Dear Readers,

In the United States (U.S.), ablation catheters are required to be approved by the Food and Drug Administration (FDA) before they can be used for cardiac ablation. However, as most electrophysiologists realize, most ablation catheters are approved for limited indications such as ablation of atrial flutter, or generically for ablation of cardiac tissue. There are no catheters specifically approved for use during ablation of atrial fibrillation (AF). Instead, AF ablation procedures are performed using catheters that are labeled for use for other indications.

So-called “off-label” use of drugs and devices is at the discretion of the physician and is common in the U.S. However, there are several problems introduced by this practice. One problem that is pertinent to the field of cardiac ablation is the problem faced by industry when trying to develop novel tools for AF ablation. At this time, companies designing a study to determine the safety and efficacy of a new ablation tool cannot perform a randomized trial comparing their new device to currently used devices, because the currently used devices are not approved by the FDA for AF ablation. Therefore, companies are left to perform a randomized trial with antiarrhythmic drug therapy as the control arm. Unfortunately, it can be very difficult to enroll patients in these types of trials, because a large number of patients with AF who are referred to an electrophysiologist are refractory to drug therapy and are often expecting to be offered an ablation procedure. Slow enrollment in AF ablation trials is one reason for the lack of progress over the past decade in the development of a better tool for AF ablation.

For various legitimate reasons, electrophysiologists performing AF ablation have moved toward the use of cooled tip ablation electrodes. In the recent A4 study that compared catheter ablation to antiarrhythmic drugs for AF (published in Circulation in December 2008), 88% of the cases were performed using an irrigated tip electrode. Although most of the procedures in the A4 study were performed outside the U.S., the saline open-irrigated RF ablation catheter has become the standard catheter for AF ablation at many U.S. centers. It is remarkable, however, that not only has this catheter never been approved by the FDA for AF ablation, it has been approved only for ablation of type I atrial flutter and recurrent drug/device refractory sustained monomorphic ventricular tachycardia due to prior myocardial infarction in adults.

Although most physicians are comfortable using drugs and devices for “off-label” uses, the manufacturers of these therapies often seek FDA approval for specific indications and labeling. For example, Biosense Webster has sought a labeling indication for the NaviStar ThermoCool catheter to be used for ablation of AF. The premarket approval (PMA) application by Biosense Webster requests to expand the indication for use to include “treatment of drug refractory symptomatic paroxysmal atrial fibrillation.” On November 20, 2008, the Circulatory System Devices Panel of the FDA met to review the ThermoCool PMA submission. The sponsor presented data from a prospective, randomized trial involving 19 centers and 167 subjects with symptomatic paroxysmal AF who were refractory or intolerant to antiarrhythmic drug therapy. Patients were randomized using a 2:1 ratio to ablation or medical therapy. Following presentation of the study data, the Panel voted unanimously in favor of “Approvable with Conditions.” A meeting summary and a list of the conditions are publicly available on the FDA website.

Assuming that the FDA follows the advice of the Panel, there are many implications of an expanded indication beyond the ability of a specific company to market AF ablation and support educational and training programs. Approval could also have a significant impact on the development of future AF ablation tools. For example, will trials already underway with drug therapy as the control arm have more difficulty enrolling patients after there is an FDA-approved device? Will companies developing AF ablation tools be permitted by the FDA in the future to design a trial where the comparison arm is ablation with an already approved catheter rather than drug therapy? Although elimination of the requirement to use drug therapy as the control arm might seem logical, in the past the FDA has required each company seeking approval for a specific therapy to replicate a study using the same design as the company that was granted initial approval. In the mid 1990s, for example, even after the FDA approved the first coronary sinus lead for cardiac resynchronization therapy, the remaining device companies were required to complete a randomized trial with medical therapy as the control arm. It is critical that initial efficacy requirements by the FDA do more good than harm to medial practice.

After a decade of using “off-label” catheters for AF ablation, FDA approval of a catheter that is already being used routinely will be welcome. It will be important, however, that if the FDA approves catheters for AF ablation, that the much-needed technological innovations in the field of AF ablation will not be impeded.

Sincerely,

Bradley P. Knight, MD, FACC, FHRS
Editor-in-Chief, EP Lab Digest