Medical Device Daily Contributing Writer

BOSTON – The aging of the world's population is having enormous consequences on healthcare in myriad ways. One of the most important is that diseases and conditions whose incidence and prevalence expands with each passing decade are gaining more attention from the medical community and the healthcare industry.

Although sudden cardiac death has been garnering the major headlines, both positive and negative, and has spawned the roughly $4 billion domestic implantable cardioverter defibrillator (ICD) industry, atrial fibrillation (AF) is increasingly gaining recognition in the cardiology world.

As it should, being the most common sustained rhythm disturbance.

More than 2 million Americans are currently afflicted with AF, with an additional 200,000 or higher being diagnosed annually. It is well known that AF increases dramatically with aging. Specifically, according to the Atrial Fibriilation Foundation (Reading, Massachusetts), while AF afflicts a modest 2.3% of the population over the age of 40, it occurs in about 6% of the population over 65 and nearly 10% of the population over 80 years of age.

It is also widely known that AF, which is characterized by erratic and dysrhythmic beating in the heart's upper chambers, is the cause of at least 15% of the annual 750,000 strokes that occur annually in the U.S.

Thus, it is no surprise that one of the key topics at this year's annual Heart Rhythm Society (HRS; Washington) meeting, which was held here for four days late last week at the new Boston Convention and Exposition Center, was devoted to the topic of AF. Numerous seminars, workshop, expert panels and evening symposium discussed this important topic.

AF is an ongoing conundrum for patients and their physicians, not only because it continues to increase with the aging population, but because its exact causes and, more importantly, successful therapies remain elusive.

Medical management is invariably the first line of AF defense. However, it has proven to be a disappointment, with poor efficacy rates and intolerable side effects for the majority of patients.

At a symposium titled “Working Together to Cure Atrial Fibrillation,” James Reiffel, MD, a cardiologist at the Columbia University School of Medicine (New York) diplomatically described the safety and efficacy of today's anti-arrhythmic drugs (AADs) as “sub-optimal.” He provided a thorough review of the modest benefits and toxicity of today's agents, discussed promising agents in the development pipeline and concluded that there are no new agents on the immediate horizon that will be significant advances to the AAD drug armamentaria.

A presentation at the Late Breaking Clinical Trial sessions on Saturday, from Pierre Jais, MD, a renowned cardiologist at Haut-Leveque Hospital (Bordeaux, France) showed that catheter ablation was far superior to AADs for AF patients who had already failed a least one drug regimen. Jais reported that ablation had a 75% success rate in stopping AF while AAD alone had a dismal 6% rate.

This landmark trial, the first to compare ablation to AAD, followed 112 patients at four centers worldwide for 12 months. Jais noted during his presentation that “patients for whom initial drug therapy is not effective should discuss with their doctors if ablation is a valid option.”

In the vacuum of mediocre AF drug therapy, device and surgical approaches have become increasingly seen as potential solutions.

Minimally invasive, percutaneous catheter ablation has evolved over the past several years from an experimental procedure to one that is commonly performed. In the U.S., for example, an estimated 15,000 to 20,000 ablations are being performed annually, with at least that many outside the U.S. Interestingly, all of these procedures are being performed “off label,” as no companies have yet secured an FDA approval for full scale marketing.

Based upon the status and progress of AF catheter ablation trials in the U.S., Medical Device Daily does not anticipate a PMA approval for at least two years and more likely three years.

The lion's share of AF ablations is now targeted at the left atrial pulmonary vein (PV). EP experts now generally agree that AF, especially the earlier stage paroxysmal (intermittent) type, is triggered in most patients by arrhythomogenic tissue that exists in the pulmonary vein.

An article in the March 6, 2006 issue of the New England Journal of Medicine (NEJM), authored by Hakan Oral, MD, et al. demonstrated that circumferential pulmonary-vein catheter ablation, using radio frequency heating, resulted in long-term relief of AF in 74% of patients with chronic atrial fibrillation. These results were seen as especially encouraging since chronic AF is generally considered to be the most challenging type of AF to cure.

However, industry observers generally do not believe that this impressive success rate is widely repeatable, as EP physicians who are considered to be the foremost catheter ablation practitioners in the world performed these procedures. Amongst their less skilled colleagues, AF ablations success rates are typically in the neighborhood of 50%.

At last year's HRS meeting, Riccardo Cappato, MD, of the Policlinico San Donato (Milan, Italy), reported on a worldwide survey of nearly 9,000 AF ablations that were performed at 100 centers between 1995 and 2002. Cappato noted that the reported success rate, defined as free of any medical management after six months, was a modest 52%, with another 24% experiencing reduced drug needs.

Another important issue is that AF ablations can be excruciatingly long, subjecting the doctor and patient to several hours in the EP cath lab.

Finally, and perhaps most importantly, the concept of what constitutes “success” is highly controversial and seen very differently across the EP world.

At a highly informative evening seminar titled “Clinical Trial Symposium and Panel Discussion,” sponsored by Atricure (West Chester, Ohio), cardiac surgeons who performed atrial fibrillation surgeries and EP physicians who do AF catheter ablation engaged in a lively and spirited discussion on this topic.

Some AF experts argued rather convincingly that symptomatic relief of AF is what matters the most. Indeed, the FDA's guidance document on AF ablations states that symptomatic relief is the most important endpoint of AF therapy.

In an excellent talk titled “Endpoints for Ablation of AFib,” Hugh Calkins, MD, director of electrophysiology at Johns Hopkins (Baltimore, Maryland), ticked off several potential measure of success in atrial fibrillation therapy.

These included elimination of all symptomatic and asymptomatic episodes of AF, elimination of only symptoms, reduction of symptoms, reduction of AF burden (a composite measure of several factors) and an improved quality of life.

Further complicating an already complex issue, Calkins posed the question “should success be defined in a different way for the various types [i.e., intermittent, persistent or chronic] of atrial fibrillation?”

Calkins also addressed the often overlooked issue of what is appropriate monitoring or reporting of AF. Is it the patient's subjective evaluation of how they feel? Should it be intermittent measurement on a random basis? Should it require continuous monitoring with an event recorder over a several day period?

He noted that in the NEJM study (reported on page 8), a significant inadequacy in reporting AF episodes may have occurred. Specifically, all patients were asked to record their rhythm for only three minutes per day and five days a week or whenever they had symptoms suggestive of atrial fibrillation.

Calkins further noted that an analysis of intensive event recording and monitoring has shown that less than 20% of all atrial fibrillation episodes are symptomatic. Thus, the 15 minutes per week of monitoring used in the NEJM study can be viewed as well below what might be necessary to capture their true incidence of AF and therefore casts doubt on the efficacy of the impressive results.

Moreover, if patients and their physicians believe that they are devoid of their AF and in normal (sinus) rhythm, they may be tempted to discontinue their anti-coagulation medication and be much more vulnerable to an embolic stroke, which could cause major morbidity or mortality.

While catheter ablation companies are mired in a long regulatory approval cycle, manufacturers of surgical ablation devices such as Atricure are moving forward with improved products.

Publicly-owned Atricure has been a leader in developing innovative tools for performing surgical ablation of AF. Initially, its radio frequency-based products addressed the market for “concomitant” AF ablation, with its devices used in conjunction with an open heart procedure. However, it has also been innovative in developing RF tools for so-called “standalone” minimally invasive surgery.

At the Atricure meeting, cardiac surgeon James Edgerton, MD, from the Texas Hospital of the Southwest (Plano, Texas) reported on a series of AF patients who underwent standalone ablation surgery.

Edgerton noted that his most recent series of patients, performed with the most current tools, have achieved excellent results. Specifically, at six-month follow-up, 84% of all patients were in normal sinus rhythm, as measured by a 21 day monitoring device. Amongst the intermittent AF patients treated, 92% were in sinus rhythm. Nearly all of these patients were able to completely eliminate their use of anti-arrhythmic medications.

Despite these encouraging results, Edgerton noted several important caveats. For example, the procedure required significant surgical skill and therefore had a steep learning curve. And the hospital length of stay was over five days on average, which most patients will be unhappy with, he said.

He also noted that the procedure needed to be improved further and that a totally endoscopic approach would really be the most exciting product development.

“I am very excited about the progress to date and look forward to the next product iterations with keen anticipation.”