Cardiac Catheter Ablation Takes Aim at Atrial Fibrillation

Clinicians hopeful randomized studies will spur regulatory clearance.
By: 
Nick Obradovich

 

February 11, 2009

The practice of cardiac catheter ablation may experience a big boost as catheter ablation systems are poised to be indicated for the treatment of atrial fibrillation (AFib).

According to the Millennium Research Group’s (MRG) U.S. Markets for Electrophysiology (EP) Mapping and Ablation Devices 2009 report, an increase in the number of catheter ablation procedures for treating AFib will fuel revenues in the EP ablation catheter market over the next five years. The ablation catheter market reportedly will exhibit strong growth from 2008 to 2013, at a compound annual rate of almost 14 percent, exceeding $480 million by the end of 2013, said the report.

Cardiologists already treat simpler forms of arrhythmias with catheter ablation such as Wolff-Parkison-White Syndrome, Type I atrial flutter and atrioventricular nodal re-entry tachycardia (AVNRT), and are making a strong push to get regulatory clearance to treat AFib, according to MRG’s report and clinicians.


The Push for Clearance

In January 2009, Medtronic Inc. agreed to acquire Ablation Frontiers, a move designed to expand Medtronic’s radiofrequency (RF) ablation technology offerings for the treatment of AFib. In 2006, Ablation Frontiers received CE Mark to begin marketing its system of catheters and the RF generator. Ablation Frontiers is conducting a clinical trial under an FDA investigational device exemption (IDE) to gain approval for permanent, or chronic, AFib in the U.S., Medtronic said.

This acquisition comes on the heels of Medtronic’s acquisition of CryoCath Technologies, a manufacturer of cryoablation treatments of AFib.

At the American Heart Association’s Scientific Sessions (AHA 2008) in November, Biosense Webster released results from its randomized clinical trial, which showed that catheter ablation outperformed anti-arrhythmic drug (AAD) therapy for the treatment of symptomatic paroxysmal AFib.

The company said the trial was a randomized, unblinded and controlled evaluation of symptomatic, paroxysmal AFib patients who were refractory to at least one AAD and had at least three episodes of AFib in the six months prior to randomization. The primary effectiveness was freedom from documented symptomatic AFib recurrence following procedural endpoint confirmation and absent new AAD use or repeat ablation outside of protocol-defined criteria. The probability of chronic success was 62.7 percent for the patients receiving Biosense Webster’s NAVISTAR THERMO-COOL catheter ablation at the nine-month evaluation period, while the probability of chronic success was 17.2 percent for AAD. The NAVISTAR THERMOCOOL Catheter ablation group experienced no device-related serious adverse events such as death, heart attack, stroke, cerebrovascular accident, heart block or atrial perforation within seven days post ablation. There was no clinically significant pulmonary vein stenosis in patients receiving ablation and the incidence of serious adverse events in the NAVISTAR THERMOCOOL Catheter group in the 90 days following initiation of therapy was observed to be about half of that in the AAD group (35.1 vs. 18.1 percent).

“The results are consistent with clinical experience,” said David Wilber, M.D., principal investigator of the study and a professor of cardiovascular science and director, division of cardiology, Loyola University Medical Center in Maywood, IL. “There have been a few other small trials that have been conducted in patients with paroxysmal AFib, which showed a similar advantage. Those trials were done with a variety of different tools, a variety of definitions of endpoints…this was probably the largest multicenter study. I think the results are encouraging because it was over a wide range of centers and had very good results.”

Dr. Wilber believes the NAVISTAR THERMOCOOL is a safe system due to its continuous irrigation feature.

“By providing continuous irrigation and cooling of the catheter tip, it helps prevent overheating of the endothelium immediately underneath the ablation catheter,” Dr. Wilber said. “This reduces the risk of charring and thrombus formation during radiofrequency energy application, and the risk of stroke and other thromboembolic events.”

As a result of the trial, the Circulatory System Devices Panel of the FDA unanimously recommended approval of Biosense Webster’s pre-market approval supplement for the NAVISTAR THERMOCOOL Catheter for the treatment of symptomatic paroxysmal AFib. Conditions for approval recommended by the review panel include a post-marketing registry and a physician education program about use of the product.

“Probably the most important part of that trial was it was one of the first times where there was regulatory approval based on that data,” said Gerald Naccarelli, M.D., professor of medicine, Penn State College of Medicine, chief, division of cardiology, Penn State Milton S. Hershey Medical Center. “We’ve been using catheters and systems approved for mapping and diagnostics and ablation of atrial flutter and other things. Through some of this data, we’re completing the loop of commercial approval. There was always this minimal amount of nervousness on if people were doing the right thing all along and the Food and Drug Administration might say ‘well, you’ve been doing this for 10 years, but you’re doing it with a bunch of devices that aren’t approved for that indication,’ so I think there was some advantage to the trial. It’s an effective system if it’s used properly.”


CABANA Trial

According to clinicians, more data is needed to understand the short and long-term outcomes of catheter ablation for the treating AFib.

“What we don’t have are prospective randomized trials,” Dr. Naccarelli said. “[There is] very little data comparing it against anti-arrhythmic drugs, how recurrences were counted. Were asymptomatic or symptomatic counted? How hard are we going to look? We know lots of people have recurrences while healing up. Are we going to count them or not? We didn’t hear back from the patient, so we assume he’s doing well and call that a cure. There are some issues related to that kind of stuff. The whole anti-coagulation issue: We don’t know what to do if these patients are chronic anti-coagulation patients, patients with hypertension diabetes, heart failure, old patients.”

The upcoming CABANA trial will go a long way in answering more clinical questions regarding treating AFib with catheter ablation, according to Drs. Naccarelli and Wilber. CABANA is designed to test whether left atrial catheter ablation treatment to eliminate AFib is superior to the current state-of-the-art therapy with either rate control or AAD for reducing total mortality (primary endpoints) and decreasing the composite endpoints of total mortality, disabling stroke, serious bleeding and cardiac arrest (secondary endpoints) in patients with untreated or incompletely treated AFib warranting therapy, according to www.clinicaltrials.org. Biosense Webster, St. Jude Medical, CryoCath, Bard and Boston Scientific all have catheter ablation systems that will be used in the trial.


Future Developments

While CABANA will help cardiologists learn much more about catheter ablation, new technologies continue to be developed and experimented with by cardiologists to better treat arrhythmias.

Dr. Wilber noted two systems that help eliminate manual manipulation of the catheter. The Sensei Robotic Catheter System and the Artisan Control Catheter by Hansen Medical are designed to robotically guide the catheter. Stereotaxis’ Gentle Touch Magnetic System guides catheter movement by manipulation of externally applied magnetic fields.

“Each of these [navigation] systems have potential advantages in that they may reduce operator variability, and allow better and more consistent contact with the heart when energy is applied,” Dr. Wilber said. “However, these systems are expensive, and also have a significant learning curve for efficient operation. The question is what the ultimate role of these systems will be. Some people think these technologies will revolutionize catheter ablation and its role in atrial fibrillation, making results more consistent across centers and operators. There are others who feel the role [of these navigators] won’t be as prominent. Whether these systems will improve the quality and consistency of ablation outcomes is unknown at present, and will be the subject of intense investigation over the next few years.”

Zayd Eldadah, M.D., Ph.D., director of cardiac arrhythmia research at The Washington Hospital Center in Washington D.C., believes cryoablation therapy is an appealing alternative energy source because of its reversibility. Ultrasound is another experimental energy source that may someday have clinical merit, but has run into technical glitch, said Dr. Eldadah.

Sidebar

Catheter Ablation vs. Surgical Ablation: An Update

The debate about catheter ablation, surgical ablation and where both fit into the continuum of treatments for arrhythmias such as atrial fibrillation (AFib) isn’t going to end anytime soon. Both technologies have made strides to treat AFib and other arrhythmias.

In November, Biosense Webster released results from its randomized clinical trial, which showed that catheter ablation outperformed anti-arrhythmic drug (AAD) therapy for the treatment of symptomatic paroxysmal AFib.

On the surgical side, vendors have been looking at ways to make surgical ablation safer.
St. Jude Medical’s Epicor Cardiac Ablation System uses High Intensity Focused Ultrasound (HIFU) energy to replicate ablation lesion sets epicardially, without the need to place the patient on a heart-lung bypass machine. This is reportedly the only surgical ablation system that doesn’t require bypass for cardiac ablation.

“With surgical ablation, most patients — about three to one — are being done in concomonent to other heart surgeries being done,” said Mark Groh, M.D., cardiothoracic surgeon Ashville Cardiovascular and Thoracic Surgeons in Ashville, NC. “If you look at the mix of patients who have atrial fibrillation, three of them will have either coronary artery disease or aortic valve disease to every one that has mitral disease. The reason that is important is that with coronary artery disease or aortic valve disease, you don’t have to open the left atrium. That’s not a required part of the operation. To open that chamber up to do ablation that is required with other devices adds incremental risk to those patients.”

Clinicians are confident that both catheter and surgical ablation have their place in treating AFib, but are fuzzy on exactly how or when those standards will be agreed on.

“We’re just going to be getting into [coming up with guidelines for surgical ablation versus catheter ablation],” Dr. Groh said. “I think a lot of surgeons, particularly myself, are naïve about a lot of what was going into establishing a program to AFib. Cardiologists expect us to be diligent in our follow up. They expect us to have results that they can look at viably. That hasn’t been something most surgeons have done ever. Most surgeons operate on a patient, see them in two or three weeks and don’t see them again. Now we’re following these patients for years. We have patients who we’ve followed for up to four years for their ablation, so that cardiologists now understand that we’re interested in taking care of this problem.”

“There are some case series reported, but there have been no randomized multicenter studies comparing surgical ablation to other forms of ablation or even drug therapy,” said David Wilber, M.D., principal investigator of the study and a professor of cardiovascular science and director, division of cardiology, Loyola University Medical Center in Maywood, IL. “One issue is that there are a variety of surgical procedures to treat atrial fibrillation. The classic surgical MAZE is an open chest procedure involving extensive lesions in both the right and left atrium, and has been established by numerous studies to be one of the most effective approaches to control AFib. It is associated with somewhat greater morbidity and risk than typical catheter ablation procedures. However, many of the current surgical procedures involve less extensive ablation, often as an attempt to reduce the invasiveness and extent of chest incisions required. These ‘less invasive’ or minimally invasive surgical procedures have not been well validated with respect to long-term outcome, or compared to other forms of AF treatment. One cannot extrapolate the results of the classic surgical MAZE to these ‘downsized’ procedures, and it is unclear whether they offer advantages over less invasive catheter ablation.

“It will probably work out that there will be some patients, and some clinical circumstances, when surgery offers a better outcome than catheter ablation,” he said.

Dr. Groh also believes that cardiologists and heart surgeons will make a strong effort to establish the proper care with respect to both procedures.

“What I really think is going to happen in the next three to five years, there will be hybridized approach,” Dr. Groh said. “Patients will be sorted as we understand what kind of ablation strategy is most advantageous for them.”

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