Cryoablation outcomes for AV nodal reentrant tachycardia
comparing 4-mm versus 6-mm electrode-tip catheters

Lena Rivard, MD, Marc Dubuc, MD, Peter G. Guerra, MD, Paul Novak, MD, Denis Roy, MD,Laurent Macle, MD, Bernard Thibault, MD, Mario Talajic, MD, Paul Khairy, MD, PhD From the Electrophysiology Service, Montreal Heart Institute, Montreal, Quebec, Canada. BACKGROUND Cryoablation is increasingly used to treat atrio-
Over a median follow-up of 155 days, recurrences were less com- ventricular nodal reentrant tachycardia (AVNRT). It is unknown mon with 6-mm electrode tips. Actuarial event-free survival rates whether larger electrode-tip cryocatheters improve outcomes at 1, 3, 6, and 12 months with 6-mm versus 4-mm electrode-tip cryocatheters were 96.7%, 93.4%, 91.9%, and 88.5% versus89.9%, 87.0%, 84.1%, and 77.1%, respectively, with no recur- OBJECTIVE This study sought to compare acute and long-term
rence thereafter (P ϭ .0457). In multivariate analyses adjusting success with 4-mm versus 6-mm electrode-tip cryocatheters for for baseline imbalances and medical therapy postablation, cryoa- blation with a 4-mm-tip catheter incurred a 2.5-fold increased risk METHODS We conducted a 2-group cohort study on 289 patients,
of recurrence (hazard ratio 2.5, 95% confidence interval 1.0 to age 45.5 Ϯ 15.9 years (76.8% female), who underwent transcath- eter cryoablation as a first-time procedure for AVNRT with 4-mm(N ϭ 152) or 6-mm (N ϭ 137) electrode-tip catheters.
CONCLUSION In patients with AVNRT, cryoablation with 6-mm
electrode-tip catheters is safe and is associated with fewer recur-
RESULTS Acute procedural success was achieved in 90.7% (95%
rences on long-term follow-up compared with 4-mm electrode-tip confidence interval 86.9% to 93.7%) with no difference between the 2 electrode-tip sizes. A shorter fluoroscopy time (16.1 Ϯ 11.3versus 20.3 Ϯ 14.9 minutes, P ϭ .0096) and trend toward briefer KEYWORDS Arrhythmia; Catheter ablation; Cryothermal energy; AV
procedural duration (166.6 Ϯ 49.1 versus 173.5 Ϯ 53.0 minutes, P ϭ NS) were noted with 6-mm electrode tips. Transient AV block (Heart Rhythm 2008;5:230 –234) 2008 Heart Rhythm Society. All occurred in 5.2%, with complete recovery in 4.4 Ϯ 2.6 seconds.
compare acute and long-term success rates with 4-mm ver- Transcatheter cryothermal slow pathway modification is an sus 6-mm electrode-tip cryocatheters for AVNRT.
effective treatment for AV nodal reentrant tachycardia(AVNRT), with a safety profile superior to that of radiofre- Study design
been raised regarding potentially lower efficacy when com- A 2-group cohort study was conducted on all patients hav- pared with RF ablation. To date, 2 pilot studies have ran- ing undergone a first transcatheter ablation procedure for domized patients with AVNRT to cryoablation with 4-mm AVNRT with cryothermal energy at the Montreal Heart electrode-tip catheters versus RF ablation. Whereas 1 re- Institute between May 1999 and February 2006. The study ported no difference in acute and long-term protocol was approved by our local institutional review the second favored RF One factor that may con- board, and all patients provided written informed consent.
tribute to lesser efficacy with 4-mm electrode-tip cryoabla- Patients with prior ablation of a different arrhythmia sub- tion is an average lesion volume less than half that created strate were included if AVNRT had not been previously by 4-mm RF It may be conjectured, therefore, targeted. Those presenting with recurrent AVNRT were that cryocatheters with larger distal electrode tips may con- excluded, regardless of whether the initial procedure uti- fer additional benefit. The purpose of this study was to Patient records were reviewed to determine clinical vari- This work was supported in part by the Canada Research Chair in ables, procedural outcomes, and arrhythmia-free survival Electrophysiology and Adult Congenital Heart Disease (Dr. Khairy). Dr.
based on routine follow-up, including clinical visits, elec- Dubuc is a consultant for CryoCath Technologies.
Address reprint
trocardiograms, Holter monitors, rhythm strips, and event requests and correspondence: Dr. Paul Khairy, Electrophysiology Ser-
recordings. Electronically stored data from electrophysiol- vice, Montreal Heart Institute, 5000 Belanger Street East, Montreal, Que- ogy procedures were reviewed and relevant parameters be- bec, Canada, H1T 1C8.(Re-ceived July 5, 2007; accepted October 3, 2007.) fore and after cryoablation retrieved, including number and 1547-5271/$ -see front matter 2008 Heart Rhythm Society. All rights reserved.
duration of applications and procedural and fluoroscopy further lowered to Ϫ80°C for up to 4 minutes, thereby The main exposure variable was size of the cryocatheter After cryocatheter positioning, a cryomapping applica- electrode tip, binomially categorized as 4-mm or 6-mm.
tion was performed to assess safety (i.e., failure of AH Primary efficacy end points were acute procedural success prolongation by more than 25% from baseline) and efficacy and long-term arrhythmia-free survival. Acute procedural (i.e., failure to induce tachycardia using a previously suc- success was defined as the inability to induce sustained cessful stimulation protocol). Cryoablation was then per- AVNRT after at least 1 cryogenic Long-term formed. Programmed stimulation was pursued during arrhythmia-free survival was defined as the absence of ob- cryoablation, and if tachycardia was reinducible, cryoabla- jectively documented supraventricular tachycardia on clin- tion was terminated and the catheter was repositioned. If no ical follow-up or of symptoms suggestive of recurrent tachycardia was inducible, the application was continued AVNRT confirmed by inducibility on repeat electrophysi- for a total of 4 minutes, provided no AH interval prolonga- ological testing. Acute procedural effects on slow pathway tion or AV block occurred. Programmed stimulation was conduction in patients with acute success were classified as: repeated after ablation. If acutely successful, observation (1) elimination of dual AV nodal physiology, (2) persistent with programmed stimulation on or off isoproterenol was dual AV nodal physiology with no AV nodal echo beats, or performed, typically for 30 minutes or more. Patients were (3) persistent dual AV nodal physiology with AV nodal discharged the next day barring any complication.
echo beats but noninducibility of tachycardia with and with- Patient follow-up
out an intravenous isoproterenol Tachycardia Time 0 was defined as time of the transcatheter cryoablation was defined as more than 3 AV nodal echo procedure. Outpatient follow-up was scheduled at 3 months Transcatheter cryoablation
with a 12-lead electrocardiogram. Holter monitoring, event Electrophysiology procedures were performed in the fasting recorders, and further clinical follow-up was at the discre- state, off all AV nodal blocking agents and antiarrhythmic tion of the treating cardiologist. To maximize completenessof follow-up, referring cardiologists were contacted by tele- drugs for Ͼ5 half-lives, and under conscious sedation pro- phone. Patient-years were accrued until the most recent vided by an anesthesiology service (i.e., continuous propo- fol infusion with boluses of midazolam and fentanyl). Adiagnostic electrophysiology study was performed using Statistical analysis
three 5F quadripolar catheters (Supreme, St. Jude Medical, Continuous variables are presented as mean Ϯ standard Minnetonka, MN) with or without a 6F or 7F decapolar deviation or median and interquartile range (25th, 75th catheter (Livewire, St. Jude Medical) introduced through percentile) depending on their distribution. Categorical right and left femoral veins and placed in standard high right variables are summarized as frequency and percentage.
atrium, His, right ventricular apex, and coronary sinus po- Two-group comparisons of baseline and procedural charac- sitions. All patients underwent atrial and ventricular pro- teristics were assessed by independent sample t tests or grammed electrical stimulation at 2 drive trains (600 msec nonparametric Mann-Whitney U tests where appropriate.
and 400 msec) with up to 2 extrastimuli, using an EP-3 Nominal variables were compared with Fisher exact tests.
computerized stimulator (EP Medsytems Inc., West Berlin, Event-free survival curves were plotted and compared using NJ). If AVNRT was not induced, the protocol was repeated the Kaplan-Meier method and log-rank statistic. A Cox on an isoproterenol infusion titrated up to 5 ␮g/min. All proportional hazards model was used to determine whether recordings were bipolar with the gain set at 0.5 mV/mm and electrode tip size was predictive of recurrent AVNRT while controlling for follow-up duration and potential confound- After completing the diagnostic study, a 7F cryocatheter ers. Two-tailed P values Ͻ.05 were considered statistically was introduced through the femoral vein and an intravenous significant. Testing was performed with SAS software ver- bolus of 2500 IU of unfractionated heparin was adminis- tered. One of two 7F quadripolar steerable cryoablationcatheter models was used, with either a 4-mm (Freezor) or 6-mm (Freezor Xtra) distal electrode tip. Catheter selection Baseline characteristics
was not randomized since the 6-mm electrode-tip catheter A total of 289 patients, age 45.5 Ϯ 15.9 years, had a first was not available for commercial use until the latter part of ablation procedure for AVNRT with 4-mm (N ϭ 152) or our study period. Consoles and catheters (CryoCath Tech- 6-mm (N ϭ 137) electrode-tip cryocatheters at the Montreal nologies Inc., Montreal, QC, Canada) have been previously Heart Institute between May 1999 and February 2006.
Procedural dates with the 4-mm electrode-tip catheter operation, cryomapping and cryoablation. In the cryomap- ranged from May 1999 to January 2007, with 2 interven- ping mode, temperature of the distal tip may be decreased to tions after January 2005. The date range with 6-mm elec- Ϫ30°C for up to 80 seconds to deliver a reversible appli- trode-tip cryocatheters was January 2004 to February 2006.
cation. In the cryoablation mode, this temperature may be All patients had inducible AVNRT, with or without an Left ventricular ejection fraction Յ40%, N (%) isoproterenol infusion. Baseline characteristics are summa- with 6-mm electrode-tip catheters (P ϭ .0252). The median time to recurrence was 30.0 (10.0 to 72.0) days and was nodifferent between the 2 electrode-tip sizes.
Acute procedural success
As depicted in actuarial recurrence-free sur- Overall acute procedural success was achieved in 90.7% of vival rates at 1, 3, 6, and 12 months with 4-mm versus 6-mm patients (95% confidence interval [CI] 86.9% to 93.7%), electrode-tip catheters were 89.9%, 87.0%, 84.1%, and with no statistical difference between 4-mm versus 6-mm 77.1% versus 96.7%, 93.4%, 91.9%, 88.5%, respectively, electrode-tip sizes (91.4%, 95% CI 86.3% to 95.2%) versus with no recurrence thereafter (P ϭ .0457). In multivariate 89.8% (95% CI 84.0% to 94.1%, P ϭ NS). In patients with Cox regression analyses adjusting for baseline imbalances acutely successful cryoablation with 4-mm or 6-mm elec- (i.e., age, hypertension, and diabetes) and medical therapy trode-tip catheters, complete elimination of slow pathway post ablation (i.e., beta-blockers and calcium channel block- conduction was achieved in 52.3% versus 52.0%, absence ers), cryoablation with a 4-mm versus 6-mm electrode-tip of AV nodal echoes despite dual AV node physiology in catheter remained an independent predictor of recurrence 7.9% versus 8.1%, and persistent AV nodal echoes but (hazard ratio 2.5, 95% CI 1.0 to 6.1, P ϭ .0420).
noninducibility on and off isoproterenol in 38.8% versus39.8%, respectively (P ϭ NS). Procedural and postproce- Cryoablation-induced AV block
Transient complete AV block occurred in 15 patients (5.2%)during a cryothermal application: 5 (3.3%) in patients with Recurrences on follow-up
4-mm electrode-tip catheters and 10 (7.3%) with 6-mm Over a median follow-up of 154.5 (110.5 to 228.3) days, 22 electrode-tip catheters (P ϭ NS). The mean duration of AV of 139 (15.8%) patients with acutely successful cryoabla- block was 4.4 Ϯ 2.6 seconds, with no significant difference tion using 4-mm electrode-tip cryocatheters experienced between 4-mm and 6-mm electrode-tip catheters. All com- recurrent AVNRT compared with 10 of 123 (8.1%) patients pletely recovered within 10 seconds. Transient AV block Procedural and postprocedural characteristics in patients with acutely successful cryoablation for AVNRT AVNRT ϭ atrioventricular nodal reentrant tachycardia.
*Nonnormally distributed continuous variables are summarized by median value and interquartile range (25th, 75th percentile).
though catheter stability is an advantage of cryoenergy,larger lesions may be produced by increasing the size of thedistal electrode tip. We hypothesized that cryoablation out-comes for AVNRT may be further improved with 6-mmelectrode-tip catheters.
Our study represents the largest cohort of patients with cryoablation for AVNRT and is the first to compare cryo-catheters. We report superior outcomes without compromis-ing safety using 6-mm electrode-tip catheters. Our overallacute success rate of 90.7% (95% CI 86.9% to 93.7%) iscomparable to prior studies, including a multicenter cohortof 103 patients (91%, 95% CI 84% to and a random-ized study that included 30 patients with cryoablation forAVNRT (93%, 95% CI 79% to Although in the Freedom from recurrence according to type of cryocatheter.
current study the 6-mm electrode-tip cryocatheter was not Kaplan-Meier recurrence-free survival rates are shown for patients having associated with a higher acute procedural success rate when undergone successful slow pathway modification for AVNRT with 6-mm compared with the 4-mm electrode-tip cryocatheter, fluo- and 4-mm electrode-tip cryocatheters. AVNRT ϭ atrioventricular nodal roscopy time was shorter and a trend toward briefer proce- Despite similar acute success rates with 4-mm and 6-mm occurred during cryomapping in 12 patients (4-mm elec- electrode-tip cryocatheters, the larger electrode tip was as- trode-tip in 4, 6-mm in 8) and cryoablation in 3 patients sociated with significantly fewer recurrences on long-term (4-mm electrode-tip in 1, 6-mm in 2). Additionally, 3 pa- follow-up. Recurrence-free survival with the 6-mm elec- tients experienced transient AV block secondary to mechan- trode-tip catheter was 91.9% at 6 months and 88.5% at 2 ical trauma (4-mm electrode-tip in 1; 6-mm in 2). No patient years, which approaches reported results with RF abla- developed permanent AV block during follow-up, and none Fortunately, safety was not compromised in required a permanent pacemaker. No other complication achieving superior long-term outcomes with the 6-mm elec- trode tip. It is unknown whether outcomes may be furthersafely improved with even larger electrode tips (i.e., 8 mm).
Although transient AV block occurred in a sizeable propor- In light of the unique safety profile of cryoenergy, some tion of patients with 6-mm electrode-tip catheters (7.3%), centers have adopted cryoablation as first-line therapy for all promptly recovered on cessation of the cryogenic appli- AVNRT. Proponents of this approach assert that inadvertent cation. Most such events transpired during cryomapping, permanent high-degree AV block has yet to be reported with a minority during cryoablation. The latter phenomenon with cryoablation. This is in contrast to the approximate 1% has been termed dynamic cryomapping to reflect a changing risk of complete AV block with RF ablation of AVNRT in temperature gradient that spreads radially from the catheter experienced Advocates of RF ablation as first- tip–tissue contact. Reversible effects on AV node conduc- line therapy for AVNRT argue that the additional safety tion occur at a temperature of approximately Ϫ30°C, which advantage is not sufficient justification considering the necessarily precedes more intense freezing temperatures of lesser efficacy of cryoablation. To date, 2 pilot studies less than Ϫ50°C to Ϫ60°C that lead to permanent cell comparing RF ablation to cryoablation with 4-mm elec- Moreover, the AV node is thought to be partic- trode-tip catheters have yielded disparate Al- though concerns over comparative acute efficacy and long-term effectiveness are valid, more definitive studies are Study limitations
The study was retrospective in nature and subject to the One plausible reason why RF ablation may produce limitations inherent to such designs. Nevertheless, all pro- superior results to cryoablation with a 4-mm electrode-tip cedural data were prospectively entered in the Montreal catheter is the creation of substantially larger lesions. In a Heart Institute’s cryoablation registry, which is systemati- randomized preclinical study of 197 ablation lesions in cally upheld. The type of cryocatheter was not randomly mongrel dogs, we previously found RF lesions to be more allocated, with 6-mm electrode-tip catheters more fre- than twice as large as cryoablation lesions produced by quently utilized in the latter half of the study. Because 4-mm electrode-tip Differences in surface area transcatheter cryoablation was first performed in our insti- rather than lesion depth accounted for these volume effects.
tution in August 1998, we deliberately initiated the study 9 One likely contributing factor is adherence of the cryocath- months later to eliminate a learning-curve effect. All inter- eter to underlying tissue. With RF energy, a brushing effect ventions with prior iterations of the 4-mm electrode-tip occurs as a result of cardiorespiratory motion during cath- cryocatheter, including the 9F version and refrigerants other eter ablation that generates larger lesion dimensions. Al- than nitrous oxide, were excluded from the study. More- over, operator bias favoring the 6-mm electrode-tip cryo- 6. Rodriguez LM, Geller JC, Tse HF, et al. Acute results of transvenous cryoab- catheter is unlikely to be substantial in light of the compa- lation of supraventricular tachycardia (atrial fibrillation, atrial flutter, Wolff-Parkinson-White syndrome, atrioventricular nodal reentry tachycardia). J Car- rable acute success rates and acute procedural outcomes.
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tantly, safety is not compromised to achieve this incremen- 10. Kimman GJ, Theuns DA, Janse PA, et al. One-year follow-up in a prospective, randomized study comparing radiofrequency and cryoablation of arrhythmias in tal benefit. Additional advantages of the larger electrode-tip Koch’s triangle: clinical symptoms and event recording. Europace 2006;8:592– catheter include shorter fluoroscopy time and possibly briefer procedural duration. In light of these results, it may 11. Kimman GP, Theuns DA, Szili-Torok T, et al. CRAVT: a prospective, random- ized study comparing transvenous cryothermal and radiofrequency ablation in be argued that the 6-mm electrode tip should replace its atrioventricular nodal re-entrant tachycardia. Eur Heart J 2004;25:2232–2237.
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