Functional heartburn: An underrecognized cause of PPI-refractory symptoms

Cleveland Clinic Journal of Medicine. 2019 December;86(12):799-806 | 10.3949/ccjm.86a.19006
December 2, 2019|Cleveland Clinic Journal of Medicine
Scott Gabbard, MD;Sonya Vijayvargiya
Author and Disclosure Information

Scott Gabbard, MD
Department of Gastroenterology, Hepatology & Nutrition, Cleveland Clinic; Assistant Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH

Sonya Vijayvargiya
Emory University, Atlanta, GA

Address: Scott Gabbard, MD, Department of Gastroenterology and Hepatology, A31, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; gabbars@ccf.org

Release date: December 1, 2019
Expiration date: November 30, 2020
Estimated time of completion: 1 hour

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ABSTRACT

Functional heartburn—persistent symptoms of esophageal reflux with no objective evidence of gastroesophageal reflux disease (GERD)—is the most common cause of failure of proton pump inhibitor (PPI) therapy, but it is often overlooked by internists and gastroenterologists.

KEY POINTS

  • Functional heartburn accounts for more than half of all referrals for PPI-refractory GERD.
  • Diagnostic criteria require at least 3 months of symptoms in the 6 months before presentation.
  • Results of upper endoscopy with biopsy, esophageal manometry, and esophageal pH monitoring must be normal.
  • Patient education is key, with reassurance that the risk of progression to malignancy is low in the absence of Barrett esophagus, and that the condition remits spontaneously in up to 40% of cases.
  • Neuromodulators to reduce pain perception are the mainstay of treatment for functional gastrointestinal disorders such as functional heartburn. Cognitive behavioral therapy and hypnotherapy are also used as first-line treatment.

Esophageal manometry

If endoscopic and esophageal biopsy results are inconclusive, a workup for an esophageal motility disorder is the next step. Dysphagia is the most common symptom of these disorders, although the initial presenting symptom may be heartburn or regurgitation that persists despite PPI therapy.

Manometry is used to test for motility disorders such as achalasia and esophageal spasm.10 After applying a local anesthetic inside the nares, the clinician inserts a flexible catheter (about 4 mm in diameter) with 36 pressure sensors spaced at 1-cm intervals into the nares and passes it through the esophagus and lower esophageal sphincter. The patient then swallows liquid, and the sensors relay the esophageal response, creating a topographic plot that shows esophageal peristalsis and lower esophageal sphincter relaxation.

Achalasia is identified by incomplete lower esophageal sphincter relaxation combined with 100% failed peristalsis in the body of the esophagus. Esophageal spasms are identified by a shortened distal latency, which corresponds to premature contraction of the esophagus during peristalsis.11

Esophageal pH testing

Measuring esophageal pH levels is an important step to quantify gastroesophageal reflux and determine if symptoms occur during reflux events. According to the updated Porto GERD consensus group recommendations,12 a pH test is positive if the acid exposure time is greater than 6% of the testing period. Testing the pH differentiates between GERD (abnormal acid exposure), reflux hypersensitivity (normal acid exposure, strong correlation between symptoms and reflux events), and functional heartburn (normal acid exposure, negative correlation between reflux events and symptoms).5 For this test, a pH probe is placed in the esophagus transnasally or endoscopically. The probe records esophageal pH levels for 24 to 96 hours in an outpatient setting. Antisecretory therapy needs to be withheld for 7 to 10 days before the test.

Transnasal pH probe. For this approach, a thin catheter is inserted through the nares and advanced until the tip is 5 cm proximal to the lower esophageal sphincter. (The placement is guided by the results of esophageal manometry, which is done immediately before pH catheter placement.) The tube is secured with clear tape on the side of the patient’s face, and the end is connected to a portable recorder that compiles the data. The patient pushes a button on the recorder when experiencing heartburn symptoms. (A nurse instructs the patient on proper procedure.) After 24 hours, the patient either removes the catheter or has the clinic remove it. The pH and symptom data are downloaded and analyzed.

Transnasal pH testing can be combined with impedance measurement, which can detect nonacid reflux or weakly acid reflux. However, the clinical significance of this measurement is unclear, as multiple studies have found total acid exposure time to be a better predictor of response to therapy than weakly acid or nonacid reflux.12

Wireless pH probe. This method uses a disposable, catheter-free, capsule device to measure esophageal pH. The capsule, about the size of a gel capsule or pencil eraser, is attached to the patient’s esophageal lining, usually during upper endoscopy. The capsule records pH levels in the lower esophagus for 48 to 96 hours and transmits the data wirelessly to a receiver the patient wears. The patient pushes buttons on the receiver to record symptom-specific data when experiencing heartburn, chest pain, regurgitation, or cough. The capsule detaches from the esophagus spontaneously, generally within 7 days, and is passed out of the body through a bowel movement.

Diagnosing functional heartburn

Figure 2. High-resolution esophageal manometry in our patient shows normal esophageal resting pressure and relaxation, and a distal latency of 7.5 seconds, indicating normal peristalsis.
Figure 2. High-resolution esophageal manometry in our patient shows normal esophageal resting pressure and relaxation, and a distal latency of 7.5 seconds, indicating normal peristalsis. It also shows a distal contractile integral of 2,368 mm Hg-sec-cm, a measure of the pressure, duration, and vertical length of the distal esophageal contraction. The vertical axis shows the length along the esophagus from upper to lower, and the horizontal axis shows time. The color depicts pressure from low (blue) to high (red); note how the waves of contraction (high pressure) proceed from proximal (top) to distal (bottom).
The Rome IV diagnostic criteria for functional heartburn5 require that a patient experience retrosternal burning, discomfort, or pain at least twice a week for at least 6 months. By definition, the symptoms have not responded to antisecretory drugs (an H2-receptor antagonist or PPI) in optimal doses. Also, inflammatory disorders such as erosive esophagitis and eosinophilic esophagitis and motility disorders such as achalasia (Table 1) need to be ruled out.

CASE CONTINUED: NORMAL RESULTS ON TESTING

Figure 3. In our patient with functional heartburn, 24-hour wireless esophageal pH testing showed a pH greater than 4 (the conventional cutoff in esophageal pH testing) for most of the test.
Figure 3. In our patient with functional heartburn, 24-hour wireless esophageal pH testing showed a pH greater than 4 (the conventional cutoff in esophageal pH testing) for most of the test. During the test, the patient recorded experiencing heartburn 67 times (gray diamonds); her esophageal pH was below 4 for just 3 of the 67 events. This pH test is consistent with a diagnosis of functional heartburn. The vertical axis shows the pH from 0 to 8, with a midline at 4. The horizontal axis shows a 24-hour period from noon to noon.
The patient undergoes esophageal manometry and esophagogastro-duodenoscopy with placement of a wireless pH probe. Results of esophageal manometry are normal. She has normal lower esophageal resting pressure and relaxation and normal peristalsis in the esophagus body (Figure 2). Wireless pH testing shows a total acid exposure time of 1.7% and a strongly negative symptom association with heartburn, chest pain, and regurgitation (Figure 3).

Based on these results, her condition is diagnosed as functional heartburn, consistent with the Rome IV criteria.5