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 VO L . - , N O . - , 2 0 1 8

ª 2 0 1 8 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

Cryoablation for Perinodal ArrhythmiaSubstrates in Patients With CongenitalHeart Disease and Displaced AVConduction Systems

Pablo Ávila, MD,a,b Francis Bessière, MD, MS,a Blandine Mondésert, MD,a Sylvia Abadir, MD,a Annie Dore, MD,a

François-Pierre Mongeon, MD, MS,a Marc Dubuc, MD,a Paul Khairy, MD, PHDa

ABSTRACT

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OBJECTIVES The purpose of this study was to assess the safety and efficacy of cryoablation for perinodal substrates in

patients with congenital heart disease (CHD) and a displaced atrioventricular (AV) conduction system or an AV conduction

system location that was difficult to predict.

BACKGROUND Catheter ablation for perinodal arrhythmias in patients with CHD may incur higher risks due to un-

conventional or difficult to predict locations of the AV conduction system. Cryoablation carries theoretical advantages for

such patients but has not been studied in this setting.

METHODS A total of 35 patients with CHD underwent cryoablation for perinodal substrates at the Montreal Heart

Institute between 2006 and 2016. Ten of these patients, age 33�13 years, 60% male, had AV conduction systems that

were displaced or of uncertain location and underwent cryoablation (6-mm electrode-tip catheter) for 12 perinodal ar-

rhythmias: AV nodal re-entrant tachycardia (n¼4), non-automatic focal atrial tachycardia (n¼4), septal intra-atrial re-

entrant tachycardia (n¼3), and para-Hisian automatic focal atrial tachycardia (n¼1). Four patients had single-ventricle

physiology and had undergone Fontan palliation (3 atriopulmonary and 1 intracardiac total cavopulmonary connection), 4

underwent repair of AV septal defects, 1 had congenitally corrected transposition of the great arteries (TGA), and 1 had

TGA with a Mustard baffle.

RESULTS Cryoablation was acutely successful in 9 of 12 targeted arrhythmias (75%) with no procedural complication.

Crossover to radiofrequency ablation successfully eliminated the remaining 3 arrhythmias at sites deemed safe by cry-

oablation, with no complication. Over a follow-up period of 26 (interquartile range: 15 to 64) months, 1 of 9 successfully

cryoablated arrhythmias recurred.

CONCLUSIONS Cryoablation is feasible, safe, and moderately effective for perinodal arrhythmia substrates in patients

with various forms of CHD associated with AV conduction systems that are displaced or in locations that cannot be

reliably predicted. (J Am Coll Cardiol EP 2018;-:-–-) © 2018 by the American College of Cardiology Foundation.

N 2405-500X/$36.00 https://doi.org/10.1016/j.jacep.2018.05.026

m the aAdult Congenital Heart Center, Montreal Heart Institute, Université de Montréal, Montreal, Quebec, Canada; and the

epartment of Cardiology and Centro de Investigación Biomédica en Red Enfermedades Cardiovaculares (CIBERCV), Hospital

egorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Universidad Complutense, Madrid, Spain. Supported by

Montreal Heart Institute Foundation. Dr. Ávila has received research support from the Alfonso Martín Escudero Foundation,

ain. Dr. Bessière is supported by the French Federation of Cardiology. Dr. Khairy holds the Research Chair in Electrophysiology

d Congenital Heart Disease. Dr. Dubuc has consulted for Medtronic CryoCath LP. All other authors have reported that they have

relationships relevant to the contents of this paper to disclose.

authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ in-

tutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit

JACC: Clinical Electrophysiology author instructions page.

nuscript received July 12, 2017; revised manuscript received May 22, 2018, accepted May 29, 2018.

ABBR EV I A T I ON S

AND ACRONYMS

AV = atrioventricular

AVNRT = atrioventricular

nodal re-entrant tachycardia

AVSD = atrioventricular septal

defect

ccTGA = congenitally

corrected transposition of the

great arteries

CHD = congenital heart disease

RF = radiofrequency

TGA = transposition of the

great arteries

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S upraventricular arrhythmias are themost common long-term complica-tions in the aging population with

congenital heart diseases (CHD), the leadingcause of morbidity and impaired quality oflife and an important cause of mortality(1,2). While intra-atrial re-entrant tachy-cardia (IART) is the most prevalentarrhythmia in patients with CHD (3–6), othersubstrates include focal atrial tachycardia,atrioventricular (AV) nodal re-entrant tachy-cardia (AVNRT), and accessory pathway-mediated tachycardia (7,8).

Although radiofrequency (RF) energy is

the most common modality used for catheter ablationin CHD, cryoablation offers theoretical advantages forperinodal substrates, including the ability to titratetemperatures to produce reversible effects prior tocellular destruction and enhanced catheter stabilitydue to adhesion of the catheter tip to the endocardialsurface (9–11). These features may be particularlyadvantageous in the setting of perinodal arrhythmiasubstrates when the AV conduction system is dis-placed or of ambiguous location, as in congenitallycorrected transposition of the great arteries (ccTGA),atrioventricular septal defects (AVSD), and singleventricles (7,12–14). Although averting damage to theAV node is a preoccupation in treatment for all pa-tients, AV block can be particularly poorly tolerated inthose with complex CHD. Moreover, lack of venousaccess may prohibit ventricular endocardial lead im-plantation should the need arise. In light of theseunique challenges, we assessed safety and efficacy ofcryoablation for perinodal substrates in patients withCHD and an AV conduction system location that wasdisplaced or difficult to predict.

METHODS

STUDY POPULATION. A total of 35 patients with CHDunderwent cryoablation for perinodal substrates atthe Montreal Heart Institute between 2006 and 2016.Among these patients, 25 had an AV node locatedwithin the usual confines of Koch’s triangle and un-derwent cryoablation for AVNRT (n ¼ 17), septalaccessory pathways (n ¼ 6), and perinodal atrialtachycardias (n ¼ 3); 1 subject had both AVNRT and aseptal accessory pathway. The study focused on theremaining 10 patients with 12 perinodal arrhythmias.All patients were identified through our registry ofcatheter ablation in CHD. Hospital records werethoroughly reviewed, and data for demographics,type of CHD, previous surgeries, symptoms, proce-dural characteristics, complications, and follow-up

were extracted. Written informed consent wasobtained for all procedures. The study was approvedby our local institutional review board.

ELECTROPHYSIOLOGICAL STUDY. Procedures wereperformed with subjects under conscious sedation.All antiarrhythmic drugs were discontinued for $5half-lives. None of the patients received amiodaroneprior to the intervention. Vascular access was ob-tained through femoral and/or jugular veins accord-ing to patient anatomy. Prior to electrophysiologicaltesting, conventional or rotational angiography wasperformed at the discretion of the operator. All pro-cedures were performed with at least 2 catheters: areference catheter and a roving ablation catheter.Additional quadripolar and decapolar diagnosticcatheters were placed in accessible cardiac chambersdepending on patient anatomy. A 3-dimensional (3D)electroanatomical mapping system was used in allpatients (Ensite NavX or Velocity; St. Jude Medical,Minneapolis, Minnesota; or CARTO; Biosense-Webster, Diamond Bar, California). If required,access to the pulmonary venous atrium in patientswith a Mustard baffle or total cavopulmonary Fontanconnection (TCPC) was obtained through a baffle leakor fenestration if present or by a transbaffle or trans-conduit puncture, using a conventional transseptalneedle (BRK-1; St. Jude Medical) or an RF perforationneedle (Baylis, Montreal, Québec, Canada). For pro-cedures in the pulmonary venous atrium, heparin wasadministered and adjusted to maintain a targetedactivated clotting time of 300 to 350 s.

Whenever the clinical arrhythmia was not presentat the beginning of the procedure, it was induced byprogrammed electrical stimulation. Diagnostic testingwas performed using standard criteria (15).

CATHETER ABLATION PROCEDURE. In all cases,cryoablation was performed using a 6-mmelectrode-tipped catheter (Freezor Xtra; MedtronicCryoCath LP, Montreal, Québec, Canada). Cry-omapping was achieved at �30�C for 30 to 60 s and,if efficacy and safety were confirmed, the tempera-ture was lowered to �80�C for an additional 4 min.Vigilant monitoring of AV conduction wasperformed throughout the application. A doublefreeze-thaw cycle was applied at the site of success.Procedural endpoints included noninducibility byprogrammed electrical stimulation with up to 2atrial extrastimuli and decremental atrial burstpacing from 400 to 200 ms with and without anisoproterenol infusion. In addition, complete elimi-nation of slow-pathway conduction was targeted inpatients with AVNRT (16). All patients wereobserved for a period of 30-min to 60-min following

TABLE 1 Characteristics of Patients With Cryoablation of Perinodal Substrates With

Standard and Nonstandard AV Node Locations

CharacteristicStandard AV NodeLocation, n ¼ 25

Nonstandard AV NodeLocation, n ¼ 10 p Value

Age at time of procedure, yrs 32 � 15 33 � 13 0.653

Males (%) 10 (40) 6 (60) 0.454

Arrhythmia type (%) 0.003

AV nodal re-entrant tachycardia 17 (68) 4 (40)

Accessory pathway 6 (24) 0 (0)

Intra-atrial re-entrant tachycardia 0 (0) 3 (30)

Focal atrial tachycardia 4 (16) 5 (50)

Predominant type of congenitalheart disease (%)

NA

Sinus venosus or secundum ASD 9 (36) 0 (0)

Ebstein anomaly 6 (24) 0 (0)

PS with or without ASD 4 (16) 0 (0)

Tetralogy of Fallot 2 (8) 1 (10)*

VSD with or without ASD 2 (8) 0 (0)

Aortic stenosis 1 (4) 0 (0)

Mitral stenosis, AoCo, VSD 1 (4) 0 (0)

Single ventricle/Fontan 0 (0) 4 (40)

Atrioventricular septal defect 0 (0) 4 (40)*

Congenitally corrected TGA 0 (0) 1 (10)

TGA with Mustard baffle 0 (0) 1 (10)

Procedural characteristics

Procedural duration, h 3.6 (2.9–5.4) 5.5 (4.5, 8.5) 0.028

Fluoroscopy time, min 28 (12–45) 26 (10–36) 0.513

Ablation time, min 35.5 (13.8–43.2) 30.3 (16.5–57.2) 0.764

Number of ablation lesions 11 (8–16) 5 (5–11) 0.226

*One patient with tetralogy of Fallot also had an atrioventricular septal defect. Values are n (%), or median(interquartile range).

AoCo ¼ aortic coarctation; ASD ¼ atrial septal defect; AV ¼ atrioventricular; NA ¼ not applicable; PS ¼pulmonary stenosis; TGA ¼ transposition of the great arteries; VSD ¼ ventricular septal defect.

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successful ablation. Crossover to RF energy wasperformed at the discretion of the operator afterexhaustive attempts at cryoablation had faileddespite the absence of AV prolongation during cry-othermal applications in the area of interest.

ENDPOINTS AND FOLLOW-UP. The primary efficacyendpoint was acute procedural success. The second-ary efficacy endpoint was absence of recurrent,sustained (>30 s) tachycardia during long-termfollow-up, whether symptomatic or asymptomatic.All patients were followed for 3 months after catheterablation with 12-lead electrocardiography and 24-hHolter monitoring, with biannual or yearly follow-up thereafter, depending on clinical circumstances.Acute major complications and all other adverseevents were noted.

STATISTICAL ANALYSIS. Continuous variables aresummarized as mean � SD or median and inter-quartile range (25th and 75th percentiles), dependingon normality of distribution, and were comparedusing the Mann-Whitney rank-sum U test. Categoricalvariables are represented as frequencies and per-centages. Comparisons were performed using Fisherexact tests. Two-tailed p values <0.05 were consid-ered statistically significant. Statistical analyses wereperformed using SPSS Statistics version 20.0 software(SPSS, Chicago, Illinois).

RESULTS

PATIENT CHARACTERISTICS. Table 1 summarizesthe characteristics of patients with cryoablation ofperinodal substrates with (n ¼ 25 patients) andwithout (n ¼ 10 patients) an AV node in the standardlocation within Koch’s triangle. Twelve procedureswere performed in 10 patients, 33 � 13 years of age, 6males (60%) whose AV conduction system was dis-placed or difficult to predict (Table 2). In short, 4patients (Table 2, patients 1, 6, 7, and 9) had single-ventricle physiology with Fontan surgery (3 atrio-pulmonary and 1 intracardiac TCPC), 4 had repairedAVSDs (Table 2, patients 3, 4, 5, and 10), 1 had TGAwith a Mustard baffle (Table 2, patient 2), and 1 hadccTGA (Table 2, patient 8). All patients had recurrentsymptomatic, sustained, documented supraventricu-lar tachycardias. Median time from symptom onset tocatheter ablation was 13 months (interquartile range[IQR]: 7 to 72 months). All but 1 patient had a previoushospital admission requiring pharmacological orelectrical cardioversion. Eight patients (80%)received at least 1 antiarrhythmic drug prior to abla-tion, and all patients with Fontan surgery were takingoral anticoagulants.

ARRHYTHMIA CHARACTERISTICS. A total of 12 peri-nodal arrhythmias, median cycle length 360 ms (IQR:310-390 ms), were targeted during 12 procedures:AVNRT (n¼4), non-automatic focal atrial tachycardia(NAFAT; n¼4), septal IART (n¼3), and para-Hisianautomatic focal atrial tachycardia (n¼1). Anatomiclandmarks were assessed by using fluoroscopy andconventional (n ¼ 4) or rotational angiography (n ¼4), with 3D electroanatomic mapping performed in all(EnSite [St. Jude Medical] in 11 patients and CARTO[Biosense-Webster] in 1 patient). In all cases, theperinodal arrhythmia was determined to be the clin-ically relevant tachycardia. In 4 cases (25%), addi-tional arrhythmias were ablated during the sameprocedure. As noted in Table 1, the medianproceduralduration was 5.5 h (IQR: 4.5 to 8.5 h), which wassignificantly longer than for patients with standardAV node locations (median: 3.6 h [IQR: 2.9 to 5.4 h];p ¼ 0.028). However, fluoroscopy and ablation timeswere not significantly different.

PROCEDURAL OUTCOME AND LONG-TERM FOLLOW-UP. Cryoa-blation was acutely successful for 9 of 12 targeted

TABLE 2 Characteristics of Patients With a Displaced AV Conduction System or a System Whose Location Is Difficult to Predict

Patient SexAge,yrs Type of CHD

Age atsurgery, yrs Previous Surgeries Arrhythmia

SymptomDuration, mo

CL,ms Access

AcuteSuccess Recurrence

1 F 35 Tricuspid atresia;RA-PA Fontan

12 Right and left SPshunts

Para-Hisian NAFAT 6 260 Femoral þ �

2 M 50 TGA with Mustardbaffle

5 None Para-Hisian NAFAT 36 380 Jugular þ �

3 F 25 AVSD repair 4 None AVNRT 10 350 Femoral þ �4 F 32 AVSD repair 4 None AVNRT 7 320 Femoral þ �

Para-Hisian automatic AT 5 330 Femoral; Transseptal þ þ (1 mo)

5 F 52 AVSD repair 3 None AVNRT 14 300 Femoral þ �6 M 24 DILV; intracardiac

TCPC Fontan14 Right and left SP

shunts;Glenn shunt

Para-Hisian NAFAT 73 440 Femoral; Transbaffle þ �Septal NAFAT 5 570 Femoral; Transbaffle � NA

7 M 22 DIRV; RA-PA Fontan 4 SP shunt Anteroseptal IART 72 245 Femoral þ �8 M 47 Unoperated ccTGA NA NA AVNRT 360 340 Femoral � NA

9 M 27 Tricuspid atresia;RA-PA Fontan

3 SP shunt Anteroseptal IART 12 280 Femoral � NA

10 F 13 AVSD and TOF repair 1 None Septal IART 3 380 Femoral þ �

Values shown are n (%).

AT ¼ atrial tachycardia; AVNRT ¼ atrioventricular nodal re-entrant tachycardia; AVSD ¼ atrioventricular septal defect; ccTGA ¼ congenitally corrected TGA; CHD ¼ congenital heart disease; CL ¼ cyclelength; DILV ¼ double-inlet left ventricle; DIRV ¼ double-inlet right ventricle; F ¼ female; IART ¼ intra-atrial re-entrant tachycardia; M ¼ male; NA ¼ not applicable; NAFAT ¼ nonautomatic focal atrialtachycardia; RA-PA ¼ right atrium-to-pulmonary artery; SP ¼ systemic-pulmonary; TCPC ¼ total cavopulmonary connection; TGA ¼ transposition of the great arteries; TOF ¼ tetralogy of Fallot.

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arrhythmias (75%), which was not significantlydifferent from 24 of 26 successfully ablated perinodalsubstrates (92%) in patients with standard AV nodelocations (p ¼ 0.301). No procedural complicationoccurred, with AV conduction remaining unaltered inall. Crossover to RF ablation successfully eliminatedthe remaining 3 arrhythmias at sites tested anddeemed to be safe by cryoablation. Similarly, successwas obtained upon crossover to RF energy in 2 con-trols with normally positioned AV conduction sys-tems, both of whom had focal septal atrialtachycardias in the setting of atrial septal defects(ASDs). No complication occurred with RF ablation.

Over a median follow-up of 26 months (IQR: 15 to64 months), 1 of 9 successfully ablated arrhythmiasrecurred 1 month after the procedure, which was notsignificantly different from 1 of 24 arrhythmias inpatients with normally positioned AV conductionsystems followed for 33 months (IQR: 7 to 67 months;p ¼ 0.477). The 1 patient with a recurrence wasmanaged pharmacologically with a good response.None of the arrhythmias requiring RF ablationrecurred. All patients were alive and in sinus rhythmat the end of follow-up.

PROCEDURAL DETAILS ACCORDING TO ARRHYTHMIA

SUBSTRATE. AVNRT in the sett ing of a d isp lacedAV conduct ion system. Cryoablation for AVNRTwas performed in 2 patients with surgically repairedAVSDs and 1 patient with nonoperated ccTGA. Forthe first patient with an AVSD (Table 2, patient 3),the slow pathway was ablated superior to the

inferiorly displaced compact AV node (Figure 1). Forthe second and third patients (Table 2, patients 4and 5), the slow pathway was eliminated below thedisplaced His bundle, inferior to the ostium of thecoronary sinus. The fourth patient with ccTGA andS,L,L (situs solitus, L-looped, ventricles, and L-transposed great arteries) segmental anatomy(Table 2, patient 8) had atypical (slow-slow) AVNRT.Although the AV node was displaced superiorly, asexpected, the slow pathway was nevertheless foundin a conventional location within the middle thirdof the L-looped variant of Koch’s triangle. Initialsuccess was obtained with cryoablation but withsubsequent recurrence. Crossover to RF ablation atthe same location eliminated slow-pathwayconduction.

Focal at r ia l tachycard ia (n [ 5) . Cryoablation wasused to treat 5 septal focal atrial tachycardias, 4 ofwhich were para-Hisian in 4 patients with AVSDrepair (n ¼ 1), TGA and a Mustard baffle (n ¼ 1),and single-ventricle physiology with Fontan surgery(n ¼ 2). The patient with AVSD repair (Table 2, patient4) had previously undergone successful cryoablationof AVNRT. A second electrophysiological study per-formed a few months later confirmed the absence ofrecurrent slow-pathway conduction. However, a focalautomatic atrial tachycardia was mapped through atransbaffle approach to the septal portion of the pul-monary venous atrium in proximity to the Hisrecording. Cryoablation with a 6-mm electrode-tipped catheter terminated tachycardia and

FIGURE 1 Cryoablation of AVNRT in a Patient With a Repaired AVSD and Inverted Slow

and Fast Pathways

(A) A 3D electroanatomic map depicts retrograde fast pathway activation during AVNRT in

a left lateral view. Green spheres indicate sites where His bundle electrograms were

recorded. Local activation times are color-coded, with the site of earliest atrial activation in

white, below the inferiorly displaced His bundle. Blue circles indicate sites where

cryomapping had no effect on slow pathway conduction. Successful cryomapping and

subsequent cryoablation of the slow pathway were performed at the yellow circles,

superior to the His bundle. (B) Tachycardia terminates during cryomapping of the slow

pathway with antegrade block. Shown are recordings from surface ECG leads I, aVF, and

V1, distal cryocatheter at the slow pathway site, His bundle (His), distal CS, and RV.

AVNRT ¼ atrioventricular nodal re-entrant tachycardia; AVSD ¼ atrioventricular septal

defect; CS ¼ coronary sinus; ECG ¼ electrocardiography; IVC ¼ inferior vena cava;

SVC ¼ superior vena cava.

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rendered it noninducible. The patient with TGA and aMustard baffle (Table 2, patient 2) had an obstructedinferior vena cava. A septal NAFAT was successfullycryoablated by means of a right jugular venousapproach adjacent to a His signal recorded in thesystemic venous atrium (17) (Figure 2). A patient withtricuspid atresia and classic Fontan surgery (Table 2,patient 1) successfully underwent cryoablation of apara-Hisian NAFAT near the ostium of the coronarysinus (Figure 3). Finally, a patient with a double-inletleft ventricle and an intracardiac TCPC Fontan(Table 2, patient 6) successfully underwent cryoa-blation of a para-Hisian NAFAT through a transbafflepuncture (Figure 4). Two years later, the patientpresented with a new and much slower NAFAT higheralong the septum in the left atrium. Cryoablation wasunsuccessful, but crossover to RF ablation eliminatedthe tachycardia with no subsequent recurrence.Int ra-atr ia l re -entrant tachycard ia (n [ 3) . Twopatients with atriopulmonary Fontan surgery (Table 2,patients 7 and 9) had IART circuits between septal scarand an atretic tricuspid valve, with critical isthmuseslocated in anterior or mid-septal regions. Cryoablationwas used as first-line therapy given the uncertainty inlocalizing the AV conduction system. IART was suc-cessfully terminated, with bidirectional conductionblock obtained in 1 patient (Table 2, patient 7). In thesecond patient (Table 2, patient 9), IART was termi-nated upon crossover to irrigated RF ablation at sitestested by cryoenergy, with no prolongation of AVconduction. Finally, a patient with a repaired AVSDand tetralogy of Fallot (Table 2, patient 10) had anIART circuit around the primum ASD patch(Figure 5). Two potential critical isthmuses wereidentified between the ASD patch and either thecoronary sinus or the tricuspid annulus. The latterwas targeted with cryothermal energy consideringthe proximity of the inferiorly displaced AV node tothe coronary sinus. A linear lesion between thepatch and tricuspid annulus was applied where low-voltage–fractionated signals were observed. There,cryomapping and cryoablation successfully inter-rupted the IART and rendered the patient non-inducible with no subsequent recurrence.

DISCUSSION

Several forms of CHD are associated with a displacedAV conduction system, the location of which isdetermined in part by concordance and morphologyof the AV connection, alignment and position of theventricular septum, and looping pattern of ventricu-lar architecture. Herein, we describe a series of pa-tients with perinodal arrhythmia substrates and CHD

associated with an AV node location that was dis-placed or was difficult to predict such that catheterablation carried an increased risk of AV block. In ourexperience, cryoablation proved to be safe in all casesand was moderately effective in treating complexperinodal substrates including AVNRT, NAFAT, IART,and automatic focal atrial tachycardia in patients withccTGA, AVSD, univentricular hearts, and Mustard andFontan surgery.

In ccTGA, the ventricular septum is typically notaligned with the atrial septum as a result of thewedged position of the pulmonary outflow tract (12).

FIGURE 2 Cryoablation of a Para-Hisian Focal Atrial Tachycardia by Means of a Jugular Venous Approach

Cryoablation of a para-Hisian focal atrial tachycardia by means of a jugular venous approach in a patient with D-transposition of the great arteries, obstructed inferior

vena cava, and Mustard baffle. (A) Contrast angiography was performed using a pigtail catheter positioned in the superior limb of the Mustard baffle through a jugular

venous approach. (B) Position of the mapping catheter at the site of earliest activation is shown (asterisk) during nonautomatic focal atrial tachycardia in the systemic

venous atrium. (C) Three-dimensional electroanatomic map, along with the position of the 6-mm electrode-tipped cryocatheter adjacent to the site of successful

ablation (asterisk). Reversible prolongation of the A-to-H interval occurred at the red circle next to the successful ablation site. Blue circle indicates sites where

cryomapping had no effect. LAA ¼ left atrial appendage; MV ¼ mitral valve; other abbreviations as in Figure 1.

FIGURE 3 Cryoabl

(A) Contrast angiogr

right atrium and with

best His recording is

pulmonary artery; N

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As such, a standard AV node cannot come into contactwith a ventricular conduction system. Instead, ananterolaterally displaced AV node connects to theHis–Purkinje conduction system below the atrial

ation of Para-Hisian NAFAT in a Patient With Tricuspid Atresia and an Atr

aphy of an atriopulmonary Fontan procedure through a pigtail catheter. Decap

in the CS. (B) Location of successful cryoablation of the NAFAT is indicated b

indicated by the yellow sphere anterior to the CS ostium. The green circle ind

AFAT ¼ nonautomatic focal atrial tachycardia; all other abbreviations as in F

appendage. In an AVSD, which primarily affects theAV junction, lack of atrial and ventricular septalcontinuity determines the course of the conductionsystem. Koch’s triangle, although present, does not

iopulmonary Fontan Procedure

olar catheters were positioned along the septal portion of the dilated

y the asterisk. (C) A 3D electroanatomic map is shown. The site of the

icates the site of successful cryomapping and cryoablation. LPA ¼ left

igures 1 and 2.

FIGURE 4 Cryoablation of a Para-Hisian NAFAT Through a Transbaffle Puncture in a Patient With a Double-Inlet Left Ventricle and Intracardiac Lateral Tunnel

TCPC Fontan Procedure

(A) Contrast angiography of the intracardiac TCPC Fontan is shown. (B) A right anterior oblique view of the transseptal needle is shown. A reference catheter (Ref)

consisting of a transvenous pacemaker lead was screwed onto the lateral wall of the TCPC through the right internal jugular vein. (C) Position of the cryocatheter at the

site of successful ablation of the NAFAT by transbaffle access is shown (asterisk). (D) Three-dimensional electroanatomic maps of the TCPC and neo-LA in anterior and

posterior views. His bundle recordings are marked by yellow circles. The site of successful cryoablation of the peri-Hisian NAFAT is indicated by the green circle. LA ¼ left

atrium; RPA ¼ right pulmonary artery; TCPC ¼ total cavopulmonary connection; other abbreviations as in Figures 1, 2, and 3.

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contain the AV node. Rather, it is displaced posteri-orly along the atrial septum, just above the AV junc-tion and anterior to the ostium of the coronary sinus(13,18) (Figures 1 and 5).

In hearts with univentricular connections, predic-tion rules regarding location of the AV node arehelpful but may be misleading. In a double-inlet leftventricle, the AV node is typically displaced

FIGURE 5 IART Around the Septal Patch in a Patient With a

Repaired AVSD and Tetralogy of Fallot

A left lateral view of a 3D electroanatomic map shows the IART

circuit rotating clockwise around the primum ASD patch. Yellow

circles indicate the location of the inferiorly displayed His bundle

in the setting of an AVSD. White circles represent cryoablation

sites connecting the ASD patch to the tricuspid annulus. The IART

circuit was terminated and rendered noninducible by cryoa-

blation. ASD ¼ atrial septal defect; IART ¼ intra-atrial re-entrant

tachycardia; other abbreviations as in Figures 1 and 2.

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anterolaterally (19). However, in our patient with apara-Hisian NAFAT and double-inlet left ventricle,the AV node was displaced inferiorly (Figure 4),underscoring marked interindividual variationsdespite similarly labeled defects. In patients withtricuspid atresia, the AV conduction system cannot benormally located owing to the absence of a right AVconnection. The AV node is typically found on thefloor of the right atrium adjacent to the mouth ofcoronary sinus (Figure 3) and central fibrous body,which is sometimes recognizable by a dimple (i.e.,blind-ending right atrium) (20). Location of the AVnode can be variable in patients with double-inletright ventricles. When an overriding tricuspid valveis predominantly connected to a morphological rightventricle, the AV node can be normally positioned.However, depending on the orientation of theseptum, the node may be more posterior than usual.

Current expert consensus statements in pediatricand congenital electrophysiology support the use ofcryoablation as a Class IIA indication for septal sub-strates (21,22), considering the established safety

profile (23–27). Several factors including operatorexperience, optimization of the ablation site, rapidtime to desirable effect (e.g., <10 s), larger cathetertips (i.e., 6 or 8 mm as opposed to 4 mm), rapidcooling rates, lower target temperatures, andrepeated freeze-thaw cycles have been associatedwith a lower risk of recurrence (25,28). Our resultsfurther extend the utility of cryoablation for septalsubstrates to patients with a displaced or uncertainlocation of the AV node. Nevertheless, in 3 cases,cryoablation was unsuccessful and crossover to RFwas required to eliminate the targeted arrhythmia. Inall such cases, cryoablation was believed to be helpfulin better delineating the AV conduction system and/or providing additional safety data for subsequent RFablation. A prototype of a hybrid cryothermal-RFablation catheter, which may be of interest for suchperinodal substrates, has previously been described(29) but is not yet commercially available.

A clear understanding of 3D anatomy is essentialfor optimizing catheter ablation outcomes in patientswith complex CHD. Integration of 3D images acquiredby computed tomography, cardiac magnetic reso-nance imaging, or rotational angiography providesvaluable road maps to guide electroanatomic map-ping. Mapping resolution is influenced by electrodesize and interelectrode spacing. Although differencesbetween 6-mm and 4-mm electrode-tipped cathetersmay have a substantial impact on mapping resolutionwithin low-voltage areas, the impact on normalvoltage amplitudes, such as His signals, is lessmarked (30). Moreover, 4-mm cryocatheters producesubstantially smaller lesions (31), such that the tradeoff between mapping resolution and lesion effec-tiveness generally favors 6-mm cryocatheters.

Identifying the compact AV node and slowpathway in patients with AVNRT and a displaced AVconduction system can be challenging. Our generalapproach is to mark the location of the His signal,induce AVNRT, and electroanatomically map retro-grade atrial activation (i.e., fast pathway for typicalAVNRT or slow pathway for atypical AVNRT). Cry-omapping at the suspected slow pathway site is thenperformed in tachycardia, with subsequent cryoa-blation if tachycardia is terminated by block in theslow pathway and the site is deemed to be safe(Figure 1B). The 1 case of AVNRT that was not suc-cessfully cryoablated was in a patient with ccTGA.Interestingly, the slow pathway was effectivelyeliminated by RF ablation in the L-looped version ofKoch’s triangle despite the anterolaterally displacedAV node. A series by Liao et al. (32) described

PERSPECTIVES

COMPETENCY IN MEDICAL KNOWLEDGE: Some forms of

congenital heart disease, such as AVSD, ccTGA, and certain types

of univentricular hearts, are associated with displaced AV

conduction systems. Catheter ablation of perinodal substrates

should be undertaken with care in patients with AV nodes that

are displaced or are of uncertain location. Cryoablation is

feasible, safe, and moderately effective as a first-line treatment

modality in this context.

TRANSLATIONAL OUTLOOK: Multicenter studies are

required to provide more accurate estimates regarding the safety

and efficacy of cryoablation for perinodal substrates in patients

with displaced or uncertain AV node locations, and to compare

this strategy with other technologies such as remote magneti-

cally guided RF ablation.

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 . - , N O . - , 2 0 1 8 Ávila et al.- 2 0 1 8 :- –- Cryoablation in Congenital Heart Disease

9

slow-pathway modification with RF ablation in themid-septum in 5 of 8 cases with ccTGA and in theposterior septum in the remaining 3 cases. In 4 casesof attempted ablation of AVNRT in patients withccTGA, as reported by Upadhyay et al. (14), 2 weresuccessful from a conventional, albeit L-looped, slowpathway location. Treatment failed in 1 case despitemultiple attempts from both sides of the atrialseptum, with AV block that transiently occurredduring cryoablation and fully resolved upon promptinterruption of therapy. These findings further high-light the potential safety benefits that cryothermalenergy can provide for arrhythmia substrates in riskylocations within complex anatomies.

An alternative approach that has been proposed inpatients with CHD and arrhythmia substrates in high-risk locations is the use of remote magneticallyguided catheter ablation (33). Advantages includegreater catheter stability, enhanced catheter maneu-verability, excellent 3D image integration, and areduction in radiation exposure. The system is not yetcompatible with cryocatheters such that reliablereversible lesions cannot be applied.

STUDY LIMITATIONS. This study is observational andinvolves a limited number of patients with variedperinodal substrates and heterogeneous forms ofCHD. The lack of comparisons to RF ablation limitsfirm conclusions regarding the relative merits of the 2energy sources. Cases were performed in a singlereferral center for complex ablations in CHD withextensive experience in cryoablation, such thatresults may not be extrapolated to sites with limitedproficiency in CHD or cryoablation. As highlighted byconsensus statements, electrophysiologic proceduresin patients with moderate or complex CHD or com-plex arrhythmias should be performed in regionalreferral centers by cardiac electrophysiologists withexpertise in CHD and in laboratories with appropriatepersonnel and equipment (22).

CONCLUSIONS

In our experience, cryoablation was a feasible andsafe treatment for perinodal arrhythmia substrates inpatients with varied forms of CHD associated with adisplaced AV conduction system, including AVSDs,ccTGA, and univentricular hearts. It could be helpfulin localizing and eliminating slow-pathway inputs tocompact AV nodes situated outside the usual confinesof Koch’s triangle and in targeting septal re-entrantscircuits and perinodal or peri-Hisian focal tachy-cardia sources. Moderate effectiveness was observedin this case series, with crossover to RF energyrequired in a minority of cases.

ADDRESS FOR CORRESPONDENCE: Dr. Paul Khairy,Montreal Heart Institute Adult Congenital Center,Montreal Heart Institute, 5000 Belanger Street East,Montreal, Quebec, Canada H1T 1C8. E-mail: paul.khairy@umontreal.ca.

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KEY WORDS AV node, conduction system,congenital heart disease, cryoablation,supraventricular tachycardia