Impact of Cryoballoon Ablation on Electrophysiology Lab Efficiency During the Treatment of Patients With Persistent Atrial Fibrillation: A Subanalysis of the STOP Persistent AF Study

Abstract

Background. The volume of atrial fibrillation (AF) catheter ablation procedures has increased to address the growing patient population with AF; however, the impact of cryoballoon ablation on electrophysiology (EP) lab throughput is under-studied when treating patients with persistent AF (PsAF). Objective. To assess EP lab utilization associated with cryoballoon ablation for the treatment of patients with PsAF and to evaluate mechanisms that optimize hospital resources. Methods. Procedural data derived from the STOP Persistent AF trial were input into a discrete event simulation to assess EP lab utilization during AF ablation procedures. Patient and physician delays and lab occupancy times were modeled in a nominal and efficient EP lab setting over 1000 days. Accounting for variation in procedural times, we evaluated the number of days in which preplanned pulmonary vein isolation (PVI) cases resulted in overtime or excess time for non-ablation EP cases within a given lab day. A sensitivity analysis determined the parameters that most strongly influenced EP lab throughput. Results. Lab occupancy times for the Nominal Use (NU) case included 165 procedures, and the High-Efficiency Use (HEU) case was derived from 69 procedures conducted at sites with faster procedure times than average. The HEU case had shorter lab occupancy times than the NU case (158 ± 32 minutes vs 188 ± 51 minutes, respectively). In the NU case, a total of 2000 procedures were conducted, with 28 lab days (2.8%) extending into overtime and 900 lab days (90%) exhibiting excess time for a non-ablation EP case. In the HEU case, a total of 3000 procedures were conducted, with 87 lab days (8.7%) extending into overtime and 635 lab days (63.5%) exhibiting excess time for a non-ablation EP case. The model was most sensitive to lab occupancy duration and the time of day that overtime started. Conclusions. Cryoballoon ablation for the treatment of patients with PsAF confers EP lab efficiencies that can support 3 PVI cases in a lab day.

Key words: catheter ablation, cryoballoon, pulmonary vein isolation

Reprinted with permission from J INVASIVE CARDIOL. 2021;33(7):E522-E530.

T

he incidence and prevalence of atrial fibrillation (AF) is growing along with an aging population.^1,2 Consequently, the volume of AF catheter ablation procedures is increasing to address the expanding AF population.³ Pulmonary vein isolation (PVI) via catheter ablation is the established treatment for patients with drug-refractory, symptomatic paroxysmal AF that has been demonstrated to be safe and effective in randomized trials and real-world clinical evidence.^4-7 Using a PVI strategy of ablation, the Arctic Front Advance cryoballoon catheter (Medtronic) recently was approved by the United States Food and Drug Administration as a safe and effective treatment for patients with drug-refractory persistent AF (PsAF), defined as episode duration <6 months.⁸

Historically, AF ablation procedures were relatively long and unpredictable in duration.^4,9,10 Also, AF ablation procedures require specialized expertise, facilities, and equipment. The growing AF population combined with the required specialty equipment necessitates intentional management of limited hospital resources. Since initial publications, which reported improved lab efficiencies with the use of the cryoballoon compared with point-by-point radiofrequency (RF) ablation catheters,^10,11 operator experience with cryoablation has grown and technological advancements in cryoablation have contributed to reduced PVI procedure times.^6,8 However, the impact of operator experience, technological advancement, and the expanded PsAF indication on electrophysiology (EP) lab efficiency is unknown. Thus, this analysis was designed to evaluate EP lab utilization afforded by the cryoablation system for the treatment of patients with PsAF and to assess mechanisms that improve lab throughput and optimize hospital resources.

Methods

Procedural measurements within STOP Persistent AF. The STOP Persistent AF clinical trial (NCT03012841) was a prospective, multicenter, single-arm study that evaluated the safety and efficacy of PVI achieved by cryoablation (Arctic Front Advance; Medtronic) in patients with drug-refractory (to class I or III antiarrhythmic drugs) PsAF, defined as episode duration <6 months.⁸ The cryoablation procedure has been previously described.^4-6,8 A transesophageal echocardiogram (TEE) was optional or required depending on patient rhythm and anticoagulation status and was allowed either on the day of or the day prior to the cryoablation procedure. The cryoballoon catheter was delivered into the left atrium with a FlexCath advance sheath (Medtronic) after trans-septal puncture. An interlumen guidewire or dedicated mapping catheter (Achieve; Medtronic) guided the cryoballoon to the antral surface of the PV, and the cryoablation was initiated. Cryoballoon dosing was physician determined. PVI touch-up by the Freezor catheter was allowed, and medically necessary focal ablation to create a cavo-tricuspid isthmus (CTI) line was permitted. Acute PVI could be tested with isoproterenol and/or adenosine. Total procedure time was defined as the time from the first venous access to the time of last sheath removal. Total lab occupancy time was defined as the elapsed time between the subject entering and leaving the EP lab.

Discrete event simulation model operation. A discrete event simulation model was used to evaluate EP lab utilization based on PVI ablation procedure lab occupancy times reported in the STOP Persistent AF trial. Discrete event simulations are designed to model the complexity of interactions among different entities in a real-world system and have been used to model the efficient use of resources in various healthcare settings.^12,13 These simulations are based on a stochastic time series of individual, granular events representative of realistic occurrences. Entities in a discrete event simulation (eg, people or critical resources) are treated distinctly from each other, having unique characteristics and memory, and are drawn from a detailed probabilistic characterization derived from real-world data and experience. SIMUL8 professional version 26.0 (SIMUL8 Corporation) was used for the discrete event simulation in this analysis.

The model used for this analysis has been previously described.¹¹ In brief, patients, physicians, support staff, and the EP lab were each explicit entities that independently influenced lab occupancy times for PVI procedures in the model, as they do in clinical practice. Physician and patient entities had the potential to cause delays in case start times, which were based on random delay values drawn from defined distributions (Table 1). A PVI procedure began in the discrete event simulation after patient and physician delays were accounted for (ie, all entities were simultaneously available), and its total duration was selected randomly from the probability distribution of lab occupancy times. After the lab occupancy completion time, all entities were released back into the model, and the process was repeated for all procedures preplanned for a given day according to either block or as-available room scheduling (Figure 1). This process was repeated over 1000 days to account for variation between days. The metrics collected from the discrete event simulation included the percentage of days in which the preplanned PVI procedures led to overtime or resulted in excess time for 1 or 2 additional non-ablation cases in the EP lab (eg, pacemaker implants, implantable cardioverter defibrillator replacements, etc).

Model inputs. Lab occupancy times were derived from the STOP Persistent AF clinical study and represented a weighted blend of PVI-only cases and those with right atrial flutter line ablation in addition to PVI. Two distinct simulations were created and compared: (1) the nominal use (NU) case represented a standard EP schedule designed to complete 2 PVI cases in a day; and (2) the high-efficiency use (HEU) case represented an enhanced schedule designed to complete 3 PVI cases in a day. The primary analysis for the NU and HEU cases was denoted as the base case analysis (Table 1). For both NU and HEU base case analyses, the first PVI case was scheduled for 7:30 am, and 60 and 150 minutes were required at the end of the day for 1 and 2 add-on, non-ablation cases in the EP lab, respectively.

Nominal use case. NU case lab occupancy times were derived from all procedures conducted in the STOP Persistent AF clinical study. Lab occupancy time associated with a procedure was modeled to start according to block schedule times. There was no attempt to start the second procedure earlier in the event the first procedure ended earlier than expected. The first case in the block schedule began at 7:30 am, and the second procedure began at 11:00 am in the NU base case. Operational delays based on qualitative research were assumed in the model, including: (1) room turnover time of 45 minutes; (2) patient delays between 0-15 minutes; and (3) physician delays between 0-60 minutes. Overtime pay for the EP lab staff was assumed to begin at 5:30 pm.

High-efficiency use case. HEU case lab occupancy times were derived from cases performed at a subset of STOP Persistent AF trial sites that met the following criteria: (1) had at least five procedures in the study; and (2) had a site-based average lab occupancy time shorter than the overall study average. The first PVI case was scheduled to begin at 7:30 am. Lab occupancy was modeled to start as soon as the lab and resources became available if a prior procedure and associated lab occupancy time ended early. Based on qualitative research, room turnover time was reduced to 30 minutes, and patient delays (0-10 minutes) and physician delays (0-15 minutes) were reduced as compared with the NU case. Overtime for the EP lab staff was assumed to begin at 6:00 pm (rather than 5:30 pm) to model EP labs that schedule staff for longer shifts fewer days per week or labs that use a split shift schedule (some staff start early in the morning and others come in later in the day) to enable slightly longer days. Model inputs are summarized in Table 1.

Model validation and sensitivity analysis. Lab occupancy times and case begin/end wall times (defined as the clock time of day when cases began or ended) from the STOP Persistent AF study were compared with the base-case simulated values to validate the model. In addition, a sensitivity analysis was performed on the NU and HEU cases by individually varying the separate time components (while keeping all other assumptions and inputs constant), including: (1) mean lab occupancy time; (2) room turnover time; and (3) lab shift end. The values of the variables used for this sensitivity analysis are given in Table 1. A value denoted as “high” is the high-end of the range for the variables, and “low” is numerically lower than the base case value based on ranges for each parameter ascertained through the methods described above. For the sensitivity analysis, low-efficiency lab occupancy times were derived from cases within STOP Persistent AF trial sites that met the following criteria: (1) had at least 5 procedures in the study and (2) had a site-based average lab occupancy time longer than the overall study average. As the discrete event simulation is stochastic in nature, a separate probabilistic sensitivity analysis was not performed.

Statistical analysis. Lab occupancy time variability was characterized using Gamma or Weibull distributions. The base simulation was run for 1000 lab days, which resulted in mean simulated lab occupancy times within 3% of the expected mean derived from the clinical trial with 95% confidence. Primary model outputs were reported as the percentage of days leading to overtime or time remaining for addition procedures. Lab occupancy wall time data were visually characterized to compare actual study data vs simulated data. All descriptive raw lab occupancy time data from the STOP Persistent AF study were reported as mean, 10th percentile, and 90th percentile.

Results

Lab occupancy time distributions. The lab occupancy time distribution for the NU case was derived from the full STOP Persistent AF dataset, including 165 procedures (115 PVI only, 50 PVI and flutter ablation) from 25 study sites. The lab occupancy time distribution for the HEU case was derived from 69 procedures (37 PVI only, 32 PVI and flutter ablation) from 7 of the 25 sites that matched 2 criteria: (1) performed at least 5 cases in the trial; and (2) had site average procedure times shorter than the overall study average. The clinical characteristics, treatment details, and clinical outcomes of these patients were previously published.⁷

Site-specific average lab occupancy times ranged from 117-297 minutes across the 25 trial sites (Figure 2A). Average lab occupancy times were 188 ± 51 minutes for the NU case and 158 ± 32 minutes for the HEU case (Figure 2B). The 10th percentile of lab occupancy times was 17 minutes shorter for HEU vs NU procedures (NU = 137 minutes; HEU = 120 minutes). The 90th percentile of lab occupancy times was 59 minutes shorter for HEU vs NU procedures (NU = 252 minutes; HEU = 193 minutes). Detailed procedure time distributions were fit to a one-sided gamma distribution (Supplemental Figure S1) as input to the discrete event simulation model.

Base case EP lab efficiencies. For the NU case, 2000 total PVI procedures were performed over 1000 days, with 28 lab days (2.8%) resulting in PVI case lab occupancy durations that extended into overtime. In total, 900 lab days (90%) had time remaining for 1 additional non-ablation EP case, and 587 lab days (58.7%) had time remaining for 2 additional non-ablation EP cases without requiring staff overtime. For the HEU case, 3000 total PVI procedures were performed over 1000 days, with 87 lab days (8.7%) resulting in PVI case lab occupancy times that extended into overtime; 635 lab days (63.5%) resulted in time remaining for 1 additional non-ablation EP case and 67 lab days (6.7%) resulted in time remaining for 2 additional non-ablation EP cases (Table 2).

Influence of operations on lab efficiency. Representative simulated case time distributions are included in Figure 3. Wall times for the beginning and end of lab occupancy were similar between study data and simulated cases (Supplemental Figure S2). Low-efficiency lab occupancy time (used only for this sensitivity analysis) was derived from 41 procedures (37 PVI only, 4 PVI and flutter ablation) and averaged 215 ± 42 minutes.

The results of the sensitivity analysis for the overtime days metric are shown in Figure 4, and the results for 1 and 2 add-on case metrics are shown in Supplemental Figure S3 (available online). The discrete event simulation model was most sensitive to changes in lab occupancy time distributions, followed by changes in the time of day both cases and overtime started. There was a higher incidence of overtime and fewer days with add-on procedures when lab occupancy times were longer, cases started later, and overtime started earlier in the day.

Discussion

To our knowledge, this is the first evaluation of the impact of cryoballoon ablation for the treatment of patients with PsAF on overall EP lab efficiencies. The data support the feasibility of moving from 2 to 3 PVI cryoablation cases within an EP lab day. Average cryoballoon PVI ablation lab occupancy times allowed 2 cryoablation procedures to be performed in a single EP lab without overtime on 97% of days, with 60% of days having enough time for 2 additional non-ablation EP procedures to be performed. HEU cases allowed 3 cryoballoon PVI procedures to be completed in a single EP lab without overtime >90% of days, with 60% of days having excess time after the third PVI case to complete a non-ablation procedure in the EP lab. Lab occupancy times and the length of the standard EP lab day had the greatest impact on overall EP lab efficiencies. The discrete event simulation data demonstrate that cryoballoon ablation procedures can optimize the utilization of the EP lab to meet the needs of a growing AF patient population.

Cryoablation procedural efficiency. The Value PVI study found that the PVI ablation procedure time for the treatment of patients with paroxysmal AF using the first-generation cryoballoon (Arctic Front) was 174 minutes compared with 200 minutes for PVI procedures completed with focal RF catheter ablation.¹⁰ Also, a study that modeled lab occupancy times derived from the FAST PVI study found that reduced average and variability of procedure times with the first-generation cryoballoon led to meaningful reductions in overtime and an opportunity to perform more procedures with fixed EP lab resources as compared with focal RF catheter ablation.¹¹ Increased operator experience combined with improved ablation technology has changed AF ablation procedure times since these initial reports.

Technological advancement in both ablation modalities (ie, Arctic Front Advance cryoballoon and contact-force sensing focal RF catheters) have contributed to shortened PVI ablation times. Indeed, the improved cooling mechanism of the cryoballoon resulted in more efficient transfer of energy, contributed to the adoption of shortened and tailored cryoballoon dosing paradigms, and resulted in enhanced procedural efficiencies.^14-16 Likewise, recent studies using contact-force RF have reported shorter procedure times.^17,18 This was illustrated by the recent CIRCA-DOSE trial, in which contact-force RF-PVI procedure duration was 165 minutes and cryoballoon ablation with 4-minute or 2-minute applications was 143 minutes and 131 minutes, respectively.¹⁹ Similar to observations in paroxysmal AF, the mean procedure time for the treatment of patients with PsAF was shorter with cryoablation (121 minutes) in the STOP Persistent AF trial compared with focal contact-force RF ablation (178 minutes) in the PRECEPT trial.^8,20 However, it must be acknowledged that the two aforementioned trials did have study design differences (eg, a PVI-only strategy of ablation was used in 55.5% of the PRECEPT study cohort). Overall, improved procedure efficiency afforded by a cryoballoon PVI approach may provide an EP lab resource efficiency advantage while maintaining similar safety and efficacy outcomes for patients with PsAF.^8,20

EP lab operational parameters. This report establishes for the first time that consistently performing 3 PVI cases per day using the cryoballoon ablation catheter is achievable in United States hospitals. The PVI cases used to derive this simulation represent typical cryoballoon ablation PVI procedures with variable delivery of preablation ultrasound imaging, adjunctive usage of right atrial flutter line ablation, and/or postablation adenosine and/or isoproterenol testing. Adjunctive techniques to PVI do not prohibit a HEU case. Indeed, in this analysis, sites with average lab occupancy times shorter than the overall study average (those used to characterize times for the HEU case) had a higher proportion of cases that included right atrial flutter ablation lines in addition to PVI than the NU case.

While 3 PVI cases per lab day is not currently the normal condition, this model demonstrates it is achievable with keen focus on 2 operational areas. Overall lab occupancy time had the greatest impact on EP lab throughput. Optimizing lab occupancy time may begin with reasonable and consistent improvements in “skin-to-skin” procedure time, which can be influenced by catheter technology choice and the associated ablation modality learning curve for the operator and staff. The cryoballoon catheter may support reductions in lab occupancy time as both procedure times and operator learning curve have been demonstrated to be shorter than focal RF ablation catheters.^19,21 Additional procedural options like adoption of tailored dosing for cryoablation procedures may further enhance procedural efficiency.^15,16 The second operational area that most influenced lab efficiency was the overall scheduling approach of the ablation day in the EP lab. Adjustments to enhance efficiencies in the lab schedule could include extending the length of standard lab hours per day (ie, earlier first case start time and later overtime start) by instating split nursing shifts, improving the efficiency of room turnover processes, and removing the restriction in subsequent case start times imposed by block scheduling.

Clinical implications. Efficient EP lab operations can improve the patient experience, the number of patients treated, and the EP lab staff experience. Unpredictable and long-duration PVI ablation cases can contribute to overtime costs to the hospital and turnover of the EP lab staff. Some EP lab operations attempt to manage overtime costs by using longer shift times, split shifts, or flex time on subsequent days, which can reduce overtime costs but may cause stress for the EP staff.²² In addition to staff satisfaction and overtime cost savings, predictable and efficient PVI case times provide the opportunity to perform add-on cases, which may allow treatment for more patients and limit additional overnight stays. Flexibility in “open-time” may also accommodate emergent cases in addition to more preplanned procedures. Finally, a standard EP lab (2 AF ablations per day) that moved to the HEU model (3 cases per day) would reduce the wait-time for patients scheduled for an AF ablation by 50%. This would facilitate timely catheter ablation, which has been demonstrated to improve AF ablation outcomes.^23,24

Study limitations. Our analysis has several limitations that should be acknowledged. This is a posthoc analysis of the original clinical study; however, the data collection forms for the trial were specifically designed to collect data to support an analysis of lab efficiency. This analysis only assessed the cryoballoon technology and did not directly compare results with other ablation modalities (including RF catheter ablation). Real-world variation of certain parameters such as shift begin/end times and block scheduling details were not modeled, but the parameters were chosen to be representative of a typical hospital and based on qualitative research. Generalized financial modeling was beyond the scope of this study, as costs associated with the ablation catheter, adjunctive tools, sedation method, hospital length of stay, and EP lab staff vary between hospitals. Instead, the focus of this analysis was the impact of efficiency on procedure volume and risk of overtime, and the data were not translated into direct financial metrics.

Conclusion

Cryoablation supports EP lab efficiencies that address the growing AF population indicated for catheter ablation, and cryoballoon ablation confers EP lab efficiency and flexibility to increase the number of both PVI and non-ablation EP cases within a lab day. The discrete event simulation model indicated that dedication to efficiency can support an EP lab transition from 2 to 3 PVI cases per day, and multiple cryoablation procedures for the treatment of patients with PsAF can be completed in a lab day with few overtime days and consistent excess time for additional non-ablation cases. 

Acknowledgment. The authors thank Jennifer Diouf, Christopher Anderson, Fred Kueffer, and Hae Lim of Medtronic, Inc. for their support of the STOP Persistent AF trial and all the trial sites and investigators that contributed to this data set.

Funding: This study was sponsored by Medtronic, Inc.

Clinical Trial Registration: Clinicaltrials.gov Identifier NCT03012841

Disclosure: Dr. Su reports consulting fees, honoraria, and research grants from Medtronic. Reece Holbrook, Alicia Sale, and Dr. Braegelmann are employed by Medtronic, Inc. Dr. Calkins reports honoraria and consulting fees from Medtronic. The remaining authors report no conflicts of interest regarding the contents herein.

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