Terminating ventricular tachyarrhythmias using far-field low-voltage stimuli: mechanisms and delivery protocols

Abstract

Background: Low-voltage termination of ventricular tachycardia (VT) and atrial fibrillation has shown promising results; however, the mechanisms and full range of applications remain unexplored.

Objectives: To elucidate the mechanisms for low-voltage cardioversion and defibrillation and to develop an optimal low-voltage defibrillation protocol.

Methods: We developed a detailed magnetic resonance imaging-based computational model of the rabbit right ventricular wall. We applied multiple low-voltage far-field stimuli of various strengths (≤1 V/cm) and stimulation rates in VT and ventricular fibrillation (VF).

Results: Of the 5 stimulation rates tested, stimuli applied at 16% or 88% of the VT cycle length (CL) were most effective in cardioverting VT, the mechanism being consecutive excitable gap decreases. Stimuli given at 88% of the VF CL defibrillated successfully, whereas a faster stimulation rate (16%) often failed because the fast stimuli did not capture enough tissue. In this model, defibrillation threshold energy for multiple low-voltage stimuli at 88% of VF CL was 0.58% of the defibrillation threshold energy for a single strong biphasic shock. Based on the simulation results, a novel 2-stage defibrillation protocol was proposed. The first stage converted VF into VT by applying low-voltage stimuli at times of maximal excitable gap, capturing large tissue volume and synchronizing depolarization; the second stage terminated VT. The energy required for successful defibrillation using this protocol was 57.42% of the energy for low-voltage defibrillation when stimulating at 88% of VF CL.

Conclusions: A novel 2-stage low-voltage defibrillation protocol using the excitable gap extent to time multiple stimuli defibrillated VF with the least energy by first converting VF into VT and then terminating VT.

Keywords: AF; CL; Computer simulation; DFT; Electric countershock; Electric stimulation; RV; Tachycardia, Ventricular; V(m); VEP; VF; VT; Ventricular fibrillation; atrial fibrillation; cycle length; defibrillation threshold; extracellular potential; right ventricle/ventricular; transmembrane potential; ventricular fibrillation; ventricular tachycardia; virtual electrode polarization; Φ(e).

Figure 1

A: Sample MRI slices. Left image taken from apical, right image from basal position. B: The same MRI slices as in panel A after bath removal, segmentation, and cropping of RV wall. C: Long (left) and short (right) axis views of the high-resolution rabbit RV model. Grey boxes mark the pacing electrodes, colored lines mark the far-field electrodes, and colored arrows mark the electric field directions. The long axis view shows the endocardial microstructures (especially trabecular grooves). The inset provides a detailed view of the high-resolution finite-element mesh.

Figure 2

A: Mean cardioversion success rates for different stimulation rates and strengths (means taken over electrode setups to better differentiate between outcomes from stimulation rates). Data points representing means are shown as diamonds. B: Mean number of stimuli and stimulation energy required for successful cardioversion at different stimulation strengths (means taken over electrode setups and stimulation rates to illustrate trend). Data points representing means shown as diamonds.

Figure 3

A: Differences in activation time (Δt) between control and cardioversion simulations after the first stimulus. Blue colors represent earlier activation after stimulation compared to control (i.e., wavefront advancement), red colors mark later activation after stimulation than control. Areas enclosed by the yellow lines were activated 0–40ms or 0–22% of VT CL after the stimulus, areas enclosed by the dashed pink lines were activated 40–110ms or 22–60% of VT CL after the stimulus, and areas enclosed by the dotted green lines were activated at the end of the post-stimulus VT cycle. Small insets show epicardial maps. The activation map on the right shows control activation time. Arrows mark the direction of propagation. At the end of the cycle, the wavefront was advanced after stimulation compared to control (blue areas enclosed by dotted green lines in Δt maps), regardless of electrode configuration. B: Activation maps and Δt maps over several cycles show the accumulation of wavefront advancement effects leading to the consumption of the excitable gap after several stimuli.

Figure 4

A: V_m maps before (left) and after (right) VEPs induced a new wavefront following one stimulus of 289mV/cm strength given from setup 1. The transmural views show post-stimulus excited tissue in the trabecular grooves, caused by VEPs, but no excited tissue at the coronary vasculature. B: Activation maps show VT termination due to collision of VT wavefront with the new VEP-induced wavefront for the same simulation as in panel A. The transmural view shows that the shock-induced wavefront originated in the trabecular grooves. Light grey arrows mark direction of propagation.

Figure 5

A: Defibrillation success rates for monophasic (lines; data points shown as diamonds) and biphasic (non-diamond symbols) stimuli as a function of stimulus strength and at 16% and 88% of VF CL. B: Mean number of stimuli and stimulation energy required for successful defibrillation attempts (means taken over electrode setups and stimulation rates). Diamonds show data points representing means for monophasic stimuli. C: Mean number of stimuli and mean stimulation energy required for defibrillation attempts at different “phases” of VF after 500mV/cm stimuli administered at 88% VF CL (means taken over electrode setups). Defibrillation was successful regardless of the timing of the initial stimulus. D: Mean DFTs of single biphasic shocks and of multiple low-voltage monophasic stimuli (means over electrode setups).

Figure 6

A: The volume of excitable tissue (measured as percentage of excitable nodes in the mesh) during successful defibrillation at 88% VF CL (red) and failed defibrillation at 16% VF CL (green) after 500mV/cm stimuli given from electrode setup 2. Thin vertical lines mark onsets of stimuli. B: The excitable volume during successful 500mV/cm, 88% VF CL defibrillation stimuli delivered at different “phases” of VF. The blue line represents excitable volume when the first stimulus was administered from setup 1 100ms earlier than the initial stimuli in the protocols presented in panel A. The brown line marks the excitable volume in the case when the initial stimulus was administered from setup 2 50ms later than the first stimuli in the protocols shown in panel A. Thin vertical lines mark onsets of stimuli.

Figure 7

A: Top panel: The excitable volume during a defibrillation attempt from electrode setup 1 where 250mV/cm stimuli were delivered at timings when the amount of excitable tissue was maximal. Lower panels: V_m maps of defibrillation attempt. VF was converted to VT with these appropriately timed stimuli, but VT remained stable and did not terminate. B: Top panel: Excitable volume during defibrillation attempt from electrode setup 2 where 250mV/cm stimuli were delivered at timings when the excitable tissue was maximal. Lower panels: V_m maps of defibrillation attempt. VF was converted to VT, and VT was then terminated with additional stimuli from setup 2. Thin vertical lines in top panels mark onsets of stimuli.

Figure 8

A: Comparison of the mean number of stimuli and energy required for successful defibrillation following 250mV/cm stimuli at 88% VF CL and using the two-stage defibrillation protocol (means taken over electrode setups). B: V_m maps of successful defibrillation with the two-stage defibrillation protocol compared to control V_m maps. With this two-stage defibrillation protocol, VF was converted into VT, which was then successfully terminated.