What is the best next step for a patient with a history of Gastroesophageal Reflux Disease (GERD) on maximum dose of Proton Pump Inhibitor (PPI) with mild improvement and a normal endoscopy?

Best Next Step: 24-Hour pH Monitoring Off PPI

The best next step is to perform prolonged wireless pH monitoring off PPI therapy (96-hour preferred if available, or 24-hour pH-impedance monitoring) to confirm whether true GERD exists or if this patient has a functional esophageal disorder. 1

Rationale for pH Monitoring

This patient has already completed endoscopy showing no erosive disease (no Los Angeles B or greater esophagitis, no Barrett's esophagus), and has only mild improvement on maximum-dose PPI therapy. According to the 2022 AGA guidelines, this clinical scenario mandates objective reflux testing to establish whether GERD truly exists before continuing long-term acid suppression. 1

Key principle: When symptoms do not respond adequately to PPI therapy AND endoscopy shows no erosive disease, you must perform prolonged wireless pH monitoring off medication to confirm and phenotype GERD or rule it out entirely. 1

Why Not the Other Options?

Why Not Add H2 Receptor Antagonist (Option D)?

• Adding an H2RA to PPI therapy has no evidence of improved efficacy and should NOT be done empirically. 2
• H2RAs are only appropriate as adjunctive therapy for specific phenotypes (e.g., nocturnal symptoms) AFTER GERD is objectively proven, not as empiric add-on therapy. 1
• The AGA explicitly states that adjunctive pharmacotherapy should be personalized to the GERD phenotype, not used empirically. 1

Why Not Nissen Fundoplication (Option B)?

• Surgical intervention requires proven GERD first. 1, 3
• The 2022 AGA guidelines state that laparoscopic fundoplication and magnetic sphincter augmentation are effective surgical options "in patients with proven GERD" in carefully selected patients. 1
• Proceeding to surgery without objective confirmation of pathological reflux would be inappropriate and potentially harmful.

Why Not Manometry First (Option C)?

• Manometry is not the immediate next step in this clinical scenario. 1
• Manometry becomes relevant AFTER pH monitoring confirms GERD, to evaluate esophageal motor function and localize the lower esophageal sphincter for proper pH probe placement. 2
• High-resolution manometry may be considered to evaluate for rumination syndrome or esophageal motor disorders in patients with normal acid exposure who have functional disorders. 1

The Diagnostic Algorithm

Step 1: Perform pH Monitoring Off PPI

• Discontinue PPI for 2-4 weeks before testing whenever possible. 1
• Preferred test: 96-hour wireless pH monitoring (Bravo capsule) if available, as it provides superior diagnostic accuracy. 1
• Alternative: 24-hour catheter-based pH-impedance monitoring if wireless monitoring unavailable or if expertise in frame-by-frame interpretation exists. 1

Step 2: Interpret Results Based on Acid Exposure Time (AET)

If AET <4.0% on all days (normal acid exposure): 1

• Patient does NOT have GERD and likely has functional heartburn or reflux hypersensitivity
• PPI should be weaned off unless symptoms clearly escalate off therapy
• Consider referral for cognitive behavioral therapy, hypnotherapy, or pharmacologic neuromodulation 1
• High-resolution manometry may be considered to evaluate for rumination syndrome or motor disorders 1

If AET >4.0% on ≥1 day (elevated acid exposure): 1

• Confirms true GERD
• Los Angeles B or greater esophagitis and/or ≥2 days with AET >6% strongly support GERD diagnosis 1
• Optimize PPI therapy: ensure proper timing (30-60 minutes before meals), consider switching to different PPI, or escalate to twice-daily dosing 1
• Consider adjunctive pharmacotherapy personalized to phenotype 1

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 empirically add H2RAs or other adjunctive agents without objective confirmation of GERD. 2
• Do NOT proceed to surgical intervention without proven GERD on objective testing. 1
• Do NOT perform pH monitoring while ON PPI as the initial diagnostic test in this scenario - testing should be done OFF PPI to establish the diagnosis. 1 (pH monitoring ON PPI is reserved for patients with already-proven GERD to determine mechanisms of persistent symptoms) 1

Additional Considerations

• Research shows that 25-42% of patients on once-daily PPI and 10-20% on twice-daily PPI have persistent symptoms. 4
• Studies demonstrate that most patients with refractory heartburn do not have acid reflux on objective testing. 5
• Normal acid exposure on 96-hour wireless study has an odds ratio of 10.0 for predicting successful PPI withdrawal. 1

Answer: A. 24h pH monitoring study (preferably 96-hour wireless pH monitoring off PPI therapy)