Medical Device Daily Executive Editor

DENVER — If there is a regulatory/off-label-use limbo for medical devices, one of the featured technologies residing there certainly must be catheter ablation to treat atrial fibrillation (AF).

The interventional method of creating lesions in the atrium vs. the surgical approach is receiving increasing off-label use — and catheter manufacturers are developing a growing number of technological advances for these uses — but approval in the U.S. for any of the device systems for this application seems far over the regulatory horizon.

While physicians may be doing as many as 60,000 catheter-based AF procedures worldwide each year (though no one knows the real number), there are no FDA approvals for any devices for this specific application (though many for general soft-tissue use).

Much of the reason for this regulatory vacuum appears to lie in the difficulty of the specific application and the lack of standard protocols for this strategy, adding up to a broad lack of clinical study data — at least not enough deemed acceptable by the FDA.

Attempting to reverse the latter of these two difficulties, key cardiovascular associations on both sides of the Atlantic unveiled a new report at the scientific sessions of the Heart Rhythm Society (HRS; Washington) this week in an attempt to provide some agreements about the procedure, what has held it back thus far and what needs to be done to push it forward. Besides the HRS, the groups are the American College of Cardiology (Washington), the American Heart Association (Dallas), the Society of Thoracic Surgeons (Chicago), the European Heart Rhythm Association (EHRA; Sophia Antipolis, France) and the European Cardiac Arrhythmia Society (ECAS).

While the report seems pitched to create a baseline for improved data-gathering for reimbursement and regulatory approvals, the three presenters of the report downplayed those possibilities. Rather, they tended to emphasize the need to develop consistencies in carrying out and assessing these procedures.

The report concentrates on the "consensus" of practitioners who most often agreed on certain practices, via anonymous surveying, but this did not mean there was always total agreement. The primary area of consensus was on the practice of "targeting" the pulmonary vein (PV) "and/or PV antrum [as] the cornerstone for most AF ablation procedures." The goal of this is "complete electrical isolation."

Asked concerning practices where there may have been no general agreement, Hugh Calkins, MD, director of electrophysiology at Johns Hopkins University (Baltimore) and chair of the HRS task force that developed the report, said that there were differences of opinion concerning how to treat what is termed "persistent" AF, that is, when the initial treatment failed to reduce the arrhythmia.

Additionally, Calkins said there were varied opinions concerning the use of an initial "aggressive" approach to ablation vs. a "step-wise" approach, adding that he personally favored the step-wise strategy.

Overall, Calkins, along with the two other presenters – Josep Brugada, MD, of Hospital Clinic, University of Barcelona, representing EHRA; and Riccardo Cappato, MD, Arrhythmia and EP Center (Milan, Italy), representing ECAS — indicated that there has been a less than rigorous approach to the use of catheter-based ablation. And they agreed on the need for a great deal more evidence concerning a variety of endpoints.

Thus far, according to the report, ablation to treat AF, whether the surgical or catheter approach, has been focused on improving the patient's quality of life, and it said that there has been no evidence to demonstrate longer-term endpoints, such as the ability to prolong life or avoid stroke and other co-morbidities.

Other than quality of life, these longer-term endpoints, the report says, "have not been systematically evaluated as part of a large randomized clinical trial and are therefore unproven."

And the report says that catheter ablation for AF should not be considered for primary therapy but is best used in "the presence of symptomatic AF refractory or intolerance to at least one Class 1 or 3 antiarrhythmic medication."

Overall, the 34-page report (43, given the list of research references) offers a rather daunting group of challenges for pushing forward with research in this area. These include a list of 14 "unresolved questions" concerning clinical trial considerations and a list of 21 standards for better understanding the safety and efficacy of AF ablation.

These standards are needed, the report says, because: "There are substantial differences in treatment modalities, endpoints of acute and long-term success, post-ablation blanking periods, follow-up, redo and cross-over treatments, as well as variability in accounting for asymptomatic AF, and incomplete accounting for adverse events occurring beyond the first week of therapy."

The report refers to the pilot-phase Catheter Ablation versus antiarrhythmic Drug for Atrial Fibrillation (CABANA) trial, being conducted by St. Jude Medical (St. Paul, Minnesota) as providing large enough enrollment over a long-enough period to offer data concerning mortality and the effect of catheter ablation "in those with advancing age, underlying heart disease, and more established AF, which will be applicable to a broader range of patients commonly seen in real life clinical practice."

It refers to other ongoing FDA trials but says: "Since most of these investigations are industry-sponsored, these studies have almost universally limited enrollment to patients with paroxysmal AF without underlying disease." Their limitations, it says, include "short follow-up durations, and restrictive inclusion and exclusion criteria."

Other needs detailed by the report include recommendations for procedure training, patient selection, follow-on drug use and follow-on monitoring.

A handful of device manufacturers will be happy with the report because specifically named therein.

It refers to the CARTO system from Biosense Webster (Diamond Bar, California) and the NavX system from Endocardial Solutions (Minneapolis) as the "two most widely used systems" for mapping and identification of ablation sites.

It also cites Stereotaxis (St. Louis) and Hansen Medical (Mountain View, California) for the development of remote catheter navigation to avoid "orthopedic problems related to prolonged use of protective lead aprons."

But as to the effectiveness of these mapping technologies, it says, "studies are not available to demonstrate that either of these systems shortens procedure time, improves outcomes of ablation, or improves the safety profile of these and other complex ablation procedures."