Defining a Clinical Phenotype: A Retrospective Comparative Analysis of Patients With Distal Esophageal Spasm (DES) and Normal High-Resolution Esophageal Manometry

Introduction: Distal Esophageal Spasm (DES) is a rare and poorly understood disorder defined as at least 20% premature contractions on High Resolution esophageal Manometry (HRM) per Chicago Classification (CC). DES has a heterogeneous presentation and can be incidentally found on HRM. CC v4.0 stipulates that DES is clinically relevant only if patients present with dysphagia or chest pain. The association between DES and gastroesophageal reflux disease (GERD) is not fully established. This study aims to define a clinical phenotype of DES by examining clinical differences between DES and normal findings on HRM. Methods: A retrospective cohort study was conducted comparing subjects with DES, defined by CC v4.0, to subjects without any CC v3.0 or 4.0 motility disorder on HRM from 2/2020-12/2022. Patients with type III achalasia or prior foregut surgery were excluded. A diagnosis of GERD was defined as having Los Angeles Grade C/D esophagitis or Barrett’s on endoscopy, and/or a positive 24–48-hour reflux testing. To compare characteristics of DES to normal HRM subjects, descriptive and univariate analysis was used. Results: A total of 99 DES and 66 normal HRM subjects met inclusion criteria (Table 1). DES patients were older (57.8 yrs, 52.2 yrs, P=0.023) and had a higher mean BMI (29.5, 26.3, P=0.001). Opiate use was similar between groups (8.6%, 6.1%, P=0.763). Proton Pump Inhibitors (PPIs) were commonly used in both groups (82%, 77%, P=0.49), though more patients with DES underwent reflux testing on PPIs (P < 0.001). HRMs Among DES subjects, 75% underwent HRM as a prerequisite for GERD testing, and 14% had HRM to investigate dysphagia or chest pain. The presence of objectively diagnosed GERD did not differ among groups (47%, 56%, P=0.45). Normal HRM subjects more frequently had a positive symptom associated probability (42%, 21%, P=0.043). DES patients were not more likely to have hiatal hernias based on HRM, but when present, hernias were larger in size (2.5 cm, 1.8 cm, P=0.013). Conclusion: A clinical phenotype for DES, distinct from that of patients with normal HRM, could not be identified. DES often is found incidentally in patients undergoing HRM for pre-GERD testing, though DES patients do not have a higher prevalence of GERD. The lack of a clear clinical phenotype validates CC v4.0 recommendations to consider an HRM DES diagnosis only in the context of clinical presentation. Prospective studies should be performed to elucidate the pathophysiology and treatment targets for DES patients. Table 1. - DES vs normal HRM patient characteristics, symptoms, manometric and GERD testing findings Characteristics n (%)/mean (sd)/ (median [IQR]) DES Normal Motility N 99 66 EGD Performed 89 (89.9) 56 (84.8) pH Testing Performed 66 (66.7) 51 (77.3) 24-Hour Impedance Testing 58 (58.6) 47 (71.2) 48-Hour Testing 8 (8.1) 4 (6.1) Demographics P-value Age at Time of Manometry 57.83 (15.22) 52.18 (15.97)) 0.023 BMI 29.45 (6.46) 26.34 (5.86) 0.001 Sex Male 39 (39.4) 23 (34.8) 0.67 Race/Ethnicity 0.596 White (Non-Hispanic) 48 (49) 27 (41.5) Black (Non-Hispanic) 12 (12.2) 11 (16.9) Asian 3 (3.1) 4 (6.2) Other (Non-Hispanic) 14 (14.3) 12 (18.5) Hispanic 21 (21.4) 11 (16.9) Medical History History of Tobacco Use 40 (40.4) 19 (28.8) 0.174 History of Alcohol Use 53 (53.5) 33 (50.0) 0.775 Current PPI Use 82 (82.8) 51 (77.3) 0.494 Any Current Opioid Use 8 (8.2) 4 (6.1) 0.763 Diabetes 11 (11.1) 12 (18.5) 0.25 Connective tissue diseases 5 (5.1) 7 (10.6) 0.225 Reason HRM Performed 0.042 Dysphagia/Non-Cardiac Chest Pain Symptoms 14 (14.1) 8 (12.1) For GERD Testing 75 (75.8) 41 (62.1) Dysphagia/Non-Cardiac Chest Pain & GERD Testing 9 (9.1) 10 (15.2) Other: Dyspepsia, Sore Throat, Hiatal Hernia 1 (1) 5 (7.6 Pre-Lung Transplant 0 2 (3.0) Presenting Symptoms Abdominal pain 33 (33.3) 20 (30.3) 0.812 Chest pain 15 (15.2) 10 (15.2) 1 Choking 9 (9.1) 2 (3.0) 1 Cough 26 (26.3) 13 (19.7) 0.432 Dysphagia 38 (38.4) 21 (31.8) 0.486 Globus sensation 24 (24.2) 17 (25.8) 0.971 Heartburn 62 (62.6) 40 (60.6) 0.922 Nausea/vomiting 21 (21.2) 16 (24.2) 0.79 Regurgitation 36 (36.4) 25 (37.9) 0.974 GERD (LA Grade C, D, Barrett’s or +pH testing) 32 (47.1) 29 (55.8) 0.446 pH Testing Performed pH Testing Performed On PPI 45 (45.5) 15 (22.7) <0.001 Symptom Index > 50 15 (36.6) 21 (45.7) 0.523 Symptom Association Probability > 95 9 (20.5) 20 (41.7) 0.043 Manometry Findings Presence of Hiatal Hernia 86 (86.9) 55 (83.3) 0.685 Size of Hiatal Hernia (cm) 2.50 [1.52, 3.98] 1.80 [1.15, 2.75] 0.013 LES Basal Pressure (mmHg) 26.75 (16.98) 24.00 (12.84) 0.264 Incomplete Bolus Clearance (%) 70.00 [40.00, 100.00] 30.00 [10.00, 60.00] < 0.001 Mean Distal Contractile Integral 1503.45 (1049.14) 1525.72 (868.29) 0.888