The Promise of Pulsed-Field Ablation: Cautious Optimism Amid Some Unknowns

With the recent approvals of two pulsed-field ablation (PFA) systems, US physicians now have additional options for treating their patients with atrial fibrillation (AF). Even those who are balking at the initial high cost of the new technology envision PFA taking on much of the AF ablation workload from conventional radiofrequency and cryoballoon catheters.

PFA comes with faster procedural times and lower risks of serious complications like damage to the esophagus and phrenic nerve, along with comparable outcomes in terms of rhythm control compared with thermal technologies. It is the improved efficiency and better safety that have electrophysiologists (EPs) predicting a major shift in how they’ll be performing AF ablation moving forward, despite some unresolved questions about the long-term durability of the ablations, the impact of silent cerebral lesions seen on MRI after the procedure, integration with mapping systems, and others.

The first PFA approval from the US Food and Drug Administration came late last year, with the PulseSelect system (Medtronic) gaining indications for both paroxysmal and persistent AF. Then, in January, the FDA approved the Farapulse system (Boston Scientific) for the treatment of paroxysmal AF.

K.R. Julian Chun, MD (CardioAngiologisches Centrum Bethanien, Frankfurt, Germany), has been performing PFA for about 3 years now, with the Farapulse system having gained CE Mark approval in Europe in January 2021.

Discussing what US physicians might expect in the coming years based on what happened in Germany, while acknowledging differences between the European and US markets, Chun said that PFA “has the potential to be a disruptive technology in the field which could change the landscape of traditional AF ablation.”

What PFA Brings to the Table for Safety

Electrophysiologists have gotten good at using radiofrequency and cryoballoon ablation, which have been around decades, but there are some concerns with these thermal technologies. The energy they deliver has the potential to spread beyond the myocardium into surrounding structures like the esophagus and phrenic nerve, raising the risk of serious complications. PFA, on the other hand, ablates through electroporation, delivering high-energy electrical pulses that breach cell membranes. It appears to be relatively specific to myocardial tissue, limiting collateral damage.

This improved safety is one of the major selling points for PFA. In the MANIFEST-17K study out of Europe, for instance, rates of major complications were low overall, with none of the more than 17,000 patients developing atrio-esophageal fistula, pulmonary vein stenosis, or persistent phrenic nerve injury. Phrenic nerve palsy that resolved by discharge occurred in 0.06%.

[This] has the potential to be a disruptive technology in the field which could change the landscape of traditional AF ablation. K.R. Julian Chun

For Oussama Wazni, MD (Cleveland Clinic, OH), the main advantage of PFA is safety during pulmonary vein isolation and the ability to ablate more on the posterior wall without having to worry about the esophagus. Avoiding problems with the phrenic nerve is a plus, too. “If it turns out that we can safely and consistently ablate in areas where we think the phrenic nerve may be an issue, and not have phrenic nerve paralysis, then I think that’s also something that’s reassuring,” he said.

Improving the safety of ablation is important, Devi Nair, MD (St. Bernards Medical Center, Jonesboro, AR), stressed, because it is an elective procedure done largely to improve symptoms and quality of life. She noted that injury to the esophagus can be fatal.

Improved Efficiency, Similar Outcomes

PFA also can generally be performed more quickly than either radiofrequency or cryoballoon ablation. In ADVENT, PFA had shorter mean total procedure time (106 vs 123 min), left atrial dwell time (59 vs 84 min), and ablation time (29 vs 50 min), albeit with a longer fluoroscopy time (mean 21 v 14 min). And in the PULSED AF trial of the PulseSelect system, the median left atrial dwell time was about 60 minutes, which included a protocol-mandated 20-minute waiting period. Taking that out, procedures took about 30 to 40 minutes, much shorter than the 1.5 to 2 hours typical with thermal ablations.

Chun noted that after workflow adjustments, AF ablation cases lasting around 30 minutes have become standard of care in Germany.

Studies have shown that PFA has similar efficacy in terms of arrhythmia outcomes when compared with thermal ablation with radiofrequency or cryoballoon catheters. For instance, in the ADVENT trial, the first randomized comparison of PFA and thermal techniques, freedom from a variety of arrhythmia-related endpoints was 73.3% in patients treated with the Farapulse system and 71.3% with conventional ablation.

Nair noted that in the European registry studies and even the investigational device exemption trials here in the United States, PFA was compared against thermal ablation techniques that have been refined over many years, and the fact that they have stood up well in terms of efficacy indicates that the learning curve for PFA is short.

Extending the Reach of Ablation

PFA also seems to be associated with slightly better patient satisfaction—at least anecdotally—compared with thermal ablation.

Michael Shehata, MD (Smidt Heart Institute at Cedars-Sinai, Los Angeles, CA), principal investigator for the ADVANTAGE AF trial, which is evaluating the Farapulse system in patients with persistent AF, said that based on his personal experience with PFA, “I don’t see any real significant postablation symptoms in terms of inflammation, pericarditis, chest pain, anything like that that you sometimes saw with thermal ablations.”

Considering that, along with the improved safety profile, shorter procedures, and similar outcomes, PFA may allow for more patients to undergo AF ablation than would have been able to before, multiple physicians indicated. In particular, EP labs that can perform more ablations per day will start to be able to work through their waiting lists more quickly.

The added safety will open this therapy to a lot of populations that I would have hesitated [to treat] in the past. Devi Nair

Beyond this, Nair said, “the added safety will open this therapy to a lot of populations that I would have hesitated [to treat] in the past.” She pointed to patients at both the younger and older ends of the age spectrum where physicians might want to wait a bit or try more antiarrhythmic drugs before intervening with ablation. “To me, I think this will help hopefully move the therapy into truly first-line therapy.”

Chun agreed with this, adding that the reproducibility and technical ease of PFA may allow for ablation of patient populations that wouldn’t necessarily undergo a procedure at the first sign of the arrhythmia. He noted that his group has done some research on using PFA for patients in the emergency department and in those with heart failure with preserved ejection fraction. “I would expect moving into patient cohorts which we typically would not ablate in the first place right now.”

“The way I would put it,” Wazni said, “is that it may decrease the threshold to offer an ablation in certain patient groups.”

Some Notes of Caution

Amidst all the enthusiasm for PFA, however, there are still some unanswered questions as physicians think about how integrate the technology into their practices.

PFA is still a relatively new technology in the earlier generations of catheter design, which contrasts with radiofrequency and cryoballoon systems that have been around for many years. Thus, Nair said, there’s still a lot to learn about PFA—in terms of both safety and efficacy—as the number of real-world cases grows.

Nair noted that the MANIFEST-17K registry from Europe demonstrated the overall safety of PFA but revealed some cases of rarer complications, including hemolysis leading to acute renal failure and coronary spasm, both of which are considered manageable.

“As you start seeing the system being used in the real world . . . we will start seeing all the other things we potentially didn’t see in IDE trials,” which are conducted at selected sites with experienced operators and monitored very carefully, Nair said, highlighting the need to collect real-world data as PFA rolls out.

Multiple EPs also indicated that there will be a learning curve with PFA, particularly for operators used to performing radiofrequency ablation. Manipulation of the PFA catheters is more similar to use of cryoballoon catheters, they indicated.

Wazni cautioned new users of PFA to be careful when maneuvering the larger catheters in the left atrium to avoid perforations, noting that in the ADVENT trial, one patient died from a perforation related to catheter manipulation.

Shehata and others suggested that there’s the possibility the safety profile might change as PFA goes into wider use out in the community. “But at least in the initial preclinical work and then the clinical work that was done, it doesn’t seem that this technology has a safety disadvantage—if anything, it seems like it has a slight advantage over current thermal techniques,” he said.

Prior studies of PFA have shown that there is a risk of silent cerebral lesions detected by MRI after the procedure, but it’s unclear whether that is related to the PFA catheters themselves, the large-bore sheaths allowing air to enter the bloodstream, or the high-energy pulses. “I don’t think it’s alarming to me yet, but it’s something I’m going to keep an eye on,” Nair said.

Durability of the lesions created by PFA and how that compares to radiofrequency or cryoballoon ablation is another open question.

“It seems to be the efficacy is on par with current thermal ablation techniques, but I think that’s a thing we have to really keep an eye on,” Shehata said. “If we’re doing cases in half the amount of time but half the patients are coming back, that’s not a good thing.”

Overall, he said, “I think there’s a lot of enthusiasts of PFA, because of its efficiency, but only time will tell as we start to use the technology a little bit more . . . does it have any significant disadvantages?”

The Economics of PFA

As with any new technology, the cost of PFA exceeds that of radiofrequency or cryoballoon ablation, and several EPs agreed this might influence how quickly it gets adopted. Nair said her group has been involved in the clinical trials since 2021, so they had budgeted to be able to introduce PFA as soon as it was approved. But other centers will need to work the costs in to future budgets, she added. “You can’t just bring in a new technology overnight.”

Shehata called the price difference between PFA systems and others “significant.” Compared with either radiofrequency or cryoballoon ablation with a diagnostic mapping catheter, PFA comes in at about $2,000 more per case, he said, noting, however, that with rebates based on certain procedural volumes, the cost of PFA has been brought closer to what the system pays for the other modalities.

“The initial price uplift is quite significant if you don’t meet those target rebates,” he said, agreeing the issue could present a barrier for smaller centers looking to introduce PFA.

Speaking from the perspective of someone who has no personal experience with PFA but who is considering it for his center, Sumit Verma, MD (Baptist Heart & Vascular Institute, Pensacola, FL), said that cost is a major determinant of uptake right now. At his own center, “the cost that we’re seeing being proposed is just prohibitively high,” Verma reported. “What the companies are saying is that you can do more per day and sort of make up for it, but it’s just not going to work with those numbers.”

The way I would put it is that it may decrease the threshold to offer an ablation in certain patient groups. Oussama Wazni

Finances will vary based on the type of procedures that are being performed and what add-ons are used. Things like mapping systems, steerable sheaths, or intracardiac echocardiography all come with additional costs. But for AF ablations, the workhorse for EP labs, “hospitals don’t have a huge margin on these,” Verma said. “Then if you’re being told that, ‘Okay, now it’s going to cost you $5,000 more per case,’ that margin just doesn’t exist for the vast majority of hospitals.”

This presents a good opportunity for hospitals and industry to figure out ways to deal with cost, Verma said, suggesting that companies might start bundling PFA with other technologies they have, like left atrial appendage occlusion devices.

Ultimately, though, PFA will gain wide uptake, Verma predicted, suggesting that having two competing PFA devices at the moment should help reduce costs. “It’s inevitable. I think every good program will be using PFA, and they should,” he said. “I think from what we’re hearing, it’s better for patient comfort. It’s a quicker procedure. It’s painless apparently. So there’s advantages and we’re just going to have to figure out how to make it work.”

Asked about how they are dealing with concerns about cost, representatives of Boston Scientific and Medtronic both highlighted the benefits of their PFA systems, including their safety profiles and improved efficiency.

“We feel the Farapulse PFA system is priced to support broad adoption commensurate with the benefits . . . and discuss such benefits with customers considering this new technology for their institutions,” a Boston Scientific spokesperson said.

And a Medtronic spokesperson said, “Physicians’ feedback to our PFA catheter has been excellent as they seek new ways to treat the rapidly growing population of A-fib patients. PFA catheters will be priced at a premium to current catheters on the market. We work with each of our customers to provide them with the best solutions for their unique needs, including PFA and other products across the cardiac ablation solutions spectrum.”

Excitement and ‘Cautious Enthusiasm’ Around PFA

In spite of some caution and uncertainties, the EPs interviewed by TCTMD were generally positive on what PFA will offer to the field in the coming years.

“It’s an exciting time for our patients. People have to be cautious [and] take it step-by-step, and eventually I think it’s a welcome development for our patients.”

How much share of the AF ablation load PFA will take depends on multiple factors, including cost, availability of the various devices, the type of procedural sedation used, and others, Chun said. But in the next few years, he predicted, “it will take a very, very big chunk of the AF ablation part.”

Nair foresees about 80% of EP labs starting to use at least one PFA system by the end of 2025. After just a short period of commercial availability, she said that her lab is doing about 70% of AF ablations with PFA and the other 30% with radiofrequency; previously, the mix was about 60% radiofrequency and 40% cryoballoon. This could change moving forward, she said, noting that cost is going to be a major determinant.

It's “a little early for us to say, but we’ll wait and see,” Nair said. She added: “I’m an eternal optimist . . . with cautious enthusiasm is what I would say.”

Shehata said he wouldn’t be surprised to see PFA used in 75% to 80% of AF ablation cases. “Once those barriers to entry in terms of cost are dealt with [and] if the efficacy holds up and there’s no huge safety signals that start to pop up, I can’t imagine that providers that do these procedures once they get their hands on this kind of technology are going to want to go back to cryothermal or RF ablation,” he said.

He added that he and his colleagues were “impressed” with the Farapulse system when using it in the clinical trials. “We were enthusiastic about adopting it early and that’s why when it first got commercial release we went ahead and got it right away,” Shehata said. “We’re excited. I think the future is pretty bright.”