Biophysical principles of pulsed field ablation.
7 affiliations
- 1ICEmB at DIET, Sapienza University of Rome, Rome, Italy.
- 2National Italian Agency for Energy, New Technologies and Sustainable Economic Development ENEA, Division of Biotechnologies, via Anguillarese 301, Rome 00123, Italy.
- 3Université Paris-Saclay, CNRS, Gustave Roussy, Biologie du cancer et Métabolisme, 94805, Villejuif, France.
- 4Department of Mechanical and Industrial Engineering, University of Massachusetts Amherst, Amherst, MA, USA.
- 5Medical Affairs, Boston Scientific S.p.A., Viale Enrico Forlanini 23, 20134 Milan, Italy.
- 6Department of Electrophysiology, Alfried Krupp Hospital, Essen, Germany.
- 7Department of Medicine, Witten/Herdecke University, Witten, Germany.
Abstract
Pulsed field ablation (PFA) is emerging as a major advance in cardiac ablation because it induces irreversible electroporation rather than relying primarily on thermal injury. This article provides an overview of the core biophysical principles underlying PFA, focusing on concepts broadly relevant across systems and clinical applications. Externally applied pulsed electric fields interact with biological tissues and affect their transmembrane potential. When a critical threshold is exceeded, nanoscale aqueous pores form in the lipid bilayer, initiating electroporation. Depending on pulse amplitude, duration, number, repetition frequency, waveform, and tissue characteristics, membrane permeabilization may remain reversible or progress to irreversible injury and cell death. This article focuses on the fundamental biophysical principles of electroporation that underpin PFA. The article outlines how membrane charging, cell geometry, and tissue heterogeneity influence electric field distribution and biological response and explains why lesion formation depends on both field intensity and exposure conditions. It also summarizes the molecular basis of pore formation, the potential contribution of lipid peroxidation and membrane proteins, and the downstream processes linking sustained permeability to loss of homeostasis and delayed cell death. Finally, it places cardiac PFA in the broader context of electroporation-based therapies developed in oncology, drug delivery, and gene transfer, while highlighting the remaining need for cardiomyocyte-specific mechanistic evidence to further optimize safety, precision, and durability.
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BibTeX
@article{apollonio2026biophysical,
title = {{Biophysical principles of pulsed field ablation.}},
author = {Francesca Apollonio and Francesca Camera and Micaela Liberti and Caterina Merla and Lluis M Mir and Carmen Pisano and Poompavai Sadasivam and Govindarajan Srimathveeravalli and Maura Casciola and Kars Neven},
journal = {Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology},
year = {2026},
month = oct,
doi = {10.1093/europace/euag229},
url = {https://europepmc.org/article/MED/42905914},
note = {CC BY},
}
RIS
TY - JOUR
TI - Biophysical principles of pulsed field ablation.
AU - Francesca Apollonio
AU - Francesca Camera
AU - Micaela Liberti
AU - Caterina Merla
AU - Lluis M Mir
AU - Carmen Pisano
AU - Poompavai Sadasivam
AU - Govindarajan Srimathveeravalli
AU - Maura Casciola
AU - Kars Neven
PY - 2026
DA - 2026/10/01
JO - Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology
DO - 10.1093/europace/euag229
UR - https://europepmc.org/article/MED/42905914
AB - Pulsed field ablation (PFA) is emerging as a major advance in cardiac ablation because it induces irreversible electroporation rather than relying primarily on thermal injury. This article provides an overview of the core biophysical principles underlying PFA, focusing on concepts broadly relevant across systems and clinical applications. Externally applied pulsed electric fields interact with biological tissues and affect their transmembrane potential. When a critical threshold is exceeded, nanoscale aqueous pores form in the lipid bilayer, initiating electroporation. Depending on pulse amplitude, duration, number, repetition frequency, waveform, and tissue characteristics, membrane permeabilization may remain reversible or progress to irreversible injury and cell death. This article focuses on the fundamental biophysical principles of electroporation that underpin PFA. The article outlines how membrane charging, cell geometry, and tissue heterogeneity influence electric field distribution and biological response and explains why lesion formation depends on both field intensity and exposure conditions. It also summarizes the molecular basis of pore formation, the potential contribution of lipid peroxidation and membrane proteins, and the downstream processes linking sustained permeability to loss of homeostasis and delayed cell death. Finally, it places cardiac PFA in the broader context of electroporation-based therapies developed in oncology, drug delivery, and gene transfer, while highlighting the remaining need for cardiomyocyte-specific mechanistic evidence to further optimize safety, precision, and durability.
SN - 1099-5129
SN - 1532-2092
ER -