C. Prakash Gyawali, MD
Director, Neurogastroenterology Program
Director, Fellowship Training Program
Washington University School of Medicine in St. Louis
St. Louis, Missouri

Symptomatic gastroesophageal reflux disease (GERD) is estimated to affect 18% to 28% of the US population.1 An empirical trial of proton pump inhibitors (PPIs) is a common starting point. Endoscopy is performed when alarm symptoms (eg, dysphagia, anemia, weight loss) are present, or if symptoms do not improve with PPIs.2 Esophageal physiologic testing further evaluates persisting esophageal symptoms, especially if symptoms are atypical for reflux (eg, cough, hoarseness, globus, chest pain).3

Case Presentation

A 37-year-old man is referred with postprandial heartburn that worsened in the past year. Heartburn partially improved with omeprazole 40 mg before breakfast, without further benefit from a second dose before dinner. Intermittent dysphagia prompted an upper endoscopy, which was normal including biopsies. Cardiac work up was negative. The referral sought anti-reflux surgery as the next step.

Upon office evaluation, the patient reported daily retrosternal burning and tightness that worsened during periods of stress, and was temporarily relieved with antacids. A constant tightness of the throat (globus) during symptomatic periods was originally interpreted as dysphagia. He described anxiety and a past diagnosis of irritable bowel syndrome (IBS). Esophageal physiologic testing was planned.

Esophageal high-resolution manometry revealed 7 sequences with suboptimal contraction vigor (distal contractile integral <450 mm and 3 failed sequences, fulfilling the criteria for ineffective esophageal motility (IEM; Figure 1A).4 However, esophageal body contraction vigor intensified with multiple rapid swallows, a provocative test that evaluates esophageal peristaltic reserve (Figure 1B).5 The esophagogastric junction morphology was normal. The pH study, performed off PPIs for 10 days, revealed physiologic total acid exposure time (AET, 0.9%). There were 51 reflux episodes and 37 heartburn events, of which 21 correlated with reflux episodes (ie, occurred within 2 minutes of a reflux episode; Figure 2). Therefore, symptom association probability (SAP) was positive (SAP, 99%; P<0.001) and positive symptom index (56.8%), indicating a chance relationship between heartburn and reflux events, was less than 0.1%. A diagnosis of reflux hypersensitivity was made.6

Figure 1. Esophageal high-resolution manometry demonstrated ineffective esophageal motility with peristaltic reserve.
A) An example of an ineffective sequence (distal contractile integral 196 mm
B) Multiple rapid swallows demonstrating augmentation of contraction after this provocative test, indicating peristaltic reserve.
Figure 2. A section of the ambulatory pH study, showing 3 reflux episodes.
Two of these episodes are followed by symptom events (dashed line) when the patient pressed his event marker button on the pH recorder.
Images courtesy of C. Prakash Gyawali, MD.

These findings on esophageal physiologic testing directed management. With a normal AET, anti-reflux surgery was not appropriate, but daily PPI use was maintained since the patient reported partial benefit. Since multiple reflux episodes were identified, baclofen (a GABAB agonist that can reduce reflux episodes)7 was added. Finally, since reflux hypersensitivity was identified with background anxiety and IBS, venlafaxine was introduced as a sensory neuromodulator.6 The manometric conclusion of IEM with peristaltic reserve did not affect management, as this is a minor motor disorder.4 There was significant symptom improvement with this treatment; the patient was pleased with the outcome.


Ambulatory pH or pH-impedance monitoring off PPIs can establish or rule out significant esophageal reflux burden in unproven GERD. In patients with proven GERD (ie, prior erosive esophagitis, long-segment Barrett’s esophagus, prior abnormal pH or pH-impedance study), pH-impedance testing on maximal PPI therapy determines whether persisting symptoms are related to GERD. Using AET and symptom reflux association, the 2 parameters that predict symptom outcome,8 reflux burden can be phenotyped into good reflux evidence (elevated AET with or without positive SAP), reflux hypersensitivity (normal AET with positive SAP), and functional symptoms (normal AET, negative SAP), with implications for eventual management.9 Esophageal high-resolution manometry can evaluate for motor disorders that mimic reflux symptoms. A systematic approach that augments presenting symptoms and PPI response with parameters from esophageal physiologic tests therefore guides evaluation and management of reflux symptoms.


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