Study On Esophageal Motility And Anti-reflux Barrier Function In Patients With Heartburn Symptom And Negative Endoscopic Findings Based On Rome ? Criteria

Objective:To investigate the classification of heartburn phenotypes with negative upper endoscopy based on Rome IV diagnostic criteria and to explore more effective diagnostic procedures and improve classification methods.Moreover,the characteristics of esophageal motility and esophagogastric junction(EGJ)metrics as anti-reflux barrier were evaluated among non-erosive reflux disease(NERD),reflux hypersensitivity(RH),functional heartburn(FH)and unclassified.Methods:A retrospective study was performed among heartburn patients from 2011 to 2018 in a tertiary hospital.The 24-hour p H monitoring and PPI test were used to distinguish these phenotypes based on Rome IV criteria.Heartburn patients with negative endoscopy were classified into NERD group,RH group,FH group,and unclassified group.At the same time,20 healthy volunteers in the center were selected as normal control group.High-resolution manometry(HRM)metrics including EGJ parameters and peristalsis parameters were analyzed.Esophageal motility disorders according to the Chicago Classification version 3.0(CC v3.0)was also assessed.Results:1.According to the diagnostic procedure of this study,136 patients were finally enrolled based on the Rome IV diagnostic criteria,including 59 males and 77 females,aged(50.13±16.07)years old.Among them,35 patients with positive esophageal acid exposure time(AET)and pathological acid reflux were classified into the NERD group,43 patients with AET-negative,normal acid exposure but a positive symptom association probability(SAP)were classified into the reflux hypersensitivity group,48 patients with negative AET and SAP results but an ineffective response to PPI treatment were defined as FH,and 10 patients with negative AET and SAP but an effective response to PPI,who used to be defined as FH,were classified into unclassified group.2.No statistically significant differences were reached in gender,body mass and BMI among the NERD group,the reflux high-sensitivity group,the functional heartburn group,the unclassified group and the healthy controls(P>0.05).In terms of age,patients in the NERD group were significantly higher than that in the reflux hypersensitivity group(P<0.01).The age of NERD group,reflux hypersensitivity group,functional heartburn group and unclassified group were all higher than healthy control group,it showed that significant differences within the groups(P<0.01);However,significant differences were not observed in age among the NERD group,the functional heartburn group and the unclassified group(P>0.05).3.Based on Rome IV diagnostic criteria,the HRM parameters(including length of the lower esophageal sphincter(LES),End expiratory esophageal sphincter resting pressure(LESP),LESP respiratory mean,4 seconds integrated relaxation pressure(4s-IRP),distal contraction delay(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))had no significant differences among the NERD group,the reflux hypersensitivity group,the functional heartburn group and the unclassified group or compared with the control group(P>0.05).Distal contractile integral(DCI)were significant lower in the NERD group and the unclassified group than in the normal control group(P=0.01,0.03,P<0.05);The UESP of the unclassified group was significant lower than the normal control group(P=0.02).Additionally,significant differences in EGJ subtypes could be observed among the NERD group,the reflux hypersensitivity group,the functional heartburn group and the unclassified group(P=0.02).The unclassified patients had more hiatal hernias,followed by NERD group,which was significantly higher than that of RH group and FH group.4.There was no significant difference in the esophageal motility types among NERD group,reflux hypersensitivity group,functional heartburn group and unclassified group(P>0.05).5.Based on the Rome III diagnostic criteria: 88 patients with AET-positive,pathological acid reflux,an effective response to PPI treatment,high-sensitivity esophagus who were classified into NERD group,48 patients with AET and SAP results negative and an ineffective response to PPI who were defined as FH.No significant difference in EGJ-CI,esophageal motility types and EGJ morphology were observed between the NERD group and the functional heartburn group(P>0.05).Conclusion:1.For different phenotypes of heartburn patients with negative endoscopy,they should be definitely classified according to the effective diagnostic procedure,combined with HRM,24-hour p H monitoring and PPI test.The unclassified patients with negative endoscopy and p H results but an effective response to PPIs should be separated to have a further evaluation.2.However,monitoring the HRM parameters of LES and EGJ-CI have limited effect in distinguishing different heartburn phenotypes with negative endoscopy.