Prevention of complications during atrial fibrillation ablation with the second-generation cryoballoon

Pulmonary vein isolation (PVI) is a cornerstone procedure for the treatment of
atrial fibrillation (AF), since 90-95% of the triggers originate from the
pulmonary veins (PVs). PVI can be performed with a cryoballon, which has an
efficacy of approximately 70% at one-year follow-up. The most frequent
complication of cryoballoon ablation is the occurrence of phrenic nerve palsy,
which can cause dyspnea. The distance between the phrenic nerve and the
superior right PV, as measured on a CT-scan, seems to predict the risk of this
complication. The most feared complication is atria-esophageal fistula, which
often has a fatal course.

Recently, the original cryoballoon catheter was modified leading to more
homogeneous and deeper cooling of the balloon. Improved cooling may lead to
higher rates of permanent PV isolation with reduced energy application times,
increasing the efficacy of the ablation. The first study results indeed show a
shorter time to PVI (an average of 52 instead of 79 seconds).
The number of complications has also increased however. Phrenic nerve palsy was
found in 8% of the procedures performed with the old balloon compared to 24%
with the new balloon.
Gastroscopy can be used to evaluate if any esophageal lesions have occurred as
a result of cryoballoon ablation. After ablation with the old balloon, no
lesions were objectified. Ablation with the new balloon resulted in esophageal
lesions in 12% of patients. A temperature below 12 degrees, measured with a
temperature probe located in the esophageal lumen, was found to predict the
occurrence of these lesions.

At this moment, the optimal cryoenergy application duration with the new
balloon is unknown. To maximize the efficacy, the maufacturer advises 2
4-minute applications. A recent study showed that PVI already occurs in 81% of
the PVs after 1 freeze. To increase efficacy, it is possible to identify
incomplete PVI by infusion of adenosine. If PV potentials re-occur during
adenosine infusion, so-called dormant conduction, the chance of PV reconnection
increases. Identification and treatment of dormant conduction after ablation
with the old balloon was found to increase ablation efficacy at 1-year
follow-up.

Altogether, these data suggest that reducing cryoenergy application time with
the new cryoballoon catheter may reduce complication rate while maintaining the
efficacy, especially when the presence of DC is evaluated with adenosine and,
if present, is treated with additional ablation.

To evaluate different cryoenergy application times using absence of DC as a
surrogate for permanent PV isolation to establish optimal duration for
formation of contiguous lesions and prevention of right PNP and esophageal
thermal lesions during ablation with the second-generation cryoballoon

The study will be performed with 3 groups. Seventy-five patients will be 1:1:1
randomized to a single cryoenergy application continuing for 90, 120 or 150
seconds after PVI. Both acute PV isolation and isolation after a 30-minute
waiting period will be established. If reconnection occurs, one or more
additional cryoballoon applications will be performed. Thirty minutes after
PVI, adenosine will be infused in increasing doses up to 30 mg until at least
one beat of AV-block is observed to assess the presence of dormant conduction.
If DC is present, additional cryoenergy applications using the same protocol as
above. This procedure will be repeated until no more DC is observed for each
vein.

a temperature probe (Sensitherm, St. Jude Medical) will be placed in the
esophagus to monitor luminal esophageal temperature (LET) throughout the entire
procedure. If a LET of < 12 degrees is reached, ablation will be discontinued.
If a LET of <12 degrees is observed during ablation, a gastroesophageal
endoscopy is performed within 2 days after ablation.
Phrenic nerve pacing from the superior vena cava will be performed during
ablation of the right PVs to prevent right phrenic nerve injury. In case of
reduced capture, cryoballoon ablation will immediately be discontinued. In case
PNP occurred during ablation, potential related complaints will be registered
and a chest X-ray will be performed if necessary.

Follow-up will be performed at 3, 6 and 12 months after ablation as part of
standard clinical care. Efficacy of the procedure is assessed by symptoms,
12-lead ECG and 24-hour holter recordings. Registration of any atrial
arrhythmia on ECG or an episode of >30 seconds on holter after a 3-month
blanking period is defined as AF-recurrence and ablation failure.

The 3 groups undergo cryoballoon ablation with the new balloon, with a duration
of cryoenergy application of 90, 120 or 150 seconds after PVI.

By decreasing cryoenergy application duration, the efficacy of the procdure may
decrease. This may lead to a higher number of patients that need to undergo a
second procedure and/or more patients that need anti-arrhythmic medication. We
will try to prevent this by evaluating PVI in multiple ways and at multiple
timepoints. The risk of complications is expected to decrease when cryoenergy
application times a shortened, which is a benefit for the patients.