Contraction Reserve Research Articles

Impact of Esophageal Motility on Microbiome Alterations in Symptomatic Gastroesophageal Reflux Disease Patients With Negative Endoscopy: Exploring the Role of Ineffective Esophageal Motility and Contraction Reserve.

Ineffective esophageal motility (IEM) is common in patients with gastroesophageal reflux disease (GERD) and can be associated with poor esophageal contraction reserve on multiple rapid swallows. Alterations in the esophageal microbiome have been reported in GERD, but the relationship to presence or absence of contraction reserve in IEM patients has not been evaluated. We aim to investigate whether contraction reserve influences esophageal microbiome alterations in patients with GERD and IEM. We prospectively enrolled GERD patients with normal endoscopy and evaluated esophageal motility and contraction reserve with multiple rapid swallows during high-resolution manometry. The esophageal mucosa was biopsied for DNA extraction and 16S ribosomal RNA gene V3-V4 (Illumina)/full-length (Pacbio) amplicon sequencing analysis. Among the 56 recruited patients, 20 had normal motility (NM), 19 had IEM with contraction reserve (IEM-R), and 17 had IEM without contraction reserve (IEM-NR). Esophageal microbiome analysis showed a significant decrease in microbial richness in patients with IEM-NR when compared to NM. The beta diversity revealed different microbiome profiles between patients with NM or IEM-R and IEM-NR (P = 0.037). Several esophageal bacterial taxa were characteristic in patients with IEM-NR, including reduced Prevotella spp. and Veillonella dispar, and enriched Fusobacterium nucleatum. In a microbiome-based random forest model for predicting IEM-NR, an area under the receiver operating characteristic curve of 0.81 was yielded. In symptomatic GERD patients with normal endoscopic findings, the esophageal microbiome differs based on contraction reserve among IEM. Absent contraction reserve appears to alter the physiology and microbiota of the esophagus.

Esophageal motor abnormalities in gastroesophageal reflux disorders.

Gastroesophageal reflux disease (GERD), a prevalent condition with multifactorial pathogenesis, involves esophageal motor dysmotility as a key contributing factor to its development. When suspected GERD patients have an inadequate response to proton-pump inhibitor (PPI) therapy and normal upper endoscopy results, high-resolution manometry (HRM) is utilized to rule out alternative diagnosis such as achalasia spectrum disorders, rumination, or supragastric belching. At present, HRM continues to provide supportive evidence for diagnosing GERD and determining the appropriate treatment. This review focuses on the existing understanding of the connection between esophageal motor findings and the pathogenesis of GERD, along with the significance of esophageal HRM in managing GERD patients. The International GERD Consensus Working Group introduced a three-step method, assessing the esophagogastric junction (EGJ), esophageal body motility, and contraction reserve with multiple rapid swallow (MRS) maneuvers. Crucial HRM abnormalities in GERD include frequent transient lower esophageal sphincter relaxations, disrupted EGJ, and esophageal body hypomotility. Emerging HRM metrics like EGJ-contractile integral and innovative provocative maneuver like straight leg raise have the potential to enhance our understanding of factors contributing to GERD, thereby increasing the value of HRM performed in patients who experience symptoms suspected of GERD.

Contraction reserve in high resolution manometry is correlated with lower esophageal acid exposure time in patients with normal esophageal motility: A retrospective observational study.

In high resolution manometry (HRM), distal contractile integral post multiple rapid swallow augmentation is considered as contraction reserve. The relationship between contraction reserve and esophageal acid reflux remains unclear. The aim of this study was to explore the correlation between contraction reserve and esophageal acid exposure in ineffective esophageal motility (IEM) and normal HRM. Patients who underwent HRM and ambulatory reflux monitoring were retrospectively screened. Those with diagnosis of normal HRM or IEM were included in the analysis. The proportion of patients with abnormal acid exposure time (AET) was compared between patients with and without contraction reserve. Multivariate regression analysis was performed to determine the predictors of abnormal AET and contraction reserve. A total of 338 patients, including 264 normal HRM and 74 IEM, were included in the analysis. In patients with normal HRM, proportion of abnormal total AET (AET > 6.0%) was significantly lower in patients with supine contraction reserve than patients without contraction reserve (13.85% vs. 24.63%, p = 0.027). Multivariate regression analysis showed that supine contraction reserve could independently predict abnormal total AET (OR = 0.468, 95% CI: 0.249-0.948, p = 0.034), while upright contraction reserve trended strongly (OR = 0.558, 95% CI: 0.290-1.071, p = 0.079). Subgroup analysis showed that upright contraction reserve was an independent predictor of abnormal total AET in patients with 50-70% infective swallows (OR = 0.205, 95% CI: 0.051-0.821, p = 0.025), whereas supine contraction reserve did not have predictive value (p = 0.359). Supine contraction reserve correlates with esophageal acid reflux in patients with normal HRM, while only upright contraction reserve correlates with esophageal acid reflux in patients with infective swallows of 50-70%.

Phosphodiesterase 5 (PDE-5) inhibitors (sildenafil, tadalafil, and vardenafil) effects on esophageal motility: a systematic review

BackgroundEsophageal motility disorders are a group of disorders associated with dysfunctional swallowing resulting from impaired neuromuscular coordination. Phosphodiesterase 5 (PDE-5) inhibitors induce smooth relaxation and are proposed as a treatment option for esophageal motility disorders such as achalasia.MethodsThis study is conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We systematically searched MEDLINE/ PubMed, Scopus, EMBASE, and Web of Science databases for esophageal outcomes of individuals treated with PDE5 inhibitors. A random effect meta-analysis was conducted.ResultsA total of 14 studies were included. They were conducted in different countries, with Korea and Italy having the highest number of articles. The main drug assessed was sildenafil. PDE-5 inhibitors resulted in a significant reduction in lower esophageal sphincter pressure (SMD − 1.69, 95% CI: -2.39 to -0.99) and the amplitude of contractions (SMD − 2.04, 95% CI: -2.97 to -1.11). Residual pressure was not significantly different between the placebo and sildenafil groups (SMD − 0.24, 95% CI: -1.20 to 0.72). Furthermore, a recent study reported contractile integral, stating that ingestion of sildenafil leads to a significant reduction in distal contractile integral and a significant increase in proximal contractile integral.ConclusionPDE-5 inhibitors significantly reduce LES resting pressure and esophageal peristaltic vigor, decreasing esophageal body contractility and contraction reserve. Therefore, using these drugs in patients affected by esophageal motility disorders may potentially improve their condition regarding symptom relief and prevention of further associated complications. Future reports investigating larger sample size is necessary in order to establish definite evidence regarding the efficacy of these drugs.

Solid bolus swallows during high-resolution manometry complement multiple rapid swallows in predicting symptoms following antireflux surgery.

Solid bolus swallows (SBS) assess esophageal peristalsis on high-resolution manometry (HRM). It remains unknown if increase in contraction vigor (contraction reserve) following SBS (SBS-CR) provides information similar to that observed following multiple rapid swallows (MRS-CR). Clinical and HRM data from adult patients (n=96, age 58.2years, 61.5% female) undergoing esophageal testing prior to anti-reflux surgery (ARS) were analyzed if both MRS and SBS were available, and compared to similar data from healthy asymptomatic volunteers (n=18, age 27.5years, 55.6% female). Patients reported esophageal symptoms before and after ARS using 5-point Likert scales evaluating symptom frequency and severity; scores for each patient were averaged to determine global symptoms. Distal contractile integral (DCI) from single swallows was compared to MRS DCI and SBS DCI; the ratio of single swallow DCI to MRS DCI or SBS DCI ≥1 determined the presence of contraction reserve. Multiple rapid swallows CR was concordant with SBS CR in 55.6% of healthy volunteers, 100% of absent contractility, 100% of ineffective esophageal motility (IEM) and 56.9% without IEM. Correlation between MRS DCI and SBS DCI was highest when IEM criteria were met (Spearman's rho 0.998). While neither MRS CR nor SBS CR presence differed by presenting symptoms or global symptom score at baseline, post-ARS global symptom burden was highest in the absence of both MRS CR and SBS CR, especially in patients with esophageal hypomotility using Chicago Classification version 4.0 criteria (p=0.03). Multiple rapid swallows and SBS are complementary in predicting post-ARS symptom burden.

Chicago Classification update (V4.0): Technical review on diagnostic criteria for ineffective esophageal motility and absent contractility.

Esophageal hypomotility disorders manifest with abnormal esophageal body contraction vigor, breaks in peristaltic integrity, or failure of peristalsis in the context of normal lower esophageal sphincter relaxation on esophageal high-resolution manometry (HRM). The Chicago Classification version 4.0 recognizes two hypomotility disorders, ineffective esophageal motility (IEM) and absent contractility, while fragmented peristalsis has been incorporated into the IEM definition. Updated criteria for ineffective swallows consist of weak esophageal body contraction vigor measured using distal contractile integral (DCI, 100-450mmHg·cm·s), transition zone defects >5cm measured using a 20mmHg isobaric contour, or failure of peristalsis (DCI<100mmHg·cm·s). More than 70% ineffective swallows and/or ≥50% failed swallows are required for a conclusive diagnosis of IEM. When the diagnosis is inconclusive (50%-70% ineffective swallows), supplementary evidence from multiple rapid swallows (absence of contraction reserve), barium radiography (abnormal bolus clearance), or HRM with impedance (abnormal bolus clearance) could support a diagnosis of IEM. Absent contractility requires 100% failed peristalsis, consistent with previous versions of the classification. Consideration needs to be given for the possibility of achalasia in absent contractility with dysphagia despite normal IRP, and alternate complementary tests (including timed upright barium esophagram and functional lumen imaging probe) are recommended to confirm or refute the presence of achalasia. Future research to quantify esophageal bolus retention on stationary HRM with impedance and to understand contraction vigor thresholds that predict bolus clearance will provide further refinement to diagnostic criteria for esophageal hypomotility disorders in future iterations of the Chicago Classification.

Assessment of the Multiple Rapid Swallows Test for Gauging Esophageal Reflux Burden in Patients with Refractory Gastroesophageal Reflux Disease.

BackgroundThe multiple rapid swallows (MRS) test is used to assess esophageal contraction reserve. In this study, we characterized the expression of the MRS test in patients with reflux burden and other symptomatic phenotypes with refractory gastroesophageal reflux disease (rGERD).Material/MethodsPatients with rGERD who underwent high-resolution manometry (HRM) and esophageal pH-impedance monitoring (EIM) between September 2018 and January 2020 were retrospectively studied.ResultsWe enrolled 151 patients and divided them into 4 phenotypes according to the results of EIM. In phenotype 1, the MRS distal contractile integral (DCI) was significantly positively correlated with acid-liquid reflux episodes. In phenotype 2, lower esophageal sphincter pressure (LES) length was significantly positively correlated with MRS DCI, and MRS/single-swallow (SS) DCI ratio. In phenotype 3, MRS DCI was negatively correlated with the DeMeester score, acid exposure time (AET), upright AET, long-term acid reflux episodes, acid-mixed reflux episodes, recumbent acid reflux episodes, and total acid reflux episodes. There was a significant negative correlation between MRS/SS DCI and recumbent acid reflux episodes. In phenotype 4, nonacid-liquid episodes and recumbent nonacid reflux episodes were significantly higher in the abnormal MRS group. However, acid-gas episodes, weakly acid-gas episodes, and upright gas reflux episodes were higher in the normal MRS group than in the abnormal MRS group.ConclusionsEsophageal contraction reserve is heterogeneous within the reflux burden and symptomatic phenotypes of patients with rGERD.

Patterns of esophageal dysmotility elicited by multiple rapid swallows

High-resolution manometry (HRM) is a gastrointestinal motility diagnostic system that measures intraluminal pressures using closely aligned sensors. Multiple rapid swallows (MRS) are used in conjunction with HRM to assess esophageal physiology prior to anti-reflux and hiatal hernia procedures. A retrospective, qualitative study was conducted on 90 patients who underwent HRM with MRS in a single community clinic. 80 patients met the inclusion criteria. MRS testing consisted of rapid 2mL swallows in 2-3s intervals with patients in a seated, upright position. Clinical information was reviewed including indications for HRM, prior diagnostic workup, manometry, distal contractile integral (DCI), and integrated residual pressure (IRP). HRM studies were visualized using Manoview Analysis Software v3.0 (Medtronic). Certain esophageal dysmotility and pressurization manometry patterns were previously undetected on HRM alone. In our study, the addition of MRS was clinically helpful in (1) assessing contraction reserve, (2) highlighting features of jackhammer, (3) stimulating esophageal spasm, and (4) visualizing distal esophageal pressurization pattern with mechanical obstruction. Additionally, abnormal pathophysiology such as (5) paradoxical LES contraction (achalasia) and (6) loss of deglutition inhibition were identified. MRS had a diagnostic utility of 21.25% (n = 17) among the 80 patients. An intolerance rate of 7.7% (n = 7) was observed in patients unable to complete the protocol. Augmentation of HRM with MRS produces unique manometric features that have clinical utility in uncovering esophageal disorders. MRS provocation testing is a practical, inexpensive, well-tolerated addition to HRM that may yield useful clinical information to guide complicated diagnoses and medical management.

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.

Contraction Reserve With Ineffective Esophageal Motility on Esophageal High-Resolution Manometry is Associated With Lower Acid Exposure Times Compared With Absent Contraction Reserve.

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. 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. 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. Contraction reserve affects esophageal reflux burden in nonsevere IEM. Segregating IEM into severe and nonsevere cohorts has clinical value.

Postreflux swallow-induced peristaltic wave index from pH-impedance monitoring associates with esophageal body motility and esophageal acid burden.

Postreflux swallow-induced peristaltic wave (PSPW) on pH-impedance monitoring and contraction vigor on high-resolution manometry (HRM) both assess esophageal peristaltic response. We aimed to evaluate relationships between PSPW and esophageal peristalsis on HRM in the context of reflux disease in this multicenter cohort study. pH-impedance and HRM studies performed on patients with persisting reflux symptoms were reviewed from 6 centers (5 in Europe and 1 in US). Total, upright and supine acid exposure time (AET) were evaluated from pH-impedance studies; PSPW index (PSPWI) and mean nocturnal baseline impedance (MNBI) were calculated using standard methodology. Esophageal body contraction vigor was analyzed using distal contractile integral (DCI), and DCI ratio>1 between single swallows and multiple rapid swallows (MRS) defined presence of contraction reserve. Student's t test, ANOVA, and linear regression were utilized to investigate relationships between PSPW, contraction vigor, and contraction reserve. Of 296 patients (52.8±0.8yr, 63% F), median PSPWI was 0.475. Only 24.0% had intact DCI; the remainder had varying degrees of hypomotility. As hypomotility increased, PSPWI and MNBI decreased significantly, while total AET and reflux episodes had an inverse response (P≤.002 for each). MRS data were available in 167 (56.4%), 72.5% had contraction reserve. MRS cohorts with normal PSPWI had significantly lower reflux burden compared to low PSPWI, regardless of presence or absence of contraction reserve (P≤.001). PSPWI correlates with esophageal hypomotility and reflux burden, and complements clinical reflux evaluation. Intact PSPW is more relevant to esophageal reflux clearance than contraction reserve.

Ineffective esophageal motility and bolus clearance. A study with combined high-resolution manometry and impedance in asymptomatic controls and patients.

The definition and relevance of ineffective esophageal motility (IEM) remains debated. Our aim was to determine motility patterns and symptoms associated with IEM defined as impaired bolus clearance. To define altered bolus clearance, normal range of swallows with complete bolus transit (CBT) on high-resolution impedance manometry (HRIM) was determined in 44 asymptomatic controls. The results were then applied to a cohort of 81 patients with esophageal symptoms to determine the motility patterns which best predicted altered bolus clearance. Subsequently, in a cohort of 281 consecutive patients the identified motility patterns were compared with patients' customary symptoms. In asymptomatic controls, the normal range of swallows with CBT was 50%-100%. In patients, altered bolus transit (<50% CBT) was only associated with 30% or more failed contractions (P<.001). Neither weak peristalsis nor absence of contraction reserve (CR) was associated with altered bolus clearance. The patterns which best predicted altered bolus clearance were failed contractions ≥30% (specificity 88.2% and sensitivity of 84.6%), and ≥70% ineffective (failed+weak) contractions (sensitivity 84.6% and specificity 80.9%). No motility pattern was correlated to symptom scores. Based on bolus clearance assessed by HRIM, ≥30% failed contractions and ≥70% ineffective contractions have the best sensitivity and specificity to predict altered bolus clearance. Weak contractions and absence of CR are not relevant with respect to bolus clearance.

Influence of sildenafil on esophageal motor function in humans: Studies using high-resolution manometry.

Sildenafil induces smooth muscle relaxation of the esophagus by blocking type 5 phosphodiesterase that degrades cyclic guanine monophosphate. We aimed to characterize the effects of sildenafil on esophageal peristalsis and contraction reserve using high-resolution manometry (HRM). Fifteen healthy adults (12 men, age 21-39, mean 27years) participated in this study using HRM following either sildenafil 50mg or placebo. HRM with ten wet swallows and five multiple rapid swallows was performed in all participants. HRM metrics included esophagogastric junction contractile integral (EGJ-CI), basal lower esophageal sphincter (LES) pressure, 4-second integrated relaxation pressure (IRP-4s), distal contractile integral (DCI), distal latency, resting upper esophageal sphincter pressure (UESP), and the response to MRS. Sildenafil significantly lowered EGJ-CI (P<.001), LES pressure (P=.04), IRP-4s (P=.02), and DCI (P<.001). There was no difference in UESP (P=.87) between sildenafil and placebo. Sildenafil significantly decreased peristaltic vigor, inducing absent peristalsis in 12 subjects and ineffective esophageal motility in 3 subjects. Peristaltic response and augmentation following MRS were significantly inhibited following sildenafil (7% vs 100%, P<.001, and none vs 73%, P<.001). Sildenafil attenuates EGJ barrier function, resting LES pressure, and LES relaxation. Both esophageal body contractility and contraction reserve are inhibited by sildenafil in healthy adults.

Minor esophageal functional disorders: are they relevant?

High resolution esophageal manometry (HRM) has expanded understanding of esophageal motor function. The Chicago Classification scheme has allowed systematic categorization of the myriad of manometric parameters identified during HRM. Multichannel intraluminal impedance pH has enhanced ambulatory reflux monitoring through complete assessment of esophageal content transit. However, the clinical implications of identified minor esophageal functional disorders remain unclear. Esophagogastric junction outlet obstruction is defined by esophagogastric junction obstruction with preserved peristalsis and may be managed expectantly, or in a manner similar to achalasia. Hypercontractile esophagus has been associated with dysphagia and non-cardiac chest pain, but the clinical significance is unclear as a majority of patients will improve without specific therapy. Additionally, these findings may be confounded by chronic opiate use. Ineffective esophageal motility is characterized by diminished esophageal contraction amplitude, potentially causing dysphagia and GERD. However, this is commonly identified in asymptomatic volunteers and may represent a normal variant. The multiple rapid swallow sequence can assess esophageal contraction reserve, which may predict post fundoplication dysphagia. The post-swallow induced peristaltic wave can serve as a surrogate of gastric refluxate clearance, providing important prognostic value. However, the associated time burden and lack of alternative therapeutic options limit its clinical utility. Minor esophageal functional disorders provide new therapeutic targets for symptomatic patients. However, these findings have inconsistent associations with symptoms and poorly defined therapeutic options. Minor esophageal function disorders should not be interpreted in isolation, with management decisions accounting for clinical, endoscopic, and radiographic factors in addition.

Factors predicting loss of cervical lordosis following cervical laminoplasty: A critical review

Background:Laminoplasty is a method of posterior cervical decompression which indirectly decompresses the spinal column. Unfortunately, many patients undergoing laminoplasty develops postoperative loss of cervical lordosis (LCL) or kyphotic alignment of cervical spine even though they have sufficient preoperative lordosis which results in poor surgical outcome.Objective:We would like to highlight the relationship between various radiological parameters of cervical alignment and postoperative LCL in patients undergoing laminoplasty.Methods:We performed extensive literature search using PubMed, Google Scholar, and Web of Science for relevant articles that report factors affecting cervical alignment following laminoplasty.Results:On reviewing the literature, patients with high T1 slope have more lordotic alignment of cervical spine preoperatively. They also have more chances of LCL following laminoplasty. C2–C7 sagittal vertical axis (SVA) has no role in predicting LCL following laminoplasty though patients with low T1 slope (≤20°) and high C2–C7 SVA (>22 mm) had correction of kyphotic deformity following laminoplasty. C2–C7 lordosis, Neck Tilt, cervical range of motion, and thoracic kyphosis has no predictive value for LCL. Lower value of T1 slope (T1S-CL) and CL/T1S has more incidence of developing LCL following laminoplasty. The role of C2–C3 disc angle has not yet been evaluated in patients undergoing laminoplasty. Dynamic extension reserve determines the contraction reserve of SPMLC and lower dynamic extension reserve is associated with higher chances of LCL following laminoplasty.Conclusions:Cervical lordotic alignment is important in maintaining cervical sagittal balance which ultimately is responsible for global spinal sagittal balance and horizontal gaze. Among various radiological parameters, T1 Slope has been reported to be the most important factor affecting cervical alignment following laminoplasty.

Effects of GABA-B agonist baclofen on esophageal motility: Studies using high-resolution manometry.

Baclofen inhibits transient lower esophageal sphincter (LES) relaxation. This study aimed to investigate the effect of baclofen on esophageal peristaltic function and contraction reserve in healthy adults using high-resolution manometry (HRM). Fifteen subjects underwent HRM with ten water swallows and five multiple rapid swallows (MRS) 90minutes after oral intake of either baclofen or placebo on separate days at least 1week apart. HRM parameters assessed included esophagogastric junction contractile integral (EGJ-CI), resting LES pressure, 4-second integrated relaxation pressure (IRP-4s), distal contractile integral (DCI), distal latency, peristaltic breaks, resting upper esophageal sphincter (UES) pressure, and contractile response to MRS. Baclofen significantly increased EGJ-CI (P=.007), IRP-4s (P=.003), and LES pressure (P=.004). UES pressure, latency, and DCI were similar between baclofen and placebo (P=.87, P=.84, and P=.54, respectively). There was no difference in contractile response and peristaltic augmentation following MRS between baclofen and placebo (93% vs 100%, P=.30; 53% vs. 73%, P=.26, respectively). Baclofen increases resting LES pressure and EGJ barrier function, but has no effect on primary peristalsis or contraction reserve.

The Utility of Esophageal Motility Testing in Gastroesophageal Reflux Disease (GERD).

Here, we discuss how esophageal motor testing plays important roles in patients with suspected gastroesophageal reflux disease (GERD). In addition to guiding appropriate placement of catheters for ambulatory reflux monitoring, esophageal high-resolution manometry (HRM) rules out confounding diagnoses, such as achalasia spectrum disorders, that can present with symptoms similar to that of GERD, but are managed very differently. HRM performed with impedance in the post-prandial setting (PP-HRIM) can assess for rumination syndrome or supragastric belching, which should be directed towards behavioral interventions. The recent GERD Classification of Motor Function recommends a hierarchical approach, focusing on (1) the esophagogastric junction (EGJ), (2) the esophageal body, and (3) esophageal contraction reserve, which can be assessed with provocative maneuvers at HRM, such as multiple rapid swallows (MRS). This approach can inform the appropriate tailoring of antireflux surgery. Novel esophageal motility metrics, such as the EGJ-contractile integral from HRM, or post-reflux swallow-induced peristaltic wave indices from 24-h pH-impedance monitoring, may also assist with GERD diagnosis. Assessment of esophageal motor function can contribute in a significant manner to the care of patients with suspected GERD, particularly when esophageal symptoms do not improve with antisecretory therapy, and/or when surgical or endoscopic antireflux therapies are under consideration.

Evaluation of Esophageal Contraction Reserve Using HRM in Symptomatic Esophageal Disease.

Esophageal high resolution manometry (HRM) is the gold standard for assessment of esophageal motor disorders, but motor responses to the standard 5 mL water swallow protocol may not provide precision in defining minor motor disorders. Provocative maneuvers, particularly multiple rapid swallows (MRS), have been used to assess deglutitive inhibition during the repetitive swallows, and the contractile response following the final swallow of the sequence. The augmentation of esophageal smooth muscle contraction following MRS is termed contraction reserve. This is determined as the ratio between esophageal body contraction vigor (distal contractile integral, DCI) following MRS to the mean DCI after single swallows, which is ≥1 in the presence of contraction reserve. Reliable assessment of contraction reserve requires the performance of 3 MRS maneuvers during HRM. Absence of contraction reserve is associated with a higher likelihood of late postfundoplication dysphagia and may correlate with higher esophageal reflux burden on ambulatory reflux monitoring. Esophageal motor responses to abdominal compression, functional lumen imaging probe (FLIP) balloon distension, and pharmacologic testing (using edrophonium and cisapride) may correlate with contraction reserve. Other provocative tests useful during HRM include rapid drink challenge, solid and viscous swallows, and standardized test meals, which are more useful in evaluation of esophageal outflow obstruction and dysphagia syndromes than in identification of contraction reserve. Provocative maneuvers have been recommended as part of routine HRM protocols, and while useful clinical information can be gleaned from these maneuvers, further research is necessary to determine the precise role of provocative testing in clinical esophagology.

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

Ineffective esophageal motility (IEM) is a heterogenous minor motility disorder diagnosed when ≥50% ineffective peristaltic sequences (distal contractile integral <450mm Hgcms) 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. 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.

Provocative testing in patients with jackhammer esophagus: evidence for altered neural control.

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.