Ineffective Esophageal Motility: Discard or Discover?

Ineffective Esophageal Motility: Discard or Discover? Ineffective esophageal motility (IEM) is defined as 70% or more ineffective or 50% or more failed swallows during high resolution manometry (HRM) according to the recently released Chicago Classification Criteria v4.0. ¹ As a field, we are at a crossroads—we need a conclusion for the 30-plus-year long epic of IEM. Precisely, we need to decide whether we consider IEM a cause of clinically relevant esophageal dysmotility or not; that is, should IEM be an actionable entity when found in the setting of dysphagia or gastroesophageal reflux disease (GERD), or not.

In the present article by Reddy et. all, titled “Medical Therapy for Ineffective Esophageal Motility: A Systematic Review,” the authors aimed to perform a meta-analysis of randomized controlled trials (RCTs) for medical therapies in IEM. Not surprisingly, they were unable to conduct a meta-analysis due to the paucity of high-quality RCTs with similar outcome measures. Ultimately in their systematic review, they included 6 studies. Of these, 5 studies assessed manometric outcomes, and a single study included manometric outcomes along with symptom outcomes of the Gastroesophageal Reflux Disease Healthcare-Related Quality-of-Life (GERD-HRQL) and the Mayo Dysphagia Questionnaires (MDQ). The trials studied the effect of various serotonin receptor agonists and bethanechol individually in a total of 65 patients. Key findings from the systematic review are that (a) mosapride and prucalopride lowered threshold volumes required to generate secondary peristalsis and increased the frequency and efficiency of secondary peristalsis, (b) sumatriptan improved the total number of swallows and primary esophageal motor waves, (c) bethanechol increased the proportion of peristaltic swallows, esophageal contractions pressures, and the frequency of complete liquid bolus transit, and (d) buspirone did not show an effect on manometric parameters or the GERD-HRQL and MDQ scores.

The present study is an accurate representation of the current conundrum in IEM. The lack of high-quality studies with controlled outcomes speaks to the declining interest in investigation of IEM as a clinical entity. Many experts increasingly believe that IEM has little relevance in dysphagic patients. Similarly, the dogma of tailored fundoplication for GERD based on pre-operative manometry has lost credibility due to newer evidence suggesting little basis for this practice.^2,3 But should we really be equating IEM on HRM with functional dysphagia? Prior to our current hyper-focus on obstructive disorders of the esophagogastric junction outflow obstruction, IEM was perhaps the most common and impressive physiologic entity we noted on HRM. ⁴ Although the progress we have made with cognitive-based interventions for esophageal disorders is commendable, in my mind, we should always strive to optimize physiology first.

The present study, although limited in its ability to draw strong conclusions, suggests a potential to improve esophageal physiology in IEM patients. The therapies assessed are relatively safe and are available for other gastrointestinal and non-gastrointestinal indications. Prucalopride is approved in the US as maintenance therapy for chronic idiopathic constipation. Additionally, there is a renewed interest in assessing secondary esophageal peristalsis with the increased clinical role of functional lumen imaging probe (FLIP) topography. ⁵ Thus, I would argue for the expansion of systematic diagnosis and treatment-related investigations in IEM. It is conceivable that, particularly serotonin receptor agonists, could have a therapeutic benefit in IEM as monotherapy or in combination with swallowing behavior modifications and cognitive behavioral therapy for patients with dysphagia. In patients with GERD, perhaps the addition of medical therapy for IEM can present an option to target the precise physiology leading to increased acid exposure and allow for subsets of patients to reduce proton-pump inhibitor (PPI) use and avoid anti-reflux procedures.

In conclusion, in the current era of increased focus on spastic esophageal disorders and disorders of esophagogastric junction obstruction outflow obstruction, the present study justifies a look to the past and the fundamentals of esophageal physiology. Indeed, it is not time to discard, but rather to discover, new frontiers in management of IEM.

Anand S. JainDivision of Digestive Diseases Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA