NATIONAL HARBOR, MD. – , setting the stage for the device to become the first to receive U.S. labeling for catheter ablation in this atrial fibrillation population.
Thecryoballoon, used on 165 patients with persistent atrial fibrillation (AFib) enrolled in the trial, produced a 55% rate of treatment success, including freedom from recurrent AFib during 12 months of follow-up, and produced one prespecified serious adverse event in the primary safety endpoint.
Both results easily surpassed the prespecified performance goals set by negotiation with the FDA,, said at the annual International AF Symposium. The trial design included no control group and instead assessed safety and efficacy against prespecified standards set by the regulatory agency.
The cryoballoon “showed excellent performance. I don’t see how this could possibly be turned down by the FDA,” said Dr. Calkins, professor of medicine and director of the cardiac arrhythmia service at Johns Hopkins Medicine in Baltimore.
Cardiac electrophysiologists have for years routinely performed catheter ablation procedures on patients with persistent AFib even though the devices, based on ablation by radiofrequency or by chilling, have been labeled for use only in treating patients with paroxysmal AFib. Although this off-label use has not resulted in any problems with health insurance coverage, Dr. Calkins said, it has kept manufacturers from marketing their ablation devices for use in persistent AFib patients.
If the reported data result in labeling for the tested cryoballoon for persistant AFib patients, “it will have a big impact,” he predicted. “People have used cryoballoons for ablating persistent AFib for years, but this would put more fuel in the fire, both the [very positive] safety and efficacy data, and getting an FDA label, which is worth a lot,” he said in an interview.
But Dr. Calkins stopped short of anticipating that the results would convince operators experienced and focused on performing radiofrequency ablation to switch to cryo devices for treating persistent AFib patients. “People are pretty stuck in their ways,” he noted, and reports are expected soon from pivotal trials that are now testing various radiofrequency devices, as well as other types of cryo devices, in persistent AFib patients, so the range of device options labeled for this population may soon grow even more.
Thetrial ran at 25 sites in the United States, Canada, and Japan during March 2017-August 2019, and included 165 adults with symptomatic, persistent AFib who had not responded to at least one antiarrhythmic drug and had a history of AFib episodes lasting at least 7 days but with no episodes persisting for 6 months or longer. The study excluded patients with prior ablation or left atrial surgery, a recent cerebrovascular event, substantially reduced left ventricular function, or substantial left atrial enlargement.
The enrolled patients were an average 65 years of age and 70% were men. Patients had been diagnosed with paroxysmal AFib an average of 5 years before study entry and with persistent AFib a little over 6 months before entry. The most recent AFib episode of enrolled patients averaged about 60 days, on average they had been unsuccessfully treated with just over one antiarrhythmic drug, and on average they had previously undergone about two cardioversions, after which their arrhythmia recurred.
The primary efficacy endpoint – a 55% rate of acute procedural success plus freedom from AFib recurrence during the 9 months following a 90-day blanking period immediately after ablation plus no added or increased antiarrhythmic drugs – significantly exceeded the prespecified performance goal of a 40% rate, Dr. Calkins reported. The study used the standard measure of recurrence as any 30-second or longer AFib episode detected during a weekly ECG telemonitoring session or during 48-hour ambulatory ECG monitoring at 6- and 12-month follow-ups or during in-office 12-lead ECG assessment at 3-, 6-, and 12-month follow-up. Twelve-month follow-up occurred for 145 of the enrolled patients.
The only prespecified primary safety event was one episode of cardiac perforation, which occurred during a repeat procedure. This rate of one safety event among 165 patients (0.6%) fell well within the prespecified safety performance goal of no more than 13%. In addition to this perforation, five additional serious adverse events (3%) occurred that were attributable to the cryoballoon treatment, including two cases of vascular pseudoaneurysm, one puncture-site hematoma, one case of pericarditis, and one episode of atrial tachycardia. Four additional serious adverse events occurred that were attributable to the ablation procedure (one acute cardiac failure, one postprocedure ileus, one respiratory failure, and one urinary tract infection), for an overall serious event rate of 5%.
During follow-up, 13% of patients had a repeat ablation procedure, following an initial ablation limited to pulmonary-vein isolation (PVI). The overall rate of 1-year efficacy, including the relatively low rate of need for redo ablation, “are an impressive endorsement of a PVI-only strategy” for initial ablation, Dr. Calkins said. “I’m a strong believer in PVI only for the first ablation for both paroxysmal and persistent AFib.”
He also noted that the 30-second threshold for scoring recurrent arrhythmia episodes following the 90-day blanking period after ablation was a very conservative measure of treatment failure, but it continues to define recurrence in this and many other current AFib ablation studies because it is the historical criteria for measuring ablation success or failure. It is especially important to maintain this criteria in a study that relied on prespecified performance criteria rather than a control arm for judging efficacy, Dr. Calkins said.
The study also included three quality-of-life measures. Patient scores on the Atrial Fibrillation Effect on Quality-of-Life () questionnaire rose by an average of nearly 26 points from baseline to 12 months, a statistically significant and clinically meaningful increase. Scores on both the physical and mental domains of the Short Form-12 ( ) improved from baseline by an average of about five points on each subscale, also statistically significant and clinically meaningful changes. Patients also reported statistically significant and in some cases substantial reductions in the prevalence rates of each of five different AFib symptoms: dizziness, dyspnea, fatigue, palpitations, and rapid heartbeat.
The study was funded by Medtronic, the company that markets the tested cryoballoon (Arctic Front Advance). Dr. Calkins has been a consultant to and has received honoraria from Medtronic, as well as from Abbott, AtriCure, Boehringer Ingelheim, Boston Scientific, and Johnson & Johnson.