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CMEEarn Category I CME credit by reading this article and "Nonsurgical management of osteoarthritis of the knee" and successfully completing the post-test. Successful completion is defined as a cumulative score of at least 70% correct. This material has been reviewed and is approved for 1 hour of clinical Category I (Preapproved) CME credit by the AAPA. The term of approval is for 1 year from the publication date of December 2005.
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Chest pain is significant not only because of the health problem it might indicate but also because of how much it costs the health care system and how greatly it affects the lives of patients. Most persons who are evaluated in a primary care setting will have a noncardiac cause of their symptoms.1 Even so, the importance of ruling out possible cardiac pathology usually leads to expensive and complicated workups.
In the United States, the complaint of chest pain leads to more than 6 million hospital admissions and more than $8 billion in health care costs annually,2 with cardiac causes found in only 20% of admissions.3 Even after removing patients with known cardiac disease, a population-based study in Australia revealed that 33% of the polled population had had noncardiac chest pain (NCCP) at some time.2 Conservatively extrapolated to the US population, this could mean up to 80 million patients presenting to clinics with NCCP.2
Accurately diagnosing and treating patients with musculoskeletal, GI, psychological, and other causes for NCCP can be challenging. Nevertheless, all possible causes should be explored because patients with NCCP can have significant long-term morbidity due to their pain.2 All practitioners should assess for cardiac disease and be aware of the variety of noncardiac causes of chest pain in order to begin appropriate therapy.
Evaluate all patients presenting with chest pain initially for possible cardiac causes. A careful, thorough history looking for cardiac risk factors, followed by a 12-lead ECG, chest radiograph, and serial measurements of cardiac enzymes, should help determine whether the patient’s pain is cardiac in nature.4 If the patient is stable and the etiology is still unclear, referral for a cardiology consult, echocardiography, or stress ECG is warranted.4
Once a cardiac cause has been ruled out, consider the differential diagnosis for chest pain. A survey of primary care centers in Michigan revealed that musculoskeletal conditions were responsible for 36% of cases of chest pain, followed by GI (19%), nonspecific (16%), psychiatric (7.5%), and pulmonary (5%) conditions.1 The three most common misunderstood causes of NCCP are musculoskeletal, GI, and psychosocial.
Fractures of any of the bones of the thoracic wall can cause chest pain, as can localized inflammation or dislocation of the costosternal, sternoclavicular, or costochondral joints due to traumatic, rheumatic, or idiopathic conditions. Strains of the pectoralis or intercostal muscles may cause pain, while muscle or joint pain from the shoulders or spine can also be referred to the chest.5 In particular, low cervical spine and T1 nerve roots supply the pectoralis muscles, and while they more commonly refer pain to the scapulae, they can cause chest pain.6 Herpes zoster infection may also have a prodrome of severe unilateral chest pain that radiates along a dermatome.
Any history of new or excessive physical activity is important, as are trauma to the thorax, shoulder, or back or a history of rheumatic diseases, such as rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, fibromyalgia, or sternocostoclavicular hyperostosis. A history of a cough or dyspnea can indicate musculoskeletal chest pain from intercostal muscle strain. Musculoskeletal pain tends to have a deep, aching quality that is hard to localize. Questions about systemic signs such as weight loss and night sweats are important to rule out serious illnesses.6
The physical evaluation should begin with observation of the chest wall for obvious deformities or inflammation. The hallmark of musculoskeletal chest pain is pain that is reproducible with palpation or with active/passive range of motion (ROM) movements of the joints and musculature of the affected area. Palpate and use such ROM exercises to test areas with potential for referred pain, such as the cervical and thoracic spine. Consider the diagnosis of fibromyalgia, particularly with the discovery of trigger points, in female patients younger than 60 years who present with concomitant psychiatric issues, sleep problems, or chronic muscle pain. Specific pain syndromes such as costochondritis usually have multiple tender costosternal joints with minimal swelling, while Tietze’s syndrome usually manifests with one particularly painful joint and significant local swelling.6 A thorough clinical examination of the heart, lungs, and abdomen is also necessary. Pay particular attention to the skin since herpes zoster and psoriatic arthritis can have associated rashes and can cause musculoskeletal chest pain.7
If palpation or active/passive ROM movements of the area of discomfort reproduce the pain, the pain is likely to be musculoskeletal. No other tests may be necessary in patients without risk factors or a history that suggests systemic illnesses or fractures. Posteroanterior and lateral chest radiographs are cost-effective ways to identify dislocations or solid tumors, and CT can be particularly useful in elucidating sternal or sternoclavicular structure as well as soft tissue swelling. An elevated ESR may indicate a rheumatic process in a patient with other clinical signs, such as myalgias and joint tenderness. Should the patient’s clinical picture and history warrant it, further workup with more specific tests, such as those for antinuclear antibodies or rheumatoid factor, may be helpful. If a joint infection is suspected, a CBC, Gram’s stain, and culture of joint aspirate should be ordered.7
For most patients with musculoskeletal chest pain, education to relieve anxiety is part of the first-line treatment. The patient should suspend or limit any activities that exacerbate the pain and expect a gradual resolution of symptoms over time. NSAIDs are useful to manage pain and reduce mild inflammation.8 Most severe, acute causes of musculoskeletal chest pain, such as rib fracture, can be managed with short-term use of opioids such as hydrocodone or oxycodone. Inflammatory diseases like costochondritis can be safely and successfully treated with joint injections of triamcinolone plus 1% lidocaine.9 Tricyclic antidepressants (TCAs) are useful in treating generalized pain and are particularly effective for neurogenic pain, such as that from herpes zoster.10 Herpes zoster infections should be treated with an antiviral agent such as acyclovir, valacyclovir, or famciclovir within 48 to 72 hours of the eruption to limit the outbreak’s duration.11
Gastroesophageal reflux disease (GERD) can cause substernal chest pain and is the most common cause of GI-associated chest pain.12 Abnormalities in esophageal function can produce chest pain and exacerbate GERD. Studies using esophageal manometry to evaluate patients with NCCP have found hypotensive tone of the lower esophageal sphincter (LES) to be the most common abnormality. A decrease in sphincter tone allows gastric contents and acid to reflux back into the esophagus, causing irritation to the esophageal lining, which may be perceived as chest pain.13 Recent research suggests that patients with GERD can have a CNS-mediated hypersensitivity to the acid irritation that results in a longer and more severe sensation of chest pain.14
Abnormal contractions of portions of the esophagus can also cause chest pain. Nutcracker esophagus is one of the most common and is due to high-amplitude contractions of the distal esophagus. The etiology of these contractions is unknown, but acid irritation of the esophageal mucosa has been implicated. Another contraction abnormality is hypertensive LES pressure, which has been found in 10% of patients with NCCP and abnormal manometry results.13 Another 10% of this group have nonspecific esophageal motor disorders that can be caused by peristaltic abnormalities such as nontransmitted or retrograde contractions and incomplete LES relaxation. Other causes are achalasia (absence of LES relaxation with swallowing) and diffuse esophageal spasms of 20% to 100% of the esophageal musculature.15 Less common esophageal abnormalities are Mallory-Weiss tears and Zenker’s diverticulum of the esophagus. Cholecystitis and pancreatitis can also cause chest pain and left shoulder discomfort because of diaphragmatic or phrenic nerve irritation.
Since GERD is the most common cause of GI-associated chest pain, questions that tease out this possible diagnosis are important. A history of heartburn is a significant risk factor, independent of other GI complaints, age, and gender. Dysphagia and acid regurgitation are also significant risk factors, although not independently predictive.2 Ask whether the pain is associated with supine or prone positions and if it occurs postprandially or after eating spicy or fatty foods, all of which can suggest GERD.
A history of dysphagia can indicate possible esophageal motility dysfunction or, in association with late regurgitation, Zenker’s diverticulum.12,13 Mallory-Weiss tears are the most common lacerations of the esophagus and are associated with chronic alcohol abuse and with severe vomiting or coughing. An abrupt onset of chest pain while vomiting or coughing and subsequent hematemesis are characteristic.16
The physical examination, although important, is somewhat limited in chest pain with a GI source. It should include a thorough abdominal examination noting particular tender points, especially those along the epigastrium, that could indicate peptic ulcer disease, pancreatitis, or Murphy’s sign. A digital rectal examination and stool guaiac test can help determine whether GI bleeding is present.
Ambulatory 24-hour esophageal pH monitoring can identify GERD-associated chest pain with 60% to 90% sensitivity and 85% to 100% specificity.17 However, this test is expensive, invasive, and not always available. A 2-week course of moderate to high doses of a proton pump inhibitor (PPI) is an effective and cost-saving test, with 71% to 90% sensitivity and 67% to 88% specificity.17,18 If a PPI reduces or resolves the pain, GERD is likely the cause. If a PPI does not reduce the pain or does so only minimally, a referral for ambulatory esophageal pH monitoring is advised.19 Ambulatory monitoring is advantageous because spikes in esophageal pH can be correlated with the patient’s symptoms. Barium swallows and upper endoscopy are poor diagnostic tests for GERD-related chest pain and should be used only when other tests are nondiagnostic or when Mallory-Weiss tears or Zenker’s diverticulum is suspected. Esophageal manometry may be useful in patients with suspected esophageal dysmotility or dysphagia, although correlation between dysmotility and chest pain events is only 20% to 30%.17
Laboratory tests do not generally help to diagnose the more common GI causes of NCCP, but certain blood tests can be useful in more atypical cases. While they have limited sensitivity, tests for amylase and lipase levels can be useful in diagnosing pancreatitis, and serum Helicobacter pylori testing can be helpful if the pain is thought to be due to peptic ulcer. CT can aid in the diagnosis of pancreatitis when amylase and lipase levels are indeterminate or do not match the clinical picture. Ultrasonography is the diagnostic test of choice for biliary pathology, followed by CT in uncertain cases.20
Respond to patients who have GI-associated NCCP with reassurance that the pain is probably not cardiac. Encourage the patient to reduce fat intake, avoid foods that cause reflux, and stop smoking.17 While omeprazole has been the only PPI tested, any PPI should be effective as a first-line treatment for GERD-related NCCP.17 Studies show that omeprazole significantly decreases the number and severity of chest pain episodes.17 Start with double the usual dosage, titrating down to the lowest effective dosage for long-term administration.17 Laparoscopic fundoplication is 85% to 90% effective in reducing chest pain, but it carries with it the complications and cost of surgery and should not be a first-line treatment.17
Pain from suspected esophageal dysmotility disorders tends to respond well to low dosages of imipramine and trazodone.19 A small study showing significant improvement in chest pain symptoms with the use of sertraline opens the possibility of using selective serotonin receptor inhibitors (SSRIs) to control NCCP.21 Several studies have tested whether calcium channel blockers are effective against confirmed dysmotility disorders. While they have shown some promise, their use has been controversial.19 Endoscopic band ligation and injections of epinephrine are effective treatments for Mallory-Weiss tears, and endoscopy or open surgery can be used to treat Zenker’s diverticulum.22,23
A relationship between certain psychological disorders and NCCP has long been recognized. Among patients presenting to both inpatient and outpatient cardiology services for chest pain, 25% to 56% have panic disorder, the most common psychological malady associated with NCCP.24 Of patients with NCCP, 15% to 60% have associated panic disorder.24
While the mechanisms behind the physiology of psychiatric NCCP are not clear, several studies have shown a relationship between hyperventilation, which is known to induce panic attacks, and esophageal spasms.25 The theory is that these spasms are the chest pains experienced by the patient. However, carbon dioxide is known to induce panic and cause chest pain, but it does so without effect on the esophagus and its physiology remains unclear. Since panic causes an imbalance in several areas of the CNS, including the serotonin and noradrenergic systems, centrally mediated visceral hypersensitivity may also play a role.19 A hypersensitivity to visceral pain, particularly esophageal, could trigger the classic panic cycle of anxiety: catastrophic misunderstanding of symptoms, leading to more anxiety, leading to more misunderstanding, leading to further anxiety, and so forth.24
Generalized anxiety disorder, obsessive-compul-sive disorder (OCD), and major depressive disorder have also been implicated as contributors to NCCP, but to a much lesser degree.26 Little is known about the physiology of the chest pain associated with these disorders.
When assessing a patient with possible psychogenic chest pain, rule out potential cardiac causes first. After reasonable assurance that the cardiovascular system is not causing the pain, questions concerning the patient’s mental health are appropriate.
Ask direct, specific questions about the symptoms of panic disorder: brief, intense feelings of doom, profuse sweating, dizziness, palpitations, shortness of breath, paresthesias, or a sensation of choking. Patients with panic disorder may have agoraphobia or other phobias regarding certain places or situations. Questions about recent stressors such as job loss, divorce, or the death of a loved one can be helpful in assessing a patient’s current psychological state.24 Generalized anxiety disorder, marked by long-term worry or anxiety, may include restlessness, easy tiring, muscle tension, sleep disturbances, and irritability.27 OCD and major depressive disorder are less common causes of NCCP. Ask questions about irritable bowel syndrome, other psychiatric illnesses, and the family history of psychiatric illnesses.19 Panic disorder that manifests as chest pain tends to affect women younger than 30 years with no family history of cardiac disease, but anyone can be affected.25 Pay special attention to signs of self-abuse or illicit drug use that could also indicate mental illness or depression. A complete physical examination, while necessary, is generally not helpful in diagnosing psychiatric causes of chest pain.
Several questionnaires are available to help with screening. The Hospital Anxiety and Depression Scale (HADS), the Patient Health Questionnaire (PHQ), and a screening question that simply asks if the patient has ever had a sudden feeling of anxiety or panic all have good sensitivity and specificity in identifying panic disorder. Although the single question had only 78% specificity, at 93% sensitivity it is probably the most efficient screening tool available.28 If a patient is exhibiting severe symptoms of one or more of these disorders, or if the provider is uncomfortable managing these issues, then the patient should be referred to a mental health specialist.
When a patient’s chest pain has a psychiatric cause, reassurance and encouragement are vital. The patient may require regular clinic follow-up. In addition to reassurance, both antidepressants and cognitive behavior therapy (CBT) are effective and can be used simultaneously.24
Pharmacotherapeutic possibilities include trazodone, imipramine, benzodiazepines, and SSRIs, although trazodone or imipramine in low dosages are preferred.29 Trazodone, 25 to 50 mg at bedtime, reduces symptoms of NCCP and insomnia.29 Imipramine (25 mg) significantly decreases NCCP regardless of coexisting esophageal or psychiatric illnesses, but it has significant anticholinergic side effects.24 Benzodiazepines work quickly and effectively in patients with panic disorder and concomitant NCCP, but use should generally be short term to avoid physical dependence. One approach to managing patients with severe panic disorder and NCCP is to prescribe a short course of a low-dose benzodiazepine until the patient can be seen by a mental health professional for further care.19 SSRIs have a more encouraging side-effect profile than benzodiazepines, although only one small study found them effective in patients with NCCP.21
CBT is also useful for treating NCCP. Studies show that treated patients have a 48% to 80% improvement in symptoms over control populations and that these improvements persist for at least 2 years after cessation of therapy.19,24
Patients with NCCP rarely fit neatly into one of the previously discussed categories. Indeed, NCCP often has multiple causes, and the clinician should bear this in mind. For patients with atypical chest pain and few cardiac risk factors, questions designed to elicit a psychiatric cause for the pain might be asked early in the evaluation, to avoid making a psychiatric diagnosis a diagnosis of exclusion.19 Although studies looking for a connection between GERD and psychological disorders have often been inconclusive or flawed, there is evidence that psychological issues are quite significant for about 30% of patients with GERD.25 Furthermore, a patient suffering from panic or generalized anxiety who is frequently tense could have musculoskeletal chest pain due to this tension.
Although the pathophysiology of some NCCP remains a mystery, a vital part of managing affected patients—particularly those inclined toward anxiety and panic—is active reassurance that their pain is most likely not cardiac. Active reassurance involves not only what clinicians say but also what they do. For example, only one third of physicians in one study discontinued or suggested discontinuing drugs that patients had been taking when their chest pain was thought to be cardiac in origin, even after the pain was determined to have a noncardiac cause.30 Taking such a step would do more than prevent possible iatrogenic complications. It also would send a strong message of reassurance to the patient.
The long-term outlook for patients with NCCP is good, with a 10-year mortality rate of less than 1%.19 However, many patients suffer significant morbidity from their pain and are more likely to be seen by a primary health care provider than are members of the general population.19 Patients who suffer from NCCP are slightly more likely to use the health care system than are those with cardiac chest pain. Those with low-grade NCCP are five times more likely to present to a provider than are patients with severe NCCP.2,3,30 Not only do these patients present more often, but the majority will continue to have pain 5 years after being seen and have a significantly worse quality of life based on the severity of their pain.2
The burden on both the medical system and the patient with NCCP is significant. The clinician should take care to rule out potential cardiac causes of chest pain, particularly in patients with known risk factors. Just as important, however, is being prepared to identify and treat the more common causes of NCCP.
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