Comparison of Resource Utilization of Pulmonary Vein Isolation: Cryoablation Versus RF Ablation With Three-Dimensional Mapping in the Value PVI Study

Abstract: Background. Point-to-point focal radiofrequency (RF) catheter ablation for aberrant pulmonary vein triggers that manifest into atrial fibrillation (AF) is the traditional method for treating symptomatic drug-resistant paroxysmal AF (PAF) when an ablation procedure is warranted. More recently, pulmonary vein isolation (PVI) using the cryoballoon has been demonstrated to be safe and effective (STOP AF clinical trial). Currently, two small studies have reviewed the procedural efficiency when comparing cryoballoon to focal RF catheter ablation procedures; however, no multicenter study has yet reported on this comparison of the two types of ablation catheters. Methods. A multicenter retrospective chart extraction and evaluation was conducted at seven geographically mixed cardiac care centers. The study examined procedural variables during ablation for PVI in PAF patients. Results. In several procedural measurements, the two modalities were comparable in efficiencies, including: acute PVI >96%; length of hospital stay at approximately 27 hours; and about 30% usage of adenosine after procedural testing. However, when compared to RF catheters, the cryoballoon procedure demonstrated a 13% reduction in laboratory occupancy time (247 min vs 283 min), a 13% reduction in procedure time (174 min vs 200 min), and a 21% reduction in fluoroscopy time (33 min vs 42 min). Additionally, when comparing the material usage of both cryoballoon and RF catheters, the cryoballoon used more radiopaque contrast agent (78 cc vs 29 cc) while using less intraprocedural saline (1234 cc vs 2386 cc), intracardiac echocardiography (88% vs 99%), three-dimensional electroanatomic mapping (30% vs 87%), and fewer transseptal punctures (1.5 vs 1.9). Conclusion. This study is the first United States multicenter examination to report the procedural comparisons between the cryoballoon and focal RF catheters when used for the treatment of PAF patients. In this hospital chart review study, potential advantages were found when operating the cryoballoon with regard to hospital resource allocation. There was no statistical difference between cryoballoon and RF catheters for acute PVI success during the ablation procedure. 

J INVASIVE CARDIOL 2014;26(6):268-272

Key words: atrial fibrillation, cryoablation, cryoballoon, radiofrequency ablation, and pulmonary vein isolation

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Pulmonary vein isolation (PVI) has been demonstrated to be one of the cornerstones of the ablation strategy during the therapeutic treatment of atrial fibrillation (AF).¹ The original work done by Haïssaguerre established the presence and importance of spontaneous ectopic beats that originated in the pulmonary vein (PV).² Based upon this clinical research, there have been a variety of tools developed to isolate these asynchronous triggers. In the United States (US), there are two types of commercially available ablation catheters that are Food and Drug Administration (FDA) approved: the cryoballoon (Medtronic, Inc), and a variety of focal radiofrequency (RF) catheters. In our study, the examination of RF catheters included the family of open irrigated RF catheters (ThermoCool and ThermoCool SF, Biosense Webster; and Safire BLU, St Jude Medical) and non-irrigated catheters (Blazer, Boston Scientific). 

Historically, when paroxysmal AF (PAF) patients are symptomatic and refractory to antiarrhythmic drug (AAD) therapy, focal RF ablation catheters have been used to deliver heat energy and ablate cardiac tissue.¹ In the cryoballoon system, ultra-cold therapy is delivered to the PV antrum and heat is removed from the contacting tissue. The completion of the STOP AF clinical trial has established the safety and efficacy profile of the cryoablation system.³ Yet, only a few single-center studies have examined the procedural efficiencies of the cryoballoon system in any detail.^4-6

Currently, larger multicenter evaluations are being conducted that will directly compare the cryoballoon to focal RF catheters. FIRE AND ICE (ClinicalTrials.gov NCT01490814), FREEZE cohort (ClinicalTrials.gov NCT01360008), and FreezeAF (ClinicalTrials.gov NCT00774566) are all prospective multicenter evaluations that will evaluate cryoballoon and RF catheters with regard to safety, efficacy, and efficiency. CABANA (ClinicalTrials.gov, NCT00911508) is an international, multicenter study designed to prospectively compare ablation therapy to antiarrhythmic medical therapy in the treatment of AF, and includes both cryoablation and RF catheter ablation. However, until these larger clinical studies are completed, there is still a need to examine cryoballoon and focal RF ablation catheters in a multicenter comparison of procedural efficiencies. In the current study, experienced users of both cryoballoon and RF catheters compared their hospital experience with both catheters.

Methods

The Value PVI study, which was sponsored by Medtronic, Inc, was conducted as a retrospective chart collection for PAF patients undergoing PVI ablation. The study was undertaken at seven geographically diverse US centers, including university teaching hospitals and regional specialized cardiac facilities. The institutional review board (IRB) at each hospital approved the study using their own policies and staff. Patient chart abstraction and data collections were conducted by using an independent contract research organization (CRO) and clinical hospital staff. Medtronic employees were not permitted to collect patient charts or data by rule of several participating hospital IRBs due to patient privacy and study data integrity.

The initial collection design was to attempt to collect 25 cryoballoon patient charts and 25 focal RF patient charts at each of the seven participating hospitals (350 patient charts total). All data were extracted from patient charts and recorded onto a clinical report form (CRF). Data elements recorded were a mix of hospital resource allocation and procedural efficiency. Hospital resources evaluated included medical equipment usage, anesthesia selection, pharmaceutical testing agents, and imaging equipment. Procedural efficiency measures were denoted as room occupancy, procedural times, and length of hospitalization.

Inclusion criteria were: a PAF diagnosis; a first AF ablation procedure; and PVI ablation by either cryoballoon or focal RF catheter. Exclusion criteria were: previous left atrial (LA) ablation; procedure dates older than January 1, 2011; procedures occurring during a physician’s learning curve (procedures 1-25 with each catheter); and LA substrate ablations beyond PVI. As a retrospective collection, patients were already treated by either cryoballoon or RF catheter based on physician discretion and patient consultation.

All chart collections encompassed only those procedures that occurred between January 1, 2011 and May 31, 2013, and collections were made in reverse chronological order at each site. Of note, patient charts older than January 1, 2011 were not included in this study so that catheter performance evaluations could be made on the most currently available technology and practices. Also, the first 25 procedures of either cryoballoon or RF catheter usage were excluded in order to avoid learning-curve influence on the data set. Data points were only recorded from clinical hospital charts and left blank when not present. No extrapolation of data was allowed when recording information onto the CRF, and all CRFs were transferred into an electronic database by a CRO for statistical analyses. 

Statistical analyses. All descriptive statistics are recorded as means with reported standard error of the mean, and all means are reported with the number of individual patient charts calculated for that statistic in parentheses. For comparisons of continuous variables, a two-sample Student’s t-test was used to determine statistically significant interactions. Discrete variables were analyzed using the Fisher exact test. Statistical significance was set at P<.05. This study did not test a prospective hypothesis and no adjustments were made for the multiplicity of testing.

Results

The entire study was based on 348 patient charts (220 cryoballoon and 128 RF procedures). At two participating centers, the RF procedures were either older than the exclusion criteria or the RF charts were at the neighboring hospital where original IRB approval was not awarded. For those two hospital centers, the decision was made to collect 50 total cryoablation charts and no RF charts. By collecting 50 cryoablation charts at these two sites, the attempt was to reflect a collection set (50 charts) that was similar in size and time interval to the other five sites. However, the data for this study were examined by both including and excluding the two “cryoballoon-only” sites.

When all seven hospitals were examined in the data set, these recordings were denoted as “Seven Cryo Sites.” Also, a second data evaluation was conducted with only the five hospitals that supplied both cryoballoon and RF procedures, which encompassed 252 patient charts (124 cryoballoon and 128 RF procedures), and these cryoballoon data were designated as “Five Cryo Sites.” Of note, the cryoballoon procedures at these two centers (that only supplied cryoablation data) were not on either extreme of procedure times. The data from these two centers did not have outliers, and the mean times at each center were never the fastest or slowest times among the other five participating centers. Lastly, 20 patient charts were removed from this study before data analyses and marked as screen failures because of non-compliance to inclusion and/or exclusion criteria.

During the collection of patient chart data, Medtronic released a second-generation cryoballoon (CB-2). In this study, cryoballoon procedures were conducted with a mix of cryoballoon catheters, including the first-generation cryoballoons (CB-1): 16% were 23 mm Arctic Front (23 mm CB-1); 78% were 28 mm Arctic Front (28 mm CB-1); 1% were 23 mm Arctic Front Advance (23 mm CB-2); and 5% were 28 mm Arctic Front Advance (28 mm CB-2). The predominant cryoballoon catheter used in this study was the 28 mm CB-1 design. By comparison, 92% of the RF ablations were conducted with the Biosense Webster line of open irrigated catheters, including the ThermoCool and ThermoCool SF catheters. The remaining RF procedures were completed with either the Safire BLU catheter (St Jude Medical, 1% of the procedures) or the Blazer catheter (Boston Scientific, 7% of the procedures).

Within the study collection, there was no statistical difference between cryoballoon and RF catheters for acute PVI success during the ablation procedure, and all acute success was greater than 96% in the entire retrospective study. Table 1 reports the patient demographics that were represented in these 348 hospital charts, and the patients only differed statistically by the presentation of diabetes, with a significantly higher incidence in the RF patients (23% vs 13% when testing RF vs Seven Cryo Sites; P=.02).

The data in Table 2 were collected to highlight the similarities and differences between the cryoballoon and RF ablation procedures. When comparing the cryoballoon procedures to RF ablations, there was a statistically lower number of transseptal punctures, intracardiac echocardiography (ICE) imaging, three-dimensional (3D) electroanatomic mapping, and saline fluid usage during the cryoballoon procedures (P<.001 for all comparisons). The RF ablations used about 1000 cc more saline per procedure, most of which was attributed to the use of irrigated RF catheters. Conversely, the RF procedures required significantly less radiopaque contrast agent (P<.001). 

The decision to employ conscious sedation versus general anesthesia was variable among operators and institutions. For the Five Cryo Sites group, less general anesthesia was used in cryoballoon than in RF cases (P<.001; Table 2). In regard to postprocedural testing, adenosine after testing was utilized to the same proportionality between both cryoballoon and RF ablation catheters. Additionally, when comparing the Five Cryo Sites group to RF ablations, there was no difference in the usage of isoproterenol after testing or any postprocedural pharmaceutical testing (which included any single or combined usage of adenosine or isoproterenol). However, when comparing the Seven Cryo Sites group to RF ablations, there was less use of isoproterenol after procedural testing (P<.01) and consequently less usage of any postprocedural pharmacologic testing (P=.02).

In Table 3, the data demonstrate the procedural efficiencies that were detected when using the cryoballoon catheter compared to RF ablation catheters. In this time measurement data set, there were no statistical differences between the Seven Cryo Sites group and the Five Cryo Sites group. EP lab occupancy was recorded as the time denoted from patient entrance into the procedure room until patient exit, and in this study the Seven Cryo Sites group EP lab occupancy time was significantly shorter compared to RF ablation lab occupancy. There was a 36 minute difference (13%) in room occupancy when comparing the Seven Cryo Sites group to RF ablation procedures (246.8 ± 3.1 min vs 283.1 ± 4.7 min, respectively; P<.001). The study also documented how often lab occupancy was shorter than 3.5 hours as a measure of efficient procedure predictability (Table 2). In more than 80% of the cryoballoon procedures, the EP laboratory was vacated within 3.5 hours, whereas the RF ablations achieved this same measure in 63% of the procedures. 

Procedure time (Table 3) was denoted as the period from first vascular entrance (typically a groin puncture) until last sheath exit. It was common to have the primary physician make the initial groin puncture while the last sheath exit was pulled by a member of the hospital staff. There was a 26 minute (13%) procedure time difference when comparing the Seven Cryo Sites group to RF catheter ablations (173.5 ± 3.1 min vs 199.8 ± 4.3 min, respectively; P<.001). LA dwell time was documented as the period from first transseptal puncture until last catheter was withdrawn across the interatrial septum into the right atrium, and there was a 19 minute difference (11%)when comparing the Seven Cryo Sites group to RF ablations (147.9 ± 3.2 min vs 166.7 ± 4.4 min, respectively; P=.01). Fluoroscopy time also was recorded during this study, and it was 9 minutes (21%) shorter, when comparing the Seven Cryo Sites group to RF procedures (33.3 ± 1.0 min vs 42.4 ± 1.8 min, respectively; P<.001). Lastly, the study determined that length of patient stay in the hospital was likely dictated primarily by hospital policy, and patient discharge was near 24 hours for either procedure with no statistical differences (26.6 hr cryoablation discharge vs 27.6 hr RF ablation discharge). 

Discussion

By utilizing a multicenter retrospective chart abstraction design, this study was able to compare several measures of resource utilization in cryoballoon as opposed to focal RF catheters during PVI ablation for PAF. In general, the patient demographics were extremely similar, with only one statistically significant difference resulting in the higher occurrence of diabetes in the RF ablation group. There were similarities and differences procedurally when comparing the cryoballoon to RF ablation procedures. 

Most differences were attributed to the essential design distinctions between catheters. For instance, 93% of the RF catheters used in this study were open irrigated catheters (64% ThermoCool, 28% ThermoCool SF, and 1% Safire BLU), which are built for use with a 3D electroanatomic mapping system. This combinational usage resulted in the 87% procedural usage of 3D mapping during RF ablations compared to less than 30% usage during cryoballoon procedures. Also, the use of irrigated RF catheters led to the increased usage of saline during a procedure. Somewhat surprisingly, the average total amount of crystalloid infusion (IV plus catheter irrigation) was similar (P=.33) regardless of which ThermoCool catheter was used during the ablation. When the ThermoCool SF catheter was used, a mean of 2564 cc of saline fluid was delivered to the patient compared to a mean of 2339 cc when a ThermoCool catheter was employed.

In comparison, significantly more contrast agent was used in cryoballoon cases than in RF cases (78.3 cc vs 29.3 cc). During cryoballoon catheter ablation, radiopaque contrast agent is commonly delivered through the inner lumen of the cryoballoon to assess balloon occlusion.⁷ When cryoballoon-to-PV occlusion is established, the user will assess the retention of contrast agent in the distal PV by fluoroscopy. By comparison, the usage of radiopaque contrast agent during the RF procedures was predominantly used during left atrial angiography. Either of these factors (volume of saline or contrast agent usage) could be of importance in an individual patient, for example, with renal insufficiency or systolic heart failure. Minimizing usage of both may potentially benefit the patient.

Double transseptal punctures were performed in the majority of RF cases, with deployment of a second sheath for placement of the circular mapping catheter. In contrast, a single transseptal puncture technique was used more often in the cryoballoon cases. This was facilitated by the use of a circular mapping catheter deployed through the inner lumen of the cryoballoon (Achieve Mapping Catheter, Medtronic, Inc).⁸ 

When comparing CB-1 to RF catheters for procedural efficiencies, only two recent evaluations have been completed, and both studies were single-center evaluations with smaller patient populations.^5,6 In the paper published by Linhart et al, a German center compared 20 cryoballoon-treated patients with 20 focal RF-ablated patients and found no significant differences in procedure time, fluoroscopy time, or AF recurrence. Similarly, the study by Mandell et al compared 62 cryoballoon ablations to 62 RF ablations in a US single-center examination, and the data demonstrated no statistical difference in fluoroscopy time or procedural time when excluding the re-isolation procedures and protamine administration. 

The study by Mandell et al was conducted in an experienced RF ablation center during their first experience with the cryoballoon catheter, and the data demonstrated a typical cryoballoon “learning curve” that occurs between the first 20 to 25 procedures.³ When comparing the first 31 cryoballoon ablations to the last 31 cryoballoon procedures, the Mandell et al study observed a shortening of fluoroscopy times and a trend toward shorter procedural times. 

In our study, cryoballoon EP lab occupancy time was on average 36 minutes shorter than focal RF ablation procedures, with about 80% of the cryoballoon procedures having lab occupancy of 3.5 hours or less. The majority of the time differential was related to the time required to create a 3D electroanatomic map and application of catheter ablations. To a lesser degree, other time differentials were accounted for during a shorter waiting period and less usage of postablation pharmacologic challenge in the cryoballoon group. 

Study limitations. This study was intended to evaluate the utilization of laboratory resources and assess laboratory efficiency as measured by the various time measurements described. However, this study did not set out to test a prospective hypothesis and no adjustments were formulated for the multiplicity of testing. Additionally, only acute measures of success (PVI at the end of the procedure and absence of serious adverse events) were assessed. Assessment of long-term efficacy was not included as part of this study. It was conducted as a retrospective chart abstraction and review. As such, it is well established that errors in confounding and bias are more common in retrospective studies compared to prospective studies. Most importantly, chart reviews are not subject to the use of randomization and control arms. 

Conclusion

The Value PVI study used a retrospective chart abstraction and review to examine procedural efficiencies between the cryoballoon and point-to-point focal RF catheter performance. Review of the data demonstrated measurable differences that were found during the employment of the cryoballoon system when treating PAF patients. These potential cryoballoon advantages could possibly be used to positively affect hospital resource allocation. 

The apparent differences that were observed in this study (procedure time and hospital resources) will have to be confirmed in prospective randomized controlled trials, which are currently ongoing. After these trials are completed, a comparative benefit versus cost/risk assessment can be potentially made by evaluating short- and long-term outcomes of these competing approaches. Importantly, each catheter type was able to achieve >96% acute PVI, and there was no statistically difference between performance with regard to this measurement.

Acknowledgments. Many hospital staff members, research coordinators, and IRB staff members were instrumental in the execution of this study. We would like to thank some of them in alphabetical order and appreciate all their efforts: Margaret Amaya, Deborah Carney, Rachel Donegan, Martha Green, Elizabeth Illing, Jane Jackson, Anita Kemp, Kathryn Koh, Katherine Kramer, Dana Long, Monica Martinez, Claudia Mattil, Mary Parga, Lynn Peterson, Kristi Picardi, Doreen Robinson, Natalie Settele, and Victoria Taylor.

References

1. Calkins H, Kuck KH, Cappato R, et al. 2012 HRS/EHRA/ECAS Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation: recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design. Europace. 2012;14(4):528-606.
2. 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(10):659-666.
3. Packer DL, Kowal RC, Wheelan KR, et al. Cryoballoon ablation of pulmonary veins for paroxysmal atrial fibrillation: first results of the North American Arctic Front (STOP AF) pivotal trial. J Am Coll Cardiol. 2013;61(16):1713-1723.
4. Fürnkranz A, Bordignon S, Schmidt B, et al. Improved procedural efficacy of pulmonary vein isolation using the novel second-generation cryoballoon. J Cardiovasc Electrophysiol. 2013;24(5):492-497. 
5. Linhart M, Bellmann B, Mittmann-Braun E, et al. Comparison of cryoballoon and radiofrequency ablation of pulmonary veins in 40 patients with paroxysmal atrial fibrillation: a case-control study. J Cardiovasc Electrophysiol. 2009;20(12):1343-1348.
6. Mandell J, Amico F, Parekh S, et al. Early experience with the cryoablation balloon procedure for the treatment of atrial fibrillation by an experienced radiofrequency catheter ablation center. J Invasive Cardiol. 2013;25(6):288-292.
7. Van Belle Y, Janse P, Rivero-Ayerza MJ, et al. Pulmonary vein isolation using an occluding cryoballoon for circumferential ablation: feasibility, complications, and short-term outcome. Eur Heart J. 2007;28(18):2231-2237.
8. Chierchia GB, de Asmundis C, Namdar M, et al. Pulmonary vein isolation during cryoballoon ablation using the novel Achieve inner lumen mapping catheter: a feasibility study. Europace. 2012;14(7):962-967.

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From the ¹The Heart Hospital Baylor Plano, Plano, Texas; ²St. Anthony Hospital, Lakewood, Colorado; ³Piedmont Healthcare, Atlanta, Georgia; ⁴Medtronic, Inc, Minneapolis, Minnesota; ⁵Saint Thomas Hospital, Nashville, Tennessee; ⁶Staten Island University Hospital, Staten Island, New York; ⁷Memorial University Medical Center, Savannah, Georgia; and ⁸Santa Rosa Memorial Hospital, Santa Rosa, California.

Funding: This study was funded in part by Medtronic, Inc.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr DeVille is the lead investigator of this study; he serves as a faculty member, receiving compensation for physician teaching programs with Medtronic, Inc, Stereotaxis, and Biosense Webster, and participates in research studies with each of these companies. Dr Svinarich serves on an advisory board for Medtronic, Inc, and receives honoraria for teaching and speaking for Medtronic, Inc, Forest, and Sanofi-Aventis. Dr Dan is a physician training consultant for Medtronic, Inc, and is a speaker for Medtronic, Inc, St. Jude, and Sorin. Dr Wickliffe is a physician training consultant for Medtronic, Inc. Dr Lim is an employee of Medtronic, Inc. Lisa Plummer is an employee of Medtronic, Inc. Dr Baker is a faculty member who receives compensation for physician teaching programs with Medtronic, Inc. Dr Kowalski is a faculty member who receives compensation for physician teaching programs with Medtronic, Inc. Dr Chang-Sing serves on the national EP advisory board for Medtronic, Inc., and he participated as PI and co-investigator for several Medtronic, Inc clinical trials. Dr Kantipudi, Dr Baydoun, and Dr Jenkins have no disclosures.

Manuscript submitted September 30, 2013, provisional acceptance given December 9, 2013, final version accepted March 18, 2014.

Address for correspondence: J. Brian DeVille, MD, FACC, FHRS, Cardiac Electrophysiologist, Arrhythmia Management, 1820 Preston Park Blvd, Plano, TX 75093. Email: THHBPEP@baylorhealth.edu