Ineffective Esophageal Motility Patients Research Articles

Ineffective esophageal motility: Characterization and outcomes across pediatric neurogastroenterology and motility centers in the United States.

Ineffective esophageal motility (IEM) on high-resolution manometry (HRM) is not consistently associated with specific clinical syndromes or outcomes. We evaluated the prevalence, clinical features, management, and outcomes of pediatric IEM patients across the United States. Clinical and manometric characteristics of children undergoing esophageal HRM during 2021-2022 were collected from 12 pediatric motility centers. Clinical presentation, test results, management strategies, and outcomes were compared between children with IEM and normal HRM. Of 236 children (median age 15 years, 63.6% female, 79.2% Caucasian), 62 (23.6%) patients had IEM, and 174 (73.7%) patients had normal HRM, with similar demographics, medical history, clinical presentation, and median symptom duration. Reflux monitoring was performed more often for IEM patients (25.8% vs. 8.6%, p = 0.002), but other adjunctive testing was similar. Among 101 patients with follow-up, symptomatic cohorts declined in both groups in relation to the initial presentation (p > 0.107 for each comparison) with management targeting symptoms, particularly acid suppression. Though prokinetics were used more often and behavioral therapy less often in IEM (p ≤ 0.015 for each comparison), symptom outcomes were similar between IEM and normal HRM. Despite a higher proportion with residual dysphagia on follow-up in IEM (64.0% vs. 39.1%, p = 0.043), an alternate mechanism for dysphagia was identified more often in IEM (68.8%) compared to normal HRM (27.8%, p = 0.017). IEM is a descriptive manometric pattern rather than a clinical diagnosis requiring specific intervention in children. Management based on clinical presentation provides consistent symptom outcomes.

Multicentric short term and safety study of ineffective esophageal motility patients treated with RefluxStop device

Gastroesophageal reflux disease (GERD) presents a general health problem with a variety of symptoms and an impairment of life quality. Conservative therapies do not offer sufficient symptom relief in up to 30% of patients. Patients who suffer from ineffective esophageal motility (IEM) and also GERD may exhibit symptoms ranging from mild to severe. In cases where surgical intervention becomes necessary for this diverse group of patients, it is important to consider the potential occurrence of postoperative dysphagia. RefluxStop is a new alternative anti-reflux surgery potentially reducing postoperative dysphagia rates. In this bicentric tertiary hospital observational study consecutive patients diagnosed with PPI refractory GERD and IEM that received RefluxStop implantation were included. A first safety and efficacy evaluation including clinical examination and GERD-HRQL questionnaire was conducted. 40 patients (25 male and 15 female) were included. 31 patients (77.5%) were on PPI at time of surgery, with mean acid exposure time of 8.14% ± 2.53. The median hospital stay was 3 days. Postoperative QoL improved significantly measured by GERD HRQL total score from 32.83 ± 5.08 to 6.6 ± 3.71 (p < 0.001). A 84% reduction of PPI usage (p < 0.001) was noted. 36 patients (90%) showed gone or improved symptoms and were satisfied at first follow-up. Two severe adverse events need mentioning: one postoperative slipping of the RefluxStop with need of immediate revisional operation on the first postoperative day (Clavien–Dindo Score 3b) and one device migration with no necessary further intervention. RefluxStop device implantation is safe and efficient in the short term follow up in patients with GERD and IEM. Further studies and longer follow-up are necessary to prove long-lasting positive effects.

Effects of Codeine on Esophageal Peristalsis in Patients With Ineffective Esophageal Motility: Studies Using High-resolution Manometry.

This study aims to evaluate the effects of acute codeine administration on primary and secondary esophageal peristalsis in patients with ineffective esophageal motility (IEM). Eighteen IEM patients (8 women; mean age 37.8 years, range 23-64 years) were enrolled in the study. The patients underwent high-resolution manometry exams, consisting of 10 single wet swallows, multiple rapid swallows, and ten 20 mL rapid air injections to trigger secondary peristalsis. All participants completed 2 separate sessions, including acute administration of codeine (60 mg) and placebo, in a randomized order. Codeine significantly increased the distal contractile integral (566 ± 81 mmHg∙s∙cm vs 247 ± 36 mmHg∙s∙cm, P = 0.001) and shortened distal latency (5.7 ± 0.2 seconds vs 6.5 ± 0.1 seconds, P < 0.001) for primary peristalsis compared with these parameters after placebo treatment. The mean total break length decreased significantly after codeine treatment compared with the length after placebo (P = 0.003). Codeine significantly increased esophagogastric junction-contractile integral (P = 0.028) but did not change the 4-second integrated relaxation pressure (P = 0.794). Codeine significantly decreased the frequency of weak (P = 0.039) and failed contractions (P = 0.009), resulting in increased frequency of normal primary peristalsis (P < 0.136). No significant differences in the ratio of impaired multiple rapid swallows inhibition and parameters of secondary peristalsis were detected. In IEM patients, acute administration of codeine increases contraction vigor and reduces distal latency of primary esophageal peristalsis, but has no effect on secondary peristalsis. Future studies are required to further elucidate clinical relevance of these findings, especially in the setting of gastroesophageal reflux disease with IEM.

Chicago Classification Version 4.0 Improves Stratification of Ineffective Esophageal Motility Patients into Clinically Meaningful Subtypes: A Two-Center International Study.

The 4th iteration of the Chicago Classification (CC v4.0) for esophageal motility disorders offers more restrictive criteria for the diagnosis of Ineffective Esophageal Motility (IEM) compared to version 3.0 (CC v3.0). In light of the updated criteria for IEM, we aimed to characterize and compare the patients who retained their IEM diagnosis to those who were reclassified as normal motility, and to evaluate the clinical impact of the newly introduced CC v4.0. We performed a retrospective case-control study. We included all individuals who underwent a high-resolution manometry (HRM) between 2020 and 2021 at two centers. Consecutive studies reported as IEM according to the CC v3.0 were reanalyzed according to the CC v4.0. We compared demographics, clinical, manometry, and pH-monitoring parameters. Out of 452 manometry studies, 154 (34%) met criteria for IEM as per the CC v3.0 (CC v3.0 IEM group). Of those, 39 (25%) studies were reclassified as normal studies according to the CC v4.0 (CC v4.0 normal group), while the remaining 115 studies (25% of the overall cohort) retained an IEM diagnosis (CC v4.0 IEM group). The CC v4.0 normal group had more recovered contractions during solid swallows (p = 0.01), less ineffective swallows (p = 0.04), and lower acid exposure time (p = 0.02) compared to the CC4.0 IEM group. Under CC v4.0 criteria, fewer patients are diagnosed with IEM. Those diagnosed with IEM had worse esophageal function and higher acid burden. Though further studies are needed to confirm these findings, our results indicate that CC v4.0 criteria restrict the IEM diagnosis to a more clinically meaningful population.

Dysphagia Worsens With Increasing Ineffective Swallows Among Patients With Ineffective Esophageal Motility.

Ineffective esophageal motility (IEM) is the most common motility disorder identified on esophageal high-resolution manometry (HRM), but patients with this finding may be asymptomatic. Therefore, we aimed to identify specific HRM findings predictive of symptoms in IEM. Adult patients (≥18y) who underwent HRM between March 2016 and July 2019 were retrospectively evaluated and reclassified according to Chicago Classification 4.0 (CC4.0). Demographic information, HRM parameters, and gastroesophageal reflux disease Health-Related Quality of Life Questionnaire responses were captured among those with normal manometry or IEM. We evaluated the association between heartburn, regurgitation, and dysphagia, with respect to HRM findings including ineffective swallows. Of 379 patients, 243 (64.1%) had a normal manometry, 136 (35.9%) were on IEM spectrum, and 73 (19.3%) had conclusive IEM by CC4.0. Mean dysphagia scores were significantly higher in those with conclusive IEM compared with those with normal HRM (2.00 vs. 1.36, P=0.002), as was the percentage of individuals reporting dysphagia affecting daily activities (21.9% vs. 11.4%, P=0.02). Heartburn and regurgitation symptoms did not differ between groups. In a multivariable model of IEM patients, the percentage of ineffective swallows independently predicted a higher dysphagia burden (β regression coefficient: 0.032, P=0.04). Applying the CC4.0 definition for conclusive IEM identifies a group of patients with worse dysphagia symptoms. Within this group, the percentage of ineffective swallows was an independent predictor of dysphagia severity. These findings may help practitioners and patients contextualize the heterogeneous diagnosis of IEM.

Medical Therapy for Ineffective Esophageal Motility: A Systematic Review

Background: Ineffective esophageal motility (IEM) is a commonly identified disorder of peristalsis. Although often asymptomatic, IEM can be associated with dysphagia. Aside from treating co-existing gastroesophageal reflux disease and sources of mechanical obstruction, few options are available for management in this context. We therefore systematically reviewed the literature to identify randomized controlled trials (RCTs) for medical treatments of IEM. Methods: MEDLINE, Embase, Cochrane Library, and Web of Science were searched using controlled vocabulary and keywords to identify RCTs from inception through 9/22/2021. Prospective studies evaluating medical therapy to improve dysphagia in adults with IEM were included. The risk of bias was assessed using the revised Cochrane risk-of-bias tool. Results: Among 1046 studies identified, 6 (0.58%) met inclusion criteria with a total of 65 patients. Most studies evaluated serotonin receptor agonists (buspirone, mosapride, prucalopride, and sumatriptan), primarily assessing changes on esophageal high-resolution manometry parameters, and only 1 study evaluated patient reported outcomes. Overall, medical therapy improved these pooled outcomes in 5 (83%) studies. Although treatment endpoints varied, the risk of bias in study reporting was low for 4 studies and uncertain for 2 studies. Conclusions: There are currently few therapeutic options available for IEM patients with symptomatic non-obstructive dysphagia. Our systematic review identified 6 studies utilizing medical therapy in patients with IEM, and a majority demonstrated an improvement in HRM parameters. Medical therapy may therefore be considered in this context, but additional studies are warranted to assess for similar improvement in patient symptoms.

Comparing Patients Diagnosed With Ineffective Esophageal Motility by the Chicago Classification Version 3.0 and Version 4.0 Criteria.

The Chicago Classification version 4.0 (CCv4.0) of ineffective esophageal motility (IEM) is more stringent than the Chicago Classification version 3.0 (CCv3.0) definition. We aimed to compare the clinical and manometric features of patients meeting CCv4.0 IEM criteria (group 1) versus patients meeting CCv3.0 IEM but not CCv4.0 criteria (group 2). We collected retrospective clinical, manometric, endoscopic, and radiographic data on 174 adults diagnosed with IEM from 2011 to 2019. Complete bolus clearance was defined as evidence of exit of the bolus by impedance measurement at all distal recording sites. Barium studies included barium swallow, modified barium swallow, and barium upper gastrointestinal series studies, and collected data from these reports include abnormal motility and delay in the passage of liquid barium or barium tablet. These data along with other clinical and manometric data were analyzed using comparison and correlation tests. All records were reviewed for repeated studies and the stability of the manometric diagnoses. Most demographic and clinical variables were not different between the groups. A lower mean lower esophageal sphincter pressure was correlated with greater percent of ineffective swallows in group 1 (n = 128) (r = -0.2495, P = 0.0050) and not in group 2. In group 1, increased percent of failed contractions on manometry was associated with increased incomplete bolus clearance (r = 0.3689, P = 0.0001). No such association was observed in group 2. A lower median integrated relaxation pressure was correlated with greater percent of ineffective contractions in group 1 (r = -0.1825, P = 0.0407) and not group 2. Symptom of dysphagia was more prevalent (51.6% versus 69.6%, P = 0.0347) in group 2. Dysphagia was not associated with intrabolus pressure, bolus clearance, barium delay, or weak or failed contractions in either group. In the small number of subjects with repeated studies, a CCv4.0 diagnosis appeared more stable over time. CCv4.0 IEM was associated with worse esophageal function indicated by reduced bolus clearance. Most other features studied did not differ. Symptom presentation cannot predict if patients are likely to have IEM by CCv4.0. Dysphagia was not associated with worse motility, suggesting it may not be primarily dependent on bolus transit.

Assessment of Esophageal Motility Disorders in Patients With Refractory Gastroesophageal Reflux Disease

There is insufficient data about esophageal body dysmotility in patients with refractory gastroesophageal reflux disease (RGERD) and inadequate response to proton pump inhibitors (PPIs) treatment. This study aimed to assess esophageal motility disorder and reflux parameters among these patients by high-resolution manometry (HRM) and intraluminal impedance and pH (MII‐pH) monitoring after stopping PPI therapy. A retrospective study was conducted among 100 RGERD patients admitted to Taleghani Hospital (Tehran, Iran) for one year. More than half of them were males (55%). Their mean age was 47.10±6.92, and 50% of patients had ineffective esophageal motility (IEM). Middle, distal, and proximal esophageal pressure (MEP, DEP, and PEP), lower esophageal sphincter (LES) basal pressure (LESP), integrated relaxation pressure (IRP), distal contractile integral (DCI), large breaks, upper esophageal sphincter basal pressure (UESP), and LES length (LESL) in IEM patients were significantly lower than the patients with normal esophageal motility (P&lt;0.001). Furthermore, there were more patients in the IEM group with long-term and abnormal weakly acid reflux compared with the non-IEM group (P&lt;0.05). It seems that the evaluation of reflux parameters and esophageal motility could lead to additional insights into the pathophysiological mechanisms of RGERD. Nevertheless, further studies are suggested to evaluate the effects of esophageal motility disorders among RGERD patients.

From Chicago classification v3.0 to v4.0: Diagnostic changes and clinical implications.

The Chicago Classification (CC) used to define esophageal motility disorders in high-resolution manometry (HRM) has evolved over time. Our aim was to compare the frequency of motility disorders diagnosed with the last two versions (CCv3.0 and CCv4.0) and to evaluate symptoms severity according to the diagnoses. From June to December 2020, patients who underwent esophageal HRM with swallows in supine and sitting positions were included. HRM studies were retrospectively analyzed using CCv3.0 and CCv4.0. Symptoms severity and quality of life were assessed with validated standardized questionnaires. Among the 130 patients included (73 women, mean age 52 years), motility disorder diagnoses remained unchanged in 102 patients (78%) with both CC. The 3 patients with esophago-gastric junction outflow obstruction (EGJOO) with CCv3.0 were EGJOO, ineffective esophageal motility (IEM) and normal with CCv4.0. Twenty-four out of 63 IEM diagnosed with the CCv3.0 (38%) turned into normal motility with the CCv4.0. Whatever the CC used, brief esophageal dysphagia questionnaire score was significantly higher in patients with EGJ relaxation disorders compared to those with IEM (25 (0-34) vs 0 (0-19), p= 0.01). Gastro-Esophageal Reflux disease questionnaire (GERD-Q) score was higher in patients with IEM with both CC compared to those who turned to normal with CCv4.0. While motility disorders diagnoses remained mainly unchanged with both CC, IEM was less frequent with CCv4.0 compared to CCv3.0. The higher GERD-Q score in IEM patients with CCv4.0 suggests that CCv4.0 might identify IEM more likely associated with GERD.

The Supportive Role of Provocative Maneuvers and Impedance Clearance in Detecting Ineffective Esophageal Motility.

Ineffective esophageal motility (IEM) is one of the most common esophageal motility disorders. However, the definition of IEM has evolved. Chicago classification version 4.0 (CCv4.0) made IEM parameters more stringent with greater than 70% of ineffective wet swallows (WS) necessary to diagnose conclusive IEM. Of the ineffective swallows, 50-70% are deemed "inconclusive cases". This study sought to determine whether provocative maneuvers, including multiple rapid swallows (MRS) and apple viscous swallows (AVS), and impedance clearance can provide supportive information for inconclusive IEM disorders based on CCv4.0. Esophageal motility data on 100 patients were analyzed. All patients completed WS and at least one additional swallow test (MRS and/or AVS). Patients were classified as having conclusive IEM, inconclusive IEM, or normal motility. IEM features detected on MRS/AVS and incomplete bolus clearance were recorded. Percentage of agreement between IEM features and incomplete bolus clearance was calculated for each motility group. Ten patients had conclusive IEM, nine had inconclusive IEM, and 32 had normal motility. There was 70% agreement between IEM features and incomplete bolus clearance with conclusive IEM, 33% agreement with inconclusive IEM, and 9% agreement with normal motility. There was significantly more agreement in the conclusive and inconclusive IEM groups than in the normal motility group (P = 0.0003). Combinational follow-up testing with provocative maneuvers and impedance clearance may assist with risk stratification of IEM patients and assist in further management of inconclusive IEM. MRS and AVS can detect unique IEM features that may help with preoperative management of inconclusive IEM.

Ineffective esophageal motility assessment in patients with and without pathological esophageal acid reflux.

Ineffective esophageal motility (IEM), defined as minor esophageal motility disorder, is also the most common esophageal motility disorder. The relationship between gastro-esophageal reflux disease is still controversial. Our aim in this study is to evaluate whether there are differences in terms of demographic, endoscopic, or motility findings between IEM patients with pathological esophageal acid reflux and physiological reflux.Patients diagnosed with IEM according to the Chicago classification v3 with high-resolution manometry (HRM) before acid monitoring constituted the study group of our investigation. The patients were divided into 2 groups as patients with pathological esophageal reflux and patients with physiological reflux according to 24-hour acid monitoring. Demographic data, endoscopic findings, and HRM findings were compared between 2 groups.A total of 62 patients who were diagnosed with IEM according to the Chicago classification v3 were included in the study. Patients in the physiological reflux group were 7 years younger on average than the pathological reflux group. Esophagitis rates were significantly higher in the pathological reflux group (P = .033). Lower esophageal sphincter resting pressure, integrated relaxation pressure, and the presence of hernia were found to be similar in the 2 groups (P = 392, P = 182, P = 657, respectively). The rate of severe IEM was also similar between the 2 groups (P = .143).The fact that the physiological reflux patient group is younger may suggest that the IEM develops in the early period and then reflux accompanies the picture with advancing age.

Analysis of contractile segment impedance during straight leg raise maneuver using high-resolution impedance manometry increases diagnostic yield in reflux disease.

Contractile segment impedance (CSI) obtained from high-resolution impedance manometry (HRIM) is a measure of mucosal integrity that predicts gastroesophageal reflux disease (GERD). While straight leg raise (SLR) maneuver augments esophageal peristaltic vigor, it remains unclear whether SLR affects CSI values. This study was aimed to evaluate whether CSI with SLR is feasible and useful to complement the diagnosis of GERD. We prospectively recruited 48 patients with typical GERD symptoms who underwent esophagogastroduodenoscopy, HRIM with SLR maneuver, and multichannel intraluminal impedance-pH (MII-pH) testing. The capability of mean nocturnal baseline impedance (MNBI), resting baseline impedance (RBI), CSI with or without SLR maneuver in predicting GERD was assessed using receiver operating characteristics (ROC) analysis. Among 20 GERD patients and 28 non-GERD patients, all values of impedance-based metrics were lower in GERD patients compared to non-GERD patients (p<0.001). For GERD identification, area under receiver operating characteristic curve (AUROC) values of CSI with SLR maneuver, CSI, MNBI, and RBI were 0.901, 0.858, 0.865, and 0.797. Particularly in ineffective esophageal motility (IEM) patients, SLR maneuver increased mean distal contractile integral from 436 to 828.7mmHg.s.cm (p=0.018) and enhanced AUROC values of CSI for GERD identification from 0.917 to 0.958. CSI measurement during HRIM appears to be a reliable, time-saving, and less invasive tool for complementing GERD diagnosis. Our results also suggest a simple SLR maneuver during HRIM could enhance diagnostic accuracy of CSI for GERD identification especially in IEM patients.

Impact of ineffective esophageal motility on secondary peristalsis: Studies with high-resolution manometry.

The aim was to investigate whether there is a difference in secondary peristalsis on high-resolution manometry (HRM) among gastroesophageal reflux disease (GERD) patients with and without ineffective esophageal motility (IEM), and healthy individuals. Twenty-eight GERD patients and seventeen healthy controls were included. Secondary peristalsis was stimulated by a rapid injection of 20ml air in mid-esophagus. We compared HRM metrics and the response and effective rate of triggering secondary peristalsis between patients with and without IEM and healthy controls. Sixteen patients had IEM, and the remaining 12 had normal manometry. By triggering of secondary peristalsis, patients without IEM and healthy controls had significantly higher distal contractile integral (DCI) values than IEM patients (p=0.006). A successful secondary peristalsis was triggered more frequently in healthy controls than in GERD patients with normal peristalsis or IEM (56.9% vs. 20.2% vs. 9.1%, all p<0.001). The effective rate which determined as DCI>450mmHg.cm.s was higher in healthy controls compared to patients with normal peristalsis (36.5% vs. 19.4%, p<0.001) and IEM (36.5% vs. 6.3%, p<0.001). Patients with IEM had lower successful triggering response (9.1% vs. 20.2%) and effective secondary peristalsis (6.3% vs. 19.4%) compared with patients without IEM (p<0.001). Our work has demonstrated that GERD patients, in particular those with IEM, have significant defects in the triggering of secondary peristalsis on HRM. HRM helps characterize esophageal secondary peristalsis which exhibits differently in patients with and without IEM.

Application of a novel straight leg raise test during high-resolution manometry can predict esophageal contractile reserve in patients with gastroesophageal reflux disease.

Increased intra-abdominal pressure from abdominal compression augments esophageal peristalsis during high-resolution manometry (HRM), and straight leg raise (SLR) while supine increases intra-abdominal pressure. We determined if water swallows performed during SLR can mimic contraction reserve seen with multiple rapid swallows (MRS). Consecutive patients evaluated for GERD symptoms completed validated GERD questionnaires, esophageal HRM, and upper endoscopy. Distal contractile integral (DCI) was analyzed during single water swallows (10×5mL), MRS (5×2mL), and during SLR (5x5mL). Peristaltic breaks were measured using software tools with a 20mmHg isobaric contour. Univariate correlational analyses were performed to compare esophageal motor patterns and DCI values during single water swallows, MRS, and SLR. Of 103 study patients (mean age: 46.7±12.3years, 56.3% female), 50 (48.5%) had ineffective esophageal motility (IEM). Contraction reserve was observed on MRS in 62% with IEM, and 35.8% with normal motility (p=0.008). DCI was significantly higher during SLR compared to mean single swallow DCI in both IEM and normal motility patients (p<0.001 for each comparison). In IEM patients, SLR significantly reduced swallows with peristaltic breaks (6.1±3.7 vs 3.6±3.6; p<0.001) and shortened the length of the largest break (4.8±3.4 vs 3.0±3.0cm; p<0.001). DCI response following MRS correlated with DCI with swallows during SLR, with a correlational coefficient (Pearson's r) of 0.70 (p<0.001). Swallowing against the resistance of increased intra-abdominal pressure from SLR improves esophageal body peristaltic performance and predicts esophageal body contraction reserve.

S0439 Prucalopride Improves Esophageal Contractility Ineffective Esophageal Motility: Prospective Clinical Trial

INTRODUCTION: Ineffective esophageal motility (IEM) is a manometric diagnosis defined by the Chicago Classification (v3.0) as ≥50% of swallows achieving a distal contractile integral (DCI) of < 450 mmHg-cm-s and maybe associated with dysphagia. This pilot study assesses the effectiveness of prucalopride a 5-HT4 enterokinetic drug in IEM patients with dysphagia. METHODS: Symptomatic patients with dysphagia diagnosed with IEM following high-resolution manometry (HRM) with impedance at a tertiary care motility lab were enrolled between August 2017 and September 2019. Patients with uncontrolled GERD (DeMeester score >14.7), endoscopic erosive esophagitis, eosinophilic esophagitis, use of other prokinetic drugs, or narcotics were excluded. Patients received prucalopride 4mg PO once daily for 5 days and then underwent repeat HRM. Outcome measures included pre- and post- prucalopride esophageal HRM values, dysphagia symptom questionnaire (DSQ), and quality of life (Eq5d-3L). These outcomes were compared with paired T-test, Wilcoxon signed ranks test and McNemar test as appropriate. Patients were classified into definite or indefinite for heartburn, acid regurgitation, and GERD based on the MDQ-30 subscale. IRB-approved study (NCT03244553). RESULTS: Twenty-nine patients were enrolled; analysis was performed on twenty-five patients (13M:12F; mean age of 53.3 yrs (±13.97 SD) who completed the study. All patients had symptoms of dysphagia to solids. 76% of patients were on a PPI. The median time and IQR between baseline and post-HRM were 12 [8–18] wks. 18 patients (72%) had an improvement in mean DCI. There was a significant increase in DCI (mean 727.1 ± 548.7 vs 439.5 ± 286.7, P = 0.006), maximum DCI (mean 1198.7 ± 1198.67819.8 ± 540.5, P = 0.013), and decrease in the percentage of failed swallows (median 40 [IQR 25–70] vs 20 [10–50], P = 0.05), and acid regurgitation (P = 0.05) after prucalopride use. No improvement was seen in dysphagia or quality of life. Change in DCI correlated weakly with IRP (Spearman’s r =0.461, P = 0.021). The most common side effects were headaches (48%) and diarrhea (52%). A majority of patients (88%) reported a side effect, leading to discontinuation in 4%. CONCLUSION: In this short duration pilot study, prucalopride significantly improved the DCI, maximum DCI, number of failed swallows, and acid regurgitation in patients with IEM; however, no improvement in dysphagia or quality of life was seen. This pilot study warrants a larger study.Table 1.: Pairwise comparison of manometric values and patient-reported outcomes pre- and post- prucalopride therapyFigure 1.: Representative Pre and post-HRM picture of 3 patients who displayed significant improvement after prucalopride.

Pressure-impedance analysis: Assist the diagnosis and classification of ineffective esophageal motility disorder.

We elucidated the clinical significance of distal contractile integral-to-esophageal impedance integral (EII) ratio (DCIIR) in ineffective esophageal motility (IEM) adult patients. We recruited 101 patients with IEM (48.38±1.58years) and 42 matched healthy volunteers (44.28±1.85years) in this case-control study. All subjects underwent esophageal high-resolution impedance manometry from October 2014 to May 2018. The diagnosis of IEM was based on the Chicago Classification version 3.0. The EII, EII ratio, and DCIIR were analyzed by matlab software. The EII, EII ratio, and DCIIR calculated at an impedance threshold of 1500Ω (EII1500, EII ratio1500, and DCIIR1500, respectively) were significantly lower in the IEM group than in healthy controls (P<0.0001, <0.0001, and <0.0001, respectively). Receiver operating characteristic analysis showed that DCIIR1500<0.008mmHg/Ω, EII1500>71000Ω.s.cm, and EII ratio1500 >0.43 were all predictive of IEM. Only DCIIR1500<0.008mmHg/Ω remained significant in diagnosing IEM in the multivariate logistic regression analysis (odds ratio=72.13, P<0.001). The DCIIR1500 is negatively correlated with Eckardt score and the Reflux Disease Questionnaire (correlation coefficient=-0.2844 and -0.3136; P=0.0006 and 0.0002, respectively). Receiver operating characteristic analysis further showed that a DCIIR1500 cut-off of 0.002mmHg/Ω achieved the best differentiation between the IEM-alternans and IEM-persistens subtypes among IEM patients (P<0.001). The novel pressure-impedance parameter of high-resolution impedance manometry, DCIIR1500, may assist in the diagnosis and classification of IEM and correlated with clinical symptoms.

Analysis of clinical features and motility characteristics of ineffective esophageal motility

Objective To clarify the correlation between the clinical characteristics, esophageal motility features and esophageal acid exposure in patients with ineffective esophageal motility (IEM). Methods From January 2016 to March 2018, at Peking University First Hospital, 22 IEM patients diagnosed by esophagus high-resolution manometry (HRM) and 24 individuals with normal HRM results were enrolled. Clinical features, parameters of esophageal HRM and results of esophageal 24-hour pH monitoring of IEM patients and the individuals with normal HRM results were compared. According to the median distal contraction integral (DCI) of ten swallows, the IEM patients were divided into mild-IEM group (DCI 250-450 mmHg·s·cm (1 mmHg=0.133 kPa)) (14 cases) and severe-IEM group (DCI<250 mmHg·s·cm) (eight cases). The clinical features and esophageal motility were compared between normal HRM group, mild-IEM group and severe-IEM group. T test, chi-square test and one-way analysis of various were used for statistical analysis. Results The age of IEM group was older than that of normal HRM group ((64.5±11.2) years vs. (50.3±18.2) years), and the difference was statistically significant (t=-3.135, P=0.003). The lower esophageal sphincter pressure (LESP) of IEM group was lower than that of normal HRM group ((17.0±6.8) mmHg vs. (22.3±7.2) mmHg), and the difference was statistically significant (t=2.516, P=0.016). There were 15 cases in normal HRM group and 14 patients in IEM group who underwent esophageal 24-hour pH monitoring and there were five and two patients with abnormal acid exposure time (AET) in normal HRM group and IEM group, respectively. The length of proximal esophageal body (PEB) pressure zone of severe-IEM group was shorter than those of normal HRM group and mild-IEM group ((2.8±1.5) cm vs.(4.2±0.7) cm and (4.6±0.9) cm), and the differences were statistically significant (t=2.397 and 3.432, P=0.044 and 0.003). The integrated relaxation pressure (IRP) and LESP of normal HRM group were both higher than those of mild-IEM group ((9.3±2.9) mmHg vs. (7.2±3.3) mmHg, (22.3±7.2) mmHg vs. (15.4±7.1) mmHg), and the differences were statistically significant (t=2.148 and 2.843, P=0.038 and 0.007). There were six and eight patients in mild-IEM group and severe-IEM group who underwent esophageal 24-hour pH monitoring, respectively, and two patients in mild-IEM had abnormal AET. Conclusions The LESP of IEM patients is low. The clinical features and AET of IEM patients are not associated with the severity of IEM. In patients with severe IEM, the proximal and distal esophageal contractility is weakened, and the length of PEB pressure zone is shortened. Key words: Esophageal sphincter, upper; Ineffective esophageal motility; High-resolution manometry; Proximal esophageal body

High-Resolution Manometry Diagnosis of Ineffective Esophageal Motility Is Associated with Higher Reflux Burden.

Ineffective esophageal motility (IEM) is the most commonly diagnosed abnormality on high-resolution manometry (HRM). However, the clinical significance of IEM and associated reflux burden remains unclear. Our primary aim was to compare reflux patterns between IEM versus normal motility on HRM. HRM and reflux studies in patients with IEM and normal motility were retrospectively reviewed. Esophageal pressure topography parameters, reflux variables, and patient-reported outcome questionnaires were explored. A total of 239 patients with IEM were explored. Of these, 146 underwent reflux monitoring. Additionally, 100 patients with normal HRM all of whom had undergone reflux monitoring were included. IEM patients were more likely to have an abnormal number of reflux events compared to normal (22.7% vs. 9.0%, p < 0.01). Including only off-proton pump inhibitor (PPI) testing, IEM patients had higher mean total acid exposure time (AET) and total reflux events compared to normal motility (p = 0.02). Within IEM patients, higher AET modestly correlated with increased percentage of impaired swallows. Increased reflux events modestly correlated with higher impaired swallows and decreased lower esophageal sphincter (LES) resting pressure. Reflux burden increased with higher esophagogastric junction (EGJ) subtype, driven mostly by subtype III, although there was no difference in the distribution of EGJ subtypes between the IEM and normal HRM cohorts. Patients with HRM diagnosis of IEM may be more prone to acid reflux while off-PPI and non-acid reflux while on-PPI. Reflux burden appears to be worse in IEM patients who have lower resting LES pressure, higher EGJ subtype, or higher percentage of impaired swallows.

Influence of prucalopride on esophageal secondary peristalsis in reflux patients with ineffective motility.

Ineffective esophageal motility (IEM) is associated with gastroesophageal reflux disease. Secondary peristalsis contributes to esophageal clearance. Prucalopride promotes secondary peristalsis by stimulating 5-hydroxytrypatamine 4 receptors in the esophagus. We aimed to determine whether prucalopride would augment secondary peristalsis in gastroesophageal reflux disease patients with IEM. After a baseline recording of primary peristalsis, secondary peristalsis was stimulated by slow and rapid mid-esophageal injections of air in 15 patients with IEM. Two separate sessions with 4-mg oral prucalopride or placebo were randomly performed. Prucalopride significantly increased primary peristaltic wave amplitude (68.1±10.0 vs 55.5±8.8mmHg, P=0.02). The threshold volume for triggering secondary peristalsis was significantly decreased by prucalopride during slow (9.3±0.8 vs 12.0±0.8mL; P=0.04) and rapid air injection (4.9±0.3 vs 7.1±0.1mL; P=0.01). Secondary peristalsis was triggered more frequently after application of prucalopride (55% [43-70%]) than placebo (45% [33-50%]) (P=0.008). Prucalopride did not change pressure wave amplitudes during slow air injection (84.6±8.1 vs 57.4±13.8mmHg; P=0.19) or pressure wave amplitudes during rapid air injection (84.2±8.6 vs 69.5±12.9mmHg; P=0.09). Prucalopride enhances primary peristalsis and mechanosensitivity of secondary peristalsis with limited impact on secondary peristaltic activities in IEM patients. Our study suggests that prucalopride appears to be useful in augmenting secondary peristalsis in patients with IEM only via sensory modulation of esophageal secondary peristalsis.

Severity of ineffective esophageal motility is associated with utilization of skeletal muscle relaxant medications.

Ineffective esophageal motility (IEM) is the most common finding on high-resolution esophageal manometry (HREM). The underlying mechanisms for IEM remain to be fully elucidated. The aim of this study was to determine if utilization of skeletal muscle relaxants is associated with IEM, and with more severe subtypes of the disorder. Patients with diagnosis of IEM were gender and age matched to patients with normal HREM. Demographic information, symptoms, endoscopic findings, medication usage and medical comorbidities were recorded. Patients with a diagnosis of IEM were divided into subgroups based on mean distal contractile integral (DCI) and percentage of ineffective swallows, and assessed for clinically significant differences among patients with varying severity of underlying IEM. A total of 118 patients were included in each group. There were no significant clinical differences between the group of patients with IEM and the group of patients with normal manometry. Within the group of IEM patients, those with mean DCI<250mmHg/s/cm were more likely to be prescribed skeletal muscle relaxants (27.8% vs 11.0%, P=.044), and those using skeletal muscle relaxants had a larger mean percentage of ineffective swallows (81.1% vs 71.5%, P=.029). There were no significant differences across mean DCI subgroups in usage of any other medication, or in any of the demographic variables or disease comorbidities examined in this study. Use of skeletal muscle relaxants is associated with more severe IEM, which may suggest a causal association between this class of medications and weaker esophageal peristalsis.