Functional Heartburn

Functional heartburn is retrosternal burning discomfort or pain that is not explained by gastro oesophageal reflux disease, an oesophageal motility disorder, or a structural cause, and that does not respond to optimal acid suppression. The diagnosis requires a normal endoscopy, normal oesophageal acid exposure, no symptom association with reflux events, and no eosinophilic oesophagitis or major motility disorder.

• It is the commonest diagnosis in patients with persistent heartburn despite proton pump inhibitor therapy (about 20 to 30% of those with heartburn who undergo reflux testing off acid suppression, and up to 30 to 50% of those who are refractory to a twice daily proton pump inhibitor), and it has a prevalence of about 2 to 3% of the general population in some studies.
• Mechanisms: oesophageal visceral hypersensitivity (peripheral and central sensitisation) to normal physiological stimuli (acid, mechanical distension, temperature, and chemical irritants), dysfunction of descending pain modulation, psychological factors (anxiety, depression, somatisation, hypervigilance, and stress), and an overlap with other functional gastrointestinal disorders (irritable bowel syndrome, functional dyspepsia).
• Typical patients: women (about 2 times as often as men), younger adults (aged 30 to 50 years), with higher levels of anxiety and a history of abuse, and a normal body mass index (unlike reflux disease, where obesity is common).
• The condition is chronic, with a fluctuating course, and has a major impact on quality of life, sleep and work. Cancer risk is not increased.
• Overlap: some patients have both gastro oesophageal reflux disease and functional heartburn, so the symptoms may only partly respond to acid suppression.

• Burning retrosternal pain or discomfort (with or without regurgitation) at least twice a week for the last 3 months, with onset at least 6 months before, that does not improve with proton pump inhibitor therapy (taken twice daily for at least 8 weeks, correctly timed before meals).
• Symptoms may be triggered by meals, stress, and certain foods, and they are often not related to lying down or bending. Associated features include globus, epigastric burning, bloating, belching, nausea, and other functional symptoms, and mood disturbance.
• Examination is normal. Check weight and look for features of anxiety, and examine the abdomen.
• Differential diagnosis: gastro oesophageal reflux disease (non-erosive and erosive), reflux hypersensitivity, eosinophilic oesophagitis, achalasia and other motility disorders, oesophageal spasm, pill oesophagitis, infectious oesophagitis (Candida, herpes, cytomegalovirus), peptic ulcer disease, functional dyspepsia, gastroparesis, biliary disease, angina and other cardiac disease, rumination, and bile reflux.
• Red flags: dysphagia, odynophagia, weight loss, persistent vomiting, gastrointestinal bleeding or iron deficiency anaemia, a palpable mass, age over 55 years with new symptoms, a family history of upper gastrointestinal cancer, Barrett oesophagus, chest pain on exertion, and hoarseness or cough with persistent symptoms.
• Complications: poor sleep, anxiety, depression, reduced work capacity, excess proton pump inhibitor use with adverse effects, repeated investigation, and rarely unnecessary antireflux surgery.

• A diagnosis of exclusion that requires objective testing in patients whose symptoms persist despite proton pump inhibitor therapy. Confirm adherence and correct timing (30 to 60 minutes before meals) of the proton pump inhibitor before testing.
• Upper endoscopy (off proton pump inhibitor, or on treatment if the aim is to assess response): no erosive oesophagitis of grade B or higher, no Barrett oesophagus, no peptic stricture, no eosinophilic oesophagitis (take biopsies from the proximal and distal oesophagus), and no mass.
• Ambulatory reflux monitoring off acid suppression (a wireless pH capsule for 96 hours, or a catheter based pH-impedance study for 24 hours, after stopping proton pump inhibitors for 7 days and H2 receptor antagonists for 3 days): the acid exposure time is below 4% (normal), the number of reflux episodes is normal (below 40 in 24 hours on impedance), and there is no positive association between symptoms and reflux events. An acid exposure time of 4 to 6% is inconclusive.
• Oesophageal high resolution manometry to exclude achalasia, absent contractility, and other major motility disorders, and to confirm normal peristalsis.
• Additional tests as indicated: barium swallow for dysphagia, gastric emptying study for nausea and early satiety, abdominal ultrasound, cardiac assessment (electrocardiogram, exercise testing) for chest pain, and Helicobacter pylori testing.
• Screen for anxiety, depression and somatic symptom disorder.

• Make a positive diagnosis and explain the condition, with reassurance that it is not dangerous or related to acid damage, and that the sensitivity of the oesophagus is the problem. Avoid repeated testing.
• Stop unnecessary acid suppression: if there has been no benefit from an 8 week course of a proton pump inhibitor, stop it (by tapering over 2 to 4 weeks, for example halving the dose weekly, and using an alginate or antacid for rebound symptoms). Rebound acid hypersecretion can cause transient symptoms for 2 to 4 weeks.
• Neuromodulators (the first line drug treatment for visceral hypersensitivity):
  • Amitriptyline 10 mg orally at night, increased by 10 mg every 1 to 2 weeks to 25 to 50 mg at night, or nortriptyline 10 to 25 mg at night, or imipramine 10 to 25 mg at night, for at least 8 to 12 weeks. Adverse effects: dry mouth, constipation, drowsiness, weight gain, and QT prolongation. Avoid in glaucoma, urinary retention, recent myocardial infarction, and in those taking serotonergic drugs.
  • Citalopram 10 to 20 mg orally once daily, or sertraline 25 to 50 mg once daily (increased to 100 mg), for 8 to 12 weeks, especially for comorbid anxiety or depression. Escitalopram 5 to 10 mg once daily is an alternative.
  • Trazodone 50 to 100 mg at night, or venlafaxine extended release 37.5 to 75 mg once daily, or duloxetine 30 to 60 mg once daily, are options for refractory symptoms.
  • Review the response at 8 to 12 weeks. If there is benefit, continue for 6 to 12 months before gradual withdrawal.
• Psychological therapies: cognitive behavioural therapy (6 to 12 sessions), hypnotherapy directed at the gut, mindfulness based therapy, and diaphragmatic breathing, which reduce oesophageal hypervigilance and improve symptoms.
• Symptom relief: alginate (sodium alginate and potassium bicarbonate 10 to 20 mL after meals and at bedtime), or calcium carbonate antacid 500 to 1000 mg as needed for up to 2 to 3 times daily, for short term relief.
• Lifestyle: regular meals, avoiding known trigger foods, stress reduction, regular exercise, adequate sleep, and stopping smoking. Weight loss is helpful when overweight.
• Avoid antireflux surgery, repeated endoscopy and further courses of acid suppression, because there is no benefit for functional heartburn.
• Special groups:
  • Pregnancy: use lifestyle measures, alginate, calcium carbonate antacids, and, when needed, a proton pump inhibitor (omeprazole 20 mg daily). Avoid neuromodulators unless necessary.
  • Elderly: investigate more readily for cancer and cardiac disease, and use lower doses of neuromodulators (amitriptyline 10 mg, or sertraline 25 mg), avoiding tricyclics in those with falls or cognitive impairment.
  • Children and adolescents: exclude organic disease, give reassurance, and use psychological therapy. Avoid medication where possible.
  • Renal and hepatic impairment: use lower doses of neuromodulators.
  • Cardiac disease: exclude angina and QT-prolonging combinations before starting tricyclics or citalopram.
• Follow up: review at 4 to 8 weeks after stopping or tapering the proton pump inhibitor and starting the neuromodulator, and then every 3 to 6 months. Refer to a gastroenterologist for refractory symptoms, diagnostic doubt, or abnormal test findings, and to a psychologist for severe anxiety or somatic symptoms.