View - Medtronic CryoCath LP

1
The Permanency of Pulmonary Vein Isolation Using a Balloon
Cryoablation Catheter
HUMERA AHMED, B.A., ∗ PETR NEUZIL, M.D., Ph.D.† JAN SKODA, M.D.,†
ANDRE D’AVILA, M.D., ∗ DAVID M. DONALDSON, M.D.,‡ MARGARET C. LARAGY, B.S.,‡
and VIVEK Y. REDDY, M.D. ∗ ,†
From the Cardiac Arrhythmia Services of the ∗ Mount Sinai Hospital, New York, New York, USA; †Homolka Hospital, Prague, Czech
Republic; and ‡Massachusetts General Hospital, Boston, Massachusetts, USA
Chronic PV Isolation With the Cryoballoon. Background: Because of its technical feasibility and
presumed safety benefits, balloon cryoablation is being increasingly employed for pulmonary vein (PV)
isolation. While acute isolation has been demonstrated in most patients, little data are available on the
chronic durability of cryoballoon lesions.
Methods and Results: Twelve atrial fibrillation patients underwent PV isolation using either a 23-mm or
28-mm cryoballoon. For each vein, after electrical isolation was verified with the use of a circular mapping
cathether, 2 bonus balloon ablation lesions were placed. Gaps in balloon occlusion were overcome using
either a spot cryocatheter or a “pull-down” technique. A prespecified second procedure was performed
at 8–12 weeks to assess for long-term PV isolation. Acute PV isolation was achieved in all PVs in the
patient cohort (n = 48 PVs), using the cryoballoon alone in 47/48 PVs (98%); a “pull-down” technique was
employed for 5 PVs (1 right superior pulmonary vein, 2 right inferior pulmonary veins, and 2 left inferior
pulmonary veins). The gap in the remaining vein was ablated with a spot cryocatheter. During the second
mapping procedure, 42 of 48 PVs (88%) remained isolated. One vein had reconnected in 2 patients, while
2 veins had reconnected in another 2 patients. All PVs initially isolated with the “pull-down” technique
remained isolated at the second procedure.
Conclusions: Cryoballoon ablation allows for durable PV isolation with the use of a single balloon. With
maintained chronic isolation in most PVs, it may represent a significant step toward consistent and lasting
ablation procedures. (J Cardiovasc Electrophysiol, Vol. pp. 1-7)
atrial fibrillation, catheter ablation, cryoablation, pulmonary veins
Introduction
In the treatment of patients with paroxysmal atrial fibrillation
(PAF), the foremost goal of catheter ablation is
achieving permanent electrical isolation of the pulmonary
veins (PVs). 1-8 The standard technique involves using a
spot radiofrequency (RF) catheter to place point-by-point
circumferential lesions around the PVs. While conceptually
straightforward, the procedure is complicated by anatomical
challenges posed by an angular left atrial–pulmonary vein
(LA–PV) junction without clear demarcations, as well as
catheter instability exacerbated by biological “noise” such as
respiratory and cardiac motion.
V. Reddy and P. Neuzil have received research grant support from Cryocath
Technologies, Inc.
A. d’Avila received compensation for participation on a speaker’s bureau
relevant to this topic.
Address for correspondence: Vivek Y. Reddy, M.D., Cardiac Arrhythmia
Service, Mount Sinai School of Medicine, Zena and Michael A. Weiner
Cardiovascular Institute, One Gustave L. Levy Place, Box 1030, New York,
NY 10029, USA. Fax: 646-537-9691; E-mail: vivek.reddy@mountsinai.org
Manuscript received 16 July 2009; Revised manuscript received 29 November
2009; Accepted for publication 30 November 2009.
doi: 10.1111/j.1540-8167.2009.01703.x
Even when procedural success can be obtained acutely,
the prevailing evidence suggests a considerable rate of PV
electrical reconnection over time. This is further supported
by a 15–50% rate of clinical atrial fibrillation (AF) recurrence
over a given follow-up period—a rate that undoubtedly represents
an underestimation of the actual incidence of electrical
PV reconnection. Indeed, repeat studies have revealed that
when such PAF patients do present with clinical recurrences,
the most common finding is the reconnection of at least one
PV. Once these gaps in the circumferential lesion sets are
identified and ablated during the second procedure, patients
are typically free from further clinical recurrences. Therefore,
what remains elusive in patients undergoing catheter
ablation for PAF is permanent PV isolation with a single
procedure.
As a result, various ablation technologies are being developed
that aim to standardize the PV isolation procedure—
foremost among these being balloon ablation catheters. 9-13
To date, the largest global experience with such technology
involves the cryoballoon (Cryocath Technologies, Inc.,
Kirkland, Canada)—a balloon catheter designed for inflation
at the PV ostium, thereby allowing for temporary occlusion
of PV blood flow and circumferential ostial contact. 14 With
optimal positioning, it has been demonstrated that electrical
isolation can be obtained acutely with the delivery of a single,
240-second lesion. 15,16
Yet, because of its comparative novelty, the rate of chronic
PV reconnection has not yet been examined independent
of clinical outcome. Therefore, in a sequential series of

2 Journal of Cardiovascular Electrophysiology Vol. No.
patients undergoing catheter cryoballoon ablation for PAF,
we systematically examined the rate of PV reconnection
following ablation. Because almost all patients had an implantable
loop recorder, clinical outcome and symptoms were
also recorded.
Methods
In this prospective, consecutive series of 12 patients with
PAF and documented failure of at least one membrane-active
antiarrhythmic drug (AAD), catheter ablation was performed
using a cryoballoon catheter (23 mm or 28 mm). When necessary,
an 8-mm-tip spot cryocatheter (Cryocath Technologies,
Inc.) was employed to ablate gaps. All procedures were performed
after obtaining written informed consent according
to the institutional guidelines at Homolka Hospital, Prague,
Czech Republic.
Cryoballoon Ablation
The cryoablation balloon system (Cryocath Technologies,
Inc.) has previously been described in detail. Briefly, the system
consists of a deflectable catheter with a balloon-within-aballoon
design, wherein cryo-refrigerant (N 2 O) is delivered
into the inner balloon. While deflated, the balloon catheter
is deployed through a 12-French deflectable sheath. Once in
the LA, the balloon is inflated and positioned at the PV ostium
to temporarily occlude blood flow from the targeted PV
(Fig. 1). After placement and occlusion have been verified
with the distal injection of contrast on fluoroscopy, cryothermal
energy delivery is initiated, and all tissue in contact with
the balloon is ablated. When adequate tissue apposition cannot
be achieved, as indicated by a leak observed on intracardiac
echo (ICE; Acunav, Siemens-Ultrasound, Inc. Issaquah,
WA, USA) or contrast fluoroscopy, a “pull-down” technique
can be employed. The “pull-down” involves waiting for the
balloon to adhere to the superior aspect of the targeted vein
(typically ∼75 seconds), followed by catheter and shaft deflection
to pull the balloon downward so as to achieve contact
with the inferior portion of the vein, thereby eliminating the
inferior gap (Fig. 2). Alternatively, a spot cryocatheter may
be used to ablate gaps in circumferential lesion sets.
Index Procedure
Procedures were performed with either conscious sedation
or general anesthesia. After standard femoral vascular access,
dual transseptal punctures were performed with fluoroscopic
and ICE guidance. Intravenous heparin was administered before
the transseptal puncture. At the start of the procedure, a
multielectrode circular mapping catheter (Lasso, Biosense-
Webster, Inc., Diamond Bar, CA, USA) was used to record
PV electrograms. Each cryolesion was delivered with a target
time of 240 seconds; premature lesion termination occurred
if there was evidence of impending phrenic nerve damage.
Following each application of energy, the circular mapping
catheter was used to assess for electrical isolation; accurate
placement of the mapping catheter (within the first 2–3 cm
of the PV antrum) was ensured with ICE guidance. After
electrical isolation was demonstrated at the targeted vein, 2
additional “bonus” lesions were delivered to that vein. Sixty
minutes after the termination of ablation energy, intravenous
isoproterenol was administered, and all veins were reassessed
with the circular mapping catheter. Prior to the ablation procedure,
an implantable loop recorder (Reveal XT, Medtronic,
Inc., Minneapolis, MN, USA) had been placed. A relatively
long baseline time for automatic detection was employed
to effectively prevent overwhelming the device’s memory
with short interferences, such as those caused by the pectoral
muscles. In addition, patients with clinical symptoms and/or
a greater frequency of automatic detection were asked to return
for a greater number of office visits to allow for more
frequent device interrogation. Although clinical episodes did
frequently correlate with AF on the loop recorder, they often
represented premature atrial couplets (PACs).
EP Study/Re-Ablation
All patients (n = 12) underwent a second EP study 8–
12 weeks after the index ablation procedure, during which
a circular mapping catheter was again used to assess for
continued isolation of each PV. This prespecified procedure
was performed regardless of patient symptoms. As in the
index procedure, ICE imaging was employed to verify the
ostial positioning of the circular mapping catheter. The implantable
loop recorder was also interrogated at this time,
and compared with patient reported symptoms.
Figure 1. Occlusion of targeted PV with balloon cryocatheter. Fluoroscopic
image depicting complete occlusion of the LSPV with the inflated balloon
cryocatheter, as indicated by the absence of a peri-balloon contrast leak.
The central lumen of the balloon catheter allows for the injection of contrast
into the targeted PV. PV = pulmonary vein; LSPV = left superior pulmonary
vein.
Statistical Analysis
Continuous variables are expressed as mean ± SD. The
primary endpoint of the study was evidence of the resumption
of PV electrical conductivity during a postprocedural EP
study.
The authors had full access to the data and take responsibility
for its integrity. All authors have read and agree to the
manuscript as written.

Ahmed et al. Chronic PV Isolation With the Cryoballoon 3
Figure 2. Pull-down maneuver on fluoroscopy and intracardiac echo (ICE), with associated temperature profile. Fluoroscopic images depict the cryoballoon
catheter inflated in the right inferior pulmonary vein, (A) before and (B) after a pull-down maneuver. The cryoballoon catheter has been encircled with
a dashed line. Also shown are intracardiac echo images indicating the inflated cryoballoon catheter in the right inferior pulmonary vein, with color flow
Doppler imaging PV blood flow (C) before and (D) after a pull-down maneuver. (E) Associated temperature recordings from a thermocouple located at the
tip of the balloon catheter are shown; the blue arrow indicates the time of pull-down (187 seconds), while the blue asterisk indicates the termination of the
ablation lesions.
Results
Patient Characteristics
As displayed in Table 1, the mean age of the patient cohort
(12 patients) was 54 ± 11 years and 3 (25%) were
female. As determined by preprocedural echocardiography,
the mean left ventricular ejection fraction and LA size were
68 ± 8% and 44 ± 5 mm, respectively. Eleven (92%) patients
had previously undergone implantation of a continuous loop
recorder. Structural heart disease was not present in any patient,
and the mean duration of PAF was 4 ± 2 years.
Initial Procedure
All patients underwent ablation with either the 23 mm (n =
6) or the 28 mm (n = 5) balloon. In one patient, however, both
balloon sizes were used due to concerns of impending phrenic
nerve injury (that is decreased diaphragmatic excursion with
phrenic nerve pacing during ablation of the right superior PV)
with the smaller balloon during ablation of the right superior
pulmonary vein (RSPV). A mean of 13 ± 2 balloon lesions
were delivered per patient, with 3 ± 1 lesions delivered to
each vein. Of note, only 1 bonus lesion was delivered to one
right superior (due to concern of impending phrenic nerve
palsy) and one right inferior PV.
Acute PV isolation was achieved with the balloon catheter
alone in 47 of 48 (98%) PVs following the delivery of 1 ± 1
lesion (range: 1–4): one lesion-33 PVs (70%), two-9 (19%),
three-2 (4%), four-3 (9%). In the remaining vein, 3 focal
lesions were placed with the spot cryocatheter to achieve
acute isolation. The “pull-down” technique was employed
to isolate 5 of the PVs (1 RSPV, 2 right inferior pulmonary
veins [RIPVs], and 2 left inferior pulmonary veins [LIPVs]).
At the termination of the index ablation procedure, acute
PV isolation was demonstrated in 100% of ablated veins (n =
48 PVs). Regardless of the method employed to achieve acute
isolation (i.e., balloon alone vs pull-down vs adjunctive spot
ablation), no acute PV reconnections were noted during infusion
of 20 μg/min isoproterenol at the end of the procedure.
There were no acute or delayed complications.

4 Journal of Cardiovascular Electrophysiology Vol. No.
TABLE 1
Patient Characteristics
Total Patient Cohort
(n = 12)
Demographic Information
Age (mean ± SD) 54 ± 11
Males/females 9/3
Medical History
Hypertension (n, %) 1 (8%)
CHF (n, %) 0 (0%)
Atrial flutter (n, %) 3 (25%)
CAD (n, %) 0 (0%)
Disease Characteristics
EF (%, mean ± SD) 68 ± 8
LA size (mm, mean ± SD) 44 ± 5
Duration of AF (years) 4 ± 2
Number of prior cardioversions 0.4 ± 0.7
Medication Use
No. of failed AADs (mean ± SD) 1.4 ± 0.5
Amiodarone 4 (33%)
Beta-blocker 3 (25%)
Calcium-channel blocker 1 (8%)
Propafenone 5 (42%)
Sotalol 2 (17%)
AADs = antiarrhythmic drugs; AF = atrial fibrillation; CAD = coronary
artery disease; CHF = congestive heart failure; EF = ejection fraction;
LA = left atrial; SD = standard deviation.
been placed. Clinical AF recurrences were documented in 3
of the 4 patients with chronic PV reconnections; 1 patient
(patient 2, see Table 2) with 2 PV reconnections did not have
any AF recurrences and reported no symptoms. On the other
hand, 1 patient (patient 4, see Table 2) with preserved isolation
of all PVs had symptomatic recurrences (presumably
from an extra-PV trigger, though this did not manifest during
the second procedure). One patient (patient 1) with preserved
chronic PV isolation and no documented AF recurrences had
brief (∼2 seconds) episodes of palpitations.
On a per vein basis, the success of chronic PV isolation
was 91.7% (11/12) for the LSPV, 75.0% (9/12) for the LIPV,
91.7% (11/12) for the RSPV, and 91.7% (11/12) for the RIPV.
Overall, the probability of PV reconnection was not related to
the number of balloon ablation lesions required to isolate the
target PV during the initial procedure (Table 3). Also, there
was no difference in the chronic reconnection rate for PVs
ablated with the 23 mm (2 of 23 PVs, 9%) or 28 mm (3 of 24
PVs, 13%) balloon alone (p = 0.98). In addition, the 2 rightsided
PVs that received only 1 bonus lesion during the initial
procedure remained isolated. PV reconnection was observed
in the one PV for which the spot catheter was required to
achieve electrical isolation. Of note, for those 5 PVs initially
isolated using the pull-down technique, the chronic electrical
isolation rate was 5/5 (100%).
Second Procedure
Ten ± 2 weeks after the index ablation procedure, the repeat
study revealed continued electrical isolation in 42 of 48
(88%) PVs. The resumption of electrical conductivity was
observed in 4 patients and 6 veins—2 patients had one reconnection
each, while the other 2 had two PV reconnections
each (Table 2). An analysis of focal gaps in these patients
revealed one gap per vein, predominantly occurring in the
inferior aspect of the vein (Figs. 3 and 4). The majority of
reconnections were observed in the LIPV (3 of 6); one reconnection
each was observed in the RSPV, RIPV, and left
superior pulmonary vein (LSPV).
Prior to the second procedure, the continuous loop
recorder was interrogated for the 11 patients in whom it had
Discussion
Although the relationship between chronic PV reconnection
and clinical outcome continues to be debated, there is
increasing consensus that if safely achievable, the desirable
endpoint for the ablation procedure for patients with PAF is
permanent electrical PV isolation. 1-8,17-21 In practice, however,
the resumption of PV electrical conductivity is common
following RF catheter ablation for AF. The limited data acquired
from PV re-mapping in patients with AF recurrence
following cryoballoon ablation suggest that the rate of PV
reconnection is similarly high.
In the present study, however, a systematic assessment of
lesion integrity revealed that isolation was maintained in a
majority of PVs at 3 months following cryoballoon ablation
for PAF. Interrogation of the continuous loop recorder in 11
TABLE 2
Assessment of Chronic PV Isolation at Second Procedure
Patient No. LSPV LIPV RSPV RIPV Recurrences Symptoms
1 + + + + No Yes
2 + − + − No No
3 + − + + Yes Yes
4 + + + + Yes Yes
5 + − + + Yes Yes
6 + + + + No No
7 + + + + No No
8 + + + + No No
9 + + + + — No
10 + + + + No No
11 + + + + No No
12 − + − + Yes Yes
Total 11/12 (92%) 9/12 (75%) 11/12 (92%) 11/12 (92%) 4/12(33%) 5/12(42%)
LIPV = left inferior pulmonary vein; LSPV = left superior pulmonary vein; RIPV = right inferior pulmonary vein; RSPV = right superior pulmonary vein;
– denotes PV electrical reconnection; + denotes maintained chronic isolation.

Ahmed et al. Chronic PV Isolation With the Cryoballoon 5
Figure 3. Identification of a chronic focal reconnection. At the time of the remapping procedure in patient 3, a focal reconnection of the left inferior PV was
seen. With the circular mapping catheter positioned in the left inferior PV, repetitive firing from the PV was observed (bracket = short nonsustained run of
atrial fibrillation; arrow = a single concealed PV extrasystole; asterisk = sinus beat). The PV was then isolated with a single ablation lesion placed by a
focal cryocatheter at the inferior aspect of the vein (fluoroscopy image in left anterior oblique view).
of 12 patients revealed symptomatic AF recurrence in 3 of
4 patients with PV reconnections and 1 of 7 without. Of interest,
an examination of gaps in circumferential lesion sets
for the 4 patients exhibiting PV reconnection revealed that
the majority occurred in the LIPV. For all veins, one focal
gap was observed per vein and, for the most part, these gaps
were located in the inferior aspects of the veins. In addition,
there was no difference in the rate of electrical reconnection
when a 23-mm balloon catheter was employed, as opposed
to the larger 28-mm balloon. Chronic isolation was maintained
for all PVs in which the pull-down technique was
employed.
Prior Studies
Three months after RF ablation in patients with paroxysmal
or persistent AF, Cappato et al. documented an overall
rate of PV electrical reconnection approaching 80%, despite
the attainment of acute ostial isolation in 96% of targeted
veins. 22 In a similar series, Nanthakumar et al. explored the
rate of PV reconnection at 3 months in 15 patients with symptomatic,
recurrent AF following an index ablation procedure
performed with either RF or cryo spot ablation. 23 Resumption
of electrical conductivity was observed in ≥ 2 veins in
all patients.
Similar data for patients with documented AF recurrence
following cryoballoon ablation were found in 14 patients
undergoing a repeat ablation procedure for symptomatic, recurrent
AF: PV electrical reconnection was observed in ≥ 1
PV per patient, with the majority of reconnections observed
in the left-sided PVs. 24 Following a second procedure in 8
of the patients, during which only the PVs were re-isolated,
the patients were free from AF during the follow-up period
of 8 months. These results confirm that chronic clinical success
is indeed feasible, albeit in this series requiring a high
incidence of a second procedure. This may be due to the nature
of cryoablation, which attains a maximal rate of cooling
after the delivery of an initial, priming lesion to a region of
tissue. 25 This implies improved energy transduction with the
delivery of subsequent lesions—introducing the notion that
the high rate of chronic procedural success in our series may
be due, at least in part, to the delivery of the 2 bonus lesions
once isolation had been verified.
While these studies established the virtual universality
of chronic PV reconnection following the use of both conventional
and newer, balloon-based methods of catheter ablation,
the relationship between long-term clinical success
and maintained PV isolation remains debated. In a pivotal
study, however, Verma et al. examined PV conduction at 3
months following an index procedure with spot RF ablation,
in a series of AF patients at varying levels of clinical
efficacy. 26 They found that the majority (86%) of patients
TABLE 3
Breakdown of Chronic PV Isolation, Based on the Number of Lesions
Required for Isolation During the Initial Procedure
Chronic Isolation
No. of Lesions Total Chronic
Required for Isolation Veins YES NO Success Rate (%)
Figure 4. Location of chronic focal PV reconnections. A schematic representation
of the pulmonary veins indicating the location of chronic gaps in
isolation, as well as the associated interval between the local atrial and PV
potentials.
4 3 3 0 100%
3 2 1 1 50%
2 9 9 0 100%
1 33 29 4 88%
Total 47 42 5 89%
For those veins in which acute isolation (as observed in the second procedure)
was achieved with the balloon catheter only, the rate of successful
chronic PV isolation is broken down by the number of ablation lesions required
to obtain acute isolation.

6 Journal of Cardiovascular Electrophysiology Vol. No.
in sinus rhythm off of all AADs had no PV reconnections;
in contrast, all patients with recurrent AF despite the use
of AADs had reconnections in ≥1 PV—suggesting a direct
relationship between PV reconnection and the degree of clinical
success following an index ablation procedure. This is
confirmed in our own experience, given that of the 4 patients
with symptomatic AF recurrences at 3 months, only 1 did
not have reconnections in ≥1PV.
Present Study
While the limited patient number precludes definitive conclusions
from this study, the rate of chronic PV isolation was
88% at 3 months following an index procedure for PAF, with
an associated clinical success rate of 67%. Furthermore, it
was demonstrated that this relatively high rate of chronic procedural
success could be obtained in most patients with a single
balloon—whether the 23 mm or the 28 mm balloon—as
no difference in chronic success rates was observed between
the 2 catheter sizes.
An analysis of the location of gaps in reconnected PVs
revealed that the majority occurred in the LIPV; for all veins,
gaps were predominantly found in the inferior region of
the vein. This study also revealed chronic success in PVs
for which the pull-down technique was employed. Both of
these results are consistent with the limitations of the balloon
catheter itself—namely, the inability to conform to the highly
variable PV anatomy. This results in inferior gaps to occlusion,
which are particularly troublesome during ablation of
the ovaloid left-sided PVs. Rapid temperature decreases observed
with the pull-down technique suggest its utility in
closing inferior leaks, and thereby maximizing the delivery
of energy to the PV ostium.
Limitations
The second EP study was performed 8–12 weeks after the
index ablation procedure, leaving the possibility that further
reconnections may have been observed had the intervening
period been greater. However, our clinical experience would
indicate that PAF patients with recurrent AF are typically
clinically quiescent for several weeks, and begin to exhibit
clinical symptoms between 3 and 4 weeks of the initial procedure.
This has given us the impression that PV reconnection,
when observed, likely occurs within 1 month after the index
ablation procedure. As such, the 8–12 week window employed
in this study allows for an accurate representation
and analysis of long-term PV reconnection.
It is unclear from this study whether bonus ablation lesions
are necessary to achieve permanent PV isolation. However,
this was addressed in an earlier series of 7 patients undergoing
cryoballoon ablation, but without the delivery of bonus
ablation lesions. In this series, the rate of chronic PV isolation
(at 3 months during a prespecified second procedure
regardless of clinical symptoms) was only 14%. However,
this anecdotal experience was limited by the fact that the
series had been performed early in our experience with the
cryoballoon catheter. But based on this earlier experience,
and the present more favorable experience when placing 2
bonus lesions/PV, our current clinical practice is to place 2
bonus lesions per PV.
Definitive conclusions are also limited by the relatively
small number of patients included in this study. However,
the complexity of the study design—that is, a prespecified
second EP study regardless of symptomatology after the first
procedure—was a limiting factor in enrollment. Further randomized
studies are required to confirm our results, as well
as to determine whether it would be equally effective to deliver
only one bonus lesion (or even no bonus lesion) to each
PV.
Conclusion
A high rate of chronic PV isolation can be achieved with
balloon cryoablation. This may play an important role in
obtaining the ultimate, albeit somewhat elusive goal of consistently
achieving permanent isolation with a single procedure.
References
1. Haïssaguerre M, Jais P, Shah DC, Garrigue S, Takahashi A, Lavergne T,
Hocini M, Peng JT, Roudaut R, Clémenty J: Electrophysiological end
point for catheter ablation of atrial fibrillation initiated from multiple
pulmonary venous foci. Circulation 2000;101:1409-1417.
2. Jais P, Weerasooriya R, Shah DC, Hocini M, Macle L, Choi K-J,
Scavee C, Haïssaguerre M, Clémenty J: Ablation therapy for atrial
fibrillation (AF): Past, present and future. Cardiovasc Res 2002;54:337-
346.
3. Chen S-A, Hsieh M-H, Tai C-T, Tsai C-F, Prakash VS, Yu W-C, Hsu
T-L, Ding Y-A, Chang M-S: Initiation of atrial fibrillation by ectopic
beats originating from the pulmonary veins: Electrophysiological characteristics,
pharmacological responses, and effects of radiofrequency
ablation. Circulation 1999;100:1879-1886.
4. Marrouche NF, Dresing T, Cole C, Bash D, Saad E, Krzysztof B, Pavia
SV, Schweikert R, Saliba W, Abdul-Karim A, Pisano E, Fanelli R,
Tchou P, Natale A: Circular mapping and ablation of the pulmonary
vein for treatment of atrial fibrillation: Impact of different catheter
technologies. J Am Coll Cardiol 2002;40:464-474.
5. Oral H, Knight BP, Tada H, Ozaydin M, Chugh A, Hassan S, Scharf
C, Lai SWK, Greenstein R, Pelosi F, Strickberger A, Morady F: Pulmonary
vein isolation for paroxysmal and persistent atrial fibrillation.
Circulation 2002;105:1077-1081.
6. Gerstenfeld EP, Guerra P, Sparks PB, Russo AM, Nayak H, Lin D, Pulliam
W, Siddique S, Marchlinski FE: Clinical outcome after radiofrequency
catheter ablation of focal atrial fibrillation triggers. J Cardiovasc
Electrophysiol 2001;12:900-908.
7. Pappone C, Rosanio S, Augello G, Vicedomini G, Mazzone P, Gulletta
S, Gugliotta F, Pappone A, Santinelli V, Tortoriello V, Sala S, Zangrillo
A, Crescenzi G, Benussi S, Alfieri O: Mortality, morbidity, and
quality of life after circumferential pulmonary vein ablation for atrial
fibrillation. J Am Coll Cardiol 2003;42:185-197.
8. Ouyang F, Bansch D, Ernst S, Schaumann A, Hachiya H, Chen M,
Chun J, Falk P, Khanedani A, Antz M, Kuck K-H: Complete isolation
of left atrium surrounding the pulmonary veins: New insights from
the double-lasso technique in paroxysmal atrial fibrillation. Circulation
2004;110:2090-2096.
9. Natale A, Pisano E, Shewchik J, Bash D, Fanelli R, Potenza D, Santarelli
P, Schweikert R, White R, Saliba W, KKanagaratnam L, Tchou P,
Lesh M: First human experience with pulmonary vein isolation using
a through-the-balloon circumferential ultrasound ablation system for
recurrent atrial fibrillation. Circulation 2000;102:1879-1882.
10. Saliba W, Wilber D, Packer D, Marrouche N, Schweikert R, Pisano E,
Shewchik J, Bash D, Fanelli R, Potenza D, Santarelli P, Tchou P, Natale
A: Circumferential ultrasound ablation for pulmonary vein isolation:
Analysis of acute and chronic failures. J Cardiovasc Electrophysiol
2002;13:957-961.
11. Keane D: New catheter ablation techniques for the treatment of cardiac
arrhythmias. Card Electrophysiol Rev 2002;6:341-348.
12. Reddy VY, Neuzil P, Themisotoclakis S, Bonso A, Rossillo A, Raviele
A, Saliba W, Schwiekert R, Ernst S, Kuck K-H, Ruskin J, Natale A:
Long-term single-procedure clinical results with an endoscopic balloon
ablation catheter for pulmonary vein isolation in patients with atrial
fibrillation. Circulation 2006;114:II-747.
13. Wright M, Haissaguerre M, Knecht S, Matsuo S, O’Neill MD, Nault
I, Lellouche N, Hocini M, Sacher F, Jais P: State of the art: Catheter
ablation of AF. J Cardiovasc Electrophysiol 2008;19:583-592.

Ahmed et al. Chronic PV Isolation With the Cryoballoon 7
14. Siklody CH, Minners J, Allgeier M, Allgeier H-J, Jander N, Weber R,
Schiebeling-Romer J, Neumann F-J, Kalusche D, Arentz T: Cryoballoon
pulmonary vein isolation guided by transesophageal echocardiography:
Novel aspects of an emerging ablation technique. J Cardiovasc
Electrophysiol 2009;20:1197-1202.
15. Reddy VY, Neuzil P, Pitschner HF, Kuniss M, Kralovec S, Kanova
M, Laragy M, Mihalik TA, Taborsky M, Ruskin JN: Clinical experience
with a balloon cryoablation catheter for pulmonary vein isolation
in patients with atrial fibrillation: One-year results. Circulation
2005;112:II491-492.
16. Chun KRJ, Furnkranz A, Metzner A, Schmidt B, Tilz R, Zerm T, Koster
I, Nuyens D, Wissner E, Ouyang F, Kuck KH: Cryoballoon pulmonary
vein isolation with real-time recordings from the pulmonary veins. J
Cardiovasc Electrophysiol 2009;20:1203-1210
17. Wittkampf FH, Vonken E, Derksen R, Loh P, Velthuis B, Wever
EFD, Boersma LVA, Rensing BJ, Cramer M-J: Pulmonary vein ostium
geometry analysis by magnetic resonance angiography. Circulation
2003;107:21-23.
18. Kato R, Lickfett L, Meininger G, Dickfield T, Wu R, Juang G, Angkeow
P, LaCorte J, Bluemke D, Berger R, Halperin HR, Calkins H: Pulmonary
vein anatomy in patients undergoing catheter ablation of atrial
fibrillation: Lessons learned by use of magnetic resonance imaging.
Circulation 2003;107:2004-2010.
19. Ahmed J, Sohal S, Malchano ZJ, Holmvang G, Ruskin JN,
Reddy VY: Three-dimensional analysis of pulmonary venous ostial
and antral anatomy: Implications for balloon catheter-based pulmonary
vein isolation. J Cardiovasc Electrophysiol 2006;17:251-
255.
20. Kanj MH, Wazni OM, Natale A: How to do circular mapping catheterguided
pulmonary vein antrum isolation: The Cleveland Clinic approach.
Heart Rhythm 2006;3:866-869.
21. Pratola C, Baldo E, Notarstefano P, Toselli T, Ferrari R: Radiofrequency
ablation of atrial fibrillation: Is the persistence of all intraprocedural targets
necessary for long-term maintenance of sinus rhythm Circulation
2008;117:136-143.
22. Cappato R, Negroni S, Pecora D, Bentivegna S, Lupo PP, Carolei A,
Esposito C, Furlanello F, Ambroggi LD: Prospective assessment of
late conduction: Recurrence across radiofrequency lesions producing
electrical disconnection at the pulmonary vein ostium in patients with
atrial fibrillation. Circulation 2003;108:1599-1604.
23. Nanthakumar K, Plumb VJ, Epstein AE, Veenhuyzen GD, Link D,
Kay GN: Resumption of electrical conductivity in previously isolated
pulmonary veins: Rationale for a different strategy Circulation
2004;109:1226-1229
24. Neuser H, Schneider MAE, Fröhner S, Bohm C, Koller ML, Kerber S,
Schumacher B: Atrial fibrillation relapse after pulmonary vein isolation
with cryo technique: Is repeated cold isolation medically useful
Presented at the German Cardiac Society meeting 2008.
25. Bradley HJ, Saarel EV, Terrill M, Terrill M, Gutierrez L, Kelly M,
Etheridge SP: The priming effect in catheter cryoablation: Are all
freezes the same Heart Rhythm 2008;5:S143.
26. Verma A, Kilicaslan F, Pisano E, Marrouche NF, Fanelli R, Brachmann
J, Geunther J, Potenza D, Martin DO, Cummings J, Burkhardt D,
Saliba W, Schweikert RA, Natale A: Response of atrial fibrillation to
pulmonary vein antrum isolation is directly related to resumption and
delay of pulmonary vein conduction. Circulation 2005;112:627-635.