Chapter 77. Chest Pain

1. What signs and symptoms point to a serious cause of chest pain?

2. What key historical elements will help to narrow the differential diagnosis?

3. What studies should be ordered?

According to the 2006 National Hospital Ambulatory Medical Care Survey, 6,392,000 patients presented to emergency departments with a chief complaint of chest pain or related symptoms. Of those, 1,976,000 patients were admitted to the hospital, with a mean length of stay of 3.7 days. Chest pain was the principal admitting diagnosis in 5.4% of all admitted patients.

Because the morbidity and mortality is high if clinicians “miss” a cardiac presentation of chest pain, a significant portion of these admissions are specifically for the purpose of ruling out myocardial infarction. In one study of patients presenting to an emergency department with complaints consistent with cardiac ischemia, 17% ultimately had cardiac ischemia, while 27% had stable angina or other cardiac conditions. Fifty-five percent had noncardiac conditions causing their symptoms. The wide differential diagnosis for this heterogeneous group of patients includes nonischemic life-threatening etiologies as well as more benign causes. Unfortunately, in this study, 2.1% of the patients with acute myocardial infarction were erroneously discharged; this figure plays prominently in the low threshold to admit patients with chest pain.

Chest pain also occurs in patients already admitted to the hospital for other reasons. These patients have already suffered some degree of physical decompensation and the occurrence of chest pain may indicate illness, a complication of hospitalization, or a patient's response to a very stressful situation. The hospitalist must evaluate the possibility of an immediate life-threatening event, consider the entire differential of possible etiologies, and integrate this information with the patient's prior clinical diagnoses and course.

Rapid Assessment

The initial evaluation of a patient reporting chest pain requires the rapid identification and treatment of any life-threatening conditions. These include the five “do-not-miss” causes of chest pain: (1) aortic dissection, (2) acute myocardial infarction, (3) pulmonary embolism, (4) pneumothorax, and (5) esophageal rupture (Table 77-1) . The electrocardiogram (ECG) is the most important screening intervention for early risk stratification and is often performed at the point of triage as one of the “vital signs.”

All potentially unstable patients with chest pain should have an intravenous line, supplemental oxygen, and a cardiac monitor placed as soon as possible. This can be accomplished even before the arrival of the physician at the patient's bedside. The ECG, chest pain characteristics, prior history of coronary artery disease (CAD), and age are independent predictors of acute MI. Although the traditional risk factors for CAD predict long-term risk of disease, they are less helpful in predicting acute MI, and a primary focus on risk factors could be misleading for patients with ACS but with few risk factors. Therefore, an initial risk stratification assessment should include a review of the ECG, analysis of current vital signs, and a targeted history and physical examination. A stat portable chest radiograph should be ordered. With this information, patients can be assigned to one of four classes:

1. Those with new ST-segment elevations on initial ECG. (These patients should receive immediate consideration for emergent reperfusion therapy.)

2. Those without ST-segment elevation on initial ECG but who are at high risk on the basis of ECG findings, hemodynamic instability, or history. (These patients should be admitted and consideration should be given for immediate antiplatelet and antithrombotic treatment if no contraindications.)

3. Those who have no objective evidence of ACS but have symptoms that warrant evaluation. (These patients form the “low risk” chest pain cohort that constitutes the majority of patients undergoing ED evaluation for chest pain.)

4. Those who have an obvious noncardiac cause for symptoms.

Patients with hemodynamic instability, persistent ECG changes, or ongoing symptoms should be evaluated for emergent coronary angiography. Patients with an obvious noncardiac cause for symptoms would be managed, depending on the alternative diagnosis.

History

The history remains critically important in initial risk stratification because objective evidence including a diagnostic ECG is only present in a minority of patients. Once emergency conditions have been ruled out or stabilized, a targeted history should be used to identify and prioritize a list of differential possibilities (Table 77-2) . The examiner needs to determine what portions of the history and physical examination are relevant to the clinical questions of whether the patient's symptoms and signs point to cardiac disease or to other serious causes requiring immediate intervention and, if the evaluation is taking place in the emergency department, whether the patient requires admission to the hospital. Coronary artery disease (CAD) is the leading cause of death for both men and women, and most patients with a prior history of CAD should be admitted to the hospital if they present with chest pain and have a clinical presentation that could be consistent for acute coronary syndrome. For this reason, in patients presenting with chest pain, obtaining a prior history of angina or known CAD is essential to determining if the patient's current symptoms suggest either an acute coronary syndrome (ACS) or unstable angina (USA).

More than 30 years ago, the Coronary Artery Surgery Study (CASS) enrolled 18,844 men and 6,097 women after coronary angiography. Using the reported chest pain characteristics, they classified patients as having definite angina, probable angina, probably not having angina, and definitely not having angina. Combining all patients classed as probably not and definitely not having angina as having nonischemic pain was subsequently shown to discriminate between patients with CAD and those with negative ETT and coronary angiograms. Even today, this scheme is used to facilitate decision making. Classic symptoms of angina include chest heaviness, pressure, tightness, or burning (sometimes with vigorous denial of pain), provocation by physical or emotional stress or cold, relief by rest, radiation to neck, jaw, or shoulder, duration >2 minutes and <20 minutes (unless MI), +/– dyspnea, nausea, and vomiting, diaphoresis, presyncope, and palpitations (Table 77-3).

Patients should be questioned regarding the nature of their “discomfort” (as some patients may not believe that they are experiencing chest pain). Additional questioning should include location, onset, character, severity, radiation, alleviating and exacerbating factors, time course, history of similar episodes, and associated symptoms such as diaphoresis, shortness of breath, and nausea and vomiting. Early questioning about prior experiences of identical symptoms may save considerable time and effort, but one must take care to avoid premature closure in diagnostic decision making, especially when myocardial ischemia is a possibility.

Pain Characteristics

The “PQRST” (provocative/palliative factors, quality, radiation, severity, timing) approach can be used to qualify the different aspects of the patient's pain and suggest likely etiologies. Physicians should be aware that differences in gender, culture, and underlying pathology may lead to differences in the experience and description of pain. Atypical presentations of ACS are more likely in the elderly and women, especially those over the age of 65, and include symptoms such as dyspnea, epigastric discomfort, and palpitations. In one study of patients with active cardiac ischemia, women reported pain in the neck area while men were more likely to feel pain in the shoulder. Women were more likely to describe their pain as sharp, hot, burning, throbbing, or pressing. In addition, women were more likely to experience various nonpain symptoms, such as trembling, upset stomach, shortness of breath, postprandial pain, palpitations, and neck or throat sensations.Despite anecdotal evidence, most studies have not found a significant increase in the prevalence of unrecognized or atypical presentations in diabetics.

Provocative and Palliative Factors

Pain associated with exertion (physical exercise, stress, or sexual intercourse) is often due to cardiac causes. Pain with swallowing suggests an esophageal disorder. Patients with pain that reliably occurs after eating likely have a gastrointestinal etiology; however, some patients with coronary disease have postprandial angina (typically after dinner) in addition to rest angina. One possible mechanism for postprandial angina involves increased myocardial oxygen demand after food intake, but studies suggest that a decrease in coronary blood flow (steal phenomenon) may play a role. In contrast, improvement with food or antacids suggests peptic ulcer disease or gastritis. Pleuritic pain is worst with deep inspiration and suggests pulmonary disease, pericarditis, or a musculoskeletal etiology. In one study, 47% of all patients who were evaluated for and ultimately found to have pulmonary embolism reported pleuritic pain. However, 17% of all patients found to have pulmonary embolism reported chest pain that was nonpleuritic. Pain that is worse with exertion and better with rest is suggestive of cardiac ischemia or pulmonary embolism. More commonly pleuritic but sometimes severe, steady, and retrosternal, the pain of acute pericarditis is classically worst with lying flat and improved with leaning forward. Musculoskeletal pain will be reliably triggered by specific movements. An important consideration is that improvement with nitroglycerin or mucosal anesthesia (“GI cocktail”) is not helpful for distinguishing cardiac from noncardiac causes of pain. Physicians should use these medicines as appropriate to relieve pain but avoid the error of using the patient's response to guide decision making. Likewise, pain with chest wall palpation should not be used to exclude a cardiac etiology for chest pain.

Quality

The patient's description of the quality of pain should be noted (Table 77-4). In the International Registry of Acute Aortic Dissection (IRAD) study, 50.6% of patients with aortic dissection described a ripping or tearing sensation. In contrast, the pain of myocardial ischemia is classically described as heavy, squeezing, crushing, or pressure. Sharp pain is most typical of pulmonary, musculoskeletal, or gastrointestinal causes; however, beware of the imprecision of the term sharp, which to some patients simply means intense. Burning pain can be seen in cardiac and gastrointestinal disease. Patients suffering from herpes zoster may also report a burning sensation. The nature of the chest pain does not definitely discriminate cardiac from noncardiac chest pain. Keep in mind that “atypical” descriptions of pain are quite common in patients with myocardial ischemia, including sharp, stabbing or, less commonly, pleuritic pain. For example, pain described as pressure-like or squeezing has a Likelihood Ratio (LR) of less than 2 and hence does not reliably distinguish cardiac disease from other causes of chest pain such as esophagitis. Likewise, a pleuritic, stabbing chest pain that has a LR of 0.2 – 0.3 may reduce the likelihood that the chest pain is cardiac in origin but it does not rule it out.

Radiation

A description of pain radiation may be helpful. Patients suffering from cardiac ischemia will often describe radiation down the left arm or up into the neck or jaw. Interestingly, right arm radiation was also shown to have an increased predictive value for true myocardial ischemia in one study (radiation to the left arm LR 2.0; right arm LR 3.0; both arms LR 7.0). Aortic dissection should be suspected in patients complaining of pain radiating to the back, especially the interscapular area. This can also occur with posterior ulcers as well as with myocardial ischemia. Radiation to the trapezius ridge is a feature of pericarditis. Kehr's sign refers to pain felt at the tip of the scapula that is a referred symptom from diaphragmatic irritation due to intraabdominal pathology. Conditions causing this symptom are generally serious (ie, splenic rupture or acute cholecystitis), so a careful abdominal exam should be performed in all patients reporting shoulder pain without a clear thoracic etiology.

Severity

The severity of pain reported is dependent on each patient's pain tolerance. Very severe pain with signs of distress should bring to mind aortic dissection, acute myocardial infarction, acute pulmonary embolism, acute pericarditis, tension pneumothorax, or ruptured esophagus. Quantifying pain on a scale from 1 to 10 enables assessment of treatment response.

Timing

Pain from cardiac ischemia generally lasts minutes; myocardial infarction pain can last for hours. Pain lasting for seconds is not due to myocardial ischemia, and can be a helpful feature in narrowing the differential. Likewise, constant pain for days to weeks is very unlikely to be cardiac in nature. Myocardial infarction follows circadian rhythms and is more likely to occur in the morning. Pain that is maximal at sudden onset can be due to pneumothorax, pulmonary embolism, or aortic dissection. Patients with herpes zoster can have pain lasting for days before the rash appears.

Associated Symptoms

While taking the history, the physician should note associated symptoms volunteered by the patient, in addition to inquiring about the presence of others. Prominent dyspnea should raise concern for pulmonary or myocardial/pericardial etiology. Nausea and vomiting are associated with cardiac disease as well as gastrointestinal disease. Diaphoresis is also associated with cardiac disease but may simply be a marker of severe pain. Diaphoretic patients with chest pain should be assumed to have an emergency condition until proven otherwise. Belching or sour taste in the mouth often represents reflux, but nausea and belching may accompany cardiac ischemia, classically when the inferior myocardial wall is involved. Generalized fatigue with recent illness may indicate myocarditis or pericarditis. Severe emotional distress may trigger acute stress-induced or takotsubo cardiomyopathy, which can present with or without chest pain. Fever, night sweats, and weight loss should suggest cancer and possible complications. Syncope with chest pain could be due to ischemia-induced arrhythmia, severe aortic stenosis, aortic dissection, or massive pulmonary embolism. Stroke symptoms can occur in Type A aortic dissections when the carotid arteries are involved.

Risk Factors

The presence or absence of risk factors for CAD does not change the likelihood of cardiac disease sufficiently to discriminate between those who might have the disease and those who do not require admission to the hospital. Although the presence of risk factors for CAD may change the prior probability of CAD and are useful in assessing the risk in populations, the absence of these risk factors alone does not sufficiently reduce the likelihood of CAD in individual patients to allow discharge without considering other factors. The presence of chest pain as in this case and/or ECG changes remain predictive of cardiac ischemia in the acute setting, even in the absence of risk factors of CAD.

Male gender, age over 55 years, family history of CAD, known CAD, vascular disease (cerebrovascular, peripheral vascular disease), diabetes mellitus, hypercholesterolemia, hypertension, and tobacco use are recognized as risk factors for CAD. Cocaine is a risk factor for acute myocardial ischemia as well as atherosclerosis, and a history of recent cocaine use by a patient complaining of chest pain should prompt consideration of CAD work-up. As mentioned previously, the absence of these risk factors is not sufficient to exclude ACS. For example, in a 40-year-old patient with anginal chest pain the risk of CAD is roughly 6%; smoking increases this risk to 13%. However, physicians cannot afford to miss the 6% of patients who have significant CAD, so the absence of a smoking history or other risk factors should not remove consideration of ACS.

The symptoms and signs of chest pain in acute PE depend upon the size of embolism. Small to medium sized emboli may cause dyspnea, chest pain, cough, tachypnea, tachycardia, mild fever (<39 degrees), and wheezing in <5% of patients. Massive pulmonary emboli may cause syncope, chest pain, dyspnea, and signs of right ventricular (RV) dysfunction (RV heave, RV S3, JVP, soft systolic murmur of tricuspid regurgitation). Because these symptoms are nonspecific for PE and are commonly associated with other potentially life-threatening causes of chest pain, risk factors for PE do help guide the clinical decision making process. A prior history of venous thromboembolism (VTE), known cancer, or known hypercoagulable states place the patient with dyspnea, pleuritic chest pain, apprehension, cough, diaphoresis, hemoptysis, or syncope into a high risk category. For patients that have never had a VTE, asking about risk factors can guide further testing and the decision to admit the patient to the hospital.

As most pulmonary emboli result from deep vein thrombosis, the risk factors are the same for both entities. Patients with pulmonary embolism will most often have at least one risk factor, and those who do not are often found later to have occult cancer or coagulation abnormalities. Common risk factors for deep vein thrombosis include immobilization (paresis, paralysis), institutionalization or hospitalization within the previous three months, recent surgery, central venous procedure, cancer, pregnancy, estrogen and progestin drugs, inherited thrombophilias, coagulation disorders, trauma, acute inflammatory diseases, acute infection, chronic obstructive pulmonary disease, certain renal diseases, and heart failure. A case-control study in Olmsted County, Minnesota, found the following risk factors most predictive for first-time VTE: hospital or nursing home residence, surgery, trauma, cancer, chemotherapy, neurologic disease with paresis, central venous catheter or pacemaker, varicose veins, and superficial vein thrombosis.

Results have been mixed in studies of smoking as a risk factor for pulmonary embolism. Obesity, heavy smoking, and hypertension were found to be risk factors for pulmonary embolism specifically in women in one study. Prolonged air travel increases risk, especially in flights lasting more than eight hours.

The most common risk factor for aortic dissection is systemic hypertension. Other recognized risk factors include history of connective tissue disease (such as Marfan syndrome or Elhers-Danlos syndrome), vasculitis, prior heart or valvular surgery, Turner syndrome, crack cocaine use, positive family history, and cardiac catheterization.

Risk factors for spontaneous pneumothorax include positive family history, chronic obstructive pulmonary disease, cystic fibrosis, Marfan syndrome, smoking, homocystinuria, and extrapelvic endometriosis. Occasionally, spontaneous pneumothorax occurs in otherwise healthy individuals, classically in tall young men. In addition, patients infected with the human immunodeficiency virus are at increased risk for pneumothorax resulting as a complication of Pneumocystis jirovecii or mycobacterial infection. Patients already hospitalized may develop pneumothorax as an iatrogenic complication of a procedure (thoracentesis or central line placement).

The Physical Examination

The physical examination is often normal in patients with chest pain, even when serious pathology is present. However, certain signs can be helpful for risk stratification and for determining symptom etiology. As mentioned above, overall appearance combined with vital signs including pulse oximetry should be noted early in the assessment. Tachycardia and hypotension are ominous signs in the patient with chest pain and may require intervention to prevent cardiovascular collapse. Tachypnea can be subtle; the clinician should measure this vital sign independently if suspicious despite a normal documented respiratory rate, as it is the most common sign of pulmonary embolism. New fever can direct the workup toward infectious etiologies but low-grade fever is a nonspecific finding and may also be associated with pulmonary embolism, myocardial infarction, pneumonia, and pericarditis. New hypoxia is a clue to either cardiac (pump failure with CHF) or serious pulmonary pathology. However, a normal oxygen saturation level or A-a gradient does not rule out PE. In one study of angiographically proven PE, 17% of patients had a pO2 greater than 80 mm Hg and 5% had a pO2 >100 mm Hg. The A-a gradient is no more accurate than the O2 saturation and not all patients will be hypoxic or have tachypnea or tachycardia.

It is important to perform cardiac auscultation in a quiet room and ask the patient to lean forward. Using the diaphragm of the stethoscope, the examiner should listen for regurgitant murmurs and pericardial friction rubs. The finding of a new systolic mitral insufficiency murmur might indicate myocardial ischemia, a flail mitral leaflet, or decompensated heart failure and puts the patient in a high risk category. A new murmur of tricuspid insufficiency might signal right ventricular overload from PE. A diastolic murmur may reflect acute aortic insufficiency and aortic dissection. Any new murmur, especially in the presence of fever, may signify endocarditis. A pericardial friction rub classically occurs in three phases corresponding with atrial systole, ventricular systole, and ventricular diastole. However, it is uncommon to hear all three phases, and the rub may be transiently heard. The examiner is mostly likely to appreciate the friction rub by firmly placing the diaphragm of the stethoscope over the left lower sternal border with the patient leaning forward after an exhalation. The examiner should ask the patient to stop breathing for a few seconds to distinguish a pericardial from pleural rub. A pericardial friction rub does not always specify primary acute pericarditis. It may also be associated with a large transmural acute MI. A pleural rub may be present in patients with pulmonary embolism, effusion, pneumonia, or pleuritis. Hannan's crunch is synchronous with the heartbeat and indicates mediastinal or pericardial air suggestive of ruptured esophagus, pneumothorax, or tracheobronchial tree injury. An S3 or S4 gallop could signal changes in ventricular compliance and function and an accentuated P2 (second heart sound louder over the pulmonic area) is consistent with pulmonary hypertension.

Pulmonary examination may reveal unilateral absent or decreased breath sounds in patients with pneumothorax. Rales may indicate acute heart failure in the patient experiencing myocardial infarction, atelectasis (commonly seen with splinting from PE, trauma, or musculoskeletal pain), or pneumonia. Abdominal examination should focus on identifying potential abdominal causes of chest pain, such as biliary disease, pancreatitis, or trauma.

The musculoskeletal exam may reveal chest wall tenderness that exactly mimics the patient's symptoms. It is important to note that tenderness may be present along with myocardial ischemia in some patients. In fact, up to 15% of patients with chest wall tenderness on palpation that reproduces their pain will have an acute MI.

Lower extremities should be examined for signs of heart failure or deep vein thrombosis.

Electrocardiography

Myocardial Ischemia

Inpatients reporting chest pain should have an ECG, and comparison with prior ECGs should be made to assess for dynamic changes.

ST-segment elevation: The ESC/ACCF/AHA/WHF committee for the definition of myocardial infarction established specific ECG criteria for ST-segment elevation myocardial infarction including 2 mm of ST segment elevation in the precordial leads for men (1.5 mm for women) and greater than 1 mm in other leads. The elevations must be present in at least two contiguous leads, corresponding to a specific arterial territory. A new left bundle branch block should be treated similarly to ST-segment elevation in the appropriate patient, with immediate reperfusion therapy.

Many patients will have alternate causes of ST-segment elevation (benign early repolarization, left ventricular aneurysm, pericarditis, hyperkalemia, bundle branch block, Prinzmetals angina) so experience interpreting ECGs and comparison with old ECGs is critical.

Bundle branch block and paced rhythms make ECG interpretation challenging. The Sgarbossa criteria assign points to significant ECG findings in the presence of an old left bundle branch block: concordant ST-segment elevation of 1 mm or more in any lead (5 points), ST segment depression of 1mm or more in leads V1, V2, or V3 (3 points), discordant ST-segment elevation of 5 mm or more (2 points). A score of at least 3 is associated with high specificity for myocardial infarction but low sensitivity. In patients with LBBB or paced rhythms, the finding of ST-segment elevation ≥5 mm in leads with a negative QRS complex is highly specific for myocardial infarction.

Identification of inferior wall myocardial infarction should be followed by careful examination for evidence of posterior wall involvement (V1 ST depression), conduction disturbance (Wenckebach, bradycardia, or complete heart block) and right ventricular infarction (right-sided ECG, lead rV4).

ST-Segment Depression

ST-segment depression (0.5 mm or greater) predicts increased risk of myocardial ischemia. The greater the extent of depression, the higher the risk of MI and death. Posterior leads may help differentiate the patient with anterior ST-segment depression who has ischemia from the patient who has an acute posterior wall MI.

T-Wave Inversion

These indicate lower risk than ST depressions. Likewise, the presence of Q-waves is less predictive of adverse cardiac events than ST-segment depression or elevation.

Pulmonary Embolism

The findings of right ventricular strain, S1Q3T3, and new incomplete right bundle branch block may suggest pulmonary embolism but are not sensitive. Sinus tachycardia is the most common rhythm disturbance. Atrial fibrillation is seen in a small percentage of patients with pulmonary embolism but is rarely the only sign pointing to that diagnosis.

Limitations

Although often abnormal in small- to medium-sized pulmonary emboli, the ECG is nonspecific and is normal in 23% of patients with submassive PE and 6% of patients with massive PE. For this reason, a normal ECG by itself cannot guide decision making relating to further diagnostic workup.

Pericarditis

Characteristic findings include diffuse ST-segment elevation that may be confused with acute MI or early repolarization. The lack of regional ischemic changes (ie, diffuse rather than localized ST elevations), as well as a suggestive history and cardiac examination will help distinguish this entity from acute MI.

Classic stages of ECG changes in pericarditis are:

Stage I (first few weeks of pericardial inflammation)

• Diffuse concave-upward ST-segment elevation with concordance of T waves
• ST-segment depression in aVR or V1
• PR-segment depression in all leads except aVR and V1
• Low voltage
• Absence of ST-segment changes

Stage II (days to several weeks)

• ST segments returning to baseline
• T-wave flattening

Stage III (end of second or third week)

• T-wave inversion

Stage IV (lasts up to three months)

• Gradual resolution of T-wave inversion

The classic four stages of ECG changes occur in only 50% of patients, and the ECG may be normal in 10% of patients. Some of the changes are nonspecific and may be confused with myocardial infarction or early repolarization.

Additional Considerations

The findings of electrical alternans or low voltage in an ECG for a patient with chest pain should prompt consideration of pericardial effusion or hemorrhage. ECG abnormalities are common after stroke. Cerebral T waves (deep, symmetric T-wave inversions) are classically seen with subarachnoid hemorrhage. ST-segment deviations may occur in stroke patients as well, sometimes making differentiation between stroke and myocardial infarction difficult in difficult-to-assess patients.

Laboratory Testing

Patients admitted to the hospital with chest pain or who develop chest pain while hospitalized should have basic laboratory tests performed, including a metabolic panel and complete blood count. Additional laboratory tests may be sent based upon clinical suspicion. Cardiac biomarkers and D-dimer assays are discussed below. Patients with possible intra-abdominal pathology should also have liver enzymes and a lipase ordered. Cardiac biomarkers should be drawn as a baseline but should not deter admission as they may initially be negative despite ischemia.

Cardiac biomarkers: A current definition of myocardial infarction involves typical rise and/or fall of cardiac biomarkers, along with ischemic symptoms, ischemic EKG findings (ST-segment deviation, Q waves), and/or coronary artery intervention.Thus, cardiac biomarkers are essential in the work-up of patients suspected of having cardiac etiology of their chest pain.

Creatine kinase (CK) and the CK-MB isoform (unique to the myocardium) have similar temporal patterns in cases of myocardial injury, rising within 4 to 8 hours and peaking between 12 and 24 hours (slightly earlier for CK-MB). CK-MB is cleared within 36 to 48 hours, and CK is cleared within 3 to 4 days. Troponin levels rise within 6 hours, peak after 12 hours, and are cleared after 7 to 14 days.

Troponins exhibit superior sensitivity and specificity when compared with CK and CK-MB for the diagnosis of myocardial infarction and help identify those patients at increased short- and long-term risk. Elevations identify patients who would benefit from aggressive treatment such as antithrombotic, antiplatelet, and coronary intervention. Cardiac troponin I has a higher specificity than cardiac troponin T, as it is not found in skeletal muscle. Some advisory groups argue for use of CK-MB to diagnose reinfarction, but others prefer troponin for this purpose as well.

Cutoff values for troponins, CK, and CK-MB vary by institutions. CK-MB in healthy patients generally ranges up to 5 microg/L or <3% of the total CK. Higher values are abnormal and may be due to myocardial injury or several other conditions generally easily differentiated based upon clinical grounds. There is ongoing debate regarding whether rises in serum biomarkers represent only irreversible or both reversible and irreversible injury, but rising cardiac biomarkers should be assumed to indicate at-risk myocardium. Likewise, the “normal range” of cardiac troponin is a troublesome concept, as any detectable troponin level has been shown to have prognostic significance and may be a marker of chronic as well as acute disease.

Troponins may be elevated in patients with renal failure who do not have evidence of myocardial damage. This is possibly due to decreased clearance as well as increased incidence of comorbid pathology (including pathology seen at the cellular level). These patients also have a high rate of coronary disease. Therefore, an appropriate serial rise in troponin is more helpful than an elevated, stable value for the diagnosis of myocardial infarction. Other conditions associated with increased troponin values include massive pulmonary embolism, myocarditis, cardiopulmonary resuscitation, cardioversion, heart failure, stroke, stress cardiomyopathy, and demand ischemia (Table 77-5).

A typical “rule-out” protocol after negative initial troponin often includes additional troponins at regular intervals (sometimes as frequently as every three hours) and a final troponin at the end of six to nine hours. Limitations: Although troponin is not detected in the blood of healthy people and is the standard criterion for the diagnosis of MI, the biomarker lacks sensitivity for USA.

D-dimer: The D-dimer is formed during breakdown of thrombi, occurring in cases of venous thromboembolism (VTE) but also as an integral part of the body's repair mechanism in other conditions (Table 77-6). The use of D-dimer in the appropriate patient can exclude pulmonary embolism as a cause of chest pain. The test demonstrates high sensitivity with poor specificity overall, but assays differ significantly in their sensitivities. ELISA assays are more sensitive than latex or erythrocyte agglutination assays for diagnosis of pulmonary embolism and are thus preferred. The Wells score defines low, moderate, and high risk patients. Evidence suggests that a low Wells score combined with a negative D-dimer result (less than 500 ng/mL) is sufficient to exclude pulmonary embolism (Table 77-7).

The use of D-dimer testing may be of limited to no value in patients who are already hospitalized at the time of suspected pulmonary embolism, in contrast to those whose initial presentation is consistent with this diagnosis. Although the D-dimer has a very high negative predictive value, the test is not useful in cases of high pretest clinical probability. The usefulness of the test in patients with concomitant diseases is also limited. In pregnancy, not only are D-dimer levels typically elevated, but a negative D-dimer does not rule out VTE. The specificity of the D-dimer also decreases with increasing age. In 1 study, D-dimer allowed exclusion of VTE in roughly 52% of patients 40 years of age or less as compared to only 5% of those 80 years old. Hence, it should only be ordered in patients with a low clinical pretest probability of PE. It does not add any additional diagnostic value in those patients who need to proceed directly to imaging.

Imaging

Patients reporting chest pain should have a chest radiograph taken. Lateral decubitus imaging is most sensitive for diagnosing pneumothorax (with the affected side positioned higher than the unaffected side), but pneumothoraces of at least 100 mL should be visible on upright films. Supine films may miss much larger pneumothoraces. Mediastinal air should raise concern for ruptured esophagus or airway. A widened mediastinum may be seen simply due to technique, but it is also associated with aortic dissection, seen in 61.6% of dissections in one study.

Computed tomography with contrast is commonly used to detect pulmonary embolism, and the historical gold standard, pulmonary angiography, is rarely needed. Studies have suggested a negative CT scan is sufficient in ruling out the diagnosis for patients with a low or moderate pretest probability, but high suspicion combined with a negative scan should prompt consideration of further workup. Further workup for high risk patients may include pulmonary angiography or lower-extremity venous ultrasound. Some institutions perform CT venography immediately after CT pulmonary angiography in order to increase sensitivity for thromboembolic disease but this requires an increased exposure to contrast.

Computed tomography is often the initial test for evaluation of aortic dissection, but transesophageal echocardiography is an excellent alternative and can be performed at the bedside. Magnetic resonance imaging is useful for imaging chronic dissections to determine whether an interval change has occurred.

Bedside echocardiography is a noninvasive imaging modality that can be rapidly performed to assist diagnosis and management of several conditions associated with chest pain. Specifically, its use should be considered for patients with suspected acute valvular disease, aortic dissection, pericardial effusion, or unexplained hemodynamic instability. It may also be helpful for distinguishing acute MI from pericarditis, with important treatment implications.

Stress Testing

Hospitalists are increasingly asked to manage the workup of chest pain patients who are at low but not negligible risk for coronary disease. The admission status of these patients will vary by institution. Chest pain “observation units” are becoming more popular and may be staffed by emergency physicians, hospitalists, cardiologists, or midlevel providers. The general goal of these units is to expedite the workup of patients at low risk for an acute coronary syndrome. After a negative evaluation with serial biomarkers and ECGs, further risk stratification with stress testing is often performed to identify patients with missed acute coronary syndrome and those at high risk for early adverse events.

Choosing which type of stress test to use will depend on the characteristics of the patient, resources available, and the policies of the institution, as well as the information desired. Exercise ECG testing without imaging is the preferred test in most patients with interpretable ECGs and adequate exercise capacity. Exercise testing with echocardiography or radionuclide myocardial perfusion imaging will allow localization of abnormalities. Patients who are unable to exercise can undergo pharmacologic stress testing with dipyridamole, adenosine, or dobutamine. Dobutamine echocardiography, however, should be avoided in patients who may be suffering from active or unstable ischemia.

In general, patients with ongoing chest pain should be managed as if they have unstable angina. However, low-risk patients with no prior history of myocardial infarction may have rest imaging performed with myocardial perfusion imaging or echocardiography. Coronary computed tomographic angiography shows promise in single-center studies for excluding acute coronary syndromes in patients with no history of myocardial infarction or known coronary disease, but this alternative to stress testing requires further validation of efficacy, cost effectiveness, and safety before widespread use can be endorsed.

Stress testing is useful both for diagnostic and prognostic purposes in patients suspected of having coronary heart disease, but due to the test characteristics, diagnostic testing should not be performed in patients with a very low pretest probability (based upon any of several validated decision aids) of having disease, as most positive tests in this setting represent false positives. Women have been noted to exhibit more false positives on stress testing, though current recommendations do not differ for men and women.

Some patients assessed to be at low risk for acute coronary syndrome may be safely discharged for outpatient stress testing within 72 hours in accordance with the 2007 ACC/AHA guidelines. Prior to discharge, these patients should have undergone at least a 6–12 hour observation period with two or three sets of negative cardiac enzymes and have normal or unchanged ECGs. One observational study found this to be a safe and feasible approach associated with a low risk of short-term adverse outcomes. Of 871 low risk patients undergoing outpatient stress testing, 2% had coronary artery disease requiring intervention and 0.3% had a myocardial infarction within six months. Importantly, the stress test appointment was made for the patient at the time of evaluation, and 92.2% of patients completed the outpatient stress test. Seventy-six did not have the test completed due to cancellation of the test or failure to keep the appointment. Available follow-up on 67 of these 76 patients showed no adverse cardiac events. This strategy is not appropriate for patients with questionable compliance with follow-up appointments. Direct scheduling and/or verbal communication with the primary care physician is advisable. Patients with a positive (and possibly indeterminate) stress test result should have a cardiology consultation while in the hospital. Those with negative results may be discharged.

As is true for many aspects of hospital-based medicine, hospitalists are uniquely positioned to enact quality improvement measures that will benefit chest pain patients. These measures will be institution specific, but several general considerations deserve attention. It is important to avoid the pitfall of placing too much diagnostic importance on an individual patient's response to therapy. However, treating pain adequately should be a primary goal implemented early in the evaluation of a chest pain patient, regardless of presumed etiology. The hospitalist is tasked with coordinating all aspects of a patient's care, and effective communication among healthcare workers is paramount. In addition, patient-centered care requires effective communication and understanding of the hospital experience from the patient perspective. Knowledge and respect for patients' needs and concerns can diminish the helplessness many feel during admission to the hospital. Standardizing chest pain algorithms, especially for acute coronary syndrome evaluation, can save considerable time and effort and if accepted institution-wide, may allow discharge of low-risk emergency department patients who would have otherwise been admitted. Lastly, taking time to communicate and coordinate with primary care physicians will enable earlier discharges and improve overall patient care.

The symptom of chest pain suggests a wide diff erential diagnosis that can be narrowed by a careful history, physical examination, and appropriate testing to rule out life-threatening disorders. Most patients will turn out to have non-lifethreatening disorders. Although these patients likely do not require continued hospitalization, they should receive education about the most likely diagnosis, treatment, what symptoms would prompt a reassessment and where this should occur, and follow-up with their primary care physicians.