How to diagnose GERC more effectively: reflections on post-reflux swallow-induced peristaltic wave index and mean nocturnal baseline impedance.

INTRODUCTION: Post-reflux swallow-induced peristaltic wave index (PSPWI) and mean nocturnal baseline impedance (MNBI) are novel parameters reflect esophageal clearance capacity and mucosal integrity. They hold potential in aiding the recognition of gastroesophageal reflux-induced chronic cough (GERC). Our study aims to investigate their diagnostic value in GERC. METHODS: This study included patients suspected GERC. General information and relevant laboratory examinations were collected, and final diagnosis were determined following guidelines for chronic cough. The parameters of multichannel intraluminal impedance-pH monitoring (MII-pH) in patients were analyzed and compared to explore their diagnostic value in GERC. RESULTS: A total of 186 patients were enrolled in this study. The diagnostic value of PSPWI for GERC was significant, with the area under the working curve (AUC) of 0.757 and a cutoff value of 39.4%, which was not statistically different from that of acid exposure time (AET) (p > 0.05). The combined diagnostic value of AET > 4.4% and PSPWI < 39.4% was superior to using AET > 4.4% alone (p < 0.05). Additionally, MNBI and distal MNBI also contributed to the diagnosis of GERC, with AUC values of 0.639 and 0.624, respectively. AET > 4.4% or PSPWI < 39.4% is associated with a 44% reduction in missed diagnoses of non-acid GERC compared to AET > 6.0% or symptom association probability (SAP) ≥ 95%, and may be more favorable for identifying GERC. CONCLUSION: The diagnostic value of PSPWI for GERC is comparable to that of AET. Combining PSPWI < 39.4% or AET > 4.4% can improve the diagnostic efficiency by reducing the risk of missed diagnoses in cases where non-acid reflux is predominant. Distal MNBI and MNBI can serve as secondary reference indices in the diagnosis of GERC.

Effects of different ablation settings on lesion dimensions in an ex vivo swine heart model: Baseline impedance, irrigant, and electrode configuration.

INTRODUCTION: Intramural or epicardial locations of the arrhythmogenic substrate are regarded as one of the main reasons for radiofrequency (RF) catheter ablation failure. This study aims to conduct a comprehensive analysis of various factors including baseline impedance, irrigant and electrode configuration at similar ablation index (AI) value. METHODS: In 12 ex vivo swine hearts, RF ablation was performed at a target AI value of 500 and a multistep impedance load (100-180 Ω) in 4 settings: (1) conventional unipolar configuration with an irrigant of normal saline (NS); (2) conventional unipolar configuration with an irrigant of half normal saline (HNS); (3) bipolar configuration with an irrigant of NS; (4) sequential unipolar configuration with an irrigant of NS. The relationships between lesion dimensions and above factors were examined. RESULTS: Baseline impedance had a strong negative linear correlation with lesion dimensions at a certain AI. The correlation coefficient between baseline impedance and depth, width, and volume were R = -0.890, R = -0.755 and R = -0.813, respectively (p < .01). There were 10 (total: 10/100, 10%; bipolar: 10/25, 40%) transmural lesions during the whole procedure. Bipolar ablation resulted in significantly deeper lesion than other electrode configurations. Other comparisons in our experiment did not achieve statistical significance. CONCLUSION: There is a strong negative linear correlation between baseline impedance and lesion dimensions at a certain AI value. Baseline impedance has an influence on the overall lesion dimensions among irrigated fluid and ablation configurations. Over a threshold impedance of 150 Ω, the predictive accuracy of AI can be compromised.

Esophageal chemical clearance and mucosa integrity values in refractory gastroesophageal reflux disease patients with different esophageal dynamics.

OBJECTIVES: Esophageal post-reflux swallow-induced peristaltic wave index (PSPWI) and mean nocturnal baseline impedance (MNBI), novel impedance-based markers of reflux burden, are associated with esophageal dynamics. We aim to investigate the characteristics of PSPWI and MNBI in Chinese refractory gastroesophageal reflux disease (RGERD) patients with different esophageal dynamic changes. MATERIALS AND METHODS: 201 RGERD and 76 functional heartburn patients, undergone off-PPI endoscopy, esophageal manometry and impedance-pH monitoring, were included. Comparisons of conventional and novel impedance-pH metrics were made among different esophageal dynamics groups. Receiver operating-characteristic analyses were utilized to evaluate the diagnostic efficacy of PSPWI and MNBI in differentiating abnormal esophageal dynamics. Correlations were used to investigate their associated factors. RESULTS: PSPWI and MNBI of RGERD with esophagogastric junction (EGJ) injury and esophageal dysmotility were lower than EGJ injury alone or normal dynamics (p < 0.05 for both comparisons). PSPWI with esophageal peristalsis abnormality was lower than EGJ injury (p = 0.049), while MNBI showed no statistical difference. PSPWI, MNBI and their combination have auxiliary diagnostic values for esophageal peristalsis [area under the curves (AUCs): 0.683, 0.656, 0.708)] while only their combination for EGJ injury (AUC: 0.610). And they positively correlated with esophageal motility while negatively correlated with ineffective swallows and acid reflux events. CONCLUSIONS: PSPWI and MNBI, indicating impairment of esophageal chemical clearance and mucosa integrity, were lower in RGERD patients with multiple esophageal dynamic injuries than single injuries or normal dynamics. Moreover, they provided useful contributing information for potential dynamic injuries if manometry has already been found normal or marginal.

The Role of Mean Nocturnal Baseline Impedance and Post-Reflux Swallow-Induced Peristaltic Wave Index in the Diagnosis and Treatment of Gastroesophageal Reflux Disease.

BACKGROUND: As living standards improve, more and more people are becoming overweight or obese, which has led to a gradual increase in the incidence of gastroesophageal reflux disease (GERD). Esophageal multichannel intraluminal impedance pH monitoring is a technique widely used in the clinical diagnosis of GERD. Commonly used traditional impedance parameters include acid exposure time, number of reflux episodes, symptom association probability, and symptom index. Recently, mean nocturnal baseline impedance (MNBI) and post-reflux swallow-induced peristaltic wave (PSPW) index have been proposed as novel impedance parameters to evaluate esophageal mucosal integrity and esophageal chemical clearance, respectively. It was also pointed out that the MNBI and PSPW index can improve the diagnostic value of impedance pH monitoring and predict the treatment outcome of GERD. SUMMARY: MNBI and PSPW index are objective and reliable novel impedance parameters with high applicability and reproducibility, which are able to improve the diagnostic yield of impedance pH monitoring and predict treatment outcomes in GERD patients. KEY MESSAGES: In this paper, we mainly review the research progress of the MNBI and the PSPW index in the diagnosis and treatment of GERD.

Novel Diagnostic Techniques in the Evaluation of Gastroesophageal Reflux Disease (GERD).

In our present clinical paradigm, patient symptoms and presentation in the setting of traditional findings from endoscopy (erosive esophagitis, Barrett's esophagus, reflux-mediated stenosis), esophageal high-resolution manometry, and/or ambulatory reflux monitoring (distal esophageal acid exposure time, numbers of reflux events, reflux-symptom association) guide the care of patients with suspected GERD. However, novel metrics and techniques acquired from or performed at endoscopy, manometry, or pH-impedance monitoring, beyond conventional evaluation, are of great interest to the gastroenterology community given the frequent (and sometimes challenging) presentation of suspected GERD. These novel and evolving diagnostic approaches have the potential to enhance the evaluation of these patients and optimize their management. In this invited review, we discuss the present evidence and potential clinical utility of selected GERD metrics and techniques of interest at endoscopy (dilated intercellular spaces, mucosal impedance), manometry (contractile integral, impedance analysis, straight leg raise, multiple rapid swallow maneuvers), and reflux monitoring (mean nocturnal baseline impedance, post-reflux swallow-induced peristaltic wave indices), and how these tools may be most optimally adopted and utilized for clinical care (Fig. 1).

Evaluation of lesion characteristics and baseline impedance on high-power short-duration radiofrequency catheter ablation using computer simulation.

Myocardium baseline impedance (BI) is an important factor in ablation effectiveness. This study examined the performance of low-power and long-duration (LPLD), high-power and short-duration (HPSD) ablation at different BIs by computer simulation. A 3D model of the ablation region was constructed for simulation, and in vitro experiments were performed to validate the simulation. Three ablation power and duration configurations of 30 W/30 s, 50 W/10 s, and 90 W/5 s were used for simulation with BI values of 90, 100, 110, 120, 130, and 140 Ω. Roll-off time and ablation volume were measured to evaluate ablation results. The simulation is consistent with the in vitro experiments. When BI is changed from 90 [Formula: see text] to 140 [Formula: see text], the lesion volume over 50 °C with BI of 140 [Formula: see text] was reduced by 6.3%, 6.7%, and 7.3% for 30 W/30 s, 50 W/10 s, and 90 W/5 s configurations, respectively, and the lesion volume over 100 °C was reduced by 62.8%, 49.7%, and 22.5% under 30 W/30 s, 50 W/10 s, and 90 W/5 s, respectively. Simulation results revealed that HPSD (vHPSD) and LPLD ablation were more affected by changes in BI in the lesion volumes over 50 °C and 100 °C, respectively, and demonstrated that resistive and conductive heating were the main heating effects in HPSD (vHPSD) and LPLD, respectively.

Impact of baseline impedance of pulmonary vein antrum on success of catheter ablation for paroxysmal atrial fibrillation guided by ablation index.

OBJECTIVE: Ablation index (AI) is an effective ablation quality marker. Impedance is also an important factor for lesion formation. The present study evaluated the influence of the baseline impedance in the effect of ablation for atrial fibrillation (AF) guided by AI. METHODS: This was a retrospective study. 101 patients with paroxysmal AF (PAF) were enrolled. All patients underwent radiofrequency ablation guided by the same AI strategy. The ablation strategy was pulmonary vein (PV) isolation with non-PV triggers ablation. The baseline impedance of the ablation points was recorded. The patients were followed up every 3 months or so. RESULTS: During a median follow-up of 12 (4-14) months, freedom from AF/atrial tachycardia recurrence were 82.2%. No difference existed in baseline characteristics between the success group and the recurrence group. The average baseline impedance was 124.3 ± 9.7 Ω. The baseline impedance of the ablation points in success group was lower compared to the recurrence group (122.9 ± 9.4 vs. 130.5 ± 8.8 Ω, P < 0.01). The ratio of impedance drop in the success group was higher than the recurrence group ([8.8 ± 1.4]% vs. [8.1 ± 1.2]%, P = 0.03). Multivariate analysis revealed that baseline impedance, PAF duration and AI were the independent predictors of AF recurrence. The cumulative free of recurrence rate of low-impedance group (≤ 124 Ω, n = 54) was higher than that of high-impedance group. CONCLUSION: Baseline impedance correlates with clinical outcome of radiofrequency ablation for PAF guided by AI. Higher impedance in the same AI strategy may result in an ineffective lesion which probably causes recurrence.

Evaluation of Gastroesophageal Reflux Disease 1 Year after Esophageal Atresia Repair: Paradigms Lost from a Single Snapshot?

OBJECTIVE: To analyze the findings of both multichannel intraluminal impedance with pH (MII-pH) and endoscopy/histopathology in children with esophageal atresia at age 1 year, according to current recommendations for the evaluation of gastroesophageal reflux disease (GERD) in esophageal atresia. STUDY DESIGN: We retrospectively reviewed both MII-pH and endoscopy/histopathology performed in 1-year-old children with esophageal atresia who were followed up in accordance with international recommendations. Demographic data and clinical characteristics were also reviewed to investigate factors associated with abnormal GERD investigations. RESULTS: In our study cohort of 48 children with esophageal atresia, microscopic esophagitis was found in 33 (69%) and pathological esophageal acid exposure on MII-pH was detected in 12 (25%). Among baseline variables, only the presence of long-gap esophageal atresia was associated with abnormal MII-pH. Distal baseline impedance was significantly lower in patients with microscopic esophagitis, and it showed a very good diagnostic performance in predicting histological changes. CONCLUSIONS: Histological esophagitis is highly prevalent at 1 year after esophageal atresia repair, but our results do not support a definitive causative role of acid-induced GERD. Instead, they support the hypothesis that chronic stasis in the dysmotile esophagus might lead to histological changes. MII-pH may be a helpful tool in selecting patients who need closer endoscopic surveillance and/or benefit from acid suppression.

Mean Nocturnal Baseline Impedance Correlates With Symptom Outcome When Acid Exposure Time Is Inconclusive on Esophageal Reflux Monitoring.

BACKGROUND & AIMS: Abnormal acid exposure time (AET) is associated with good outcomes of symptoms from antireflux therapy. Low esophageal mean nocturnal baseline impedance (MNBI) is an additional marker of reflux disease. We aimed to evaluate the value of MNBI when analysis of AET produces borderline or inconclusive results. METHODS: We studied a retrospective cohort of 371 patients (mean age, 54.5 ± 0.7 y; 60.0% female) who had persistent reflux symptoms after treatment and underwent ambulatory pH-impedance monitoring off antisecretory therapy at 1 tertiary center in Europe or 1 in the United States. Total AET was determined from pH impedance studies (pathologic, >6%; physiologic, <4%; borderline or inconclusive, 4%-6%). Baseline impedance values were calculated at the 5-cm impedance channel at 3 nocturnal 10-minute periods and averaged to yield MNBI (abnormal, <2292 ohms). The primary outcome was response to antireflux therapy, defined as global symptom improvement of 50% or greater on patients' answers on standardized visual analog scales. RESULTS: Among the 371 patients, 107 (28.8%) had pathologic AET and 234 (63.1%) had abnormal MNBI. Low MNBI was concordant in 99.1% of patients with pathologic AET, in 91.2% with borderline AET, and in 33.7% with physiologic AET. During 38.7 ± 0.8 months of follow-up evaluation, 43.0% of patients had improved symptoms with medical therapy and 76.2% had improved symptoms with surgical antireflux therapy (P < .0001). When MNBI was low, response to medical therapy did not differ significantly between patients with borderline AET and patients with pathologic AET (P = .44), but did differ significantly when each group was compared with patients with physiologic AET, regardless of whether MNBI was normal or low (P < .0001 for each comparison). CONCLUSIONS: When low, MNBI identifies patients with pathologic and borderline AET who respond to antireflux therapy. MNBI analysis complements AET in defining esophageal reflux burden. MNBI correlates with response of symptoms to antireflux therapy.

A study of proximal esophageal baseline impedance in identifying and predicting laryngopharyngeal reflux.

BACKGROUND AND AIM: Laryngopharyngeal reflux (LPR) is caused by the reflux of gastric contents beyond the esophagus into the larynx and pharynx. However, upper esophageal sphincter (UES) motility and proximal esophagus reflux parameters are poorly studied. This study aims to explore the characteristics of UES motility and reflux parameter among LPR patients. METHODS: Patients with laryngopharyngeal symptoms only (L), patients with laryngopharyngeal symptoms and typical esophageal symptoms (L + E), patients with typical esophageal symptoms only (E), and healthy controls (H) were retrospectively included. Physiological profiles were studied and compared among groups using both high-resolution manometry and pH-impedance monitoring, including UES basal pressure, residual pressure, relaxation duration time, recovery time, the time to nadir pressure, UES length, proximal contractile integral, and proximal mean nocturnal baseline impedance (MNBI). Patients' symptom outcomes were also analyzed. RESULTS: A total of 242 patients were included. Proximal MNBI was significantly lower in patients with both laryngopharyngeal and esophageal symptoms (17 cm above low esophageal sphincter [LES]: L vs L + E vs E vs H = 3689.7 vs 2500.0 vs 3073.0 vs 3996.0; 15 cm above LES: L vs L + E vs E vs H = 3155.9 vs 2553.4 vs 3198.9 vs 2985.2; P < 0.001). Patients responded to proton pump inhibitor treatment also had lower proximal MNBI than those who did not (17 cm above LES: 1834.0 vs 3500.0; 15 cm above LES: 1946.5 vs 3432.6; P < 0.001). CONCLUSION: Decreased proximal MNBI can not only identify LPR patients but also predict patients' symptom outcomes.

Esophageal contractile segment impedance from high-resolution impedance manometry correlates with mean nocturnal baseline impedance and acid exposure time from 24-hour pH-impedance monitoring.

Esophageal baseline impedance (BI) acquired during esophageal contraction (contractile segment impedance [CSI]) is proposed to improve BI accuracy in gastroesophageal reflux disease (GERD). We evaluated associations between CSI and conventional and novel GERD metrics. We analyzed high-resolution impedance manometry (HRIM) and ambulatory pH-impedance studies from 51 patients (58.6 ± 1.5 years; 26% F) with GERD symptoms studied off antisecretory therapy. Patients with achalasia or absent contractility were excluded. CSI (averaged across 10 swallows) and BI-HRIM (from the resting landmark phase) were acquired from the distal impedance sensors (distal sensor and 5 cm above the lower esophageal sphincter). Acid exposure time (AET) and mean nocturnal baseline impedance (MNBI) were calculated. Associations between CSI, BI-HRIM, MNBI, and AET were evaluated using correlation (Pearson) and receiver operating characteristic (ROC) analysis. Presenting symptoms included heartburn (67%), regurgitation (12%), cough (12%), and chest pain (10%). CSI-distal and CSI-5 each correlated with BI-HRIM, AET, and distal MNBI. Associations with AET were numerically stronger for CSI-distal (r = -0.46) and BI-HRIM-distal (r = -0.44) than CSI-5 (r = -0.33), BI-HRIM-5 (r = -0.28), or distal MNBI (r < -0.36). When compared to AET <4%, patients with AET >6% had significantly lower CSI-distal and BI-HRIM-distal values but not CSI-5, BI-HRIM-5, or MNBI. ROC areas under the curve for AET >6% were numerically higher for CSI-distal (0.81) than BI-HRIM-distal (0.77), distal MNBI (0.68-0.75), CSI-5 (0.68), or BI-HRIM-5 (0.68). CSI from HRIM studies inversely correlates with pathologic AET and has potential to augment the evaluation of GERD.

Is There a Role for pH Impedance Monitoring in Identifying Eosinophilic Esophagitis in Children with Esophageal Atresia?

OBJECTIVES: To evaluate clinical, endoscopic, and pH-impedance measures in a cohort of children with esophageal atresia and concomitant eosinophilic esophagitis (EoE) and compared it with disease-matched controls, to identify predictive factors for the development of EoE and esophageal stricture. STUDY DESIGN: We reviewed 63 patients with esophageal atresia assessed for refractory upper gastrointestinal symptoms between January 2015 and September 2017 at 2 tertiary referral centers. All patients underwent upper gastrointestinal endoscopy and pH-impedance monitoring. Based on esophageal histology, patients were classified as (1) esophageal atresia without evidence of esophagitis; (2) esophageal atresia with evidence of esophagitis (including esophageal eosinophilia not meeting the criteria for EoE); (3) esophageal atresia with concomitant EoE. Age and sex matched patients with gastroesophageal reflux disease were used as disease controls. RESULTS: The presence of atopy and peripheral eosinophilia at baseline were significantly associated with EoE (P < .05). Although there was a tendency toward an increased number of strictures in patients with esophageal atresia-EoE, this did not reach statistical significance (P = .06). Higher esophageal acid exposure time and lower baseline impedance values were significantly associated with eosinophilic infiltration (P < .05 and P < .01, respectively). Using logistic regression analysis, the presence of mucosal eosinophilia was the most predictive factor for stricture formation (P < .05). CONCLUSIONS: A history of atopy and the presence of peripheral eosinophilia in patients with esophageal atresia are predictive factors for the development of EoE, which in turn is a predictive factor for stricture occurrence. Higher esophageal acid exposure time and lower baseline impedance are associated with esophageal eosinophilic infiltration, suggesting their value in selecting which patients with esophageal atresia should undergo endoscopic examination.

Convenient Method of Measuring Baseline Impedance for Distinguishing Patients with Functional Heartburn from those with Proton Pump Inhibitor-Resistant Endoscopic Negative Reflux Disease.

BACKGROUND: Combined 24-h intraesophageal pH-multichannel intraluminal impedance (24MII-pH) used for assessing gastroesophageal reflux disease by measuring baseline impedance (BI) requires a 24-h measuring period. In the present study, we developed a quick method of measuring BI and evaluated its usefulness in classifying patients with proton pump inhibitor (PPI)-refractory non-erosive reflux diseases (NERD) as having functional heartburn (FH) or endoscopic-negative reflux disease (ENRD). METHODS: Ninety-one NERD patients without esophageal motility disorder underwent 24MII-pH monitoring while on a PPI. The measurements of the mean nocturnal BI (MNBI) and short MNBI were assessed at 3 times (at about 1: 00, 2: 00, and 3: 00 am) for 10 min and 30 s respectively. The measurement of the simple mean BI (MBI) was performed once 30 s at about 11: 00 am. RESULTS: Ninety-one patients were divided into 2 groups: 59 with ENRD and 32 with FH. The cutoff, specificity, and sensitivity for distinguishing patients with FH were as follows: MNBI, 2,874.1 Ω, 72%, and 72%; short MNBI, 2,857.6 Ω, 74%, and 84%; and simple MBI, 2,874.1 Ω, 86%, and 78% respectively. CONCLUSION: Measuring the simple MBI is a quick method and is useful for distinguishing patients with FH from those in a cohort with PPI-refractory NERD.

The assessment of the esophageal motility of children with esophageal disorders by the detailed observation of the pH-multichannel intraluminal impedance waveform and baseline impedance: screening test potential.

BACKGROUND: The present study aimed to evaluate whether the detailed observation of pH/MII waveforms and the analysis of baseline impedance (BI) values could detect esophageal dysmotility in pediatric patients with esophageal disorders. PATIENTS AND METHODS: Eleven patients with congenital esophageal disorder in whom pH/MII was conducted from April 2011 to June 2015, were enrolled in this study. The diagnoses of the patients were as follows: postoperative esophageal atresia (EA), n = 6; esophageal achalasia (EAch), n = 4; and congenital esophageal stenosis (CES), n = 1. The characteristics of the pH/MII waveform, pathological GERD, BI value, and the average BI value of the 2 distal channels (distal BI; DBI) were analyzed in each disorder. RESULTS: Two EA (33%) patients and one EAch (25%) patient were diagnosed with GERD. The mean DBI values of the EA, EAch and CES patients was 912 ± 550, 2153 ± 915 and 1392 Ω, respectively. The EA patients showed consistently low DBI values. One CES patient and two infantile EAch patients showed postprandial prolonged low DBI values. Whereas, the pH/MII waveforms of the adolescent EAch patients were difficult to interpret due to their extremely low BI values. CONCLUSIONS: The present study demonstrated that the detailed observation of the pH/MII waveforms in all channels and the analysis of BI were useful for evaluating esophageal motility in children with congenital esophageal disorders. In particular, infantile patients with EAch showed DBI findings that were distinct from those of adult EAch patients. Considering the difficulty of performing esophageal manometry in young children, the detailed observation of the pH/MII waveform may help in the diagnosis of esophageal dysmotility in children.

Analyses of the relationship between a 'number of reflux episodes' exceeding 70 and the pH index in neurologically impaired children by evaluating esophageal combined pH-multichannel intraluminal impedance measurements.

BACKGROUND: The present study aimed to evaluate the characteristics associated with a number of reflux episodes (NoRE) of 70 by comparing the clinical and multichannel intraluminal impedance pH measurements (pH/MII) and pH index (pHI) in neurologically impaired (NI) children. PATIENTS AND METHODS: NI children (1-16 years of age) in whom pH/MII had been measured for GERD study were enrolled in this study. All children were divided into NoRE >70 or ≤70 and pHI >4.0 or ≤4.0, >5.0 or ≤5.0 or >7.0 or ≤7.0. In addition, the NI children with pHI >4.0, >5.0 and >7.0 were subdivided into NoRE >70 and ≤70 groups. The clinical and pH/MII measurements were compared between each of the two groups. The cutoff values of pHI and baseline impedance (BI) (Z6) were calculated to discriminate NoRE >70 and ≤70. RESULTS: A total of 61 NI children were enrolled in this study. There was a significant difference in the acid-related parameters, the NoRE (nonacid) and BI between NoRE >70 and ≤70, acid-related parameters and BI between pHI >4.0 and ≤4.0, >5.0 and ≤5.0 and >7.0 and ≤7.0 groups. Furthermore, a significant difference was still observed in the BI between NoRE >70 and ≤70 groups among patients with pHI >4.0, >5.0 or >7.0. The cutoff values of pHI and BI (Z6) for discriminating NoRE >70 and ≤70 were 9.2 and 1049Ω, respectively. CONCLUSION: The present study indicates that NoRE 70 corresponds to GERD in which patients suffer severe acid exposure with pH of around 9% and esophageal mucosal damage with low BI value in NI children.

Evaluation of Esophageal Mucosal Integrity in Patients with Gastroesophageal Reflux Disease.

BACKGROUND: Impaired esophageal mucosal integrity plays a role in causing symptoms of gastroesophageal reflux disease (GERD). Recently, the assessment of esophageal baseline impedance (BI) using the multichannel intraluminal impedance-pH (MII-pH) test was suggested as a surrogate technique for the study of esophageal mucosal integrity and was reported to be useful in distinguishing GERD from non-GERD. However, measuring BI requires a 24-h testing period, is complicated, and causes considerable patient discomfort. SUMMARY: Recently, endoscopy-guided catheters that can measure mucosal impedance (MI) and mucosal admittance (MA), which is the inverse of impedance, were developed, and their usefulness in measuring MI and MA for the diagnosis of GERD has been reported. In these studies, esophageal MI values were significantly lower in patients with GERD than in those without GERD. In contrast, esophageal MA was significantly higher in patients with GERD than in those without. Furthermore, we reported that MA is inversely correlated with BI and correlated with acid exposure time. Key Messages: Endoscopy-guided real-time measurement of MI and MA may allow the estimation of mucosal integrity and may be a useful diagnostic tool for patients with GERD in a manner similar to 24-h MII-pH monitoring.

Esophageal mucosal integrity improves after laparoscopic antireflux surgery in children with gastroesophageal reflux disease.

BACKGROUND: Esophageal intraluminal baseline impedance reflects the conductivity of the esophageal mucosa and may be an instrument for in vivo evaluation of mucosal integrity in children with gastroesophageal reflux disease (GERD). Laparoscopic antireflux surgery (LARS) is a well-established treatment option for children with proton pump inhibitory (PPI) therapy resistant GERD. The effect of LARS in children on baseline impedance has not been studied in detail. The aim of this study was to evaluate the effect of LARS on baseline impedance in children with GERD. METHODS: This is a prospective, multicenter, nationwide cohort study (Dutch national trial registry: NTR2934) including 25 patients [12 males, median age 6 (range 2-18) years] with PPI-resistant GERD scheduled to undergo LARS. Twenty-four hour multichannel intraluminal impedance pH monitoring (MII-pH monitoring) was performed before and 3 months after LARS. Baseline impedance was evaluated during consecutive 2-h intervals in the 24-h tracings. RESULTS: LARS reduced acid exposure time from 8.5 % (6.0-16.2 %) to 0.8 % (0.2-2.8 %), p < 0.001. Distal baseline impedance increased after LARS from 2445 Ω (1147-3277 Ω) to 3792 Ω (3087-4700 Ω), p < 0.001. Preoperative baseline impedance strongly correlated with acid exposure time (r -0.76, p < 0.001); however, no association between symptomatic outcome and baseline impedance was identified. CONCLUSIONS: LARS significantly increased baseline impedance likely reflecting recovery of mucosal integrity. As the change in baseline impedance was not associated with the clinical outcome of LARS, other factors besides mucosal integrity may contribute to symptom perception in children with GERD.

Impedance-pH Monitoring for Diagnosis of Reflux Disease: New Perspectives.

Heartburn is the most specific symptom of gastroesophageal reflux disease (GERD). In clinical practice, heartburn relief by a proton pump inhibitor (PPI) trial does suffice to confirm GERD. However, an objective diagnosis of GERD is required before anti-reflux endoscopic or surgical interventions, independently from PPI response. Thus, since normal findings at upper endoscopy are detected in the majority of patients with heartburn, reflux monitoring is often required. When traditional catheter-based or wireless pH tests are used, reflux episodes are conventionally identified by pH drops below 4.0 units. Combined impedance-pH monitoring has the advantage to provide a comprehensive assessment of both physical and chemical properties of refluxate and the distinction between acid and weakly acidic refluxes, both proven to cause heartburn. Unfortunately, the conventional impedance-pH parameters, namely acid exposure time and number of reflux events, are characterized by suboptimal diagnostic sensitivity, and the reliability of symptom-reflux association indexes remains questionable. Therefore, novel impedance parameters, namely the post-reflux swallow-induced peristaltic wave (PSPW) index and the mean nocturnal baseline impedance (MNBI), have recently been proposed in order to achieve a better diagnostic yield. In fact, they proved to be highly accurate in distinguishing reflux-related from reflux-unrelated heartburn, off- as well as on-PPI therapy. Currently, manual review of impedance-pH tracings is needed because of the modest accuracy of available software tools for automated analysis. PSPW index and MNBI are highly applicable and reproducible, and their calculation requires a few additional minutes during the manual review of impedance-pH tracings. So far, we believe that PSPW index and MNBI are ready for prime time and should become part of the standard analysis of impedance-pH tracings for GERD diagnosis in patients with endoscopy-negative heartburn.

Biomarkers of Reflux Disease.

Gastroesophageal reflux disease (GERD) encompasses an array of disorders unified by the reflux of gastric contents. Because there are many potential disease manifestations, esophageal and extraesophageal, there is no single biomarker of the entire disease spectrum; a set of GERD biomarkers that each quantifies specific aspects of GERD-related pathology might be needed. We review recent reports of biomarkers of GERD, specifically in relation to endoscopically negative esophageal disease and excluding conventional pH-impedance monitoring. We consider histopathologic biomarkers, baseline impedance, and serologic assays to determine that most markers are based on manifestations of impaired esophageal mucosal integrity, which is based on increased ionic and molecular permeability, and/or destruction of tight junctions. Impaired mucosal integrity quantified by baseline mucosal impedance, proteolytic fragments of junctional proteins, or histopathologic features has emerged as a promising GERD biomarker.

Analyses of the Post-reflux Swallow-induced Peristaltic Wave Index and Nocturnal Baseline Impedance Parameters Increase the Diagnostic Yield of Impedance-pH Monitoring of Patients With Reflux Disease.

BACKGROUND & AIMS: Analyses of impedance parameters such as the post-reflux swallow-induced peristaltic wave (PSPW) index and the mean nocturnal baseline impedance (MNBI) have been proposed to increase the accuracy of diagnosis of reflux disease. We assessed whether these improve the diagnostic yield of impedance pH monitoring of reflux disease. METHODS: We performed a prospective study of consecutive patients with proton pump inhibitor-responsive heartburn who underwent 24-hour impedance pH monitoring at hospitals in Italy from January 2011 through December 2013. Reviewers blindly analyzed off-therapy impedance pH tracings from 289 patients with proton pump inhibitor-responsive heartburn, 68 with erosive reflux disease and 221 with non-erosive reflux disease (NERD), along with 50 healthy individuals (controls). The PSPW index, the MNBI, the esophageal acid exposure time, the number of total refluxes, and the bolus exposure were calculated, as well as the symptom association probability (SAP) and the symptom index (SI). RESULTS: In receiver operating characteristic analysis, the area under curve of the PSPW index (0.977; 95% confidence interval, 0.961-0.993) was significantly greater than that of the other impedance pH parameters in identifying patients with reflux disease (P < .001). The PSPW index and the MNBI identified patients with erosive reflux disease with the highest level of sensitivity (100% and 91%, respectively), as well as the 118 pH-positive (99% and 86%) and 103 pH-negative (77% and 56%) cases of NERD. The PSPW index and the MNBI identified pH-negative NERD with the highest level of sensitivity; values were 82% and 52% for the 65 SAP-positive and/or SI-positive cases and 68% and 63% for the 38 SAP-negative and SI-negative cases. Diagnoses of NERD were confirmed by pH-only criteria, including those that were positive on the basis of the SAP or SI, for 165 of 221 cases (75%) and by impedance pH criteria for 216 of 221 cases (98%) (P = .001). CONCLUSIONS: The PSPW index and the MNBI increase the diagnostic yield of impedance pH monitoring of patients with reflux disease. Analysis of impedance pH data by calculating the PSPW index and the MNBI can increase the accuracy of diagnosis of patients with reflux disease, compared with pH-only data.