The Ballooning Use of Cryo

In December 2010, the U.S. Food and Drug Administration (FDA) approved the Medtronic Arctic Front^® Cardiac CryoAblation Catheter system for ablation of medically refractory, paroxysmal atrial fibrillation (AF). Shortly afterwards, the cryoballoon became widely adopted at many medical centers in the United States. This adoption occurred in the absence of published, peer-reviewed, U.S. randomized clinical trial data on its long-term efficacy. There are probably many factors that resulted in its rapid dissemination and adoption. One factor is that there have been data published demonstrating the safety and efficacy of the cryoballoon to achieve pulmonary vein (PV) isolation. Other factors include local competition, a sense that the procedure can be done more quickly with the cryoballoon, a culture of early adoption of new technology, effective marketing and industry support for cases, and desperation by those who have been doing AF ablation to finally have a tool other than a standard radiofrequency (RF) electrode catheter to isolate the pulmonary veins. Nonetheless, there has been little in terms of long-term outcomes data to support using the cryoballoon instead of conventional radiofrequency ablation.

Fortunately, in the March 2013 issue of the Journal of the American College of Cardiology (JACC), two large studies of the cryoballoon were published. One study is the long-awaited publication of the U.S. multicenter, randomized STOP-AF trial.¹ The preliminary data from this trial were first presented at the ACC conference three years ago. It is not clear why there was such a delay between completion of the trial and publication of the full manuscript in a peer-reviewed journal. However, the data are important because they come from the pivotal U.S. trial that led to FDA approval. The second study is a very large, single-center, prospective observational study of the long-term outcomes of 605 patients who underwent cryoablation in Germany.² 

There are important similarities and differences between these two studies. Not surprisingly, successful PV isolation of all four PVs with just the balloon was similar in each study, and was achieved in about 90% of patients. In addition, single-procedure success rates were also similar in each study, ranging from 58–62%. Both the small (23 mm) and large (29 mm) size balloons were used in half of the patients in the European single-center trial — the use of the smaller balloons or both balloons was associated with better success rates. The success rates are disappointingly low, especially since in the STOP-AF trial, freedom from AF after ablation while being treated with a previously ineffective antiarrhythmic drug at the same or a lower dose was considered a treatment success. On the other hand, a recurrence was defined as “any detectable AF after the blanking period.” Using that endpoint fails to account for the benefit enjoyed by patients who have a high AF burden and do well except for a few rare episodes of AF during follow-up.

Regarding safety, there were few major complications, and PV stenosis was rare. The most concerning complication in these studies was phrenic nerve injury. Despite the frequent use of the smaller balloon in the European trial, the rate of phrenic nerve injury was lower in the European trial at 2% compared to 11% in the U.S. trial. The fact that phrenic nerve injury was much more common in a multicenter trial compared to a single-center trial suggests that operator experience may be key to avoiding it.

In the absence of clinical trials directly comparing the cryoballoon to standard irrigated RF ablation — the only other FDA-approved ablation tool for AF — it is difficult to make a case that cryoablation should be used in all patients undergoing ablation for paroxysmal AF. Indirect comparisons would suggest that there is no evidence that the outcomes associated with the cryoballoon are better than they are for RF. However, the data from the STOP-AF trial may not apply to the current common practice of using exclusively the 28 mm second generation balloon, and a circular mapping catheter through the shaft of the balloon catheter to monitor for conduction block during a freeze. There is also no evidence that the cryoballoon is safer. It is now clear that complications such as left atrial-esophageal fistula formation that were thought not to be possible with the cryoballoon, can definitely occur and can be lethal.³ However, for many users of the cryoballoon, the same motivators that resulted in its early adoption continue to hold. There is no doubt that for many physicians, the cryoballoon, especially the newer generation balloon, allows the procedure to be done more quickly. Probably the biggest reason that adoption of the cryoballoon has not been even greater is cost.

Based on the data from these two cryoballoon ablation trials, including single-procedure success rates of about 60%, one can conclude that the cryoballoon is safe and effective and may be comparable to RF for catheter ablation of AF. However, much work is needed to improve a procedure that is designed to tackle a problem as big as AF.

References

1. Packer DL, Kowal RC, Wheelan KR, et al, for the STOP AF Cryoablation Investigators. 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;61:1713-1723.

2. Vogt J, Heintze J, Gutleben KJ, Muntean B, Horstkotte D, Nölker G. Long-term outcomes after cryoballoon pulmonary vein isolation: results from a prospective study in 605 patients. J Am Coll Cardiol. 2013;61:1707-1712.

3. Stockigt F, Schrickel JW, Andrie R, Lickfett L. Atrioesophageal fistula after cryoballoon pulmonary vein isolation. J Cardiovasc Electrophysiol. 2012;23:1254-1257.