Heartburn refractory to proton-pump inhibitors.

The most appropriate diagnostic and therapeutic approach to patients with heartburn that persists despite the use of proton-pump inhibitor (PPI) therapy currently is not known. In general, patients with heartburn refractory to PPIs may have more than one explanation for their persistent symptoms. These include uncontrolled esophageal acid exposure ("PPI failure") in a small subset of patients, as well as other potential etiologies in the majority of patients who have controlled esophageal acid exposure on PPI therapy ("PPI success"). Some potential explanations for persistent heartburn in this latter group include hypersensitivity to acid reflux, nonacidic or duodenogastric esophageal reflux, as well as functional heartburn. Patients who present with heartburn refractory to PPIs should be investigated further to determine the potential cause. We believe the diagnostic modality with the most clinical usefulness is 24-hour pH and multichannel intraluminal impedance monitoring with symptom index performed while the patient is on high-dose PPI therapy. This approach allows the patient to be properly categorized and also identifies a substantial proportion of patients who will have functional heartburn, a condition that should discourage the use of endoscopic or surgical therapies. Therapeutic options for patients with heartburn refractory to PPIs are limited and have not been thoroughly studied. As a result of the paucity of information, we favor a therapeutic approach based on the outcome of diagnostic testing.