Ablation & Afib: Zapping Barriers to Success

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Medtronic-Arctic-Front-Advance-Cryoballoon.jpg - Medtronic Arctic Front Advance Cryoballoon
Medtronic’s Arctic Front Advance Cryoballoon.

Some like it hot; some like it cold. Whether by radio frequency (RF) or cryoballoon, ablation interventions have been edging out medical therapy as an efficacious treatment for atrial fibrillation in some patients. But that doesn’t always translate into success, either clinically or financially. Costs, recurrences and lack of proof that the procedures offer a stroke benefit pose challenges.

“From observational studies, we really don’t have evidence that ablation reduces stroke risk,” says Douglas L. Packer, MD, a cardiologist at the Mayo Clinic in Rochester, Minn. “We have great evidence that it reduces symptoms, increases quality of life and eliminates atrial fibrillation in many but not all patients. We need (large clinical trials) to know whether ablation is of substantial stroke benefit.”

Principal investigator of STOP AF and the ongoing CABANA trial, Packer straddles both the now known and the still unknown. STOP AF, a randomized, controlled clinical trial, evaluated the effectiveness and safety of Medtronic’s Arctic Front cryoballoon in patients with symptomatic paroxysmal atrial fibrillation who had failed on at least one antiarrythmic drug (J Am Coll Cardiol 2013;61:1713-1723). But its follow-up was only one year with a patient cohort of 245. CABANA (Catheter Ablation Versus Antiarrhythmic Drug Therapy for Atrial Fibrillation) will randomize 2,200 patients with atrial fibrillation to ablation or drug therapy for a five-year follow-up.

CABANA’s completion date is still years away, though. In the meantime, technologies continue to evolve amid a changing fiscal landscape.

Putting it in practice

Atrial fibrillation statistics

  • Between 2.7 million and 6.1 million adults in the U.S. have the disease
  • That figure is expected to double in the next 25 years
  • Treatment costs total $26 billion in the U.S. annually
  • More than 467,000 hospitalizations and 99,000 deaths annually are attributed to the condition

Source: J Am Coll Cardiol online March 28, 2014

Results from recent ablation trials have given electrophysiologists more confidence to move forward with ablation programs. In the Medtronic-sponsored STOP AF trial, for instance, physicians achieved pulmonary vein isolation using the cryoballoon alone in 83 percent of patients. Patients treated with cryoablation had a 12-month treatment success rate of 70 percent compared with 7 percent of the patients treated with antiarrhythmic drugs.

The overall serious adverse event rates at 12 months were similar in the two groups, but researchers noted that ablation-related complications such as pulmonary vein stenosis and phrenic nerve injury were possible.

“STOP AF was looking at patients who have paroxysmal atrial fibrillation in the absence of underlying disease, so it is very representative of patients with relatively early atrial fibrillation,” Packer says. “If you look at a typical practice, the most common variety of atrial fibrillation is paroxysmal.”

Trials evaluating catheter ablation have reported rates on par with STOP AF. The ThermoCool AF Trial enrolled a patient population somewhat similar to STOP AF and randomized them to either ablation treatment with Biosense Webster’s ThermoCool catheter or antiarrhythmic drug therapy (JAMA 2010;303[4]:333-340). At nine months, 66 percent of the ablation group was atrial fibrillation-free compared with 16 percent of the drug group with a 30-day treatment-related adverse event rate of 9 percent vs. 5 percent. Biosense Webster sponsored the trial.  

Guidelines in the U.S. and Europe recommend catheter ablation performed by a trained electrophysiologist as a treatment for patients with paroxysmal atrial fibrillation who have failed or can’t tolerate at least one antiarrhythmic drug. More recently, the 2014 Guideline for the Management of Patients with Atrial Fibrillation in the U.S. called for an additional role for RF ablation. With several RF catheters and the Arctic Front cryoballoon and catheter system FDA-approved for paroxysmal atrial fibrillation, operators now have options in their treatment decisions. Some physicians welcome the efficiency of the cryoballoon, which doesn’t require point-by-point delivery in several applications to isolate the pulmonary vein. Others favor the versatility of RF catheter ablation, which also can be performed efficiently in the hands of a proficient operator.

“Some labs find they can get through an isolation procedure more quickly with cryo,” says Matthew R. Reynolds, MD, MSc, a cardiologist at Lahey Hospital and Medical Center in Burlington, Mass., and a ThermoCool AF investigator who has experience with both approaches. “That is not universal. Some people are very fast with RF.”

He adds that the cryoballoon specifically targets the pulmonary veins. “In patients where you want to do more than simply isolate the veins, there may be an advantage for an RF catheter, which with a single catheter allows you to isolate the veins and then do whatever ancillary ablation you think is necessary or optimal.”

The six electrophysiologists at Spectrum Health in Grand Rapids, Mich., prefer cryoballoon ablation for isolating the pulmonary vein in patients with paroxysmal atrial fibrillation, says Spectrum Health’s Andre Gauri, MD, because it is “a relatively simple approach and, most importantly, highly effective.” His practice has achieved a success rate of more than 80 percent with cryo; but for ablating beyond pulmonary vein isolation, he and his colleagues use RF catheters.

And it is not the energy source that poses a dichotomy, Gauri proposes, citing investigational technologies that use RF but in a seamless rather than traditional point-by-point “spot welding” approach. “It is point-by-point vs. more of a one lesion that ablates the whole vein.”

Costs & margins

The first goal in an atrial fibrillation program is to assure quality outcomes, acknowledges Sharon Van Beek, electrophysiology manager at Spectrum Health. As a business manager, she evaluates resources and costs to obtain efficiencies in the electrophysiology lab. The practice has been growing steadily, from about 600 ablations in 2007 to about 1,100 in 2012. In 2012, it became a dedicated cost center.

Shorter procedure times and a high success rate have allowed her to schedule more ablations and chip away at a backlog of patients. “[A cryoablation] is pretty consistently getting to be a two hour procedure whereas ablations were 10 hours when they first came out,” she says. She schedules four hours for an RF ablation, which Gauri points out may be a more complicated case.

Gauri estimates that he typically performs three procedures a day. “I would never try to do three RFs in a day just because of fatigue,” he says.   

But cryoablation’s promise of faster, less painstaking procedures is not a given. Just as with mastering point-by-point RF, there is a learning curve, and implementing cryo may prove costly. Electrophysiologists at Winthrop University Hospital in Mineola, N.Y., shared their experience using cryoablation in their program between December 2010 and July 2012 (J Invasive Cardiol 2013;25[6]:288-292). In a comparison of 62 RF ablations and 62 ablations using the cryoballoon, they calculated that cryoablations took 45 minutes longer to perform, had a similar fluoroscopy rate, required infusion of protamine more often and cost the hospital almost $7,500 more.

The immediate success rate was higher with cryoablation, at 97 percent vs. 94 percent for RF, and there was no significant difference in complications. But the higher hospital cost prompted the physicians to question the overall value.

Currently there is only one cryoballon device commercially available in the U.S., observes Reynolds, who is also director the Economics and Quality of Life Research Center at the Harvard Clinical Research Center in Boston. With no competing vendor, hospitals may not be in a position to negotiate prices—although Van Beek may have found options to help trim down costs. Her team identified catheters that might be substituted within the Medtronic cryoballoon package.

“That would be $300 less a catheter,” she says. “You can use that as a negotiation point, or if the doctors say, ‘They work just as well. I don’t mind using them,’ then we could always trial it [and] save money that way.”

Van Beek is conducting an analysis looking at the cost per case per physician that she will share with electrophysiologists to help them better understand the financial impact of their practices. “We don’t let money rule our judgment,” she says. She describes a scenario where the physician performing a cryoablation encounters a different type of arrhythmia than had been detected previously. “So you do a roofline ablation using another catheter. The cost of that case just went sky high. I need to show them that this is what happens. Not that you can’t do it, but to be aware.” 

What Reynolds describes as the shifting sands of reimbursement only complicates efforts to achieve positive profit margins. For calendar year 2013, the Centers for Medicare & Medicaid Services decided to reduce the work value in new ablation codes. “Last year we took a hit and this year we are getting it back, I heard as much as 17 percent,” Van Beek says.

First-line therapy

Andrea Natale, MD, executive medical director of the Texas Cardiac Arrhythmia Institute at St. David’s Medical Center in Austin, and colleagues in the RAAFT-2 study propose that RF ablation can play a role as a primary treatment for patients with paroxysmal atrial fibrillation. RAAFT-2 (Radiofrequency Ablation vs. Antiarrhythmic Drugs for Atrial Fibrillation Treatment) was a multicenter randomized controlled clinical trial that compared RF ablation with antiarrhythmic drugs in treatment-naïve patients with paroxysmal atrial fibrillation (JAMA 2014;311:692-699). Biosense Webster provided the funding.

They enrolled patients between 2006 and 2010 and followed them for 24 months. Of the 61 patients in the standard care group, 72.1 percent had a recurrence of any kind of atrial tachyarrhythmia lasting 30 seconds or more compared with 54.5 percent of the 66 patients in the ablation group. The ablation group had a lower rate of recurrence of symptomatic atrial fibrillation, atrial flutter or tachycardia compared with standard care (47 percent vs. 59 percent). There were no strokes or deaths in either group, but the ablation group had a higher percentage of serious adverse events, at 9 percent vs. 5 percent for the group treated with antiarrhythmic drugs.

“It is fair to say that with RAAFT-2 and other studies that will be published, it is now reasonable as a first-line therapy in that patient population,” Natale says. The patients in RAAFT-2 were relatively young, with a mean age in the mid-50s, with no or little evidence of structural heart disease.

High rates of recurrence, either with ablation as a first-line or second-line treatment, may undermine the potential benefit of treatment. Packer says the recurrence rate is at least 30 percent after ablations, regardless of the energy source. “Some of those will go away, maybe one third, after the irritation and inflammation of the ablative intervention passes,” he says. “Some of them require medical therapy and some require repeat ablation.” 

Reducing the redo rate

Repeat ablations place added burden on the patient, the healthcare system and the provider as well. Nassir F. Marrouche, MD, director of the electrophysiology lab at the University of Utah Health Sciences Center in Salt Lake City, has shown in DECAAF that delayed enhancement MR imaging can be a useful tool for stratifying patients for catheter ablation. DECAAF (Delayed-Enhancement MRI Determinant of Successful Radiofrequency Catheter Ablation on Atrial Fibrillation) enrolled 329 patients between 2010 and 2011 with atrial fibrillation who underwent catheter ablation (mostly RF) and were followed for at least one year. Less than 30 days before the procedure, patients underwent delayed enhancement MRI of the left atrium to quantify the degree of atrial fibrosis.

They found that the percent of atrial fibrosis was strongly associated with recurrent arrhythmia, defined as recurrence as any episode of atrial fibrillation, atrial flutter or tachycardia of at least 30 seconds that occurred after the 90-day blanking period. By day 325, the unadjusted cumulative incidence of recurrent arrhythmia was 15.3 percent for stage 1 (detected fibrosis of less than 10 percent of the atrial wall), 32.6 percent for stage 2 (10 percent or greater but less than 20 percent), 45.9 percent for stage 3 (20 percent or greater but less than 30 percent) and 51.1 percent for stage 4 (30 percent or greater). By day 475, it was 15.3 percent, 35.8 percent, 45.9 percent and 69.4 percent, respectively.

“We think the future of ablation will never sustain repeat ablation,” Marrouche says. “What we did in DECAAF is show that you can choose people who have a higher success rate,” which correlates into needing fewer second procedures. “That is a dilemma all of us, patients and the health system, are facing.”

The University of Utah started applying the MRI screening protocol systematically about 20 months ago. Results have shown that stage 1 patients have an 85 percent chance of being atrial fibrillation-free, according to Marrouche. By comparison, stage 4 patients have a 7 percent chance. “When we started ruling patients out, the success rate in all-comers increased to 70 to 75 percent at two years.”

MR imaging further helps identify stage 2 to 3 patients who may or may not benefit from ablation. “If you have more than 20 percent fibrotic changes on MRI you should look at the type of fibrosis,” he advises. “Is it everywhere in the heart or localized? If is localized you can give it a shot; there is about a 50 percent chance. If it is generalized, then I would not touch it.”

MRI adds to the cost of the procedure, which Marrouche argues is offset by savings from avoiding repeat procedures. MRI also requires proper training; 17.3 percent of DECAAF patients were not evaluated because of poor quality MRI imaging, primarily due to technologist error. He says technologists typically gained competency after imaging five patients.

Evolving technologies

The cryo and RF fields continue to evolve. The FDA-approved cryoballoon has undergone iterative changes that may facilitate use, with mixed reports on its effect on outcomes. One nonrandomized study that compared the older and newer device reported shorter procedures with the newer device but an uptick in transient phrenic nerve palsy (HeartRhythm 2014;11:386-393). The authors identified a reliable intraprocedural predictor of phrenic nerve palsy that might reduce the incidence of this complication. Another study comparing the old and newer devices found an 80 percent success rate at one year (Cir Arrhythm Electrophysiol online March 8, 2014). 

FDA approval of Biosense Webster’s ThermoCool SmartTouch catheter may increase the efficacy of RF procedures. The device provides real-time, contact force measurements during an RF ablation to help ensure consistent contact. In the SMART-AF trial, whose results Natale unveiled at Heart Rhythm 2013, about 74 percent of patients with drug-refractory symptomatic paroxysmal atrial fibrillation were atrial fibrillation-free at 12 months, with success rates more than 10 percentage points higher when operators stayed within a targeted contact force range more than 85 percent of the time.

“The technology is improving to help physicians do a better job with the experience they have,” Natale says.

Besides redesigns of approved products, several cryo and RF investigational devices are progressing through trials, Reynolds says. “There is iteration in both areas and hopefully that will translate into clinical improvement in both areas.”

But the ultimate goal with ablation remains a reduced stroke risk. “The stroke risk component is very concerning because it is devastating,” Packer says. On that front, the jury is out until CABANA and other large-scale randomized trials provide credible evidence. “The issues of effectiveness and other safety issues like complication rates need to be very closely examined. The good news is electrophysiology in general has been willing to take a very hard look at those kinds of questions and outcomes.”


Calculating ablation’s value

Ablation as a second-line treatment in patients with atrial fibrillation proved cost-effective using either radiofrequency (RF) catheters or cryoballoon ablation in two separate analyses. Better outcomes or higher costs could tilt the value higher or lower, though.

Matthew R. Reynolds, MD, MSc, a cardiologist and director the Economics and Quality of Life Research Center at the Harvard Clinical Research Center in Boston, led two studies that evaluated the cost-effectiveness of ablation compared with antiarrhythmic drug therapy in drug-refractory patients with paroxysmal atrial fibrillation. The studies took the perspective of the healthcare system; a U.S. perspective for the RF approach (Circ Arrhythm Electrophysiol 2009;2:362-369) and a United Kingdom payer perspective for the cryoballoon (Europace, online Jan. 2, 2014).

Both analyses showed ablation to be reasonably cost-effective but the overall value was sensitive to procedure costs and outcomes. “Any time you move the effectiveness needle, you can make the cost-effectiveness better or worse,” Reynolds points out.

Ablation, like many cardiovascular treatment strategies, carries upfront costs. “Whether the patient benefits or not, you have spent the money,” he says. Practices that reduce the need for repeat procedures or screen out patients less likely to benefit therefore boost the value of ablation.

Reynolds noted that the studies applied data from trials that evaluated RF and cryoballoon ablation in patients with paroxysmal atrial fibrillation. “The patient populations that have been involved in these randomized trials compared to the atrial fibrillation population as a whole are relatively young and healthy. If you move outside of those populations, the effectiveness falls and the cost-effectiveness could be less favorable.”

 - Ablation's Value