Persistent Atrial Fibrillation Ablation: Ongoing Challenges Defining the Target Population and Substrate

Catheter ablation (CA) is a well-established treatment for paroxysmal atrial fibrillation (AF), but outcomes in persistent AF can be suboptimal. This review summarises recent evidence relating to the ideal patient population and target substrate for CA, and the techniques available. Risk scores can identify individuals with persistent AF who are more likely to benefit from CA. Pulmonary vein isolation (PVI) remains the most important ablation technique but non-pulmonary vein triggers explain the high recurrence rates in persistent AF. Novel electroanatomic mapping technologies, hybrid approaches, ethanol vein of Marshall ablation and thoracoscopic epicardial ablation are promising recent developments. Pulsed field ablation (PFA) is a new ablation modality with an excellent safety profile in trials to date; its role in persistent AF remains an area of study. Improving outcomes of CA in persistent AF remains a significant research focus, with several encouraging directions for future study.


Opinion statement
Pulmonary vein isolation (PVI) via catheter ablation (CA) is an effective treatment for individuals with paroxysmal atrial fibrillation (AF), but outcomes are suboptimal for more advanced forms of the disease.Despite extensive investigation, the electrophysiology community has thus far failed to identify supplementary ablation techniques that yield additional benefit in persistent AF.Three major areas of development in persistent AF ablation are discussed in this article: improved patient selection for CA, better identification of arrhythmic substrate and empiric ablation strategies/ lesion sets that may offer superior outcomes.Patient factors such as comorbidity burden, body mass index, duration of AF and presence of structural cardiac disease all affect ablation outcome.In the absence of an effective 'universal' ablation strategy in persistent AF, selection of good candidates based on these factors (possibly with risk scores such as FLAME) is an indispensable step.Multiple methods have been trialled to identify arrhythmic substrate within the left atrium (LA) that may be targeted during CA.MRI-identified LA fibrosis does not represent targetable substrate; however, electrophysiologic mapping techniques (either voltage mapping or functional substrate mapping) are more promising, though still require scrutiny in large randomised trials.To the dismay of the electrophysiology community, the CAPLA trial recently showed posterior wall isolation (previously thought to be the most encouraging empiric strategy) does not confer benefit over PVI alone.No other strategy has convincingly demonstrated superiority to PVI alone, though hybrid epi-

Introduction
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, with a prevalence only expected to increase in an ageing population; especially given the rise of metabolic risk factors such as hypertension and obesity [1].It is a major cause of morbidity including ischaemic stroke and heart failure, and is associated with an increased risk of dementia and death [2].
Catheter ablation (CA) is the most effective rhythm control treatment for AF [1].Evidence is mounting for the prognostic benefit of rhythm control, particularly if initiated early [3].Furthermore, CA offers benefits in quality of life for patients with symptomatic AF [4].In heart failure with reduced ejection fraction, CA may lead to myocardial recovery, especially where impaired cardiac function is directly caused by tachyarrhythmia [5].
AF induces structural and electrical remodelling of the left atrium (LA) which conduce to its own maintenance-summarised as the well-known phrase 'AF begets AF' [1].In essence, patients progress from paroxysmal to persistent AF, and attempts to restore and maintain sinus rhythm become increasingly challenging.
The pulmonary veins have long been identified as the commonest site of AF triggers, and circumferential pulmonary vein isolation (PVI) is the primary technique in AF ablation.PVI is highly effective in paroxysmal AF [6]; however, success rates are considerably lower in persistent AF, partly due to the existence of non-pulmonary vein triggers [7].
This poses two major questions.Firstly, can we prospectively identify persistent AF patients who are more likely to benefit from CA? Secondly, can a better understanding of arrhythmic substrate improve ablation outcomes?A summary of the state of the field is presented in Fig. 1.

Cardiovascular comorbidities and atrial cardiomyopathy
Cardiovascular risk factors such as obesity, sleep apnoea and hypertension are known to play a role in the natural history of AF.In the last decade, their relationship to ablation outcomes has been scrutinised.The concept of atrial cardiomyopathy, with resultant dilatation and scarring, has become well established [8].This condition is caused by cardiovascular risk factors and sets up arrhythmic substrate to initiate and perpetuate AF.
A 2015 meta-analysis of 5864 patients estimated a 13% increased risk of AF recurrence following ablation for every 5 unit increase in body mass index, though it was limited by heterogeneity and variability in diagnostic monitoring in the included studies [9].Additionally, it did not stratify findings between paroxysmal and persistent AF.Two subsequent observational studies published in 2017 examined the effect of obesity on ablation outcomes Fig. 1 A framework for optimising success of catheter ablation for persistent atrial fibrillation.Epicardial ablation refers to hybrid and convergent approaches in particular.AF, atrial fibrillation; MRI, magnetic resonance imaging; PFA, pulsed field ablation; PV, pulmonary vein; VOM, vein of Marshall.
and separated their analyses based on duration of AF [10,11].Interestingly, whilst both demonstrated poorer post-ablation outcomes with obesity in paroxysmal AF, the effect was notably absent in persistent AF, suggesting that other factors might become more prominent once AF is more advanced, overshadowing the previous influence of obesity.Importantly, addressing obesity alters the progression of AF-the 2018 REVERSE-AF study found that 88% of overweight AF patients who lost ≥ 10% body weight regressed from persistent to paroxysmal AF [12].Since CA outcomes are demonstrably superior in the paroxysmal form, it is clearly desirable to address such lifestyle factors.
Obstructive sleep apnoea (OSA) accelerates structural and electrical atrial remodelling [13], and a 2022 randomised controlled trial (RCT) of 24 patients showed that this remodelling is reversible following treatment with continuous positive airway pressure (CPAP) therapy [14].Consistent with this, Zhou et al. demonstrated that patients with OSA treated with CPAP have comparable outcomes following CA to patients without OSA [15], similar to findings reported previously in a 2014 meta-analysis [16].Data on the impact of OSA/CPAP on ablation outcomes in persistent and longstanding persistent AF are so far limited.
Hypertension is the most common associated comorbidity with AF and is a risk factor for complications such as ischaemic stroke [17].Animal studies demonstrate progression of arrhythmic left atrial substrate with uncontrolled blood pressure (BP) [18,19].It is therefore unsurprising that poorly controlled hypertension predicts recurrence of AF following CA, and this is effect is attenuated with pharmacologic control of blood pressure [20,21].
In summary, patients with untreated cardiovascular comorbidities are more likely to experience arrhythmia recurrence following ablation of AF.Treating these risk factors-which forms the 'C' component of the AF 'ABC' pathway [17]-may improve ablation success rates.In choosing our target population for CA of persistent AF, it therefore stands to reason that those with fewer comorbidities-or with the motivation to address lifestyle factors-are likely to have better outcomes.

Risk scores
To simplify the identification of suitable target populations for ablation of persistent AF, investigators have sought to develop risk scores.Previously described scores include ALARMec [22] and MB-LATER [23], both of which predict very late recurrence (beyond 12 months post-CA) with moderate success.ALARMec studied only patients following repeated ablation procedures, whereas MB-LATER included a mix of first and repeated CA; both studies covered paroxysmal and persistent AF.
More recently, a 2021 collaboration between UK and USA researchers introduced the FLAME score, which is specific to the persistent AF cohort [24•].FLAME is a weighted composite of female sex, longstanding persistent AF (> 1 year), left atrial diameter, mild-moderate mitral regurgitation and 'extreme comorbidity' (severe structural heart disease).The scoring system was created following multivariable logistic regression of data from 416 ablation procedures performed for non-paroxysmal AF, followed by prospective testing on 882 patients.In this cohort, a low score (0-1) predicted 62% success (freedom from AF recurrence at median follow-up 1.8 years) after a single procedure and 81% success after multiple (median 1.4) procedures.Limitations included a follow-up duration of less than 2 years, affecting usefulness for longer term prediction, although the Kaplan-Meier curves seemed to plateau later in the study's follow-up period with the majority of the AF recurrence occurring within the first year.Secondly, lesion sets varied widely between operators.Nonetheless, this is a potentially useful tool for identifying persistent AF patients likely to benefit from CA.

Electrophysiologic predictors
In addition to baseline characteristics and comorbidities, investigators in the last decade have turned to features of the surface electrocardiogram (ECG) or invasive electrograms to predict persistent AF ablation outcomes.Analysis of fibrillatory waves (f-waves) has shown promise for this purpose.Previously, investigators correlated manual measurement of AF cycle length (AFCL), defined as the interval time between f-waves; or f-wave amplitude with CA outcomes [25,26].They hypothesised that a shorter AFCL or lower f-wave amplitude reflected greater electrical disorganisation within the LA, suggesting more advanced remodelling and lower likelihood of achieving durable rhythm control.
Similarly, intraprocedural measurement of AFCL or its inverse, the dominant frequency (DF) from invasive electrograms predict AF termination during ablation [27] and a reduction in DFs as an ablation endpoint has shown relevance to long term freedom from AF [28].Recent developments in this area have attempted to circumvent the limitations of subjective manual measurement.Alcaraz et al. 2016 [29] and Escribano et al. 2022 [30] assessed similar indices but with the aid of computerised analysis.The latter attempted a more complete analysis of the spectral waveform of f-wave frequencies, and identified a mathematical index that predicts AF recurrence in this dataset with approximately 70% accuracy.
The processes involved in these trials are currently too abstract for widespread clinical application and should be considered hypothesis generating.Nonetheless, they demonstrate that there is value to be gained from electrophysiologic indices and this space is primed for further advancement, likely with the help of machine learning algorithms.
There are presently no published approaches for combining electrophysiologic predictors with clinical indices.Composite risk prediction models may offer improved predictive power in this challenging field of study.

Defining the target substrate-mapping techniques
Structural and electrical remodelling of the LA is well known to play a role in AF maintenance [31].Decreased conduction velocities lead to the formation of micro-and macro-reentrant circuits [32,33] and investigators have searched for means of identifying these regions of arrhythmogenic myocardium.The most studied approaches include magnetic resonance imaging (MRI) detection of left atrial fibrosis, and identification of either low-voltage areas (LVAs) or functional substrate via electroanatomic mapping.

MRI assessment of left atrial fibrosis
Delayed enhancement MRI protocols can identify left atrial fibrosis, the extent of which functions as a predictor of AF recurrence after CA.DECAAF, a prospective observational cohort study of 329 patients, demonstrated 6% increased risk of arrhythmia recurrence per 1% increase in atrial fibrosis on MRI, hypothesising that these areas may represent targetable substrate for CA [34].
In the follow-up RCT, DECAAF-II, 843 patients were randomised to either PVI + MRI guided fibrosis ablation or PVI-alone [35•].No difference between groups was observed in terms of freedom from AF at 1 year (57% vs 53.9%, p = 0.63); however, an increase in complications was observed in the fibrosisguided ablation group (2.2% vs 0%, p = 0.001).
In summary, although MRI-detected atrial fibrosis may increase the risk of AF recurrence following CA, targeted ablation of these areas does not appear to improve outcomes.

Low-voltage myocardium
Electroanatomic mapping (EAM) can identify regions of atrial myocardium with low voltage; a surrogate of fibrosis.Numerous studies-the majority small and non-randomised-have assessed whether ablating low voltage areas (LVAs) improves outcomes.Within the published literature, there is uncertainty regarding the optimal voltage cut-offs in the LA: the majority of published studies used a threshold of < 0.5 mV; however, thresholds of < 0.1 mV and < 1.0 mV have been proposed.There is an inevitable trade-off of sensitivity with specificity when selecting appropriate thresholds, and higher values may implicate > 25% of LA area; such extensive ablation may increase risk of complications including formation of new macro-reentrant circuits [36].
VOLCANO, the first RCT on this subject, found no benefit in patients who had experienced paroxysmal AF recurrence after PVI [37].More recently, ERASE-AF randomised 324 patients with persistent AF to PVI + LVA ablation or PVI-alone, demonstrating superiority of additional LVA ablation (hazard ratio 0.62, p = 0.006), whereas patients with LVA identified who underwent PVI-alone had the highest recurrence rates [38].There was, however, a trend towards increased complications in the LVA ablation group.Additionally, only around a third of patients in the intervention arm actually had LVAs to ablate; hence, two-thirds underwent PVI-alone.Further research will be required-in particular, a trial randomising patient after EAM and only including those with identifiable LVA would help to avoid such confounding.

Functional substrate identification
A more sophisticated use of EAM is the detailed examination of LA electrical activation patterns to individualise CA.Multiple such approaches have been trialled in the last decade.Earliest described was the FIRM mapping system (Focal Impulse and Rotor Modulation) which was initially purported to identify stable sources in 96% of patients [39]; however, subsequent studies revealed that FIRM-identified rotors were not spatially stable and their ablation only terminated AF in a minority (17%) [40].
The ECGi system is another novel approach that utilises non-invasive electrical data (via a wearable vest with 252 electrodes) merged with CT images to create a bi-atrial electroanatomic map.Despite encouraging CA outcomes in non-randomised studies [41], RCTs are yet to be performed and the impracticalities of the technology may affect real-word implementation.
CARTOFINDER, a module of the established CARTO mapping software, is designed to identify drivers of AF via areas of focal and rotational activation within the LA body.Ablation at these sites led to either AF termination or significant cycle length slowing in one proof-of-concept study [42].A recent trial of CARTOFINDER-guided ablation showed superior outcomes versus a 'conventional method' (PVI and non-PV trigger ablation) [43].However, procedural times in the CARTOFINDER group were, on average, 70 min longer, which makes this tool impractical in the real world.
The only tool in current clinical use is the AcQMap System, a non-contact mapping catheter that combines dipole density mapping with anatomic data from intracardiac ultrasound; the system was recently prospectively investigated in RECOVER-AF [44].The authors described 3 critical patterns of wavefront propagation which were hypothesised to represent treatable substrate: focal firing, localised rotational activity (at least 270 degrees around a given point) and localised irregular activity (pivoting of a wavefront greater than 90 degrees around an isthmus).RECOVER-AF recruited patients with recurrent AF following CA and reported success rates of 67.0%, rising to 75.7% after further repeat procedures.The most striking results were found in the subgroup of patients with prior PVI but otherwise treatment-naïve left atria (83.0% and 91.5% 1-year freedom from AF after single and multiple procedures, respectively).Although these figures sound impressive in the persistent AF cohort, it should be remembered that all patients in RECOVER-AF had undergone at least one prior PVI procedure, and it is well known that repeated procedures improve arrhythmia freedom [45].
These technologies are yet to be subjected to large randomised clinical trials.

Defining the target substrate-ablation approaches
The cornerstone of AF ablation is PVI, whereby circumferential ablation margins are created around the pulmonary veins to electrically isolate them from the left atrial myocardium.PVI-alone is an effective strategy for paroxysmal AF-with reported single-procedure efficacy of up to 90%.However, outcomes in persistent AF are disappointing-meta-analyses quote success rates from 43to 66% [46].Further precision in estimating outcomes is challenging due to heterogeneity within the published literature of post-ablation monitoring and the definition of post-ablation success or failure.Most modern trials now use AF burden as an outcome measure rather than a binary measure of recurrence/no recurrence.This conduces to viewing CA success as a continuous variable but makes comparison to older trials more challenging.
Due to the suboptimal success rates of PVI in non-paroxysmal AF, proceduralists have trialled standardised lesion sets, though results have generally been disappointing, demonstrating no clear superiority over PVI-alone.A full breakdown of the numerous techniques is beyond the scope of this review.Instead, we summarise recent developments in 3 key areas: posterior wall isolation, hybrid and convergent ablation and vein of Marshall (VOM) ablation.This is followed by a discussion on recent advances in ablation modalities.

Posterior wall isolation
The left atrial posterior wall shares a common embryological origin with the pulmonary veins and many authors hypothesised that electrical isolation would be beneficial in persistent AF.The procedure comprises ablation lines along the left atrial floor and roof, connecting the two circumferential PVI lines.
Prior trials and meta-analyses have offered conflicting findings: some (mostly non-randomised) suggesting benefit above PVI-alone; others showing no difference [47].This was not helped by significant heterogeneity between such trials, especially differences in non-standardised trial ablation protocols (some including extra techniques such as mitral annular lines).Many electrophysiologists felt that posterior wall isolation (PWI) was promising and, according to a recent EHRA survey, was one of the most popular techniques in persistent AF.
However, encouragement has lately been stifled by the CAPLA trial -a multicentre, randomised clinical trial comparing PVI with PWI versus PVIalone [48•].The study included 338 patients with persistent AF (of less than 3 years duration) who were refractory to at least one AAD.In CAPLA, PWI offered no additional benefit to PVI (freedom from atrial arrhythmia 52.4% vs 53.6%, p = 0.98), but did increase procedural times (142 min vs 121 min, p = < 0.001).The authors concluded that PWI should not be offered empirically to patients with persistent AF.Given the increased risk of ablating on the posterior wall, which sits in close proximity to the oesophagus, many practitioners have abandoned this strategy, especially in first-time ablation.Whether PWI has a role in select patients, such as those undergoing redo ablation with silent PVs remains uncertain.
At present, it remains unclear if the negative result of CAPLA is due to disconnection of the posterior wall itself being ineffective or-as many believethat true PWI may not be feasible from a purely endocardial RFA approach.

Hybrid and convergent approaches
Both hybrid and convergent ablations involve the combination of thoracoscopic epicardial ablation with catheter-based endocardial ablation.The difference lies in the timing: in hybrid approaches the patient undergoes each procedure separately (usually thoracoscopic followed by catheter ablation).Convergent ablation involves a single combined procedure by thoracic surgeon and electrophysiologist.
The first major trial in this area was CONVERGE, which randomised 153 patients to convergent ablation vs catheter ablation in a 2:1 ratio [49], finding additional benefit to a convergent approach (efficacy 67.7% vs 50.0% at 12 months, p = 0.036).A more recently published subgroup analysis examined longstanding persistent AF patients (duration > 1 year), which encompassed 65/153 patients from the original cohort [50].This analysis showed a 65.8% effectiveness of convergent arm vs 37.0% in the catheter arm at 1 year (p = 0.022), and this superiority was maintained at 18-month follow-up (60.5% vs 25.9%, p = 0.006).Though these differences are impressive, and imply that epicardial triggers are important in persistent AF recurrence it is critical to remember that epicardial access poses a higher risk of complications.Additionally, although the convergent approach improved outcomes, the intervention groups still had less than 70% procedural success, which remains disappointing.
HARTCAP-AF, a small randomised study of 41 persistent AF patients, compared convergent ablation (named hybrid in the study but completed in a single procedure) versus PVI + PWI + / − cavotricuspid isthmus (CTI) ablation [51].At 12 months, outcomes were superior in the hybrid ablation (HA group) (freedom from atrial arrhythmia 89% vs 41%).The trial included patients with significant left atrial dilatation (LA diameter up to 6 cm) and longstanding persistent AF.The study was limited by difference between cohorts at baseline: the CA group had longer AF duration than the HA group (33 vs 22 months); additionally, only 12% of the recruited patients were female, which may limit generalisability to clinical practice.
Overall, the advantage of hybrid and convergent ablation may lie in the ability to properly address epicardial connections which cannot easily be addressed with an endocardial catheter alone.Whether this advantage will still hold true in the era of pulsed field ablation remains to be seen.

Vein of marshall ethanol ablation and associated strategies
Injection of ethanol into the VOM has emerged as an additional substrate modification technique.This functions on the premise that the Marshall Bundle, an anatomic structure containing the VOM plus neuromuscular and connective tissues, is a key source of non-pulmonary vein triggers in persistent AF, and its elimination aids in establishing mitral isthmus conduction block.A recent meta-analysis revealed a superiority of RFA + VOM ablation vs RFA alone in persistent AF patients (RR of arrhythmia recurrence 0.58, 95% CI 0.35-0.96,p = 0.04), though this was subject to significant heterogeneity.VOM ablation also increased the likelihood of bidirectional mitral isthmus block (RR 1.5, 95% CI 1.34 − 1.67, p < 0.001), which may be helpful in treated atypical flutter circuits sometimes seen after unsuccessful CA in advanced AF [52].
An innovative multifaceted ablation strategy named the Marshall Plan has recently been trialled by investigators in Bordeaux, France.The strategy includes PVI, linear ablations to the left atrial dome, mitral isthmus and cavotricuspid isthmus; and ethanol ablation to the VOM.Preliminary results (10 of the planned 12 months follow-up have been completed) were presented at the EHRA congress in April 2023; the authors enrolled 120 patients with persistent AF and randomised to the Marshall Plan or PVI-alone.Following an intention-to-treat analysis, they reported 84% freedom from AF at 10 months for patients treated with the comprehensive strategy, versus 69% for the PVI group.The earlier feasibility study by the same group reported 79% freedom from atrial arrhythmia after a single procedure and 89% after up to 2 procedures [53].These are amongst the most impressive outcomes reported in persistent AF trials; however, they come at the expense of longer procedural times and possibly higher procedural risk.
A recognised disadvantage for VOM ablation is the steep operator learning curve, with the potential inability to catheterise the VOM.This leads to cross-over during trials and may render VOM ablation impossible for some patients in real-world practice.

Ablation modalities
Radiofrequency ablation (RFA) and cryoballoon (CB) are well established ablation modalities which produce similar clinical outcomes [54,55].RFA carries the advantage of allowing wider ablation margins and additional ablation of non-PV triggers, whilst CB is a less technically challenging approach which is considered easier to learn.The potential to cause thermal damage to surrounding structures is a drawback of both approaches.The resulting disadvantages are twofold: firstly, ablation may result in serious complications, such as oesophageal or phrenic nerve injury.Secondly, the existence of these complications may dissuade operators from delivering enough energy to achieve durable conduction block.
First in-human trials of a novel modality, Pulsed Field Ablation (PFA), were reported in 2019 [56].This technology generates brief electrical fields to induce 'electroporation' (creation of pores in the cell membrane) and subsequent cell death.Animal data show this process is far more specific to cardiomyocytes than RFA and CB [57,58] and indeed subsequent clinical trials have proven safety in terms of oesophageal and phrenic nerve injury [56,59].This becomes more important when ablating on the left atrial posterior wall (LAPW), given the proximity of the oesophagus.One drawback of PFA is that patients tend to require general anaesthesia (GA) due to discomfort caused by skeletal muscle contraction secondary to the electrical field.
Applicability of PFA to persistent AF has been recently investigated: PersA-FOne was a single-arm feasibility study to assess safety and durable efficacy of the Farapulse PFA catheter when applied to PVI and LAPW isolation [60].
Twenty-five patients were enrolled and underwent an index ablation procedure (PVI + LAPW isolation + / − CTI), followed by repeated electroanatomic mapping 75 days later.At repeat mapping, 96% of pulmonary veins, and 100% of LAPWs remained isolated.There were no acute or delayed catheter related complications reported; 21/25 patients underwent oesophagogastroduodenoscopy (OGD) without any oesophageal injury detected; and repeat cardiac computed tomography did not reveal any PV narrowing or other complications.
There are some noteworthy caveats to the above: firstly, the chosen outcome measure of LAPW isolation of entrance block, but not exit block, is debatable and hence the effectiveness may have been overstated.Secondly, as Tomlinson et al. raise in their editorial [61], there are concerns about cerebral microembolisation with PFA (intra-cardiac echocardiography has observed ultrasound microbubble formation during PFA) [60] with the suggestion that cerebral magnetic resonance imaging (MRI) screening should become a standard part of safety assessment in future trials.Despite such concerns, studies which have assessed the neurological safety of PFA have yet to report significant adverse outcomes [62].
PULSED-AF was a non-randomised, single-arm trial of PFA including 150 paroxysmal and 150 persistent AF patients refractory to AADs [63].This trial again demonstrated excellent safety outcomes-with an adverse event rate of 0.7%, underlining the strength of PFA.Efficacy outcomes at 1 year were, however, less encouraging: 66.2% of the paroxysmal AF cohort and 55.1% of the persistent AF cohort were free of atrial arrhythmia.These data are comparable to other forms of PVI and remind us that if PFA is to bring significant advancements in the persistent AF field, it may be through other means; possibly through facilitating appropriate ablation of relevant non-PV triggers, improving procedural times and minimising complications.Equally, PFA is a new technology with several novel catheters in development, so outcomes may improve as research improves upon existing systems.

Conclusion
In the face of mounting evidence of superiority of rhythm control in AF care, the challenge of achieving this in patients with persistent and longstanding persistent AF becomes more salient.Investigators have so far struggled to identify ablation techniques or substrate targets that confer additional benefit over PVI-alone, for which outcomes in persistent AF are unimpressive.
Prospective identification of patient cohorts more likely to benefit from catheter ablation is one method of rebalancing the scales.Risk scores, such as FLAME, can potentially identify patients who stand to derive most benefit.Similarly, analysis of electrocardiographic data may shed light on the degree of atrial remodelling, and hence the chance of a positive ablation outcome.Addressing cardiovascular risk factors both before and after ablation is likely to aid in reverse remodelling of left atrial cardiomyopathy and improve longterm outcomes in those patients who can sustain such measures.
There must be a simultaneous focus on improving ablation techniques, both to raise success rates and minimise adverse outcomes.This is a fastmoving field, and developments in recent years are perhaps more encouraging than in the previous two decades.Hybrid approaches currently boast the most promising efficacy data, though further research including meta-analysis is required.
PFA is the newest modality available.Early data suggest impressive safety outcomes and procedural times, but potentially less impressive efficacy.Further study and development of novel PFA delivery systems will hopefully provide encouraging results in coming years.

Compliance with Ethical Standards
Competing Interests Michael Griffin declares that he has no conflict of interest.Peter Calvert declares that he has no conflict of interest Dhiraj Gupta is the speaker for Boehringer Ingelheim, Biosense Webster and Boston Scientific; the proctor for Abbott and has received research grants from Medtronic, Biosense Webster and Boston Scientific.

Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.

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