A new era in catheter ablation therapy for cardiac arrhythmias appears to be underway with the emergence of irreversible electroporation, also known as pulsed-field ablation (PFA).
Cleveland Clinic is a non-profit academic medical center. Advertising on our site helps support our mission. We do not endorse non-Cleveland Clinic products or services. Policy
In December 2023, the FDA approved the first PFA system (PulseSelect, Medtronic) for the treatment of paroxysmal and persistent atrial fibrillation (AF). Previously approved in Europe, the system is expected to be commercially available in the U.S. shortly.
That same month, Cleveland Clinic enrolled the first patient in the AVANT GUARD randomized trial comparing PFA with the FARAPULSE PFA System (Boston Scientific) with anti-arrhythmic drug therapy for first-line treatment of persistent AF — the first randomized controlled study of PFA in this setting.
Evidence indicates that this nonthermal ablation method treats AF with good durability and faster procedure times than conventional ablation techniques — and, most importantly, with low risk to adjacent structures.
Details of the PFA technique, along with an overview of preclinical and clinical trial evidence, were recently explored in a State-of-the-Art Review in JACC Clinical Electrophysiology (2023;9:2008-2023) by a Cleveland Clinic author team led by Oussama Wazni, MD, MBA, Section Head of Cardiac Electrophysiology and Pacing at Cleveland Clinic.
“Pulsed-field ablation is a very promising method of arrhythmia management due to its improved safety compared with thermal ablation,” Dr. Wazni says. “We expect there will be widespread adoption of this important new technology now that pulsed-field ablation systems are beginning to become commercially available.”
PFA involves electroporation, or the delivery of rapid, high-voltage pulsed electrical fields to tissue, causing cell membranes to become permeable. Depending on the intensity of application, the result can be reversible (a technique used for gene or drug insertion into cells) or irreversible, leading to pores in the membrane and cell death (used for cardiac ablation).
The strength of electric application can be carefully titrated to destroy only cardiomyocytes and not surrounding tissues, including the esophagus, pulmonary vein and phrenic nerve, which have much higher thresholds for damage from electroporation.
“In contrast to the indiscriminate risk of collateral damage inherent in using thermal energy sources, irreversible electroporation offers the ability to focus ablation on cells implicated in atrial or ventricular arrhythmias,” Dr. Wazni explains.
Multiple preclinical in vitro and in vivo studies have been conducted on swine and canines in the atrium, epicardium and ventricle, setting the stage for clinical trials on patients. Dr. Wazni and Cleveland Clinic colleagues recently reported on the successful use of PFA following prior radiofrequency ablation in swine models, relevant for patients needing redo procedures (JACC Clin Electrophysiol. Epub 2023 Oct 27).
At least 10 clinical trials of PFA for paroxysmal or persistent AF have been completed to date, involving more than 1,200 patients using a variety of devices with catheter designs of different shapes. FDA approval of the PulseSelect system — which has a circular, lasso-type 9-electrode catheter — was based on the single-cohort PULSED AF pivotal study: efficacy was comparable to that of thermal ablation methods among patients with paroxysmal (n = 150) or persistent (n = 150) AF, and PFA entailed a very low incidence of adverse events.
In addition, data from a real-world survey of more than 17,000 patients at 106 international centers (MANIFEST-17K) were presented at the 2023 American Heart Association Scientific Sessions, using the CE-approved FARAPULSE system, which employs a pulsed-field pentaspline basket/flower ablation catheter. Overall freedom from AF after one year was 73% in paroxysmal and 58% in persistent AF, with a less than 1% rate of major adverse events.
FARAPULSE also recently underwent a randomized clinical trial (ADVENT) involving multiple U.S. centers, with 305 patients assigned to PFA. The system met the standards for noninferiority in safety and efficacy compared with thermal ablation.
Overall, evidence from clinical trials of PFA supports the following:
Other major trials of PFA are underway. One involves a lattice-tip spherical catheter design being compared with radiofrequency ablation in a multicenter randomized trial (Sphere Per-AF, Medtronic; NCT05120193) for treatment of persistent AF. More than 450 patients have been enrolled, with results expected in 2024. This device received regulatory approval in the European Union in March 2023.
Meanwhile, FARAPULSE is being investigated for persistent AF in the multicenter, single-arm, open-label ADVANTAGE AF trial (NCT05443594) and in the newly launched AVANT GUARD trial (NCT06096337). The latter study, in addition to being the first trial to assess PFA as frontline therapy for persistent AF, is the first to follow patients using implantable loop recorders. “We will determine whether PFA in the setting of persistent AF will reduce recurrence and prevent AF progression as well as heart failure,” says Dr. Wazni, who serves as lead investigator of AVANT GUARD. “This study has the potential to be practice-changing.” Outcomes will be assessed at one and three years using different endpoints.
Dr. Wazni notes that several issues related to PFA require further exploration in clinical trials. Optimal “recipes” have yet to be determined for energy intensity (voltage), pulse duration and frequency, biphasic versus monophasic pulse delivery, different electrode configurations, and variations of the diverse device designs and patient characteristics. Investigation of electroporation-induced vasospasm is also needed to develop strategies to prevent this rare but serious complication.
He also points out that comparative costs and benefits of conventional ablation relative to PFA must continually be assessed, as switching to a totally new ablation system will be costly and may not be justified at all centers. In addition to multiple PFA clinical trials, studies of conventional ablation techniques are also still ongoing.
“Even with some unanswered questions remaining, pulsed-field ablation holds great promise in making safer ablation available to more patients,” Dr. Wazni concludes. “And with continually growing operator experience, along with design and application improvements, I expect the advantages of this method will continue to increase.”
His colleague Walid Saliba, MD, agrees. “This new method of ablation could potentially revolutionize the treatment of atrial fibrillation,” says Dr. Saliba, Medical Director of Cleveland Clinic’s Atrial Fibrillation Center. “With the growing evidence favoring early ablation as first-line therapy for the treatment of many patients with atrial fibrillation, having a procedure like PFA that is faster and safer — and potentially more effective — will be appreciated by patients and physicians alike.”