ABSTRACT:
Background: High-power radiofrequency ablation (HPRFA) appears to be a
novel concept for atrial fibrillation (AF) treatment but there are
scarce data in conscious patients. The lesion size index (LSI) value has
been associated with durability of pulmonary vein isolation (PVI)
lesions.
Objectives: We hypothesised that HPRFA applications based on LSI were
not inferior to standard approach in terms of patient’s pain sensationas
well as safety, effectiveness, and procedure duration.
Methods: Retrospectively, we analysed 218 patients who had performed
ablation of AF based on LSI (LSI 4-4.5 on posterior wall, LSI 5-5.5 in
other locations) who were propensity score matched to 3 different RF
power settings: group-30W (45oC, 30 W and 25 W on
posterior wall), group-40W (45oC, 40 W) and group-50W
(45oC, 50 W).
Results: Comparing group-30W vs group-40W and group-50W, procedure and
left atrium dwell time (minutes) were 190±32, 161±41, 102±8
(p<0.0001) and 154±53, 113±29, 79±10 (p<0.0001),
respectively. With comparable number of RF applications
(p>0.05) between the groups, total RF and fluoroscopy time
(minutes) were 62±17,38±10, 28±5 (p<0.0001) and 6±3, 6±2, 4±1
(p=0.08), respectively. Number of stopped painful RF applications were
19±9, 9±5 and 7±2 (p<0.0001), respectively. No serious
complications were observed in any of the group. No difference in 1-year
ablation efficacy was observed between the groups (p=0.78).
Conclusions: HPRFA based on LSI is less painful, faster and safe in
conscious patients than standard approach with comparable effectiveness
in one year follow-up.
INTRODUCTION
Atrial fibrillation (AF) ablation is the most commonly performed
radiofrequency (RF) ablation and is usually associated with a long
procedural time and pain sensation in conscious patients. Prolonged
radiation exposure during the procedure puts the patient and the
operator at risk of malignancy and genetic abnormalities. Complications
such as asymptomatic cerebral lesions, tamponade, perforation, and also
arrhythmia recurrence are associated with longer ablation time.
Radiofrequency application works by an immediate local resistive heating
from the high‐frequency current passing through the tissue surrounding
the catheter tip and a subsequent conductive phase, where the heat
dissipation leads to deeper tissue injury [1]. The current density
diminishes as the distance from the catheter tip increases which limits
the area of resistive heating. A shorter pulse of high‐energy RF
application at a given contact force has the potential of achieving
rapid, more controlled, resistive tissue heating, and avoiding deeper,
passive, less controlled heating, which is seen with longer, low‐power
RF energy applications [1].
Technological advances have opened up the possibility to manipulate
lesion characteristics by modulating the power and duration of RF energy
[1]. Three key RF application variables: contact force, power and
duration are the main factors responsible for a lesion quality
[2,3]. The commercially available lesion size index (LSI)
incorporates these variables and also impedance in one multiparametric
factor, that has been validated prospectively resulting in a significant
long‐term success rate during AF ablation [4,5]. The LSI formula was
more predictive in terms of lesion formation than each of its components
considered alone regarding width and depth in the in vitro model
[4].
Given that the average human atrial wall thickness is 2-3 mm on the
smooth surface [6], we hypothesised that the high-power
radiofrequency ablation (HPRFA) based on LSI was sufficient to cause
thermal injury to this depth, would produce effective transmural
lesions, shorten procedure time and, by limiting collateral damage to
adjacent structures, make the procedure less painful for a patient.
The goal of this study was to compare three methods of RF ablation based
on LSI (4-4.5 on posterior wall and LSI 5-5.5 in other locations) with
different power settings: group-30W: standard RF settings of 30 Watts
(W), 45oC (25 W on posterior wall); group-40W:
moderate RF settings of 40 W, 45oC, and group-50W:
high-power RF (HPRF) settings of 50 W, 45oC.
METHODS
Patients. Retrospectively we analysed 218 patients who had performed
ablation of AF and based on inclusion (symptomatic patients with
non-valvular AF, aged:18-85, first procedure in left atrium (LA),
exclusion of thrombus in LA and left atrial appendage,
EF>45%) and exclusion (age below 18 or above 85 years,
EF<45%, previous procedure in LA, valvular AF) criteria
(Clinical Trial: NCT04250181), we identified 107 patients who were
divided into 3 groups (group-30W - standard RF settings, group-40W and
group-50W). Finally, after the patients were propensity score matched in
a 1:1:1 fashion we identified 30 patients (10 in each group) who were
analysed further. The AF type was categorised according to recent
definition as paroxysmal (PAF) and persistent (PEAF) [7]. Our study
was consistent with the principles summarized in the 1975 Declaration of
Helsinki and written informed consent was taken from all participants
accordingly (Clinical Trial: NCT04250181). Baseline demographic,
clinical and procedural characteristics and follow-up data were recorded
for all patients.
Procedure. Each procedure was performed according to a standard
protocol, previously described [8]. Briefly, all patients underwent
cardio-CT and transesophageal echocardiography (TEE) up to 48 hours
prior to the procedure. Antiarrhythmic drugs were stopped at least five
half-lives and amiodarone at least 3 months before ablation; ß-blockers
were allowed according to the protocol. An interrupted anticoagulation
approach was used. Proton pump inhibitor was given peri-procedurally.
All patients underwent the ablation under conscious ”moderate” sedation
with intravenous fentanyl only (they remained conscious and responsive
to pain throughout the procedure), without the presence of an
anaesthesiologist. Vascular access was obtained through a femoral vein.
A decapolar catheter was positioned in the coronary sinus. Transseptal
puncture was performed using a long steerable sheath (Agilis™ NxT,
Abbott, St. Paul, MN, USA). After accessing the LA, heparin was given
intravenously with a target active clotting time (ACT) of 300–350
seconds, and further monitored every 20 minutes. High-density voltage
mapping (HDVM) of the LA was performed (EnSite Precision™, Abbott, St.
Paul, MN, USA; best-duplicate algorithm) during sinus rhythm (or after
restoration of sinus rhythm with DC cardioversion) with a circular
diagnostic catheter (Advisor™ FL Sensor Enabled™, Abbott, St. Paul, MN,
USA). The diagnostic catheter was exchanged with the ablation catheter
(TactiCath™, Abbott, St. Paul, MN, USA) and antral pulmonary vein
isolation (PVI) was performed with desired contact force of 10-20 grams.
Left superior and inferior, followed by the right superior and inferior
pulmonary veins (PVs), were encircled in pairs on both sides (with
additional lines between the ipsilateral veins, if signals were observed
after complete PVs encircling) to achieve complete electrical isolation
in all PVs.
Additionally, if low voltage area (LVA, defined as 0.1-0.5 mV in bipolar
HDVM) [9] was identified it was also targeted and homogenised. The
procedure was stopped with confirmation of complete PVI (no capture of
atrial tissue observed during stimulation performed from all PVs) and
lack of potentials in homogenised LVA.
Follow-up. Prior to discharge from the EP laboratory, all patients
underwent transthoracic echocardiography to exclude pericardial
effusion. All patients were monitored overnight and oral anticoagulation
was introduced the day post-procedure. Additional echocardiography was
performed at discharge. All patients were treated with proton pump
inhibitors for 6 consecutive weeks. A blanking period of 3 months has
been considered [7]. Patients were controlled to be free of
antiarrhythmic drugs at the end of the blanking period.
Follow-up visits were scheduled for 1, 3, 6, 9, and 12 months after the
initial procedure for clinical assessment and rhythm monitoring with
7-day Holter ECG recordings at the 3rd,
6th and 12th month for the first
year. Then, bi-annual visits were scheduled with 7-day Holter monitoring
once a year. Pacemaker AF data were utilised when available. Patients
were advised to obtain an ECG, either at the same institution or
elsewhere, when feeling palpitations at times outside of the HolterECG
monitoring periods.
The outcome measures were defined as:
Procedure time: total procedure time (needle to needle time).
Left atrial dwelling time: time of LA instrumentation (from transseptal
access to removal of a catheter and a sheath).
Voltage mapping time: time needed to perform LA 3D electroanatomical map
and HDVM simultaneously.
Total RF time: time of all performed RF applications.
Total number of RF applications: number of all RF applications performed
during a procedure.
PVI time: time of isolation of all PVs defined as time from the first to
the last RF application needed to reach confirmed PVI.
PVI-RF time: total time of all RF applications needed to reach confirmed
isolation of all PVs.
PVI-Number of RF applications: number of all RF applications needed to
reach confirmed isolation of all PVs.
PVI-Time of a single RF application: time of a single RF application.
Contact force: mean contact force value reached during RF application.
Number of stopped RF applications: number of patient’s complaints due to
pain sensation- surrogate for assessment of the painfulness of the
procedure.
X-Ray time: total time of fluoroscopy.
- X-Ray dose: total dose of fluoroscopy.
Complications: both procedure-related complications and all
complications in 12 moths follow-up.
Follow-up-30s: absence any arrhythmia recurrence (AR) defined as any
documented recurrence of AF and/or atrial tachycardia (AT) and /or
atrial flutter (AFL) lasting longer than 30 seconds [10].
Follow-up-24h: absence of any AR defined as any documented recurrence of
AF and/or AT and/or AFL lasting longer than 24 hours [11].
STATISTICAL ANALYSIS
Continuous data are presented as mean ± standard deviation, discrete
data as median (interquartile range) and counts (percentage) if
categorical. A propensity score was calculated for all eligible patients
undergoing first time RF ablation for AF through binary logistic
regression with ablation modality (standard vs moderate vs HPRF
settings) as the binary outcome and baseline variables were used as
covariates for estimating the propensity score. Propensity matching was
performed in a 1:1:1 fashion using the nearest neighbour approach with a
two decimal calliper for age, sex, body mass index, type of AF, LA size,
left ventricular ejection fraction, procedure characteristics (single
transseptal puncture with steerable Agilis™ sheath, performed HDVM of LA
during sinus rhythm and RF ablation performed in sedated but fully
conscious patients with contact force TactiCath™ catheter based on LSI
settings described above. If no match could be found, then the subject
was removed from the analysis. Normal distributed variables were
analyzed using paired and unpaired t-test (two-group analysis) and ANOVA
(N-group analysis). In the case of non-normal distribution, continuous
variables were analyzed using Kruskal–Wallis H test. Kaplan–Meier
univariate analysis was used to estimate AR-free survival. All
statistical tests were 2-sided, and p<0.05 was considered
significant.
RESULTS
Patients‘ characteristics and the results are presented in Table 1 and
Table 2, respectively. Briefly:
With the comparable Voltage mapping time of LA, Total number of RF
applications and PVI-Number of RF applications, the Procedure time
(p<0.0001), Total RF time (p<0.0001) and PVI-RF time
(p<0.0001) were significantly shorter in group-40W and
group-50W as compared to group-30W. Additional LVA was identified in 6
patients and successfully homogenised.
The acute PVI was reached in all patients. The PVI-Time of a single RF
application was significantly shorter in group-40W and group-50W as
compared to group-30W (p<0.0001).
The number of stopped RF applications as a result of pain complained by
a patient was significantly lower in group-40W and group-50W as compared
to group-30W (p=0.01), i.e. the procedure was generally less painful for
a patient treated with higher RF energy (Figure 1.).
The procedure was comparably safe in all the groups of patients. No
major complications, others then related to vascular access (groin
hematoma in 2 patients, one pseudoaneurysm without need of surgical
intervention), were observed in any of the studied groups. Additionally,
shorter LA dwelling time in group-40W and group-50W (p=0.01) decreased
the risk of thromboembolic event related to LA instrumentation. No
audible pop occurred in any of the groups.
One year follow-up. Asymptomatic AF (8 hours in 7-day Holter ECG) was
found at 6th month in a patient treated with 40 W for
PEAF. Another asymptomatic AF (17 hours in 7 day Holter ECG) was
identified at the 9th month in a patient treated with
50 W for PEAF; still the episode was related to vomiting and diarrhoea
at that time. Finally, a pacemaker recording showed 4-hour-lasting
asymptomatic AF during sleep at 9th month in a PAF
patient (group-50W) already treated with CPAP for severe nocturnal apnea
(Figure 2., Figure 3).
Left atrial AT was documented in 5 patients but was symptomatic AT in 2
PEAF patients (1 patient treated with 30 W and 1 treated with 50 W).
Successful AT ablation was performed in both cases. Other 3 patients had
documented asymptomatic AT in 7-day Holter ECG monitoring in the
6th month (AT lasting 1 hour related to sudden rise in
blood pressure; patient treated with 40 W for PEAF) and at the
12th month (36 minutes in a patient treated with
standard settings for PEAF and 4 hours in a patient treated with 50 W
for PEAF).
Typical cavo-tricuspid AFL was recorded at 9-months follow-up visit in a
patient (group-30W) with a history of PAF (only pulmonary vein isolation
was performed during the index procedure); he was scheduled for elective
AFL ablation and no further AR was observed since.
Total one-year success rate (follow-up-30s and follow-up-24h) was 73%
and 87%, respectively (Figure 2., Figure 3).
- DISCUSSION
- MAIN FINDINGS
We utilised commercially available catheters and LSI to perform and
compare standard (low-power RF application), moderate and HPRF ablation
of AF in conscious patients. Our data show for the first time that in
conscious patients HPRF ablation of AF based on LSI was less painful for
a patient and faster with the same safety margin and not inferior in
outcome as compared to standard RF power approach.
THE PAINFULNESS OF THE PROCEDURE
While visceral pain is a common finding in patients who undergo catheter
ablation in the LA, esophageal warming represents the most probable
cause of a patient’s symptoms. Pain tends to be higher when the RF is
delivered near the esophagus [8]. In sedated patients, pain during
ablation is associated with esophageal temperature rise (ETR), and lack
of pain is strongly associated with absence of ETR. Pain during RF
ablation may thus serve as a predictor of esophageal heating and
potential injury [12].
We performed ablation in conscious patients who were able to endure the
entire procedure. Our results show that HPRF applications were less
painful. As was described previously, duration of each RF delivery was
correlated with pain [8]. So shortening the RF application was one
of the reason of lower pain intensity. Additionally, most of the damage
with HPRF is done during the resistive phase of ablation. Such approach
results in shallower lesions which limits collateral damage to adjacent
structures and, as a result, reduces the sensation of pain.
In case of longer standard power RF applications (group-30W) the
conductive phase of ablation produced prolonged and not fully controlled
damage of deeper structures which resulted in more painful procedure in
that cohort of conscious patients.
SHORTENING OF PROCEDURE TIME
The first report of shorter fluoroscopy times and reduction in mean RF
times when using the 50 W approach was published in 2004 [13]. It
was confirmed later in 2006 by Nilsson et al. (shorter fluoroscopy
times, a significant reduction in RF times and procedure times)
[14], by Kanj et al. in 2007 (the 50 W ablations had shorter
fluoroscopy times and atrial instrumentation times) [15] and by
Winker et al. in 2011 [16] who observed shorter fluoroscopy and
procedure times and reduction in RF time with 50 W ablation. Recently,
Chen et al.reported short procedure and fluoroscopy time in Ablation
Indexguided 50 W ablation [17]. Our results in conscious patients
are in line with previously described when general anesthesia was
applied [14-17]. We observed significant reduction in procedure
time, LA dwell time, RF time, fluoroscopy dose and time. Similarly,
Pambrun et al. also observed drastic reduction of procedural duration in
the high-power group as a result of shorter time required for lesion
creation, more first-pass PVI with fewer acute PVs reconnections
[18]. The findings were further supported with animal study with
novel HPRFA technology (90 W per 4 seconds) by Barkagan et al. [19].
OUTCOME
The single procedure success rate off antiarrhythmic therapy was
comparable to previously reported, despite the fact that we
differentiate patients based on RF power used and not type of AF (PAF,
PEAF) [10]. Taking into account that only patients with AF lasting
longer than 24 hours had an increased risk of stroke or systematic
embolism (hazard ratio 3.2), HPRFA seems to be more favourable than
standard approach with lower power settings and prolonged RF application
time [11].
SAFETY
All procedures were performed by experienced operator (MW). Our results
confirm that high-power 50 W RF ablation is a safe approach as was
reported in large cohort of patients recently [8] as well as during
Ablation Index-guided 50 W ablation [17]. Few authors described
severe complications related to 50 W ablation. Mansour observed cardiac
tamponade (5%) and a cerebrovascular accident (2.5%) when RF energy
was delivered with a maximum temperature of 60oC and
50 W power limited for 12–15 seconds at each site [13]. Pappone
reported two cases of pericardial tamponade, with no thrombo-embolic
events or cases of PV stenosis, in 560 patients treated with 100 W
applied for up to 30 seconds [20]. Different techniques and
manoeuvres were used by others to lower the complication rates with
HPRFA like short duration applications (2-15 seconds) [21] or 12 to
15 seconds at each site, [13] ”perpetual motion” of open irrigated
tip catheters every 3-10 seconds, [16] the use of a “painting”
technique where ablation catheter stayed at each site for 2 to 5 seconds
at 50 W power was moved back and forth until a small area was devoid of
electrograms [22] or Ablation Index-guided 50 W ablation [17].
Recently, the novel HPRFA approach demonstrated in swine model also
confirmed its safety profile that was comparable to conventional
ablation [19].
Our RF applications were limited by LSI and each application was started
only when the desired contact force (10-20 grams) was reached. It
resulted in mean 18 and 16 seconds RF application time in group-40W and
group-50W, respectively. In few cases where we could not stabilized the
catheter to reach contact force >10 grams but at least 5
grams were achieved, the 40 W or 50 W applications were stopped at 30
seconds even if desired LSI was not reached. Eventually, we did not
observed any major complications in any of the studied groups.
STUDY LIMITATIONS
It was retrospective observational study and performed in a small cohort
of patients. There was a small number of individuals in which RF
ablation was performed with moderate power settings of 40 W. We promptly
changed our protocol to 50 W RF ablation which limited the number of
patients in group-40W, and eventually propensity score matching
identified 30 patients included in the study.
The threshold for pain is individual for certain patient. Still, the
need to cease the RF application seems to be the best clinical surrogate
parameter for pain related to possible collateral damage to adjacent
structures.
Furthermore, ECG and Holter monitoring were recorded at limited time
points. Some episodes of AR could be missed during follow up.
CONCLUSIONS
To our best knowledge this is the first report which shows that HPRF
(40/50 W) ablation of AF based on LSI is less painful, faster and safe
procedure for a conscious patients. Its effectiveness in one year
follow-up is comparable to standard approach. Prospective randomized
trials in a larger cohort of patients are required to confirm the
benefits of such strategy.
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