What is the next step in managing a patient with gastrosophageal reflux disease (GERD) who has normal upper endoscopy findings and persistent heartburn despite taking maximum dose pantoprazole (proton pump inhibitor) for several weeks?

Ambulatory pH Impedance Monitoring Off PPI

The most appropriate next step is ambulatory pH impedance monitoring (Option D), specifically prolonged wireless pH monitoring performed OFF PPI therapy after discontinuing the medication for 2-4 weeks. 1, 2

Rationale for This Recommendation

This patient has failed maximum-dose PPI therapy despite proper administration (30 minutes before meals) and has normal endoscopy findings. The AGA explicitly states that when troublesome heartburn does not respond adequately to a PPI trial and endoscopy shows no erosive reflux disease (Los Angeles B or greater) or long-segment Barrett's esophagus, clinicians must perform prolonged wireless pH monitoring off medication to confirm whether true GERD exists or if the patient has a functional esophageal disorder. 1, 2

Why Other Options Are Incorrect

Repeat Endoscopy (Option A)

• Repeating endoscopy is not indicated because the initial endoscopy was already normal 1
• Up to 80% of symptomatic GERD patients will not have objective reflux evidence on endoscopy 1
• Without new alarm symptoms or a change in clinical presentation, repeat endoscopy adds no diagnostic value

Barium Esophagogram (Option B)

• Barium studies are not part of the recommended diagnostic algorithm for PPI-refractory GERD 1, 2
• This test does not assess acid exposure or reflux-symptom correlation, which are critical for diagnosis in this scenario

Esophageal Manometry (Option C)

• Manometry is not the next appropriate step in this clinical scenario 1
• While manometry has a role in evaluating dysphagia or before antireflux surgery, it does not confirm or rule out GERD 3, 4

Specific Testing Protocol

Testing must be performed OFF PPI therapy:

• Discontinue PPI for 2-4 weeks before testing whenever possible 1, 2
• The preferred test is 96-hour wireless pH monitoring (Bravo capsule) if available, as it provides superior diagnostic accuracy by accounting for day-to-day variability 2, 5
• Alternative: 24-hour catheter-based pH-impedance monitoring if wireless monitoring is unavailable 1, 2

Interpretation and Next Steps

If Acid Exposure Time (AET) <4.0% on all days:

• The patient does NOT have GERD and likely has functional heartburn or reflux hypersensitivity 2
• PPI therapy should be discontinued 2
• Consider neuromodulators or behavioral interventions 1

If AET >4.0% on ≥1 day:

• This confirms true GERD 2
• Consider switching to a different PPI, escalating to twice-daily dosing, or adding adjunctive therapy personalized to the GERD phenotype 1, 2

Critical Pitfalls to Avoid

• Do not continue long-term PPI without establishing a definitive diagnosis when the patient fails to respond adequately 2
• Do not perform pH monitoring while ON PPI as the initial diagnostic test - testing must be done OFF PPI to establish whether GERD truly exists 2
• Do not empirically add H2-receptor antagonists or other adjunctive agents without objective confirmation of GERD 2
• Do not proceed to surgical intervention without proven GERD on objective testing 2

Supporting Evidence

Multimodality evaluation in PPI-refractory patients changes the diagnosis in 34.5% of cases and guides alternative therapies in 42% 6. Symptoms alone are not specific enough to guide therapy, as overlap diagnoses are frequent - 67% of eosinophilic esophagitis patients and 75% of gastroparesis patients had concomitant pathologic acid reflux 6. Objective evidence-driven therapy is essential in patients with persistent symptoms despite empiric PPI therapy. 6