Real-time guidewire localization using impedance-based electroanatomic mapping: experimental results and clinical validation during cryoballoon ablation of atrial fibrillation

Abstract

Aims

Cryoballoon ablation is an emerging therapy for atrial fibrillation (AF). However, the Arctic Front cryoballoon (Medtronic) cannot be localized on current electroanatomic mapping (EAM) systems. We describe a technique to visualize guidewires in an impedance-based EAM system.

Methods and results

A novel technique for real-time guidewire localization in an EAM (Ensite Velocity, St Jude Medical) was prospectively evaluated among patients referred for cryoballoon AF ablation. The guidewire was visualized as an ‘orb’ on the EAM and localization in each of the pulmonary veins (PVs) compared with orthogonal fluoroscopy, contrast venography, and intra-cardiac echocardiography. Application of the technique in 21 consecutive patients [median age 58 (interquartile range 21); 71.4% male; 85.7% paroxysmal AF] demonstrated agreement with respect to guidewire localization in 82 of 82 (100%) PVs. Discrimination of guidewire position in the left atrial appendage from the left PVs was also demonstrated. When compared with 21 consecutive cryoballoon procedures over the same time period in which the technique was not used, fluoroscopy time was reduced [median 53.2 (25.9) vs. 72.3 (47.6) min, P = 0.008], and a trend towards reduced radiation exposure [median 372 (656.0) vs. 581 (849.9) mGy, P = 0.08] was noted, without effect on acute procedural or mid-term endpoints. Ex vivo assessment of the technique in a saline bath left atrial model demonstrated that the ‘orb’ localizes to the centroid of the exposed portion of the guidewire.

Conclusion

This simple, novel technique provides real-time, accurate guidewire localization to enable guidewire and catheter navigation during cryoballoon AF ablation.

Introduction

Since the first description of ectopic beats originating in the muscular sleeves of the pulmonary veins (PV) and initiating atrial fibrillation (AF), radiofrequency ablation (RFA) has been employed to electrically isolate the PVs from the left atrium in the treatment of AF.¹ This procedure is technically challenging and has been limited by moderate long-term success rates,^2,3 often due to reconnection of the PVs.^4,5 The cryoballoon (Arctic Front, Medtronic) is a recently introduced technology with the potential to simplify workflow. Non-randomized comparisons with RFA have shown comparable acute and medium-term outcomes with variable effects on procedure and fluoroscopy times.^6–8 The system consists of a balloon-tipped deflectable catheter which is introduced to the left atrium over a guidewire via a transseptal sheath and connected to a cryotherapy console. Accurate positioning of the balloon at the PV ostia and adequate occlusion of the veins are essential. In contrast to RFA, however, the cryoballoon catheter cannot be visualized in a three-dimensional (3D) electroanatomic mapping (EAM) system, due to a lack of electrodes or location sensors. Such systems are used in the majority of AF RFA procedures worldwide,⁹ and, anecdotally, in the majority of cryoballoon procedures in North America. In addition to delineating the complex anatomy of the left atrium, EAM systems facilitate focal ablation which is required in up to 60% of patients in published series.⁸ The manufacturer offers a proprietary hybrid guidewire/circular mapping catheter (Achieve, Medtronic), which does allow recording of PV potentials and EAM localization. However, the non-deflectable nature of this circular mapping catheter represents a significant limitation, and real-time visualization of PV isolation is observed in only 50% of veins.¹⁰ Here we describe experimental and clinical results with a simple and inexpensive method (which we dub the ‘orb’ technique) of real-time guidewire localization on an impedance-based EAM to facilitate cryoballoon catheter manipulation.

Methods

Study population

Consecutive patients referred for ablation of symptomatic drug-refractory AF and deemed suitable for either technique were offered the option of RFA or cryoballoon ablation, and included patients had elected to pursue cryoablation. Patients were divided into two groups: group 1 consisted of patients in whom the novel orb technique was used, and group 2 consisted of consecutive patients undergoing cryoballoon ablation during the same time period in whom the orb technique was not used.

Cryoballoon ablation procedure

All procedures were performed on uninterrupted warfarin or on dabigatran that had been held for two doses pre-procedure and restarted immediately post-procedure. Antiarrhythmic drugs (except amiodarone) were held five half-lives before the procedure. Procedures were performed under moderate conscious sedation or general anaesthesia, depending on patient characteristics and preference. A duodecapolar catheter was placed in the coronary sinus and used as a reference for the EAM system. Intra-cardiac echo (ICE) was used for assistance with transseptal puncture, assessment of guidewire and cryoballoon position, and the degree of PV occlusion with the cryoballoon. Prior to transseptal puncture heparin was initiated and titrated to maintain an ACT between 350 and 400s. One or two transseptal punctures were performed. One transseptal puncture was performed with an 8Fr transseptal sheath introduced through a short 11Fr sheath: a guidewire was placed into the left superior PV and both sheaths exchanged for a 12Fr outer sheath (Flexcath, Medtronic) that was advanced over the wire to the left atrium. A decapolar circular mapping catheter (Lasso, Biosense Webster or Reflexion Spiral, St Jude Medical) was used to create an EAM of the left atrium with the EnSite Velocity system (St Jude Medical). The 28 mm Arctic Front cryoballoon (Medtronic) was advanced through the outer sheath. A 0.032″ × 260 cm guidewire (Amplatz Extra Stiff, Cook Inc.) was introduced through the lumen of the cryoballoon to wire the PVs. Freezes were performed in each vein for 4 min targeting a nadir temperature of −40 to −60°C. Freezes in the right superior pulmonary vein (RSPV) and right inferior pulmonary vein (RIPV) were performed while pacing the phrenic nerve at 25 mA/4 ms from the SVC. Following ablation the veins were interrogated with the circular mapping catheter and additional freezes or ablation with either an 8 mm cryocatheter (Freezor Max, Medtronic) or a 3.5 mm irrigated tip radiofrequency energy (Celsius Thermocool, Biosense Webster) delivered until entrance and exit block was demonstrated in each vein. Antral rather than ostial isolation, as demonstrated in Figure 1, was the endpoint.

Post-procedural care and follow-up

Post-procedure, anticoagulation was resumed for a minimum of 3 months and antiarrhythmic drugs usually continued for at least 2 months. Patients were provided with a transtelephonic event recorder for the first 3 months post-ablation and encouraged to transmit weekly and during any symptoms. Further event monitoring was performed beyond 3 months if the patient had atrial arrythmias in the first 3 months or for symptoms. Twenty-four hour Holter monitoring and follow-up visits were scheduled for 3 and 6 months post ablation. Recurrence was defined as AF, flutter, or tachycardia lasting >30s.

Novel orb technique for guidewire localization

A technique for guidewire localization was developed within the above procedure and prospectively applied in the course of routine clinical practice at the discretion of three participating electrophysiologists offering cryoballoon ablation at our centre. Data extraction from the procedural and medical record was approved by our Institutional Review Board. The Amplatz Extra Stiff guidewire was connected to the Ensite Velocity system via pacing cables with alligator clips (Remington Medical Inc.), to create an electrode, allowing visualization of the guidewire tip as an orb on EAM (Figure 2). The Ensite Velocity system enables the visualization of any electrode within the heart with a high degree of accuracy and long-term stability.¹¹ The position of the wire as represented by the orb on EAM was systematically compared by the operator with its location as determined by (i) orthogonal fluoroscopy in the right anterior oblique and left anterior oblique (LAO) views and (ii) ICE. Images were stored in each modality for later analysis. Venography was then performed with the balloon inflated to assess the degree of occlusion prior to cryoablation, allowing definitive confirmation of the wire position. In cases where, during manipulation, the wire was noted to enter the left atrial appendage (LAA), correlation of the position of the orb on the EAM and differentiation from a left superior or inferior PV position was also assessed. The balloon catheter was not advanced into the LAA in any case.

Wet lab study

Impedance-based EAM systems rely upon the application of a small current to individual electrodes in an impedance field generated by three patch pairs applied to the patient. This current allows the system to determine a voltage measurement in the impedance field along each of three orthogonal axes; these measures are calibrated along the length of each axis allowing for 3D localization of individual electrodes. Most commonly, small and discrete catheter electrodes (1–8 mm) are located. As a guidewire is a linear rather than discrete conductor, we used a wet lab to characterize the exact location on the wire represented by the orb displayed by the EAM.

Assessment was carried out using a custom model of the left atrium, housed in a saline-filled bath at room temperature. Two ports allow the introduction and manipulation of catheters within the lumen of the semi-transparent model. Surface electrode patches applied to the bath allow creation of an impedance field and visualization of electrodes in the EAM system. The 3D geometry of the model left atrium was created in the EAM system using a circular mapping catheter, and multiple catheter positions compared visually and on the EAM to confirm accurate localization. The Amplatz Extra Stiff guidewire was connected as described above and introduced into the model via a plastic transseptal sheath (Fast-Cath Swartz SLO curve, St Jude Medical) and positioned in each of the four PVs plus the LAA. The position of the guidewire was then compared visually with the position of the orb on the EAM. To delineate the exact location on the wire represented by the orb, the wire and the sheath apparatus were aligned with a duodecapolar catheter with 2-2-2 mm electrode spacing (Livewire Steerable Electrophysiology Catheter, St. Jude Medical) and the sheath advanced over the wire in multiple orientations while the orb position was correlated with the proximate electrode number on the EAM.

Statistical analysis

Data were collated and analyzed by using SPSS (PASW Statistics release 18, IBM). Dichotomous variables are presented as n (%) and continuous variables as median (interquartile range). Categorical variables were compared with χ² test or Fisher's exact test, as appropriate, and continuous variables were compared with the Mann-Whitney U test. A P value of < 0.05 was considered to be statistically significant.

Results

Clinical

Demographic details of the two groups are presented in Table 1. Sixteen of 42 (38.1%) were anticoagulated with dabigatran in the periprocedural period and 26 (61.9%) with warfarin. All patients had previously failed at least one anti-arrhythmic drug and 5 (11.9%) had received a prior unsuccessful RFA procedure for AF.

Application of the technique was assessed in 82 PVs among 21 patients in the orb group. Agreement of EAM guidewire localization with operator localization using fluoroscopy, ICE, and contrast venography was 82 of 82 (100%) veins (Figure 3). In several cases, when during manipulation the guidewire entered the left atrial appendage, the orb was also displayed in the left atrial appendage on EAM and differentiation from a left superior or inferior PV position was possible (Figure 4). There were no cases of inadvertent catheter guidance into non-PV structures such as LAA or left ventricle.

Eighty-two PVs were targeted for cryoablation in the 21 patients in group 1 (2 patients had a left common ostium, in one patient the right superior PV was isolated from a prior ablation procedure, and one patient had a separate right middle PV). All targeted PVs were isolated, with 66 of 82 (80.5%) PVs isolated with use of the cryoballoon alone. Additional focal ablation was required to achieve bi-directional block in the remaining 16 PVs [1 left superior pulmonary vein (LSPV), 5 left inferior pulmonary veins (LIPVs), 2 RSPVs, and 8 RIPVs] in 9 (42.9%) patients using either an 8 mm cryocatheter (n = 4) or irrigated RF (n = 5). In group 2, 68 of 84 (81.0%) targeted PVs were isolated with the cryoballoon alone, with 3 LSPVs, 4 LIPVs, 4 RSPVs, and 5 RIPVs requiring focal ablation. Overall, 80.7% PVs were isolated with the cryoballoon alone, in 26 (61.9%) patients.

Fluoroscopy time was reduced in group 1 compared with the control group 2, along with a trend towards reduced radiation exposure (Table 2). Total procedure time was not different between the groups, nor was the number of PVs targeted, the number of PVs requiring focal ablation, or the number of patients in whom all targeted PVs were isolated by cryoballoon ablation alone (Table 2).

No immediate or late complications were observed in the orb group, while in the control group one case of right phrenic nerve paralysis occurred which had resolved by 6-month fluoroscopic follow-up.

Over a median follow-up of 203 (187.25) days, 14 of the 36 (38.9%) patients with at least 3 months of follow-up had a recurrence of atrial arrhythmia, without a difference between group 1 and group 2 [5/17 (29.4%) vs 9/19 (47.4%), P = 0.27].

Wet lab

The visualized position of the guidewire correlated with the position as represented on the EAM in 5 of 5 structures (100%). The orb localized to approximately the midpoint of that part of the guidewire outside of the sheath (the exposed part). When the sheath was then advanced over the wire into the LA so that a shorter portion of the wire was exposed, the orb localized to a more distal position, again approximately the midpoint of the exposed part. This more closely resembles clinical use, where all but the most distal length of the guidewire is insulated by the cryoballoon catheter.

To precisely characterize the exact location represented by the orb on the EAM, the Amplatz Extra Stiff guidewire and sheath apparatus were aligned with the 2-2-2 mm duodecapolar catheter and placed in the model. The sheath was then advanced over the wire while the orb position was correlated with the proximate electrode number on the EAM (Figure 5). With the sheath tip at the level of electrode 20 on the aligned duodecapolar catheter, leaving the distal 7.8 cm portion exposed, the orb was represented on the EAM at electrode 10 or 3.8 cm from the distal tip of the wire. Advancing the sheath to expose 3.0 cm of wire (correlating with electrode 8) resulted in the orb position on the EAM at the level of electrode 4 or 1.4 cm from the distal tip. Further advancing the sheath to expose only 1.4 cm of wire (correlating with electrode 4) resulted in the orb representation at electrode 2 or 0.6 cm from the distal tip. Therefore, the orb represented on the EAM appeared to correlate to the midpoint or centroid of the exposed guide wire when it is aligned linearly in the impedance field.

Discussion

We describe a simple technique that permits real-time guidewire localization using an impedance-based EAM system, which we have dubbed the ‘orb’ technique, and report its utility during cryoballoon ablation for AF. We observed correlation with traditional methods of wire localization including orthogonal fluoroscopy, ICE, and contrast venography. Use of this technique was associated with a reduction in fluoroscopy time and a trend towards reduction in radiation dose when compared with procedures performed without its use over the same time period. As perhaps expected for a technique that assists with catheter navigation rather than actual ablation, measures of acute procedural efficacy and mid-term success were not different between the groups.

In detailed assessment in a wet lab model the orb appeared to correlate with the centroid of the exposed (non-insulated) length of the Amplatz Extra Stiff guidewire. It is possible that construction of the guidewire accounts for this observation. The Amplatz Extra Stiff is constructed of an inner mandril and an outer coil which is wrapped around it. This outer coil is uniformly coated with PTFE. The mandril is replaced for the terminal 3 cm with a thinner safety wire. It is possible that this difference in materials leads to differing impedance values along the length of the wire and therefore localization to the centroid. While the EAM is designed to localize small electrodes (1–8 mm in clinical practice), the exposed portion of the guidewire will be >8 mm in most clinical scenarios and localization to the centroid in this case may reflect ‘averaging’ of the summed impedance value of the length of the wire, which is not evident in catheter electrodes due to their smaller size. In the clinical setting of cryoballoon ablation, where the majority of the LA course of the guidewire is within an insulating catheter and sheath, the exposed part is short and should lie entirely within the vein. It is therefore not surprising that the centroid rather than the tip provided excellent localization to individual PVs.

Electroanatomic mapping technology has evolved to support catheter navigation within the left atrium and reduce ionizing radiation exposure for patient and operator.¹² While randomized trials of AF ablation with and without use of an EAM system are lacking, given the complexity of the procedure, such systems have become standard worldwide.¹² By accurately localizing the guidewire, our technique addresses an inherent limitation of the cryoballoon system in a manner that is less expensive than the manufacturer's proprietary solution, which is a deformable hybrid guidewire/circular mapping catheter that assumes a circular configuration when not anatomically compressed. While the Achieve catheter does incorporate mapping as well as a guidewire function, it is not deflectable and correlation with PV isolation as judged by a traditional circular mapping catheter may be imperfect.¹³ While it has been associated with reductions in fluoroscopy and procedure times in two non-randomized comparisons,^14,15 many operators, including the authors, still prefer to use a standard circular mapping catheter to assess the PVs for bi-directional block and to pace the phrenic nerve during ablation of the right-sided PVs. In common with most US centres, we use an EAM system in all cryoballoon AF ablations to facilitate focal ablation, should it be required, and to create pre- and post-ablation voltage maps.

Our report is preliminary and subject to some limitations. Firstly, the reduction in fluoroscopy time was observed in a non-randomized comparison and as such should be viewed as hypothesis generating. Fluoroscopy times were in excess of that seen in our lab during RFA, which is likely a reflection of a learning curve with cryoballoon technology. Second, while the technique may increase procedural efficiency, it might not be expected to have any effect on acute or chronic outcomes as it assists navigation of the catheter rather than PV occlusion, energy delivery, or confirmation of PV isolation. Consistent with this, differences in acute endpoints were not seen, and the duration of follow-up in the current patient cohort does not allow us to test any effects on long-term outcome. Third, some operators elect to perform cryoballoon ablation without a mapping system at all. However, the authors find it useful when additional focal ablation is required to achieve confirmed bi-directional PV block, as was the case with just over a third of our patients in this small series. It should be noted that the procedures described in this report represent our initial experience with the cryoballoon, as reflected by the relatively high number of patients requiring ‘touch-up’ focal ablation. While this figure is consistent with other early experiences,⁸ and with a multicentre randomized controlled trial,¹⁶ lower rates of focal ablation have been reported from experienced centres in observational series.¹⁷ Fourth, this technique is not applicable to the other commercially available EAM technology, CARTO (Biosense Webster), which utilizes location sensors and cannot visualize standard electrodes. In addition, CARTO cannot currently be used in conjunction with the cryoballoon due to a system incompatibility. Lastly, differences in construction between the Amplatz Extra-Stiff wire and other guidewires might lead to differences in how the orb is represented, and operators intending to utilize this technique should familiarize themselves with the behaviour of the guidewire used.

Conclusion

This simple orb technique provides real-time and precise guidewire localization on an impedance-based EAM. The technique may be useful in cryoballoon AF ablation and was associated with reduced fluoroscopy time in our experience. Further study and experience is needed to determine to what extent it can reduce radiation exposure or streamline procedural workflow in various procedures.

Authors' contributions

All authors are involved in the concept/design of the study, data collection and analysis, and critical revision and approval of article; E.M.C. performed the statistical analysis; E.M.C., B.J.W. and D.J.C. contributed in drafting the article.

Conflict of interest: R.A.R. and B.J.W. are employees of St Jude Medical. M.J.N. participates in research sponsored by Medtronic and St Jude Medical. The other authors have no relevant conflict of interest.

References