during ventricu-lar pacing from different endocardial and epicardialsites in paced canine hearts in vivo (18).

In this study, EWI is used for the first time in apediatric population. Our aim was to investigate thefeasibility of using this transthoracic ultrasoundtechnique for the localization of AP in pediatricpatients with WPW.

METHODS

PATIENT RECRUITMENT AND STUDY DESIGN. Patientspresenting to the Columbia University Medical Centerpediatric cardiac electrophysiology laboratory fortreatment of ventricular pre-excitation by catheterablation were approached for recruitment in thisstudy. The Columbia University Institutional ReviewBoard approved all methods and procedures prior tothe onset of the study. After consent, backgrounddata were obtained through patient histories andreview of the medical record. All patients recruitedwere known to have previously recorded, evidentventricular pre-excitation on resting ECG, andpreviously acquired transthoracic echocardiography

hite

demonstrated normal cardiac anatomy and function.Two pediatric electrophysiologists predicted thelocation of the AP based on the previously recordedECG using their clinical experience and both theBoersma et al. (6) and Arruda et al. (5) algorithms.

All patients underwent EWI with a trained sonog-rapher using standard transthoracic echocardiogra-phy immediately prior to the catheter ablationprocedure. Full view of the ventricular myocardiumwas required for EWI processing; when the anatomywas not completely visible during the initial scan, thepatient was excluded from the analysis. Obtainingan EWI scan required approximately 15 min in thepre-operative area on the day of the procedure. Theprocessing of each EWI scan required approximately90 min, including generation of both 2-dimensional(2D)– and 3D-rendered isochrones (approximately70 min for 2D only). After the start of the study, theprotocol was amended to include an additionalEWI scan immediately after the catheter ablationprocedure. After generation of the EWI isochrones, alocation was assigned based on a standardizedsegmented template of the ventricles. This templatewas generated prior to the enrollment of patients andwas specifically designed for this study based onsimilar templates in the published reports with theaddition of right ventricular segments (19). Thistemplate includes 19 different segments (the basalsegmentation is similar to standard ECG algorithmswith 10 segments at the level of the atrioventricularrings in this study, compared with 8 segments in theBoersma et al. [6] algorithm and 10 in the Arruda et al.[5] algorithm) as shown in Figure 1E.

Both EWI and the clinical electrophysiologistsreading the ECG were blinded to pre-procedureplanning and the outcome of the electrophysiologystudy and ablation. The predicted AP locations basedon the isochrones and on ECG were then comparedwith the site of successful ablation or the earliest siteof activation if no ablation was attempted (Figures 1Eto 1G). When computing the localization accuracy,predictions for both EWI and clinician interpretationof ECG were considered correct if they were in thesame segment, or an adjacent segment, to the actuallocation of the AP.

ELECTROMECHANICAL WAVE IMAGING. EWI isbased on a high frame rate echocardiographysequence that transmits a single diverging waveat 2,000 frames/s, while recording a lead II ECG insynchrony with the ultrasound acquisition (20). Thefull methods pipeline is detailed in Figures 1A to 1D.Four transthoracic apical 2D views were acquired(Figure 1A) with a 2.5-MHz phased array transducer

FIGURE 1 Study Processing Pipeline—Example on a Patient With a Left Posterolateral Pathway

(A) Two-dimensional (2D) apical 4-, 3.5-, 2-, and 3-chamber (-ch) views of the heart are acquired at a high frame rate of 2,000 frames/s (fps) with a diverging ultrasound

transmit sequence. (B) Axial displacements and strains are estimated on the radiofrequency data and the myocardium is manually segmented on the first B-mode image.

(C) The zero-crossing (ZC) locations corresponding to the activation times (t act) for each point are selected on the incremental strain curves to generate the 2D iso-

chrones. (D) The 4 multi-2D electromechanical activation maps are then coregistered and an interpolation is performed around the circumference to generate the 3D-

rendered isochrones, displaying the earliest activation after QRS onset in red and latest in blue. (E) A 19-segment template of the ventricles is used to predict the

pathway location based on electromechanical wave imaging (EWI) results (10 segments around the atrioventricular rings include anteroseptal, posteroseptal, left

posterior, left posterolateral, left lateral, left anterolateral, left anterior, right anterior, right lateral, and right posterior). On the right-hand side, the 2 corresponding

cross-sectional slices of the 3D-rendered isochrone are displayed, with the earliest activated region visible posterolaterally at the valve level. (F) The Boersma et al. (6)

algorithm is performed on the 12-lead electrocardiography (ECG) to determine the accessory pathway (AP) location. (G) Both EWI and ECG location predictions are

validated against the intracardiac map and site of successful ablation. ANT ¼ anterior; ch ¼ chamber; LAO ¼ left anterior oblique; LV ¼ left ventricle; MV ¼ mitral valve;

POST ¼ posterior; RAO ¼ right anterior oblique; RV ¼ right ventricle; TV ¼ tricuspid valve.

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TABLE 1 Patient Characteristics (N ¼ 14)

Male 7 (50.0)

Age, yrs 13.8 � 2.8

On antiarrhythmic medication during EWI 0 (0.0)

Height, cm 158.5 � 16.8

Weight, kg 60.8 � 24.0

Body surface area, m2 1.63 � 0.4

Baseline intervals, ms

PR 97.4 � 19.0

QRS 115.6 � 19.4

AH 63.1 � 14.5

HV 11.8 � 8.9

Values are n (%) or mean � SD.

AH ¼ Atrio-His interval; EWI ¼ electromechanical wave imaging;HV ¼ His-Ventricle interval; PR ¼ P-R interval; QRS ¼ QRS duration.

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(P4-2; ATL/Philips, Andover, Massachusetts) con-nected to a Vantage Research scanner system (Vera-sonics Inc., Kirkland, Washington). A 90� and 14-cmdeep field of view was used to image the ventricles.However, for adolescents older than 16 years old itwas necessary to perform the scans with a larger20-cm depth, standardly used in adults, in order tocover the entire region of interest.

Manual segmentation of the myocardium wasperformed on the first B-mode frame for each viewand tracked automatically throughout the rest of thecardiac cycle (Figure 1B) (21). Motion estimation wasperformed axially on the radiofrequency data with 1Dcross-correlation tracking (22). The incremental axialstrains were then derived with a least-squares esti-mator and overlaid onto the B-mode images (23).The ventricular activation times were defined asthe zero-crossing of the strain curves, that is, thetiming of the first sign change in interframe electro-mechanical axial strain after the QRS onset (24).The zero-crossing locations were picked for w100randomly selected points in the segmented myocar-dial region of interest (Figure 1C), and the activationtimes were then interpolated throughout the entiremask to achieve a homogeneous pattern. All 2D iso-chrones display the electromechanical activation inmilliseconds, with the earliest activated region in redand the latest in blue. The 4 resulting multi-2D elec-tromechanical activation maps were later coregis-tered around the left ventricle longitudinal axis ofsymmetry. In each longitudinal slice, a linear inter-polation was performed around the circumference tosubsequently generate the 3D-rendered isochrones(Figure 1D) (25).

ELECTROPHYSIOLOGY STUDY AND ABLATION

PROCEDURES. All catheter ablation procedures wereperformed under general anesthesia usingstandard techniques, equipment, and electroanatomic

mapping (EnSite, St. Jude Medical, Inc., St. Paul,Minnesota). All patients had a surface ECG recordedfollowed by vascular access. After vascular access wasobtained, catheters were placed near the His bundle,right atrial appendage, right ventricular apex, andcoronary sinus. Pacing protocols were performed withrapid atrial pacing from the high right atrium, atrialand ventricular extrastimulus testing at baseline,and on isoproterenol. For left-sided AP, access wasobtained via transseptal puncture. Ablation wasperformed with radiofrequency or cryoablation tech-nique. AP location was determined by the site of suc-cessful ablation.

STATISTICAL ANALYSIS. Data were reported as afrequency (percentage), median (interquartile range[IQR]), or mean � SD as appropriate. Comparisons ofEWI and ECG predictions to electrophysiology studyand ablation results are shown on correlation maps.Heat maps of the correlation tables were generatedusing GraphPad Prism version 7.03 for Windows,(GraphPad Software, La Jolla, California). EWI andECG localization performances were also quantifiedwith general accuracy and segment-specific positivepredictive value and sensitivity analysis.

RESULTS

Between March 21, 2017 and May 29, 2018, 15 pediatricpatients with ventricular pre-excitation on 12-leadECG were consented for the study. All patients pre-sented for ablation of ventricular pre-excitation at theColumbia University Medical Center pediatric elec-trophysiology laboratory. All 15 patients underwenttransthoracic imaging with a trained sonographer.One patient was excluded for the inability to imagethe entire ventricular myocardium due to a pooracoustic window. The mean age of the cohort was13.8 � 2.8 years and 50% were male. Baselinecharacteristics of the patients are shown in Table 1.Six patients also underwent EWI scans after theircatheter ablation procedures.

ACCESSORY PATHWAYS. Catheter mapping andablation demonstrated a single AP in all 14 includedpatients. Specific locations based on our template(as seen in Figure 1E) included 3 left lateral, 2 leftposterolateral, 5 posteroseptal, 1 anteroseptal, 1 rightposterolateral, 1 right anterior, and 1 fasciculoven-tricular pathways with the earliest ventricularactivation in the mid-septal right ventricle. Theidentified fasciculoventricular pathway was notablated. Of the 13 patients for whom ablation wasattempted, all 13 AP (100%) were successfully abla-ted. The patient with the anteroseptal pathway was

FIGURE 2 EWI Isochrones of a 7-Year-Old Female With a Left Lateral Pathway Before and After Successful Radiofrequency Ablation

Baseline intervals in the electrophysiology laboratory showed PR as 75 ms, QRS as 93 ms, AH as 61 ms, and HV as 1 ms. For all isochrones red indicates earliest activation

and blue indicates latest activation. (A,i) Four 2D EWI isochrones of the ventricles prior to catheter ablation showing earliest area of activation in the lateral (LAT) LV.

Scale bars ¼ 2 cm are shown for spatial resolution and single-lead ECG obtained with EWI acquisition are included. (ii) Anterior view of the 3D-rendered EWI isochrone

prior to catheter ablation and color bar for activation timings. (iii) LAO cross section of the previous 3D-rendered EWI isochrone at the valve level. (iv) Electroanatomic

map in LAO view showing superior vena cava (SVC), right atrium (RA), coronary sinus (CS), His site (yellow dot), and the site of successful ablation in the lateral LV (red

dot). (v) A 12-lead ECG performed prior to catheter ablation. (B,i) Four 2D EWI isochrones of the ventricles after catheter ablation showing earliest area of activation in

the septum. (ii) Anterior view of the 3D-rendered EWI isochrone after catheter ablation showing normal sinus activation of the ventricles and color bar for activation

timings. (iii) LAO cross section of the 3D-rendered EWI isochrone at the valve level after catheter ablation. (iv) A 12-lead ECG obtained after successful catheter ablation.

SEPT ¼ septal; other abbreviations as in Figure 1.

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FIGURE 3 EWI Isochrones of a 12-Year-Old Female With a Right Lateral AP Before and After Successful Radiofrequency Ablation

Baseline intervals in the electrophysiology laboratory showed PR as 101 ms, QRS as 116 ms, AH as 85 ms, and HV as 10 ms. In all isochrones, red indicates earliest

activation and blue indicates latest activation. (A, i) Anterior view of the 3D-rendered EWI isochrone prior to catheter ablation showing earliest activation in the lateral

RV. Scale bars ¼ 2 cm are shown for spatial resolution and single-lead ECG obtained with EWI acquisition are included. (ii) Posterior view of the 3D-rendered EWI

isochrone prior to catheter ablation. (iii) LAO cross section of the previous 3D-rendered EWI isochrones at the valve level and color bar for activation timings. (iv) A 12-

lead ECG performed prior to catheter ablation. (v) Electroanatomic map in LAO view showing SVC, RA, inferior vena cava (IVC), CS, His cloud (yellow dots), and the site of

successful ablation in the posterolateral RA (red dot). (B, i) Anterior view of the 3D-rendered EWI isochrone after catheter ablation showing normal sinus activation of

the ventricles. (ii) Posterior view of the 3D-rendered EWI isochrone after catheter ablation showing normal sinus activation of the ventricles. (iii) LAO cross section of the

3D-rendered EWI isochrone at the valve level after catheter ablation and color bar for activation timings. Abbreviations as in Figures 1 and 2.

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initially not ablated secondary to mechanicaldisruption of the pathway preventing accurateintracardiac mapping. He subsequently returned tothe laboratory and was successfully ablated on thesecond attempt. Ablation was performed with radi-ofrequency current in 12 patients and with cryoa-blation technique in 1 patient. Transseptal puncturewas performed on 6 patients. Median fluoroscopytime was 0.3 (IQR: 0.1 to 3.5) min and dose of radi-ation was 13.2 (IQR: 7.0 to 70.0) mGym2 and 1 patient

underwent ablation without fluoroscopy. The meansand ranges of PR, QRS, AH, and HV intervals asdetermined by baseline measurements in the elec-trophysiology laboratory are also described inTable 1.

EWI AND ECG PREDICTIONS. EWI predicted 14 of the14 AP locations (100%) by correctly localizingthe areas of earliest ventricular activation using thesegments described in the methods section. Examples

FIGURE 4 EWI Isochrones of a 16-Year-Old Male With a Right Posteroseptal AP Before Radiofrequency Ablation

Baseline intervals in the electrophysiology laboratory showed PR as 93 ms, QRS as 143 ms, AH as 60 ms, and HV as 8 ms. For all isochrones, red indicates earliest

activation and blue indicates latest activation. (A) Anterior view of the 3D-rendered EWI isochrone prior to catheter ablation showing earliest activation in the right

posteroseptal area. The 1-lead ECG obtained with EWI acquisition is included, as well as 2-cm scale bars for spatial resolution. (B) LAO cross section of the previous 3D-

rendered EWI isochrones at the valve level and color bar for activation timings. (C) Electroanatomic map in LAO view showing SVC, RA, IVC, CS, His cloud (yellow dots),

and the site of successful ablation in the posteroseptal RA (red dot). (D) A 12-lead ECG performed prior to catheter ablation. Abbreviations as in Figures 1 to 3.

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of EWI isochrones are shown in the following figures:left lateral AP before and after ablation in Figure 2;right posterolateral AP before and after ablation inFigure 3; a posteroseptal AP before ablation inFigure 4; and a fasciculoventricular AP in Figure 5.

ECG analysis correctly predicted 11 of the 14 APlocations (78.6%) using both the Boersma et al. (6)and Arruda et al. (5) algorithms, respectively (pre-dictions in immediately adjacent segments wereconsidered correct). It should be noted that mostalgorithmic analyses, including these, do not includesegments distal to the atrioventricular rings andtherefore are not applicable for prediction of thefasciculoventricular pathway (5,6).

Correlation heat maps of AP location predictionwith EWI versus ECG are shown in Figure 6. Morequantitatively, positive predictive value and sensi-tivity analysis is provided in Table 2 for eachventricular segment and quantifies the AP localiza-tion performances of EWI versus both the Boersmaet al. (6) and Arruda et al. (5) ECG algorithms.

COMPLICATIONS. There were no complications dur-ing EWI scans and no major complications duringcatheter ablations.

DISCUSSION

In this cohort, EWI was capable of both localizing andvisualizing the earliest ventricular activation in 14 ofthe 14 included patients prior to the catheter ablationprocedures. The patients were selected because theywere presenting for catheter ablation. EWI localiza-tion was more accurate than ECG analysis with2 different algorithms in our cohort.

The safety and efficacy of WPW ablation is welldocumented, but approximately 6% of ablations arestill unsuccessful. This is variable by pathway loca-tion, from a 98% success rate for left free wall path-ways to 88% to 89% for septal pathways (3).Complications from catheter ablation of AP are rarebut can still occur. In addition, the risks of WPWablation can vary by location, such as atrioventricular

FIGURE 5 EWI Isochrones of a 17-Year-Old Female With a Fasciculoventricular AP Prior to Catheter Ablation

Baseline intervals in the electrophysiology laboratory showed PR as 121 ms, QRS as 93 ms, AH as 70 ms, and HV as 15 ms. For all isochrones, red indicates earliest

activation and blue indicates latest activation. (A) Anterior view of the 3D-rendered EWI isochrone prior to catheter ablation. No definitive area of earliest activation can

be identified. Scale bars ¼ 2 cm for spatial resolution and 1-lead ECG obtained with EWI acquisition are included. (B) Coronal slice of the previous 3D-rendered isochrone.

Earliest activation is seen in the mid-septal RV. Color bar for activation timings is included. The small gap seen in the LV apex results from a small sector of myocardium

that was unable to be imaged in the 2D 3-chamber view and therefore could not be used during the 3D interpolation as described in the methods section. (C) Cross

section of the 3D-rendered isochrone at the level of the mid ventricles. The black dashed line displayed on the coronal slice (B) corresponds to the exact level of the

cross section. (D) A 12-lead ECG acquired prior to catheter ablation. Abbreviations as in Figures 1 to 4.

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block in septal pathways, complications from trans-septal puncture in left-sided ablation, and differencesin fluoroscopy and anesthesia times based onpathway location. Some less common pathways, suchas the fasciculoventricular AP, do not require catheterablation at all. Having knowledge of the location ofthe pathway is crucial for both planning of catheterablation and patient counseling prior to the proced-ure. Adding EWI to the standard 12-lead ECG has thepotential to increase the accuracy of AP localizationprior to catheter ablation procedures.

In this cohort, EWI was capable of localizing AP in avariety of locations to an approximately 1- to 2-cm

area of myocardium in each case (see scale bars onFigures 2 to 5). EWI succeeded with a high number ofanatomic segments surrounding the atrioventricularrings; this number was consistent with or greater than12-lead ECG algorithms (10 segments at the level ofthe atrioventricular rings for EWI in this study,as seen in Figure 1E compared with 8 for the Boersmaet al. [6] algorithm and 10 for the Arruda et al. [5] al-gorithm) (4,8). In addition, EWI was able to correctlyidentify the earliest area of ventricular pre-excitationfrom a fasciculoventricular pathway. The latterwas localized distal to the atrioventricular ring in themid-ventricular septum, and no current AP

FIGURE 6 Correlation Heat Maps Comparing EWI and ECG Pathway Localizations to Intracardiac Study Results

Correlation heat maps illustrating the accuracy of EWI and clinician interpretation of ECG for localization of the imaged AP (includes 10 atrioventricular atrioventricular

ring segments as well as location of fasciculoventricular). (A) Table showing confirmed AP locations from catheter mapping (columns) compared with EWI isochrone AP

location predictions (rows). (B) Table showing intracardiac localization of AP (columns) compared with Boersma et al. (6) AP location predictions (rows). (C)

Table showing intracardiac localization of AP (columns) compared with Arruda et al. (5) AP location predictions (rows). Green represents perfect predictions; yellow

illustrates predictions in adjacent segments; and red displays wrong predictions. The numbers written in the cells correspond to the number of predicted AP for each

ventricular segment. EWI correctly predicted 100% of the AP locations. When considering adjacent segments as correct prediction, the Boersma et al. (6) and Arruda

et al. (5) algorithms correctly predicted 78.6% of the AP locations, whereas when being conservative (excluding yellow cells), only 50% and 57.1%, respectively, of the

predictions were correct. Abbreviations as in Figures 1 and 2.

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localization algorithm would predict this location. Anadvantage of EWI is its ability to locate pre-excitationin ventricular myocardium below the level of theatrioventricular rings. EWI has also been shown to becapable of localizing premature ventricular contrac-tions in a single patient and accurately illustrating thepropagation of atrial activation in normal sinusrhythm (18).

The exact spatial resolution is dependent on boththe quality of imaging and the location of thepathway and is illustrated on a case-by-case basiswith scale bars in each figure. When using 2D echo-cardiography, the location of the myocardial pointsimaged can affect the specificity of the EWI results.For example, as seen in the methods (Figure 1D), thereare 8 image samples around the left ventricle but only4 in the right ventricle. This inherently means thatthe spatial resolution of EWI will be higher for left-sided AP. Nevertheless, EWI was capable of local-izing all pathways regardless of location, assuminggood quality echocardiography.

The degree of pre-excitation did not affect theaccuracy of EWI in this cohort. Whereas most patientswere substantially pre-excited (as described inTable 1), the presence of less obvious pre-excitationdid not affect the resulting localization. Forexample, 1 patient with a left posterolateral pathway

(baseline intervals: PR: 118 ms; QRS: 103 ms; AH:46 ms; HV: 28 ms) was successfully imaged andlocalized with EWI, suggesting the usefulness of EWIin patients with minimal pre-excitation.LIMITATIONS OF EWI. EWI is primarily limited by itsreliance on high-quality ultrasound imaging. Themyocardium is required to be fully visible in theviews before EWI processing can be applied.The 1 excluded patient in which EWI could not beperformed was a female adolescent, where breasttissue resulted in a difficult acoustic window and theentire ventricular myocardium could not be imaged.Even with high-quality echocardiography, certainanatomical areas are more difficult to image in mul-tiple views. For example, the right ventricle has halfthe image sampling as the left ventricle, as seen inthe methods section (Figure 1D). Because EWI relieson having the area of interest within view, this mightlimit the spatial resolution or localization altogether.This undersampling phenomenon of 2D echocardi-ography could potentially be overcome by using EWIwith true 3D ultrasound, which would allow forimaging of all myocardium within the field of view.This has currently been shown to be feasible in open-chest canine studies and healthy volunteers (26).EWI is dependent on the presence of anterogradeventricular pre-excitation to detect the location of the

TABLE 2 EWI Versus ECG Performance for AP Localization

AP LocalizationMethods

GlobalAccuracy

(%)

Ventricular Segments

ANT SEPT POST SEPT Fasciculoventricular Left LAT Left POST LAT Right LAT Right ANT

PPV S PPV S PPV S PPV S PPV S PPV S PPV S

EWI 100.0 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00

Boersma et al. (6) 50.078.6*

0.25 1.00 1.00 0.40 0 0 0.75 1.00 0 0 0.33 1.00 0 0

Arruda et al. (5) 57.178.6*

0.33 1.00 0.75 0.60 0 0 0.67 0.67 0 0 0.50 1.00 1.00 1.00

*When prediction is immediately adjacent, the segment is considered correct.

ANT ¼ anterior; AP ¼ accessory pathway; ECG ¼ electrocardiography; EWI ¼ electromechanical wave imaging; LAT ¼ lateral; POST ¼ posterior; PPV ¼ positive predictive value; S ¼ sensitivity;SEPT ¼ septal.

PERSPECTIVES

COMPETENCY IN MEDICAL KNOWLEDGE: This

work has implications and applications in the areas of

patient care and procedure skills.

TRANSLATIONAL OUTLOOK: This study is the

first to use EWI for localization of AP in pediatric pa-

tients. Previously published EWI manuscripts have a

few selected adult cases. This study has a larger

cohort than previous studies and is the first pediatric

study. However, more validation is required for EWI in

AP, and EWI’s potential use in arrhythmias needs

further investigation.

Melki 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 . 4 , 2 0 1 9

Transthoracic Echocardiographic Localization of Accessory Pathways A P R I L 2 0 1 9 : 4 2 7 – 3 7

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AP. As demonstrated in this study, even minimal pre-excitation is sufficient, but this technique is obvi-ously not applicable in patients with concealed AP.

STUDY LIMITATIONS. This is a study in a small cohortof 15 WPW patients imaged with EWI. This studydemonstrates the technique and suggests its poten-tial uses, but the limited sample size prevents anal-ysis on clinical measures, and this study does notcomment on the effect of EWI on clinical outcomes.The blinding of the treating electrophysiologist to theEWI results prevents analysis of EWI’s effect on theprocedures. Given the limited number of patients,certain pathway locations were not included. Inaddition, this is a single-center study of pediatricpatients. This was a select population deemed suit-able and selected for catheter ablation; thereforethese results may not be generalizable to all patientswith ventricular pre-excitation. Given the smallsample size, further study is needed to both validateEWI and determine its effect in clinical practice.

CONCLUSIONS

EWI was shown to be capable of consistently local-izing AP in variable locations more frequently thanthe 12-lead ECG did in a pediatric patient population.A higher correlation was obtained between the elec-troanatomic mapping results and EWI predictionsthan against ECG predictions. EWI isochrones canalso provide more detailed anatomical visualization.These findings indicate that this modality has the

potential to better inform a treating electrophysiolo-gist on the precise AP location in pre-proceduralplanning as well as post-procedural assessment.

ACKNOWLEDGMENTS The authors express their verygreat appreciation to Vincent Sayseng, MS, and KokiNakanishi, MD, for their time and valuable assistanceacquiring part of the data. The authors also thankJulien Grondin, PhD, for his helpful discussions.

ADDRESS FOR CORRESPONDENCE: Dr. Elisa E.Konofagou, Biomedical Engineering, ColumbiaUniversity Medical Center, 630 West 168th Street,Physicians and Surgeons 19-418, New York,New York 10032. E-mail: ek2191@columbia.edu.

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KEY WORDS accessory pathway, catheterablation, echocardiography, treatmentplanning, ultrasound, Wolff-Parkinson-White