Esophageal Chest Pain

3 Interesting Facts of Esophageal Chest Pain

1. Functional chest pain of presumed esophageal origin is a chronic, unexplained midline chest pain.
2. •Epigastric pain syndrome can be divided into the meal-related postprandial distress syndrome, and meal-unrelated epigastric pain syndrome. It belongs to the family of functional gastrointestinal (GI) disorders (also referred to as disorders of brain-gut interactions) that comprise a wide spectrum of often overlapping chronic GI disorders that are common in both the adult and pediatric populations. ¹
3. •In the absence of disease-specific biomarkers, the functional chest pain of presumed esophageal origin is classified by symptoms and the absence of other conditions that can account for the symptoms. Despite the benign prognosis, it can affect health-related quality of life at least as much as organic diseases. Because effective pharmacologic therapies are limited, management may include cognitive behavioral, dietary, and alternative medicine approaches. ²

Epidemiology & Demographics ²

• •Functional chest pain is quite common, with prevalence rates as high as 25%, evenly divided between men and women. Its prevalence appears to decline with advancing age.
• •Chest pain of esophageal origin may be indistinguishable from angina pectoris to patients and their health care providers. The esophagus and heart are anatomically adjacent and share innervation. In fact, once cardiac disease is excluded, esophageal disorders are probably the most common causes of chest pain. Of the approximately 500,000 patients in the United States who undergo coronary angiography yearly for presumed cardiac pain, almost 30% have normal epicardial coronary arteries; of these patients, esophageal diseases may account for the symptoms in 18% to 56%. ³
• •Once symptoms occur, more than 50% of patients have persisting symptoms for longer than 6 mo. Even after the initial diagnosis, however, many patients with chronic pain undergo repeated and unnecessary diagnostic cardiac evaluations.
• •Patients with functional chest pain may have comorbid anxiety or panic attacks, but formal referral for psychologic treatment is infrequent.
• •When compared with patients who have known cardiac chest pain, patients with functional chest pain report greater impairment of health-related quality of life in the domains of mental health and vitality. These findings suggest a link between psychologic disturbance and functional chest pain, at least in a subgroup of patients.

Etiology & Risk Factors ²

• •Risk factors for developing functional chest pain are not well defined but include younger age, adversity in childhood, and a history of other functional gastrointestinal conditions.

Enhanced Perception of Visceral Pain

About 30% to 70% of patients with functional GI disorders have an altered perception of visceral afferent stimuli (“visceral hypersensitivity”), in which normally innocuous stimuli, such as physiologic contractions, distention by food or gas, or chemical stimulation of the intestine (bile salts, microbial signaling molecules), stomach, or esophagus (hydrochloric acid, bile acids), lead to the sensation of pain or discomfort. The stimulus may be spontaneous peristaltic activity or result from distention by luminal contents, such as ingested food, liquids, gas, or feces. Visceral hypersensitivity may be associated with aberrant referral of visceral sensations to a particular body area, and this referral is often atypical in location and larger compared with most individuals. Many patients also have enhanced perception of somatic and auditory stimuli, consistent with general alterations in sensory processing and modulation systems.

Altered Stress Responsiveness

Abnormal autonomic and neuroendocrine responses to psychosocial stressors are a key feature of functional GI disorders and may play an important role in both its cause and its exacerbation. For example, stressful events are more likely to lead to abdominal pain and a change in stool pattern in patients with irritable bowel syndrome compared with healthy controls, and stress has been correlated with bowel symptoms and physician visit. Patients with a functional GI disorder report more lifetime stressful events than healthy controls, including a higher frequency and severity of early adverse life events.

Pathophysiology ²

• •The pathophysiology of functional GI disorders remains incompletely understood. A growing consensus suggests alterations in bidirectional interactions between the brain and the gut (brain-gut axis), with variable contributions of peripheral (gut microbiota and their metabolites, mucosal immune activation, motility, bile acids) and central factors (enhanced perception of visceral signals by the central nervous system and hyperresponsiveness to stress).
• •Altered signaling from the nervous system to the GI tract via the autonomic nervous system can modulate esophago-gastrointestinal function, as well as the microbial composition and function of the gut.
• •Functional GI disorders are defined by symptomatic criteria that include different subsets of patients who exhibit different patterns of the brain-gut axis dysregulation and that result in varying abnormalities in GI motility, secretion, immune function, or visceral sensitivity.
• •Despite this heterogeneity, however, functional GI disorders all share certain features, including a greater prevalence in women, enhanced sensitivity to stress, enhanced perception of visceral signals, the frequent coexistence of psychiatric and chronic pain disorders, and the response to centrally targeted pharmacologic and nonpharmacologic therapies.

Clinical Manifestations

Presenting Signs & Symptoms:²⁰

• •Patients with functional chest pain may complain of pain that is typical for myocardial ischemia or of pain with a variety of characteristics that would be considered atypical for ischemia.
• •The location of pain is typically substernal, but radiation to the arm and neck can be described.
• •The pain typically is not precipitated by exertion and may persist for hours. Nitroglycerin may sometimes be helpful acutely in patients with coexisting esophageal spasm. Patients may describe the discomfort using a variety of adjectives, and those descriptions may be indistinguishable from angina.
• •Esophageal chest pain is usually described as a squeezing or burning substernal sensation that radiates to the back, neck, jaw, or arms.
• •Although not always related to swallowing, the pain can be triggered by ingestion of hot or cold liquids. It may awaken the patient from sleep and can worsen during periods of emotional stress.
• •The duration of pain ranges from minutes to hours and may occur intermittently over several days.
• •Although pain can be severe, causing the patient to become ashen and perspire, it often abates spontaneously and may be eased with antacids. Occasionally the pain is so severe that narcotics or nitroglycerin are required for relief. Close questioning reveals that most patients with chest pain of esophageal origin have other esophageal symptoms, but chest pain is the only esophageal complaint in about 10% of cases. ⁴

 Diagnosis ⁵

• •The clinical history does not enable the physician to reliably distinguish between a cardiac and esophageal cause of chest pain. In fact, gastroesophageal reflux may be triggered by exercise ⁶ and cause exertional chest pain that mimics angina pectoris, even during treadmill testing.
• •Features suggestive of an esophageal origin include pain that continues for hours, is retrosternal without lateral radiation, interrupts sleep or is related to meals, and is relieved with antacids.
• •The presence of other esophageal symptoms helps establish an esophageal cause of pain. However, as many as 50% of patients with cardiac pain also have one or more symptoms of esophageal disease. ⁷ Furthermore, relief of pain with sublingual nitroglycerin has been shown not to be specific for a coronary origin of pain. ⁸ Cardiac and esophagealdisease increase in frequency as people grow older, and both problems may not only coexist but also interact to produce chest pain.
• •To make the diagnosis, cardiac causes, gastroesophageal reflux, and well-defined esophageal motility disorders (achalasia, scleroderma) must be excluded.
• •Patients who present with chest pain suspicious for angina should undergo prompt cardiac evaluation.
• •In patients with an initially negative cardiac evaluation, causes of functional chest pain can be categorized based on historical features (Box E1), and repeated cardiac evaluation for recurrent pain is of low yield.
• •Clinical features, such as association with certain foods or pain location, can help differentiate between acid-induced versus non–acid-related causes.
• •Patients with prominent chest wall pain and tenderness on palpation or with changes in pain with movement usually have musculoskeletal rather than esophageal pain. The remaining patients may have an esophageal source of pain and should be divided into patients with and without alarm symptoms, such as weight loss, progressive dysphagia, or anemia. Upper endoscopy is useful in patients with alarm features but is of lower yield in patients without them.

Differential Diagnosis of Functional Chest Pain

Organic Esophageal Causes

Gastroesophageal reflux disease

Achalasia

Virus- or pill-induced esophagitis Eosinophilic esophagitis

Nongastrointestinal Causes

Cardiac chest pain

Chest wall pain

Pulmonary disease

Panic attack

ome IV Diagnostic Criteria for Functional Chest Pain of Presumed Esophageal Origin ∗

∗The criteria must be fulfilled for the last 3 mo with the onset of symptoms at least 6 mo before diagnosis, with a frequency of at least once a week.

From Goldman L, Schafer AI: Goldman-Cecil medicine, ed 26, Philadelphia, 2019, Elsevier.

Must include all of the following:

• 1.Retrosternal chest pain or discomfort; cardiac causes should be excluded
• 2.Absence of associated esophageal symptoms, such as heartburn and dysphagia
• 3.Absence of evidence that gastroesophageal reflux or eosinophilic esophagitis are the cause of the symptom
• 4.Absence of major esophageal motor disorders (e.g., achalasia/esophageal-gastric outflow obstruction, diffuse esophageal spasm, jackhammer esophagus, absent peristalsis)

History & Physical Examination

• •Esophageal chest pain is often described as an epigastric and substernal sensation not accompanied by heartburn or dysphagia.
• •The physical examination is generally normal, although epigastric tenderness may be present. In contrast to gastroparesis, a succussion splash indicative of delayed gastric emptying is typically absent.

Laboratory Tests

Evaluation for H. pylori (may be performed by stool antigen, urea breath test, or gastric biopsy)

Imaging Studies

• •Esophageal manometry to rule out spastic or hypercontractile motility disorder.
• •Ambulatory pH testing to exclude gastroesophageal reflux. Ambulatory pH testing can document pathologic amounts of acid reflux or a correlation between acid reflux and chest pain in up to 50% of patients in whom a cardiac cause has been excluded. ⁹ The advent of a tube-free wireless system for gastroesophageal reflux monitoring has allowed a longer and more comfortable monitoring period, which increases the likelihood of observing a correlation between pain and an acid event.
• •Intraluminal ultrasound can be used in selected patients to identify abnormal sustained contractions of the longitudinal smooth muscle.

Diagnostic Procedures

Upper endoscopic examination is useful to exclude malignancy, gastropathy, peptic ulcerations, and esophagitis. However, invasive testing in the absence of alarm features should be considered only in a minority of symptomatic patients, such as patients older than 50 yr with new-onset or changing symptoms or a poor response to initial therapy.

Differential Diagnosis

Box E1 summarizes the differential diagnosis of functional chest pain. Alarm symptoms associated with an underlying upper GI malignancy are described in Box E3.

BOX E3

Alarm Symptoms Associated with an Underlying Upper Gastrointestinal Malignancy

From Goldman L, Schafer AI: Goldman-Cecil medicine, ed 26, Philadelphia, 2019, Elsevier.

• Unintentional weight loss
• New-onset dyspepsia after age 55 yr
• Dysphagia
• Persistent vomiting
• Any overt gastrointestinal bleeding, hematemesis, or melena
• Family history of esophageal or gastric cancer
• Iron deficiency anemia
• Palpable abdominal mass or lymph node

 Treatment ⁵

• •Many patients with functional chest pain or heartburn will have atypical GERD and should be given a therapeutic trial of a proton pump inhibitor (e.g., omeprazole, 20 mg daily). ¹⁰ Patients who respond to a 1- to 2-wk trial of daily proton pump inhibitor likely have acid-related symptoms and should be treated for GERD. Chest pain may respond to acid inhibition even if a coexisting motility disturbance is present. ¹¹ In patients whose response is equivocal, a longer proton pump inhibitor trial of 4 to 8 wk, endoscopy, or 24-hr pH testing can be considered.
• •For patients who do not respond to a proton pump inhibitor, a disorder of esophageal motility or visceral hypersensitivity may be present. Esophageal motility disorders, such as high-amplitude contractions (“nutcracker esophagus”) or diffuse esophageal spasm, can be identified by high-resolution esophageal manometry, but the low concordance between symptoms and manometric findings suggests that such testing should be performed only in highly selected patients based on the advice of a gastroenterologist. If a spastic or hypercontractile motility disorder is discovered on manometry, an attempt at lowering esophageal pressure with nitrates or a calcium channel blocker is appropriate, although some patients with chest pain and a motility disorder will respond better to agents directed at lowering visceral sensitivity.
• •For both functional chest pain and functional heartburn, low-dose tricyclic antidepressants (e.g., amitriptyline, imipramine, or desipramine, 10 to 50 mg per day) may be useful, particularly in patients suspected to have visceral hypersensitivity. Comorbid psychologic symptoms should be addressed with either pharmacologic (addition of an SSRI to the tricyclic antidepressant, or trial with an SNRI) or cognitive-behavioral approaches. Even in the absence of a specific psychiatric diagnosis, abdominal breathing, mindfulness-based stress reduction, or cognitive-behavioral therapy may be of benefit.
• •In the small proportion of patients whose heartburn is caused by reflux and truly refractory to proton pump inhibitors, laparoscopic Nissen fundoplication should be considered.
• •In the patient with functional chest pain, hypervigilance and fears of cardiac diseaseshould be addressed explicitly, and the significance of a negative cardiac evaluation must be reinforced.
• •If the functional chest pain is responsive to a proton pump inhibitor trial, patients should be continued on such therapy or treated with alternative acid-suppressing medications. The optimal duration of treatment is unclear, but it is reasonable to attempt withdrawal of medication and observe patients who have remained asymptomatic for several months.

Prognosis

The natural course of functional chest pain is not well understood, likely because most patients undergo a cardiac evaluation but then may have no further evaluation of their symptoms. However, both functional chest pain and functional heartburn have a benign prognosis, although symptoms may persist and continue to diminish quality of life.