Silver Spring, MD - A US Food and Drug Administration advisory panel voted unanimously to recommend approval of the first ablation catheter designed for the treatment of atrial fibrillation. The new device, known as the NaviStar ThermoCool (BioSense Webster, Diamond Bar, CA) radiofrequency ablation catheter, would be used for the treatment of drug-refractory symptomatic paroxysmal atrial fibrillation.

The Circulatory System Devices Advisory Panel attached some conditions to its approval, however, including the creation of a registry for long-term follow-up of safety and efficacy and further study in patients with ejection fractions <40%, with and without heart failure. Most notably, the panel voted to approve only the unidirectional ablation catheter with a CARTO location sensor.

"I feel very comfortable with the acceptability of safety of this device for this indication, but I don't think I can go any further than that," said panel chair Dr Jeffrey Borer (Weill Cornell Medical College, New York). "We know what we know and we'll learn more with more data, but I think we feel comfortable that we have enough information to make a risk/benefit relationship assessment based on this device."

Other panel members said they felt comfortable with the safety and efficacy of the device, based primarily on a pivotal study comparing antiarrhythmic drug therapy and ablation in patients with paroxysmal atrial fibrillation.

"I think the device will add a very important tool to the electrophysiologist's tool kit, one that we've been using to date, but this will give us more support and the ability for the sponsor to improve training and spread the use of this catheter, which I think will be very beneficial for our patients," said panelist David Slotwiner (Long Island Jewish Medical Center, New Hyde Park, NY).

Although the FDA does not have to follow the recommendations of the advisory, it usually does.

The recommendation to approve the ablation catheter was based on results from the multicenter study comparing antiarrhythmic drug therapy and radiofrequency ablation in patients with atrial fibrillation. Dr David Wilber (Loyola University Medical Center, Chicago, IL), who first presented the results at the American Heart Association meeting earlier this month, presented the results to the panel.

I think clinical utility is a different question.

The trial, a randomized, unblended, and controlled study, included 167 patients with symptomatic paroxysmal atrial fibrillation refractory to at least one antiarrhythmic drug. Patients also had to have at least three episodes of atrial fibrillation in the six months prior to randomization.

Overall, ablation of atrial fibrillation resulted in more freedom from the arrhythmia at nine months compared with patients treated with drug therapy. There were 16 adverse events reported, with initial and prolonged hospitalization being the most common. Vascular complications were also reported, although this was not believed to be the result of this specific device. There were no reported pulmonary vein stenoses in the ablation arm.

The FDA panel spent the day hashing out the safety and effectiveness of the catheter and was particularly concerned about the large degree of variation in ablation efficacy from site to site. One non-US center, for example, reported a 100% success rate at nine months compared with the 47% success rate reported at the other sites combined. This non-US center, known as OUS-1, was the largest enrolling site in the trial and accounted for 30% of enrolled patients.

Although nobody could explain the disparate results between the centers, many on the panel, as well as FDA representatives, suggested operator experience might explain the different success rates. The NaviStar ThermoCool catheter is currently available in Europe, and many European electrophysiologists have experience using it. Yet despite analyses showing that ablation's benefit was still significant when OUS-1 was excluded, the results raised some red flags among panel members.

"What I find a little troubling is if we look at the disparity between OUS-1 and the other centers, the other centers are centers of excellence," said panelist Dr Patricia Kelley (Montana Heart Center, Missoula). "These are big, busy labs with very experienced electrophysiologists. What's a little worrisome is if we go from OUS-1 to the other centers and our effectiveness drops by half, what are we going to see when we generalize these results [to other labs]? Is the effectiveness going to fall by half again?"

The panel spent additional time discussing analyses performed by the sponsor because the statistical approach was altered mid-trial to compensate for the slowed enrollment, a change the FDA said it found acceptable. The panel also spent significant time discussing whether or not to approve catheters incompatible with the CARTO navigation system. In the end, they voted only for the ablation catheter studied, with conditions, including its use with the CARTO system.

Anyone who has a paroxysm and feels palpitations is symptomatic, and I don't know if that is a reasonable basis for doing a catheter-based ablation.

Commenting on his reason for voting to approve the device, Dr Judah Weinberger (Columbia University, New York), along with others, said he believed the sponsor demonstrated that the device was safe and effective in the paroxysmal atrial fibrillation patient, although he remained unconvinced about the catheter's overall usefulness.

"I think clinical utility is a different question," said Weinberger. "I think there is a subset of patients who will drive me crazy enough that I'm willing to send them for a catheter ablation procedure, which has a 50-50 chance of working after eight hours in the EP laboratory. There is a subset of such patients, but they don't constitute the run-of-the-mill patients with atrial fibrillation."

In discussing a potential label for the ablation catheter, some believed the label should be specific, stating that the device is to be used for the "symptom treatment" of drug-refractory atrial fibrillation. Borer went one step further.

"People are going to use this the way they are going to use it," said Borer. "But I think the issue here is that this procedure, at this moment, with the data we have, should be used in people who have unacceptably debilitating symptoms despite efforts with drug therapy. I would be very specific with that language. I don't think the device is for symptomatic atrial fibrillation. Anyone who has a paroxysm and feels palpitations is symptomatic, and I don't know if that is a reasonable basis for doing a catheter-based ablation."

Slotwiner disagreed, telling the panel that atrial-fibrillation symptoms, and a patient's perception of those symptoms, can vary day to day, so a label that is too specific is not helpful. Others felt a strict or highly specific label moved closer to legislation and away from the art of medicine, which is what is required in some patients. The panel and sponsor agreed that any label should state that ablation is not intended to eliminate the use of anticoagulation.