Gastroesophageal reflux disease

Ronnie Fass, MD, on Functional Heartburn vs Refractory GERD

The American Gastroenterological Association (AGA) has recently published a clinical practice update1 on functional heartburn, which includes 7 pieces of best practice advice written by a panel of experts.

The best practice advice includes how to differentiate functional heartburn from gastroesophageal reflux disease (GERD), use of proton-pump inhibitor (PPI) therapy, and other treatment options for patients with functional heartburn.

Lead author Ronnie Fass, MD—who is professor of medicine at Case Western Reserve University, as well as medical director of the Digestive Health Center, director of the Division of Gastroenterology and Hepatology, and head of the Esophageal and Swallowing Center at MetroHealth Medical Center in Cleveland, Ohio—answered our questions about the AGA’s clinical practice update.

CON360: To start, how did this clinical practice advice come about?

Ronnie Fass: In the last decade, it has been recognized that functional heartburn plays an import role in a large and challenging group of heartburn patients, who do not respond to any anti-reflux modality. In addition, functional heartburn overlapping with GERD is commonly diagnosed in patients with documented GERD who failed PPI treatment.

CON360: Based on the best practice advice that you and your colleagues put together, what is the best approach to diagnosing functional heartburn in adults?

RF: All patients should undergo an upper endoscopy, and if negative, esophageal biopsies should be obtained to exclude mucosal abnormalities. If all is negative, then patients should undergo reflux testing. In those without history of documented GERD (abnormal esophageal acid exposure or erosive esophagitis), PH testing should be done off PPI treatment.

In patients with documented GERD, impedance plus PH testing should be done on PPI treatment. If reflux testing is unremarkable, including symptom index and symptom association probability, patients should undergo esophageal manometry to exclude a major esophageal motor disorder. This workup can identify functional heartburn patients or functional heartburn overlapping with GERD.

CON360: PPIs are proven to improve GERD symptoms but do not have benefits for patients with functional heartburn. What therapies did you and your colleagues find are best to treat functional heartburn?

RF: Neuromodulators are the cornerstone of functional heartburn treatment. These types of medications, also named pain modulators, improve symptoms in patients with functional heartburn through their central or peripheral pain modulatory effect. They include, tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), Tegaseroid (5-HT 4 agonist), and histamine-z receptor antagonists (HzRAs).

CON360: If patients are refractory to PPIs and these other medications, what alternative therapeutic options are available?

RF: It has been demonstrated that acupuncture and hypnotherapy may also benefit patients with functional heartburn, as sole treatment or in combination with a neuromodulator.

CON360: What are the most important take-away messages for gastroenterologists who treat functional heartburn?

RF: The most important is to recognize that functional heartburn is very common, affecting up to 21% of all patients presenting with heartburn as their predominant symptom. In addition, functional heartburn is by far the most common cause for anti-reflux treatment failure in heartburn patients and in those with documented GERD. PPIs, endoscopic therapy for GERD, and anti-reflux surgery have no therapeutic benefit in functional heartburn. Whilst neuromodulators are the mainstay of treatment, some patients may require a more comprehensive approach that also includes psychological intervention and/or alternative therapy, such as acupuncture.



  1. Fass R, Zerbib F, Gyawali CP. AGA clinical practice update on functional heartburn: expert review. Gastroenterology. 2020;158(8):2286-2293.