Development and Validation of a Mucosal Impedance Contour Analysis System to Distinguish Esophageal Disorders

Abstract

Background & aims: Diagnostic testing for chronic esophageal disorders relies on histopathology analysis of biopsies or uncomfortable transnasal catheters or wireless pH monitoring, which capture abnormal intraluminal refluxate. We therefore developed a balloon mucosal impedance (MI) catheter system that instantly detects changes in esophageal mucosal integrity during endoscopy over a long segment of the esophagus. We performed a prospective study to evaluate the ability of a balloon-incorporated MI catheter to detect and evaluate esophageal disorders, including gastroesophageal reflux disease (GERD) and eosinophilic esophagitis (EoE).

Methods: We performed a prospective study of 69 patients undergoing esophagogastroduodenoscopy with or without wireless pH monitoring. Patients were classified as having GERD (erosive esophagitis or abnormal pH; n = 24), EoE (confirmed with pathology analysis of tissues from both distal and proximal esophagus; n = 21), or non-GERD (normal results from esophagogastroduodenoscopy and pH tests; n = 24). Receiver operating characteristic curves and area under the operating characteristic curve (AUC) were used to compare the accuracy of balloon MI in diagnosis. Probabilities of assignment to each group (GERD, non-GERD, or EoE) were estimated using multinomial logistic regression. Association between MI patterns and diagnoses were validated using data from patients seen at 3 separate institutions.

Results: MI pattern along the esophageal axis differed significantly (P < .01) among patients with GERD, EoE, and non-GERD. Patients with non-GERD had higher MI values along all measured segments. The MI pattern for GERD was easily distinguished from that of EoE: in patients with GERD, MI values were low in the distal esophagus and normalized along the proximal esophagus, whereas in patients with EoE, measurements were low in all segments of the esophagus. Intercept and rate of rise of MI value (slope) as distance increased from the squamocolumnar junction identified patients with GERD with an AUC = 0.67, patients with EoE with an AUC = 0.84, and patients with non-GERD with an AUC = 0.83 in the development cohort. One patient had an adverse event (reported mild chest pain after the procedure) and was discharged from the hospital without further events.

Conclusions: We developed a balloon MI catheter system that instantly detects changes in esophageal mucosal integrity during endoscopy and found it to be safe and able to identify patients with GERD, EoE, or non-GERD. We validated our findings in a separate cohort for patients. ClinicalTrials.gov ID NCT03103789.

Keywords: Diagnostic; Impedance Contour; Predictive Model; Prognostic.

Conflict of interest statement

Disclosures and Conflicts of Interest: Vanderbilt University and Diversatek Healthcare Inc. (Denver, CO, USA) jointly hold a patent on the mucosal impedance (MI) concept and device. This was disclosed to patients. MV, DK, CPG, and JP have had research funding from Diversatek Healthcare in the conduct of studies with mucosal impedance. Diversatek Healthcare had no influence on the study design, conduct, analysis or the final manuscript. There are no financial relationships between any of the other authors and Diversatek Healthcare Inc. All other authors (DP, TH, JC, MA, MM, EY) have no conflicts of interest.

Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1.

Novel MI balloon catheter with 36 channels measuring impedance axially and radially along a 10 cm length of the esophagus.

Figure 2.

A) Average MI and standard error over channels from distal to proximal esophagus (1-> 9) by diagnosis group in both internal (solid line) and external cohorts (dotted line). B) MI measurements (Ω) stratified by esophageal pathology and distance from SCJ. X-axis represents columns of impedance sensors 90 degrees apart. B) Loss of esophageal mucosal integrity results in low MI values color coded as red (seen distally in both GERD and EoE), but the MI values remained low in EoE proximally (due to pan-esophageal involvement), while it normalizes in GERD (green/yellow). Non-GERD patients have no disruption in mucosal integrity resulting in normal MI values (green and blue).

Figure 2.

A) Average MI and standard error over channels from distal to proximal esophagus (1-> 9) by diagnosis group in both internal (solid line) and external cohorts (dotted line). B) MI measurements (Ω) stratified by esophageal pathology and distance from SCJ. X-axis represents columns of impedance sensors 90 degrees apart. B) Loss of esophageal mucosal integrity results in low MI values color coded as red (seen distally in both GERD and EoE), but the MI values remained low in EoE proximally (due to pan-esophageal involvement), while it normalizes in GERD (green/yellow). Non-GERD patients have no disruption in mucosal integrity resulting in normal MI values (green and blue).

Figure 3.

Receiver operating characteristic analysis of intercept and slope of balloon MI measurements along the esophageal axis for diagnosis of GERD, EoE, and non-GERD.

Figure 4.

Predicted probabilities of GERD, non-GERD, or EoE stratified by MI intercept and slope (rate of rise from distal to proximal esophagus). Shades of colors show relative probabilities of the condition (Blue for EoE; Red for GERD; and Gray for non-GERD). Low intercept (measurement at the most distal channel) and low slope (rise of MI from distal to proximal esophagus) is suggestive of EoE (blue), while low intercept, but greater rise in slope is suggestive of GERD (red).