When chest pain doesn't come from the heart

Noncardiac chest pain (NCCP) is recurrent chest pain, resembling angina, that is not caused by heart disease. Approximately 70 million Americans — 23 percent of the population — experience NCCP, and a similar number of people are affected worldwide. Although NCCP can result from both gastrointestinal and non-GI causes, in most cases, it is esophagus-related.

"Once cardiac disease and other sources of chest pain have been ruled out — including musculoskeletal, pulmonary and nonesophageal gastrointestinal causes — it's likely that a patient's pain is esophageal in nature," says Sami R. Achem, M.D., an expert in noncardiac chest pain at Mayo Clinic in Florida.

He cautions against trying to differentiate between cardiac and esophageal chest pain without objective studies because the two are often clinically indistinguishable. Even with a thorough workup, diagnosis can be challenging, especially in people who have coexisting heart and esophageal disease, in patients who experience both heartburn and NCCP, and in those with psychological conditions that complicate diagnosis.

Gastroesophageal reflux, the most common cause

Gastroesophageal reflux is the best studied and most common contributing factor for esophagus-related chest pain — a fact Dr. Achem finds encouraging because, as he points out, "Reflux is something we can treat."

In fact, about 80 percent of people with chest pain resulting from acid reflux improve during a weeklong PPI trial, which is often undertaken before pH monitoring or other studies. Acid inhibition also has proved a safe and effective treatment, with a majority of patients showing improvement in symptoms over eight weeks.

Motility disorders

Although the relationship between NCCP and esophageal motility is controversial, approximately 30 percent of people with NCCP may have esophageal motility abnormalities. Of these, nutcracker esophagus — strong contractions in the esophageal muscles — is the most common, followed by diffuse esophageal spasm and, more rarely, achalasia.

Muscle relaxants, calcium channel blockers and sometimes injections of botulinum toxin in the esophagus are alternative treatments, although none of these agents has been appraised in large, randomized controlled clinical trials.

"There is a real art in treating these patients because we lack good published studies on how to manage them appropriately," Dr. Achem says. "Right now, we might use sublingual muscle relaxants for acute spasms and botulinum toxin long term. But if patients also have acid reflux, that must be treated first because the use of muscle relaxants can worsen existing reflux."

Esophageal hypersensitivity

About 25 percent of people with NCCP may have enhanced esophageal pain perception thresholds (visceral hypersensitivity or visceral hyperalgesia), sometimes in conjunction with dysmotility.

The basic mechanisms underlying visceral hypersensitivity or hyperalgesia aren't clear, but recent studies support the notion that neurotransmitters, particularly serotonin, are involved in mediating the pain. In addition, some people with noncardiac chest pain have coexisting psychological issues, including anxiety, depression and panic disorders, which may contribute to heightened pain sensitivity.

For patients who don't respond to other agents, low-dose tricyclic antidepressants, taken in the evening, can prove beneficial. Although the precise mechanism of action of these compounds isn't clear, it may be that they help modulate visceral hypersensitivity by blocking serotonin.

Dr. Achem cites two studies showing that antidepressants such as nortriptyline are more effective than placebo for relieving hyperalgesia. "My personal experience also indicates that they work," he says. "A good 70 percent of people do respond."

Other therapeutic options

Dr. Achem says that recent studies have implicated adenosine receptors in the development of NCCP. "Theophylline, a nonspecific adenosine receptor antagonist, reduces noncardiac chest pain significantly," he points out. "Although the drug's usefulness is limited by its narrow therapeutic index and small margin of safety, studies are under way to search for safer and more advanced adenosine antagonists. This work may also help us understand the mechanism of action of adenosine-related compounds on visceral pain."

Recent studies also suggest that cognitive therapy may be beneficial in some patients, perhaps by triggering the release of neurochemicals that relieve pain.

Although NCCP doesn't affect mortality, it has a definite impact on quality of life. People with noncardiac chest pain may continue to have symptoms for years and endure a continuous round of clinic and emergency room visits, hospitalizations and prescription medications.

In spite of advances in treatment and understanding, Dr. Achem acknowledges that NCCP remains a conundrum. "One or more factors can contribute to it. What makes it even more challenging is that several conditions may coexist in a single patient, and each needs to be addressed."