Pulsed field ablation with the pentaspline catheter compared with cryoablation for the treatment of paroxysmal atrial fibrillation in the UK NHS: a cost-comparison analysis

Abstract

Objectives

Pulsed field ablation (PFA) is a promising new ablation modality for the treatment of atrial fibrillation (AF) that has recently become available in the UK National Health Service (NHS). We provide the first known economic evaluation of the technology.

Methods

A cost-comparison model was developed to compare the expected 12-month costs of treating AF using the pentaspline PFA catheter compared with cryoablation for a single hypothetical patient. Model parameters were based on a recent cost-effectiveness analysis by the National Institute for Health and Care Excellence where possible or published literature otherwise. Deterministic sensitivity, scenario and threshold analyses were conducted.

Results

Costs for a single patient treated with PFA were −3% (−£343) less over 12 months than those who received treatment with cryoablation. PFA was associated with 16% higher catheter costs but repeat ablation costs were over 50% less, driven by a reduction in repeat ablations required. Costs of managing complications were −£211 less in total for PFA compared with cryoablation.

Conclusions

Routine adoption of PFA with the pentaspline PFA catheter looks to be as affordable for the NHS as current treatment alternative cryoablation.

Correspondence to Claire Duxbury; [email protected]

STRENGTHS AND LIMITATIONS OF THIS STUDY

• The modelling approach here is analogous to that used by National Institute for Health and Care Excellence to capture short-term outcomes as part of a recent ablation cost-effectiveness analysis, with costs and comparator clinical inputs also taken from this assessment.

• Pulsed field ablation (PFA) clinical parameters were taken from multiple single-site experiences of the pentaspline PFA catheter with limited patient numbers and follow-up duration.

• This analysis relies on clinical and cost data specific to a single PFA system, with results not generalisable to other systems.

• The uncertainty surrounding PFA data was evaluated through sensitivity, scenario and threshold analyses.

Introduction

Atrial fibrillation (AF) is a common cardiac arrhythmia affecting around 1.3 million individuals in England.¹ It poses a significant burden to patients, physicians and the National Health Service (NHS)—increasing the risk of stroke, heart failure, dementia and death, and contributing to between 0.9% and 1.6% of NHS expenditure.^2–5

Left atrial ablation is a recommended treatment for patients with symptomatic paroxysmal or persistent AF where drug treatment is unsuccessful, unsuitable or not tolerated.⁶ The procedure involves delivering ablation therapy to the left atrium—with the pulmonary veins being the main target therein—to disrupt the transmission of abnormal electrical impulses causing AF.⁷ Thermal energy, such as radiofrequency ablation or cryoablation, is conventionally used for this type of ablation. Ablation with thermal energy is known to ablate all tissue types indiscriminately, with potential risks to adjacent structures such as the oesophagus or phrenic nerve, or a risk of pulmonary vein stenosis.^{3 5}

Pulsed field ablation (PFA) is a promising new ablation modality that has recently become available in the NHS. The technology relies on an electric field generated by electrical pulses in an optimally configured waveform. This electric field is designed to preferentially target the myocardium (muscular tissue of the heart), destabilising myocardial cell membranes and causing cell death. This mechanism is known as irreversible electroporation. Non-thermal destruction of cells in this manner blocks the transmission of the abnormal signals causing AF while sparing collateral tissue often damaged by traditional thermal energy sources.^{8 9} Early clinical data have found the technology to be safe and efficacious^{8 10–15} — however, to date, there have been no studies evaluating the potential cost implications to the NHS of providing this treatment to patients. Here we perform the first known economic evaluation of the pentaspline PFA catheter, assessing the affordability of adopting this new technology in the UK NHS compared with a well-established alternative.

Methods

A cost-comparison analysis was undertaken to estimate the expected costs of treating AF using the pentaspline PFA ablation system (Farapulse, Boston Scientific, Marlborough, Massachusetts, USA; the intervention) compared with cryoablation (the comparator) from a UK NHS perspective. Unlike PFA with the pentaspline catheter or cryoablation, conventional radiofrequency ablation is not considered a ‘single-shot’ ablation technique as it requires the use of three-dimensional electroanatomical mapping systems and is recognised to need a different skill set.¹⁶ As such, it has not been included as a comparator here. The population considered in the model are patients eligible for pulmonary vein isolation for the treatment of paroxysmal AF, in line with the currently approved indication for the Farapulse pentaspline PFA catheter.¹⁷ The analysis reflects a single hypothetical patient with paroxysmal AF in whom drug treatment has been unsuccessful, unsuitable or not tolerated, as per current National Institute for Health and Care Excellence (NICE) guidelines,⁶ and who has not previously been treated with any form of left atrial ablation therapy.

Model structure

A decision tree structure (figure 1) was used to capture the 12-month period from when this patient underwent initial ablation—either with the intervention or comparator treatment—and establish whether the treatment successfully alleviated AF symptoms.

Figure 1. Decision tree for patients with symptomatic paroxysmal AF undergoing a de novo ablation procedure. The first decision node represents the choice to use a particular ablation modality for the initial procedure—that is, whether to use cryoablation or PFA with the pentaspline catheter. The decision tree also depicts two types of chance node. The first reflects the likelihood of suffering complications as a result of an ablation procedure (either de novo or repeat) and the second reflects the likelihood of AF recurring within 12 months of the de novo ablation procedure. The second decision node depicts the choice of performing a repeat ablation procedure using RF ablation should AF have recurred after the de novo procedure.

For the de novo procedure, a single decision node represents the choice to treat the patient with either the intervention, PFA or the comparator, cryoablation. Complications and AF symptom recurrence were captured for both arms, with a proportion of those with recurring symptoms being retreated using radiofrequency ablation. This is consistent with usual clinical practice in the NHS and aligns with the modelling approach taken by NICE for their recent left atrial ablation cost-effectiveness analysis.¹⁸ Complication rates are also captured for repeat procedures. Costs were assigned to all events and outcomes, with total costs for a patient treated with PFA and a patient treated cryoablation compared.

The decision to limit the analysis to 12 months was twofold: per NICE’s modelling assumptions,¹⁸ the expectation is that differential outcomes for AF recurrence or complications would only apply in the first year; furthermore, the neoteric nature of PFA for AF ablation has not yet yielded published results on clinical follow-up beyond a year. Mortality outcomes were excluded from this analysis because of a lack of clinical data to determine whether these would vary by type of ablation; the assumption therefore is that they would not differ.

All modelling was performed by using Microsoft Excel for Microsoft 365 (V.2208; Microsoft, Washington, USA).

Clinical parameters

Clinical events occurring as part of the decision tree structure above include a de novo procedure with the intervention or comparator; repeat procedures and complications or adverse events resulting from a procedure. The estimated rate of repeat procedures was calculated from an annual rate of recurrence of AF—which varies by ablation modality used for the de novo procedure—and the estimated proportion of such patients who would be offered a repeat procedure.

As detailed above, this analysis was modelled on a single patient with an event rate of 1 for de novo procedures. All other clinical events deemed relevant to ablation procedures—in line with those included in NICE’s recent ablation cost-effectiveness analysis¹⁸—were assigned event rates, as shown in table 1. All event rates for cryoablation (the comparator) and radiofrequency ablation (used for repeat procedures) were taken from NICE’s cost-effectiveness analysis.¹⁸ Except for the proportion of patients receiving a repeat ablation if AF recurred (which was based on expert advice), all other parameters reported by NICE were based on a network meta-analysis conducted to inform their modelling. While some of the clinical event rates are at variance with more contemporary real-world reports,¹⁹ given the robust nature of NICE’s analysis, and its relevance for this analysis, alternative data sources were not considered.

Table 1

Clinical input parameters

Model parameter	Ablation modality			Source
	Radiofrequency*	Cryoablation	PFA†
AF recurrence
Annual rate of recurrence, of which	n/a	0.320	0.154	10 18
Proportion receiving repeat ablation	n/a	0.800	0.800	18
Complication event rates
Oesophageal injury	0.005	0.005	0.000	10 18
Pulmonary vein stenosis	0.010	0.010	0.000	10 18
Persistent phrenic nerve palsy	0.000	0.010	0.000	10 18
Cardiac tamponade	0.010	0.004	0.004	18
Severe vascular complications	0.020	0.020	0.020	18
Stroke	0.007	0.007	0.007	18
Other severe complications	0.010	0.010	0.010	18

*Used only for repeat ablation outcomes.

†All data based on procedures using pentaspline PFA catheter.

AF, atrial fibrillation; n/a, not applicable; PFA, pulsed field ablation.

The AF recurrence rate for PFA was taken from the optimised biphasic energy PFA waveform cohort from Reddy et al.¹⁰ Consistent with the approach used for cryoablation, this study reported 1-year recurrence rates for AF only (excluding other commonly reported recurring arrhythmias such as atrial flutter or atrial tachycardia) and included both symptomatic and asymptomatic occurrences. Complication rates for oesophageal injury, pulmonary vein stenosis and persistent phrenic nerve palsy for the pentaspline PFA catheter (deemed energy-related complications associated with tissue specificity, consistent with prior preclinical and clinical studies¹¹) were also taken from this study. All other complication event rates were assumed to be the same as for cryoablation; these complications are more likely attributable to the procedural approach rather than the type of energy being used and are not expected to differ considerably between the two arms. The estimated proportion of patients presenting with a recurrence of AF who receive a repeat ablation is also assumed to be the same as for cryoablation.

Cost parameters

Cost estimates were assigned to each clinical event, including complications and ablation procedures (table 2). The latter incorporated both a procedure cost plus an ablation catheter cost to reflect the additional pass through cost the NHS is liable to pay for these devices. Complication costs were assumed to be the same across all ablation modalities.

Table 2

Cost input parameters

Model parameter	Ablation modality			Source
	Radiofrequency*	Cryoablation	PFA†
Ablation costs
Procedure	4371	4371	4371	18 20
Ablation catheter	3742	6005	6950	18 20 24
Complication costs
Oesophageal injury	26 261	26 261	26 261	18 20
Pulmonary vein stenosis	2835	2835	2835	18 20
Persistent phrenic nerve palsy	258	258	258	18 20
Cardiac tamponade	2126	2126	2126	18 20
Severe vascular complications	1418	1418	1418	18 20
Stroke	20 594	20 594	20 594	18 20
Other severe complications	1418	1418	1418	18 20

All costs reported in 2021/22 GBP to the nearest pound. Procedure and complication costs assumed to be the same across all ablation modalities.

*Used only for repeat ablation costs.

†All data are based on pentaspline PFA catheter.

PFA, pulsed field ablation.

Considering the atypical impact of the COVID-19 pandemic on recent National Cost Collection data for the NHS, we relied predominantly on costs published as part of the NICE ablation cost-effectiveness analysis¹⁸ and inflated them to 2021/22 values using the NHS Cost Inflation Index for pay and prices.²⁰ Full details of the source input values used can be found in online supplemental table S1. A list price for the pentaspline PFA catheter was provided by the manufacturer for inclusion in the analysis.

Characterising uncertainty

A one-way deterministic sensitivity analysis was conducted to evaluate the impact of varying model parameters, with each individually adjusted by ±20% and the effect on the resulting difference in total cost between PFA and cryoablation observed. Full details of the high and low input parameters used for this sensitivity analysis can be found in online supplemental table S2.

Scenario analyses were also carried out to assess the impact of using alternative clinical data for selected model parameters. In scenarios 1–3, alternative values for the annual rate of recurrence of AF for patients treated with PFA of 9.6%, 18.4% and 20% were taken from the literature.^{12 14 15} These encompass other published data on the 12-month recurrence rate for PFA to date, and while their methodology does not fully align with that of the cryoablation rates (most notably they incorporate the recurrence of other atrial arrhythmias besides AF), they are still appropriate alternatives to consider. In the fourth scenario, alternative values for complication event rates for PFA were taken from the literature.¹¹ Further details of the values used for the scenario analyses can be found in online supplemental table S3.

On completion of the above analyses, we then chose to pursue further research exploring the threshold for the pentaspline PFA catheter AF recurrence rate, at which ablation with this catheter would become cost neutral versus cryoablation. The limited published evidence on this parameter (itself a reflection of the novel nature of the technology) gives rise to uncertainty in the values used in the base case and scenario analysis. An understanding of the threshold for cost neutrality was considered a useful addition.

Patient and public involvement

No patients were involved in this study.

Results

Base case analysis

At 12 months, the total average cost per patient for those undergoing PFA was −3% (−£343) less than those who received treatment with cryoablation (table 3). De novo ablation with the pentaspline PFA catheter was more costly than cryoablation, driven by 16% higher catheter costs. In contrast, repeat ablation costs for patients undergoing cryoablation were found to be more than twice those of PFA on average. The overall cost of managing complications was −£211 less in total for PFA compared with cryoablation, equating to an almost 50% cost reduction.

Table 3

Base case results

Cost component	Costs by modality
	Cryoablation	PFA*	Δ PFA*—cryoablation
De novo ablation, of which	10 733	11 516	+783
Catheter and accessories	6005	6950	+945
Procedure	4371	4371	–
Complications	357	195	−162
Repeat ablation, of which	2171	1045	−1126
Catheter and accessories	958	461	−497
Procedure	1119	538	−580
Complications	94	45	−49
Total	12 904	12 561	−343

All costs reported in 2021/22 GBP to the nearest pound.

*All data are based on procedures using pentaspline PFA catheter.

PFA, pulsed field ablation.

Deterministic sensitivity analysis

A tornado diagram has been used to illustrate the results of the one-way deterministic sensitivity analysis (figure 2). This analysis found that the model was most sensitive to catheter costs—both that of the pentaspline PFA catheter and of cryoablation. Lower cryoablation or higher PFA catheter costs both favoured cryoablation as the more cost saving option. Conversely, higher cryoablation or lower PFA catheter cost resulted in the opposite—with cryoablation becoming increasingly more costly than PFA. The only other parameter to which the model was sensitive enough to alter the base case finding—and consequently demonstrate a lower overall cost for cryoablation rather than PFA—was the AF recurrence rate for cryoablation. Cost savings for PFA persisted when all other parameters were varied: notably, a variation of ±20% in early reported data for complication event rates or AF recurrence rate for PFA did not affect the base case finding.

Figure 2. One-way deterministic sensitivity analysis tornado diagram. AF, atrial fibrillation; PFA, pulsed field ablation.

Scenario analyses

For the first three scenario analyses, where alternative data for AF recurrence following PFA were used to populate the model, PFA with the pentaspline catheter remained cost saving versus cryoablation—by −6% (—£737), –1% (–£140) and 0% (–£31) for scenarios 1, 2 and 3 respectively (table 4). Where alternative complication rates with PFA were used as inputs, the model also remained cost saving by −3% (–£434).

Table 4

Scenario analyses

Scenario	Total cost Δ PFA*—cryoablation
Base case	−343
Scenario 1: alternative PFA rate of AF recurrence	−737
Scenario 2: alternative PFA rate of AF recurrence	−140
Scenario 3: alternative PFA rate of AF recurrence	−31
Scenario 4: alternative PFA complication event rates	−434

All costs reported in 2021/22 GBP to the nearest pound.

*All data based on procedures using pentaspline PFA catheter.

AF, atrial fibrillation; PFA, pulsed field ablation.

Threshold analysis

Using the same decision tree structure as described in figure 1, we calculated the threshold value for the PFA rate of AF recurrence at which PFA would be cost neutral with cryoablation, if all other input parameters remained as per the base case. PFA was found to be cost saving when this parameter was at or less than 20.5%—that is, when only one in five or fewer patients had a recurrence of their AF 1 year after their initial ablation treatment with PFA. At a rate of 20.5%, both cryoablation and PFA costs after 12 months were £12 904. As in the base case, higher de novo ablation costs for PFA were offset by lower repeat ablation costs.

Discussion

We found that PFA with the pentaspline catheter was a less costly treatment option over 12 months compared with cryoablation. A higher upfront cost of the pentaspline PFA catheter was more than offset by lower costs across all components of repeat ablations: catheter and accessory costs, procedure costs and complication costs. This, in part, is due to a more durable treatment effect lessening the rate of recurrence of AF for patients undergoing PFA compared with cryoablation, hence requiring fewer repeat ablations.

The reliability of the results is particularly affected by catheter costs. The pentaspline PFA catheter costs are based on a UK list price provided by the manufacturer. While this is an acceptable approach for economic analyses,^{18 21} the comparator cryoablation costs taken from the NICE assessment are based on what is defined as ‘band 1’ prices from the NHS Supply Chain catalogue. These prices are likely a lower, non-commitment price and hence artificially deflate the costs of the comparator in this analysis, understating the cost savings that this PFA system may offer versus cryoablation. Future analyses may choose to explore the impact of more directly comparable, local catheter pricing.

The cost-comparison results are also sensitive to the AF recurrence rate for cryoablation. The base case value used in our analysis comes from a robust data source²² and hence is likely to represent a reasonable estimate of this parameter. This cryoablation data are themselves based on randomised controlled trials and hence are likely to encompass similarly well-selected patients as those from the early PFA studies.

Perhaps of greater relevance here is the uncertainty surrounding the PFA-specific parameters—namely the complication event rates and AF recurrence rate—which are based on less definitive studies. For the former, deterministic sensitivity and scenario analyses showed reasonable variation in complication event rates had little effect on the overall results.

The overall cost-comparison results were more sensitive to the AF recurrence rate than the complication event rates. While a variation of ±20% in the base case AF recurrence rate did not alter the cost-saving outcome for PFA, we conducted further analyses to test the uncertainty of this parameter. An alternative rate of AF recurrence following PFA based on Lemoine et al ¹² was found to be more cost saving than the base case (−3 percentage points vs base case cost impact). A further two scenarios using data from the MANIFEST-PF real-world registry (Turagam et al ¹⁴) and the EU-PORIA registry (Schmidt et al ¹⁵) continued to show PFA was not a cost-incurring alternative to cryoablation. The subsequent threshold analysis assessed the limit of cost neutrality for this parameter to allow an evaluation of the clinical plausibility of such a value. This identified a threshold of 20.5% for the AF recurrence rate following PFA, with rates less than this resulting in cost savings overall. While it is not unrealistic to expect rates in excess of this threshold in clinical practice (particularly given the influence of operator technique¹⁰ and patient selection⁵ in the durability of any ablation procedure), the limited available published evidence with 12-month follow-up to date has not surpassed this limit. Furthermore, the costs attributed to cases of recurrent AF in our model are a conservative estimate covering the procedure and complication costs only, in line with the initial decision tree. In clinical practice, we also see additional monitoring, extra acute admissions and additional prescribed medication for these patients, the inclusion of which would disfavour cryoablation. Thus, it seems reasonable to assume PFA is likely to remain broadly cost saving or cost neutral based on early experiences with the technology.

While procedure-related complications in catheter ablation of AF have reduced since its introduction, they are still known to occur.³ The favourable safety profile of the pentaspline PFA catheter reported in the literature^{10 12 13} here equated to cost savings of over £200 per patient in the management of complications across both de novo and repeat ablations. These findings highlight the economic benefits to the NHS of this new technology. While not quantified here, it is important to also appreciate the concomitant clinical benefits of lower rates of complications provided to the patient; serious adverse events that have a negative effect on quality of life for a considerable length of time¹⁸ can be reduced or avoided. Potential improvements in quality of life may also manifest from the lower rate of recurring AF, which is known to be associated with a disutility²³ and fewer subsequent avoidable hospitalisations due to repeat ablations. There are also broader implications for hospital resource utilisation of managing lower levels of both repeat ablations and serious adverse events, as well as the societal impact of absences from work and potential environmental ramifications. The potential for more efficient use of resources and a more positive effect on patients and society more broadly is a relevant area which ought to be explored in future clinical research.

Another area worthy of further exploration is the impact—both in terms of cost and resource use—from a provider perspective. The NHS payment system is such that from a healthcare system perspective (as is adopted here), the procedural costs reimbursed to providers—and hence the overall financial impact—are equivalent for all ablation modalities. Nevertheless, differences in anaesthetic approaches or procedural duration which exist will affect the microcostings of the two ablation types being compared and may make one more agreeable to an individual provider depending on their situation and workflow.

This analysis is the first economic evaluation of the pentaspline PFA catheter and relies on early clinical data reporting on the efficacy and safety of the technology. These data rely on reported observational experiences and an indirect comparison with more widely published data on cryoablation available at the time of this analysis. Prefatory analyses such as this are important to support NHS commissioners in prioritising new technologies at an early stage. Notwithstanding the preliminary nature of the data used, this analysis offers a valuable assessment of the likely incremental cost of this promising innovation vs current treatments, complimenting other published evidence that has predominantly focused on clinical effectiveness.^{8 10–15} The affordability of new products such as the pentaspline PFA catheter is a critical aspect for commissioners to understand when making decisions on what new innovations to adopt.

Strengths and limitations

This study relies in large part on clinical and some cost data specific to the pentaspline PFA catheter that are not generalisable to other PFA systems.^{8 10 24} Future analysis will need to be undertaken to assess the relevant cost impact of other such systems as they become available to the NHS. These early clinical data are taken from multiple single-site experiences of the technology with limited patient numbers and follow-up duration. As higher quality evidence from more contemporary studies and with a more comprehensive picture of effects over longer time horizons becomes available—including the availability of the quality of life and patient-reported outcomes—more thorough economic analyses would be of value. Analyses with different economic perspectives may also be of use (eg, to reflect the direct economic impact on a provider) as the technology becomes adopted more widely across the NHS as standard practice.

The similarity of the decision tree structure used here to that developed by NICE to capture short-term clinical outcomes and costs in a recent ablation cost-effectiveness analysis could be regarded as a strength, reflecting (at least for the initial short-term view) a reasonable economic assessment approach for a technology impacting NHS finances. Cost inputs are also taken from this NICE analysis and comparator clinical inputs were taken from the network meta-analysis conducted as part of the assessment. Uncertainty around those clinical inputs taken from other studies, as highlighted above, was evaluated through sensitivity, scenario and threshold analyses.

Conclusion

This original analysis suggests PFA with the pentaspline catheter is no more expensive than cryoablation for treating patients with paroxysmal AF in the UK NHS and may have other benefits to patients and the healthcare system. Higher upfront catheter costs are offset by savings elsewhere in the patient continuum, indicating that the routine adoption of PFA could be as affordable for the NHS as existing treatments.

The authors would like to acknowledge Caroline Jacobsen for supporting a critical review of the model and Emily Woodward and Elizabeth Albrecht for providing support in the development of the manuscript.

Data availability statement

All data relevant to the study are included in the article or uploaded as online supplemental information.

Ethics statements

Patient consent for publication

Not applicable.

Ethics approval

Not applicable.

Footnote

Contributors CD, contributing as part of employment at Boston Scientific, conceptualised and designed the study, conducted the analysis and was responsible for drafting and editing of the manuscript, and is considered guarantor. DB and PMH contributed to the interpretation of the data, critically reviewed the manuscript drafts and approved the final manuscript.

Funding This study was funded by Boston Scientific.

Competing interests CD is an employee of, and shareholder in, Boston Scientific. DB has received honoraria from Medtronic, Boston Scientific, Abbott Medical and Biosense Webster. PMH has received minor speaker honoraria from Boston Scientific and Medtronic.

Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

Provenance and peer review Not commissioned; externally peer reviewed.

Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

References

¹ NHS Digital. Quality and outcomes framework, 2021-22: prevalence, achievement and Personalised care adjustments at regional and national level. 2022. Available: https://digital.nhs.uk/data-and-information/publications/statistical/quality-and-outcomes-framework-achievement-prevalence-and-exceptions-data/2021-22

² NHS England. Clinical Commissioning Policy: Catheter ablation for paroxysmal and persistent atrial fibrillation (adults), 2022. Available: https://www.england.nhs.uk/wp-content/uploads/2022/12/1903-Clinical-Commissioning-Policy-Catheter-ablation-paroxysmal-persistent-atrial-fibrillation.pdf

³ Hindricks G, Potpara T, Dagres N, et al. ESC guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic surgery (EACTS): the task force for the diagnosis and management of atrial fibrillation of the European society of cardiology (ESC) developed with the special contribution of the European heart rhythm Association (EHRA) of the ESC. Eur Heart J 2021; 42: 373–498. doi:10.1093/eurheartj/ehaa612

⁴ Burdett P, Lip GYH. Atrial fibrillation in the UK: predicting costs of an emerging epidemic recognizing and forecasting the cost drivers of atrial fibrillation-related costs. Eur Heart J Qual Care Clin Outcomes 2022; 8: 187–94. doi:10.1093/ehjqcco/qcaa093

⁵ Calkins H, Hindricks G, Cappato R, et al. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation. Heart Rhythm 2017; 14: e275–444. doi:10.1016/j.hrthm.2017.05.012

⁶ National Institute of Health and Care Excellence. NICE guideline Ng196, atrial fibrillation: diagnosis and management. 2021. Available: https://www.nice.org.uk/guidance/ng196

⁷ Haïssaguerre M, Jaïs P, Shah DC, et al. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med 1998; 339: 659–66. doi:10.1056/NEJM199809033391003

⁸ Reddy VY, Neuzil P, Koruth JS, et al. Pulsed field ablation for pulmonary vein isolation in atrial fibrillation. J Am Coll Cardiol 2019; 74: 315–26. doi:10.1016/j.jacc.2019.04.021

⁹ García-Sánchez T, Amorós-Figueras G, Jorge E, et al. Parametric study of pulsed field ablation with Biphasic Waveforms in an in vivo heart model: the role of frequency. Circ Arrhythm Electrophysiol 2022; 15: e010992. doi:10.1161/CIRCEP.122.010992

¹⁰ Reddy VY, Dukkipati SR, Neuzil P, et al. Pulsed field ablation of Paroxysmal atrial fibrillation: 1-year outcomes of IMPULSE, PEFCAT, and PEFCAT II. JACC Clin Electrophysiol 2021; 7: 614–27. doi:10.1016/j.jacep.2021.02.014

¹¹ Ekanem E, Reddy VY, Schmidt B, et al. Multi-national survey on the methods, efficacy, and safety on the post-approval clinical use of pulsed field ablation (MANIFEST-PF). Europace 2022; 24: 1256–66. doi:10.1093/europace/euac050

¹² Lemoine MD, Fink T, Mencke C, et al. Pulsed-field ablation-based pulmonary vein isolation: acute safety, efficacy and short-term follow-up in a multi-center real world scenario. Clin Res Cardiol 2023; 112: 795–806. doi:10.1007/s00392-022-02091-2

¹³ Schmidt B, Bordignon S, Tohoku S, et al. 5S study: safe and simple single shot pulmonary vein isolation with pulsed field ablation using sedation. Circ Arrhythm Electrophysiol 2022; 15: e010817. doi:10.1161/CIRCEP.121.010817

¹⁴ Turagam MK, Neuzil P, Schmidt B, et al. Safety and effectiveness of pulsed field ablation to treat atrial fibrillation: one-year outcomes from the MANIFEST-PF Registry. Circulation 2023; 148: 35–46. doi:10.1161/CIRCULATIONAHA.123.064959

¹⁵ Schmidt B, Bordignon S, Neven K, et al. European real-world outcomes with pulsed field ablatiOn in patients with symptomatic atRIAl fibrillation: lessons from the multi-centre EU-PORIA Registry. Europace 2023; 25: euad185. doi:10.1093/europace/euad185

¹⁶ de Bono J, BHRS Council. British Heart Rhythm Society Standards for Interventional Electrophysiology Study and Catheter Ablation in Adults, April 2020, 2020. Available: https://bhrs.com/wp-content/uploads/2020/04/British-Heart-Rhythm-Society-Standards-Ablation-2020-1.pdf

¹⁷ Farapulse Inc. Farawave pulsed field ablation catheter: instructions for use. LBL 1067 Rev C (EU) EN FR DE CS. 2020.

¹⁸ National Institute of Health and Care Excellence. NICE guideline Ng196, atrial fibrillation: diagnosis and management, Appendix J3 cost-effectiveness analysis, April 2021. 2021. Available: https://www.nice.org.uk/guidance/ng196/evidence/j3-ablation-costeffectiveness-analysis-pdf-326949243734

¹⁹ Tilz RR, Schmidt V, Pürerfellner H, et al. A worldwide survey on incidence, management, and prognosis of Oesophageal Fistula formation following atrial fibrillation catheter ablation: the POTTER-AF study. Eur Heart J 2023; 44: 2458–69. doi:10.1093/eurheartj/ehad250

²⁰ Jones KC, Weatherly H, Birch S, et al. Unit costs of health and social care 2021. unit costs of health and social care. personal social services research unit, Kent, UK. 2021. Available: https://doi.org/10.22024/UniKent/01.02.100519

²¹ National Institute for Health and Care Excellence. NICE health technology evaluations: the manual, processes and methods, 31 January 2022. 2022. Available: https://www.nice.org.uk/process/pmg36/resources/nice-health-technology-evaluations-the-manual-pdf-72286779244741

²² National Institute of Health and Care Excellence. NICE guideline Ng196, atrial fibrillation: diagnosis and management, Appendix J2 ablation network meta-analysis, April 2021. 2021. Available: https://www.nice.org.uk/guidance/ng196/evidence/j2-ablation-network-metaanalysis-pdf-326949243733

²³ Berg J, Lindgren P, Nieuwlaat R, et al. Factors determining utility measured with the EQ-5D in patients with atrial fibrillation. Qual Life Res 2010; 19: 381–90. doi:10.1007/s11136-010-9591-y

²⁴ NHS Supply Chain catalogue. 2023.