J Neurogastroenterol Motil 2023; 29(2): 166-173  https://doi.org/10.5056/jnm22020
Hypercontractile Esophagus: Clinical and Manometric Features From a Multicenter Korean Cohort
Yang Won Min,1 Kee Wook Jung,2 Kyoungwon Jung,3 Yu Kyung Cho,4* and Moo In Park3*; Dysphagia Study Group Under the Korean Society of Neurogastroenterology and Motility
1Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 2Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; 3Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea; and 4Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea
Correspondence to: *Yu Kyung Cho, MD, PhD
Division of Gastroenterology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, 222 Banpodaero, Seocho-gu, Seoul 06591, Korea
Tel: +82-2-2258-2064, Fax: +82-2-2258-2055, E-mail: ykcho@catholic.ac.kr
Moo In Park, MD, PhD
Department of Internal Medicine, Kosin University College of Medicine, 262 Gamcheon-ro, Seo-gu, Busan 49267, Korea Tel: +82-51-990-6719, Fax: +82-51-990-5055, E-mail: mipark@ns.kosinmed.or.kr
Yang Won Min and Kee Wook Jung contributed equally to this work.
Yu Kyung Cho and Moo In Park are equally responsible for this work.
Received: February 15, 2022; Revised: May 19, 2022; Accepted: June 3, 2022; Published online: April 30, 2023
© The Korean Society of Neurogastroenterology and Motility. All rights reserved.

cc This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background/Aims
Hypercontractile esophagus (HE) is a heterogeneous disorder with variable clinical presentations and a natural course, leading to management challenges. This study aims to investigate the characteristics of HE and evaluate its treatment outcomes.
Methods
Four Korean referral centers recruited subjects with at least 1 hypercontractile swallow (distal contraction integral > 8000 mmHg·s·cm) in this retrospective observational study. Subjects were classified according to the Chicago classification version 2.0 (CC v2.0), CC v3.0, and CC v4.0. criteria. The clinical and manometric features were also investigated. The treatment modalities and outcomes of subjects with CC v4.0 were evaluated.
Results
In total, 59 subjects with at least 1 hypercontractile swallow were analyzed. Among them, 30 (50.8%) had increased integrated relaxation pressure values without meeting the criteria for achalasia. Among the remaining 29 patients, 6 (20.7%) had only 1 hypercontractile swallowing symptom (CC v2.0) and 23 (79.3%) met both the CC v3.0 and v4.0 criteria for HE. Dysphagia (91.3%) was the most prevalent symptom, followed by chest pain (56.5%), regurgitation (52.2%), globus (34.8%), heartburn (21.7%), and belching (8.7%). Twenty (87.0%) patients received medical treatment, and 8 (47.1%) and 5 (29.4%) showed moderate and significant improvements, respectively. Proton pump inhibitors were the most common option (n = 15, 65.2%), followed by calcium channel blockers (n = 6, 26.1%). One patient received peroral endoscopic myotomy and showed significant symptom improvement.
Conclusions
Sixty-one percent of patients who meet the diagnostic criteria for the high-resolution manometry are diagnosed with symptomatic HE based CC v4.0. Chest pain and regurgitation were also observed in over half of them. The overall medical treatment efficacy was moderate.
Keywords: Chest pain; Dysphagia; Hypercontractile esophagus; Manometry
Introduction

Hypercontractile esophagus (HE) is a major disorder of peristalsis.1 The first Chicago classification (CC) of esophageal motility defined hypercontractile disorders as a single swallow with a distal contraction integral (DCI) > 8000 mmHg·s·cm. This was based on the observation that the highest DCI value observed in any swallow was 7732 mmHg·s·cm in 72 healthy subjects.2,3 Next, following the observation 8000 mmHg·s·cm DCIs occurring in healthy subjects, the CC version 3.0 (v3.0) modified the requirement for HE to ≥ 20% of swallows with a DCI > 8000 mmHg·s·cm.4 However, HE remains a heterogeneous disorder with variable clinical presentations and a natural course, which typically leads to management challenges. Therefore, the CC v4.0 requires clinically relevant symptoms (dysphagia and noncardiac chest pain) to make a diagnosis of HE in order to improve the clinical relevance.1

The prevalence of HE among patients undergoing high-resolution manometry (HRM) rages from 0.4% to 9.0%.5 The varying prevalence stems from the different diagnostic criteria, geographic factors, and small number of samples. According to a recent review, HE in women is more prevalent, occurring in those with a mean age of 65 years.5 The most common symptom was dysphagia (62.8%). In a recently published French cohort study, dysphagia was also the most common symptom (74.6%).6 However, the demographic and clinical data are still lacking, and no epidemiologic studies on this topic have been published in Asia.

The paucity of natural course data for HE has been reported.7-9 Although some patients may experience spontaneous symptoms and/or manometric resolution, some can progress to achalasia. Therefore, more data need to be collected to establish a management strategy for HE. Although the pathogenesis of HE remains to be elucidated, excessive cholinergic innervation appears to be involved in hypercontractility.10 Thus, medical treatment with calcium channel blockers (CCBs),11 phosphodiesterase-5 inhibitors,12 anticholinergics,10,13 endoscopic botulinum toxin injection, and peroral endoscopic myotomy (POEM)14,15 have been used, with varying treatment outcomes. As gastroesophageal reflux is often accompanied by HE, proton pump inhibitors (PPIs) have also been used for symptom control.6,16-18 The treatment efficacy for HE remains insufficiently studied because of the use of small sample sizes.

This study aims to investigate the clinical and manometric features of HE and evaluate treatment outcomes in a multicenter Korean cohort.

Materials and Methods

Subjects

Four Korean referral centers (Samsung Medical Center, Asan Medical Center, Kosin University College of Medicine, and Seoul St. Mary’s Hospital) participated in this retrospective observational study. A total of 5773 consecutive subjects underwent esophageal HRM between 2011 and 2021. Of these, 59 subjects had at least 1 hypercontractile swallow (DCI > 8000 mmHg·s·cm) and did not meet the criteria for achalasia.2,4 The study protocol was conducted in accordance with the Declaration of Helsinki and was approved by the Institutional Review Board at Samsung Medical Center, Seoul, Korea (No. 2021-10-035). As the present study was based on a retrospective analysis of existing data, the requirement for obtaining informed consent was waived.

Data Acquisition

Demographic and clinical data were obtained from a review of the electrical medical records. Age, sex, esophageal symptoms with duration (dysphagia, chest pain, heartburn, regurgitation, globus, and belching), treatments, and follow-up outcomes were investigated. Endoscopic pictures were also reviewed to assess the patients’ hiatal hernia, reflux esophagitis, and Hill grade.19,20 Follow-up outcomes were categorized as follows: no symptom improvement in symptoms improvement by less than 25%; moderate symptom improvement ≥ 25% but < 75%; and significant symptom improvement ≥ 75%. Due to the retrospective design, a standardized questionnaire was not used and follow-up periods varied.

Multichannel Intraluminal Impedance and Esophageal Manometry Data

Esophageal HRM studies were performed in a standard fashion, with a series of 10 swallows of 5 mL normal saline in the supine or sitting position. Two centers used the Given imaging system (Given Imaging Ltd, Los Angeles, CA, USA) and 2 used Sandhill Scientific systems (Sandhill Scientific Inc, Ranch, CO, USA). We defined an elevated median integrated relaxation pressure (IRP) of > 15 mmHg for the Given Imaging system and > 20 mmHg for the Sandhill Scientific system.4,21,22 The mean DCI, maximal DCI, number of hypercontractile swallows, median IRP, mean distal latency (DL), and complete bolus transit (CBT, %) values were calculated.4 Hypercontractile swallows were subtyped as either single peaked or multipeaked.3 Bolus entry was defined as a > 50% drop in impedance level from the baseline at the proximal recording site, and CBT was defined as a > 50% drop from the baseline, followed by an increase of at least 50% towards the original baseline at the 3 distal impedance recording sites after bolus entry.23 Multichannel intraluminal impedance findings were reported as having normal bolus transit if ≥ 80% of the liquid swallows had CBT.24-26

Statistical Methods

Data were expressed as mean ± SD, median (range), or n (%), as appropriate. Differences among the continuous and categorical variables were examined for statistical significance using Student’s t test (or Mann–Whitney U test, if appropriate) and the chi-squared test (or Fisher’s exact test, if appropriate), respectively. A two-tailed P-value of less than 0.05 was considered significant. All statistical analyses were performed using SPSS (version 24.0; IBM Corp, Armonk, NY, USA) and GraphPad Prism 9.2.0 software (GraphPad, San Diego, CA, USA).

Results

Subject Characteristics

Among 59 subjects who had at least 1 hypercontractile swallow, 30 (50.8%) also had an increased IRP value without meeting the criteria for achalasia. These 30 patients were diagnosed with esophagogastric junction outflow obstruction (EGJOO).27 However, 29 patients with normal IRP and 30 with EGJOO did not differ in terms of their baseline characteristics, except in their IRP values (Figure and Table 1). Among the 29 subjects, 6 (20.7%) had only 1 hypercontractile swallow (CC v2.0) and did not meet the CC v3.0 requirement for HE (Figure). All 23 subjects who met the CC v3.0 requirement for HE had clinically relevant symptoms meeting the CC v4.0 requirement (Figure). The prevalence of HE according to the CC v2.0 and CC v4.0 criteria was 0.5% (29/5773) and 0.4% (23/5773), respectively. The baseline characteristics did not differ between the 2 groups (only CC v2.0 vs CC v4.0), except for in the number of hypercontractile swallows (Table 2). In addition, the maximal DCI was slightly higher in the CC v4.0 group than in the only CC v2.0 group (16 795.07 ± 10 056.65 mmHg·s·cm vs 8982.57 ± 478.94 mmHg·s·cm, P = 0.071), although the difference was not statistically significant.

Table 1 . Characteristics of the Study Participants

SubjectsTotal (N = 59)Normal IRP (n = 29)Increased IRP (n = 30)P-valuea
Age (yr)60.46 ± 12.0060.62 ± 13.8860.30 ± 10.110.919
Male sex37 (62.7)20 (69.0)17 (56.7)0.422
Chief complaining symptoms0.672
Dysphagia38 (64.4)20 (69.0)18 (60.0)
Chest pain11 (18.6)6 (20.7)5 (16.7)
Heartburn4 (6.8)1 (3.4)3 (10.0)
Regurgitation2 (3.4)1 (3.4)1 (3.3)
Globus2 (3.4)0 (0.0)2 (6.7)
Others2 (3.4)1 (3.4)1 (3.3)
Symptom duration, months12 (3-24)12 (3-24)12 (3-36)0.454
Symptom prevalence
Dysphagia48 (81.4)25 (86.2)23 (76.7)0.506
Chest pain28 (47.5)17 (58.6)11 (36.7)0.120
Heartburn10 (16.9)5 (17.2)5 (16.7)1.000
Regurgitation22 (37.3)14 (48.3)8 (26.7)0.110
Globus22 (37.3)9 (31.0)13 (43.3)0.422
Belching5 (8.5)3 (10.3)2 (6.7)0.671
Manometric variables
DCI (mmHg·s·cm)9706.02 ± 9838.3111 613.19 ± 13 326.117862.42 ± 3869.070.145
Maximal DCI (mmHg·s·cm)17 846.81 ± 17 680.9515 178.69 ± 9480.4020 426.00 ± 22 900.930.258
Number of hypercontractile swallows5.0 (2.0-7.0)5.0 (1.5-7.0)4.5 (2.0-7.0)0.636
Multipeaked configuration31 (52.5)11 (37.9)17 (56.7)0.195
IRP (mmHg)20.48 ± 12.9311.70 ± 5.0128.97 ± 12.58< 0.001
DL (sec)7.31 ± 1.767.28 ± 2.117.35 ± 1.360.882
Maximal IRP (mmHg)26.37 ± 14.4617.07 ± 7.4235.37 ± 13.95< 0.001
Complete bolus transit (%)84.52 ± 24.2285.28 ± 25.0583.78 ± 23.790.814
Abnormal bolus transit12 (20.3)5 (17.2)7 (23.3)0.748
Endoscopic findings
Hiatal hernia1 (1.8)0 (0.0)1 (3.6)1.000
Reflux esophagitis0.601
None51 (91.1)25 (89.3)26 (92.9)
LA-A4 (7.1)2 (7.1)2 (7.1)
LA-B1 (1.8)1 (3.6)0 (0.0)
Gastroesophageal flap valve0.344
Hill grade 127 (48.2)12 (42.9)15 (53.6)
Hill grade 224 (42.9)12 (42.9)12 (42.9)
Hill grade 35 (8.9)4 (14.3)1 (3.6)

aComparison between normal integrated relaxation pressure (IRP) and increased IRP.

DCI, distal contractile integral; DL, distal latency; LA, Los Angeles classification.

Increased IRP is defined of > 15 mmHg for the Given Imaging system and > 20 mmHg for the Sandhill Scientific system.

Values are presented as mean ± SD, n (%), or median (interquartile range).



Table 2 . Comparison of the Characteristics of the Study Participants According to the Diagnostic Criteria

SubjectsOnly CC v2.0 (n = 6)CC v4.0 (n = 23)P-value
Age (yr)59.17 ± 16.8361.00 ± 13.410.779
Male sex4 (66.7)16 (69.6)> 0.999
Chief complaining symptoms0.352
Dysphagia4 (66.7)16 (69.6)
Chest pain1 (16.7)5 (21.7)
Heartburn0 (0.0)1 (4.3)
Regurgitation0 (0.0)1 (4.3)
Others1 (16.7)0 (0.0)
Symptom duration (mo)21 (11.5-27.0)6 (3.0-24.0)0.291
Symptom prevalence
Dysphagia4 (66.7)21 (91.3)0.180
Chest pain4 (66.7)13 (56.5)> 0.999
Heartburn0 (0.0)5 (21.7)0.553
Regurgitation2 (33.3)12 (52.2)0.651
Globus1 (16.7)8 (34.8)0.633
Belching1 (16.7)2 (8.7)0.515
Manometric variables
DCI (mmHg·s·cm)5120.38 ± 1339.1613 306.96 ± 14 529.740.185
Maximal DCI (mmHg·s·cm)8982.57 ± 478.9416 795.07 ± 10 056.650.071
Number of hypercontractile swallows1 (1-1)6 (3-9)< 0.001
Multipeaked configuration1 (16.7)10 (43.5)0.362
IRP (mmHg)10.82 ± 4.5311.93 ± 5.200.635
DL (sec)8.18 ± 3.127.04 ± 1.780.244
Maximal IRP (mmHg)17.93 ± 8.6716.84 ± 7.260.754
Complete bolus transit (%)90.00 ± 15.4984.05 ± 27.140.613
Abnormal bolus transit0 (0.0)5 (21.7)0.553
Endoscopic findings
Hiatal hernia0 (0.0)0 (0.0)> 0.999
Reflux esophagitis0.632
None6 (100.0)19 (86.4)
LA-A0 (0.0)2 (9.1)
LA-B0 (0.0)1 (4.5)
Gastroesophageal flap valve0.868
Hill grade 12 (33.3)10 (45.5)
Hill grade 23 (50.0)9 (40.9)
Hill grade 31 (16.7)3 (13.6)

CC, Chicago classification; IRP, integrated relaxation pressure; DCI, distal contractile integral; DL, distal latency; LA, Los Angeles classification.

Values are presented as mean ± SD, n (%), or median (interquartile range).



Figure 1. Flowchart of study participants. Hypercontractile swallow was defined by a distal contraction integral > 8000 mmHg·s·cm. HRM, high-resolution manometry; HS, hypercontractile swallow; IRP, integrated relaxation pressure.

Among the 23 subjects meeting the CC v4.0 criteria, 16 (69.6%) were male (Table 2). The mean age was 61.00 ± 13.41. Dysphagia (n = 16, 69.6%) was the most common chief complaint, followed by chest pain (5, 21.7%), heartburn (1, 4.3%), and regurgitation (1, 4.3%). The median duration of symptoms was 6 months (interquartile range 3-24). Dysphagia (21, 91.3%) was the most prevalent symptom, followed by chest pain (13, 56.5%), regurgitation (12, 52.2%), globus (8, 34.8%), heartburn (5, 21.7%), and belching (2, 8.7%). The mean DCI was 13 306.96 ± 14 529.74 mmHg·s·cm and median number of hypercontractile swallow was 6 (3-9). A multipeaked configuration was observed in 10 subjects (43.5%). Five subjects (21.7%) showed an abnormal bolus transit. Although hiatal hernia was not observed, 3 subjects (13.6%) had reflux esophagitis.

Treatment Outcomes

Of the 23 subjects meeting the CC v4.0 criteria, 20 (87.0%) received medical treatment (Table 3). The median follow-up period was 2 months (interquartile range 1.0-10.5). PPIs were the most common option (15, 65.2%), followed by CCBs (6, 26.1%), and anticholinergics (2, 8.7%). One subject underwent POEM. Two subjects did not receive any specific treatment. The overall efficacy of the medical treatment was good (Table 4). Eight subjects (47.1%) showed moderate improvement and 5 (29.4%) showed a significant response to medical treatment. PPIs showed 46.2% moderate and 15.4% significant symptom improvement. CCBs showed 33.3% moderate and 50% significant symptom improvement. One subject receiving anticholinergic therapy showed a moderate improvement. One patient underwent POEM. He had been suffering from chest pain unresponsive to medical treatment. Thus, POEM was conducted after confirming muscular thickening on endoscopic ultrasonography and led to significant symptom improvement. Among the 2 subjects that went without treatment, 1 was lost to follow-up and 1 continued to have chest pain during the following 60-month follow-up period.

Table 3 . Treatment Modalities Applied to the Study Participants Fulfilling the Chicago Classification Version 4.0 Criteria

TreatmentCC v4.0 (n = 23)
No treatment2 (8.7)
Medical treatment20 (87.0)
PPIs15 (65.2)
CCBs6 (26.1)
Anticholinergics2 (8.7)
POEM1 (4.3)

CC, Chicago classification; PPIs, proton pump inhibitors; CCBs, calcium channel blockers; POEM, peroral endoscopic myotomy.

Values are presented as n (%).



Table 4 . Clinical Responses to the Treatment Modalities Applied to the Study Participants Fulfilling the Chicago Classification Version 4.0 Criteria

TreatmentNo improvementModerate improvementSignificant improvement
Medical treatment (n = 17)4 (23.5)8 (47.1)5 (29.4)
PPIs (n = 13)5 (38.5)6 (46.2)2 (15.4)
CCBs (n = 6)1 (16.7)2 (33.3)3 (50.0)
Anticholinergics (n = 1)0 (0.0)1 (100.0)0 (0.0)
POEM (n = 1)0 (0.0)0 (0.0)1 (100.0)

PPIs, proton pump inhibitors; CCBs, calcium channel blockers; POEM, peroral endoscopic myotomy.

Values are presented as n (%).


Discussion

Although HE is a major disorder of peristalsis, it remains a heterogeneous disorder with variable clinical presentations and a natural course. The diagnostic criteria have been changing to improve their clinical relevance. Because the prevalence of HE is low, clinical data are lacking, leading to management challenges. This study sought to describe the clinical and manometric features of HE and evaluate its treatment outcomes using a multicenter Korean cohort.

In our cohort, the prevalence of HE according to the CC v2.0 and CC v4.0 criteria was 0.5% and 0.4%, respectively. These results are lower than those from recent North American countries (3.0-4.0%) and those from France (1.4%).5,6,28,29 However, this prevalence could be affected by many non-biologic factors such as institutions’ indications for manometry and patients’ accessibility to the test. Thus, the low prevalence of HE in our cohort needs to be interpretated in this background. Our results for mean age (mean age, 61.0 years) and male predominance (69.6%) were similar to those from France.6 However, a female predominance has also been reported.5

The most predominant characteristic of our cohort was the high prevalence of dysphagia (91.3%). According to previous reports, the prevalence of dysphagia is 60-80%.5,6,16 In a summarized review of > 500 cases, 62.8% of patients had dysphagia.5 When comparing the prevalence of dysphagia in the present study, that of the CC v4.0 group was higher than that of the CC v2.0 group (91.3% vs 66.7%, P = 0.180). Although it was not statistically significant, the mean DCI and maximal DCI values were also higher in the CC v4.0 group than in the CC v2.0 group. In addition, the mean DCI and number of hypercontractile swallows in our cohort were higher than those from 2 recently published studies.6,16 From these observations, we suggest that Korean HE patients have relatively high DCI values and a high dysphagia prevalence. Indeed, DCI is thought to be associated with dysphagia.16,30

As the pathogenesis of HE remains unclear and a paucity of relevant natural course data has been reported,7-9 the treatment of HE is challenging. When considering excessive cholinergic innervation as a crucial pathogenic mechanism,10 medication with CCBc, phosphodiesterase-5 inhibitors, and anticholinergics could be a reasonable treatment option.10-13 In the present study, 6 (85.7%) of 7 patients receiving CCBs or anticholinergics showed moderate to significant treatment responses. However, the small sample size and lack of controls should be considered when interpreting these results. POEM can also be performed. In a systemic meta-analysis, the clinical success rate of POEM for jackhammer esophagus was 72.0%.31 In our cohort, 1 patient received POEM and experienced symptom resolution. However, there are still few studies on the endoscopic treatment of HE. Thus, performing POEM more frequently in patients with HE is necessary to determine whether it could be helpful. Typical gastroesophageal reflux symptoms often accompany HE.5 Thus, PPI use or antireflux therapy for HE have been performed, even without a complete understanding of the role of reflux in HE.3,32,33 In the present study, PPIs led to 61.6% moderate to significant symptom improvement. However, well-designed, controlled studies are necessary to validate our observations.

The present study has several limitations. As the sample size was small, the power of the study was low, and some comparisons were not available like symptom response according to the chief complaints. Owing to the retrospective design, some data regarding symptoms and treatment responses might not have been well evaluated. Large prospective studies are necessary to overcome these limitations. Nevertheless, the present study is the first to report the characteristics of HE in the Korean population. Dysphagia is the most prominent symptom of Korean HE patients, and their DCI is relatively high compared to that in Western HE patients. The overall medical treatment efficacy was moderate or higher.

Financial support

None.

Conflicts of interest

None.

Author contributions

Yang Won Min contributed to data analysis and drafted the manuscript; Kee Wook Jung and Kyoungwon Jung contributed to the editing and revision of the manuscript; and Yu Kyung Cho and Moo In Park designed and coordinated the study, contributed to data interpretation, and edited the manuscript. All the authors approved the final version of the manuscript.

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