Varipulse Pulsed-Field Ablation System Safe, Effective in Pivotal Trial

Pulsed-field ablation (PFA) with a system encompassing the Varipulse catheter and Trupulse generator with integrated 3D electroanatomic mapping (all Biosense Webster) safely and effectively treats patients with paroxysmal atrial fibrillation (AF), results of the pivotal admIRE trial show.

With short procedure and PFA application times and low fluoroscopy exposure, the system was associated with a low rate of adverse events within 7 days of ablation (2.9%) and no cases of postprocedural thermal esophageal injury, coronary spasm, or hemolysis-related acute kidney injury requiring dialysis.

In terms of efficacy, the rate of freedom from atrial arrhythmias through 1 year was about 75%, which is in line with results from the earlier inspIRE study of the Varipulse system as well as studies of other PFA technologies, researchers led by Vivek Reddy, MD (Mount Sinai Fuster Heart Hospital, New York, NY), report in a study published recently online in Circulation. Reddy previously presented the results at the Heart Rhythm Society’s annual meeting in May.

What makes Varipulse stand out from the two PFA technologies that received US Food and Drug Administration approval over the past year—PulseSelect (Medtronic) and Farapulse (Boston Scientific)—is its integration of the Carto 3 electroanatomic mapping system, Reddy told TCTMD. This attribute, along with routine use of intracardiac echocardiography, reduced fluoroscopy use. One-quarter of cases, in fact, were performed with no fluoroscopy at all.

Most US electrophysiology labs already use this mapping system with other ablation modalities, and that may help uptake of the Varipulse system if it’s ultimately approved by the FDA, Reddy suggested. “My guess is that physicians would welcome having another option that's linked to a mapping system that they're used to.”

Commenting for TCTMD, Komandoor Srivathsan, MD (Mayo Clinic, Phoenix, AZ), said the admIRE results are enough to gain FDA approval for the technology, whose biggest strength is the integrated mapping system. “But does it excite me as a practitioner? The answer is no,” he added.

Other companies with PFA systems are likely to have their own mapping systems integrated soon, he said, noting that the efficacy results of Varipulse are not that different from those obtained with the other pulsed-field or thermal ablation technologies on the market.

In addition, Srivathsan cited concerns about the 1.1% rate of cerebrovascular events, which included two strokes and one TIA. “That is somewhat worrisome,” he said, adding that he doesn’t believe the issue is related to a lack of familiarity with sheath management since the study was performed at experienced centers with seasoned operators. He suggested that it could have to do with this catheter’s PFA waveform, a feature that differs between various technologies and remains proprietary to each manufacturer.

“Basically in pulse-field ablation, we are in a black box,” said Srivathsan. “None of the vendors are revealing their secret sauce.” 

Moreover, the Varipulse catheter has a lasso-like design, which failed to catch on with prior ablation modalities because of a high rate of silent cerebral embolic events, Srivathsan said. “The one other consideration about a lasso-like catheter,” he said, “is that it has a potential to get caught in the mitral valve.”

The admIRE Trial

PFA has been touted as not only a faster alternative to either radiofrequency or cryoballoon ablation, but also a safer one, as it’s believed to be less likely to damage structures surrounding the heart like the esophagus and phrenic nerve.

But as with any relatively new technology, there are some unknowns, and there has been a question about how PFA would integrate with mapping systems. “The lack of a fully integrated mapping system, a staple technology of most modern electrophysiology procedures, poses limitations in lesion creation and workflow options,” Reddy et al write.

In admIRE, a single-arm, investigational device exemption (IDE) study conducted at 30 US centers, investigators evaluated the Varipulse system with integrated Carto 3 electroanatomic mapping system, which “allows for real-time nonfluoroscopic procedural guidance and lesion indexing as well as feedback of tissue-to-catheter proximity,” according to the authors.

The analysis included 277 patients with drug-refractory, symptomatic paroxysmal AF (mean age 61.5 years; 64.3% men) who underwent ablation with the Varipulse system. Pulmonary vein isolation was successful in 100% of cases, with first-pass isolation achieved in 97.5% of targeted veins. The median time to achieve pulmonary vein isolation was 81.0 minutes, with a median of 31.0 minutes for PFA application. Median fluoroscopy time was 7.1 minutes, with 25.3% of cases done with no fluoroscopy at all.

The primary safety endpoint was a composite of device- or procedure-related death, major vascular access complications or bleeding, MI, pericarditis, heart block, permanent phrenic nerve paralysis, stroke, thromboembolism, TIA, pulmonary edema, or vagal nerve injury/gastroparesis within the first 7 days after ablation. The 2.9% rate (with a one-sided 97.5% upper confidence bound of 5.7%) came in below the performance goal of 12%.

Included in the primary safety events were three cases of pericardial tamponade, which were treated successfully. The two patients who had strokes had “largely resolved” neurological symptoms by 3 months, although one continued taking a migraine medication.

“Whereas the pathogenesis of the strokes in admIRE is unknown, it is certain that this stroke rate will improve with operator experience and attention to careful sheath management,” Reddy et al write. “It is also possible that additional enhancements to either the catheter or waveform may become necessary. Continued vigilance to potential safety issues is important as future studies are performed.”

Indeed, “this is something I think we need to keep an eye out on,” Reddy said. “But overall, we thought this was quite in line with other initial FDA trials where you have so many different operators that are performing the [procedures].”

The primary effectiveness endpoint was 12-month freedom from a composite of documented atrial tachyarrhythmias, failure to achieve pulmonary vein isolation, use of another catheter, repeat procedures (except for one redo ablation during the blanking period), use of a new or previously failed class I or III antiarrhythmic drug at a higher dose after blanking, or direct current cardioversion after blanking. The rate was 74.6% (with a one-sided 97.5% lower confidence bound of 68.5%), coming in above the 50% performance goal.

In addition, freedom from recurrent atrial fibrillation, tachycardia, or flutter after blanking was 75.4% at 1 year.

At that time point, mean improvement in Atrial Fibrillation Effect on Quality of Life total score was 32 points (P < 0.001), and 89.6% of patients said they were asymptomatic.

Healthcare use declined over follow-up as well. The rate of direct current cardioversion declined from 4.5% in the 6 months prior to study enrollment to 0.4% from 6 to 12 months after ablation, with an accompanying drop in cardiovascular hospitalizations from 3.3% to 0. The proportion of patients using a class I or III antiarrhythmic drug was 79.1% at baseline and just 6.6% from 6 to 12 months of follow-up.

Room for Another PFA System?

Asked about what will drive decisions about which PFA system to use if Varipulse eventually joins the other two on the market, Srivathsan pointed to familiarity as a primary factor. He noted that many electrophysiologists are used to the Carto 3 mapping system during radiofrequency ablations, estimating that roughly half of all AF ablations are performed with its guidance.

The question that remains, he said, is whether the Varipulse PFA technology is as good as the others. “Their strength of the mapping system might force a few physicians to use it, but the adoption rate may not be as fast as with the Farapulse,” he predicted.

Reddy said there is room for three—or even more—PFA technologies on the market. “The fact is these are not all the same type of technology. Each one is going to have its own strengths and weaknesses,” he said.

The integrated mapping system is a strength for Varipulse, although the other manufacturers are likely to have similar integration in the coming months, Reddy noted. The lasso-like design can make manipulation of the catheter a bit trickier, but it also provides more flexibility in terms of where to ablate compared with other PFA technologies, he added, saying that on balance, ease of use is roughly equivalent between Varipulse and the other catheters.

Regardless of which catheter operators choose, PFA is likely to dominate the ablation market moving forward, Srivathsan said, predicting that it will account for 90% to 95% of all procedures eventually. Uptake is being held back currently by insurance companies that continue to categorize the catheters—which are much more expensive than conventional thermal ablation catheters—as experimental, he noted.