Effect of electrical stimulation of the lower esophageal sphincter in gastroesophageal reflux disease patients refractory to proton pump inhibitors

Abstract

Aim: To evaluate the efficacy of lower esophageal sphincter (LES)-electrical stimulation therapy (EST) in a subgroup of patients that reported only partial response to proton pump inhibitors (PPIs) therapy, compared to a group of patient with complete response.

Methods: Bipolar stitch electrodes were laparoscopically placed in the LES and connected to an implantable pulse generator (EndoStim BV, the Hague, the Netherlands), placed subcutaneously in the anterior abdominal wall. Stimulation at 20 Hz, 215 μsec, 3-8 mAmp in 30 min sessions was delivered starting on day 1 post-implant. Patients were evaluated using gastroesophageal reflux disease (GERD)-HRQL, symptom diaries; esophageal pH and esophageal manometry before and up to 24 mo after therapy and results were compared between partial and complete responders.

Results: Twenty-three patients with GERD on LES-EST were enrolled and received continuous per-protocol stimulation through 12 mo and 21 patients completed 24 mo of therapy. Of the 23 patients, 16 (8 male, mean age 52.1 ± 12 years) had incomplete response to PPIs prior to LES-EST, while 7 patients (5 male, mean age 52.7 ± 4.7) had complete response to PPIs. In the sub-group with incomplete response to PPIs, median (IQR) composite GERD-HRQL score improved significantly from 9.5 (9.0-10.0) at baseline on-PPI and 24.0 (20.8-26.3) at baseline off-PPI to 2.5 (0.0-4.0) at 12-mo and 0.0 (0.0-2.5) at 24-mo follow-up (P < 0.05 compared to on-and off-PPI at baseline). Median (IQR) % 24-h esophageal pH < 4.0 at baseline in this sub-group improved significantly from 9.8% (7.8-11.5) at baseline to 3.0% (1.9-6.3) at 12 mo (P < 0.001) and 4.6% (2.0-5.8) at 24 mo follow-up (P < 0.01). At their 24-mo follow-up, 9/11 patients in this sub-group were completely free of PPI use. These results were comparable to the sub-group that reported complete response to PPI therapy at baseline. No unanticipated implantation or stimulation-related adverse events, or any untoward sensation due to stimulation were reported in either group and LES-EST was safely tolerated by both groups.

Conclusion: LES-EST is safe and effective in controlling symptoms and esophageal acid exposure in GERD patients with incomplete response to PPIs. These results were comparable to those observed PPI responders.

Keywords: Electrical stimulation; Gastroesophageal reflux; Lower esophageal sphincter; Proton pump inhibitors; Refractory gastroesophageal reflux disease.

Figure 1

Lower esophageal sphincter stimulation system. A: EndoStim^® wireless Programmer, Implantable Pulse Generator and Bipolar Stimulation Lead. Inset shows the two stimulation electrodes and the butterfly used for anchoring the electrode at the LES; B: Schematic of the EndoStim^® System Implant in a Patient: Electrode position and IPG implant location. Bipolar stitch electrodes are placed in the abdominal esophagus anteriorly in an inline configuration 1 cm apart. The lead is connected to the IPG that is implanted in the subcutaneous pocket in the anterior abdomen. IPG: Implantable pulse generator; LES: Lower esophageal sphincter.

Figure 2

Frequency of daytime and nighttime symptoms of (A) heartburn and (B) regurgitation at baseline and with lower esophageal sphincter - electrical stimulation therapy at 12 and 24 mo. Data are presented as median and interquartile range (IQR). Absence of median value or IQR bars indicate a value of zero for the listed variables. NS = Not significant, ^aP < 0.05, ^bP < 0.01, ^dP < 0.001. A: Percent days with Heartburn at baseline, 12- and 24-mo following LES-EST. There was a significant reduction in reported daytime and nighttime with heartburn at both time points compared to baseline, in both groups; B: Percent of days with Regurgitation at baseline, 12- and 24-mo following LES-EST. There was a marked reduction in reported daytime and nighttime with regurgitation at both time points compared to baseline, in the incomplete responder group and a marked reduction in these variables in the responder group. LES: Lower esophageal sphincter; EST: Electrical stimulation therapy.