About one year ago, FIRE AND ICE trial investigators reported that cryoballoon ablation (cryo) performed as well as radiofrequency ablation (RF) as a treatment for patients with drug-refractory paroxysmal atrial fibrillation. But is “as good as” good enough to change practice? The answer may be emerging just now.
Not hot, not cold reactions
The randomized controlled clinical trial FIRE AND ICE compared cryo using Medtronic’s first-generation Arctic Front or second-generation Arctic Front Advance cryoballoon with RF using one of three generations
of Biosense Webster’s ThermoCool catheters in 762 patients with paroxysmal atrial fibrillation. The results, presented in April 2016, at the American College of Cardiology (ACC) Scientific Sessions in Chicago and simultaneously published online in the New England Journal of Medicine, found no significant difference in either efficacy or safety between the two methods (N Engl J Med 2016;374:2235-45). Procedure duration was shorter in the cryo group, but fluoroscopy time was greater compared to RF. Medtronic sponsored the study.
“The endpoint in both groups was the same,” says K.R. Julian Chun, MD, a FIRE AND ICE investigator at Cardioangiologisches Centrum Bethanien in Frankfurt, Germany. “Who would be the ideal candidate for radiofrequency or cryoballoon? Just based on the data, I would have to say it doesn’t matter. Whatever you do, if you do it in experienced hands, it will be the same outcome.”
The trial required operators to have performed at least 50 ablations using one method or the other and each participating center had to have an operator proficient in each of the methods. If a new catheter was introduced, the operator had to have experience in at least 10 procedures with that catheter before including patients on that catheter in the trial.
As a consequence, Chun points out, all participating centers were proficient in RF techniques, which require careful mapping and meticulous point-by-point ablation to isolate pulmonary veins. Cryoballoon, on the other hand, is relatively simple. It uses fluoroscopic guidance to position the catheter. The operator then advances the balloon, inflates it and applies coolant for a circumferential ablation of the pulmonary vein.
Chun’s center treated 131 patients in the trial, making it the study’s second-highest volume center. The equivalence in endpoints seen in FIRE AND ICE may translate to high-volume centers like his that may perform 1,000 ablations or more annually, he says, but not necessarily to lower-volume centers with less RF acumen. “For mid-volume centers, balloon is very attractive.”
And there lies the crux. Centers with electrophysiologists who have mastered the technical challenges of RF ablation may see little value in switching to cryo, says John D. Fisher, MD, director of the Einstein-Montefiore Arrhythmia Service at the Albert Einstein College of Medicine in the Bronx and chair of the ACC’s electrophysiology section. “Noninferiority did not inspire people who were content with radiofrequency,” Fisher says.
Yet anecdotally, lower-volume centers that treat less complex patients appear to have embraced cryo, observes Michael R. Gold, MD, PhD, director of the cardiology division at the Medical University of South Carolina in Charlotte and president of the Heart Rhythm Society. “Most, if not all, centers use cryo now, where it was pretty selective before,” Gold says. “The increase has probably been more enhanced in smaller centers.”
Medtronic’s filings with the U.S. Securities and Exchange Commission add support to that notion. In its quarterly report for three months ending Oct. 28, the company credited “continued global acceptance” of its cryoablation system for a 6 percent gain in net sales in its cardiac and vascular group over the same period in the previous fiscal year.
Fisher also sees cryo as on the cusp. “We are in a lull right now before a major wave of acceptance,” he says. “It has taken a while for the other message [to be accepted]: Yes, it was noninferiority, but there were other things that would make people tilt toward cryo if they learn more details.”
Other research findings
An analysis of secondary endpoints that included total clinical events from the index procedure to participants’ exit from the trial gave cryo a statistically significant edge over RF on several fronts. The FIRE AND ICE team reported fewer repeat ablations in the cryo group vs. the RF group (11.8 percent vs. 17.6 percent); fewer