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One-third of patients with chest pain undergo negative cardiac evaluation. Patients with recurrent noncardiac chest pain thus pose a difficult clinical problem. Because CAD is common and can present atypically, it must be excluded prior to evaluation for other causes.

Causes of noncardiac chest pain may include the following.

A. Chest Wall and Thoracic Spine Disease

These are easily diagnosed by history and physical examination.

B. Gastroesophageal Reflux

Up to 50% of patients have increased amounts of gastroesophageal acid reflux or a correlation between acid reflux episodes and chest pain demonstrated on esophageal pH testing. An empiric 4-week trial of acid-suppressive therapy with a high-dose PPI is recommended (eg, omeprazole or rabeprazole, 40 mg orally twice daily; lansoprazole, 30–60 mg orally twice daily; or esomeprazole or pantoprazole, 40 mg orally twice daily), especially in patients with reflux symptoms. In patients with persistent symptoms, ambulatory esophageal pH or impedance and pH study may be useful to exclude definitively a relationship between acid and nonacid reflux episodes and chest pain events.

C. Esophageal Dysmotility

Esophageal motility abnormalities such as distal esophageal spasm or hypercontractile esophagus ("jackhammer esophagus") are uncommon causes of noncardiac chest pain. In patients with chest pain and dysphagia, a barium swallow radiograph should be obtained to look for evidence of achalasia or spastic motility disorder. Esophageal manometry is not routinely performed because of low specificity and the unlikelihood of finding a clinically significant disorder, but it may be recommended in patients with frequent symptoms.

D. Heightened Visceral Sensitivity

Some patients with noncardiac chest pain report pain in response to a variety of minor noxious stimuli such as physiologically normal amounts of acid reflux, inflation of balloons within the esophageal lumen, injection of intravenous edrophonium (a cholinergic stimulus), or intracardiac catheter manipulation. Low doses of oral antidepressants such as trazodone 50 mg or imipramine 10–50 mg reduce chest pain symptoms and are thought to reduce visceral afferent awareness. In a 2010 controlled crossover trial, over 50% of patients treated with venlafaxine, 75 mg once daily at bedtime, achieved symptomatic improvement compared with only 4% treated with placebo.

E. Psychological Disorders

A significant number of patients have underlying depression, anxiety, and panic disorder. Patients reporting dyspnea, sweating, tachycardia, suffocation, or fear of dying should be evaluated for panic disorder.

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