Journal of

Clinical Medicine

Review
Atrial Fibrillation Ablation: Current Practice and Future
Perspectives
Laura Rottner * and Andreas Metzner *

University Heart and Vascular Center, University Hospital Hamburg-Eppendorf, 20251 Hamburg, Germany
* Correspondence: [email protected] (L.R.); [email protected] (A.M.); Tel.: +49-(0)40-7410-58320 (L.R.)

Abstract: Catheter ablation to perform pulmonary vein isolation (PVI) is established as a mainstay
in rhythm control of atrial fibrillation (AF). The aim of this review is to provide an overview of
current practice and future perspectives in AF ablation. The main clinical benefit of AF ablation is the
reduction of arrhythmia-related symptoms and improvement of quality of life. Catheter ablation of
AF is recommended, in general, as a second-line therapy for patients with symptomatic paroxysmal or
persistent AF, who have failed or are intolerant to pharmacological therapy. In selected patients with
heart failure and reduced left-ventricular fraction, catheter ablation was proven to reduce all-cause
mortality. Also, optimal management of comorbidities can reduce AF recurrence after AF ablation;
therefore, multimodal risk assessment and therapy are mandatory. To date, the primary ablation
tool in widespread use is still single-tip catheter radiofrequency (RF) based ablation. Additionally,
balloon-based pulmonary vein isolation (PVI) has gained prominence, especially due to its user-
friendly nature and established safety and efficacy profile. So far, the cryoballoon (CB) is the most
studied single-shot device. CB-based PVI is characterized by high efficiency, convincing success
rates, and a beneficial safety profile. Recently, CB-PVI as a first-line therapy for AF was shown to
be superior to pharmacological treatment in terms of efficacy and was shown to reduce progression
from paroxysmal to persistent AF. In this context, CB-based PVI gains more and more importance as
a first-line treatment choice. Non-thermal energy sources, namely pulsed-field ablation (PFA), have
garnered attention due to their cardioselectivity. Although initially applied via a basket-like ablation
tool, recent developments allow for point-by-point ablation, particularly with the advent of a novel
lattice tip catheter.

Keywords: atrial fibrillation; catheter ablation; indication; patient selection; ablation technologies
Citation: Rottner, L.; Metzner, A.
Atrial Fibrillation Ablation: Current
Practice and Future Perspectives. J.
Clin. Med. 2023, 12, 7556. https://
1. Introduction
doi.org/10.3390/jcm12247556
In the late 1990s, a discovery made by Haissaguerre and colleagues, which identified
Academic Editor: Sebastien Knecht
the electrical activity in the pulmonary veins (PVs) as the primary trigger for atrial fibrilla-
Received: 14 November 2023 tion (AF) [1], prompted the electrophysiology community to abandon efforts to replicate
Revised: 27 November 2023 surgical techniques developed by Cox and his team [2]. It has become evident that excitable
Accepted: 30 November 2023 tissue within the PVs plays a central role in the occurrence of AF. Consequently, the primary
Published: 7 December 2023 approach that emerged was to disrupt the electrical connections between the PVs and
the left atrium (LA) via catheter ablation [3]. This strategy evolved from a segmental
approach, targeting the earliest site of activation at the PV ostia, to an ablation strategy
aiming at wide-area PV encircling. This was initially purely fluoroscopically guided, then
Copyright: © 2023 by the authors.
later guided by an electroanatomic mapping system [4,5].
Licensee MDPI, Basel, Switzerland.
Pulmonary vein isolation (PVI) has demonstrated a success rate between 60% and 90%
This article is an open access article
distributed under the terms and
at one-year follow-up in patients with paroxysmal AF [6–8], while success rates in persistent
conditions of the Creative Commons
or long-standing persistent AF are less favorable [9,10]. Catheter ablation for AF has been
Attribution (CC BY) license (https://
shown to be more effective with regard to maintenance of sinus rhythm when compared
creativecommons.org/licenses/by/ to pharmacological treatment [11], offers a significant improvement in quality of life [12],
4.0/). may delay or stop progression to more advanced forms of the disease [13,14], and has been

J. Clin. Med. 2023, 12, 7556. https://doi.org/10.3390/jcm12247556 https://www.mdpi.com/journal/jcm

J. Clin. Med. 2023, 12, 7556 2 of 13

proven to reduce all-cause mortality in selected patients [15]. Multiple energy sources and
various ablation tools as well as different ablation strategies have been evaluated with
regard to efficiency, efficacy, and safety [8,16]. With regard to arrhythmia-free survival and
clinical outcome after AF ablation, patient selection, simultaneous risk factor management,
as well as optimal time point for catheter ablation play a decisive role [17].
Within this review article, we summarize the current practice and future perspectives
of catheter ablation of AF.

2. Recommendations for Catheter Ablation According to Current Guidelines

The main clinical benefit of AF ablation is the reduction in arrhythmia-related symp-
toms and therefore improvement of quality of life [12,17]. The results of the EAST AFNET-4
trial have shown that an early rhythm-control strategy is associated with lower rates of
cardiovascular events when compared to usual care [18]. However, in the rhythm-control
arm, the initial choice of therapy was flecainide (36%), followed by amiodarone (20%),
dronedarone (17%) and only a minority of patients initially underwent catheter ablation
(8%). So far, no randomized controlled trial has demonstrated a significant reduction
in all-cause mortality with AF ablation in the “general” AF population. Therefore, the
indications for AF ablation have not been broadened beyond symptom reduction, and AF
ablation is not yet indicated in asymptomatic patients [17].
Catheter ablation of AF is recommended, in general, as a second-line therapy for
patients with symptomatic paroxysmal or persistent AF, who have failed or are intolerant
of class I or class III AAD therapy (class I) [17]. As an exception, in selected patients with
heart failure and reduced left ventricular fraction (HFrEF), catheter ablation was proven to
reduce all-cause mortality and re-hospitalization, and was also associated with significant
improvement of left ventricular function [15,19,20]. Thus, the CASTLE-AF trial provides
strong evidence and supports the current guideline recommendation to endorse catheter
ablation as the preferred treatment of AF in patients with HFrEF, regardless of the type of
AF (class I) [15,17].
Interventional cardiac procedures involve the potential risk of life-threatening compli-
cations [21]; however, several clinical trials considering AF ablation as a first-line therapy
could demonstrate that catheter ablation is more effective at maintaining sinus rhythm
when compared to AAD therapy [6,22,23]. Furthermore, long-term AAD therapy is known
to be more commonly associated with considerable side effects compared to ablation (17%
vs. 8%) [24]. Based on these findings and patient preferences, according to current guide-
lines, AF ablation should be considered before an AAD in patients with paroxysmal AF
episodes (class IIa) or may be considered in patients with persistent AF without risk factors
for recurrence (class IIb) [17].

3. Patient Selection and Optimal Timing for Atrial Fibrillation Ablation

There is compelling evidence indicating a strong association between the clinical pre-
sentation of AF and the outcomes following ablation. The rates of arrhythmia recurrence
tend to increase progressively in patients with paroxysmal, persistent, and long-standing
persistent AF. Consequently, the type of AF holds significant importance when assessing
whether a patient should undergo AF ablation, and these considerations still align with the
latest guideline recommendations. In addition, it is known that AF ablation may induce a
reversal of atrial remodeling and recent studies also suggest that early ablation in the dis-
ease’s progression can prevent further deterioration. The prospective, controlled ATTEST
trial, published in 2021, was conducted at 29 hospitals and medical centers across 13 coun-
tries and randomized paroxysmal AF patients in a 1:1 fashion to either radiofrequency
(RF) ablation or AAD therapy. The primary endpoint was the rate of persistent AF/atrial
tachycardia (AT) at 3 years of follow-up. The results of the study demonstrated that RF
ablation is superior to guideline-directed AAD treatment in delaying the progression from
paroxysmal to persistent AF. Recently, similar findings were published by Antrade et al.
In their study, they report the three-year follow-up of patients with paroxysmal untreated
J. Clin. Med. 2023, 12, 7556 3 of 13

AF who had been randomly assigned to undergo initial rhythm-control therapy with
cryoballoon-based PVI or to receive AAD therapy. The authors found that initial treatment
with cryoablation was associated with a lower incidence of recurrent atrial tachyarrhythmia
and, of note, lower rates of persistent forms of AF over 3 years of follow-up when compared
to pharmacological treatment. In this context, early catheter ablation—ideally in the early
stages of the disease—with safe ablation tools is gaining more and more attention.
When weighing the risks and benefits of catheter ablation as an invasive procedure,
it also makes sense to avoid ablation in patients who are considered to have a very low
probability of success due to significant and unmodifiable risk factors. However, it is
important to determine whether some of these patients could benefit from ablation de-
spite lower arrhythmia-free survival rates, as has already been shown, for example, for
patients with heart failure [15]. Recently, results of the CASTLE-HTx randomized trial have
demonstrated that even among AF patients with end-stage heart failure, the combination
of catheter ablation and guideline-directed medical therapy was associated with a lower
likelihood of a composite of death from any cause, implantation of a left ventricular assist
device, or urgent heart transplantation than medical therapy alone, which might be due
more to relevant reduction in the AF burden and a return from persistent to paroxysmal
episodes as due to complete arrhythmia-freedom [25]. In addition, data from the EAST
AFNET-4 subanalysis already support an early rhythm-control strategy in patients with a
high comorbidity burden [26]. While there are no prospective data investigating whether
this is not only for the early rhythm-control approach in general but also specifically for
catheter ablation, current knowledge suggests that a holistic therapy concept certainly plays
a crucial role in this patient population, which includes not only effective rhythm-control
by catheter ablation but also the treatment of cardiovascular risk factors [17]. Already
older observational data have shown that risk factor management can reduce the risk of
AF recurrence after AF ablation to rates comparable to those of low-risk patients. In the
ARREST-AF trial, published in 2014, risk factor management, including treatment of arterial
hypertension, lipids, diabetes, sleep apnea, reduction of smoking and alcohol consumption,
or weight loss was offered to AF patients undergoing ablation. After a median follow-up of
3.5 years, risk factor management led to a significant increase of arrhythmia-free survival
compared to controls. Thus, at present, current guidelines recommend that for a more
balanced indication for ablation in AF patients with risk factors for recurrence, the most
intensely evaluated risk predictors (including total AF duration) should be considered, and
adjusted to their preferences [17].

4. Ablation Strategies: First Step Pulmonary Vein Isolation

Since Haissaguerre et al. published a study in 1998, which revealed that PV triggers
are the most important initiators of AF, electrical isolation of the PVs using catheter ablation
has become the cornerstone for the treatment of affected patients. PVI has demonstrated
a success rate between 60 to 90% at one-year follow-up in patients with paroxysmal
AF [6–8]. Results after a single ablation procedure in patients with persistent and long-
standing persistent AF are sobering; only about 51% of the treated patients remain free of
arrhythmia-recurrence after one year and only 42% after three years of follow-up. After
several interventions, success in this population is more promising at long-term follow-up
at almost 69%; however, in the underlying meta-analysis only a few studies reported results
of ablation after more than three years [27].
The main mechanism for the recurrence of AF after primary successful PVI is the
reconnection of previously isolated PVs [28,29]. Lin et al. found that the majority of
patients with AF recurrence who underwent re-ablation procedure after a mean follow-up
of 36 months had reconnected PVs [30].
However, PVs might not be the only contributors to the intricate process of AF ini-
tiation and recurrence, and some patients may present recurrences despite durable PVI
(“PVI non-responders”). External triggers beyond the PVs, as well as the disposition of
interstitial fibrosus tissue and autonomic innervation as well as genetic predisposition, are
J. Clin. Med. 2023, 12, 7556 4 of 13

likely to be co-factors in AF occurrence. However, the extent of their involvement in AF

patients remains not fully comprehended and may vary from one patient to another.
In patients suffering from persistent and long-standing persistent AF, due to disap-
pointing ablation success rates, and in the context of so-called “PVI non-responders”, more
extensive ablation beyond PVI has been advocated. This includes linear lesions, isolation
of the left atrial appendage (LAA) or of the superior vena cava, ablation of complex frac-
tionated atrial electrograms (CFAE), rotors, non-pulmonary foci, or ganglionated plexi,
fibrosis-guided voltage and/or MRI mapping. However, research on ablation strategies be-
yond PVI, both during the index procedure [31–33] and during re-procedures with durable
PVI [34,35], has not consistently demonstrated superiority with regard to recurrence rate in
both, paroxysmal and persistent AF.
The prospective and randomized Alster-Lost AF trial assessed the outcomes of two
index ablation strategies: standalone PVI versus a stepwise approach involving PVI fol-
lowed by complex fractionated atrial electrogram (CFAE) ablation and the establishment
of linear lesions in patients with symptomatic persistent or long-standing persistent AF.
After 12 months, there were no significant differences in terms of freedom from atrial tach-
yarrhythmias between both groups [32]. Similarly, the CHASE-AF clinical trial compared
the arrhythmia-free survival between standalone PVI and a stepwise approach, which
included CFAE ablation and additional linear lesion creation in patients with persistent
AF, and also revealed no advantage for the stepwise approach [33]. Lastly, the multicenter
STAR-AF 2 trial compared PVI only and either PVI plus CFAE ablation or PVI plus creation
of left atrial (LA) linear lesions in patients suffering from persistent AF. The results of
STAR-AF 2 were in line with previous studies and could not demonstrate the benefit of
more complex ablation strategies [31]. Consequently, PVI remains the only reproducible
endpoint of AF ablation so far.
PVI can be accomplished using either a point-by-point or a single-shot technique. For
the former approach, the operator performs a point-by-point wide-area circumferential
ablation (WACA) line around the ipsilateral PV antrum using a single-tip catheter in
combination with a 3D mapping system in order to achieve PVI. In contrast, when using
a single-shot device, PVI is achieved with a single ablation application for each of the
PVs [8,36]. Furthermore, different energy sources can be used for ablation itself. Briefly, we
can divide energy sources into thermal energy (RF, cryoablation, laser) and non-thermal
energy (electroporation/pulsed-field ablation).

4.1. The Classic in the Context of AF Ablation: Radiofrequency-Based Point-by-Point PVI

RF was the first energy source employed for AF ablation and is still the most used
worldwide. RF ablation combined with an electro-anatomical mapping system allows a
significant reduction in radiation exposure [37], provides additional information, e.g., the
LA activation pattern and LA voltage, and therefore enables for additional (non-PV trigger)
ablation as well as ablation of atrial tachycardias, if needed. However, this technique
is intricate and involves a long learning curve, and even for experienced operators it
still remains challenging to achieve contiguous, transmural, and permanent lesions using
RF-based single-tip ablation [28,38].
Over time, there has been significant progress in enhancing RF catheter technologies
with the goal of creating a uniform ablation lesion set while maintaining safety. A pivotal
development in this direction was the introduction of irrigated-tip catheters. Over two
decades ago, early investigations focused on PVI using single-tip, non-irrigated catheters,
and RF delivery in a temperature-controlled mode [39]. Since the introduction of irrigated
catheters, reducing thrombus formation and therefore allowing more power delivery,
RF ablation is now predominantly performed in a power-controlled mode. Usually, RF
ablation using irrigated-tip catheters involves applying moderate power (20–40 W) for
a duration of 20–60 s. The quantity of energy delivered, as well as the level of catheter
stability and tissue contact, are the primary factors influencing the formation of enduring
lesions. The introduction of an ablation catheter equipped with contact force (CF) sensing
J. Clin. Med. 2023, 12, 7556 5 of 13

capabilities has enabled real-time assessment of both catheter contact with atrial tissue
and catheter stability. Several clinical studies have affirmed that a low CF during RF
application is associated with acute procedural failure and sites of PV reconnection [40,41].
The reported one-year arrhythmia-free survival in patients with paroxysmal and persistent
AF who underwent CF-guided RF-ablation ranges from 50–90%, respectively [42,43]. The
question of whether CF-guided AF ablation leads to favorable clinical results especially with
regard to improved safety cannot be clearly answered [44]. Furthermore, there is ongoing
speculation on whether AF ablation using CF-sensing catheters might be associated with a
higher incidence of atrioesophageal fistula formation, although similar overall complication
rates have been found [45,46]. CF-sending further enabled the development of algorithms
aiming at real-time assessment of lesion quality including the force–time integral (FT) [47],
lesion size index (LSI) [48], and ablation index (AI) [49]. When coupled with automatic
tagging and standardized workflows, aiming for contiguous lesions, the integration of
lesion indices improved outcomes [50]. Moreover, Philips and colleagues conducted a
comparison between CF-guided ablation protocol that utilized region-specific criteria
of lesion contiguity and lesion depth (“CLOSE” protocol) and conventional PVI, and
demonstrated favorable 1-year-clinical outcomes for patients suffering from paroxysmal
AF [51].
In recent times, there have been additional advancements in RF-ablation with a partic-
ular focus on a strategy known as “High Power Short Duration” (HPSD). This approach
aims to further enhance lesion quality and decrease ablation and procedure time. Contrary
to common concerns, findings from ex vivo and in vivo animal studies consistently support
the idea that HPSD ablation results in broader but more shallow lesions [52,53]. Thus,
this technique may help to prevent damage to adjacent anatomical structures, such as
the esophagus, during ablation procedures. Multiple clinical investigations, including a
pair of randomized trials, demonstrated that contiguous, index-based encirclement with
high power ablation in power-controlled mode does shorten the procedure time while
maintaining a safe and effective procedure profile [54–56].
To address the limitation of reduced accuracy in tissue temperature feedback with
conventional irrigated-tip catheters, innovative catheters equipped with multiple thermo-
couples have been developed, enabling more precise and real-time monitoring of tissue
temperature. The novel DiamondTempTM ablation system (Medtronic® , Inc., Minneapolis,
MN, USA) was designed to revive the advantages of temperature-controlled RF delivery.
The tip of the DiamondTempTM ablation catheter incorporates six externally located thermo-
couples and a network of industrial diamonds to shunt heat from the catheter tip, allowing
for precise temperature monitoring and low irrigation flow rates. The split-tip electrode pro-
vides real-time high-resolution electrograms and impedance recordings. In the randomized
Diamond AF study, the DiamondTempTM ablation system demonstrated non-inferiority
compared to standard CF-guided ablation, achieving higher overall power delivery and
reduced procedure times [57]. Also, in a real-world cohort, the DiamondTempTM ablation
system demonstrated high efficacy for PVI [58]. Likewise, a recent study demonstrated
that the CF-sensing QDOT catheter (Biosense Webster, Irvine, CA, USA), together with
temperature-controlled ablation up to 90 W during low-flow irrigation, enables high first-
pass success rates for PVI while maintaining a balanced safety and effectiveness profile [59].
In conclusion, over the past 25 years, point-by-point RF ablation has evolved into
a clinically proven, safe, and effective procedure due to standardization and ongoing
innovation. Utilizing HPSD, whether in power- or temperature-controlled mode, has made
it possible to fasten the procedure and therefore improve efficiency, all while maintaining
safety and efficacy.

4.2. Step by Step to a Second Gold Standard: Cryoballoon-Based PVI

Apart from 3D electroanatomical mapping-guided RF-based ablation, cryoballoon (CB)
ablation has emerged as an established gold standard for PVI [17]. Since its introduction into
clinical practice, far more than one million patients worldwide suffering from symptomatic
J. Clin. Med. 2023, 12, 7556 6 of 13

AF have been treated with different versions of this first single-shot device. There is a
great amount of data on the efficacy and safety of the CB, and the CB is therefore, so
far, the best studied single-shot ablation technology. CB-based PVI is characterized by
high procedural reproducibility [60] and therefore high efficiency, convincing acute, mid-,
and long-term success rates [8,61,62], and a beneficial safety profile combined with short
learning curves [63–65].
Up until 2016, CB-PVI was considered a competitor to RF current in catheter ablation of
AF. However, the FIRE and ICE trial, which enrolled patients with symptomatic paroxysmal
AF and randomly assigned them to either RF- or CB-based PVI, established the CB as an
equally effective and safe ablation technology [8]. It is worth noting that some may argue
that the FIRE and ICE trial’s results may not fully represent real-world scenarios, as it
was conducted in highly experienced electrophysiology (EP) centers. Nevertheless, the
FREEZE cohort study involved 44 centers and included over 4000 patients suffering from
paroxysmal and persistent AF, and could confirm that CB ablation was non-inferior to
RF-based ablation in terms of both efficacy and safety [66].
The effectiveness of CB ablation in treating paroxysmal AF ranges from 65–80% at one-
year follow-up [6–8]. Recently, it has been found that CB PVI, compared to pharmacological
therapy, reduces the progression of paroxysmal AF toward persistent forms of AF [14].
As already discussed, so far, ablation strategies extending beyond pure PVI have not
consistently demonstrated superiority over PVI-only approaches. Thus, PVI remains the
only established, reproducible, and therefore recommended endpoint in first ablation
procedures for AF, even in patients with persistent AF. Notably, there are rare data from
randomized trials comparing CB ablation to classic RF-based AF ablation in subjects
suffering from persistent AF. However, in the multicenter CRYO4PERSISTENT AF trial,
CB PVI for the treatment of persistent AF demonstrated a 61% single-procedure success at
12 months post-ablation. In this study, compared with baseline recordings, there were also
significantly fewer patients with arrhythmia-related symptoms at 12 months (16% vs. 92%;
p < 0.0001). The symptom reduction was supported by significant improvement in 36-Item
Short Form Health Survey composite scores and European Heart Rhythm Association score
at 12 months [67]. The FIRE and ICE II randomized outcome trial has also been specifically
designed to assess the effectiveness and safety of PVI using the CB versus RF energy in
patients with persistent AF [68]. The results of this trial are eagerly anticipated.
Data on the safety of CB-based AF ablation report an incidence of major complications
ranging from 2.0 to 7.5% [69,70]. Of note, the incidence of cardiac tamponade at CB-based
PVI has been previously reported to be considerably low with 0.2 to 0.6% [71], and CB
ablation, in general, is associated with lower risk of pericardial effusion and tamponade
when compared to RF-based AF ablation [64]. The low incidence of cardiac tamponade
during CB ablation may be mainly attributed to the over-the-wire technique and due to the
lack of overheating and therefore steam pop risk. On the other hand, PNP has proven to
be the most frequently observed complication in CB-based ablation, and in the literature,
the clinical occurrence rate of PNP during CB procedures is reported from 1.7% up to
19.5% [65,70,72,73]. However, most PNPs are asymptomatic and transient [8,67].
In accordance with current AF guidelines, a history of ineffective or non-tolerated
pharmacological treatment has traditionally been considered a prerequisite for catheter
ablation. However, as already mentioned, early rhythm control has been shown to be
favorable for reducing cardiovascular events in the main cohort of the EAST-AFNET 4 trial
and subgroup analyses [18,26]. Therefore, the most effective rhythm-control strategy, which
is catheter ablation, is gaining more and more importance [74] and within this context,
CB-PVI plays a major role as a first-line ablation tool. Three recent randomized controlled
studies suggest that adopting a first-line ablation approach for newly diagnosed AF using
the CB is not only more effective than AAD therapy but also demonstrated non-inferior
safety [6,22,23]. However, whether first-line therapy for AF using the CB or other single-
shot devices can be implemented for the general AF population certainly also depends on
J. Clin. Med. 2023, 12, 7556 7 of 13

healthcare economics and infrastructural factors, which should desirably also play a role in
future analyses on this topic.

4.3. The Revolutionary Ablation Technology: Pulsed Field Ablation

Pulsed field (PFA) is a promising technology and PFA ablation is rapidly gaining
importance in the field of AF-ablation. PFA ablation is a predominantly non-thermal energy
source that involves exposing cardiac tissue to a brief yet intense electrical field. This leads
to the creation of irreversible pores in the lipid bilayer (electroporation) and subsequent
cell death [75]. The threshold for achieving irreversible electroporation varies depending
on the type of tissue, and it is relatively low for cardiomyocytes when compared to nearby
structures [76]. PFA’s tissue selectivity was confirmed in pre-clinical and clinical studies
showing low vulnerability of nerves, vasculature, and esophageal tissue to PFA [77,78].
Literature indicates that, for equivalent lesion depths, PFA lesions are wider, larger, and
more symmetrical than RF lesions, and PFA may be advantageous over RF ablation for the
ablation of heterogeneous scar tissue [79,80].
Several catheters with varying designs (single-shot, basket-like, focal tip, and lattice
catheter) are currently in different stages of development and clinical testing. The initially
launched FARAPULSE catheter (Boston Scientific, Marlborough, MA, USA) incorporating
a basket and flower-like catheter design was evaluated in several international multicenter
surveys and trials [81–83].
In the MANIFEST international multicenter survey, acute procedural success involving
the isolation of the PVs was almost universally achieved. Complications were rare and
mainly not associated directly with PFA. The results of a multicenter registry by Schmidt
et al. [83] and other single-center studies supported these findings [84,85]. Within the
PersAFOne single-arm study, evaluating bipolar PFA using a multispline catheter for
PVI and LA posterior wall ablation, invasive remapping at 2–3 months after the index
procedure, confirmed the high durability of previously applied lesions [86]. Whereas initial
reports focused on data without control groups, the recently published ADVENT trial
compared thermal energy sources (RF and Cryoablation) versus PFA [81]. Within the
ADVENT trial among patients with paroxysmal AF undergoing catheter ablation, PFA was
non-inferior to conventional thermal ablation with respect to freedom from a composite
of initial procedural failure, documented atrial tachyarrhythmia after a 3-month blanking
period, AAD usage, cardioversion, or repeat ablation, and with respect to device- and
procedure-related serious adverse events at 1 year [81].
Overall, previous literature shows reproducible data with regard to efficacy, durability,
and safety when using PFA for catheter ablation of AF. In general, PFA can lead to typical
complications associated with AF ablation, such as vascular complications, pericardial
tamponades, and thromboembolic events. However, due to its cardioselectivity, injuries to
surrounding structures—including phrenic nerve palsy or atrioesophageal fistula, one of
the most feared and lethal complications during AF ablation [87]—appear to occur less or
not at all [82,83].
The multispline-catheter design of the FARAPULSE catheter (Boston Scientific) allows
straightforward isolation of the PVs. Successful additional substrate modification for AF
via isolation of the posterior wall was reported [86,88]. However, PFA-capable multispline
catheters lack the ability to deliver individualized, focal lesions with different energy levels
and therefore certain limitations existed targeting other tachycardias. This called for PFA
technology which is embedded in a 3D mapping platform allowing for the creation of highly
accurate high-density maps in conjunction with the opportunity to draw distinct ablation
lines with a single-tip catheter. Recently, a novel PFA system (CENTAURI; Galvanize
Therapeutics, Phoenix, AZ, USA) was introduced, which enables monopolar biphasic
PFA with commercially available, CF-sensing focal catheters in combination with their
associated 3D mapping system. First single-center experiences reported convincing results
during point-by-point PVI using this system [89]. However, besides PVI, effective and
safe ablation of other structures, critical for atrial arrhythmias, such as the left atrial mitral
J. Clin. Med. 2023, 12, 7556 8 of 13

isthmus (LAI) might be targeted during a left atrial ablation procedure. However, limited
experience exists for PFA applications in the area of the LAI. Besides a limited effect of
PFA in LA areas with thicker myocardium, complications such as coronary spasms or
narrowing have been observed in select patients [86,90]. Thus, an ablation system enabling
both PFA and a conventional thermal energy source such as RF was desirable for combining
high flexibility and safety for the ablation of atrial tachycardias. Lately, a novel mapping
and ablation platform (AfferaTM , Medtronic, Singapore) combined with a compressible
lattice-tip catheter (Sphere-9TM , Medtronic) was introduced, enabling focal ablation using
either RF or PF energy [91]. After convincing animal and preclinical studies [92], the first
in-person investigation could confirm that AF ablation with this focal RF/PF catheter
allows efficient procedures, chronic lesion durability, and satisfactory freedom from atrial
arrhythmias [93]. Further investigations of this innovative mapping and ablation tool are
eagerly awaited.

5. Conclusions
Catheter ablation has become the leading therapeutic strategy for rhythm control in
AF patients. Advances in technologies have led to increasing improvements in efficiency,
effectiveness, and safety. Continuous advancements and emerging evidence are broadening
the potential applications of catheter ablation as the primary treatment choice for AF,
potentially even for asymptomatic patients. However, despite improvements in ablations
techniques, the long-term outcomes following a single procedure are still not ideal for
patients with persistent and long-standing persistent AF. Although, according to current
literature, PVI remains the first and fundamental ablation strategy for all types of AF,
further investigations are necessary to identify alternative strategies when PVI alone proves
to be insufficient.

Author Contributions: Conceptualization, L.R. and A.M.; methodology, L.R.; writing—original

draft preparation, L.R.; writing—review and editing, A.M. All authors have read and agreed to the
published version of the manuscript.”
Funding: This research received no external funding.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: Data are contained within the article.
Conflicts of Interest: The authors declare no conflict of interest.

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