Cryoablation of Septal Accessory Pathways: Learning While Freezing

Septal accessory pathways provide the invasive electrophysiologist with serious challenges, particularly in the case of para-Hisian or mid-septal insertion sites. Although radiofrequency (RF) energy has demonstrated efficacy in the elimination of accessory AV pathway conduction, it has also been associated with a non-trivial risk of heart block.¹ Due to these concerns, many EP labs, including our own, have concluded that cryoablation is the preferred modality for the mapping and elimination of septal accessory pathways. 

The advantages of cryoablation in this setting are well reported,^2,3 and include the potential for reversing an induced AV block,⁴ the adherence of the catheter tip to the endocardium with freezing, and more discrete and controllable lesion formation.⁵ The following two cases (concealed para-Hisian pathway and mid-septal WPW) illustrate techniques and observations from our laboratory that may be useful to others gaining experience with cryoablation.

Case #1

A 41-year-old woman with a lifelong history of SVT first documented at the age of 8. She has been treated with various medications in the past, including inderal and atenolol, which proved ineffective in preventing the arrhythmia. As a child, she learned specific vagal maneuvers that were effective in terminating the arrhythmia. Prior to admission, she had several emergency room visits documenting the arrhythmia. In the first visit, a narrow-complex tachycardia was noted at a heart rate of 200 bpm and terminated with a single bolus of adenosine. She was discharged on atenolol 25 mg per day, only to represent three days later, again with SVT. Adenosine was used to terminate the arrhythmia; however, several APCs following the termination re-triggered the arrhythmia, and a second bolus of adenosine was required. In all instances, the arrhythmia was characterized as narrow complex with p-wave in the mid-ST segment and with a fixed RP interval.

A diagnostic EP study was performed using standard catheters (quad HRA, octapolar His, decapolar CS, and quad RV). The baseline ECG was normal with no ventricular pre-excitation observed during the study. SVT was easily initiated with single atrial extra-stimulus or ventricular extra-stimulus and frequently during the study with simple catheter-induced APCs. Figure 1 illustrates the effects of a single PVC given during His bundle refractoriness to advance atrial activation. A concealed septal accessory pathway participating in orthodromic AVRT was the presumptive diagnosis.

A 20-polo circular mapping catheter (HALO-XP™ Biosense Webster, Inc., a Johnson & Johnson company, Diamond Bar, California) was used to map the retrograde insertion of the accessory pathway during orthodromic tachycardia. Figure 2  illustrates the positioning of the HALO™ catheter, the His bundle catheter, and a 6 mm tip cryoablation catheter (Freezor® Xtra, CryoCath, Inc., Kirkland, Quebec, Canada) along the septal aspect of the tricuspid annulus.
Figure 3 shows corresponding intracardiac electrograms, with tightest VA coupling at poles 13,14 of the HALO catheter; the cryoablation catheter is positioned just anterior to poles 13,14 and stabilized along the tricuspid annulus with an 8 Fr guide sheath (SRO™, St. Jude Medical, St. Paul, Minnesota). A single cryo-application was initiated with the Freezor® Xtra at this location, and as shown in Figure 3, termination of the tachycardia was achieved rapidly (less than 15 seconds), before complete ice ball formation obscured the distal ablation electrocardiogram. Despite close proximity to the His bundle, antegrade conduction was observed to be stable along the His catheter throughout a single 4-minute consolidation freeze. Following delivery of the lesion and subsequent thawing, ventricular pacing was performed, documenting VA dissociation and arrhythmia non-inducibility. The patient has been symptom-free for one year since the ablation.

Several aspects of this case warrant discussion, particularly as to how cryoablation facilitated success in what might otherwise have been a very high-risk case for permanent AV block. To begin with, the close proximity of the accessory pathway to the His bundle would have rendered RF ablation during tachycardia unthinkable. Even if the RF catheter had been in the identical location, the first beat following termination of tachycardia might have revealed complete AV block that in all probability would be irreversible. The retrograde-only conducting properties of this accessory pathway would have mandated mapping during tachycardia or during adenosine infusion with ventricular pacing (probably impractical); ventricular extra-stimulation mapping would likely have resulted in retrograde fusion or induction of orthodromic tachycardia. In any event, ablation during sinus rhythm, particularly with RF, would multiply the risks to the patient, as serial lesion formation would likely be necessary with repeat testing to determine efficacy. The advantages of cryoablation, as illustrated in this case, are several-fold. Since the biological effects on electrical conduction occur early during the cryo-thermal application (between 32° C and 0° C), an early time to effect to eliminate pathway conduction suggested that the lesion was accurately localized. The property of catheter tip to tissue adherence was capitalized upon to prevent the catheter tip from “jumping” following termination of the tachycardia, and allowed for consolidation of the lesion at the accurate location with a 4-minute freeze at -85° C. Importantly, it must be noted that given less favorable circumstances, the AV node or His bundle might have been the first structures eliminated during cryo-application. Because irreversible cryo lesions require that the target tissue achieve and maintain temperatures below 0° C, the operator must pay attention to antegrade conduction throughout lesion formation and be prepared to thaw immediately. Our experience with the 6 mm and 8 mm tip CryoCath ablation catheters for routine AV node reentry cases has given us confidence in the reversibility of transient heart block, and when observed, is usually preceded by a Wenkebach conduction pattern.

Case #2

The patient is an active and athletic 19-year-old male with asymptomatic Wolff-Parkinson-White syndrome. The abnormal ECG pattern was noted during monitoring for a recent dental procedure, and he was subsequently referred for further consultation and management recommendations. He has no history of syncope, pre-syncope, chest pains or palpitations. He was advised of a small, nevertheless non-trivial risk of sudden arrhythmic death associated with the WPW syndrome, mostly in the setting of atrial fibrillation (AF), and the findings from a recent clinical study of a relative risk reduction with catheter ablation of the accessory pathway in terms of preventing future arrhythmia or SCD.⁶ After discussion with the patient and his parents regarding relative risks and alternatives, the patient consented to undergo EP study and cryoablation of his accessory pathway. The 12-lead clearly demonstrated ventricular pre-excitation, with a brisk V1-V2 R-wave transition and a superior delta wave axis in the inferior leads, consistent with a mid-septal insertion. Diagnostic EP study demonstrated the following: baseline HV interval 0 msec; AP antegrade block cycle length 300 msec, AP antegrade ERP 600/320 and 500/300; AP retrograde ERP 600/350. Orthodromic tachycardia, cycle length 290 msec, was induced with atrial premature beats. AF was induced with atrial pacing at 250 msec, was sustained and hemodynamically stable. The patient was cardioverted to sinus rhythm with a synchronized 100-joule biphasic shock.

A similar approach to Case #1 was incorporated for the mapping of this patient’s accessory pathway, except that mapping of the antegrade insertion of the pathway was feasible in this case. Due to the negative delta wave in lead II, a coronary sinus venogram was performed. There was no coronary sinus diverticulum, and mapping for earliest annular ventricular electrogram between the His bundle and coronary sinus ostium with a 6 mm tip Freezor® Xtra catheter suggested pathway insertion in the mid-septal region. A 20-pole HALO™ catheter was once again deployed to provide longitudinal discrimination of the pathway insertion along the tricuspid annulus. Figure 4 shows the intracardiac activation sequence during sinus rhythm; note that the octapolar His catheter was confirmed in the His bundle location during A1A2 pacing at AP ERP. The earliest antegrade ventricular electrocardiogram on the HALO™ catheter appears to lie between poles 8 and 9, and the ablation catheter records what appears to be a clearly definable pathway potential.
Serial cryo-applications were performed using the 6 mm tip Freezor® Xtra catheter at the site illustrated in Figure 4, impressively without success. The technique of fast mapping, a term referring to the time to effect on pathway conduction of less than 30 seconds, is relevant to the 6 mm and 8 mm tip CryoCath ablation catheters as currently available in the U.S. market. Fast mapping was utilized in this case; however, despite the presence of the apparent AP potential, no effect was observed on the pathway conduction after 7 lesions, including several lesions of over 1 minute in duration. Parameters relevant to an early time to effect (< 30 seconds) include distance of the conducting tissue from the advancing arc of cooling (dynamic thermal gradient) and the relative dimensions of the conducting pathway. Catheter tip to tissue non-adherence may lead to a failure to achieve maximum negative temperatures; however, the console issues an alarm in such instances. High flow across the tricuspid annulus may also have contributed to failure to achieve pathway block with the 6 mm tip cryoablation catheter, due to the heat sink of the blood pool limiting tissue cooling. With mapped electrograms as good as were observed in this case, we hypothesized that the pathway was located deeper in the mid-septal fat, and elected to size up to the 8 mm tip Freezor® MAX (CryoCath, Inc.).

Figure 5 illustrates the positioning of the 8 mm tip Freezor® MAX at the site of successful accessory pathway elimination, with corresponding intracardiac electrocardiograms shown in Figure 6. Reassessment of our mapping technique was performed, including re-initiation of orthodromic tachycardia with confirmation of the antegrade and retrograde insertions of the accessory pathway using the 20-pole HALO™ catheter. The retrograde insertion of the pathway during SVT appeared to be displaced more superiorly, toward the His bundle and nearest to pole 8 of the HALO™ catheter. Initial cryo-application to this site with the Freezor® MAX resulted in a time to effect (pathway elimination) of just under one minute, and the lesion was consolidated with a 5-minute freeze at -85° C. Not surprisingly, given the relatively lengthy time to effect (approximately 60 seconds), pathway conduction was noted to recover upon thawing. A second cryo application was subsequently performed at the identical location, shown in Figure 6, with a time to effect of 7 seconds. The effects of the second cryo lesion are observed in the first 4 beats to result in a progressive and definitive elimination of accessory pathway conduction, and a consolidating freeze was performed for five minutes at -85° C; the pathway conduction never returned. Note that the interference on the distal ablation electrode is a consequence of ice ball formation on the bipolar electrocardiogram. The extent of the lesion generated by the 8 mm Freezor® MAX catheter is significant, as demonstrated by truncation of the atrial electrogram at HALO™ pole 8.

Discussion

The two cases presented are illustrative of some of the unique advantages of cryoablation technology, as well as some of the specific differences between cryoablation and RF ablation. Cryoablation represents a new paradigm for the interventional electrophysiologist, and there is a definite learning curve associated with applying cryobiology to achieve effective results. Unlike RF ablation, where large lesions are achieved almost immediately and permanently, lesion formation with cryoablation is progressive over time. The physical properties of the dynamic thermal gradient, in which a slowly expanding arc of tissue cooling results in transient effects on electrical conduction at regions less than 32° C, and permanent electrical effects (ablation) at regions held below 0° C, should always be kept in mind when applying cryo lesions. With the 6 mm and 8 mm tip cryoablation catheters available in the U.S. market (CryoCath, Inc.), a technique of fast mapping is employed. This term simply refers to the fact that these catheters deliver the liquid nitrous oxide at a maximum flow rate from the onset of injection; there is a time-dependent descent to maximum negative temperatures (usually -80 to -85° C) that typically occurs in the first 20 to 30 seconds. Biological effects occurring in this timeframe (elimination of pathway conduction, for example) are good signs of proximity to the structure being ablated, and continuing the injection for 4 minutes will generally lead to permanent ablation. Conversely, failure to achieve biological effects within the first 30 seconds suggests that the ablation site may be inaccurate, and that further mapping is warranted.² Time to effect is a more generic term, and is used as a measure of time to onset of the biologic effect following initiation of the nitrous injection.

In Case #1, for example, a nearly immediate time to effect was achieved to terminate orthodromic tachycardia (less than 15 seconds), suggesting close proximity of the cryoablation tip to the accessory pathway. Had AV block been observed in the first beats following termination, an immediate thaw cycle would likely have been effective in reversing the block, as it is necessary to maintain temperatures at sub-zero for a period of several minutes to effectively ablate tissue. Since cryo-induced pathway interruption was presumed to be the mechanism for tachycardia termination, a consolidating lesion was performed for four minutes, resulting in permanent annihilation of pathway conduction.

By contrast, in Case #2 none of the sites mapped with the 6-mm catheter resulted in an early time to effect, despite what appeared to be outstanding target sites for ablation. In what amounts to be the cryoablation corollary to “learning while burning,” this case required “learning while freezing.” We hypothesized a deeper course of the pathway as it crossed the AV groove in the mid-septum, and that the inefficacy with the 6 mm tip cryoablation catheter was a function of inadequate lesion depth. Had this been a RF ablation case, the impulse might have been to increment up to a cool-tip or saline-perfused catheter for deeper penetration — probably not a good idea in such close proximity to the AV node and His bundle. We elected to size-up to the 8 mm tip cryoablation catheter to achieve the goal of deeper lesion formation. With the first cryo-application using the 8 mm tip catheter, the time to effect was just under 60 seconds, consistent with convergence of the dynamic thermal gradient with the accessory pathway. Despite a 5-minute cryo lesion, the pathway was observed to recover conduction over the first minute of thawing. Rather than move the catheter to a new location, a second lesion was performed at the same location, resulting in a nearly instantaneous time to effect of just under 7 seconds; a consolidating lesion applied at -85° C over 5 minutes resulted in permanent annihilation of pathway conduction. This phenomenon, in which a repeat lesion is performed following a thaw cycle leading to an earlier time to effect and a more permanent interruption of electrical conduction, has been coined a freeze-thaw-freeze cycle by the cryoablation community. The implication of the freeze-thaw-freeze cycle is that deeper lesion formation is facilitated following the initial lesion and subsequent osmotic cellular lysis during thawing.⁷ The biophysics of this phenomenon is a topic of ongoing investigation; however, the cryo-ablationist may wish to capitalize on the freeze-thaw-freeze cycle to achieve better long-term outcomes.

Conclusions

For accessory pathways located in the septal location, the safety margin facilitated by cryoablation has raised the EP community standard of care. The unique aspects of cryo lesion formation, including potential for reversibility, tissue adherence, preservation of underlying tissue architecture and diminished thrombus formation,7 will likely expand the role of cryoablation for this substrate and other regions of the heart where collateral tissue injury is a concern. Improvement in outcomes for individual operators will depend on increased experience and understanding of cryo lesion formation.

References

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