Review

Functional heartburn: An underrecognized cause of PPI-refractory symptoms

Scott Gabbard, MD and Sonya Vijayvargiya
Cleveland Clinic Journal of Medicine December 2019, 86 (12) 799-806; DOI: https://doi.org/10.3949/ccjm.86a.19006

Article Figures & Data

Figures

  • Figure 1
    Figure 1

    Conceptual pathophysiologic basis of functional heartburn.

  • Figure 2
    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).

  • Figure 3
    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.

Tables

  • TABLE 1

    Differential diagnosis of heartburn refractory to proton pump inhibitors

    Erosive or reflux esophagitis
    Nonerosive reflux disease
    Eosinophilic esophagitis
    Infectious esophagitis
     Viral (cytomegalovirus, herpes simplex virus)
     Fungal (Candida)
    Pill-induced esophagitis
     Antibiotics (doxycycline, tetracycline)
     Nonsteroidal anti-inflammatory drugs and aspirin
     Bisphosphonates
     Potassium
     Quinidine
    Esophageal motility disorder
     Achalasia
     Esophageal spasm or “jackhammer” esophagus
     Absent contractility, aperistalsis
    Functional esophageal disorder
     Functional heartburn
     Reflux hypersensitivity
  • TABLE 2

    Neuromodulators to treat functional esophageal disorders

    Tricyclic antidepressants
    (in descending order of efficacy and descending order of anticholinergic effects)
    Imipramine
    Amitriptyline
    Desipramine
    Nortriptyline
    Dosing: Start at 10 mg every night at bedtime; increase by 10 mg every 2–4 weeks
    Selective serotonin reuptake inhibitors
    Citalopram
    Fluoxetine
    Sertraline
    Dosing: Start at lowest dose; increase after 4–6 weeks
    Trazodone
    Dosing: Start at 50 mg every night at bedtime; increase by 50 mg every 2–4 weeks
    Serotonin and norepinephrine reuptake inhibitors
    Venlafaxine
    Duloxetine
    Dosing: Start at lowest dose; increase every 4–6 weeks as needed
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