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Copyright (c) 2021 Slovenian Medical Journal. This work is licensed under a
Creative Commons Attribution-NonCommercial 4.0 International License.
Catheter ablation for the treatment of atrial fibrillation – 
development of various technical modalities
Zdravljenje atrijske fibrilacije s katetrsko ablacijo – razvoj različnih tehničnih možnosti
Jernej Štublar,1,2 David Žižek,2 Matevž Jan,3 Tomaž Jarm,1 Damijan Miklavčič1
Abstract
Treatment of atrial fibrillation (AF) remains a rapidly developing field of cardiology characterized by continuous techno-
logical improvements and a multidisciplinary approach to problem solving. In addition to searching for improved ablation 
methods for effective and safe pulmonary vein isolation, the efforts are also dedicated to upgrade the understanding of 
apparently chaotic mechanisms of action potential propagation during AF. The mechanisms of clinical AF can be explained 
by the hypothesis of triggers and drivers. According to this hypothesis, AF is triggered by premature beats originating 
mostly from the pulmonary veins and is maintained (driven) by local regions with slow action potential propagation locat-
ed predominantly in the atrial wall where pulmonary veins enter the left atrium. Pulmonary vein isolation thus remains a 
corner stone of invasive treatment of AF.
Izvleček
Zdravljenje atrijske fibrilacije (AF) je hitro razvijajoče se področje kardiologije, pri katerem smo priča stalnemu razvoju 
različnih oblik tehničnih izboljšav in multidisciplinarnega pristopa. Poleg iskanja najprimernejšega ablacijskega načina 
za učinkovito in varno izoliranje pljučnih ven poskušamo razumeti navidezno kaotičen mehanizem prevajanja akcijskega 
potenciala med samo aritmijo. Pri razumevanju nastanka AF se je uveljavila predvsem hipoteza o sprožilcih in vzdrževalcih 
AF. AF sprožajo prezgodnji utripi, ki večinoma izvirajo iz pljučnih ven, vzdržujejo pa jo lokalna področja z upočasnjenim 
prevajanjem akcijskega potenciala, ki se pretežno nahajajo na področju izraščanja pljučnih ven iz levega preddvora. Kljub 
številnim novim pristopom pa je izoliranje pljučnih ven s katetrsko ablacijo še vedno temelj invazivnega zdravljenja AF.
1 Faculty of Electrical Engineering, University of Ljubljana, Ljubljana, Slovenia
2 Department of Cardiology, Division of Internal Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia
3 Department of Cardiovascular Surgery, Division of Surgery, University Medical Centre Ljubljana, Ljubljana, Slovenia
Correspondence / Korespondenca: Damijan Miklavčič, e: damijan.miklavcic@fe.uni-lj.si
Key words: atrial fibrillation; pulmonary vein isolation; radiofrequency ablation; balloon cryoablation; irreversible electroporation; wide 
antral circumferential ablation
Ključne besede: atrijska fibrilacija; izoliranje pljučnih ven; radiofrekvenčna ablacija; balonska krioablacija; ireverzibilna elektroporacija;   
široka obkrožitvena antralna ablacija
Received / Prispelo: 6. 5. 2020 | Accepted / Sprejeto: 8. 3. 2021
Cite as / Citirajte kot: Štublar J, Žižek D, Jan M, Jarm T, Miklavčič D. Catheter ablation for the treatment of atrial fibrillation – development 
of various technical modalities. Zdrav Vestn. 2021;90(7–8):410–19. DOI: https://doi.org/10.6016/ZdravVestn.3078
eng slo element
en article-lang
10.6016/ZdravVestn.3078 doi
6.5.2020 date-received
8.3.2021 date-accepted
Cardiovascular system Srce in obtočila discipline
Professional article Strokovni članek article-type
Catheter ablation for the treatment of atrial 
fibrillation – development of various technical 
modalities
Zdravljenje atrijske fibrilacije s katetrsko ablacijo 
– razvoj različnih tehničnih možnosti article-title
Catheter ablation for the treatment of atrial 
fibrillation Zdravljenje atrijske fibrilacije s katetrsko ablacijo alt-title
atrial fibrillation, pulmonary vein isolation, 
radiofrequency ablation, balloon cryoabla-
tion, irreversible electroporation, wide antral 
circumferential ablation
atrijska fibrilacija, izoliranje pljučnih ven, ra-
diofrekvenčna ablacija, balonska krioablacija, 
ireverzibilna elektroporacija, široka obkrožitvena 
antralna ablacija
kwd-group
The authors declare that there are no conflicts 
of interest present.
Avtorji so izjavili, da ne obstajajo nobeni 
konkurenčni interesi. conflict
year volume first month last month first page last page
2021 90 7 8 410 419
name surname aff email
Damijan Miklavčič 1 damijan.miklavcic@fe.uni-lj.si
name surname aff
Jernej Štublar 1,2
David Žižek 2
Matevž Jan 3
Tomaž Jarm 1
eng slo aff-id
Faculty of Electrical 
Engineering, University of 
Ljubljana, Ljubljana, Slovenia
Fakulteta za elektrotehniko, 
Univerza v Ljubljani, Ljubljana, 
Slovenija
1
Department of Cardiology, 
Division of Internal Medicine, 
University Medical Centre 
Ljubljana, Ljubljana, Slovenia
Klinični oddelek za kardiologijo, 
Interna klinika, Univerzitetni 
klinični center Ljubljana, 
Ljubljana, Slovenija
2
Department of Cardiovascular 
Surgery, Division of Surgery, 
University Medical Centre 
Ljubljana, Ljubljana, Slovenia
Klinični oddelek za kirurgijo 
srca in ožilja, Kirurška klinika, 
Univerzitetni klinični center 
Ljubljana, Ljubljana, Slovenija
3
Slovenian Medical Journallovenian Medical Journal
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PROFESSIONAL ARTICLE
Catheter ablation for the treatment of atrial fibrillation
1 Introduction
Among arrhythmias, atrial fibrillation (AF) is the 
most common. In Slovenia, according to the prevalence 
in comparable countries, it is estimated that there are 
15,000–30,000 patients with AF. In the ECG, the absence 
of a P wave (an organized atrial depolarization is absent) 
and irregular QRS complexes (irregular ventricular re-
polarization) are characteristic of AF. AF is a chronic 
disease in which the degree of progression is assessed 
according to the duration of the arrhythmia. It is divid-
ed into 5 groups: first detected AF; paroxysmal AF, in 
which an episode of arrhythmia with spontaneous ter-
minations lasts a maximum of 7 days; persistent AF, in 
which an episode of arrhythmia lasts more than 7 days; 
long-standing persistent AF, which lasts more than 1 
year; and permanent AF. For the efficient pumping of 
blood, atrial and ventricular action need to be coordi-
nated; in normal sinus rhythm, the atria contract ap-
proximately 200 ms before the ventricles. During AF, 
electrical activity and thus atrial contraction are entirely 
irregular, which leads to blood stasis, in particular in the 
left auricle. During blood stasis, blood clots can form, 
which makes AF the main risk factor for stroke (1,2). 
Additionally, AF causes various symptoms that negative-
ly affect the quality of life and worsens preexisting heart 
failure (3). For these reasons, treatment of AF consists of 
anticoagulants, which prevent blood clot formation, and 
drugs to prevent AF or keep patients in sinus rhythm for 
as long as possible. In AF treatment, two main strategies 
have been established: rate control and rhythm control. 
In most cases, antiarrhythmic drugs are prescribed to 
limit the rapid response of the ventricles, and in perma-
nent AF, catheter ablation can be used to sever the elec-
trical connection between the atria and ventricles; this 
also requires the insertion of a permanent cardiac pace-
maker. Maintaining sinus rhythm is indicated in parox-
ysmal and both forms of persistent AF, with treatment 
success depending on AF progression. Paroxysmal AF 
has the best prognosis. According to the 2020 European 
guidelines (4), if treatment with antiarrhythmic drugs 
(Class I, Level of Evidence A) fails, catheter ablation is 
indicated (2). In Slovenia, a little over 300 patients with 
AF are treated with catheter ablation each year, which 
places us in the middle among the European Society of 
Cardiology (ESC) members in terms of the number of 
treatments per million inhabitants (5).
2 Radiofrequency ablation for the 
treatment of AF
Catheter ablation or radiofrequency ablation (RFA) 
is the most widespread minimally invasive method of 
AF treatment, in which a high-frequency alternating 
electric current is supplied to the target tissue through 
the tip of the ablation catheter. Due to the small surface 
area of the ablation electrode and thus a high current 
density, energy in the form of heat is released on con-
tact with the myocardial tissue, which at a temperature 
higher than 50°C causes a permanent lesion, which then 
permanently terminates the action potential conduction 
in the ablated area (6). RFA causes punctiform damage 
at the contact of the catheter with the myocardial wall 
at the depth of 3–4 mm (Figure 1; E) (7). This is suffi-
cient to damage all layers of the myocardial wall from 
the endocardium to the epicardium in the wall of the left 
atrium (i.e. transmural lesion). The closed loop of the 
electrical circuit in RFA is enabled by a dispersive elec-
trode placed on the patient’s back, which with its large 
surface area ensures that the current density there is 
small enough and that there is no heating of the skin or 
other significant biological effects. The main drawback 
of RFA is the comparatively narrow temperature win-
dow between 37°C, which enables a physiological tissue 
state, and 50°C, which can cause permanent injury. The 
lesion always spreads from the higher temperature area 
with the highest current density to the lower tempera-
ture area. Two possible side effects of ablation can oc-
cur: insufficient (temporary) tissue injury instead of the 
desired permanent injury, and unwanted damage to the 
surrounding tissue, such as the oesophagus, which is lo-
cated very close to the left atrium. To prevent unwanted 
myocardial and surrounding tissue injury, all ablation 
catheters are now equipped with temperature sensors 
which automatically adjust the supplied electrical power 
according to the measured temperature at the catheter 
tip.
2.1 Pulmonary vein isolation with 
radiofrequency ablation
The main goal of RFA is pulmonary vein isolation, 
which is considered to be the most common site of 
AF triggers. Anatomically speaking, two pulmonary 
veins exit from the left and two from the right of the 
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left atrium posterior wall. The tissue characteristics of 
the junction between the pulmonary veins and the left 
atrium is complex and different to other areas of the 
heart. Individual muscle fibres in this area are capable 
of spontaneous depolarization, thus causing premature 
beats, which can act as AF triggers. Slow action poten-
tial propagation is also characteristic for the junction 
between the pulmonary veins and the left atrium, which 
enables the depolarization wave to circle inside the local 
myocardial area and acts as a driver of AF (13). Over 
20 years ago, Haïssaguerre et al. found that in patients 
with paroxysmal AF, the triggers of spontaneous prema-
ture beats are located in the pulmonary veins in 94%. 
With targeted RFA they tried to destroy the triggers in 
the pulmonary veins themselves, which they succeed-
ed in doing in only 38 out of 45 patients (84%), despite 
numerous repeat attempts. Although trigger ablation 
was not highly effective, the recurrence of AF withing 8 
months was prevented in 62% of patients after the pro-
cedure, indicating the promise of this method (14). The 
procedure was safe with only a few cases of cough and 
occasional severe pain during ablation, and one case of 
a small left atrial clot, confirmed by angiography, being 
reported. After the discovery that AF triggers are located 
in the pulmonary veins, pulmonary vein isolation (PVI) 
was established as a cornerstone of AF treatment with 
catheter ablation. During the PVI procedure, a circular 
mapping catheter (the so-called LASSO catheter, Fig-
ure 2; A) was inserted into the pulmonary vein. After the 
ablation around the pulmonary vein ostia, it was used to 
check whether complete absence of intracardiac electri-
cal signals was achieved in the pulmonary veins, as pul-
monary vein isolation is the main goal of the procedure 
(Figure 2; B). By using the LASSO catheter, very rapid 
AF triggers from the pulmonary veins were detected, 
confirming the hypothesis that states that spontaneous 
pulmonary vein electrical activity can drive AF. At the 
beginning of the method’s development, the PVI proce-
dure was used by targeting areas with earliest activation 
at the pulmonary vein ostia with ablation, achieving iso-
lation (15); the procedure was named segmental ostial 
PVI. It has been used since 2003 at the University Med-
ical Centre Ljubljana. The long-term results of the pro-
cedure on 126 patients (68% with paroxysmal AF, 32% 
with persistent AF) were published in 2013 (16). With 
repeated procedures in the 36-month follow-up period, 
symptomatic improvement was achieved in 73% (84% in 
paroxysmal AF, 48% in persistent AF) with rare compli-
cations (5.5%). These results are comparable to the data 
in the literature (17).
Figure 1: Multi-electrode PVAC GOLD catheter (A), hot balloon catheter (B), laser ablation balloon (C), cryoablation balloon 
in the pulmonary vein ostium (D). Schematic representation of the ablation catheter, used in the WACA procedure (see text 
for explanation) with a lesion cross section, also showing rinsing with saline (E) (8-12).
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PROFESSIONAL ARTICLE
Catheter ablation for the treatment of atrial fibrillation
2.2 Wide antral circumferential ablation
An important breakthrough in AF treatment with 
RFA was achieved with the development of the electri-
cal anatomical mapping system (EAM), which enables 
a traceable continuous sequence of punctate lesions 
around the pulmonary veins ostia (Figure 3). The ba-
sic idea of the method is to guarantee a continuous iso-
lation line (in contrast to the segmental ostial PVI, in 
which ablation lines are not continuous), which, in ad-
dition to pulmonary veins triggers, also covers the area 
of pulmonary veins exits from the left atrium and thus 
isolates potential AF drivers, mostly located in this ar-
ea. The procedure is named wide antral circumferential 
ablation (WACA). As early as 2014, a review of 12 studies 
demonstrated the greater effectiveness of this procedure 
in maintaining sinus rhythm compared to segmental os-
tial PVI (19). Despite the high effectiveness with almost 
100% achieved pulmonary vein isolation during the 
procedure, permanent isolation of the pulmonary veins 
remains a challenge, as the re-establishment of the elec-
trical connection between the left atrium and at least one 
pulmonary vein in as much as 62.5% within two months 
after the procedure has been described (20).
Permanent isolation of the pulmonary veins strong-
ly depends on the sufficient depth of each of the point 
lesions and the continuity of the isolation line (21), and 
acute pulmonary vein isolation (achieved during the 
Figure 2: Schematic representation of the LASSO catheter at the pulmonary vein ostium and point-by-point ablation (A). 
Representation of pulmonary vein potentials (PVP) covered with a 20-electrode LASSO catheter (B). Electrical activity 
(PVP) can clearly be seen in the first three beats, while the last beat shows successful isolation of the pulmonary vein (no 
PVP). Intracardiac signals from distant locations are marked with an asterisk (*) and remain unchanged despite successful 
pulmonary vein isolation (18). Permission to use the images has been obtained.
Figure 3: Example of a finished WACA procedure (see text for explanation). Red dots represent single-point RFA ablation 
lesions in two antral isolation lines around the exit points of the left and right pulmonary veins. The posterior view of the 
left atrium anatomy with coloured pulmonary veins (dark blue: left superior pulmonary vein, pink: left inferior pulmonary 
vein, green: right superior pulmonary vein, light blue: right inferior pulmonary vein). Image is from our own archive.
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procedure) does not have a reliable predictive value for 
permanent pulmonary vein isolation (13,21). The lesion 
depth with a constant supply of electrical power is pro-
portional to the quality of contact of the ablation cathe-
ter with the target myocardial tissue, with an increase in 
catheter tip temperature and a drop in ablation circuit 
impedance being good indicators of contact quality (22). 
As the WACA procedure uses cooled ablation catheters 
to prevent clot formation at the catheter tip, catheter tip 
temperature measurements are not adequate to assess 
the lesion depth. Therefore, circuit impedance monitor-
ing during RFA has gained validity. A preclinical study 
has shown that a drop in circuit impedance of more than 
15 Ω means that good contact of the ablation electrode 
with cardiovascular tissue has been established, but a 
drop in circuit impedance greater than 20 Ω predicts 
the risk of target tissue explosion due to heating above 
the boiling point of water (22). Steam pop is a frequent 
side effect during RFA and can cause cardiac perforation 
and pericardial bleeding, leading to cardiac tamponade, 
a life-threatening complication. There is a lack of clearly 
established guidelines for monitoring the drop in cir-
cuit impedance during the WACA procedure. In clinical 
practice, a relative drop in circuit impedance of approxi-
mately 10% has been shown as an indicator of good con-
tact between the ablation catheter and target myocardial 
tissue. In one of the first clinical studies to target a 10% 
drop in circuit impedance with each lesion made during 
the WACA procedure, permanent pulmonary vein isola-
tion was confirmed in 92% during a repeated procedure 
after 163 ± 133 days (median ± SD) (21). Contact quality 
between the ablation catheter and target myocardial tis-
sue can be monitored by using intracardiac echocardi-
ography (ICE) with probes up to 3 mm thick, which are 
inserted via guidewires through the femoral vein into 
the heart. The use of EAM and ICE systems enables the 
safe and effective use of the WACA procedure without 
radiography, which was shown in 144 consecutive pa-
tients with paroxysmal AF in Slovenia, among the first 
in the world (23).
2.3 Pulmonary vein isolation with contact 
force measuring technology
At the University Medical Centre Ljubljana, as at the 
majority of large world centre, the WACA procedure re-
mains the first and most common method of AF treat-
ment due to various technological improvements. One 
of the key improvements enables the measuring of the 
contact force (CF) between the ablation catheter tip 
and target tissue. Based on the data on the contact force 
during the procedure, we can estimate the depth of each 
individual ablation lesion. Currently, the most sophisti-
cated protocol that exploits the technological potential 
of CF ablation catheters and is supported by excellent 
clinical results has been named CLOSE-guided WACA 
(24). Based on clinical experience, the authors of the 
CLOSE-guided WACA procedure have defined the min-
imum criteria for assessing the quality of lesions, sum-
marized in the form of an ablation index (AI). It is based 
on an empirical equation, which, in addition to the con-
tact force (gram), also takes into account the input pow-
er (watt) and ablation time (second). The AI  value to as-
sess the transmural lesions is adjusted to different areas 
in the left atrium. For example, a value of 400 is enough 
to achieve a transmural lesion in the thinner posterior 
left atrial wall, while the same is true for a value of 550 
in the thickened anterior wall. The continuity of the iso-
lation line around the pulmonary veins, achieved with 
an even sequence of lesions with a maximal interlesion 
distance of 6 mm, is also important. One of the most 
important findings of the method’s authors was that not 
only the average contact force (gram) is crucial for the 
quality of the planned lesion, but above all the stability 
of the contact, which must be greater than 4 g at least 
30% of the ablation time. The most impressive result of 
their studywas a 98% rate of pulmonary vein isolation 
with the establishment of an isolation line around the 
pulmonary veins during the procedure without the need 
for additional ablations. The importance of meeting the 
criteria of the CLOSE-guided WACA protocol was fur-
ther demonstrated in three patients who had to have the 
procedure repeated due to AF recurrence. During the 
repeated procedure, they were able to identify discontin-
uous segments in the antral isolation line on which not 
all CLOSE-guided WACA criteria were met in the origi-
nal procedure (24). Despite the high effectiveness of the 
CLOSE-guided WACA protocol, no significant compli-
cations were detected in the study, indicating the safety 
of the method. As the AI value provides a very reliable 
predictive value of the lesion’s transmurality, it is pos-
sible to more accurately evaluate other parameters that 
predict the quality of change with the AI  value; a drop 
in the RFA circuit impedance, reduction of signal am-
plitude after the ablation and a change of the signal form 
after the ablation. Of all the above, only the drop in RF 
ablation circuit impedance by 18.3 ± 1.1 Ω (mean ± SD), 
a reduction of approximately 12% from baseline before 
the start of each RFA, has an equivalent predictive value 
of the transmurality of an individual lesion as AI (25).
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Catheter ablation for the treatment of atrial fibrillation
2.4 Possible complications of radiofrequency 
ablation
Threatening complications can appear in 2–3 % of 
procedures (2). They are divided into early complications, 
appearing during or immediately (up to 24 hours) after 
the procedure, or late, appearing up to 2 months after the 
procedure. The procedure mortality is very low at less 
than 0.1% (26).
During the procedure itself, due to the application 
of RF energy, cough can appear, a consequence of vas-
cular tissue heating in the pulmonary vein, signalling an 
inappropriate ablation location outside the isolation line 
around the pulmonary veins. Rarely, severe chest pain can 
appear during the procedure, indicating thermal damage 
to the pericardium or pleura. When such pain appears 
during ablation at the posterior left atrial wall, it can be 
the consequence of oesophageal heating due to its loca-
tion directly posterior to the left atrium. Pericardial effu-
sion, which can lead to cardiac tamponade, and embolic 
stroke are also among the early complications. To prevent 
clot formation and stroke, therapeutic doses of hepa-
rin should be used. Ablation catheters with cooled tips 
can also be used, in which the tip is continuously rinsed 
through small holes by heparinized saline (Figure 1; E).
An atrio-oesophageal fistula, a consequence of collat-
eral thermal injury of the oesophageal wall, also counts 
among the late complications. It is one of the most dan-
gerous complications of invasive AF treatment with a 
high mortality rate (27). It is a rare complication, appear-
ing in less than 0.5% (26).
3 Methods for pulmonary vein isolation 
with single-shot techniques
Despite the effectiveness of the WACA procedure, the 
tracing of punctate lesions is a relatively lengthy proce-
dure; the average duration of the procedure is stated to be 
up to 284 minutes (28). In addition to the duration of the 
procedure, a disadvantage is also its complexity, which 
requires long-term training of a cardiologist (28,29). 
Therefore, such treatment of AF is normally available 
only in tertiary medical institutions. Various customized 
technological solutions have emerged in the search for 
the simplification of the procedure and ensuring wider 
availability of AF ablation treatment. Simplicity is com-
mon to all of them, based on single-shot techniques: 
multi-electrode RFA, balloon cryoablation, balloon laser 
ablation and hot balloon ablation (28).
The only clinically available multi-electrode RFA 
catheter (PVAC Gold, Figure 1; A) has 9 gold electrodes, 
enabling the simultaneous supply of RFA energy. The 
widespread use of this catheter was prevented by the ex-
tremely high incidence (20%) of otherwise asymptomatic 
cerebral embolisms. This complication was not detect-
ed with a standard RFA catheter with a cooled tip used 
in the WACA procedure (28). With normal left atrium 
anatomy with four separate pulmonary veins, the use of 
different balloon catheters is also possible. All technolo-
gies have the common goal of isolating the pulmonary 
vein with only one application. The hot balloon catheter 
(Figure 1; B) has an adaptable size from 25 mm to 35 mm 
and is entirely filled with a mixture of normal saline and 
contrast for radiography visualization. The balloon can 
be heated to 75°C with an RF coil, enabling vein isolation 
in 3 minutes and an average procedure duration of less 
than 2 hours (30). Due to frequent thermal oesophageal 
injury, oesophageal cooling with cooled liquids is rec-
ommended during each application, which necessitates 
the use of general anaesthesia. The currently published 
results are comparable in effectiveness to the WACA pro-
cedure, although the first randomized clinical study has 
yet to appear. The balloon for laser ablation (Figure 1; 
C) is interesting because it is the only one that allows for 
the visualization of the anatomy and quality of contact of 
the balloon with the target myocardial tissue via a built-
in endoscopic camera. We are still waiting for the first 
randomized clinical study to evaluate the effectiveness of 
laser ablation balloon. According to the currently pub-
lished results, the procedure duration is even longer than 
the WACA procedure, making the technology less likely 
to achieve widespread use (28). 
The effectiveness of balloon cryoablation, in which 
contact between the cryoballoon catheter (Figure 1; D) 
and the target tissue is cooled with liquid nitrous oxide 
(laughing gas) up to – 60°C, was confirmed by a random-
ized study performed in 16 centres (29). Clinical equiv-
alence with the WACA procedure was proved. As the 
study was performed in centres with a large procedure 
volume where only 141 minutes were required on aver-
age for the WACA procedure, the duration of the balloon 
cryoablation procedure was only 17 minutes shorter. Bal-
loon cryoablation also has a safety profile comparable to 
the WACA procedure apart from the possible temporary 
phrenic nerve injury (2.7%), which was not detected in 
the WACA procedure. Due to its relative simplicity when 
compared to the WACA procedure, balloon cryoablation 
enabled the opening of new AF ablation treatment cen-
tres and became the method of choice in some smaller 
centres. In terms of the number of procedures in some 
European countries, such as Spain, balloon cryoablation 
is already approaching the scope of WACA (31).
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4 Prospects for the development of a 
pulmonary vein isolation method with 
irreversible electroporation
In clinical practice, various sources of ablation en-
ergy are used. In all, the mechanism of tissue injury is 
thermal, by heating or cooling tissue. The possibility of 
collateral tissue damage in the immediate vicinity of the 
target tissue is present and comparable in both heat-
ing and cooling. A short while ago, a new method for 
non-thermal target ablation of myocardial tissue, based 
on electroporation, was introduced (32-35). Electro-
poration is a phenomenon by which the permeability 
of the cell membrane is greatly increased due to forced 
transmembrane voltage by exposing cells to short 
high-voltage electric pulses. The phenomenon is also 
called electropermeabilization, as it also allows mole-
cules for which the cell membrane is otherwise imper-
meable to cross the cell membrane. Electroporation can 
be reversible if the cell membrane returns to the original 
state after a certain time after exposure to electric puls-
es. The exposed cells thus maintain homeostatic balance 
and retain their function, enabling them to survive. Ir-
reversible electroporation (IRE) occurs when the cell 
injury becomes irreversible, leading to cell death (36). 
Reversible electroporation is an established method in 
oncology with electrochemotherapy, where electropo-
ration is used to locally increase the influx of cytostatics 
into the tumour cells, thus increasing their effectiveness 
(37-39). In oncology, IRE is also established for the 
treatment of surgically or RFA-inaccessible tumours 
(40,41). Whether electroporation will be reversible or 
irreversible is most influenced by the strength of the 
electric field and the duration and number of pulses ap-
plied (Figure 4) (42).
More than a decade of preclinical and clinical studies 
points to the safety and effectiveness of the IRE ablation 
method. Despite the extraordinary variety of ablation 
catheters used and the parameters of the supplied elec-
trical pulses, no study has detected the typical compli-
cations that otherwise accompany all thermal cardiac 
ablation methods (34,35,43,44,45,46). The advantage of 
IRE is also in the extremely short time needed to per-
form the ablation (only a few ms, Figure 5; C) when 
compared to the established thermal methods (46). In 
the interim report of the first clinical study on the use 
of IRE for the treatment of AF with catheter ablation, 
PVI required a third less time than other ablation meth-
ods. By optimizing the IRE protocol, they were the first 
to confirm a 100% permanent pulmonary vein isola-
tion in a repeat electrophysiological procedure after 3 
months (47). In addition to the already described safe-
ty and speed, ablation with irreversible electroporation 
enables better achievement of transmural lesions with 
an appropriate choice of electric pulse parameters, cath-
eter and ablation protocol (Figure 5) (48,49). However, 
the development of this promising method is still in its 
infancy, despite much evidence of efficacy and safety. 
Figure 4: A: Type of electroporation depending on the strength of the electric field and the duration of each pulse. B: 
Type of electroporation depending on the strength of the electric field and the number of pulses (pulse duration 100 µs). 
(Source: The Laboratory for Biocybernetics of the Faculty of Electrical Engineering, University of Ljubljana).
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Catheter ablation for the treatment of atrial fibrillation
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We still expect that further technological improvements 
will lead to the rapid establishment of the method in 
clinical practice. Not long ago, the company Medtron-
ic announced the start of a study to obtain a licence to 
use the PulseSelectTM system, enabling treatment of 
AF with irreversible electroporation in everyday clinical 
practice (50). The Laboratory for Biocybernetics of the 
Faculty of Electrical Engineering, University of Ljublja-
na, has also contributed its rich experience in the field of 
electroporation in the development of this system.
5 Conclusion
Catheter ablation with pulmonary vein isolation is 
currently the most effective method of AF treatment. 
With technological advancements, we can expect im-
provements and new approaches to increase the avail-
ability and safety of this invasive AF treatment.
Conflict of interest
None declared.
Figure 5: Multi-electrode PVAC GOLD catheter, used to supply IRE pulses (A). A schematic representation of the amplitude 
and duration of supplied biphasic pulses (B). Display of the duration of one ablation, composed of 60 biphasic pulse cycles 
(C). Display of intracardiac electric signals in a pulmonary vein before (D, F) and after (E, G) ablation with irreversible 
electroporation (46). Permission to use the images has been obtained.
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