Pulmonary vein isolation (PVI) has become the accepted and preferred method of catheter ablation when treating patients with drug-resistant atrial fibrillation (AF)1-3; the cryoballoon catheter has become a gold standard in this PVI treatment strategy.4-6 Recent results of the FIRE AND ICE trial demonstrated an equivalent efficacy and safety profile when comparing the cryoballoon (Arctic Front family of cryoablation catheters, Medtronic) to traditional point-by-point focal radiofrequency (RF) ablation catheters with 3D electroanatomical mapping (THERMOCOOL family of focal catheters, Biosense Webster, Inc., a Johnson & Johnson company).4 Yet, the secondary analyses of the FIRE AND ICE data set have highlighted numerous endpoints regarding reinterventions and rehospitalizations whereby cryoballoon ablation is superior to focal RF catheter ablation, including a 34% reduction in cardiovascular rehospitalizations and a 33% reduction in the number of repeated catheter ablation procedures.5
When examining the long-term efficacy of a cryoballoon procedure, there are three important acute balloon-related biophysical parameters to consider when evaluating a successful PVI. First, before initiating a cryoballoon freeze application, it is critical to ensure complete PV occlusion between the balloon and the antral PV surface.7,8 Specifically, testing by imaging or physiological feedback should confirm complete balloon-to-PV occlusion with no leak detection. Second, during an application of cryo-refrigerant (freezing), the time to acute intra-ablation PV isolation (time-to-isolation, or TTI) as recorded by entrance and/or exit block testing with a dedicated balloon inner lumen circular diagnostic catheter (Achieve mapping catheter, Medtronic) is the most important parameter during the cryoapplication.7,8 When TTI is achieved in less than 90 seconds, a reasonable expectation of acute PVI can be assured; however, not all PVs can be monitored for TTI because of the short (or missing) muscular sleeve extension into the PV.7,8 Finally, after delivery of cryo-refrigerant, the interval thaw time between the cryoballoon and the PV is another hallmark of an effective cryoablation, with longer thaw durations favoring a durable lesion as a consequence of proper balloon-to-tissue contact.7,9
With regard to PV occlusion testing, the established best practice is to examine the retrograde retention of radiopaque contrast agent when viewed by fluoroscopy.8 However, other adjunctive methods can be used to reduce the usage of ionizing radiation, including use of a capnogram to assess balloon-to-PV occlusion when general anesthesia is utilized during the cryoablation procedure. Importantly, occlusion testing is the primary feedback parameter of a successful and durable PVI before a freeze is initiated during a cryoablation procedure.7-9
Materials and Methods
In this retrospective examination of observational data, we evaluated the clinical charts and electrophysiology laboratory records of 15 patients with drug-refractory and symptomatic AF treated by cryoballoon catheter ablation at Inova Fairfax Hospital in a single-arm evaluation. Specifically, the study reviewed and recorded the capnogram readings during these procedures and the concomitant cryoballoon catheter performance parameters (balloon nadir temperature, freeze duration, and TTI) during each cryoablation. The study examined patients who were treated between November 2015 and January 2016 with the second-generation cryoballoon (Arctic Front Advance, Medtronic). Each patient provided written informed consent prior to the AF ablation procedure, and this retrospective chart examination was approved by the local institutional review board.
During each procedure, patients were sedated using general anesthesia, and catheter access was achieved by a single groin site puncture via the femoral venous route. The cryoballoon catheter ablation procedure has been previously described in detail,4-9 and the procedural techniques used in this study were similar to previously published reports. In brief, echocardiography was conducted to assess the left atrium for thrombus, atrial chamber dimensions, and anatomical structures (including PV anatomy). Typically, intracardiac echocardiography and fluoroscopy were used in tandem to guide transseptal access by needle puncture. Immediately following transseptal access, a heparin bolus was delivered and an activated clotting time of at least 300 sec was maintained throughout the procedure. During catheter deployment, the cryoballoon was delivered over a guidewire via a 12 French sheath (FlexCath Advance, Medtronic). At each PV, the balloon was inflated and advanced to the PV antrum, where PV occlusion testing was performed before each freeze application. In general, a freeze-thaw-freeze strategy was used to isolate each PV,8 and PVI was confirmed by entrance and exit block testing after a 30-minute waiting period.8
During each freeze application, a capnogram was used to monitor the concentration of exhaled CO2 by side-stream sampling while the patient was sedated under general anesthesia. The typical use of the capnogram during the application of general anesthesia is to monitor the adequacy of vascular blood flow (coronary, pulmonary, and systemic).10,11 Because of the sensitivity of the capnogram to monitor end tidal CO2 (ETCO2), this method can also be utilized in parallel to evaluate the balloon-to-PV occlusion. When the cryoballoon successfully occludes a PV, the ventilation-perfusion mismatch that is created will be immediately observable as a steady decrease in ETCO2 until a nadir level is achieved at the new equilibrium. Similarly, when the cryoballoon application is completed and thawed, the ETCO2 level will quickly recover back to the prior baseline reading before balloon-to-PV occlusion was initiated. Hence, this technique can be used as an adjunctive tool to gauge PV occlusion, and it can enhance the traditional method of imaging PV occlusion by contrast agent retention (as viewed under fluoroscopy). Additionally, it can be utilized as a part of a concerted effort to reduce the radiation exposure used during the cryoablation procedure.
In this study, all data (for statistical evaluations) were captured in an electronic database with no recordings of protected health information. When data averages were used, a standard error calculation was given when reporting characteristics of the freeze parameter and ETCO2. Correlations were tested by Pearson method with the reported P-value. Analysis of variance (ANOVA) testing was conducted by a weighted-means analysis, and was used to test for differences between multiple samples. P-values ≤0.05 were considered to be statistically significant.
In this evaluation, patients were 65% male, had an average age of 63.6 years (± 10.9 years; standard deviation), and had a mean body weight of 89.4 kg (± 20.6 kg; standard deviation). During the cryoablation procedures, a freeze-thaw-refreeze method of ablation was utilized. The left superior PV (LSPV) and left inferior PV (LIPV) were ablated with an average of 2.3 cryoablations each. Similarly, the right superior PV (RSPV) had an average of 2.2 cryoapplications, while the right inferior PV (RIPV) had a mean of 2.4 freeze applications. The target ablation duration of each freeze application was a 180-sec cryoablation; however, the mean freeze duration was shorter because of early cryoapplication terminations that were typically encountered when a balloon was repositioned for a better PV occlusion (Table 1). Both the mean number of ablations per PV (P=0.942) and the mean duration of freeze at each PV (P=0.782) were not statistically different between PVs by ANOVA testing, demonstrating that all four PVs were treated consistently with regards to duration of freeze and number of cryoapplications.
When examining the relationship between balloon nadir temperature and capnogram nadir ETCO2, there was a direct correlation between the two variables with regard to the total data collection of all the PVs that were examined (Table 1 and Figure 1; P=0.0001 for Pearson correlation). When reviewing the relationship by individual PVs, the RSPV had the strongest direct correlation between balloon nadir temperature and capnogram nadir ETCO2, and in general, the correlation was stronger for the right-sided PVs compared to the left-sided PVs. Importantly, the scatter plot (Figure 1) demonstrates that low nadir ETCO2 recordings (an indicator of good PV occlusion) can be achieved in most cases without the use of ultra-low balloon nadir temperatures (≤60o C).
During the study, TTI was also recorded and was measureable in 68% of the PVs (Table 2). TTI had a total mean duration of 33 sec until acute isolation was achieved during a cryoablation freeze. The shortest duration of TTI was observed in the RSPV, which was consistent with the ability to also record the lowest capnogram nadir ETCO2. However, TTI was more often observed during cryoablation of the left-sided PVs (LSPV and LIPV TTI achieved in 80% and 73% of PVs, respectively). When TTI was measurable, only one cryoapplication was recorded at less than 90 sec (TTI), and all other recordings of TTI were less than 60 sec.
Our study demonstrated that capnogram nadir ETCO2 recordings can be used as an adjunctive method to assess balloon-to-PV occlusion during a cryoablation procedure in the treatment of patients with AF. Other studies of capnogram recording of ETCO2 during a cryoballoon ablation have been reported.12-14 In agreement with the observations made by a previous study, the RSPV has the greatest potential for reporting a successful PV occlusion because of the low nadir ETCO2 that is achievable at this particular PV.12 Simply, the anatomy and physiology of the RSPV is more sensitive to the ventilation-perfusion deficit that is measurable during a cryoballoon-to-PV occlusion. This phenomenon may be due (in part) to the superior positioning of the right superior lobe and the relative compact size of the lung lobe. Hence, under ventilation during general anesthesia, the RSPV supplies a tissue that is well ventilated/perfused and yet responsive to physiological alterations because of the compact size. Additionally, our study was also in agreement with the observation that nadir ETCO2 is achieved well in advance of a 180-sec cryoballoon ablation, and in fact, most ETCO2 nadirs are typically achieved within 60 sec of PV-to-balloon occlusion.12
When ETCO2 monitoring and TTI are used together, the two compatible and adjunctive methods can potentially reduce the reliance on fluoroscopy to confirm successful balloon occlusion. In our study, the ETCO2 monitoring seemed to work well on the right-sided PVs while TTI was more successful on the left-sided PVs. Additionally, nadir ETCO2 was positively correlated with balloon nadir temperature, which is also an indicator of a successful PV occlusion.13 However, our study scatter plot demonstrated that effective balloon-to-PV occlusion (as marked by a low nadir ETCO2 recording) can be achieved without the use of ultra-low balloon nadir temperatures (≤60o C). Also, other studies have already demonstrated that a low nadir ETCO2 recording is an effective hallmark of long-term efficacy and maintenance of sinus rhythm.13,14 Consequently, ETCO2 monitoring can be a useful tool in a cryoballoon procedure, especially on right-sided PV ablations.
Lastly, the FIRE AND ICE data set has shown proven benefits in the usage of the cryoballoon catheter to effectively reduce the occurrence of reinterventions and rehospitalizations after the index ablation procedure compared to the focal RF catheter.5 Simply, there is a clinical benefit for using the cryoballoon catheter in some patients, and as usage of the cryoballoon catheter increases, it is important to highlight these adjunctive techniques that enhance the physician user experience. Specifically, with the capnogram measurement of this ETCO2 technique, we have been able to manage the use of fluoroscopy for our patients who have a cryoballoon ablation procedure completed at Inova Fairfax Hospital by relying more on the physiological PV occlusion feedback used in this method (Figure 2).
Disclosures: The authors have no conflicts of interest to report regarding the content herein. Outside the submitted work, Dr. Lim reports he is an employee of Medtronic.
Editor’s Note: This article underwent peer review by one or more members of EP Lab Digest’s editorial board.
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