Optimal Wireless Reflux Monitoring Metrics to Predict Discontinuation of Proton Pump Inhibitor Therapy.

INTRODUCTION: Ambulatory reflux monitoring performed off proton pump inhibitor (PPI) is the gold standard diagnostic test for nonerosive gastroesophageal reflux disease (GERD). However, the diagnostic metrics and optimal duration of monitoring are not well defined. This study evaluated the performance of multiple metrics across distinct durations of wireless reflux monitoring off PPI against the ability to discontinue PPI therapy in patients with suboptimal PPI response. METHODS: This single-arm clinical trial performed over 4 years at 2 centers enrolled adults with troublesome GERD symptoms and inadequate response to > 8 weeks of PPI. Participants underwent 96-hour wireless pH monitoring off PPI. Primary outcome was whether the subject successfully discontinued PPI or resumed PPI within 3 weeks. RESULTS: Of 132 participants, 30% discontinued PPI. Among multiple metrics assessed, total acid exposure time (AET) of 4.0% performed best in predicting PPI discontinuation (odds ratio 2.9 [95% confidence interval 1.4, 6.4]; P = 0.006), with other thresholds of AET and DeMeester score performing comparably. AET was significantly higher on day 1 of monitoring compared with other days, and prognostic performance significantly declined when only assessing the first 48 hours of monitoring (area under the curve for 96 hours 0.63 vs area under the curve for 48 hours 0.57; P = 0.01). DISCUSSION: This clinical trial highlights the AET threshold of 4.0% as a high-performing prognostic marker of PPI discontinuation. 96 hours of monitoring performed better than 48 hours, in predicting ability to discontinue PPI. These data can inform current diagnostic approaches for patients with GERD symptoms who are unresponsive to PPI therapy.

Normal Values of High-resolution Manometry Parameters With Provocative Maneuvers.

BACKGROUND/AIMS: Incorporation of complementary and provocative test swallows to the high-resolution manometry (HRM) protocol offers potential to address limitations posed by HRM protocols that involve only a single swallow type. The aim of this study is to describe normal findings of a comprehensive HRM testing protocol performed on healthy asymptomatic volunteers. METHODS: Thirty healthy asymptomatic volunteers completed HRM with 5-mL liquid swallows in the supine position. They also completed 5-mL liquid swallows in the upright position, viscous swallows, solid test swallows, multiple rapid swallows, and a rapid drink challenge. HRM studies were analyzed via Chicago classification version 3.0. RESULTS: The median (5th-95th percentiles) for integrated relaxation pressure (IRP) on supine swallows was 11 (4-16) mmHg; IRP was lower than supine on upright liquid 9 (0-17) mmHg, viscous 6 (0-15) mmHg, solid 9 (1-19) mmHg, multiple rapid swallows 3 (0-12) mmHg, and rapid drink challenge 5 (-3-12) mmHg; P < 0.005. While an "elevated" IRP value was observed on 1 to 2 test maneuvers in 8/30 (27%) subjects, all 30 subjects had an IRP value < 12 mmHg on at least one of the test maneuvers. CONCLUSIONS: Normal values and findings from a comprehensive HRM testing protocol are reported based on evaluation of 30 healthy asymptomatic volunteers. Isolated "abnormalities" of IRP and contractile parameters were observed in the majority (80%) of these asymptomatic subjects, while all subjects also had normal features observed. Thus, the definition of "normal" should be recalibrated to focus on the entirety of the study and not individual metrics.

Ambulatory Reflux Monitoring Guides Proton Pump Inhibitor Discontinuation in Patients With Gastroesophageal Reflux Symptoms: A Clinical Trial.

BACKGROUND AND AIMS: Proton pump inhibitor (PPI) therapy fails to provide adequate symptom control in up to 50% of patients with gastroesophageal reflux symptoms. Although a proportion do not require ongoing PPI therapy, a diagnostic approach to identify candidates appropriate for PPI cessation is not available. This study aimed to examine the clinical utility of prolonged wireless reflux monitoring to predict the ability to discontinue PPIs. METHODS: This double-blinded clinical trial performed over 3 years at 2 centers enrolled adults with troublesome esophageal symptoms of heartburn, regurgitation, and/or chest pain and inadequate PPI response. Participants underwent prolonged wireless reflux monitoring (off PPIs for ≥7 days) and a 3-week PPI cessation intervention. Primary outcome was tolerance of PPI cessation (discontinued or resumed PPIs). Symptom burden was quantified using the Reflux Symptom Questionnaire electronic Diary (RESQ-eD). RESULTS: Of 128 enrolled, 100 participants met inclusion criteria (mean age, 48.6 years; 41 men). Thirty-four participants (34%) discontinued PPIs. The strongest predictor of PPI discontinuation was number of days with acid exposure time (AET) > 4.0% (odds ratio, 1.82; P < .001). Participants with 0 days of AET > 4.0% had a 10 times increased odds of discontinuing PPI than participants with 4 days of AET > 4.0%. Reduction in symptom burden was greater among the discontinued versus resumed PPI group (RESQ-eD, -43.7% vs -5.3%; P = .04). CONCLUSIONS: Among patients with typical reflux symptoms, inadequate PPI response, and absence of severe esophagitis, acid exposure on reflux monitoring predicted the ability to discontinue PPIs without symptom escalation. Upfront reflux monitoring off acid suppression can limit unnecessary PPI use and guide personalized management. (ClinicalTrials.gov, Number: NCT03202537).

Repetitive Antegrade Contractions: A novel response to sustained esophageal distension is modulated by cholinergic influence.

BACKGROUND & AIMS: A unique motor response to sustained esophageal distension, repetitive antegrade contractions (RACs), is observed using functional luminal imaging probe (FLIP) panometry. However, physiologic mechanisms related to this response are unexplored. This study aimed to evaluate the impact of cholinergic inhibition with atropine on the esophageal contractile response to sustained distention, including RACs, among healthy volunteers. METHODS: 8 asymptomatic volunteers (ages 22-45) were evaluated in a crossover study design with 16-cm FLIP positioned across the esophagogastric junction and distal esophagus during sedated upper endoscopy. The FLIP study involving stepwise volumetric distension was performed twice in each subject, at baseline and again after atropine (15 mcg/kg) was administered intravenously. FLIP panometry was analyzed to assess the contractile response to distension. RESULTS: Antegrade contractions, lumen-occluding contractions, and a RAC pattern were observed in 8/8, 8/8, and 7/8(88%) subjects, respectively, at baseline and in 5/8 (63%), 2/8 (25%) and 2/8 (25%) subjects after atropine. The rate of contractions in the RAC pattern was similar (6-7 contractions per minute) before and after atropine. Compared with the baseline study, distension-induced contractility was triggered at higher fill volumes after atropine. FLIP pressures were lower in response to volumetric filling after atropine than at baseline. CONCLUSIONS: The vigor and triggering of the esophageal contractile response to distension is reduced by cholinergic inhibition in asymptomatic controls. The observation that the rate of contractions did not change when patients developed repetitive contractile responses suggests that this rate is not modified by cholinergic inhibition once contractility is triggered.

Performing High-resolution Impedance Manometry After Endoscopy With Conscious Sedation Has Negligible Effects on Esophageal Motility Results.

Background/Aims: High-resolution manometry (HRM) performed without sedation is the standard procedure. However, some patients cannot tolerate transnasal placement of the manometry catheter. We aim to assess the practice of performing manometry after endoscopy with conscious sedation by evaluating its impact on esophageal motility findings. Methods: Twelve asymptomatic adult volunteers and 7 adult patients completed high-resolution impedance manometry (HRIM) approximately 1 hour after conscious sedation with midazolam and fentanyl (post-sedation) and again on a different day with no-sedation. The nosedation HRIM involved 2 series of swallows separated in time by 20 minutes (no-sedation-1 and no-sedation-2) for the volunteers; patients completed only 1 series of swallows for no-sedation HRM. Results: A motility diagnosis of normal motility was observed in all 12 volunteers post-sedation. Two volunteers had a diagnosis of borderline ineffective esophageal motility, one during the no-sedation-1 period and the other during the no-sedation-2 period; all of the other no-sedation HRIM studies yielded a normal motility diagnosis. Six of seven patients had the same diagnosis in both no-sedation and post-sedation HRM, including 1 distal esophageal spasm, 3 achalasia (2 type II and 1 type III), and 2 esophagogastric junction outflow obstruction. Only one patient's HRM classification changed from ineffective esophageal motility at no-sedation to normal esophageal motility at post-sedation. Conclusions: Performing HRIM after endoscopy with conscious sedation had minimal clinical impact on the motility diagnosis or motility parameters. Thus, this approach may be a viable alternative for patients who cannot tolerate unsedated catheter placement.