Acute Slow Wave Responses to High-Frequency Gastric Electrical Stimulation in Patients With Gastroparesis Defined by High-Resolution Mapping

Abstract

Background and aims: High-frequency gastric electrical stimulation (GES) has emerged as a therapy for gastroparesis, but the mechanism(s) of action remain unclear. There is a need to refine stimulation protocols for clinical benefit, but a lack of accurate techniques for assessing mechanisms in clinical trials, such as slow wave modulation, has hindered progress. We thereby aimed to assess acute slow wave responses to GES in gastroparesis patients using high-resolution (HR) (multi-electrode) mapping, across a range of stimulation doses achievable by the Enterra stimulation device (Medtronic Inc., MN, USA).

Materials and methods: Patients with medically refractory gastroparesis (n = 8) undergoing device implantation underwent intraoperative HR mapping (256 electrodes). Baseline recordings were followed by four protocols of increasing stimulation intensity, with washout periods. Slow wave patterns, frequency, velocity, amplitude, and dysrhythmia rates were quantified by investigators blinded to stimulation settings.

Results: There was no difference in slow wave pattern, frequency, velocity, or amplitude between baseline, washout, and stimulation periods (all p > 0.5). Dysrhythmias included ectopic pacemakers, conduction blocks, retrograde propagation, and colliding wavefronts, and dysrhythmia rates were unchanged with stimulation off vs. on (31% vs. 36% duration dysrhythmic; p > 0.5). Symptom scores and gastric emptying were improved at 5.8 month follow-up (p < 0.05).

Conclusions: High-frequency GES protocols achievable from a current commercial device did not acutely modulate slow wave activity or dysrhythmias. This study advances clinical methods for identifying and assessing therapeutic GES parameters, and can be applied in future studies on higher-energy protocols and devices.

Keywords: Diabetes mellitus; electrophysiology; high-resolution mapping; pacing; slow wave.

Figure 1

Illustration of methods. A) FPC electrode array. B) Typical positioning of the stimulator leads and distal positioning of the FPC electrode array on the stomach.

Figure 2

Example slow wave maps showing (from left to right) activation, velocity, and amplitude, during periods of A) baseline, B) low stimulation, C) medium stimulation, D) high stimulation, and E) max stimulation. Activation maps show the propagation pattern of a single wavefront, with each color band representing the area of propagation per 2 s, from red (early) to blue (late). Each dot represents an electrode, and red outlined dots signify that data was interpolated at that electrode. Velocity maps show the direction (arrow) and speed (color gradient) of propagation of the wavefront at each electrode. Amplitude maps show the slow wave amplitude at each electrode as a color gradient across the array. Example electrograms are shown in the right-most column, corresponding to the electrode positions labelled in the activation map (left-most column). The FPC electrode array was positioned in the distal antrum for these recordings, as shown in Figure 1B.

Figure 3

Average slow wave characteristics compared at baseline and each level of stimulation, including: A) longitudinal velocity, B) amplitude, and C) frequency. Washout periods with stimulation off were also performed between stimulation levels (refer to text).

Figure 4

Example dysrhythmic slow wave propagation in a A) baseline recording (stimulation off) versus B) recording during stimulation (medium protocol). i) position of the electrode array; ii) example electrograms from electrodes labelled in panel iii; iii–v) activation, velocity, and amplitude maps, respectively, as described in Figure 2.