The Study On The Novel Impedance Metrics In Gastroesophageal Reflux Disease Patients With Different Esophageal Dynamic Changes

Background and AimGastroesophageal reflux disease(GERD)has become a common chronic gastrointestinal disease,of which refractory patients bear a huge economic burden.Currently,proton pump inhibitors(PPIs)are the best choice for GERD treatment.However,there are many patients who have persistent symptoms after standard PPIs treatment and the effects are not satisfying after at least 12 weeks of double-dose PPIs,which is called refractory GERD(RGERD).Through esophageal high-resolution manometry(HRM),a test of esophageal dynamics,RGERD patients can be classified into different esophageal dynamic characteristics,such as esophagogastric junction(EGJ)barrier injury and abnormal esophageal body peristalsis.These changes were demonstrated to be correlated with the increase of esophageal acid load and the continuous reflux symptoms.Two new esophageal p H impedance parameters,postreflux swallow-induced peristaltic wave index(PSPWI)and mean nocturnal baseline impedance(MNBI)can be used to predict esophageal chemical clearance and esophageal mucosal integrity,respectively.PSPWI and MNBI also play an important role in the diagnosis and differential diagnosis of GERD and the prediction of therapeutic reactivity of PPIs.However,the characteristics of PSPWI and MNBI in RGERD patients with different esophageal dynamic changes need to be further studied.Therefore,this study aims to explore the characteristics of two esophageal novel impedance parameters,PSPWI and MNBI,in RGERD patients with EGJ barrier injury and/or esophageal body peristalsis disorder,and explore the auxiliary diagnostic value of PSPWI and MNBI in evaluating these two different esophageal dynamic abnormalities,and further reveal the potential factors related to them,so as to provide the basis for the pathogenesis and individual management of RGERD patients.MethodsIn this study,patients who were admitted to the Gastrointestinal Dynamic Center of the First Affiliated Hospital of Dalian Medical University from January 2019 to August 2022 and completed gastroscopy,esophageal HRM and 24-hour esophageal p H impedance monitoring were selected.According to strict inclusion and exclusion criteria,a total of 382 subjects were finally included,including 259 RGERD patients and 123 patients with functional heartburn(FH)matched for age and gender as the control group.According to HRM results,RGERD patients were divided into the following four subgroups,Group Ra,only EGJ barrier abnormality.Group Rb,only esophageal body peristalsis abnormality.Group Rc,both EGJ barrier and esophageal body peristalsis abnormality.Group Rd,normal EGJ barrier and esophageal body peristalsis.The differences of basic characteristics,esophageal HRM parameters and p H impedance metrics between RGERD group and FH group were compared.The differences of esophageal p H impedance parameters among the four subgroups Ra to Rd in the RGERD were further compared,especially the new esophageal impedance parameters,PSPWI and MNBI.Receiver operating characteristic(ROC)curve was used to analyze the auxiliary diagnostic value of PSPWI,MNBI and PSPWI combined with MNBI in evaluating EGJ barrier injury or abnormal esophageal peristalsis.Finally,Pearson correlation analysis was used to explore the factors associated with PSPWI and MNBI.Results1.Basic characteristics between RGERD group and FH group were compared.It showed no statistical significance in age,gender and body mass index(BMI)between the two groups(all P>0.05).The proportion of RGERD patients with typical symptoms(including acid reflux and heartburn)was higher than that of FH patients(P=0.024).2.The esophageal HRM metrics of RGERD group and FH group were compared.The number of ineffective swallows in RGERD group was higher than that in FH group(P=0.015),while esophageal distal contractile integral(DCI),lower esophageal sphincter(LES)pressure and length,and EGJ contractile integral(EGJ-CI)were significantly lower than those in FH group(P<0.05).Patients with ineffective esophageal motility(IEM)accounted for 24.3% in RGERD and 15.4% in FH(P =0.048).There was no significant difference in the proportion of patients with type III EGJ morphology between the two groups3.The esophageal p H impedance parameters between RGERD group and FH group were compared.The acid exposure time(AET),long-term reflux episodes,De Meester score and bolus exposure time(BET)of RGERD were higher than those in FH group(P <0.001 in all comparisons).In terms of reflux episodes type,the weak acid,acid,mixed,liquid and total reflux episoes in RGERD group were higher than those in FH group(P <0.001 in all comparisons),but there was no statistical significance in nonacid reflux(P =0.725).The proportion of patients with positive reflux symptom association was higher in RGERD than in FH(P <0.001).In addition,PSPWI and MNBI in RGERD group were lower than those in FH group(P=0.045,P <0.001).4.Basic characteristics among four subgroups of RGERD were compared.There were no statistically significant differences in age,gender and BMI among the four subgroups(all P>0.05).The proportion of patients with typical symptoms had no statistical significance(P=0.082).5.The esophageal p H impedance parameters of the four subgroups were compared.There were significant differences in AET,long-term reflux episodes,De Meester score,acid reflux,PSPWI and MNBI among the four subgroups(P=0.008,P=0.011,P=0.020,P=0.016,P<0.001,P=0.002).There was no significant difference between BET,other reflux types and positive symptoms association among the four subgroups.The different esophageal p H impedance parameters of the four subgroups were compared in pairs.The AET and De Meester scores in Group Rc were higher than that in Group Rd(P=0.0039,P=0.0103).The number of long-term reflux episodes in Group Ra to Rc was higher than that in Group Rd(P<0.0001).The number of acid reflux was higher in Group Ra than in Group Rb(P=0.0186).PSPWI in Group Rc was lower than that in Group Ra(P<0.0001)and Group Rd(P<0.0001),and PSPWI in Group Rb was lower than that in Group Ra(P=0.0471).MNBI in Group Rc was lower than that in Group Ra(P=0.0287)and Group Rd(P=0.0012).There was no statistical difference in the above indexes among the other groups.6.The diagnostic value of PSPWI and MNBI on esophageal dynamic changes was established by ROC curve.In terms of EGJ injury identification,the area under the curve(AUC)of PSPWI,MNBI and PSPWI combined with MNBI were 0.540,0.572 and 0.575,respectively.However,in terms of esophageal peristalsis abnormalities identification,the AUC of PSPWI,MNBI and PSPWI combined with MNBI were 0.707,0.641 and 0.724,respectively.The P values were all less than 0.05 except for the abnormal EGJ barrier identified by PSPWI.7.PSPWI and MNBI were correlated with some factors.PSPWI and MNBI were all positively correlated with DCI(all P < 0.05),but negatively correlated with age,IEM,ineffective swallow,AET,De Meester score and long-term reflux episodes(all P < 0.05), and there was no correlation with gender,LES pressure,LES length,EGJ-CI,weak acid reflux,non-acid reflux,liquid reflux,or typical symptoms.MNBI was negatively correlated with acid reflux,mixed reflux and total reflux episodes,BET,type III EGJ morphology and positive symptoms association(all P< 0.05),but not with BMI.PSPWI was negatively associated with BMI alone,but not with type III EGJ morphology,acid reflux,mixed reflux,and total reflux,BET,or positive symptoms association.In addition,there is a significant positive correlation between PSPWI and MNBI(P< 0.001).Conclusions1.EGJ barrier injury had a greater effect on reflux episodes and esophageal acid burden of RGERD patients,and combined with abnormal esophageal peristalsis could further increase the acid load.PSPWI and MNBI decreased more significantly in RGERD patients with multiple esophageal dynamic injuries than in patients with single injury or normal esophageal dynamics.PSPWI decreased more significantly in patients with esophageal body peristalsis disorder than in patients with EGJ barrier injury,but no such effect was observed in MNBI.2.When the relevant indicators of esophageal HRM in RGERD patients are normal or in a critical state,MNBI,PSPWI and MNBI combined with PSPWI provided valuable auxiliary information for evaluating potential esophageal motility disorders and EGJ barrier disorders,especially for esophageal body peristalsis disorders.The evaluating efficiency of combined indexes was higher than that of MNBI or PSPWI alone.3.In RGERD patients,MNBI and PSPWI were correlated with DCI,IEM,AET,ineffective swallow,De Meester score,long-term reflux episodes,etc.But the magnitude and direction of correlation were different.In addition,PSPWI and MNBI showed a significant positive correlation.