Cryo vs. RF Ablation: Electrophysiologists Take a Tempered Approach

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[23]: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.”

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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 direct-current cardioversions (3.2 percent vs. 6.4 percent); fewer all-cause rehospitalizations (32.6 percent vs. 41.5 percent); fewer cardiovascular rehospitalizations (23.8 percent vs. 35.9 percent); and similar improvements in quality-of-life evaluations (Eur Heart J 2016;37[38]:2858-65).

In addition, an economic analysis presented in October at the Asia Pacific Heart Rhythm Society’s Scientific Sessions in Seoul, South Korea, reported that benefits such as cryo’s fewer repeat ablations and rehospitalizations in the trial would have provided $355,005 in cost savings to the U.S. health system.

Although FIRE AND ICE found cryo and RF to be comparable in overall safety, the types of complications differ between the two methods, Gold points out, with cryo having a greater risk of phrenic nerve injury and RF with perforation. “While it may not have been statistically significant in the study, there is a general consensus those are [risks] for those two procedures.”

Chun and Fisher also see cryo offering some safety advantages over RF. In an analysis of 3,000 atrial fibrillation ablations at his center between 2010 and 2015, Chun and his colleagues found the risk of cardiac tamponade was significantly reduced in patients treated by cryoballoon or laser balloon compared with RF ablation, findings that align with FIRE AND ICE data (JACC Clin Electrophysiol, online Sept. 7, 2016).

“It came out very clear that the risk of mechanical perforation, of cardiac tamponade, is very, very low with cryoballoon,” Chun says. “This is a unique safety feature.” He also sees cryo as a safer ablation option for atrial fibrillation patients treated with anticoagulation as well as antithrombotic therapy who are at a high risk of bleeding “because of what we learned; there is a very low risk of mechanical complications.”

Lesions tend to develop more slowly with cryo than with heat sources, Fisher says, which may give the operator more of a window to reduce the likelihood of unintended damage. “With radiofrequency, the effects are often faster so that the damage may be done before you can turn off the radiofrequency generator,” he says. He adds that cryo tends to produce plug-like scar tissue with defined edges and RF more variable scarring, depending on the depth of the burn. 

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Not that simple

These favorable findings don’t relegate RF to “has-been” status as a treatment for drug-refractory atrial fibrillation, electrophysiologists say. Complex patients may not be amenable to cryo, Chun says, adding that a balloon approach may not be best for certain patients with a history of atrial flutter or atrial fibrillation. “I would go for radiofrequency because it is more flexible,” he says. “It allows me to address additional issues beyond pulmonary vein isolation.”

Fisher notes that patients with complex or peculiar anatomies may not be optimally treated by cryo, which then may require a repeat procedure. “There are individuals, and they have come through some of the trials, where the veins simply do not get isolated or where you go back and the veins apparently have been isolated but reconnect, which means they weren’t isolated in the first place,” he says. “For those patients, touchups are often done by radiofrequency because probably the actual shape of the vein in that individual is too complex for the balloon tube to force it into the shape that the balloon needs to completely freeze the tissue underneath. Some of those nooks and crannies may be best approached by radiofrequency.”

Cryo may open the door for two tiers of care: centers that offer balloon-based procedures in patients with paroxysmal atrial fibrillation who are younger, healthier and have few comorbidities; and other centers—tertiary care centers, centers of excellence or the like—with RF expertise and the knowledge and resources to treat complex cases.

Chun is agnostic about the energy source but finds the overall balloon concept compelling. “Cryo is just the first of a new family. I think in a few years many procedures will be done with a balloon but [with] all remaining issues … we also need a 3D mapping system and radiofrequency. It is not over for radiofrequency. It will be linked to more complex procedures and more sophisticated original ablations.”