Heart rhythm · 2026
Fundamentals of pulsed field ablation at the individual cardiomyocyte level.
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Jan Vid, Turk Tina, Vižintin Angelika, Rems Lea, Miklavčič Damijan
Аннотация
BACKGROUND: Pulsed field ablation (PFA) is a rapidly adopted catheter ablation method that employs high-voltage pulses to treat cardiac arrhythmias by cardiomyocyte electroporation.
OBJECTIVE: We systematically characterized cardiomyocyte responses in vitro to different PFA waveforms to better understand the transient electrophysiological effects observed in clinical PFA.
METHODS: Isolated adult rat ventricular cardiomyocytes were exposed to clinically relevant waveforms: monophasic 100 μs, biphasic 2 μs, and monophasic 200 ns pulses. Transmembrane voltage, intracellular Ca2+, and sarcomere shortening were monitored simultaneously. Computational modeling and machine learning were used to characterize the responses.
RESULTS: We observed 6 distinct response types ranging from no response to a complete loss of excitability. All 3 waveforms induced the same spectrum of responses, albeit at different electric field strengths. Cell orientation influenced thresholds in a pulse-duration-dependent manner. Modeling demonstrated that an electroporation-induced increase in membrane conductance explains the observed responses. Machine learning revealed that cells retain signatures of electroporation in their action potentials and Ca2+ transients, which differ between microsecond and submicrosecond waveforms. On a longer timescale, 12%-36% of cells that initially lost excitability recovered within ∼10 minutes.
CONCLUSION: All PFA waveforms produce similar cardiomyocyte responses through an electroporation-induced increase in membrane conductance. A substantial fraction of cells recover excitability within minutes, providing a plausible cellular explanation for the clinically observed transient loss of intracardiac electrograms following PFA and a rationale for pulsed field mapping based on reversible electroporation. Although the fundamental effects are waveform-independent, signatures in recovered cells show waveform-dependent features. These findings advance the mechanistic understanding of PFA at the cellular level.
OBJECTIVE: We systematically characterized cardiomyocyte responses in vitro to different PFA waveforms to better understand the transient electrophysiological effects observed in clinical PFA.
METHODS: Isolated adult rat ventricular cardiomyocytes were exposed to clinically relevant waveforms: monophasic 100 μs, biphasic 2 μs, and monophasic 200 ns pulses. Transmembrane voltage, intracellular Ca2+, and sarcomere shortening were monitored simultaneously. Computational modeling and machine learning were used to characterize the responses.
RESULTS: We observed 6 distinct response types ranging from no response to a complete loss of excitability. All 3 waveforms induced the same spectrum of responses, albeit at different electric field strengths. Cell orientation influenced thresholds in a pulse-duration-dependent manner. Modeling demonstrated that an electroporation-induced increase in membrane conductance explains the observed responses. Machine learning revealed that cells retain signatures of electroporation in their action potentials and Ca2+ transients, which differ between microsecond and submicrosecond waveforms. On a longer timescale, 12%-36% of cells that initially lost excitability recovered within ∼10 minutes.
CONCLUSION: All PFA waveforms produce similar cardiomyocyte responses through an electroporation-induced increase in membrane conductance. A substantial fraction of cells recover excitability within minutes, providing a plausible cellular explanation for the clinically observed transient loss of intracardiac electrograms following PFA and a rationale for pulsed field mapping based on reversible electroporation. Although the fundamental effects are waveform-independent, signatures in recovered cells show waveform-dependent features. These findings advance the mechanistic understanding of PFA at the cellular level.