Study on esophageal motility and anti-reflux barrier function in patients with heartburn symptom and negative endoscopic findings based on Rome IV criteria

Objective To evaluate esophageal motility and anti-reflux barrier function in patients with different phenotypes of heartburn and negative endoscopic findings based on the Rome Ⅳ criteria. Methods From March 2011 to November 2018, 136 patients with heartburn and negative endoscopic findings were retrospectively analyzed. The patients underwent high-resolution manometry (HRM), 24-hour pH monitoring and proton pump inhibitor (PPI) test and according to the Rome Ⅳ criteria and new diagnostic procedures, they were divided into non-erosive reflux disease (NERD) group, reflux hypersensitivity (RH) group, functional heartburn (FH) group and unclassified group. During the same period, 20 healthy volunteers were selected as healthy control group. The changes of esophageal motility and HRM were analyzed among different groups. Statistical analysis was performed using one-way analysis of variance, Kruskal-Wallis H test and chi-square test. Results According to Rome Ⅳ criteria, 35 patients were enrolled into the NERD group, 43 patients were enrolled into the RH group, 48 patients were included in the FH group, and 10 patients were enrolled into unclassified group. There were no significant differences between the NERD group, the RH group, the FH group, the unclassified group and healthy control group in the length of the lower esophageal sphincter (LES), end lower esophageal sphincter resting pressure (LESP), mean LESP, 4-second-integrated relaxation pressure (4 s-IRP), distal latency (DL) , upper esophageal sphincter residual pressure (UES-RP), upper esophageal sphincter relaxation time to nadir, upper esophageal sphincter (UES) recovery time and esophagogastric junction contractile integral (EGJ-CI, all P>0.05). The distal contractile integral (DCI) of NERD group and unclassified group were both lower than that of healthy control group (919.7 mmHg·s·cm (411.7, 1 417.9) mmHg·s·cm (1 mmHg=0.133 kPa), 535.6 mmHg·s·cm (321.4, 1 513.4) mmHg·s·cm vs. 1 322.1 mmHg·s·cm (841.6, 1 918.5) mmHg·s·cm), and the differences were statistically significant (Z=-2.62 and -2.20, P=0.01 and 0.03). The upper esophageal sphincter pressure (UESP) of the unclassified group was lower than that of the healthy control group(57.0 mmHg (31.3, 77.8) mmHg vs. 70.4 mmHg (49.4, 97.8) mmHg), and the difference was statistically significant (Z=-2.64, P=0.02). There was significant difference in esophagogastric junction (EGJ) subtypes between the NERD group, the RH group, the FH group and the unclassified group (χ2=10.85, P=0.02); the proportion of type Ⅲ patients was highest in unclassified group, followed by NERD group, which were both higher than those of RH group and FH group. There was no significant difference in the proportion of esophageal motility subtypes between NERD group, RH group, FH group and unclassified group (P>0.05). Conclusions Patients with different phenotypes of heartburn and negative endoscopy finding should be classified by efficient diagnostic procedure according to the Rome Ⅳ criteria combined with HRM, 24-hour pH monitoring and PPI test. The unclassified patients need further evaluation, especially for those with effective PPI test and negative pH monitoring. However, the evaluation of anti-reflux barrier function by the HRM parameters in patients with heartburn and negative endoscopic findings has certain limitations. Key words: Heartburn; Esophageal pH monitoring; Non-erosive reflux disease; Reflux hypersensitivity; Manometry; Rome Ⅳ