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. Introduction
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). Discussion
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.
diovasc Electrophysiol 2002;13:1082–1089.
Finally, our study did not address whether double freeze–
7. Lowe MD, Meara M, Mason J, et al. Catheter cryoablation of supraventricular
thaw cycles or additional lesions at the site of success could
arrhythmias: a painless alternative to radiofrequency energy. Pacing Clin Elec-trophysiol 2003;26:500 –503.
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8. Zrenner B, Dong J, Schreieck J, et al. Transvenous cryoablation versus radio-
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Conclusions
nodal re-entrant tachycardia: a prospective randomized pilot study. Eur Heart J
In patients with AVNRT, slow pathway modification with
9. Jensen-Urstad M, Tabrizi F, Kenneback G, et al. High success rate with cryo-
6-mm versus 4-mm electrode-tip cryocatheters is associated
mapping and cryoablation of atrioventricular nodal reentry tachycardia. Pacing
with fewer recurrences on long-term follow-up. Impor-
Clin Electrophysiol 2006;29:487– 489.
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
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4-mm counterpart as the cryocatheter of choice in adults
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Neujahr Nach dem christlich-gregorianischem Kalender beginnt hier das internationale Geschäftsjahr. Orthodoxe Weihnachten Ein Teil der orthodoxen Kirchen -darunter die von Konstantinopel, Griechenland, Rumänien und Bulgarien- hat Weihnachten so wie die Westkirchen nach GregorianischemKalender am 24./25. Dezember gefeiert; die anderen -darunter die Kirchen von Russland, Serbien, Georgien, Tsche
Zoo Biology 19:393–403 (2000) Tuberculosis in Elephants in North America Susan K. Mikota,1 R. Scott Larsen,2 and Richard J. Montali3* 1Audubon Center for Research of Endangered Species, New Orleans, Louisiana2Department of Clinical Sciences, College of Veterinary Medicine and BiomedicalSciences, Colorado State University, Fort Collins, Colorado3Department of Pathology, Smithsonian Nat