PULSAR: Globe Pulsed-Field Ablation System Performs Well in Paroxysmal AF

The Globe pulsed-field ablation system (Kardium) provides good results in patients with paroxysmal atrial fibrillation (AF) who are resistant or intolerant to antiarrhythmic drugs, according to the results of the PULSAR investigational device exemption (IDE) trial.

In the single-arm trial, 77.8% of patients remained free from atrial arrhythmias or other measures of failure at 1 year, significantly above the performance goal of 50% (P < 0.001), researchers led by Vivek Reddy, MD (Mount Sinai Fuster Heart Hospital, New York, NY), report.

There was only one primary safety event within 7 days of the index ablation (0.6%), a hemorrhagic stroke in a patient with severe hypertension and polycystic kidney disease. There were no cases of embolic stroke, permanent phrenic nerve paralysis, pericardial tamponade, esophageal complications, clinically relevant coronary spasm or hemolysis, or death.

The data, published online recently in JACC, “indicate that the multielectrode spherical array PFA catheter allows for an efficient and safe pulmonary vein isolation procedure to treat paroxysmal AF,” the authors conclude.

Pulsed-field ablation (PFA) has developed rapidly over the past several years because it performs as well as thermal ablation technologies while avoiding some of the more serious potential complications, including damage to the esophagus, pulmonary vein, and phrenic nerve. Procedures are shorter as well.

Even so, it’s still early in the field, senior author Atul Verma, MD (McGill University Health Centre, Montreal, Canada), told TCTMD. The first two PFA systems approved by the US Food and Drug Administration were PulseSelect (Medtronic) in December 2023 and Farapulse (Boston Scientific) in January 2024. Since then, several more have gained FDA approval, including the Globe this past September.

The Globe can be considered a next-generation technology, Verma said. It stands apart given its shape, relatively large size (30-mm diameter), and that its 122 individual electrodes can be hand selected to optimize energy delivery. This allows for isolation of the pulmonary veins in a single shot in many cases. The mean number of applications in PULSAR was 1.2 per vein and 4.7 per patient.

“When you think about that concept of single shot, for the first time, I would say, we actually have a catheter that within one shot can really truly isolate the veins,” Verma said.

The ablations appear to be durable as well. In a sample of 11 patients who required redo procedures, 95% of pulmonary veins remained isolated. “You would think that you would see a lot of reconnections in those patients, and yet we didn’t,” Verma said. Those findings, however, should be considered hypothesis-generating, the investigators say.

The PULSAR IDE Trial

PULSAR, conducted at 12 sites in the United States, Europe, and Canada, enrolled patients with symptomatic paroxysmal AF who were resistant or intolerant to at least one class I or III antiarrhythmic drug. There were 183 total patients, including 19 roll-in cases during which operators gained experience with the system and 164 patients (mean age 65 years; 40% women) for the pivotal portion of the study. Mean CHA₂DS₂-VASc score was 2.1, and mean left atrial diameter was 3.8 cm.

All patients underwent pulmonary vein isolation with the Globe, an all-in-one system that has mapping, pacing, contact-sensing, and ablation (with either pulsed-field or radiofrequency energy) capabilities. Mean mapping time was 9.0 min, transpired ablation time was 25.6 min, left atrial catheter dwell time was 59.9 min, fluoroscopy time was 9.2 min, and total procedure time was 95.8 min. That indicates an efficient procedure, according to the investigators.

All pulmonary veins were acutely isolated, with 94% of veins isolated by the first energy application.

The primary effectiveness endpoint was a composite of freedom from atrial arrhythmia episodes lasting at least 30 seconds (assessed by weekly and symptom-driven remote transtelephonic monitoring, 24-Holter monitoring, and 12-lead ECGs) and freedom from other failure modes (failure to achieve pulmonary vein isolation, repeat ablations or cardioversion, and the use of new or increased doses of class I or III antiarrhythmic drugs). More than three-quarters of patients achieved this goal, although the investigators acknowledge that that figure is “almost certainly an overestimate” because continuous invasive ECG monitoring wasn’t used in the trial.

Quality of life assessed using the Atrial Fibrillation Effect on Quality of Life (AFEQT) total score, a secondary endpoint, improved from a mean of 65.2 at baseline to 92.8 at 12 months.

The primary safety endpoint was primary adverse events within 7 days of the index ablation procedure, with the observed rate coming in well below the safety performance goal of 14% (P < 0.001). There were three additional patients with serious adverse events that were device- or procedure-related: aspiration during intubation for a patient undergoing general anesthesia, pericarditis/Dressler syndrome, and urinary retention.

A pulmonary vein stenosis substudy of 33 patients showed that none had moderate or severe narrowing of the pulmonary vein on CT.

Where Will the Globe Fit In?

In an accompanying editorial, Boris Schmidt, MD, and K.R. Julian Chun, MD (both from Cardioangiologisches Centrum Bethanien, Agaplesion Markus Krankenhaus, Frankfurt am Main, Germany), call the PULSAR results “remarkable,” pointing to the single primary safety event, the durability of ablation, and the rate of freedom from arrhythmia recurrence.

But they take a critical look at the system, as well, noting the large size of the device (a 16-Fr catheter delivered through a 21-Fr outer diameter sheath and a 30-mm-diameter globe), the large number of electrodes, and the multiple functions. “On the first glance, the device seems overengineered for the purpose of achieving simple pulmonary vein isolation compared with other commercial catheter solutions,” Schmidt and Chun write. They add that the large outer sheath for transseptal access raises concerns about iatrogenic atrial septal defects and may be relevant when thinking about postprocedural hemostasis and same-day discharge. Cost, too, could be an issue.

Even so, they write, the Globe system comes with little to no learning curve because there is not much need for navigation to ensure proper positioning and gives operators the ability to select the optimal number of electrodes for ablation and minimize the delivery of energy into the bloodstream, which may reduce the risk of hemolysis.

“The most innovative potential of the global array lies in the capability to simultaneously record intracardiac electrograms from 122 distinct electrodes,” Schmidt and Chun say. “This will allow us to improve our understanding of electrical phenomena present during atrial fibrillation and may help to identify drivers, rotors, and other arrhythmogenic sources. Thus, it may be a unique mapping and ablation solution for patients with persistent AF or with AF independently from the pulmonary veins.”

Speaking with TCTMD, Schmidt agreed with Verma in saying that the Globe currently “is the only true single-shot PFA device.”

The sophistication of the Globe, which will likely come at a higher price point compared with other PFA catheters, may translate into it being “a device that is only used for more complex patients and more complex cases,” Schmidt said.

Verma acknowledged that “it is a big catheter and you could say that it may be difficult to handle.” But, he said, the transpired ablation time was short and left atrial catheter dwell time was about 60 minutes, which included a mandatory 20-minute waiting period.

“This catheter was really designed to make it as easy as possible for anyone to use it,” Verma commented. “And I can tell you that from my own personal experience of using the catheter, it takes a little bit of time to prep the equipment, flush it all out, make sure there’s no air bubbles, etc.

“But once you introduce the Globe within the atrium, it’s extremely easy to move. It’s extremely easy to maneuver,” he continued. “It shows you, using its flow map, exactly where the pulmonary veins are. You can design your own lesion set very, very easily. So honestly, it was really, really quite simple. I think anyone could use this.”

The Future of PFA

Irrespective of which catheter is chosen, PFA will likely remain the dominant modality, particularly for pulmonary vein isolation. “There is only limited space for thermal ablation modalities for pulmonary vein isolation procedures, because we have so many potent and safe PFA devices that are foreshortening our procedure times and potentially making it safer,” Schmidt said.

Operators are learning a lot in a very short period of time, Verma said. “PFA has taken off in a way that no other technology has in electrophysiology or even in cardiology as a whole. We are going through technologies and generations and developments with a speed that I’ve never seen.”

Nonetheless, physicians and researchers also are learning that PFA “is not 100% infallible,” Verma said.

“Like anything else, there are always problems that can arise. We’ve certainly gotten rid of pulmonary vein stenosis, esophageal fistulas, phrenic nerve palsies. But we have rare complications like coronary spasm, hemolysis, late vasospasm,” he noted. “But again, if we can reduce the number of deliveries, reduce the amount of energy that’s being diverted into the bloodstream, and really focus on the veins and not necessarily using it in areas where it’s contraindicated, then I think as technologies improve, we’re going to continue to see a reduction in these rare but real events that can happen with PFA.”