Study Highlights Safety and Effectiveness of Pulsed Field Ablation for Treating Atrial Fibrillation

Pulsed Field Ablation (PFA) demonstrates promising safety and efficacy in real-world clinical practice, according to a study published in Nature Medicine.

The MANIFEST-17K trial, a large-scale retrospective study, evaluated outcomes in more than 17 000 patients treated across 106 centers in 20 countries, offering a comprehensive assessment of PFA’s role in atrial fibrillation (AF) management.

AF is the most common sustained cardiac arrhythmia, significantly impacting quality of life and increasing morbidity and mortality. Traditional thermal ablation methods, while effective, carry risks such as pulmonary vein stenosis, atrioesophageal fistula formation, and phrenic nerve injury. PFA, a nonthermal modality, targets myocardial tissue with ultrarapid electrical pulses, reducing collateral damage to surrounding structures.

“PFA is an emerging AF ablation modality with an important degree of preferentiality to myocardial tissue damage,” discussed Emmanuel Ekanem, Icahn School of Medicine at Mount Sinai in New York, NY, and Winchester Cardiology and Vascular Medicine, Winchester Medical Center Valley Health, Winchester, VA, and coauthors. “By delivering ultrarapid (microsecond to nanosecond) electrical pulses to generate strong electrical fields, PFA can produce irreversible nanoscale pore formation culminating in cellular death.”

The study revealed a remarkably low major complication rate of 0.98%, with vascular complications (0.30%) and pericardial tamponade (0.36%) being the most common. There were no reported cases of atrioesophageal fistula formation, pulmonary vein stenosis, or persistent phrenic nerve injury—complications associated with traditional thermal ablation techniques.

One of the most significant findings was the absence of esophageal complications, a critical safety concern in AF ablation procedures. The study also reported a low incidence of stroke (0.12%) and a rare mortality rate of 0.03% (5 cases).

The research highlighted some PFA-specific adverse events, including transient phrenic nerve paresis (0.06%) and coronary artery spasm (0.14%). However, these complications were generally manageable and resolved quickly.

Interestingly, the study observed a learning curve effect, with a trend towards reduced complication rates compared to the initial MANIFEST-PF cohort. This suggests that as operators gain more experience with PFA, the safety profile may continue to improve.

This large-scale analysis confirms findings from prior trials, such as the EU-PORIA registry and the ADVENT trial, which demonstrated the noninferiority of PFA compared with thermal ablation methods. The study also underscores the importance of a learning curve in PFA adoption, with reductions in adverse events observed over time as operators gained experience.

While the results are encouraging, the study acknowledges potential limitations. Adverse events unique to PFA may emerge with further widespread use, as was observed with other modalities like cryoballoon ablation. Long-term safety data and further research are essential to fully understand PFA's risks and benefits in broader patient populations.

“In a ‘real-world’ setting of an unselected AF patient population, PFA demonstrated a safety profile consistent with an important degree of preferentiality to myocardial tissue ablation, with no evidence of esophageal complications, and with a low rate of major complications,” concluded the study authors.

Reference

Ekanem E, Neuzil P, Reichlin T, et al. Safety of pulsed field ablation in more than 17,000 patients with atrial fibrillation in the MANIFEST-17K study. Nat Med. 2024;30(7):2020-2029. doi:10.1038/s41591-024-03114-3