A study published today in The New England Journal of Medicine found that in patients seen for heartburn unresponsive to treatment with proton pump inhibitors (PPIs), an extensive, systematic workup revealed truly PPI-refractory and reflux-related heartburn in only a minority of cases.

In other words, most patients with heartburn unrelieved by PPIs did not have gastroesophageal reflux disease (GERD) causing the symptom. Furthermore, for the selected subgroup identified as having reflux-related, PPI-refractory heartburn, surgery that corrects reflux was significantly superior (67% success rate) to continued medical therapy (28% success rate).

Study researchers, which include lead author Stuart Spechler, MD, Chief of Gastroenterology at Baylor University Medical Center in Dallas, and Rhonda Souza, MD, co-director (with Dr. Spechler) of Baylor Scott & White Research Institute’s Center for Esophageal Research, enrolled 366 patients to determine what was causing their heartburn, why they were still experiencing symptoms despite using PPIs, and what the best treatment option was for PPI-refractory heartburn. The study was sponsored by the VA Cooperative Studies Program.

One in five adults in the US have GERD, with the annual costs for managing the disease estimated to exceed $12 billion. Patients with heartburn, the cardinal symptom of GERD, report reduced work productivity and significant impairments in health-related quality of life.

PPIs are drugs that stop acid production in the stomach and are generally considered the best medical treatment for GERD. However, 30%-40% of people with symptoms assumed to be due to GERD still complain of heartburn and other GERD symptoms while taking PPIs, and little high-quality information has been available on why these symptoms persist despite treatment.

Researchers found that a majority of people who complain of persistent heartburn despite using PPIs actually do not have GERD causing their heartburn, but instead have a variety of other disorders that create a burning sensation in the chest indistinguishable from GERD-induced heartburn. The study utilized an extensive series of tests designed to look for non-GERD causes of heartburn, and to determine whether heartburn was associated with the reflux of stomach contents into the esophagus before pursuing surgical treatment options.

“Many people assume that if you have heartburn that means you have GERD, but that is just not true. Physicians considering recommending an operation to treat GERD should be sure that their patients really have GERD causing their heartburn, and that heartburn isn’t being caused by something completely different,” said Dr. Spechler. “Being sure requires a systematic evaluation with tests that include endoscopy, esophageal manometry (which tests for esophageal muscle disorders that can cause the sensation of heartburn), and esophageal impedance-pH monitoring (which detects episodes of reflux and their association with symptoms). These tests are necessary before resorting to surgery because if the heartburn isn’t caused by GERD, then the surgery won’t help and can only make things worse,” he added.

Of the 366 patients screened, only 78 could be positively identified as having heartburn that was GERD-related. Those patients underwent an anti-reflux surgical treatment that turned out to be significantly more effective than PPIs in addressing their heartburn.

“Our finding that you can choose PPI-refractory patients for surgery and predict a good outcome if they have the proper workup is a very important clinical finding, and it should direct how patients are referred to surgery for GERD,” said Dr. Spechler. “Before this study, furthermore, it was not at all clear that patients with heartburn due to non-acid reflux would respond well to an operation,” he added.

Spechler points out an additional finding ­of interest—42 of the 366 patients referred for evaluation in the research trial because of PPI-refractory heartburn actually had GERD that would respond to PPIs, but the patients were taking the medications improperly.

Once they were explicitly instructed how to take the medication—30 minutes before meals—their heartburn was controlled. For patients with PPI-refractory heartburn, this simple maneuver might spare them an extensive work-up.