Absence of Arrhythmogenicity with Biphasic Pulsed Electric Fields Delivered to Porcine Airways

Abstract

Pulsed electric field (PEF) technologies treat many types of tissue. Many systems mandate synchronization to the cardiac cycle to avoid the induction of cardiac arrhythmias. Significant differences between PEF systems make the assessment of cardiac safety from one technology to another challenging. A growing body of evidence suggests that shorter duration biphasic pulses obviate the need for cardiac synchronization, even when delivered in a monopolar fashion. This study theoretically evaluates the risk profile of different PEF parameters. It then tests a monopolar, biphasic, microsecond-scale PEF technology for arrhythmogenic potential. PEF applications of increasing likelihood to induce an arrhythmia were delivered. The energy was delivered throughout the cardiac cycle, including both single and multiple packets, and then with concentrated delivery on the t-wave. There were no sustained changes to the electrocardiogram waveform or to the cardiac rhythm, despite delivering energy during the most vulnerable phase of the cardiac cycle, and delivery of multiple packets of PEF energy across the cardiac cycle. Only isolated premature-atrial contractions (PAC) were observed. This study provides evidence that certain varieties of biphasic, monopolar PEF delivery do not require synchronized energy delivery to prevent harmful arrhythmias.

Keywords: Arrhythmia; Cardiac gating; Cardiac synchronization; ECG; ECG-sync; Electroporation.

Fig. 1

PEF system setup: A PEF generator connected to a cardiac monitor and expandable basket electrode was used to deliver energy. The energy is returned through a dispersive electrode

Fig. 2

Numerical Simulation representative results. (a) Numerical simulation geometry. (b–d) Cross-sectional view of electrical conductivity, electric field, and voltage distributions into simulated lung parenchymal tissue. Grid = 5 mm

Fig. 3

PEF cardiac effect sensitivity and relation to a basic treatment. (Top) Activation and fibrillation voltage thresholds as a function of pulse duration for a single monophasic pulse. (Bottom) Numerical simulation tissue voltage exposure for a basic monopolar basket electrode in the airway with different applied voltages. Activation and fibrillation voltage thresholds for selected pulses are superimposed, conveying the low activation threshold for all pulse durations, but very high fibrillation thresholds for pulses ≤ 10 µs

Fig. 4

(a) Fluoroscopic image of bronchoscope in the left main bronchus of the swine with deployment of the basket electrode (b-d) Representative swine CT scans are provided with proximity to the epicardial surface measured in the axial (b, 1.96 mm), coronal (c, 5.97 mm and 4.74 mm), and sagittal (d, 7.06 mm) planes

Fig. 5

Examples of cardiac effects from asynchronous PEF delivery. There may be no change (top left), an artifactual change in the immediate heartbeat ECG due to signal interference (top right), a PAC without ventricular conduction that briefly delays the subsequent heartbeat (bottom left), or a PAC that conducts through to the ventricle resulting in an early heartbeat (bottom right). The two PAC conditions are seen to alter that specific R–R interval but have no residual effect beyond the subsequent heartbeat. Black arrows and numbers denote the time interval from QRS complex to PEF delivery. Red bars and numbers denote when the PEF packet was delivered and the PEF packet number