Health Questions and Answers

Esophageal Cause of Chest Pain

When should the clinician consider an esophageal cause of chest pain?
The concept of the esophagus as the origin of chest pain is not new. More than a century ago, Sir William Osler hypothesized that esophageal spasm represented one cause of chest pain in soldiers during wartime. A recent multicenter study reported that 55% of patients attending the emergency department for chest pain did not have cardiac pain. However, coronary artery disease (CAD) is the most serious and life-threatening cause of chest pain. It should therefore be excluded as a potential diagnosis prior to pursuing esophageal investigations.

Does history help to discriminate cardiac from esophageal chest pain?
Yes and no. A sharp pain localized by one finger at the fifth intercostal space in the midclavicular line with onset at rest in a 20-year-old woman is unlikely to be caused by coronary artery disease. Certain features in a patient’s presenting history help clearly to differentiate between causes. However, many studies have shown sufficient overlap of all features to preclude certain diagnosis on the basis of symptoms alone. The description of pain by some patients with a known esophageal source and no cardiac disease mimics exactly the classic description of angina pectoris, including pain on exertion. One study from Belgium documented normal coronary angiograms in 25% of patients regarded by cardiologists as having myocardial ischemia on the basis of symptoms. In one half of these patients, a probable esophageal cause could be identified.

Does a normal coronary angiogram exclude all cardiac diagnoses?
No. Cardiac abnormalities other than CAD can be found in patients with chest pain, including mitral valve prolapse and microvascular angina. Exclusion of mitral valve prolapse requires echocardiography, whereas microvascular angina can be excluded only by the complicated procedure of measuring coronary artery resistance during stimulation with ergonovine and rapid atrial pacing.
However, studies suggesting that pain is no more common in patients with mitral valve prolapse or microvascular angina than in the general population question whether in fact these abnormalities produce pain. If they do, the mechanism is unclear. Furthermore, the prognosis is excellent, with the mortality rate being no different from that of the general population. Finally, a positive association between these cardiac abnormalities and esophageal motility disorders suggests a common or associated cause-either a generalized smooth muscle defect or heightened visceral nociception. It is therefore appropriate to search for an esophageal cause, after excluding coronary artery disease.

What are the noncardiac causes of chest pain? How common are they?
Gastroesophageal reflux disease (GERD) is the most frequent esophageal cause of chest pain. In most studies it accounts for up to 50% of all cases of unexplained chest pain (UCP). Esophageal dysmotility can be diagnosed in another 25-30% of cases. Of the remaining 20-30%, one third to one half can be explained by a musculoskeletal source, such as costochondritis (Tietze’s syndrome) and chest-wall pain syndromes. Psychological disorders, acting either independently or as cofactors, are responsible for many of these pain syndromes. Panic disorder, in particular, must be considered.

Because gastroesophageal reflux disease is the most likely diagnosis, is a trial of acid suppression acceptable?

Yes. A therapeutic trial of acid suppression is relatively inexpensive, noninvasive, and easy to perform, and may avoid further investigation. However, adequate doses of appropriate medication must be used. Current studies suggest that a proton pump inhibitor (PPI; omeprazole, 20 mg; lansoprazole, 30 mg; rabeprazole, 20 mg; pantoprazole, 40 mg; or esomeprazole, 20 mg) be given twice daily before meals for a period of 4-8 weeks. This test produces both false-negative and false-positive results. In patients who do not have relief of symptoms, the tendency is to conclude that GERD is not the cause of the pain. This conclusion cannot be made with complete certainty without ambulatory monitoring of intragastric and intraesophageal pH, while the patient continues PPI therapy. False positives may occur because of a placebo response that can be particularly high in functional gastrointestinal disorders. One study of patients with presumed esophageal chest pain noted a placebo response of 36%.

How is esophageal pH monitoring performed?
Esophageal pH monitoring is performed after an overnight fast. The level of acidity is measured by an intraesophageal electrode of either glass or antimony. The electrode is placed 5 cm above the upper border of the lower esophageal sphincter (LES), as previously determined by manometry.
An antimony electrode is thinner (2-mm diameter) but requires the use of a silver/silver chloride reference electrode either incorporated in the catheter or attached to the patient’s chest. The electrode is passed transnasally, and pH is recorded for a minimum of 16 hours. Patients are encouraged to follow their usual routine. Data are recorded on a portable recording device with marker buttons that allow the patient to indicate timing of meals, bed rest, and symptoms. A diary card is also completed to corroborate the timings. All information is transferred to a computer on completion of the study and analyzed both visually and by specialized software.

How can esophageal motility abnormalities cause chest pain?
The mechanism or mechanisms by which motility abnormalities may cause chest pain are poorly understood. Specific mechanoreceptors have been identified in the esophageal mucosal and muscle layers. Abnormal contractions per se may be sufficient to stimulate these receptors and cause pain. Alternatively, the mechanoreceptors may be stimulated by esophageal distention, as a result of failed LES relaxation or retention of the bolus within the esophageal body. Yet another possibility is alteration of the threshold for esophageal sensation, which “tunes in” the patient to changes in esophageal pressure. A further theory is that high tension in the esophageal wall inhibits esophageal blood flow, causing myoischemia. However, the esophagus has an extensive blood supply, and contractions are unlikely to be sufficiently prolonged to induce ischemia. It is also possible that dysmotility per se is not the cause of pain. Rather, it may represent an epiphenomenon that, like pain, is induced by another, unrecognized process. This emphasizes that simply diagnosing an esophageal motility disorder does not prove that it is the cause of the patient’s pain. Occasionally, during routine manometry, a patient develops pain coincident with abnormal wave forms, demonstrating a closer link between the dysmotility and the pain. More typically, the patient remains asymptomatic.

Can esophageal pain be provoked during testing?
Yes. In an attempt to provoke symptoms, additional measures analogous to the exercise stress test used by cardiologists may be used to stimulate the esophagus. Options include:

  1. acid infusion
  2. pharmacologic stimulation
  3. intraesophageal balloon distention.

For many years, it was believed that GERD caused chest pain by inducing dysmotility. Although this theory does not appear to be correct, acid perfusion (Bernstein test) is still used occasionally as a diagnostic test in UCP. Typically, 60-80 mL of 0.1 N hydrochloric acid are infused into the esophagus at a rate of 6-8 mL/min without the patient’s knowledge, followed by a similar infusion of saline. The test is positive only if

  1. it reproduces the patient’s typical symptoms during acid infusion
  2. the symptoms disappear or do not recur during saline infusion.

Chemoreceptors are present in the esophageal mucosa. Patients with a positive Bernstein test demonstrate acid sensitivity and should be treated for GERD-induced chest pain. Ambulatory pH monitoring with specific evaluation of symptom associations with pH decreases has largely made the Bernstein test obsolete.
Various pharmacologic agents have been used to stimulate the esophageal smooth muscle. The current choice is the cholinesterase inhibitor edrophonium (80 mg/kg intravenously). After injection, even in normal subjects, esophageal smooth muscle responds with increased peristaltic amplitude and duration during swallows. The test is regarded as positive only if it reproduces the patient’s typical pain.
Intraesophageal balloon distention (IEBD) involves the graduated inflation of a latex balloon within the esophagus, until pain or a predetermined maximal volume is reached. This test has the advantage of being specific to the esophagus and may reproduce the pain by a mechanism not dissimilar to that of dysmotility. It is positive only if it induces a patient’s typical pain at an inflation volume that does not induce pain in normal subjects. Balloon distention has been shown to be reproducible and has the highest yield of all available provocation tests. Of the three forms of provocation, acid and edrophonium typically induce symptoms in 20% of cases; balloon distention has double this yield.

How does provocation testing compare with combined ambulatory monitoring of both motility and pH?
All esophageal provocation tests have one major drawback-they are not physiologic. In an attempt to record the motility tracing during spontaneous chest pain, longer periods of manometry have been performed. However, this is little used outside research institutions.
Are there any emerging technologies for investigation of unexplained chest pain?
Yes. Multichannel intraluminal impedance (MII) is a new methodology that can detect intraesophageal events, including the reflux or nonpassage of boluses of air or liquid. This has potential benefits for the diagnosis of both nonacid reflux and motility abnormalities.
Monitoring of brain activity in response to esophageal stimulation has advanced our understanding of the central processing of UCP. New technologies in this area include analysis of cerebral-evoked potentials, functional MRI, and PET scanning.

What is visceral hypersensitivity? Define the “irritable esophagus.”
Many patients with UCP have lower thresholds to pain, in response to IEBD, than normal individuals. This finding is believed to be due to visceral hypersensitivity or altered nociception. For some patients, the problem may not be due to abnormal contractions but rather to abnormal perception of normal events, including peristaltic muscle contractions, physiologic quantities of acid reflux, and luminal distention by air or food. Combined pH and manometric monitoring has identified patients who are sensitive to both acid and motility events. This condition is described as the irritable esophagus. Research analyzing cerebral-evoked potential responses to esophageal stimulation suggests that the abnormality is due to central interpretation rather than abnormal firing of the peripheral nociceptors.

Does unexplained chest pain have a psychological component?
Yes. All disease has a psychological element; illness is interpreted according to personality and previous experiences. This maxim appears to be particularly true for UCP. Psychological abnormalities have been documented in 34-59% of patients with UCP and are present in all of the causes described previously. Psychiatric diagnoses are probably most prevalent in patients with esophageal motility abnormalities (84% in one study). Psychological factors, therefore, must be considered in the management of patients with UCP, including the possibility of panic attacks. Patients with high psychological scores are particularly susceptible to an initial placebo response to medication, but, in the long-term, treatment is ineffective. If such patients are identified, specific therapies can address the problem. Patients with high psychological scores have a worse prognosis and experience increased disability attributed to the illness.

What are the treatment options for nonreflux esophageal chest pain?
Esophageal motility abnormalities. Calcium antagonists, nitrates, and anticholinergic agents are the primary treatments aimed at motility dysfunction, that is, the spastic component. If the pain is only occasional, short-acting nitrates or calcium antagonists may be taken sublingually as needed. More frequent episodes of chest pain are better managed by regular therapy with a long-acting preparation. Although such medications may have a dramatic effect on esophageal pressures, their symptomatic efficacy is often disappointing. Benzodiazepines both reduce skeletal muscular contractions and modify sensory pathways. They have had limited success in esophageal motility abnormalities.

Visceral hypersensitivity. Drugs used to modify sensory pathways include anxiolytics and antidepressants. The largest body of evidence is for imipramine and other tricyclic antidepressants. They have been shown to be effective in low doses, suggesting that the effect is not due primarily to antidepressant activity.

Psychological and behavioral therapies. Various psychological and behavioral therapies have been tried in small-scale studies. Relaxation therapy has met with some success and can be taught easily to patients who are willing to acknowledge the psychological element in their disease. Reassurance is an intervention that is available to all physicians. The ability to demonstrate a definite esophageal abnormality as an explanation for chest pain is of significant therapeutic benefit. The frequency of both pain and office visits for treatment of pain decreases after such reassurances.

Additional therapies. Both empiric dilatation with a bougie and more specific targeting of a hypertensive LES with pneumatic dilatation have had limited success in some patients. Surgical myotomy may be of benefit to some patients with diffuse esophageal spasm or nutcracker esophagus. However, such interventions have documented complications and should be reserved for the rare, severely disabled patient.

Are there any emerging treatment options?
Yes. Several studies have demonstrated good symptom response to botulinum toxin injection among patients with chest pain and hypermotility disorders. By contrast, chest pain patients with ineffective esophageal motility derived little benefit from the 5-HT1 agonist sumatriptan when it was used to improve muscle contractility. Theophylline significantly increased pain thresholds in patients with functional chest pain, possibly acting by altering adenosine-mediated nociception. Additional novel interventions can be anticipated with the increased understanding of how the brain processes visceral stimuli.

Can abnormal belching or aerophagia cause chest pain?
Esophageal distention, whether by reflux of gastric contents, impaction of a food bolus, or entrapment of air, can cause chest pain. In several well-documented cases, gaseous esophageal distention was secondary to an abnormal belch reflex. Normally, the upper esophageal sphincter relaxes in response to distention with air. When this response fails, pain may occur.

What is the prognosis for patients with unexplained chest pain?
Patients with UCP have a poor functional outcome. Their quality of life is poor compared with healthy controls. They continue to consult a physician or visit the emergency department an average of twice per year, with an average of one hospitalization per year. If the patient does not have coronary artery disease, making a positive esophageal diagnosis significantly reduces such behavior. Despite ongoing morbidity, the mortality rate of these patients (<1% per annum) is the same as for the general population.

Date last updated: April 03, 2010

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