Pulsed field ablation (PFA) is an emerging energy source for atrial fibrillation (AF) ablation, noted for its potential safety benefits, including a lower risk of injury to surrounding tissues. A large, real-world study has now provided extensive data on the safety of this technology in a broad patient population.¹

Mechanism of Action

PFA utilises pulsed electric fields to create pores in cell membranes (electroporation), leading to cell death. This modality is considered tissue-selective, with a preference for ablating myocardial tissue while aiming to spare adjacent structures such as the oesophagus and phrenic nerve.

Methodology

The MANIFEST-US study was a retrospective, multicentre analysis designed to evaluate the real-world safety of the pentaspline PFA catheter in the United States.¹ Data were collected from 102 participating centres between February 2024 and July 2025.

The study included a total of 41,968 patients. The median patient age was 68 years, and 56% were male. The majority of patients (73%) were undergoing their first ablation procedure, primarily for paroxysmal AF (54%) or persistent AF (37%). Pulmonary vein isolation was performed in 93% of cases, often supplemented with extravenous lesions on the posterior wall (57%), cavotricuspid isthmus (31%), or mitral isthmus (14%). The main outcomes were the incidence of major and minor procedure-related adverse events (AEs).

Results and Findings

The rate of major AEs was low, occurring in just 0.63% of patients. These included cardiac tamponade (0.16%), vascular injury requiring intervention (0.18%), and stroke (0.10%). Notably, there were no reported cases of oesophageal fistula, persistent phrenic nerve paralysis, or pulmonary vein stenosis.

Minor complications were reported in 2.05% of patients, with the most common being vascular issues (0.96%), pericarditis (0.52%), and self-limited oesophageal dysmotility (0.04%).

The 30-day mortality rate was 0.04%. Other rare AEs included coronary spasm (0.10%) and acute renal failure requiring dialysis (0.02%). The study also noted a potential signal for rare (0.019%) unexplained sudden death or cardiac arrest.

In Practice and Interpretation

This large-scale analysis provides reassurance regarding the safety of PFA in a diverse, real-world setting. The MANIFEST-US investigators concluded that in this cohort, “PFA demonstrated a safety profile consistent with preferentiality to functional myocardial tissue ablation, without evidence of esophageal fistula or pulmonary vein stenosis.”¹ The low rate of major complications, particularly the absence of some of the most feared complications associated with thermal ablation, supports its growing use. The investigators noted that these data indicate that the initial implementation of pentaspline PFA has been “overall safe.”

References

1. Turagam MK, Aryana A, Day JD, et al. Multicenter Study on the Safety of Pulsed Field Ablation in Over 40,000 Patients: MANIFEST-US. JACC. 2026;87(2):172-193. https://doi.org/10.1016/j.jacc.2025.10.051

2. Ekanem E, Reddy VY, Schmidt B, et al. Multi-national survey on the methods, efficacy, and safety on the post-approval clinical use of pulsed field ablation (MANIFEST-PF). Europace. 2022;24(8):1256-1266. https://doi.org/10.1093/europace/euac050

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