A practical approach to ineffective esophageal motility

Background and purpose:

Ineffective esophageal motility is the most frequently diagnosed esophageal motility abnormality and characterized by diminished esophageal peristaltic vigor and frequent weak, absent, and/or fragmented peristalsis on high-resolution esophageal manometry. Despite its commonplace occurrence, this condition can often provoke uncertainty for both patients and clinicians. Although the diagnostic criteria used to define this condition has generally become more stringent over time, it is unclear whether the updated criteria result in a more precise clinical diagnosis. While ineffective esophageal motility is often implicated with symptoms of dysphagia and gastroesophageal reflux disease, the strength of these associations remains unclear. In this review, we share a practical approach to ineffective esophageal motility highlighting its definition and evolution over time, commonly associated clinical symptoms, and important management and treatment considerations. We also share the significance of this condition in patients undergoing evaluation for anti-reflux surgery and consideration for lung transplantation.

Introduction

Ineffective esophageal motility (IEM), the most frequently diagnosed esophageal motility abnormality¹, is characterized by diminished esophageal peristaltic vigor and frequent weak, absent, and/or fragmented peristalsis on high-resolution manometry (HRM). While commonly associated with esophageal dysfunction and gastroesophageal reflux disease (GERD), IEM does not necessarily result in symptomatic abnormal bolus transit² and is often nonprogressive and non-durable, with many patients reporting minimal symptoms longitudinally or having normal findings on subsequent HRM.^3,4 Additionally, in patients with IEM, esophageal symptoms can often improve with conservative symptomatic management over long-term follow-up.⁵ Further, intermittent weak peristaltic contractions are relatively common in healthy individuals which attenuates its clinical significance.

Despite these uncertainties, the notion that their esophageal motility is ‘ineffective’ commonly provokes health-related anxiety in patients. From a clinician standpoint, the finding of IEM can lead to diagnostic and therapeutic uncertainty triggering a downstream cascade of low-yield testing and ineffective pharmacologic therapies with significant costs and potential risks.

In this review, we highlight a practical approach to IEM, a condition that often confers limited clinical significance, yet can have significant effects on patients.

Definition and evolution of IEM

The manometric definition of IEM has become more stringent over time. In the 1990s, the diagnosis required presence of ≥30% ineffective swallows based on conventional, low-resolution manometry.⁶ In Chicago classification (CC)v1.0, this manometric pattern was referred to as hypotensive peristalsis that occurred intermittently or frequently. In CCv2.0, it was defined as weak or frequent failed peristalsis. The term IEM was reintroduced in CCv3.0 (2014) defined as ≥50% ineffective swallows.⁷ In CCv3.0, IEM was further considered a minor, rather than major, disorder of peristalsis and different from fragmented peristalsis. The CCv4.0 (2021) defines a conclusive diagnosis of IEM as >70% ineffective swallows or ≥50% failed peristalsis with normal median integrated relaxation pressure (IRP).⁸ An ineffective swallow encompasses swallows with a weak contraction (distal contractile integral (DCI) ≥100 mmHg·s·cm and <450 mmHg·s·cm), failed peristalsis (DCI <100 mmHg·s·cm), or fragmentation (transition zone defects >5 cm) (Figure 1).^8,9 Additionally, CCv4.0 has eliminated the terminology of major and minor disorders of peristalsis.

Figure 1.

In contrast to a normal swallow (A), manometric findings that support a diagnosis of IEM include failed swallows (B), weak swallows (C), and fragmented swallows (D). The presence (E) of augmentation on multiple repetitive swallow sequence is also illustrated.

Adjunct provocative maneuvers performed with HRM and assessment of bolus transit in combined manometry-impedance may help support a diagnosis of IEM and suggest its clinical significance. These include a lack of contraction reserve in response to multiple repetitive swallows (MRS) and abnormal bolus clearance with impedance.^8,9 A normal MRS response demonstrates peristaltic augmentation for the final swallow of the sequence, termed peristaltic reserve.⁹ Normal peristaltic reserve is defined by a ratio of DCI on MRS to the mean DCI of 10 single swallows being greater than 1, or in other words, the contractile augmentation following MRS to be more robust than that of single swallows (Figure 1). Notably, approximately 20% of healthy, asymptomatic individuals may have an abnormal peristaltic reserve highlighting the limited predictive value of this metric in isolation. Given this limitation, up to 3 MRS sequences are performed with normal peristaltic reserve defined by DCI ratio >1 for at least 1 sequence.¹⁰ Another adjunct provocative maneuver may include addition of solid food swallows to single water swallows.¹¹

As with other areas of the gastrointestinal tract, opioids have been shown to affect esophageal motility and have the potential to result in opioid-induced esophageal dysfunction.¹² In addition, acute administration of opioids has been shown to alter esophageal peristalsis in IEM.¹³ For this reason, HRM should ideally be performed off opioids whenever clinically feasible to best understand esophageal motility without the effect of such medications.

Renewed clinical relevance with the updated IEM definition?

While the criteria required to diagnose IEM have become more stringent with CCv4.0, it remains unclear whether this definition results in a more precise clinical diagnosis given a lack of outcome studies required to better define a gold standard measure. IEM may be present in asymptomatic healthy adults with estimates ranging from 10% (CCv4.0) to 17% (CCv3.0).^14,15 As the best predictors of abnormal bolus clearance on HRM have been shown to be ≥30% failed contractions and ≥70% ineffective contractions, a threshold of >70% ineffective swallows (CCv4.0) may theoretically identify more clinically significant disease compared to a threshold of ≥50% ineffective swallows (CCv3.0).¹⁶ Studies comparing manometric diagnoses by CCv3.0 and CCv4.0 have found that approximately one-third of patients with IEM based on CCv3.0 were classified as normal by CCv4.0.^17,18 For example, in a retrospective study of HRMs between 2014–2021, 66 patients met criteria for IEM by CCv3.0, of which 41 (62%) retained IEM by CCv4.0.¹⁹ While those with IEM by CCv4.0 had higher esophageal acid exposure time and DeMeester scores and less adequate peristaltic reserve, there was no difference in bolus clearance between groups.¹⁹ Additionally, the study did not explore treatment outcomes in patients that retained IEM diagnosis leaving uncertainty regarding its clinical significance. While it is clear that the more stringent definition of IEM in CCv4.0 results in fewer diagnoses, whether this translates to greater clinical relevance remains to be seen.

Clinical symptoms, management, and treatment

In this section, we review clinical symptoms commonly associated with IEM and propose a management algorithm (Figure 2). In general, there remains an unclear association between IEM and esophageal symptoms. In patients with no significant symptoms incidentally found to have IEM, patients should be reassured that there is no evidence for progression to clinically relevant conditions. In patients with esophageal symptoms and a finding of IEM, the clinician should seek to determine the clinical relevance of IEM to the patient’s presentation.²⁰

Figure 2.

An algorithm for diagnosis and management of IEM.

Relationship to Dysphagia

Dysphagia, often to both solids and liquids, is commonly associated with IEM. In a retrospective study of 379 patients, IEM was associated with higher mean dysphagia symptom scores and a greater percentage of patients reporting dysphagia affecting daily activities compared to those with normal motility.²¹ However, dysphagia (assessed using a questionnaire) was overall not severe (2 vs. 1.36 out of 5, p<0.01) as only a minority reported dysphagia affecting daily activities. This underscores the lack of clarity regarding the clinical significance of this association.

In patients with dysphagia, esophagogastroduodenoscopy (EGD) should first be performed to rule out structural causes that could account for such symptoms. In patients with normal appearing EGD, esophageal biopsies should be obtained from both the proximal and distal esophagus to rule out underlying eosinophilic esophagitis (EoE) which can sometimes present with normal appearing esophagus or only exhibit subtle abnormalities. A finding of IEM is not uncommon in patients with EoE undergoing HRM studies²², underscoring the need to first rule out structural causes with EGD and esophageal biopsies.

In patients with negative endoscopic evaluation, complementary testing such as barium esophagram or combined manometry-impedance should be considered to further assess bolus transit. As there is no definite medical therapy which reliably accelerates esophageal transit, management relies on reassurance and dietary and lifestyle modification. Recommendations may include cutting food into small pieces, chewing food thoroughly, eating in upright position, performing hard swallows, and consuming foods along with liquids, particularly carbonated beverages, to facilitate esophageal emptying.⁹ A careful medication review may help identify potential agents contributing to esophageal dysmotility.

In patients with persistent symptoms, pharmacologic therapy may be considered although evidence for their efficacy is largely lacking. Prokinetics are often considered, including serotonin modulating agents (prucalopride or mosapride), muscarinic receptor modulating agents (bethanechol), or motilin receptor agonists (erythromycin).²³ However, the mechanism of these agents is typically an augmentation of esophageal contractile force, which does not necessarily correspond to improvement in esophageal transit. Of these agents, mosapride has been demonstrated to shorten esophageal transit time.²⁴ Metoclopramide, a dopamine-2 receptor blocker, often considered first-line in gastroparesis has not shown effectiveness in IEM and given its side-effect profile, including risk of extrapyramidal manifestations, is not recommended.^9,23,25 Given a paucity of data and questionable efficacy for these treatment options, they should not be used routinely in clinical practice unless conservative measures fail and a shared patient-physician decision is made acknowledging major limitations and limited effectiveness. In patients where there appears to be overlap with disorders of the gut-brain axis or visceral hypersensitivity, neuromodulators may also play an important role to decrease symptom intensity, recognizing that these agents have no effect on peristaltic strength.

While IEM is a distinct condition from absent contractility (100% failed peristalsis with normal IRP), in patients with dysphagia as a predominant symptom and manometric findings most suggestive of absent contractility with a normal IRP, achalasia should be a consideration as some patients with type I achalasia can present with absent peristalsis and technically normal IRP without pressurization. In these patients, adjunctive testing such as timed barium esophagram with barium tablet to assess esophageal emptying and/or endoluminal functional lumen imaging probe (EndoFLIP) to assess lower esophageal sphincter distensibility and diameter may be helpful to rule out the possibility of underlying achalasia.

Association with and treatment of GERD in IEM

While typical GERD symptoms (heartburn and/or regurgitation) are often associated with IEM, whether a causal relationship exists between GERD and IEM is uncertain. Furthermore, the direction of this possible causality is unclear: GERD could lead to decreased peristaltic contractility as a result of reflux-induced damage, or perhaps having ineffective motility makes a patient prone to GERD because of decreased ability to clear refluxate. As highlighted above, IEM based on CCv4.0 is more likely with GERD symptoms than prior definitions. In a cross-sectional study of 3826 patients in Vietnam, conclusive IEM had nearly a two-fold increased risk of moderate-severe erosive esophagitis (LA grade B-D) compared to normal motility.²⁶ In contrast, other studies have found no association between IEM and GERD.^21,27 These conflicting studies highlight the controversy of attributing IEM to the inflammatory component of GERD versus the effect of chronic GERD on esophageal muscle and nerve function.

As such, the presence of IEM on HRM alone is not sufficient to establish a diagnosis of GERD. Based on patient symptoms, pH testing off acid suppression can be considered to evaluate for objective GERD. In patients with typical GERD symptoms, a limited trial of acid suppression therapy may be considered, although these agents do not improve esophageal peristalsis.²⁸ In patients with IEM presenting with symptoms consistent with gastroesophageal reflux and pH testing demonstrating pathologic GERD, efforts should first be made to optimize GERD management rather than the IEM pattern itself.²⁰ Notably, there does not appear to be a clear association between atypical GERD symptoms (i.e., laryngopharyngeal reflux) and IEM although this patient population requires further study.

Special populations

Anti-reflux surgery and procedures

The presence of IEM merits discussion in patients with objective GERD undergoing evaluation for anti-reflux surgery. The primary concern in this population is the development of postoperative dysphagia after 360° (Nissen) fundoplication.

Multiple studies have failed to demonstrate a significant difference in development of postoperative dysphagia in patients undergoing anti-reflux surgery with or without underlying IEM. In a retrospective study of 487 patients who underwent laparoscopic fundoplication, more patients with esophageal dysmotility underwent Toupet fundoplication (77%) while the majority with normal motility underwent Nissen fundoplication (82%).²⁹ Patients with esophageal dysmotility had similar postoperative dysphagia scores, GERD symptoms, and quality of life metrics compared to those with normal motility.²⁹ In another single-center, retrospective study comparing outcomes after laparoscopic anti-reflux surgery in patients with and without IEM, patients in both groups had comparable benefits in reflux reduction (IEM, 81% vs. non-IEM, 72%).³⁰ While patients without IEM had greater improvement in dysphagia (44% vs. 27%), satisfaction rates between both groups were similar at around 80%.³⁰ Subgroup analyses showed no differences in postoperative outcomes, including GERD and dysphagia.³⁰ In another single-center study of patients with IEM that underwent Nissen fundoplication, 78% of those with preoperative dysphagia had resolution of their symptoms.³¹ Among 22 patients that did not have preoperative dysphagia, 14% developed dysphagia postoperatively; however, no repeat surgery was required in these patients during follow-up.³¹ In another study comparing postoperative outcomes in patients with and without IEM that underwent Nissen fundoplication, no differences in postoperative dysphagia, symptom relief, quality of life, gas-bloat syndrome, inability to belch or vomit, or revision surgery existed between groups.³² Similarly, IEM does not appear to be associated with significant adverse outcomes in those undergoing magnetic sphincter augmentation³³ although its relevance in patients undergoing endoscopic fundoplication has not been well-studied.

While the risk of post-fundoplication dysphagia in patients with IEM appears low, the absence of peristaltic reserve on MRS may predict post-fundoplication dysphagia.¹⁰ In a retrospective study of 157 patients with GERD that underwent anti-reflux surgery, lack of contraction reserve was independently associated with late post-fundoplication dysphagia.³⁴ However, most patients with post-fundoplication dysphagia could be successfully treated conservatively or with endoscopic dilation.³⁴ Further, MRS results can be heterogenous even for individual patients in the same study, highlighting the need for caution when utilizing results in clinical practice.

Consequently, IEM should not represent an absolute contraindication for Nissen fundoplication. However, in patients with IEM undergoing work-up for anti-reflux surgery, the absence of peristaltic reserve on MRS may help identify those at risk for postoperative dysphagia and in this subset of patients, aggressive medical management for GERD or partial fundoplication rather than Nissen fundoplication may be considered.

Lung transplant evaluation

Patients undergoing lung transplant evaluation also undergo reflux and esophageal motility testing, primarily to help identify GERD which can result in allograft dysfunction after transplant. A finding of IEM does not represent a contraindication to lung transplant. In fact, IEM may be present in 19% of patients undergoing lung transplant evaluation.³⁵ In a retrospective cohort study comparing patients that underwent lung transplant and underwent HRM both before and after transplant, there was a significant increase in esophageal contractility posttransplant (increase in mean DCI from 1470 to 2549 mmHg·s·cm) and 80% of patients were noted to have an increase in DCI posttransplant.³⁶ Nine patients with IEM or fragmented peristalsis pretransplant had normal motility posttransplant.³⁶ Based on current knowledge, the presence of IEM should not affect the decision to proceed with transplant, nor should it impact candidacy for anti-reflux surgery following lung transplant if this is needed to control reflux.

Future directions

CCv4.0 requires adjunctive data to manometric findings for esophagogastric junction outflow obstruction, with a clinical diagnosis requiring an elevated IRP in both supine and upright positions, intrabolus pressurization, compatible symptoms (dysphagia and/or non-cardiac chest pain), and supportive findings on timed barium esophagram or functional lumen impedance planimetry. Similarly, IEM should be viewed as a manometric pattern in isolation whose clinical importance is likely found in combination with symptoms and other objective measures that support abnormal esophageal bolus transit.

Future directions should include further study of the impact of IEM diagnosis on patients (i.e., quality of life), outcome studies to better define the clinical significance of IEM, development of tools to better highlight the present understanding of IEM (to address patient concerns), and refinement, revision, or altogether a change in terminology of this manometric pattern to make it overall less alarming for patients.

As highlighted previously, IEM can be associated with significant patient concerns as the name confers that their esophagus is ‘ineffective’ and dysfunctional. Not only can this increase patient anxiety and worry, but it can also trigger a cascade of low-yield testing unlikely to change management. As such, perhaps we should consider replacing the term IEM to describe weak peristalsis. In this regard, it would seem worthwhile to engage in efforts to develop revised terminology that more accurately captures our present understanding of this manometric pattern and conveys a less worrisome meaning to patients receiving this manometric diagnosis. As our understanding of this condition evolves, perhaps the proper name to describe this condition will become more readily apparent.

Take-home points

CCv4.0 defines IEM as >70% of ineffective swallows or ≥50% failed peristalsis with normal IRP. Provocative maneuvers such as lack of contraction reserve on MRS and abnormal bolus clearance on barium esophagram or HRM with impedance may suggest clinical relevance. While the newest definition should result in fewer diagnoses of IEM, it is unclear whether these more selective cases are more clinically relevant. While clinical symptoms implicated with IEM include dysphagia and GERD, the strength of these associations remains unclear. The mainstay of management is conservative care with dietary and lifestyle changes and treatment of GERD when present. A few medical treatment options exist but with very limited data to support their use. Anti-reflux surgery appears safe in patients with IEM and the absence of augmentation on MRS may help identify those at increased risk for postoperative dysphagia.

Data availability:

Data availability not applicable as no new datasets were generated for this study. All authors had access to the data discussed in this review article.