Peer Reviewed


C. Prakash Gyawali, MD, on Functional Heartburn Overlapping With GERD

In a recent study, researchers compared functional heartburn/reflux hypersensitivity (FH/RH) with overlap FH/RH coexisting with gastroesophageal reflux disease (GERD).1

They used pH-impedance testing both on- and off-therapy and validated questionnaires to define symptoms, affective state, anxiety and depression, visceral sensitivity, and functional diagnoses among 19 patients with RH (10 with overlap RH), 60 with FH (31 with overlap FH) and 26 with non-erosive reflux disease (NERD). Overall, they found that the clinical, psychological, and functional profiles of patients with FH/RH were similar to those with overlap FH/RH.

Consultant360 reached out to author C. Prakash Gyawali, MD, MRCP, director of the GI Fellowship Training Program and Neurogastroenterology and Motility Program at Washington University School of Medicine, to learn more about this study.

Consultant360: Why was it important to examine the differences between conventional functional heartburn/reflux hypersensitivity (FH/RH) and FH/RH overlapping with gastroesophageal reflux disease?

C. Prakash Gyawali, MD, MRCP: Conventional FH/RH are easily recognized when esophageal reflux monitoring studies are performed off proton pump inhibitor (PPI), as these patients do not have abnormal acid burden. FH/RH overlapping with GERD is more difficult to diagnose, as it requires a subsequent pH-impedance study performed on twice-daily PPI after initial confirmation of GERD. However, the basic underlying mechanisms are similar to conventional FH/RH in that the psychologic profile was similar between conventional and overlap FH/RH. Thus, management of overlapping FH/RH will also be similar to conventional FH/RH, except for the fact that GERD management needs to continue in overlap FH/RH. The bottom line is that for symptom improvement, mechanisms of symptom generation need to be targeted, and our study findings indicate that some symptomatic patients with GERD have more than one mechanism for ongoing symptoms.

C360: Did any of your findings surprise you? Why or why not?”

CPG: Our findings seemed to suggest that patients with normal baseline impedance had an even higher likelihood of abnormal psychological profiles, suggesting that acid burden alone may not be as accurate as evaluating baseline impedance. As background, normal baseline impedance implies that esophageal mucosal integrity is normal, while low baseline impedance might suggest compromise of mucosal integrity, potentially from GERD. Since acid exposure time can vary from day to day, and since pH-impedance monitoring only evaluates a 24-hour period, it is easy to understand how the pH-impedance study might have been performed on the patient’s best day (ie lowest acid burden day), worst day, or average day, and acid exposure time would reflect this, while baseline impedance would reflect a longer term consequence of abnormal reflux burden or lack thereof.

C360: How do your findings contribute to the existing literature about this topic?

CPG: When patients with proven GERD (ie patients with prior conclusive evidence of GERD) continue to have symptoms, it is important to determine if their symptoms are related to ongoing abnormal acid burden, or due to esophageal visceral hypersensitivity or hypervigilance mechanisms that FH/RH represent. When overlapping RH/FH is diagnosed, management can focus on adjunctive neuromodulators or behavioral therapy, in contrast to escalation of reflux management when abnormal reflux burden is identified. In another study we published in Gastroenterology,2 we showed that abnormal reflux burden on pH impedance monitoring in patients with proven GERD taking twice-daily PPIs benefits from antireflux surgery. So the distinction of FH/RH from abnormal reflux burden in patients with proven GERD studied with pH impedance monitoring on twice-daily PPI helps further phenotype symptomatic GERD patients, and allows precision management of ongoing symptoms.

C360: Are there any remaining knowledge gaps that should be examined by future studies?

CPG: It will be important to evaluate larger patient populations using some of the newer pH-impedance metrics such as mean nocturnal baseline impedance, and perhaps the post-reflux swallow induced peristaltic wave (PSPW) index, to determine if the diagnosis of FH/RH can be further refined and distinguished from NERD. Also, differences between FH and RH need to be further elucidated.


  1. Rengarajan A, Pomarat M, Zerbib F, Gyawali CP. Overlap of functional heartburn and reflux hypersensitivity with proven gastroesophageal reflux disease. Neurogastroenterol. Motil.2021;33(6):e14056.
  2. Gyawali CP, Tutuian R, Zerbib F, et al. Value of ph-impedance monitoring performed 'on' bid proton pump inhibitor therapy to identify need for escalation of reflux management. Gastro. Published online July 13, 2021. doi: 10.1053/j.gastro.2021.07.004