Debate continues regarding the relative pros and cons of cryoballoon ablation (CBA) compared to point-by-point radiofrequency ablation (RFA) to achieve pulmonary vein isolation (PVI) as a treatment for paroxysmal atrial fibrillation (PAF). The potential advantages of CBA include a more uniform and wider ablation zone, single transseptal access, less endothelial disruption, and decreased procedural times. The potential disadvantages include a higher rate of phrenic nerve injury, a larger sheath size, inability to use the cryoballoon for ablation of other structures such as the cavotricuspid isthmus targeted during the same procedure, and higher costs.
The largest, randomized trial comparing CBA to RFA — the FIRE AND ICE trial — was simultaneously published in the New England Journal of Medicine and presented on on April 4th as a Late-Breaking Clinical Trial during the American College of Cardiology’s 65th Annual Scientific Session in Chicago. The FIRE AND ICE trial was a prospective, multicenter, controlled, non-inferiority trial that compared the efficacy and safety of PVI using the Medtronic Arctic Front™ Cryoballoon Catheters versus the Biosense Webster THERMOCOOL® point-by-point radiofrequency ablation catheters with the CARTO® 3D mapping system in patients with medically refractory PAF. The study was funded by Medtronic, which manufactures the cryoballoon.1 A total of 762 subjects were randomized in a 1:1 ratio at 16 sites in eight countries in Europe. The primary efficacy endpoint was a creative and considerate composite of time to first documented recurrence of AF >30 sec/atrial tachycardia (AT)/atrial flutter (AFL), prescription of an antiarrhythmic drug, or re-ablation, whichever comes first with a blanking period of three months after the initial procedure. The primary safety endpoint was a composite of all-cause death, all-cause stroke/transient ischemic attack (TIA), and serious treatment-related adverse events.
The results of the study were that CBA was noninferior to RFA with respect to efficacy, and there were no significant differences in safety. The success rates at one year were nearly identical at about 65%. Ablation with the cryoballoon was faster but with slightly higher fluoroscopy times. Although there was no overall difference in the composite safety endpoint, and no statistically significant differences between specific complications rates, which were all relatively low, there was an appearance of tradeoffs. For example, there was a higher rate of phrenic nerve injury (PNI) unresolved at discharge with CBA compared to RFA (2.7% vs 0%), but a lower rate of groin complications, post-ablation ATs, and pericardial effusions with CBA.
One limitation of FIRE AND ICE is that this study, like most AF ablation trials, includes a 90-day blanking period. Although there is logic behind this trial design to allow for a healing phase after the procedure, there is a sense by most electrophysiologists familiar with both technologies and data from several publications that the incidence of post-ablation ATs during the blanking period is much lower after CBA compared to RFA. These tachycardias during the first few weeks after ablation can be difficult to manage and can lead to a bad patient experience, but are not accounted for in the efficacy analyses of these studies. Future trials should consider post-ablation ATs in the blanking period as part of the composite complication endpoint.
Another limitation of the trial was that the ablation technology evolved during the study; improvements in the ablation tools resulted in use of Biosense Webster’s THERMOCOOL SMARTTOUCH® catheter with contact force sensing in about one-quarter of the RFA cases, and use of the second-generation cryoballoon in about three-quarters of the CBA cases. The authors attempted to account for this shift by performing additional analyses of the efficacy performance data based on catheter type, but failed to detect any statistically significant differences. This may have been due to smaller sample sizes of each group, because visually, the curves representing failure rates suggest that the addition of contact force had no benefit on efficacy in the RFA group, but use of the second-generation cryoballoon may have improved efficacy in the CBA group.
The FIRE AND ICE study is a landmark trial and establishes CBA as good an ablation tool as RFA for patients with PAF. However, based on these results, those who currently have a preference between burning or freezing will likely not change their minds, and the debate will continue as to whether, with currently available technology, CBA is better than RFA or not.
- Kuck KH, Brugada J, Fürnkranz A, et al. Cryoballoon or radiofrequency ablation for paroxysmal atrial fibrillation. N Engl J Med. 2016 Apr 4. [E-pub ahead of print]