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Background: Acid exposure time (AET) is considered the most useful parameter to predict response of reflux-related heartburn to medical or surgical treatment. However, recent studies showed high rates of heartburn response to proton pump inhibitor (PPI) therapy in patients with normal AET. We aimed to compare the efficacy of postreflux swallow-induced peristaltic wave (PSPW) index and mean nocturnal baseline impedance (MNBI) with AET in linking PPI-responsive heartburn to reflux., Methods: Off-therapy impedance-pH tracings from 425 patients, 317 with PPI-responsive and 108 with PPI-refractory heartburn were blindly re-analyzed. Demographic and endoscopic characteristics, conventional impedance-pH variables, PSPW index, and MNBI were assessed with multivariate logistic regression to identify factors independently associated with PPI responsiveness. Prediction models were developed to assess the strength of reflux linkage with factors independently associated with PPI responsiveness by calculating the area under the curve (AUC) at receiver-operating-characteristic (ROC) analysis., Key Results: At multivariate logistic regression analysis, AET, MNBI, and PSPW index were the only factors independently associated with PPI responsiveness, abnormal values found in 60%, 76%, and 92% of PPI-responsive cases (P<.017). At ROC analysis, PSPW index (AUC:.794, P=.002) and MNBI (AUC: 0.742, P=.003), both separately and combined (AUC: 0.811, P<.001) linked reflux with PPI-responsiveness better than AET (AUC: 0.687)., Conclusions & Inferences: AET, PSPW index, and MNBI are independently associated with PPI-responsive heartburn. PSPW index and MNBI can link PPI-responsive heartburn to reflux better than AET and should become part of the standard analysis of impedance-pH tracings., (© 2017 John Wiley & Sons Ltd.)

Background: On-therapy impedance-pH monitoring in proton pump inhibitor (PPI)-refractory gastroesophageal reflux disease (GERD) yielded conflicting results. We aimed to assess the diagnostic value of postreflux swallow-induced peristaltic wave (PSPW) index and mean nocturnal baseline impedance (MNBI) in PPI-refractory heartburn., Methods: On-therapy impedance-pH tracings from 189 consecutive patients with PPI-refractory heartburn were blindly reviewed. Patients were subdivided into refractory reflux esophagitis (RRE), healed reflux esophagitis (HRE), non-erosive reflux disease (NERD), and functional heartburn (FH) according to endoscopic and conventional impedance-pH findings. The diagnostic accuracy of PSPW index and MNBI in separating NERD from FH was assessed with receiver-operating-characteristic (ROC) analysis. Objectively documented persistent reflux remission at 3-year follow-up in 53 patients who underwent laparoscopic fundoplication served to evaluate PSPW index and MNBI as independent predictors of PPI-refractory GERD confirmed by positive surgical outcome., Key Results: Median PSPW index and MNBI values were significantly lower in 39 RRE (16%; 1145 Ω) than in 41 HRE (25%; 1741 Ω) and in 68 NERD (29%; 2374 Ω) patients, and in all three GERD subgroups compared to 41 FH cases (67%; 3488 Ω) (P<.008). At ROC analysis, comparing NERD to FH the area under the curve was 0.886 with PSPW index and 0.677 with MNBI (P=.005). PSPW index was an independent predictor of PPI-refractory GERD (odds ratio 0.6983, P=.012)., Conclusions & Inferences: At on-therapy impedance-pH monitoring, PSPW index and MNBI efficiently distinguish PPI-refractory NERD from FH. The PSPW index represents an independent predictor of PPI-refractory GERD., (© 2016 John Wiley & Sons Ltd.)

Background: Multiple rapid swallowing (MRS) during high-resolution manometry (HRM) is increasingly utilized as provocative test to assess esophageal peristaltic reserve. The aim of this study was to evaluate the correlation between MRS response and impedance and pH (MII-pH) parameters in endoscopy negative heartburn (ENH) patients., Methods: We enrolled consecutive ENH patients, who underwent HRM and MII-pH study, with a selected MII-pH profile: abnormal MII-pH (pH+/MII+); normal MII-pH (pH-/MII-). HRM was performed with 10 wet swallows (WS) and one MRS. Mean distal contractile integral (DCI) during WS and MRS were calculated. MII-pH parameters including acid exposure time (AET), reflux events, baseline impedance levels (BI) and the efficacy of chemical clearance evaluated with the postreflux swallow-induced peristaltic wave (PSPW) index were measured., Key Results: We analyzed 103 patients: 49 MII+/pH+ (27 male), and 54 MII-/pH- (19 male). Mean age was similar between the two groups. As expected, mean AET and number of refluxes were higher in pH+/MII+ (p < 0.05). HRM was normal in all selected patients. Mean DCI-WS was similar between two groups (p = n.s.). Mean DCI-MRS- was higher in MII-/pH- vs MII+/pH+ (p < 0.05). The increase in DCI-MRS was inversely correlated with AET (-0.699; p < 0.001) and directly correlated with BI values (0.631; p < 0.001) and PSPW index (0.626; p < 0.001)., Conclusions & Inferences: Following MRS, patients with abnormal impedance-pH test showed suboptimal contraction response as compared with those with normal impedance-pH test. Moreover, MRS response was inversely correlated with AET and directly correlated with BI values and PSPW index., (© 2015 John Wiley & Sons Ltd.)

Background: Recently, it has been suggested that low esophageal basal impedance may reflect impaired mucosal integrity and increased acid sensitivity. We aimed to compare baseline impedance levels in patients with heartburn and pathophysiological characteristics related to functional heartburn (FH) divided into two groups on the basis of symptom relief after proton pump inhibitors (PPIs)., Methods: Patients with heartburn and negative endoscopy were treated with esomeprazole or pantoprazole 40 mg daily for 8 weeks. According to MII-pH (off therapy) analysis, patients with normal acid exposure time (AET), normal reflux number, and lack of association between symptoms and refluxes were selected; of whom 30 patients with a symptom relief higher than 50% after PPIs composed Group A, and 30 patients, matched for sex and age, without symptom relief composed Group B. A group of 20 healthy volunteers (HVs) was enrolled. For each patient and HV, we evaluated the baseline impedance levels at channel 3, during the overnight rest, at three different times., Key Results: Group A (vs Group B) showed an increase in the following parameters: mean AET (1.4 ± 0.8% vs 0.5 ± 0.6%), mean reflux number (30.4 ± 8.7 vs 24 ± 6.9), proximal reflux number (11.1 ± 5.2 vs 8.2 ± 3.6), acid reflux number (17.9 ± 6.1 vs 10.7 ± 6.9). Baseline impedance levels were lower in Group A than in Group B and in HVs (p < 0.001)., Conclusions & Inferences: Evaluating baseline impedance levels in patients with heartburn and normal AET could achieve a better understanding of pathophysiology in reflux disease patients, and could improve the distinction between FH and hypersensitive esophagus., (© 2014 John Wiley & Sons Ltd.)

Background: A short-course of proton pump inhibitors (PPIs) is often used to confirm gastroesophageal reflux disease (GERD). However, some patients with PPI responsive heartburn do not seem to have evidence of GERD on impedance-pH monitoring (MII-pH). The aim of the study was to evaluate patients with reflux symptoms and a negative endoscopy, who well respond to PPIs with MII-pH., Methods: We enrolled 312 patients with GERD symptoms and negative endoscopy: 144 reported well-controlled symptoms after 8-week PPIs and 155 were non-responders. Symptom relief was evaluated with GERD Impact Scale and visual analog scale score. All patients underwent MII-pH off-therapy. Thirteen patients were excluded from analysis. Patients were grouped as follows: non-erosive reflux disease (NERD; increased acid exposure time, AET); hypersensitive esophagus (HE; normal AET, positive symptom association, SI/SAP); MII-pH-/PPI+ (normal AET, negative SI/SAP) in the responder group; MII-pH-/PPI- in non-responders., Key Results: MII-pH in PPI responders (symptom relief during PPI therapy > 75%) showed: 79/144 NERD (54.9%); 37/144 HE (25.7%); 28/144 MII-pH-/PPI+ (19.4%). MII-pH-/PPI+ patients reported the same symptom relief when compared with NERD and HE. In non-responder (symptom relief during PPI therapy < 50%) group, 27/155 patients were NERD (17.4%); 53/155 were HE (34.2%); 75/155 were MII-pH-/PPI- (48.4%). NERD diagnosis was significantly higher in responder group (p < 0.01)., Conclusions & Inferences: In a substantial subgroup of patients responding to PPI with typical reflux symptoms, the diagnosis of GERD cannot be confirmed with pH-impedance monitoring. Proton pump inhibitor response and presence of typical symptoms are thus not reliable predictors of the diagnosis and antireflux surgery should always be preceded by reflux monitoring., (© 2013 John Wiley & Sons Ltd.)