Transvenous Catheter Ice Mapping and Cryoablation of the Atrioventricular Node in Dogs

Reprinted with permission fromPACING AND CLINICAl ELECTROPHYSIOLOGY, Volume 22. NO.10 October 1999

Copyright ©1999 by Futura Publishing Company, Inc., Armonk, NY 10504-0418

Transvenous Catheter Ice Mappingand Cryoablation of the AtrioventricularNode in DogsMARC DUBUC, DENIS ROY, BERNARD THIBAULT, ANIQUE DUCHARME,JEAN-CLAUDE TARDIF, CHRISTINE VILLEMAIRE, TACK KI LEUNG,*and MARIO TALAJIC

From the Department of Medicine, and the *Department of Pathology, Montreal Heart Institute,Montreal, Quebec, Canada

DUBUC, M., ET AL.: Transvenous Catheter Ice Mapping and Cryoablation of the Atrioventricular Node inDogs. While radiofrequency catheter ablation is very effective, it does not allow for prediction of successprior to full delivery of the energy. We investigated the use of cryoablation using a new catheter on the AVnode to determine (1) if a successful site might be identified prior to the ablation itself, and (2) the pa-rameters of cryoablation of the AV node using a new cryocatheter. In eight dogs, the cryoablation catheterwas advanced to the AV node to produce transient high degree AV block by lowering the temperature toa minimum of -4OºC (ice mapping). Transient high degree AVnode block was obtained in seven of eightanimals at a mean temperature of -39.9 ± 11.6°C. No significant pathological modification was found inall animals but one and, in all cases, electrophysiological parameters of the AVnode measured before, 20minutes, 60 minutes, and up to 56 days after cryoapplication were not significantly different. In the 12other dogs, after ice mapping, cryoablation of the AV node was attempted with a single freeze-thaw cyclein 6 dogs (group I) and a double freeze-thaw cycle in the other 6 dogs (group II). Chronic complete AVblock was obtained in only one animal in group I compared to all animals in group II. Ablation of the AVnode is effective with a double freeze-thaw cycle using a percutaneous catheter cryoablation system. Icemapping of the area allows for identification of the targeted site. (PACE 1999; 22:1488-1498)

mapping, catheter ablation, atrioventricular node, electrophysiology

Introduction

Catheter ablation is a very effective and well-recognized treatment of cardiac arrhythmias.1—4

The current approach produces a small discrete le-sion by delivering (RF) current be-tween a catheter tip electrode and a skin electrode.Although its success rate is high for the treatmentof supraventricular tachycardias in which the ar-rhythmogenic zone is relatively small, RF current is

Supported by the Fonds De La Recherche En Santé du Québec(FRSQ).Address for reprints: Marc Dubuc, M.D., Montreal HeartInstitute, 5000 Street East, Montreal, Quebec H1TlC8, Canada. Fax: (514) 376-1355; e-mail: [email protected]

Received October 27, 1998; revised December 29, 1998; ac-cepted January 11, 1999.

less effective in disorders with a larger arrhythmicsubstrate such as ventricular tachycardia associ-ated with coronary artery disease5 or atrial fibrilla-tion.6 In addition, the effects of RF applications at aspecific site cannot be predicted before the actualcurrent delivery. As a result, patients undergoingRF ablation frequently receive several lesion-pro-ducing RF applications at nonsuccessful sites be-fore a successful site is identified. A percutaneouscatheter ablation method that allows for pre-dictable results of a given application, and whichhas the potential to create larger lesions whenneeded, is presently not available clinically. Priorsurgical experience has demonstrated that the arearesponsible for an arrhythmia can be identified bysuppressing its electrical activity with a hand-heldcryoprobe prior to production of an irreversiblestate (ice mapping).7,8 Typically, temperaturesaround 0°C produce transient loss of electrical

1488 October 1999 PACE, Vol. 22

CRYOCATHETER ABLATION

function whereas lower temperatures (-60°C) pro-duce irreversible damage. We recently demon-strated the feasibility of ablating cardiac tissue byusing a percutaneous cryoablation catheter.9 Thissystem is capable of cooling cardiac tissue to a widerange of target temperatures and can be used toevaluate potential targets before definitive ablation.

Recent experience with cryoablation in theliver, prostate, and skin has shown that a series oftwo freezing cycles results in greater tissue injurywith a larger lesion than a single freeze-thaw cy-cle.10—15 In addition, ultrasonography has proved tobe a sensitive and reliable method to measure thedimensions of cryolesions in these tissues and hasbecome the imaging modality of choice to addressthis question. Indeed, the ability of ultrasound toallow serial assessment of successive freeze-thawcycles in the same location offers a distinct advan-tage over histology. Ultrasound examination alsopermits continuous observation of the growth ofthe ice ball over time during each cycle and thismay further help to define the optimal freezing pa-rameters. It is unclear to what extent these princi-ples apply during cardiac catheter cryoablation.

The goals of the present study were threefold:(1) to determine whether conduction of the atri-

Electricalconnector

oventricular (AV) node can be transiently inter-rupted by cooling the AV nodal area with com-plete recovery after passive rewarming (ice map-ping) using a transvenous catheter cryoablationsystem; (2) to assess the ability of catheter cryoab-lation to permanently abolish conduction of theAV node with prior ice mapping of the target area;and (3) to compare the strategies of single versusdouble freeze-thaw cycle for ablation of the AVnode using electrophysiological, histological, andintracardiac echocardiographic assessments.

MethodsAll animal experiments were approved by the

Montreal Heart Institute Animal Care and UseCommittee following the guidelines of the Cana-dian Council on Animal Care.

Cryoablation System

A new steerable 9 Fr catheter with a 4-mm tip electrode using Freon@ (ice mapping study) orGenetron® AZ-20 (cryoablation study) (CryoCathTechnologies Inc., Montreal, Quebec, Canada) as arefrigerant fluid was used (Fig. 1). The cry-ocatheter has a hollow shaft with a closed elec-

Lever controlstip curvature

Flexible 9 French

Micro-tube injects refrigerant into tip

Evaporation of refrigerantcauses low tip temperature

Figure 1. Schematic of the cardiac cryocatheter.

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DUBUC, ET AL.

trode tip. Temperature is recorded at the distal tipby using an integrated thermocouple. The catheterhas four electrodes at its distal end, the distalclosed cooling electrode tip as well as three prox-imal ring electrodes. These four electrodes can beused for cardiac pacing and intracardiac electro-gram recording. The console delivers the refriger-ant fluid under pressure into an inner delivery lu-men to the distal electrode. A liquid-to-gas phasechange takes place in the cryogenic fluid when theliquid passes into the tip, which is maintained un-der vacuum. This transformation translates intorapid and extreme cooling to temperatures as lowas -60ºC. The gas is conducted away from the tipthrough the vacuum return lumen and is collectedin the console.16

Animal Studies

Twenty mongrel dogs weighing 30.2 ± 8.7 kgwere studied. After induction of anesthesia withpentobarbital sodium (25-30 mg/kg body weight),each dog was intubated and ventilated at20-25/min with a positive pressure Harvard res-pirator (Harvard Apparatus, South Natick, MA,USA) using room air supplemented with oxygen.Surface ECG leads I, II, and III were recorded con-tinuously. Two 9 Fr introducers were inserted intothe right femoral vein. Under fluoroscopic guid-ance, a cryoablation catheter was advanced to theAV junction and positioned to record His-bundleactivity. A standard quadripolar electrodecatheter was positioned at the right ventricularapex. Intracardiac electrograms were amplifiedand filtered (30-500 Hz bandpass filters) andrecorded on an optical disk. Heparin was admin-istered intravenously throughout the procedureand the dosage was adjusted to maintain a partialthromboplastin time at least twice the normallevel.

Ice Mapping of the AV Node

In eight dogs, the cryoablation catheter wasadvanced to the AV junction and was positionedusing standard criteria for ablation of the AVn o d e . 1 7 Cryoapplication with progressive lower-ing of the temperature to a minimum of -40°C wasdone in the AV nodal area. As soon as high degreeAV block or lengthening of the PR interval by >50% was obtained, cryoapplication was stopped.

If no effect on conduction was noted with a tem-perature of -40°C, the cryocatheter was relocatedand cryoapplication was repeated. Electrophysio-logical evaluation of the AV node was also doneimmediately prior to cryoapplications and at 20and 60 minutes after the successful cryoapplica-tion. Animals were kept alive and sacrificed after0-56 days. Repeat electrophysiological evaluationof AV conduction was performed before sacrifice.Afterwards, the hearts were removed for patholog-ical evaluation.

Cryoablation of the AV Node

In 12 dogs, cryoablation was performed to ob-tain complete AV node block. In these experi-ments, freezing was continued at the lowest at-tainable temperature after the induction of highdegree AV block. If no high degree AV block oc-curred despite freezing to a temperature of -4OºCcryoablation was stopped and the catheter wasrepositioned. Freezing was repeated until high de-gree AV block was obtained, using the same cry-omapping criteria. After a successfully icemapped area was found, freezing was maintainedat the lowest attainable temperature for 5 minutes(single freeze-thaw cycle) in the first six animals(group I). In the following six animals (group II),the site of interest was frozen for 5 minutes twiceallowing complete recovery to body temperaturebetween both cycles (double freeze-thaw cycle).Acute success was defined as the persistence ofcomplete AV block 30 minutes after the lastcryoapplication. Chronic success was defined asthe persistence of complete AV block at the timeof sacrifice. Animals were sacrificed 0-56 days af-ter the procedure and hearts were removed forpathological evaluation.

Intracardiac Echocardiography

The intracardiac echocardiographic systemcomprised a 12.5-MHz rotating ultrasound trans-ducer mounted on the tip of a 6.2 Fr blunt-tippedcatheter (Boston Scientific Corp., Watertown, MA,USA) and a dedicated imaging console (HP SonosIntravascular, Andover, MA, USA). The best axialand lateral resolutions of the system are 0.2 and 0.5mm, respectively. Intracardiac echocardiographywas performed in all group II animals undergoingcryoablation of the AV node. The intracardiac ul-



trasound catheter was inserted through the left ysis of variance were used when appropriate. Re-femoral vein and advanced in the right atrium. Theultrasound catheter was manipulated to obtain op-timal images of the cryoablation catheter tip,which was identified by its characteristic fan-shaped acoustic shadow. The tip of the cryoabla-tion catheter was evaluated for adequacy of contactwith the endocardium before each application.Echocardiographic monitoring was continuouslyperformed before, during, and for at least 1 minuteafter every cryoapplication. Intracardiac echocar-diographic images were recorded on S-VHS video-tape for subsequent review. The width of cryole-sions was measured offline using electroniccalipers by an echocardiographer blinded to thefreezing cycle number and parameters, to the acuteand chronic outcome, and to the results of histo-logical measurements. Because it is not possible tomeasure cryolesion depth due to posterior acousticshadowing, lesion (ice ball) volume was calculatedusing the hemisphere formula: X X0.5), where w = width of the lesion. Serial echocar-diographic measurements were made to quantitatethe growth of the ice ball during cryoapplication.Final lesion dimensions were measured at the endof the freezing cycle.

Pathological Evaluation

After the animals were sacrificed, hearts wereremoved and immediately fixed in TISSUFIX(Laboratoire Chaput, Montreal , Quebec, Canada)at room temperature and were examined 48 hourslater. During gross examination, dimensions of thelesions were measured. Afterwards, tissue speci-mens were embedded in paraffin and were di-vided in 5 µm-thick sections and appropriatelystained with hematoxylin-phloxin-safran (HPS)for histological examination. Macroscopic evalua-tion of the conduction system was performed inall the animals, and serial histological sectionswere done along its path. Volumes of all visible le-sions were estimated by using the formula

which calculates the volume ofone half of a prolate ellipsoid, where 1 = length,w = width, and d = depth of the lesion.

sults were considered significant at a P value of< 0.05.

Apart from its larger size (9 Fr), handling andpositioning of the cryocatheters were similar tostandard RF ablation catheters. Before all cryoap-plications, endocardial contact was ensured in astandard fashion for catheter ablation. In all groupII animals, this contact was further confirmed byintracardiac echocardiography.

Ice Mapping of the AV Node

Significant conduction abnormalities of theAV node were obtained in seven of eight animalsat a temperature of -33.9 ± 11.6°C. Five dogs hadtransient complete AV block (Fig. 2), one animaldeveloped 2:1 AV block and another had atype I second degree AV block. In one animal,no modification of AV nodal conduction was ob-tained despite nine cryoapplications; how-ever, reversible right bundle branch block(RBBB) occurred after some applications. Re-versible RBBB also occurred in two other animalswhen the cryocatheter was positioned more dis-tally on the AV conduction system. The timecourse of electrophysiological and tempera-ture changes is shown in Fig. 2E. Fifteen to 30seconds were needed before the target tem-perature was achieved. Upon stopping refriger-ant fluid flow, catheter temperature returned tobody temperature within 10-20 seconds. In allcases, AV conduction completely recoveredwithin a few minutes after ice mapping. A total of6 ± 3 (range 2-10) potential sites were evaluatedbefore transient AV block was produced. Electro-physiological data for this group of experimentsare shown in Fig. 3; sinus cycle length, AH inter-val, HV interval, Wenckebach cycle length, andeffective refractory period of the AV node mea-sured before, 20 minutes, 60 minutes, and up to56 days after cryoapplication were not signifi-cantly different.

Statistical Analysis Cryoablation of the AV Node

All data are expressed as mean ± SD. Stu- Table I shows the results of cryoablation ofdent’s t-test, Wilcoxon signed-rank test, and anal- the AV node. Electrical noise appeared on the in-

PACE, Vol. 22 October 1491

Figure 2. The intracardiac tr and surface ECG of dog 8 in which we reversibly blocked atrioventricular(AV) conduction. (A) Before cryoablation. (B) A f t e r 30 seconds of cryoapplication, complete AVnode conduction block was obtained. Typically, during application, electrical noise appears onthe intracardiac recording wi th loss of the e lectrogram due to ice bal l format ion on the cathetertip. This usually occurs around -20 to -30°C.. (C) When cooling fluid injection is stopped, 1:1conduct ion resumes af ter 7 seconds. (D) After 10 minutes , AV nodal conduct ion i s normal ized (D1,lead dis ta l -uni , unipolar recording from the t ip e lec trode; ablat, b ipolar recording between thetip and the first ring electrode). (E) This figure shows simultaneous low speed recordings of tiptemperature ( t ip T ° ) , catheter, and surface ECG of the same event . Temperature is lowered to -36°Cin < 15 seconds with the appearance of high degree AV block after 30 seconds. Cooling fluidinjection is stopped at 35 seconds and 1:1 AV conduction resumed in < 10 seconds. The tiptemperature re turns to body temperature progress ive ly over the next 20 seconds .



600

500

400

300

200

1 0 0

0SCL AH H V E R P

Figure 3. Electrophysiological data. SCL = sinus cyclelength; AH = AH interval; HV = HV interval; WCL =Wenckebach cycle length; ERP = effective refractoryperiod of the atrioventricular node; PRE = prior tosuccessful cryoapplication; T1 = 20 minutes aftercryoapplication; T2 = 60 minutes after cryoapplicationT 3 = O-56 days after cryoapplication.

tracardiac recording from the tip of the ablationcatheter in all the animals during cryoapplica-tions with loss of the electrogram (Fig. 4). Thecatheter tip adhered firmly to the endocardialsurface, allowing stable catheter contact through-out the cryoapplication. Accelerated junctional

rhythm was observed for a few (5-16) seconds af-ter cryoablation in group I (single freeze-thaw cy-cle) and also in group II dogs (double freeze-thawcycle), but only after the first 5-minute cryoap-plication and was never observed after the sec-ond freezing cycle. A total of 5.5 ± 6.2 cryoap-plications (cryomapping) were done in group Iversus 7.3 ±4.1 in group II (P = NS). No differ-ence was found between the temperature reachedat the tip of the catheter in group I versus groupII (-54.3 ± 2.4°C vs -57.8 ± 4.2°C). Complete AVblock was achieved acutely in three of six ani-mals in group I versus in six of six in group II. AVconduction resumed in two of the three animalswith acute success in group I, 24 hours (dog 5)and 8 days (dog 4) after the last cryoapplication.Thus, only one of six animals remained inchronic AV block after a single freeze-thaw cycle.In contrast, all the animals in group II remainedin complete AV block at the time of sacrifice.Thus, only one of six animals remained inchronic AV block after cryoablation with a singlefreeze-thaw cycle whereas the six animals withcryoablation with double freeze-thaw cycles hadpermanent AV block,

Table I.

Catheter Ablation of the AV Node

Results

Dog

Temperature Sacrifice Application Acute Chronic(Days) (No) Success* Success†

Group I (single 1 -56 7 3f reeze- thaw 2 -56 8 4cyc le ) 3 -56 8 4

4 -53 23 25 -55 9 26 -50 1 4 18

Mean ± SD -54.3 ± 2.4 11.5 ± 6.2 5.5 ±6.2

f reeze- thaw 8 -61 1 7 6cyc le ) 9 -60 42 1 3

1 0 -58 28 31 1 -57 28 31 2 -50 22 8

Mean ± SD -57.8 ± 4.2 25.7 ± 9.4 7.3 ± 4.1

3/6++

+

+

+

6

-

++-I-+++

/6 6/6

*Persistence of complete AV block 30 minutes after the last cryoapplication; †Persistence of complete AV blockat the time of sacrifice; AV = atrioventricular.


Group I I (doub le 7 -61 1 7 1 1

6

DUBUC, ET AL.

40Temperature (Celsius)

20 .

0

-20

-40

-60

Surface ECG

Figure 4. Simultaneous recordings of tip temperature, intracardiac (catheter), and surface ECGduring cryoabla t ion in dog 2 (group II) . After 17 seconds of appl ica t ion, comple te a tr ioventr icular(AV) nodal block was obtained. A minimum temperature of -60°C was achieved. Complete AVblock persisted until sacrifice.

Intracardiac Echocardiography

Adequate contact between the cryoablationcatheter tip and the endocardium was demon-strated before applications in all group II dogs.During cryoapplications, ice ball formation wasclearly identified by intracardiac echocardiogra-phy as an hypoechoic zone bordered laterally by aslightly hyperechoic rim and with posterioracoustic shadowing (Fig. 5). The ice ball appearedapproximately 4 seconds after initiating the freez-ing cycle and preceded the presence of electro-physiological abnormalities by approximately 10seconds, There was no evidence of microcavita-tion (gas) during cryoapplications. The size of theice ball grew progressively during the first 3 min-utes of the freezing cycles (P < 0.05 for lesion

width at 1 vs 2 minutes and 2 vs 3 minutes), and itremained stable for the last 2 minutes (Fig. 6). Thesame result was reported by Hunt et a1.18 wherefurther prolongation of exposure t ime beyond 3minutes did not result in any further increase inlesion dimension or volume. The final volume ofthe ice ball was 49.8 ± 53.9 mm3 at the end of thefirst cryoapplication and it increased to 66.9 ±70.9 mm3 after the second freezing cycle. This31% increase in final ice ball volume was not sta-tistically significant (P = 0.067). The ice ball pro-gressively decreased in size and completely dis-appeared a few seconds after freezing wasstopped, at which time the posterior acousticshadowing suddenly disappeared. We were notable to detect any residual lesion with ultrasoundexamination at the end of the freeze-thaw cycles.



Figure 5. Intracardiac echocardiography monitoring ofice ball formation during catheter cryoablation. The icebal l i s seen as a hypoechoic zone wi th poster ior acoust icshadowing (arrow). RA = right atrium; RV = rightventricle; arrowhead = tricuspid valve.

In particular, there was no hypoechoic or hypere-choic region and no defect in endocardial conti-nuity visible on intracardiac echocardiography atthe site of application after cryoablation.

7 ,

6-

5 -

4

3 -

2

0 1 2 3 4 5 6

Time (min)** = p < O . O 5

Figure 6. A plot of lesion size [length) over time(minutes) in a l l the animals . **Lesion s ize i s s igni f icant lydifferent between 1 and 2 minutes and also between 2and 3 minutes (P < 0.05). There is no difference after 3minutes.

P a t h o l o g y

Pathological evaluation (Table II) showed nodamage to the AV node in all but one animal whohad isolated ice mapping. In this particular dog,the AV node was found to be more superficialthan usual and its superior portion was replacedwith connective tissue. In addition, temperatures<-50°C unexpectedly occurred in the experi-ment. Small hemorrhagic lesions and fibrosis inthe tissues surrounding the AV node, such as thetricuspid valve and the endocardium, were ob-served in seven of the eight animals undergoingmapping. These changes were significantly moremarked in the animals in which permanent abla-tion of the AV node was attempted and/or pro-duced. Gross pathological evaluation showed thepresence of a whitish area of scar tissue in all ofthe dogs (groups I and II). Lesion volumes were42.1 ± 25.0 mm3 (range 9.4-51.3) in group I and185.8 ± 184.2 mm3 (range 20.9-523.6) in group II(P = 0.18). Microscopic evaluation (Fig. 7A)showed lesions well demarcated from normal tis-sue in the AV nodal area with the presence of re-placement fibrosis and no evidence of viablecells in group II. Incomplete necrosis and viablecells were observed within the lesions in group I(Fig. 7B).

No significant clinical complications werenoted during the study. However, a small pul-monary infarct compatible with embolism wasfound at pathological evaluation in one dog whohad complete ablation of the AV node.

Discussion

Reversible Ice Mapping

Our results demonstrate that reversible icemapping of a potential arrhythmogenic site is feasi-ble using a percutaneous cryoablation catheter. Sig-nificant effects on AV nodal conduction wereachieved in all but one animal (7/8). In each case,AV conduction resumed within seconds after freez-ing was stopped and was not significantly differentfrom premapping values. Pathological evaluationrevealed minimal tissue damage particularly to thestructures surrounding the targeted area. Some ofthese lesions may be related to the mechanicaltrauma caused by the manipulation of the catheterin the area or, since the console was controlled


DUBUC. ET AL.

Dog Time AfterNo. Ablation

Table II.

Pathology Results in Dogs After Ice Mapping of the AV Node

Pathological Findings

Microscopic

Approaches Penetrating Bundle SurroundingGross to AV Node AV Node Branches Branches Structures

1 9d NL Connective tissue withn e o v a s c u l a r i z a t i o no f t h e t o p p o r t i o n o fnode (l/3) 0.6x2.0m m

N I

NI NL N L S l i g h t t h i c k e n i n go f t h ee n d o c a r d i u mwith fibrosis inA V n o d e a r e a

Thrombus ons e p t a l l e a f l e to f t h eincuspid valve

N L

2 7 d H e m o r r h a g i c l e s i o ni n center o f t h efibrous body

NI N L Fibrovasculartissue inp r o x i m a lp o r t i o n o fR B B

Fibrosis on RBB7 d

7 d6w

Od

8w

H e m o r r h a g i c l e s i o no n s e p t a l l e a f l e t o ft r i c u s p i d v a l v e

N LFibrosis on septal

l e a f l e t o f t r i c u s p i dv a l v e

H e m o r r h a g i c l e s i o no n e n d o c a r d i u mc l o s e t o A V n o d e

S m a l l a r e a o f f i b r o s i si n t r i a n g l e o f K o c h

N I N L N L

NL N L N L N L NLNL NL NL N L N L

NL N L N L N L N L

NL N L N L N L F i b r o a d i p o s er e p l a c e m e n tof tissueabove the Hisb u n d l e

F i b r o t i ce n d o c a r d i u mi n A V n o d ea r e a

8 2w . NL NL NL NL N L

AV = atrioventricular; d = days; w = weeks; NL = normal; RBB = right bundle branch.

manually, to the unwanted low temperature that the node in these animals. A minimum tempera-occasionally occurred during some cryoapplica- ture of -33.9 ± 11.6ºC was necessary to obtain a re-tions (range -5 to -55°C). Subsequent refinement versible effect on AV nodal conduction with theof the cryoablation system has allowed automation percutaneous cryocatheter while a temperature ofof this feature, thus eliminating this possibility. only 0°C was required in prior surgical reports.’The AV node itself was free of damage except in This is explained in part by the warming effect ofone animal where its superior portion was fibrotic the blood pool circulating around the freezing tipafter ice mapping. In this case, excessive tempera- during catheter cryoapplication on the endocardialture lowering occurred inadvertently and the AV tissue since during surgical mapping of the AVnode was more superficial than usual. Other exper- node under normothermic conditions there is noiments in which temperatures of < -50°C occurred blood flow around the cryoprobe creating a “ther-were not associated with damage to the AV node. mal sink.” In addition to this, a progressive tem-Presumably, this was due to the deeper location of perature gradient is established between the



Figure 7. (A) Low power photomicrograph of a singlefreeze-thaw cycle lesion made on animal 4 (group I).There is presence of viable nodal cells within the lesion.Complete atrioven tricular (AV) nodal block wasachieved acutely in this animal, but AV conductionresumed 24 hours after the cryoablation (hematoxylin-phloxin-safran [HPS] s t a i n i n g ) . ( B ) L o w p o w e rphotomicrograph of a double freeze-thaw cycle lesionmade on animal 11 (group II). No viable nodal cells areseen within the lesion (HPS staining).

catheter tip and the adjacent cardiac tissue. Thus,the catheter tip temperature recorded in these ex-periments overestimates deeper tissue cooling. Asa result of this phenomenon, ice mapping of an ar-rhythmogenic site, which is deeply located in themyocardial wall, will probably have some perma-nent effect on the tissue between the endocardiumin contact with the cryocatheter electrode and thetargeted area. This mechanism may account forsome of the pathological changes observed with icemapping of the AV node.

The reversibility of ice mapping is a poten-tially important advantage over the RF approachbecause it may allow prediction of a successful ab-lation site before the creation of a larger irre-versible lesion. In addition to avoiding the produc-tion of unwanted lesions, reversible ice mappingcould also be used for the ablation of arrhythmo-genic sites located close to critical areas such as theAV node where an irreversible lesion has greateruntowards effects. Even though reversible ice map-ping of the AV node is possible with a cryoablationcatheter, catheter cryomapping of different ar-rhythmogenic substrates located elsewhere in theheart remains to be investigated.

Catheter Cryoablation of the AV Node

Transvenous catheter ablat ion has alreadybeen reported by Gillette et a l . 1 9 , 2 0 but there wasno recording or pacing electrodes instal led ontheir 11 Fr catheter. Accurate localization of thecryolesion needed the use of a separate catheterfor recording. Chronically, five of eight animals(swine) remained in complete AV block after 6weeks of observation. We used a 9 Fr catheter withrecording and pacing electrodes installed at itsdistal end imitating clinically used catheters.

Ablation of the AV node with a cryocathetercan be achieved with a high success rate (6/6),which is comparable to RF catheter ablation. How-ever, we found that double freeze-thaw cycles wereneeded to ensure acute and chronic success. Ourhistological findings demonstrate more completenecrosis with double freeze-thaw cycles, comparedto single cryoapplications. These findings are sim-ilar to what has been observed during cryoablationof other t issues such as the skin, l iver , andprostate.10,15 Lesions were larger on intracardiacechocardiography and histology in the doublefreeze-thaw cycle group (group II) compared to thesingle cycle group (group I). The difference be-tween the groups was not statistically significantdue to the wide range of lesion volumes. However,the complex anatomy of the AV nodal area is notwell suited for measurements of lesion volume onpathology. Monitoring of the growth of the ice ballwith intracardiac echocardiography has providedpotentially important information concerning opti-mal freezing parameters. Indeed, ice ball volumeproduced by cryoablation with a refrigerant fluid

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DUBUC, ET AL.

did not increase after the first 3 minutes of acryoapplication. These findings are similar to whathas been observed for a liquid carbon dioxide cry-oprobe.18 If further studies confirm that cryoappli-cations of 3-minute and 5-minute durations resultin lesions of similar sizes, the shorter freezing cy-cles will be preferred in the clinical setting. Thereare other notable differences on intracardiacechocardiography between cryoablation and RFand microwave ablations. The absence of micro-cavitations (gas formation) during cryoablation andof detectable residual lesions after the applicationcontrast with their universal presence with other

approaches. In conclusion, ablation of the AV nodeis possible and highly effective using a percuta-neous catheter cryoablation system. Ice mapping ofthe area allows for identification of the targetedsite. Subsequent applications of double free-thawcycle results in permanent block. Further studiesare needed to better understand the cryobiology ofthe heart and evaluate the potential of this technol-ogy in larger arrhythmogenic substrates.

Acknowledgments: We thank Emma De Blasio for hertechnical assistance and Luce Bégin for typing the manuscript.

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Transvenous Catheter Ice Mapping and Cryoablation of the Atrioventricular Node in Dogs

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