Pulsed field ablation (PFA) is an emerging energy source for atrial fibrillation (AF) ablation, noted for its promising safety profile. A large, real-world study, MANIFEST-US, has provided extensive data on the safety and utilisation of the pentaspline PFA catheter in the United States.¹
Mechanism of Action
PFA is a non-thermal ablation modality that uses pulsed electric fields to create lesions through irreversible electroporation. This mechanism offers a degree of myocardial tissue selectivity, which may reduce the risk of injury to adjacent structures such as the oesophagus and phrenic nerve compared to thermal ablation techniques.²
Methodology
The MANIFEST-US study was a retrospective analysis involving 102 US centres.¹ Data were collected from 41,968 patients who underwent PFA with the pentaspline catheter between February 2024 and July 2025. 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, with additional extravenous lesions created on the posterior wall (57%), cavotricuspid isthmus (31%), or mitral isthmus (14%). The main outcome was the incidence of major and minor procedure-related adverse events (AEs).
Results
The study found a low rate of major AEs, occurring in 0.63% of patients. The most common major AEs were vascular injury requiring intervention (0.18%), cardiac tamponade (0.16%), 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, predominantly vascular issues (0.96%) and pericarditis (0.52%). Other rare AEs included coronary spasm (0.10%), self-limited oesophageal dysmotility (0.04%), and acute renal failure requiring dialysis (0.02%). The 30-day mortality rate was 0.04%, with a potential signal for rare (0.019%) unexplained sudden death or cardiac arrest.
In Practice
The investigators concluded that in a real-world setting of unselected US patients, PFA demonstrated a safety profile consistent with its preferentiality for myocardial tissue. As the authors state, “The major complication rate was ~0.6%—mostly vascular AEs and pericardial tamponade. Stroke (~1 in 1,000) and death (~1 in 2,000) were rare.”¹ These findings suggest that the initial implementation of pentaspline PFA in a broad patient population has been safe overall.
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. J Am Coll Cardiol. 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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