Use of three-dimensional computed tomography overlay for real-time cryoballoon ablation in atrial fibrillation reduces radiation dose and contrast dye
Use of three-dimensional computed tomography overlay for real-time cryoballoon ablation in atrial fibrillation reduces radiation dose and contrast dye
B. Oude Velthuis 0 1 2 3
M. Molenaar 0 1 2 3
H. G. Reinhart Dorman 0 1 2 3
J. Y. Stevenhagen 0 1 2 3
M. F. Scholten 0 1 2 3
J. van der Palen 0 1 2 3
J. M. van Opstal 0 1 2 3
0 Department of Cardiology, Bravis Ziekenhuis , Roosendaal , The Netherlands
1 Thorax Centre Twente, Medisch Spectrum Twente , Enschede , The Netherlands
2 Medical School Twente, Medisch Spectrum Twente , Enschede , The Netherlands
3 Department of Research methodology, Methods and Data Analysis, University of Twente , Enschede , The Netherlands
Aims Cryoballoon pulmonary vein (PV) isolation in patients with atrial fibrillation has proven to be effective in short-term and long-term follow-up. To visualise the PV anatomy, pre-ablation contrast pulmonary venography is commonly performed. Three-dimensional (3D) computed tomography (CT) overlay is a new technique creating a live 3D image of the left atrium by integrating a previously obtained CT scan during fluoroscopy. To evaluate the benefits of 3D CT overlay during cryoballoon ablation, we studied the use of 3D CT overlay versus contrast pulmonary venography in a randomised fashion in patients with paroxysmal atrial fibrillation undergoing cryoballoon PV isolation. Methods and results Between October 2012 and June 2013, 30 patients accepted for PV isolation were randomised to cryoballoon PV isolation using either 3D CT overlay or contrast pulmonary venography. All patients underwent a pre-procedural cardiac CT for evaluation of the anatomy of the left atrium (LA) and the PVs. In the 3D CT overlay group, a 3D reconstruction of the LA and PVs was made. An overlay of the CT reconstruction was then projected over live fluoroscopy. Patients in the contrast pulmonary venography group received significantly more contrast agent (77.1 ± 21.2 cc vs 40.1 ± 17.6 cc, p < 0.001) and radiation (43.0 ± 21.9 Gy.cm2 vs 28.41 ± 11.7 Gy.cm2, p = 0.04) than subjects in the 3D CT overlay group. There was no difference in total procedure time, fluoroscopy time and the amount of cryoapplications between the two groups. Conclusion The use of 3D CT overlay decreases radiation and contrast dye exposure and can assist in guiding cryoballoon-based PV isolation.
Atrial fibrillation; Pulmonary vein isolation; Ablation; Cryoballoon
Atrial fibrillation (AF) is the most common arrhythmia,
affecting approximately 1.5–2% of the general population
. In 1998, the pulmonary veins (PVs) were identified as
potential targets for the invasive treatment of AF .
PV isolation is an effective treatment for patients with
symptomatic paroxysmal AF and recommended in
international guidelines . Ablation success rates at 12 months
range between 66 and 89% [3–5]. However, radiofrequency
ablation requires tedious point-to-point delivery of multiple
applications to isolate PVs . As a result, more
circular ablation catheters have been developed facilitating PV
isolation. Ablation using a cryoballoon has been proven
effective in short and long-term follow-up, with equal efficacy
and safety, compared with the conventional radiofrequency
Pre-procedural contrast pulmonary venography is
commonly performed to visualise the PV anatomy. Fluoroscopy
is inherently associated with significant radiation exposure
for both the patient and operator. Improved visualisation
using iodine-based contrast agents is dose-dependent
related to acute and chronic kidney failure. Several techniques
have been evaluated to optimise the visualisation during the
cryoablation procedure, such as the use of real-time
threedimensional oesophageal echocardiography .
Three-dimensional (3D) computed tomography (CT)
overlay creates a live 3D image during the procedure by
integrating fluoroscopy with a previous CT scan or newly
taken rotational angiographic 3D images of the left atrium
(LA) and it has been shown to assist in
radiofrequencybased PV isolation . 3D CT overlay can facilitate
optimal positioning of the cryoballoon and reduce contrast
medium use and radiation exposure. Better positioning
of the balloon can decrease the necessity for additional
application(s) during PV isolation, using extra balloon or
catheter cryoapplications to achieve PV isolation. To
evaluate the benefits of 3D CT overlay during cryoballoon
ablation, we studied the use of 3D CT overlay versus
contrast pulmonary venography in a randomised fashion
in consecutive patients with paroxysmal AF undergoing
cryoballoon PV isolation.
Patients were eligible for enrolment in the study when they
were accepted for percutaneous PV isolation for
paroxysmal AF, as defined in the current guidelines . The
exclusion criteria were as follows: (1) Patients with persistent
AF, as defined in the current guidelines ; (2) A left
atrial diameter of more than 50 mm in the parasternal long
axis on transthoracic echocardiography; (3) Previous
pulmonary vein isolation ablation (epicardial or endocardial);
(4) Previous cardiac surgery; (5) Significant valvular
disease present on echo (mitral or aortic valve regurgitation
above grade 2, moderate to severe mitral or aortic stenosis);
(6) Concomitant cardiac surgery needed; (7) Left
ventricular ejection fraction <40%; (8) Hypertrophic (obstructive)
cardiomyopathy or dilated cardiomyopathy defined as an
ejection fraction <40%; (9) Pregnancy; (10) Myocardial
infarction within the previous 3 months; (11) AF secondary
to electrolyte imbalance, thyroid disease, other reversible or
non-cardiovascular causes for AF. Patients were recruited in
the outpatient clinic and included in the study after signed
informed consent was obtained.
After inclusion, patients were randomised to cryoballoon
PV isolation using 3D CT overlay or contrast pulmonary
venography. All patients underwent a pre-procedural
cardiac CT for evaluation of the anatomy of the LA and the
PVs. If the patient’s PV anatomy was not suitable for
cryoballoon ablation, the patient was excluded. Patients were
also excluded if the PVs could not be isolated with the
cryoballoon alone during the procedure.
Sample size calculation
To reach statistical significance of 20% difference between
the two groups regarding fluoroscopy time and contrast
medium, we used the following parameters for power
calculation: alpha = 5%; power = 80%; and assuming equal
standard deviations in each group. Requiring 47 patients
for fluoroscopy time and 17 for contrast medium. An
interim analysis would be performed after 30 inclusions in
consultation with the medical research ethics committee.
Pre-procedural cardiac CT
The pre-procedural contrast-enhanced cardiac CT was
performed using a 64 multi-slice scanner (Toshiba
Aquillion 64, Tokyo, Japan). Images were obtained at 120 kV and
300 mAs. Rotation time was 0.4 ms. The thickness of the
reconstructed image slices was 0.3 mm. During a
20-second end/expiratory breath hold, 80 ml contrast (Visipaque
320, GE Healthcare A.S., Oslo, Norway) was injected. An
ECG-triggered scan was timed at 50% of the average
interbeat (RR) interval.
Two electrophysiologists (MS and JvO) with extensive
experience in cryoballoon ablation performed the procedures.
All patients were on oral vitamin-K antagonists with the
international normalised ratio between 2.5 and 3.5. Vitamin K
antagonists were continued during the procedure . All
procedures were performed under general anaesthesia and
arterial blood pressure was continuously monitored. Venous
access was obtained from the right and left femoral vein.
A diagnostic catheter (EP XT CS 4p, BARD Medical Inc.,
GA, USA) was positioned in the coronary sinus for
stimulation of the LA. The LA was accessed by a transseptal
puncture with a Brockenbrough needle monitored by
intracardiac echocardiography (St. Jude Medical, MN, USA), first
with a SL-O sheath (St. Jude Medical, MN, USA), changed
over a 0.32 F wire to a steerable 12 F sheath (Flexcath,
Medtronic Inc., MN, USA). During the procedure, heparin
was given to achieve an activated clotting time of >350 s.
The use of a 23 or 28 mm balloon was based on the PV
3D CT overlay group
Before the start of the procedure, the CT images were
imported into the EP Navigator workstation (Philips Medical
Systems, Best, the Netherlands) to create a 3D digital
reconstruction of the anatomy of the LA and the PVs as
previously described . An automated reconstruction tool was
used. Manual correction tools were used for optimisation
Fig. 1 Example of a left atrial 3D CT overlay on the live fluoroscopy.
The Achieve catheter is inserted into the left superior PV. A 4-pole
catheter is placed in the coronary sinus
of this reconstruction. An overlay of the CT reconstruction
was then applied over live fluoroscopy and registration was
performed using anatomical landmarks, catheter positions
and contrast boluses in both superior PVs. Validation of the
correct registration was performed in anteroposterior and
lateral views (Fig. 1).
Contrast pulmonary venography group
After transseptal puncture, a 7 French NIH catheter (Cordis,
Miami Lakes, FL, USA) was introduced and contrast was
delivered to each single PV. High definition
cinematographic images of the PVs were made in left and right
anterior oblique projections.
We used the Arctic Front Advance cryoballoon (Arctic
Front Advance, Medtronic Inc., MN, USA). The 28-mm
balloon was used in 21 patients. A multipolar catheter
(Achieve, Medtronic Inc., MN, USA) was inserted through
the inner lumen of the balloon to assess PV signals before,
during and after the ablation and to guide the positioning of
the balloon, after which the total assembly was introduced
into the LA. After inflation, the cryoballoon was advanced
to occlude the PV and a contrast bolus was administered
to confirm total occlusion. In general, two consecutive
applications were delivered for each PV, varying from 180 to
240 s, depending on temperatures reached. During isolation
of the right PVs, the right phrenic nerve was continuously
stimulated by a catheter placed in the superior vena cava. If
the diaphragm excursions diminished during cryoablation,
the ablation was immediately stopped using the double stop
technique . Bidirectional block was confirmed for each
vein. After a 30-minute waiting period, all four PVs were
checked for reconduction and adenosine was administered
to reveal dormant PV potentials.
Effective dose is a convenient quantity to estimate the
stochastic risk of radiation applied to patients in
interventional procedures . Radiation of cardiac CT was
measured as dose length product. The dose length product
was converted to the effective dose by using a conversion
factor of 0.014 mSv Gy1 cm1 . Radiation of
fluoroscopy was measured in dose area product (DAP). The
DAP was converted to the effective dose by using a
conversion coefficient of 0.188 mSv Gy1 cm2 . For the 3D
CT overlay group, the main effective dose was calculated
by adding the previously mentioned conversion indices for
the cardiac CT and radiation of fluoroscopy.
Procedure time, number of applications, radiation
exposure and contrast agent
The total procedure time was defined as the total time
between the first puncture of the femoral vein and the end of
the procedure. The following were documented: (1) The
time from the first puncture of the femoral vein to the
transseptal puncture; (2) The total number of cryoballoon
applications; (3) The total fluoroscopy time; (4) The
total radiation dose; and (5) The total amount of contrast
agent used. We registered the total amount of contrast used
for any kind of image enhancement and for determination
of the grade of occlusion during cryoablation. We
therefore reported contrast usage in both groups for any reason
other than visualising the PVs. In the pulmonary
venography group, the amount of contrast agent used for PV
visualisation alone was also registered.
After the intervention, patients were scheduled for four
outpatient clinic visits at 1, 3, 6 and 12 months.
Antiarrhythmic drugs were withdrawn after a stabilisation period of
90 days after the initial procedure and post-procedural
experienced AF burden. Prior to the outpatient clinic visits at
3, 6 and 12 months, a 7-day auto-triggered event
recording was performed using a Vitaphone recorder (Vitaphone
GmbH, Mannheim, Germany) [19, 20]. An episode of AF
is defined as an episode of at least 30 s’ duration.
Results were analysed using the SPSS 17.0 software (SPSS
Inc., Chicago, IL, USA). Independent samples T-test was
used for numerical normally distributed data and the χ2 test
was used for categorical variables. P-value <0.05 was
considered statistically significant.
From October 2012 until June 2013, 30 patients were
enrolled in the study. Two patients were excluded because PV
isolation could not be completed with the cryoballoon alone
and additional radiofrequency applications during the same
procedure were needed to achieve PV isolation (equal
distribution in both groups). Table 1 shows the baseline
characteristics. Mean age was 57.3 ± 8.9 years. Hypertension
was present in six subjects (21.4%). Mean CHADS2-VASc
score was 0.8. Mean corrected left atrial end/diastolic
volume was 25.1 ± 7.2 cc/m2. Anticoagulation was used by
nine patients (32.1%) at the time of randomisation. No
significant differences were found between the two operators.
Table 2 shows radiation doses and amounts of contrast.
Patients in the contrast pulmonary venography group received
significantly more contrast agent than subjects in the 3D
CT overlay group. Furthermore, patients in the direct
fluoroscopy group received more radiation, as expressed in the
DAP-value. There were no differences in fluoroscopy time,
number of cryoapplications and total procedure time
between the two groups. No statistical differences were found
Data are expressed in mean ± SD or absolute number and percentage
AF Atrial fibrillation, CAD Coronary artery disease, CHF Congestive heart failure (Ejection Fraction <40%), OSAS Obstructive sleep apnoea
syndrome, TIA Transient ischaemic attack, CVA Cerebral vascular attack, ECV Electrical cardioversion, BMI Body mass index, LA Left atrium,
NS Not significant
Data are expressed in mean ± SD
PV angio Pulmonary vein angiography, DAP Dose area product, TSP Transseptal puncture, NS Not significant
with p < 0.05 using an intention-to-treat analysis involving
all randomised patients.
Complications were present in three patients (10.7%). In
one patient (direct fluoroscopy group), the procedure was
complicated by permanent vagal nerve injury, resulting in
gastric paralysis. One patient (3D CT overlay group) had
transient gastric paralysis. One patient (direct fluoroscopy
group) suffered from transient right hemidiaphragm
paralysis. After the occurrence of vagal nerve injuries, a
thermoprobe (SensiTherm, St. Jude Medical, MN, USA) was
introduced in our PV procedures to monitor oesophageal
temperatures during PV isolation, after which this complication
did not longer occur .
At a mean follow-up of 11.9 ± 3.9 months (median
12 months), the success rate without continuation of
antiarrhythmic therapy was 78.6% (22 patients). No difference
in recurrence of AF was detected between 3D CT overlay
and the contrast group (12 vs 10 p = 0.55). One patient was
lost to follow-up. Four patients were treated in a second
procedure using radiofrequency ablation with touch-up of
isolation gaps. Successful isolation of all PVs could not be
reached in 1 patient, for which a successful video-assisted
thoracoscopy PV isolation was performed. Prolonged
follow-up for 9.6 ± 3.5 months (median 10 months) showed
This study shows the feasibility of 3D CT overlay in PV
isolation using the cryoballoon and demonstrates
significantly less radiation and use of contrast in comparison to
contrast pulmonary venography. The use of 3D CT overlay
has several benefits over direct fluoroscopy. As the 3D CT
overlay image supplies a 3D navigation map, manoeuvring
and placing the cryoballoon becomes more straightforward.
This has also been demonstrated for 3D transoesophageal
echocardiography . The relative difference in radiation
dose and radiation time can be explained by the fact that,
for cinematographic images of the PV angiograms, a higher
resolution was needed.
Contrast-induced acute kidney injury is an important
complication of the use of iodinated contrast media, which
accounts for a significant number of cases of
hospital-acquired acute kidney injury . As PV isolation is
increasingly becoming standard therapy for patients with AF, it is
essential to optimise patient safety. We realise that a CT
scan requires radiation and contrast agent as well. In our
study population, a pre-procedural CT scan was performed
on all subjects. The amount of contrast agent (Visipaque
320) was 80 or 90 cc. Main dose length product of the CT
scan in our study population was 841.3 ± 255.5 mGy.cm.
Using the conversion factor of 0.014 mSv Gy1 cm1 ,
this results in a main effective dose of 11.8 mSv. The
combined effective dose in the 3D CT overlay group is still
lower in comparison to that of the direct fluoroscopy group.
However, ideally the radiation and contrast agent
necessary for the CT scan is avoided as well. This can be done
by using a 3D overlay from magnetic resonance imaging
(MRI). Recently, we successfully used a 3D MRI overlay
in PV isolation with the cryoballoon in two patients.
Although MRI was not used in this study, it could replace the
CT scan for the 3D overlay and even further reduce total
radiation and contrast dye exposure.
Complications were present in three (10.7%) patients,
two minor complications and one major. In all three cases,
the 23-mm balloon was used. Andrade et al. demonstrated
that the smaller balloon is associated with a high
incidence of phrenic nerve palsy . We report two cases
of vagal nerve injury. Kuwahara et al. reported
peri-oesophageal nerve injury as a complication of PV isolation
with radiofrequency energy in 11/3695 patients .
Recent reports also demonstrate an increased incidence of
oesophageal thermal lesions using the second-generation
28mm cryoballoon . We introduced continuous
measurement of luminal oesophageal temperature after this
complication, after which no vagal nerve injuries occurred. The
study was terminated prematurely due to a significant
difference in radiation dosage at interim analysis. Therefore,
the study was underpowered with regard to the contrast
dosage determined by our initial power analysis.
The use of 3D CT overlay has several benefits over direct
fluoroscopy. As the 3D CT overlay image supplies a 3D
navigation map, manoeuvring and placing the cryoballoon
becomes more straightforward.
The present study shows that the use of 3D CT
overlay has the potential to reduce radiation dose and exposure
to contrast dye in cryoballoon-based PV isolation. Even
though the study population is limited, the results show
a clear benefit of this technique. We expect an additional
advantage of 3D MRI overlay with respect to radiation dose.
More research into this technique is necessary and will be
Conflict of interest B. Oude Velthuis, M. Molenaar, H.G.
Reinhart Dorman, J.Y. Stevenhagen, M.F. Scholten, J. van der Palen and
J.M. van Opstal declare that they have no competing interests.
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