Parametric Study of Pulsed Field Ablation With Biphasic Waveforms in an In Vivo Heart Model: The Role of Frequency

García-Sánchez, Tomás; Amorós-Figueras, Gerard; Jorge, Esther; Campos, María C; Maor, Elad; Guerra, José M.; Ivorra, Antoni

doi:10.1161/circep.122.010992

Cited by 13 publications

(20 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is consistent with previous in vivo and in vitro reports, including recent studies utilizing hiPSC-CMs. 13,14,33,34,37,41 In regions of the culture subjected to lower field intensities, a delayed recovery of electric activity could be detected. These findings further emphasize that initial electric silencing following PFA does not necessarily translate into durable lesions, and that recovery of electric activity may occur over the course of hours/days.…”

Section: Discussionmentioning

confidence: 99%

Utilizing Human-Induced Pluripotent Stem Cells to Study Cardiac Electroporation Pulsed-Field Ablation

Maizels,

Heller,

Landesberg

et al. 2024

Circ: Arrhythmia and Electrophysiology

Self Cite

View full text Add to dashboard Cite

BACKGROUND: Electroporation is a promising nonthermal ablation method for cardiac arrhythmia treatment. Although initial clinical studies found electroporation pulsed-field ablation (PFA) both safe and efficacious, there are significant knowledge gaps concerning the mechanistic nature and electrophysiological consequences of cardiomyocyte electroporation, contributed by the paucity of suitable human in vitro models. Here, we aimed to establish and characterize a functional in vitro model based on human-induced pluripotent stem cells (hiPSCs)-derived cardiac tissue, and to study the fundamentals of cardiac PFA. METHODS: hiPSC-derived cardiomyocytes were seeded as circular cell sheets and subjected to different PFA protocols. Detailed optical mapping, cellular, and molecular characterization was performed to study PFA mechanisms and electrophysiological outcomes. Results: PFA generated electrically silenced lesions within the hiPSC-derived cardiac circular cell sheets, resulting in areas of conduction block. Both reversible and irreversible electroporation components were identified. Significant electroporation reversibility was documented within 5 to 15-minute post-PFA. Irreversibly electroporated regions persisted at 24-hour post-PFA. Per single pulse, high-frequency PFA was less efficacious than standard (monophasic) PFA, whereas increasing pulse-number augmented lesion size and diminished reversible electroporation. PFA augmentation could also be achieved by increasing extracellular Ca 2+ levels. Flow-cytometry experiments revealed that regulated cell death played an important role following PFA. Assessing for PFA antiarrhythmic properties, sustainable lines of electric block could be generated using PFA, which could either terminate or isolate arrhythmic activity in the hiPSC-derived cardiac circular cell sheets. CONCLUSIONS: Cardiac electroporation may be studied utilizing hiPSC-derived cardiac tissue, whereas providing novel insights into PFA temporal and electrophysiological characteristics, facilitating electroporation protocol optimization, screening for potential PFA-sensitizers, and investigating the mechanistic nature of PFA antiarrhythmic properties.

show abstract

Section: Discussionmentioning

confidence: 99%

Utilizing Human-Induced Pluripotent Stem Cells to Study Cardiac Electroporation Pulsed-Field Ablation

Maizels,

Heller,

Landesberg

et al. 2024

Circ: Arrhythmia and Electrophysiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Tomás et al [ 32 ] applied PFA on the epicardium of a rat, and the record of the optical temperature probe located at the point of contact between the electrode and the tissue showed that the temperature sharply increased during each pulse and subsequently slowly dissipated by conduction between consecutive pulses. The characteristics of the maximum temperature curve of myocardium during PFA in this study are consistent with the above.…”

Section: Discussionmentioning

confidence: 99%

“…In this study, the size of the myocardial ablation volume is in cubic mm, and the difference in the size of the myocardial ablation volume between the CHT method and CFD method is insignificant for values less than 1 mm 3 since this value is approximate to the deviation (±0.5 mm) observed in experimental studies [ 5 ]. Likewise, the differences in the maximum temperature of myocardium and blood between the CHT method and CFD method are considered insignificant for values less than 1 °C since this value is the system security (±0.5 °C) of the temperature fiber optic sensor used to measure the temperature rise during PFA [ 32 ].…”

Section: Methodsmentioning

confidence: 99%

Comparative Analysis of Temperature Rise between Convective Heat Transfer Method and Computational Fluid Dynamics Method in an Anatomy-Based Left Atrium Model during Pulsed Field Ablation: A Computational Study

Zang

et al. 2023

JCDD

View full text Add to dashboard Cite

The non-thermal effects are considered one of the prominent advantages of pulsed field ablation (PFA). However, at higher PFA doses, the temperature rise in the tissue during PFA may exceed the thermal damage threshold, at which time intracardiac pulsatile blood flow plays a crucial role in suppressing this temperature rise. This study aims to compare the effect of heat dissipation of the different methods in simulating the pulsatile blood flow during PFA. This study first constructed an anatomy-based left atrium (LA) model and then applied the convective heat transfer (CHT) method and the computational fluid dynamics (CFD) method to the model, respectively, and the thermal convective coefficients used in the CHT method are 984 (W/m2*K) (blood-myocardium interface) and 4372 (W/m2*K) (blood–catheter interface), respectively. Then, it compared the effect of the above two methods on the maximum temperature of myocardium and blood, as well as the myocardial ablation volumes caused by irreversible electroporation (IRE) and hyperthermia under different PFA parameters. Compared with the CFD method, the CHT method underestimates the maximum temperature of myocardium and blood; the differences in the maximum temperature of myocardium and blood between the two methods at the end of the last pulse are significant (>1 °C), and the differences in the maximum temperature of blood at the end of the last pulse interval are significant (>1 °C) only at a pulse amplitude greater than 1000 V or pulse number greater than 10. Under the same pulse amplitude and different heat dissipation methods, the IRE ablation volumes are the same. Compared with the CFD method, the CHT method underestimates the hyperthermia ablation volume; the differences in the hyperthermia ablation volume are significant (>1 mm3) only at a pulse amplitude greater than 1000 V, a pulse interval of 250 ms, or a pulse number greater than 10. Additionally, the hyperthermia ablation isosurfaces are completely wrapped by the IRE ablation isosurfaces in the myocardium. Thus, during PFA, compared with the CFD method, the CHT method cannot accurately simulate the maximum myocardial temperature; however, except at the above PFA parameters, the CHT method can accurately simulate the maximum blood temperature and the myocardial ablation volume caused by IRE and hyperthermia. Additionally, within the range of the PFA parameters used in this study, the temperature rise during PFA may not lead to the appearance of additional hyperthermia ablation areas beyond the IRE ablation area in the myocardium.

show abstract

“…From a clinical perspective, the level of muscle contractions observed would require the use of general anesthesia and neuromuscular blockade. As previously shown, 11 waveform could be optimized to reduce muscle contractions.…”

Section: Limitationsmentioning

confidence: 94%

“…The waveform used was validated in a previous study in small animals. 11 Namely, it consisted in a sequence 10 biphasic bursts with 100 μs duration for each burst. The bursts were delivered with a 1 second delay between them (ie, 10 seconds total treatment duration per point).…”

Section: Methodsmentioning

confidence: 99%

Dynamics of High-Density Unipolar Epicardial Electrograms During PFA

Amorós-Figueras

Casabella-Ramon

Moreno-Weidmann

et al. 2023

Circ: Arrhythmia and Electrophysiology

Self Cite

View full text Add to dashboard Cite

BACKGROUND: Pulsed field ablation (PFA) is a novel nonthermal cardiac ablation technology based on irreversible electroporation (IRE). While areas of IRE lead to durable lesions, the surrounding regions, where reversible electroporation occurs, recover. The behavior of local electrograms in areas of different electroporation levels remains unknown. The goal of this study is to characterize electrogram dynamics after PFA in IRE and reversible electroporation areas. METHODS: A total of 6 domestic swine were used. PFA was applied in the epicardium of the right and left ventricles using a focal monopolar catheter. Additional radiofrequency ablations were performed. Epicardial unipolar electrograms were acquired at baseline and for 60 minutes post PFA/radiofrequency ablation using a high-density electrode matrix attached to the epicardium. Electrogram dynamics were analyzed in areas corresponding to different levels of electroporation. Acute lesion formation was assessed after 3 to 5 hours by triphenyl tetrazolium chloride staining. RESULTS: Electrogram analysis demonstrated a clear association between electrogram changes and the level of electroporation. Immediately after PFA, electrograms displayed the following: a significant decrease in R/S-wave amplitude; a large elevation of the ST-segment; and a large decrease in their |(dV/dt)| max . Marked changes in electrograms were observed beyond the lesion area. Thereafter, a gradual recovery was observed. The evolution of all the electrogram parameters throughout the 60 minutes after PFA was significantly different ( P <0.05) between the IRE and reversible electroporation areas. Acute lesion staining showed significantly larger depth for PFA lesions compared with radiofrequency ablation. Conclusions: This study shows that unipolar electrograms can differentiate between reversible electroporation and IRE areas during the first 30 minutes post ablation. Differences after the first 30 minutes are less evident. Our findings could result useful for immediate lesion assessment after PFA and warrant further investigation.

show abstract

Parametric Study of Pulsed Field Ablation With Biphasic Waveforms in an In Vivo Heart Model: The Role of Frequency

Cited by 13 publications

References 56 publications

Utilizing Human-Induced Pluripotent Stem Cells to Study Cardiac Electroporation Pulsed-Field Ablation

Utilizing Human-Induced Pluripotent Stem Cells to Study Cardiac Electroporation Pulsed-Field Ablation

Comparative Analysis of Temperature Rise between Convective Heat Transfer Method and Computational Fluid Dynamics Method in an Anatomy-Based Left Atrium Model during Pulsed Field Ablation: A Computational Study

Dynamics of High-Density Unipolar Epicardial Electrograms During PFA

Contact Info

Product

Resources

About