Ineffective esophageal motility: Concepts, future directions, and conclusions from the Stanford 2018 symposium

Abstract

Background: Ineffective esophageal motility (IEM) is a heterogenous minor motility disorder diagnosed when ≥50% ineffective peristaltic sequences (distal contractile integral <450 mm Hg cm s) coexist with normal lower esophageal sphincter relaxation (integrated relaxation pressure < upper limit of normal) on esophageal high-resolution manometry (HRM). Ineffective esophageal motility is not consistently related to disease states or symptoms and may be seen in asymptomatic healthy individuals.

Purpose: A 1-day symposium of esophageal experts reviewed existing literature on IEM, and this review represents the conclusions from the symposium. Severe IEM (>70% ineffective sequences) is associated with higher esophageal reflux burden, particularly while supine, but milder variants do not progress over time or consistently impact quality of life. Ineffective esophageal motility can be further characterized using provocative maneuvers during HRM, especially multiple rapid swallows, where augmentation of smooth muscle contraction defines contraction reserve. The presence of contraction reserve may predict better prognosis, lesser reflux burden and confidence in a standard fundoplication for surgical management of reflux. Other provocative maneuvers (solid swallows, standardized test meal, rapid drink challenge) are useful to characterize bolus transit in IEM. No effective pharmacotherapy exists, and current managements target symptoms and concurrent reflux. Novel testing modalities (baseline and mucosal impedance, functional lumen imaging probe) show promise in elucidating pathophysiology and stratifying IEM phenotypes. Specific prokinetic agents targeting esophageal smooth muscle need to be developed for precision management.

Keywords: contraction reserve; dysphagia; gastroesophageal reflux disease; high-resolution manometry; ineffective esophageal motility; multiple rapid swallows.

FIGURE 1

High-resolution impedance manometry showing ineffective esophageal motility (IEM) with contraction reserve. There were 60% ineffective swallows with distal contractile integral (DCI) <450 mm Hg cm s, meeting the Chicago Classification 3.0 criteria for IEM (≥50% ineffective swallows). There was a combination of weak (DCI < 450 mm Hg cm s but >100 mm Hg cm s) and failed (DCI < 100 mm Hg cm s) swallows. The violet overlay represents bolus presence on stationary impedance. (A) A weak swallow with DCI 420 mm Hg cm s and incomplete bolus transit on stationary impedance. (B) A failed swallow with no contraction and incomplete bolus transit. (C) Multiple rapid swallows, demonstrating augmentation of smooth muscle contraction following the final swallow of the sequence (contraction reserve), and adequate bolus transit

FIGURE 2

Pathophysiology of ineffective esophageal motility (IEM). Neural control of esophageal smooth muscle contraction from the brain stem vagal nuclei is modulated by peripheral sensory data from the esophagus through vagal afferents, and by central inputs to the brain stem. Central and peripheral neural dysfunction can contribute to ineffective esophageal smooth muscle peristalsis. Muscle dysfunction can either be primary, a consequence of gastroesophageal reflux disease (GERD), or related to other factors influencing muscle function, including smooth muscle disorders and medications. However, IEM as currently defined is a manometric diagnosis and may be a normal variant without clinical consequences. Only severe IEM (with >70% ineffective swallows) has been implicated in abnormal esophageal reflux burden and dysphagia

FIGURE 3

Diagnosis of ineffective esophageal motility (IEM) is based on ≥50% ineffective supine primary swallows during high-resolution manometry (HRM) or high-resolution impedance manometry (HRIM). Supplementary evaluation can be personalized based on the clinical scenario being evaluated, using provocative tests. For instance, demonstration of contraction reserve during pre-operative HRM increases confidence in standard antireflux surgery (ARS) for the management of concurrent GERD. Secondary peristalsis can be evaluated during sedated endoscopy using functional lumen imaging probe (FLIP), but its role in clinical evaluation of IEM remains undefined

FIGURE 4

Adjunctive evaluation of esophageal peristaltic performance using novel metrics and techniques. (A) Functional lumen imaging probe (FLIP) topography with lumen changes representing repetitive antegrade contractions as a response to luminal distension. These secondary peristaltic waves represent the ability of the esophagus to generate distension-induced secondary peristalsis. (B) A pH-impedance study demonstrating a reflux episode (upward arrow) followed by a postreflux swallow-induced peristaltic wave (PSPW) within 30 s of the end of the reflux episode. This represents the ability of esophageal neural connections to generate reflux-induced primary peristalsis, bringing salivary bicarbonate to neutralize esophageal mucosal acidification from the reflux episode

FIGURE 5

Evaluation of reflux-induced mucosal integrity using baseline and mucosal impedance. (A) Normal mean nocturnal baseline impedance (MNBI) when baseline impedance is measured on an ambulatory pH-impedance study over a 10-min period during quiet sleep without swallows or other artifacts. Values above 2292 Ω in the distal esophagus are considered within normal range. (B) Low MNBI in a patient with GERD. (C) Mucosal impedance topograph using a second generation mucosal impedance probe with two strips of 9 impedance sensors mounted on a balloon to ensure adequate contact with the esophageal mucosa. Red colors indicate low mucosal impedance in the distal esophagus in this patient with GERD