Differentiating Functional Heartburn From Other Reflux Disorders

Amanda Balbi

Senior Managing Editor, Consultant360

Balbi A. Differentiating functional heartburn from other reflux disorders. Consultant360. Published online August 5, 2021.


The terms “heartburn” and “gastroesophageal reflux disease” (GERD) are often used interchangeably. However, differences in etiologies impact treatment options and outcomes (Figure). With an estimated 60 million US adults experiencing heartburn of some kind, it is important to distinguish between reflux disorders in order to prescribe appropriate treatment without causing additional harm. This review outlines the most common reflux disorders, as well as how to diagnose and treat each based on the current clinical guidelines.1

Reflux distinctions
Source: Grewal DK. Gastroesophageal reflux disease. Talk presented at: Practical Updates in Primary Care 2021 Virtual Series; July 17-19, 2021; Virtual.


Functional Heartburn

Functional heartburn is a symptom of acid reflux and GERD. It occurs when acid from the stomach moves back into the esophagus. Because the esophagus is more sensitive than the stomach, the burning sensation is difficult for patients to pinpoint, but the heart is not affected. Patients might think they are having a heart attack, when they may only have severe functional heartburn.2

For any suspected reflux disease, endoscopic examination is indicated for patients who fail empirical proton-pump inhibitor (PPI) therapy.1 Functional heartburn is diagnosed via upper endoscopy examination with esophageal biopsies, esophageal high-resolution manometry, and pH monitoring off PPI therapy.1 The following Rome IV criteria must be met to diagnose functional heartburn:3

  • Burning retrosternal discomfort or pain
  • No symptom relief despite optimal antisecretory therapy (PPIs)
  • Absence of evidence that GERD or eosinophilic esophagitis is the cause of the symptom
  • Absence of major esophageal motor disorders


Another important distinction is etiology. Research has suggested a nociceptive pathophysiologic mechanism in functional heartburn that sets it apart from GERD, making it possible for patients to have functional heartburn and GERD overlap syndrome.1 According to Rome IV criteria, overlap syndrome is present when “heartburn persists despite maximal PPI therapy in patients with history of proven GERD, and pH impedance testing on PPI therapy demonstrates physiologic acid exposure without reflux-symptom association.”1,3

Since PPI therapy is not effective for treating functional heartburn, the guidelines recommend prescribing neuromodulators—tricyclic antidepressants, selective serotonin reuptake inhibitors, tegaserod, and histamine-2 receptor antagonists—as either primary therapy for functional heartburn alone or as add-on therapy for overlap syndrome.1 Acupuncture and hypnotherapy may also be beneficial as monotherapy or adjunctive therapy.1

Gastroesophageal Reflux Disease

GERD is a chronic, more severe form of acid reflux. It is diagnosed when acid reflux occurs more than 2 times per week, and inflammation in the esophagus is present. Upon endoscopic examination, advanced erosion of the esophagus may be noted. Moreover, long-term damage to the esophagus can lead to esophageal cancer.2

GERD is defined by the Rome IV criteria as an “elevated acid exposure time and/or symptom reflux association.”3 It is diagnosed based on history, physical findings at presentation, endoscopic evaluation, ambulatory reflux monitoring, and response to antisecretory therapy.2,4 pH monitoring should also be employed.4

Because there is a strong association between GERD and obesity, patients should be counseled on weight management and lifestyle modification, including stopping smoking, losing weight, eating fewer fatty foods, and eating less or fewer spicy foods. Other treatment options include antacids, histamine-receptor antagonists, or PPI therapy. Surgery may be indicated for patients who are refractory to these therapies and whose symptoms are unchanged after lifestyle modifications.4

Nonerosive Reflux Disease

Patients presenting with NERD will have the same symptoms as patients with functional heartburn or GERD. However, endoscopic examination will reveal no acid erosion in the esophagus.1,5 Moreover, some definitions of NERD also include pH level, which might help differentiate patients with functional heartburn and NERD.5

24-hour esophageal impedance and pH monitoring is recommended to better understand reflux characteristics.6 The etiology of NERD is believed to be increased transient lower esophageal sphincter relaxations.5 Counseling on lifestyle modifications is recommended, along with standard PPI therapy for 2 to 4 weeks. If symptoms persist, the PPI dose should be increased.6

The current guidelines recommend on-demand or standard PPI therapy over histamine-receptor antagonists.4 Over-the-counter antacids may also relive symptoms.4


There are subtle but important differences between functional heartburn and other reflux disorders. Knowing how to differentiate between the disorders will help you diagnose your patients more quickly and prescribe more-appropriate therapies.


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

2. Marcin J. What are the differences between heartburn, acid reflux, and GERD? Healthline. Updated April 9, 2020. Accessed August 5, 2021.

3. Rome IV criteria. The Rome Foundation. Published January 16, 2016. Accessed August 5, 2021.

4. Katz PO, Gerson LB, Vela MF. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol. 2013;108(3):308-329.

5. Patel D, Fass R, Vaezi M. Untangling Nonerosive Reflux Disease From Functional Heartburn. Clin Gastroenterol Hepatol. 2021;19(7):1314-1326.

6. Chen CL, Hsu PI. Current advances in the diagnosis and treatment of nonerosive reflux disease. Gastroenterol Res Pract. 2013;2013:653989.