State-of-the-art pulsed field ablation for cardiac arrhythmias: ongoing evolution and future perspective

Abstract

Pulsed field ablation (PFA) is an innovative approach in the field of cardiac electrophysiology aimed at treating cardiac arrhythmias. Unlike traditional catheter ablation energies, which use radiofrequency or cryothermal energy to create lesions in the heart, PFA utilizes pulsed electric fields to induce irreversible electroporation, leading to targeted tissue destruction. This state-of-the-art review summarizes biophysical principles and clinical applications of PFA, highlighting its potential advantages over conventional ablation methods. Clinical data of contemporary PFA devices are discussed, which combine predictable procedural outcomes and a reduced risk of thermal collateral damage. Overall, these technological developments have propelled the rapid evolution of contemporary PFA catheters, with future advancements potentially impacting patient care.

Keywords: Catheter ablation; Electroporation; Energy sources; Pulsed field.

Graphical Abstract

Figure 1

When a cell is exposed to sufficiently high electric field, by delivery of high-voltage electric pulses to tissue, a transmembrane voltage is induced, which leads to pore formation, lipid oxidation, and protein damage, rendering cell membrane permeable. Due to increased membrane permeability, ions and molecules flow in and out of the cells including Na⁻ and K⁺ ions that are depolarizing cell and Ca²⁺, which all results in increased intracellular Ca. At the same time, DAMP molecules—known to trigger immune response in tissue—leak out of the cell. Inflow of Ca can trigger other secondary processes like contraction and disassembly of cortical cytoskeleton and contributes to ATP depletion. Following membrane resealing, its conductivity still remains somewhat larger than before electroporation. The cell struggles to regain its homoeostasis by triggering its repair mechanisms, including heat shock proteins known also as chaperons required in protein (re)folding. Cell death depends on intensity of electroporation and may occur rapidly/immediately after exposure to electric pulses or can occur after several hours or even day(s). The processes described are highly dynamic and start in nanoseconds to microseconds and last for hours. ATP, adenosine triphosphate; DAMP, danger-associated molecular pattern; ROS, reactive oxygen species.

Figure 2

Most of pulse parameters were selected by manufacturers during the development, testing, and optimization of the system (pulse generator and catheter) and may differ from PFA system to PFA system. These pulse parameters (pulse amplitude, pulse width, number of pulses, interphase, and interpulse delay) may have profound effect on effectiveness and risks: lesion size, electrode/catheter breakdown risk, bubble formation, temperature rise and potential thermal damage, electrical arcing, barotrauma risk, and emboli risk and are therefore most often not available to the operator to change, i.e. are locked. In most system, there is little to no choices left to the operators and these in a limited range and with some limitations. There are but few parameters left that can be controlled during PFA procedure. Most often subject to variations and choices: T_k—number of trains/PFA deliveries, time between deliveries (usually longer times are preferred to avoid temperature rise due to stacking effect), and pulse amplitude (voltage). It must be however emphasized that effects and risks depend in often non-linear relation to pulse parameters and that many of the outcomes (effects and risks) depend on multiple parameters. Optimization of the waveform and pulse parameters can be considered a multi-parameter optimization with conflicting requirements. PFA, pulsed field ablation.

Figure 3

Closest to the catheter/electrode, the electric field and current density are the highest and decrease rapidly with the (radial) distance. This means that cells depending on the distance from the catheter will be exposed to higher or lower electric field and will be ‘electroporated’ to a different extent. Those exposed to highest electric field may die immediately, those exposed to somewhat lower intensity may die with a considerable delay, whereas cells exposed to even lower electric field may be electroporated only transiently and may recover. During the period of time of reversible electroporation, these cells may not be able to produce and conduct action potentials and will be electrically silent (noted as absence of electrograms). With high number of pulses of high voltage, inevitably tissue will be heated by Joule heating, which may cause some cell (closest to the catheter) to be thermally damaged.

Figure 4

The evolution of novel and contemporary PFA devices. Recent approval resulted in rapid real-world adoption. For more details, see text and Tables 2 and 3. PFA, pulsed field ablation; RF, radiofrequency.

Figure 5

Pulsed field ablation practical considerations. Pulsed field as an energy form is less contact force sensitive, since the electrical field spreads into tissues surrounding the catheter. However, pre-clinical data show that tissue contact has a direct effect on lesion depth and durability. Currently, catheter visualization, navigation, and contact assessment are primarily based on fluoroscopy, intracardiac echocardiography, or simplified impendence-based 3D mapping. In future, sophisticated concepts regarding catheter navigation and contact assessment will evolve (Figure 4). If deep sedation instead of general anaesthesia was used, PFA typically stimulates skeletal muscles and the phrenic nerve. In this scenario, a stabilizing guidewire may be beneficial reducing the risk of device dislocation but needs to balanced vs. the risk of mechanical trauma. (A) The pentaspline device position can be assessed in comparison with selective PV angiograms. In addition, the interaction between splines and tissue adds valuable information regarding local contact (arrow). (B) Alternatively, the pentaspline devices can be visualized within a 3D mapping system with impedance-based catheter localization. However, the device is displayed only as a circular structure, reducing catheter positioning accuracy. (C) Real-time catheter localization may be also assessed using intracardiac echo: besides embedded costs, this seems to be a viable alternative to reduce X-ray exposure (courtesy of Bart Moulder). (D) Future 3D mapping integration and lesion visualization of repetitive pentaspline applications (courtesy of Melanie Gunawardene). PFA, pulsed field ablation.

Figure 6

(A, B) VT ablation in the near future will take advantage of image integration combined with centimetric ablation electrodes positioned on CT channels (in between areas of block as circled in white) after registration in the navigation system. (C ) Illustrates pulsed field ablation lesions as imaged acutely after three deliveries placed in the LV septum of a sheep using the AFFERA system. Two additional lesions are visible on that acute late gadolinium enhancement MRI in the RV. Lesion size (D) is extracted from acute MRI. Such a lesion would allow a ‘single shot approach’ to block a channel. LV, left ventricle; RV, right ventricle.