麻豆传媒

The electroporation approach to pulmonary vein isolation fared well in the first-in-human experience, researchers reported.

Pulsed field ablation (PFA) succeeded in electrically isolating all targeted pulmonary veins among 81 patients with symptomatic paroxysmal atrial fibrillation (Afib) resistant to drugs, according to Vivek Reddy, MD, of the Icahn School of Medicine at Mount Sinai, New York City, and colleagues.

The sole safety event that occurred was a pericardial tamponade, they reported in the .

"Importantly, there were no clinical instances of pulmonary vein stenosis, stroke or TIA [transient ischemic attack], or atrioesophageal fistula. There were also no instances of phrenic nerve injury despite frequent phrenic capture during PFA pulses to the right superior PV [pulmonary vein]," the investigators noted.

Behind PFA is electroporation, a technique of using electric fields to increase cell membrane permeability and, when conducted above a certain threshold, force irreversible cell death.

Its utility in catheter ablation for Afib is due to the the fact that cardiomyocytes have particularly low thresholds to these electric fields such that they can be selectively ablated with minimal collateral damage to the esophageal or phrenic nerves.

In contrast, today's options of radiofrequency or cryoenergy ablation result in indiscriminate tissue destruction.

Safety is the biggest benefit of PFA and the "results of this first in human study are very impressive to say the least," commented John Day, MD, of Intermountain Medical Center Heart Institute in Salt Lake City, Utah.

If further studies support these findings, PFA could "disrupt the Afib ablation market" as it shortens procedure times and decreases the need for redo procedures. "I could easily see this technology replacing radiofrequency and cryo energy sources for the treatment of Afib," he speculated.

"Medical use of reversible electroporation started 30 years ago with electrochemotherapy, which increases cell permeability to chemotherapeutics. Irreversible electroporation is the presumed mechanism behind direct current ablation, used in the 1980s for arrhythmias before being supplanted by thermal ablation to circumvent issues such as barotrauma and inhomogeneous lesion formation," according to an accompanying editorial.

"This energy source is now staging a comeback as PFA, modified to circumvent those issues," continued Sanjiv M. Narayan, MD, PHD, and Tina Baykaner, MD, MPH, both of Stanford University in California.

Yet the downside is that fluoroscopy is required, Reddy and colleagues said.

They conducted two first-in-human studies at Homolka Hospital, Prague, and the Centre Hospitalier Universitaire de Bordeaux, France. These studies, IMPULSE and PEFCAT, followed people treated with the older- and newer-generation Farapulse systems, respectively.

The older device isolated pulmonary veins with monophasic waveforms and was tested in 15 people under general anesthesia. Another 66 underwent conscious sedation as they were treated with the newer system, which uses biphasic waveforms.

Altogether, 315 pulmonary veins were targeted. Study participants were on average age 58 and 74% men.

Procedure times averaged 92.2 minutes and the mean fluoroscopy time was 13.1 min. It took no more than 3 minutes to administer the ablative PFA pulses at an average of 6.4 pulse applications per pulmonary vein.

"There were no PFA catheter-related complications associated with deployment failure, catheter entrapment within the PVs or valvular apparatus, or evidence of charring or thrombus upon catheter removal," Reddy's group reported.

Nor were there any atrial or ventricular tachyarrhythmias or significant repolarization abnormalities.

"All patients had unremarkable recovery without evidence of significant thoracic or upper extremity muscular discomfort or neurological motor or sensory symptoms post-procedure," they added.

Durability of the procedure was only 18% around 3 months for the cohort treated with the monophasic waveform. Subsequent patients who had the procedure done with the optimized biphasic waveform had 100% durability at that point.

Not all patients returned for electrophysiological remapping, however, and the sample was small to begin with, the investigators acknowledged.

"As with any novel technology, the study raises important questions," said Narayan and Baykaner. "First, long-term arrhythmia freedom is unclear. Intermediate outcomes are very promising, yet median follow-up was 120 days and the predictive value of isolated PVs for long-term outcome is unclear."

Moreover, the myocardial selectivity of electroporation is no guarantee of improved success with pulmonary vein isolation, the editorialist suggested.

Nevertheless, the data presented by Reddy and colleagues' team are "extremely promising," according to Mintu Turakhia, MD, of Stanford University and the VA Palo Alto Health Care System in California.

"The technology does what it is supposed to, which is to isolate quickly. Moreover, these first in-human trials showed remarkable safety and reasonable procedure times. I look forward to seeing how the needle moves even further as this gets more refined," Turakhia, who was not involved in the study, told 麻豆传媒.