OBJECTIVES: Symptoms are inconsistently associated with esophageal motor findings on high-resolution manometry (HRM). We aimed to evaluate predictors of dysphagia severity, including esophageal hypervigilance and visceral anxiety, among patients evaluated with HRM. METHODS: Adult patients undergoing HRM at 4 academic medical centers (United States and France) were prospectively evaluated. HRM was completed and analyzed per the Chicago Classification v3.0. Validated symptom scores, including the Brief Esophageal Dysphagia Questionnaire and Esophageal Hypervigilance and Anxiety Scale, were completed at the time of HRM. RESULTS: Two hundred thirty-six patients, aged 18–85 (mean 53) years, 65% female, were included. Approximately 59 (25%) patients had a major motor disorder on HRM: 19 achalasia, 24 esophagogastric junction outflow obstruction, 12 absent contractility, and 4 jackhammer. Approximately 177 (75%) patients did not have a major motor disorder: 71 ineffective esophageal motility and 106 normal motility. Having a major motor disorder was a significant predictor of dysphagia severity (R2adj = 0.049, P < 0.001), but the Esophageal Hypervigilance and Anxiety Scale score carried a predictive relationship of Brief Esophageal Dysphagia Questionnaire that was 2-fold higher than having a major motor disorder: R2adj = 0.118 (P < 0.001). This finding remained when evaluated by the major motor disorder group. HRM metrics were nonsignificant. DISCUSSION: In a prospective, international multicenter study, we found that esophageal hypervigilance and visceral anxiety were the strongest predictors of dysphagia severity among patients evaluated with HRM. Thus, an assessment of esophageal hypervigilance and visceral anxiety is important to incorporate when evaluating symptom severity in clinical practice and research studies.

INTRODUCTION: Ineffective esophageal motility (IEM) is a minor motor disorder with potential reflux implications. Contraction reserve, manifested as augmentation of esophageal body contraction after multiple rapid swallows (MRS), may affect esophageal acid exposure time (AET) in IEM. METHODS: Esophageal high-resolution manometry (HRM) and ambulatory reflux monitoring studies were reviewed over 2 years to identify patients with normal HRM, IEM (≥50% ineffective swallows), and absent contractility (100% failed swallows). Single swallows and MRS were analyzed using HRM software tools (distal contractile integral, DCI) to determine contraction reserve (mean MRS DCI to mean single swallow DCI ratio >1). Univariate analysis and multivariable regression analyses were performed to determine motor predictors of abnormal AET in the context of contraction reserve. RESULTS: Of 191 eligible patients, 57.1% had normal HRM, 37.2% had IEM, and 5.8% had absent contractility. Contraction reserve had no affect on AET in normal HRM. Nonsevere IEM (5–7 ineffective swallows) demonstrated significantly lower proportions with abnormal AET in the presence of contraction reserve (30.4%) compared with severe IEM (8–10 ineffective swallows) (75.0%, P = 0.03). Abnormal AET proportions in nonsevere IEM with contraction reserve (32.7%) resembled normal HRM (33.0%, P = 0.96), whereas that in severe IEM with (46.2%) or without contraction reserve (50.0%) resembled absent contractility (54.5%, P ≥ 0.6). Multivariable analysis demonstrated contraction reserve to be an independent predictor of lower upright AET in nonsevere (odds ratio 0.44, 95% confidence interval 0.23–0.88) but not severe IEM. DISCUSSION: Contraction reserve affects esophageal reflux burden in nonsevere IEM. Segregating IEM into severe and nonsevere cohorts has clinical value.

Jackhammer esophagus (JE) is a hypercontractile disorder, the pathogenesis of which is incompletely understood. Multiple rapid swallows (MRS) and rapid drink challenge (RDC) are complementary tests used during high-resolution manometry (HRM) that evaluate inhibitory and excitatory neuromuscular function and latent obstruction, respectively. Our aim was to evaluate esophageal pathophysiology using MRS and RDC in 83 JE patients (28 men; median age: 63 yr; IQR: 54–70 yr). Twenty-one healthy subjects (11 men; median age: 28 yr; range: 26–30 yr) were used as a control group. All patients underwent solid-state HRM with ten 5-ml single swallows (SS) and one to three 10-ml MRS; 34 patients also underwent RDC. Data are shown as median (interquartile range). Abnormal motor inhibition was noted during at least one MRS test in 48% of JE patients compared with 29% of controls ( P = 0.29). Mean distal contractile integral (DCI) after MRS was significantly lower than after SS [6,028 (3,678–9,267) mmHg·cm·s vs. 7,514 (6,238–9,197) mmHg·cm·s, P = 0.02], as was highest DCI ( P < 0.0001). Consequently, 66% of JE patients had no contraction reserve. At least one variable of obstruction during RDC (performed in 34 patients) was outside the normal range in 25 (74%) of JE patients. Both highest DCI after SS and pressure gradient across the esophagogastric junction (EGJ) during RDC were higher in patients with dysphagia versus those without ( P = 0.04 and 0.01, respectively). Our data suggest altered neural control in JE patients with heterogeneity in inhibitory function. Furthermore, some patients had latent EGJ obstruction during RDC, which correlated with the presence of dysphagia. NEW & NOTEWORTHY Presence of abnormal inhibition was observed during multiple rapid swallows (MRS) in some but not all patients with jackhammer esophagus (JE). Unlike healthy subjects, JE patients were more strongly stimulated after single swallows than after MRS. An obstructive pattern was frequently observed during rapid drink challenge (RDC) and was related to presence of dysphagia. MRS and RDC during high-resolution manometry are useful to show individual pathophysiological patterns in JE and may guide optimal therapeutic strategies.

Background Esophageal hypercontractility can manifest with and without esophagogastric junction (EGJ) outflow obstruction. We investigated clinical presentations and motility patterns in patients with esophageal hypercontractile disorders. Methods Esophageal HRM studies fulfilling Chicago Classification 3.0 criteria for jackhammer esophagus (distal contractile integral, DCI >8000 mmHg.cm.s in ≥ 20% swallows) with (n = 30) and without (n = 83) EGJ obstruction (integrated relaxation pressure, IRP > 15 mm Hg) were retrospectively reviewed from five centers (4 in Europe, 1 in US). Single swallows (SS) and multiple rapid swallows (MRS) were analyzed using HRM software tools (IRP, DCI, distal latency, DL); MRS: SS DCI ratio >1 defined contraction reserve. Comparison groups were achalasia type 3 (n = 72, positive control for abnormal inhibition and EGJ obstruction) and healthy controls (n = 18). Symptoms, HRM metrics, and MRS contraction reserve were analyzed within jackhammer subgroups and comparison groups. Key Results The esophageal smooth muscle was excessively stimulated at baseline in jackhammer subgroups, with lack of augmentation following MRS identified more often compared with controls (P = .003) and type 3 achalasia (P = .07). Consistently abnormal inhibition was identified in type 3 achalasia (47%), and to a lower extent in jackhammer with obstruction (37%, P = .33), jackhammer esophagus (28%, P = .01), and controls (11%, P < .01 compared with type 3 achalasia). Perceptive symptoms (heartburn, chest pain) were common in jackhammer esophagus (P < .01 compared with type 3 achalasia), while transit symptoms (dysphagia) were more frequent with presence of EGJ obstruction (P ≤ .01 compared with jackhammer without obstruction). Conclusions and inferences The balance of excessive excitation and abnormal inhibition defines clinical and manometric manifestations in esophageal hypercontractile disorders.

Elevated integrated relaxation pressure (IRP) on esophageal high-resolution manometry (HRM) identifies obstructive processes at the esophagogastric junction (EGJ). Our aim was to determine whether intrabolus pressure (IBP) can identify structural EGJ processes when IRP is normal. In this observational cohort study, adult patients with dysphagia and undergoing HRM were evaluated for endoscopic evidence of structural EGJ processes (strictures, rings, hiatus hernia) in the setting of normal IRP. HRM metrics [IRP, distal contractile integral (DCI), distal latency (DL), IBP, and EGJ contractile integral (EGJ-CI)] were compared among 74 patients with structural EGJ findings (62.8 ± 1.6 yr, 67.6% women), 27 patients with normal EGD (52.9 ± 3.2 yr, 70.3% women), and 21 healthy controls (27.6 ± 0.6 yr, 52.4% women). Findings were validated in 85 consecutive symptomatic patients to address clinical utility. In the primary cohort, mean IBP (18.4 ± 0.9 mmHg) was higher with structural EGJ findings compared with dysphagia with normal EGD (13.5 ± 1.1 mmHg, = 0.002) and healthy controls (10.9 ± 0.9 mmHg, < 0.001). However, mean IRP, DCI, DL, and EGJ-CI were similar across groups ( > 0.05 for each comparison). During multiple rapid swallows, IBP remained higher in the structural findings group compared with controls ( = 0.02). Similar analysis of the prospective validation cohort confirmed IBP elevation in structural EGJ processes, but correlation with dysphagia could not be demonstrated. We conclude that elevated IBP predicts the presence of structural EGJ processes even when IRP is normal, but correlation with dysphagia is suboptimal. Integrated relaxation pressure (IRP) above the upper limit of normal defines esophageal outflow obstruction using high-resolution manometry. In patients with normal IRP, elevated intrabolus pressure (IBP) can be a surrogate marker for a structural restrictive or obstructive process at the esophagogastric junction (EGJ). This has the potential to augment the clinical value of esophageal HRM by raising suspicion for a structural EGJ process when IBP is elevated.