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Tintinalli's Emergency Medicine > Section 7: Cardiovascular Disease > Chapter 49.
Approach to Chest Pain >
Overview
Approximately 5 percent of all U.S. ED visits, or about 5 million visits a year, are for
chest pain, but accurate diagnosis remains a challenge.1,2 This chapter covers the
approach to acute chest pain, with attention to identifying patients with potentially
serious disorders.
Pathophysiology of Chest Pain
Stimulation of visceral or somatic afferent pain fibers results in two distinct pain
syndromes. The dermis and parietal pleura are innervated by somatic pain fibers, which
enter the spinal cord at specific levels and are arranged in dermatomal patterns. Visceral
pain fibers are found in internal organs, such as the heart and blood vessels, the
esophagus, and the visceral pleura. These visceral pain fibers enter the spinal cord at
multiple levels and map to areas on the parietal cortex corresponding to the cord levels
shared with the somatic fibers. Pain from somatic fibers is usually easily described,
precisely located, and experienced as a sharp sensation, whereas pain from visceral fibers
is more difficult to describe and is imprecisely localized. Accordingly, those experiencing
visceral pain are more likely to use terms such as discomfort, heaviness, or aching.
Patients frequently misinterpret the origin of visceral pain, because it is often referred to a
different area of the body corresponding to an adjacent somatic nerve. For example,
diaphragmatic irritation can present as shoulder pain, and arm pain may actually
represent myocardial ischemia.
Gender, age, comorbidities, medications, drugs, and alcohol may interact with
psychological and cultural influences to affect the patient's perception and
communication of pain.
Definitions
The phrase acute chest pain, commonly used in emergency medicine, deserves definition.
The term acute means of sudden or recent onset. While there is no precise time period
defined, in common practice acute means that the patient stops his or her usual activity to
seek medical attention, typically within minutes to hours. Some studies of acute chest
pain patients in the ED limit entry to those with chest pain of less than 24-h duration. The
term chest in this context means a location described by the patient on the anterior thorax,
from xiphoid to suprasternal notch and between the right and left midaxillary lines. This
is because the major serious thoracic disorders typically manifest symptoms localized to
the anterior thorax. While it is true that pain localized to the back, between the base of the
neck and the lumbar region, is on the thorax cage, in isolation, pain localized to this
region is approached differently (see Chap. 282). That said, there are occasional patients
with serious and life-threatening intrathoracic disorders who will manifest a location of
their most intense pain outside the boundaries noted above. In addition, some patients
may have migratory pain that has moved out of the anterior chest by the time the patient
reaches medical attention. Therefore, clinicians are encouraged to include within their
differential diagnosis important and significant intrathoracic disorders when patients
describe pain in adjacent regions; e.g., epigastric, neck and jaw, and arm. The term pain
describes a noxious uncomfortable sensation. However, pain perception and description
vary widely, and patients may use terms such as ache or discomfort. Alternative
descriptions are common in the elderly. Similar to alternative locations, clinicians should
be attuned to variation in the patient's description of the noxious sensation. In summary,
acute chest pain refers to (1) recent onset, typically less than 24 h, that causes the patient
to seek prompt medical attention, (2) location described on the anterior thorax, and (3) a
noxious uncomfortable sensation distressing to the patient.
Initial Approach
The initial approach to acute chest pain recognizes that some causes are serious and lifethreatening, and prompt medical attention may prevent death and limit morbidity.
Therefore, patients should be triaged promptly. Patients with visceral-type chest pain
(defined below), significantly abnormal pulse or blood pressure measurements, or with
dyspnea should be placed directly into a treatment bed, a cardiac monitor initiated, an
intravenous line established, oxygen administered, and an ECG ordered. Other less welldefined patients also deserve expeditious evaluation, and experienced triage officers and
nurses often have a "gut" feeling about certain patients; that insight should be respected.
The initial evaluation should focus on immediate life threats: ensuring adequate airway,
breathing, and circulation. The vital signs should be assessed and repeated at regular
intervals as determined by the patient's condition. The initial history should focus on
specific questions concerning the character of the chest pain, the presence of associated
symptoms, and a history of cardiopulmonary conditions. The patient is asked to grade
pain intensity in order to follow response to therapy. A 0 to 10 scale is commonly used,
with 10 being the worst pain the patient can imagine and 0 being no pain at all. Focused
cardiac, pulmonary, and vascular examinations should follow.
If immediate life threats are not detected or have already been addressed, a more
extensive evaluation can be preformed. This "secondary survey" consists of a history that
defines symptoms more precisely. Chest pain should be assessed like other pain
syndromes, with specific questions concerning quality, location, radiation or migration,
severity, time and character of onset, progression, provoking factors, relieving factors,
and associated symptoms. If the pain has been episodic, the frequency of pain episodes
should be assessed over the past weeks to better determine progression. Risk factors for
cardiopulmonary disease should be assessed. The physical examination during this phase
should complete those body systems not evaluated initially as well as rechecking
abnormalities noted before. Many organizations have developed structured history and
physician examination forms for acute chest pain to direct the information-gathering
process and organize the diagnostic approach. Such structured records are particularly
helpful to less experienced physicians. Further diagnostic testing is directed by the
history and physical examination.
Categorization
A useful initial approach is to classify patients into three categories: (1) chest wall pain,
(2) pleuritic or respiratory chest pain, and (3) visceral chest pain. Chest wall pain is a
somatic pain, usually described as sharp in quality, that can be precisely localized (often
with one fingertip) and is reproducible by direct palpation and/or chest wall movement
during stretching or twisting. Pleuritic chest pain is also a somatic pain, usually described
as sharp in quality that is distinctly worsened by breathing or coughing. The term
pleuritic is potentially confusing; more than the pleura moves during respiration, and
disorders other than "pleurisy" may be worse with respiration. Visceral chest pain is
poorly localized and usually described as aching or heaviness. Important causes of chest
pain within each category are noted in Table 49-1.
Table 49-1 Important Causes of Acute Chest Pain
Chest Wall Pain Pleuritic Pain Visceral Pain
Costosternal syndrome Pulmonary embolism Typical exertional angina
Costochrondritis (Tietze syndrome) Pneumonia Atypical (nonexertional) angina
Precordial catch syndrome Spontaneous pneumothorax Unstable angina
Slipping rib syndrome Pericarditis Acute myocardial infarction
Xiphodynia Pleurisy Aortic dissection
Radicular syndromes Pericarditis
Intercostal nerve syndromes Esophageal reflux or spasm
Fibromyalgia Esophageal rupture
Mitral valve prolapse
A very useful principle in the clinical assessment of acute chest pain is that, with rare
exception, chest pain diagnosis is a composite picture, no one fact or observation make
the diagnosis. The challenge to the clinician is to take the often-confusing history and
nondiagnostic physician examination and select the useful features that guide further
assessment, management, and disposition.
Assessment of risk factors for cardiovascular disease can play a role in patient
assessment. Specifically, the presence of risk factors for coronary artery disease (cigarette
smoking, diabetes, hypertension, hypercholesterolemia, family history), aortic dissection
(middle aged, male gender, hypertension, Marfan syndrome), and pulmonary embolism
(hypercoagulable diathesis, malignancy, recent immobilization or surgery) are useful in
judging the probability of these diagnoses. Likewise, age can be used to assess the
probability of atherosclerotic disease; clinically significant coronary artery disease is rare
in patients under the age of 30. Acute cocaine use has been associated with acute
myocardial infarction, and chronic cocaine use is associated with accelerated
atherosclerosis and severe coronary artery disease (see Chap. 168). However, youth or
absence of risk factors does not completely eliminate any potentially serious cause of
acute chest pain.
The patient's medical record should be reviewed. The current ECG should be compared
with previous tracings. Results of prior cardiac studies (echocardiograms, stress testing,
or catheterizations), esophageal studies (endoscopy, oral contrast swallowing studies),
gastrointestinal studies (ultrasound, computed tomography), or pulmonary studies
(spirometry) should be reviewed and present symptoms interpreted in comparison with
these results. In general, cardiac stress studies within the previous 6 months and coronary
angiography within the prior 2 years are considered to likely reflect the current state of
the coronary circulation.
A practice to be decried is the use of therapeutic trials in acute chest pain; usually in the
form of (1) a "gastrointestinal (GI) cocktail" containing an antacid, antispasmodic, and
local anesthetic for gastroesophageal reflux, (2) nitroglycerin for myocardial ischemia,
and (3) nonsteroidal anti-inflammatories for chest wall pain. The placebo effect makes it
difficult to interpret a positive response; patients with definite myocardial ischemia have
been reported as experiencing complete pain relief with a GI cocktail. In addition,
nitroglycerin is a smooth muscle dilator and may produce relief in esophageal spasm and
biliary colic as well as myocardial ischemia. The analgesic properties of nonsteroidal
anti-inflammatories are not specific for any location.
Ischemic Equivalents
A confounding observation is that many patients with acute coronary syndrome (ACS,
defined below), perhaps as high as 40 percent, do not describe chest pain as their
predominant symptom.3 The absence of chest pain leads to delayed or inadequate antiischemic therapy and increased inhospital mortality.4
Truly silent myocardial ischemia does occur, but these patients are not likely to come to
the ED. For those that do, ischemic equivalents or atypical presentations are important to
note: dyspnea at rest or with less exertion compared to the patient's previous baseline;
shoulder, arm, or jaw discomfort; nausea; lightheadedness; generalized weakness; acute
change in mental status; or diaphoresis. Epigastric or upper abdominal discomfort can be
the presenting symptom of myocardial ischemia. Patients with sensory impairment due to
diabetes, advanced age, psychiatric disease, or altered mental status are more likely to
present with atypical symptoms with ACS. Atypical presentations of ACS also occur
more frequently in women and non-white populations compared to white males.5
Differential Diagnosis
When patients present with acute chest pain due to myocardial ischemia, the term acute
coronary syndrome, or ACS, is used because, on initial assessment, it is not possible to
determine if the patient has an acute myocardial infarction (AMI) or unstable angina
(UA). ACS is a common cause of acute chest pain; in a typical ED population of adults
over the age of 30 presenting with visceral-type chest pain, about 15 percent will have
AMI and 25 to 30 percent will have UA.1
The pain of myocardial ischemia is almost always retrosternal and diffuse, usually
described as a heaviness or pressure, and commonly radiates, usually to the neck or left
arm (see Chap. 50). In exertional angina, the pain is episodic, lasting minutes (usually
<10 min and not seconds or hours), provoked by exertion, and relieved by rest or
sublingual nitroglycerin. Exertional angina is most often due to atherosclerotic disease of
the epicardial coronary arteries that restricts blood flow. In atypical angina, the pain is the
same as that with exertional angina, but pain occurs at rest. Atypical angina appears to be
caused by coronary artery spasm. In about two-thirds of patients with atypical angina,
coronary artery lesions are seen, and patients may have exertional as well as rest pain. In
both exertional angina and atypical angina, the pattern is stable in terms of frequency of
episodes, severity, ease of provocation, and response to rest or nitroglycerin. In UA, the
episodic anginal pain has changed its pattern; it is either (1) of new onset (less than 1 to 2
months), (2) more frequent, easily provoked, more severe, or difficult to relieve, or (3)
occurring at rest for prolonged spells (>20 min). UA is a potentially serious condition and
patients are at high risk for early AMI or death. In AMI, the pain is usually persistent
(>20 min), severe, and associated with symptoms of dyspnea, diaphoresis, or nausea.
In ACS, the most useful test is an ECG for both detecting myocardial ischemia and risk
stratification. Using the initial ECG, the incidence of AMI is approximately 80 percent
for patients with new ST-segment elevation greater than 1 mm in two contiguous leads,
about 20 percent in patients with new ST-segment depression or T-wave inversion, but
less than 4 percent in patients without either of these two patterns.
Pulmonary embolism is common and life-threatening and is a diagnosis that can be
missed in the ED due to the frequently atypical nature of its presentation. Pulmonary
embolism can manifest with any combination of chest pain, dyspnea, syncope, shock,
and/or hypoxia (see Chap. 56). The pain associated with a PE occurs when inflammation
of the parietal pleura overlying the infarction causes chest pain that is generally sharp and
related to respiration. Dyspnea, fever, cough, and/or hemoptysis also may be present, and
the chest wall may be tender to palpation. Patients with massive PEs often present with
unstable vital signs and the classic presentation of sharp, pleuritic chest pain and dyspnea
associated with tachypnea, tachycardia, and hypoxemia. A clinical scoring system may be
useful in categorizing patients into low (about 10 percent), intermediate (about 40
percent), and high (about 80 percent) prevalence for PE.6
Risk factors for aortic dissection include atherosclerosis, uncontrolled hypertension,
coarctation of the aorta, bicuspid aortic valves, aortic stenosis, Marfan syndrome, EhlersDanlos syndrome, and pregnancy (see Chap. 58). The pain of aortic dissection, i.e.,
midline substernal chest pain, is classically described as tearing, ripping, or searing and
radiating to the interscapular area of the back. Typically, the pain is at its worst at
symptom onset and is often felt above and below the diaphragm. Symptoms of
"secondary" pathologies resulting from arterial branch occlusions, such as stroke, AMI,
or limb ischemia, may overshadow the clinical presentation of the dissection and make an
accurate diagnosis difficult. No combination of clinical factors or chest radiography
findings are adequate to exclude the diagnosis of aortic dissection, and specific imaging
studies are usually required.7
Spontaneous pneumothorax may occur due to sudden changes in barometric pressure, in
smokers or patients with chronic obstructive pulmonary disease or idiopathic pleural bleb
disease, or in those with another pulmonary pathology (see Chap. 66). Patients usually
complain of a sudden, sharp, lancinating, pleuritic chest pain and dyspnea. Auscultation
of the lungs may reveal absence of breath sounds on the ipsilateral side and
hyperresonance to percussion, but clinical impression alone is unreliable. Diagnosis of a
simple pneumothorax is made by chest radiography.
Esophageal rupture (Boerhaave syndrome) is a rare but potentially life-threatening cause
of chest pain. Patients classically present with a history of substernal, sharp chest pain of
sudden onset that occurs immediately after an episode of forceful vomiting (see Chap.
75). The patient is usually ill-appearing, dyspneic, and diaphoretic. The physical
examination is often normal but may reveal evidence of pneumothorax or subcutaneous
air. Chest radiography may be normal or may demonstrate pleural effusion (left more
common than right), pneumothorax, pneumomediastinum, pneumoperitoneum, and/or
subcutaneous air. The diagnosis can be confirmed by a study with water-soluble contrast.
The pain of acute pericarditis is typically acute, sharp, severe, and constant (see Chap.
55). It is usually described as substernal, with radiation to the back, neck, or shoulders,
and is exacerbated by lying down and by inspiration. It is classically described as being
relieved by leaning forward. A pericardial friction rub is the most important diagnostic
finding. The ECG may show diffuse ST-segment elevation and T-wave inversion. In
addition, depression of the PR segment is a highly specific ECG finding for pericarditis.
Pneumonia can produce chest pain or discomfort that is usually sharp and pleuritic (see
Chap. 63). It is usually associated with fever, cough, and possibly hypoxia. Physical
examination may reveal rales over the affected lobes, decreased breath sounds, and signs
of consolidation (i.e., bronchial breath sounds). A chest radiograph confirms the
diagnosis.
Mitral valve prolapse (MVP) is the most frequently diagnosed cardiac valvular
abnormality and is more commonly diagnosed in women than in men. The discomfort of
MVP often occurs at rest, is atypical for myocardial ischemia, and can be associated with
dizziness, hyperventilation, anxiety, depression, palpitations, and fatigue (see Chap. 54).
The discomfort may be related to papillary muscle tension, and many patients benefit
from the administration of -adrenergic blocking agents. Two-dimensional
echocardiography is the diagnostic tool of choice and, with physical examination
findings, helps to stratify patients into high- and low-risk categories for developing
serious complications. Palpitations and every type of supraventricular or ventricular
dysrhythmia have been associated with MVP.
Musculoskeletal or chest wall pain syndromes are characterized by highly localized,
sharp, positional chest pain. Pain that is completely reproducible by light to moderate
palpation of a discrete area of the chest wall often represents pain of musculoskeletal
origin, although chest wall tenderness occurs in some patients with PE and myocardial
ischemia. Costochondritis is an inflammation of the costal cartilages and/or their sternal
articulations and causes chest pain that is variably sharp, dull, and/or increased with
respirations. Tietze syndrome is a particular cause of costochondral pain related to
fusiform swelling in one or more upper costal cartilages and has a pain pattern similar to
that of other costochondral syndromes. Xiphodynia is another inflammatory process that
causes sharp, pleuritic chest pain reproduced by light palpation over the xiphoid process.
Texidor twinge or precordial catch syndrome is described as a short, lancinating chest
discomfort that occurs in episodic bunches lasting 1 to 2 min near the cardiac apex
associated with inspiration and poor posture and inactivity.
Gastrointestinal disorders cannot be reliably discriminated from myocardial ischemia by
history and examination alone. Dyspepsia syndromes, including gastroesophageal reflux,
often produce pain described as burning or gnawing, usually in the lower half of the
chest, and often accompanied by a brackish or acidic taste in the back of the mouth (see
Chap. 75). The recumbent position usually exacerbates the symptoms, and although the
pain is typically relieved with antacids, this therapeutic response also can be observed in
myocardial ischemia. Esophageal spasm is often associated with reflux disease and is
characterized by a sudden onset of dull, tight, or gripping substernal chest pain,
frequently precipitated by the consumption of hot or cold liquids or a large food bolus
and often lasting for hours (see Chap. 75). The pain also responds to sublingual
nitroglycerin (although supposedly with a slight delay).
Peptic ulcer disease is classically characterized as a postprandial, dull, boring pain in the
midepigastric region (see Chap. 77). Patients often describe being awakened from sleep
by discomfort. Duodenal ulcer pain is usually relieved after eating food, in contrast to
gastric ulcer symptoms, which are often exacerbated by eating. Symptomatic relief is
usually achieved by antacid medications. Acute pancreatitis and biliary tract disease
present with right upper quadrant or epigastric pain and tenderness but also can present
with chest pain.
Panic disorder (PD) is defined as a syndrome characterized by recurrent unexpected panic
attacks (discrete periods of intense fear or discomfort) with at least four of the following
symptoms: palpitations, diaphoresis, tremor, dyspnea, choking, chest pain or discomfort,
nausea, dizziness, derealization or depersonalization, fear of losing control or dying,
paresthesias, chills or hot flushes (see Chap. 292). The diagnosis can be made only in the
absence of direct physiologic effects of a substance disorder, a general medical condition,
or symptoms better accounted for by another mental disorder. Several studies have used
standardized screening tools to evaluate ED chest pain patients for PD and have reported
an incidence of 17 to 32 percent. In a small trial, investigators found that ED physicians
can successfully diagnose PD by using a brief screening procedure, and they suggested
that PD patients could benefit from the initiation of specific pharmacologic therapy
(serotonin reuptake inhibitors) in the ED.8 Many patients with PD and other anxiety
disorders have elevated baseline sympathetic tone, that may be an independent risk factor
for coronary artery disease (CAD). In fact, when all ED chest pain patients were screened
for PD, 25 percent of those screening positive had a discharge diagnosis of ACS (9.3
percent) or stable angina pectoris (15.7 percent).9 Thus, PD always must be considered a
diagnosis of exclusion.
Ancillary Testing
Ancillary testing in acute chest pain generally utilizes electrocardiography, measurement
of serum markers of myocardial injury, and/or imaging studies to detect intrathoracic
pathology. The specific studies are chosen according to the clinical circumstances. That
said, because ACS is the most common potentially serious cause of acute chest pain,
clinical studies and common practice focus on the use of the ECG and serum marker
measurement to detect or exclude acute myocardial injury. The remainder of this chapter
will focus on this topic. The use of ancillary tests in other conditions are discussed in
their respective chapters.
Electrocardiography
Due to the importance of early diagnosis of AMI (and, hence, reduced delay of
thrombolytic treatment), the American College of Cardiology/American Heart
Association (ACC/AHA) guidelines for management of patients with AMI recommend
standing orders that all patients with "ischemic-type pain" have a 12-lead ECG performed
within 10 min of arrival and that the ECG be handed directly to the treating physician for
immediate interpretation.10 Considering the difficulty of defining "ischemic-type" pain
and the frequency of atypical presentations, it may be prudent to extend this protocol to
all adult patients with chest pain or other symptoms of possible ischemia.
The normal myocardium depolarizes from endocardium to epicardium and repolarizes in
the opposite direction. Ischemic myocardium remains electrically less positive than
nonischemic myocardium at the end of depolarization. This creates an electrical potential
between normal and ischemic myocardium during depolarization and results in STsegment elevation in an overlying electrode. Conversely, if the electrode is located over
normal myocardium opposite an ischemic region, ST-segment depression will be seen. If
ischemia is limited to the subendocardial area, an overlying electrode will be separated
from the ischemic tissue by a layer of normal myocardium, resulting in an electrical
potential pointed inward from the normal to ischemic tissue, resulting in ST-segment
depression.
Myocardial ischemia can also delay the repolarization process. In extensive or transmural
ischemia, the direction of repolarization is reversed so that recovery occurs from
endocardium to epicardium, resulting in T-wave inversions in an overlying electrode. In
subendocardial ischemia, the delay does not alter the normal recovery process
(epicardium to endocardium), so T waves are not inverted. However, because normal
epicardium repolarization is unopposed due to delayed subendocardial repolarization, the
T wave in an overlying electrode may be larger than normal (called hyperacute T waves)
After infarction, the area of necrosis is electrically silent, not able to depolarize. During
ventricular depolarization, initial electrical activity will be generated in normal
myocardium, away from the infarcted area. This results in an electrical potential directed
from the infarcted area toward normal myocardium, causing an abnormal initial negative
deflection (pathologic Q waves) in the QRS complex of overlying electrodes.
Occasionally, small Q waves (called septal Q waves) are seen in the limb or lateral
precordial ECG leads. Pathologic Q-waves are distinguished by their duration (greater
than 40 ms) and depth (greater than 25 percent of the corresponding R wave).
The ECG is an important tool in the detection of acute infarction and conduction
blocks.11 Also, the ECG can help identify the infarct-related artery and help predict
reperfusion. The sensitivity of the initial ECG for the diagnosis of AMI has been
extensively studied. Approximately half of patients with AMI have diagnostic changes on
their initial ECG with new ST-segment elevation greater than 1 mm in two contiguous
leads. Another 20 to 30 percent will have new ST-segment or T-wave inversion
suggestive of myocardial ischemia. About 10 to 20 percent will have ST-segment
depressions and T-wave inversions similar to that seen on previous tracings. About 10
percent have nonspecific ST-segment and T-wave abnormalities. Only about 1 to 5
percent of AMI patients will have a truly normal initial ECG.
The sensitivity of the initial ECG in unstable angina is less well defined, probably
because the diagnosis is clinical as there is no "gold standard" against which to evaluate a
diagnostic test. In addition, the initial ECG would not be expected to be abnormal if a
patient with UA presents during a pain-free period.
The positive predictive value of the different ECG patterns has also been studied. For
new ST-segment elevation, the positive predictive value for AMI is about 80 percent. For
new ST-segment depression and T-wave inversions, the positive predictive value is about
20 percent for AMI and between 14 and 43 percent for UA. With acute chest pain and an
initial ECG showing preexisting ST-segment depressions and T-wave inversions, the
positive predictive value is about 4 percent for AMI and 21 to 48 percent for UA. Thus,
the standard 12-lead ECG is useful in conjunction with the clinical history for detection
of ACS.
Variations on the standard 12-lead ECG have been proposed. One approach uses a
continuous 12-lead ECG monitor that records (but does not print) a new 12-lead ECG
every 20 s. When the ST-segment baseline is altered from the previous tracing, an alarm
is raised and a copy of the new ECG is shared or printed. This technology is potentially
useful for monitoring patients with ongoing pain and a nondiagnostic initial ECG.12
Because of the costs, concerns regarding labile ST-segment and T-wave changes from
patient movement and respiration, and a lack of ED-based prospective studies,
continuous 12-lead ECG monitoring cannot be recommended for routine use.
Electrocardiograms with added leads—for a total of 15, 18, and 22 leads—have been
studied. In general, adding more leads increases the sensitivity for AMI detection, but
reduces specificity. The only generally agreed upon extension to the standard 12-lead
ECG is the use of right-sided precordial leads in the setting of acute inferior myocardial
infarction in order to detect right ventricular involvement.13
Risk stratification based on the initial ED ECG also has been suggested as a way of
improving ED decision making. Although the initial ECG cannot exclude AMI, stable
ED patients whose initial ECG is without ischemic changes are at low risk of subsequent
life-threatening complications and usually can be managed in a non-intensive-care
setting. Conversely, patients whose initial ECG demonstrates ischemic changes (STsegment depression or T-wave inversion), even in the absence of confirmed AMI, are at
significantly greater risk of short- and long-term morbidity and mortality and should be
managed accordingly.
Serum Markers of Myocardial Injury
Creatine Kinase, Creatine Kinase Isoenzymes, and Isoforms
Creatine kinase (CK; adenosine triphosphate creatine N-phosphotransferase) is an
intracellular enzyme involved in the transfer of high-energy phosphate groups from ATP
to creatine. Although found in small quantities in many tissues, CK is present in large
concentrations in cardiac and skeletal muscle and the brain. The enzyme is a dimer
composed of two subunits, each of which may be the M (muscle) type or the B (brain)
type, thus creating three distinct dimers, or isoenzymes: CK-BB, CK-MM, and CK-MB.
Type CK-BB predominates in brain tissue, whereas skeletal muscle consists mostly of
CK-MM, in addition to CK-MB in small amounts. The "cardiac isoenzyme," CK-MB,
accounts for 14 to 42 percent of total cardiac muscle enzyme activity, thus the
predominant enzyme in the heart is actually CK-MM.
The quantitative and temporal patterns of appearance and disappearance of CK and its
isoenzymes in the blood occur in a reproducible manner but can vary considerably
depending on the amount of CK released from cells, the amount of perfusion of damaged
tissues, and the rate of clearance by the reticuloendothelial system. The CK levels usually
become abnormally high within 4 to 8 h after coronary artery occlusion (onset of
symptoms), peak between 12 and 24 h, and return to normal between 3 and 4 days
(Figure 49-1). Reports of the sensitivity of total CK vary from 93 to 100 percent, whereas
the specificity is lower (57 to 86 percent), owing to the presence of CK in other tissues.
Thus, this marker's usefulness is limited. The CK-MB isoenzyme curve parallels the total
CK curve, with levels detectable 4 to 8 h after onset of symptoms (see Figure 49-1). Type
CK-MB may peak slightly earlier than total CK, and it is cleared more rapidly, usually
within 48 h (vs. 72 to 96 h). Using CK-MB and the ratio of CK-MB to total CK, most
studies have reported sensitivity and specificity to be greater than 95 percent. Cutoff
values vary between techniques, laboratories, and populations, but CK-MB values in
healthy controls may be up to 5 g/L and up to 5 percent of total CK. Historically, CK-MB
had been universally adopted as the gold standard for diagnosis of AMI. Although
specificity is generally improved over total CK, 37 conditions other than AMI have been
associated with elevated CK-MB levels (Table 49-2). Fortunately, most of these
conditions can be easily differentiated from AMI on clinical grounds. The relatively rapid
return of elevated CK-MB levels to normal is another potential disadvantage, because of
the possibility of missing the diagnosis in patients presenting later in the course of AMI.
However, this rapid clearance may be used to a different advantage, because it enables
the identification of infarct extension and reinfarction.
Fig. 49-1.
Typical pattern of serum marker elevation after AMI. Abbreviations: CK-MB =creatine
kinase-MB isoenzyme; cTnI = cardiac troponin I; cTnT = cardiac troponin T; LD1 =
lactate dehydrogenase isoenzyme 1; MLC = myosin light chain.
Table 49-2 Conditions Associated with Elevated CK-MB Levels
Common Uncommon Rare Unclear
Unstable angina, acute coronary ischemia Congestive heart failure Isolated case in
normal person Acromegaly
Inflammatory heart diseases Coronary artery disease after stress test Hypothermia
Cardiomyopathies Angina pectoris Rocky Mountain spotted fever
Circulatory failure and shock Valvular defects Typhoid fever
Cardiac surgery Tachycardia Chronic bronchitis
Cardiac trauma Cardiac catheterization Lumbago
Skeletal muscle trauma (severe) Electrical countershock Febrile disorder
Dermatomyositis, polymyositis Noncardiac surgery
Myopathic disorders Brain and head trauma
Muscular dystrophy, especially Duchenne Peripartum period
Extreme exercise Miscellaneous drug overdoses
Malignant hyperthermia CO poisoning
Reye syndrome Prostatic cancer
Rhabdomyolysis of any cause
Delirium tremens
Ethanol poisoning (chronic)
Abbreviation: CK-MB =creatine kinase, subunits muscle and brain.
The 4- to 8-h delay in CK-MB detection after onset of symptoms has been overcome in
part with the development of rapid assays for CK-MB isoforms (subforms). The
isoenzymes CK-MM, CK-MB, and CK-BB are dimeric molecules consisting of three
different combinations of two monomers, M and B. On its release from damaged cells,
the M monomer found in tissue CK (Mt) is acted on by an enzyme present in serum,
carboxypeptidase N, which cleaves off the C-terminal lysine. This action results in its
conversion into the M monomer found in serum CK (Ms). Newly released unmodified
CK-MtB (or CK-MB2) is enzymatically changed into CK-MsB (or CK-MB1). Because
the rate of this conversion is limited, CK-MB2 activity reflects new recent release into
the serum. By measuring MB2 activity (>1 U/L) and the MB2:MB1 ratio (>1.5),
infarction can be detected before the total level of CK-MB exceeds the normal range.
Although this method has reported early (<6 h of symptom onset) sensitivity and
specificity for AMI of 95.7 percent and 93.9 percent, respectively, technical difficulties
with the assay system have thus far limited clinical acceptance.14
Myoglobin
Myoglobin is a small (17,500 Da), heme-containing protein found in striated (skeletal)
and cardiac muscle cells. When disrupted, these cells rapidly release myoglobin into the
serum. After AMI, serum myoglobin levels begin to rise within 3 h of onset of symptoms
and are abnormally elevated in 80 to 100 percent of patients at 6 to 8 h, peak at 4 to 9 h
(see Figure 49-1), and with normal kidney function return to baseline within 24 h from
symptom onset. A false-negative result may occur if the test is performed after
myoglobin has already been cleared from the serum. False positives also abound, because
the myoglobin found in myocardium is indistinguishable from that found in skeletal
muscle. Fortunately, conditions that also result in myoglobin release usually can be
clinically diagnosed. By excluding those patients with known trauma, renal failure, or
cocaine use, one study found myoglobin's "clinical specificity" to be equivalent to that of
CK-MB and troponin.15
Troponins I and T
The troponin complex is the main regulatory protein of the thin filament of the myofibrils
that regulate the Ca2+-dependent ATP hydrolysis of actomyosin. The troponin complex
consists of three subunits: an inhibitory subunit (troponin I), a tropomyosin-binding
subunit (troponin T), and a calcium-binding subunit (troponin C). Immunoassays based
on the significant heterogeneity in amino acid sequences can detect the specific isoforms.
The cardiac isoform of troponin I is not found in skeletal muscle during any stage of
development and therefore is associated only with myocardial necrosis.
After AMI, cardiac troponin I (cTnI) and troponin T (cTnT) become elevated after
approximately 6 h, peak at 12 h, and remain elevated for 7 to 10 days. Both have a higher
specificity for myocardial necrosis than CK-MB in selected subsets of patients, such as
those presenting late in the course of AMI or those with recent surgery, a cocaine habit,
or skeletal muscle disease. Both troponins have been shown to have high sensitivity and
specificity for AMI in ED patients with chest pain and among those with possible
ischemic equivalents. Elevation of either cardiac troponin also predicts subsequent
cardiovascular complications independent of CK-MB and the ECG.16
Interpretation of troponin results in the presence of renal failure is an area of controversy.
Although only troponin T has been found in skeletal muscle biopsies of patients with
renal failure, troponins I and T are sometimes elevated in renal patients without other
evidence of cardiac disease. Further, there have been conflicting reports as to the
prognostic significance of elevated levels of either troponin in patients with renal failure.
Other Markers
Other markers of myocardial ischemia or infarction are currently being evaluated for
utility: myoglobin/carbonic anhydrase III combinations, glycogen phosphorylase BB, and
myosin light chains, to name three. In addition, markers of inflammation (e.g., C-reactive
protein), platelet activation and adhesion (e.g., P-selectin and other integrins), and cardiac
function (B-type natriuretic peptide, or BNP) are theoretically attractive as indicators of
ACS. C-reactive protein and BNP have some prognostic value in patients with possible
ACS, but their overall role in diagnosis remains to be determined.
Clinical Applications of Myocardial Marker Measurements
The current literature supports the inclusion of myocardial marker measurements in
protocols governing the ED evaluation of patients with chest pain for four distinct
purposes. The first three applications are discussed below, while the fourth use of an
accelerated marker curve is discussed later in Chap. 50.
Early Diagnosis of AMI
In those patients whose initial ECG is diagnostic for AMI, no further marker testing is
required before initiation of appropriate interventions. In patients with a nondiagnostic
ECG, AMI cannot be definitively excluded within the first few hours from symptom
onset. However, some AMI patients with nondiagnostic initial ECGs will have positive
marker tests upon ED arrival, and many more will develop positive tests during the first
few hours after presentation.
In AMI, the initial CK-MB measurement obtained upon ED arrival is elevated in about
30 to 50 percent of patients.17 By serial measures at 2- to 3-h intervals, diagnostic
increases in CK-MB can be obtained in 80 to 96 percent of AMI patients during the
initial six hours. The same principle can be applied with serial measurements of cTnI and
cTnT. Owing to its earlier release into serum after coronary artery occlusion, myoglobin
has a potential advantage over CK-MB and troponin for early diagnosis of AMI. Using a
panel of markers (myoglobin, CK-MB, and cTnI) performed upon arrival and after 3 h, it
is possible to detect over 90 percent of AMI patients.17,18
Identifying "Missed MI" Patients
Single-sample myocardial marker measurements cannot be used to exclude the diagnosis
of AMI in the ED. However, routine incorporation of marker testing into patient-care
algorithms for those patients deemed sufficiently low risk so that they are slated for
discharge without definitive AMI rule-out has been shown to identify some patients
(admitted and discharged from the ED) with unsuspected MI.19 Further, a strategy using
two CK-MB measurements drawn 3 h apart for patients selected for discharge will
identify ACS patients. Although these strategies have not been validated, these and
several other studies suggest that ED patients slated for discharge after evaluation for
chest pain and ischemic equivalents may benefit from at least one myocardial marker
measurement.
Early Risk Stratification
Increased use of newer anti-ischemic therapies (angiographic interventions and
antiplatelet and antithrombotic drugs), although improving outcomes, carries risks and
high costs. Thus, a selective approach to their use is required. Several investigations have
suggested that markers of myocardial injury can be used successfully in the ED to rapidly
identify those patients most likely to benefit from a more aggressive approach. Numerous
investigations have demonstrated that early ED testing of CK-MB, myoglobin, troponin
T, or troponin I yields clinically useful prognostic data for adverse events, and that
simultaneous testing of troponin and CK-MB may identify additional high-risk patients
as opposed to testing for one marker.
After reviewing this evidence, the Joint European Society of Cardiology/American
College of Cardiology Committee for the Redefinition of MI reported in 2000 that there
is "no discernible threshold below which an elevated value for cardiac troponin would be
deemed harmless. All elevated values are associated with a worsened prognosis."20
Unfortunately, the threshold values historically suggested by the manufacturers of
laboratory assays for CK-MB, troponin, and other myocardial markers have been
determined based on the traditional definition of MI and are therefore inadequate for risk
stratification. Recognizing this, the joint committee went on to recommend that new
threshold values for each marker be established at the 99th percentile of the values for an
appropriate reference control (normal) group. Because this recommendation has not been
uniformly accepted and implemented by hospital laboratories, to optimally use the
prognostic information offered by ED myocardial marker testing, emergency physicians
should be aware of the appropriate threshold values for risk stratification and for MI
diagnosis in their individual institutions.
Point of Care Testing
With current monoclonal antibody technology, qualitative and quantitative cardiac
marker panels for CK-MB, troponin I and T, and myoglobin are available for use at the
bedside. A quantitative assay for BNP has also been developed for bedside use. Most
point of care cardiac marker testing panels provide results within 15 to 20 min, generally
faster than most hospital laboratories. Rapid bedside results would be theoretically useful
when the results would affect early therapy (e.g., initiation of glycoprotein IIb/IIIa
inhibitors) or alter disposition (e.g., primary percutaneous coronary intervention instead
of medical therapy). Rapid bedside cardiac marker assessment may also be useful when
the initial ECG is rendered difficult to evaluate due to preexisting ventricular conduction
blocks or chronic ventricular pacing. The overall value of rapid bedside cardiac marker
detection remains to be determined.
Computerized Decision Aids
To facilitate more accurate disposition decisions and thereby reduce mounting health care
costs, several investigators tried to develop computerized decision aids or computerbased triage protocols for ED patients with chest pain. Unfortunately, no simple
algorithm has proven both safe and effective for ED-based triage of acute chest pain
patients.
Other methods, such as multivariate analysis and artificial neural networks, have been
used to develop predictive instruments. Actual clinical use of the most studied of these
decision aids, the Acute Cardiac Ischemia Time-Insensitive Predictive Instrument (ACITIPI), resulted in a decrease of 26 percent in cardiac care unit admissions and an increase
of 47 percent in ED discharges to home without increasing the number of missed AMIs.
The ACI-TIPI uses a logistic regression formula that evaluates the probability of acute
ischemia by analyzing specific history and ECG characteristics. The instrument has been
incorporated into computerized ECG machines in the ED, and the result is printed
directly onto the ECG tracing.21
An artificial neural network is a nonlinear statistical program that can recognize complex
patterns and maintain accuracy even when some of the required data are missing. This
theoretically enables users to apply the tool in real time even when they do not have all of
the required data elements called for in the stratification model. The accuracy of one such
tool was hypothetically tested in 2204 patients. The network demonstrated a significant
improvement over physician decision making, with a sensitivity of 94.5 percent and a
specificity of 95.5 percent for the diagnosis of AMI.22 A more recent instrument has
been developed to include diagnoses in the overall spectrum of myocardial ischemia.23
Despite the demonstration of diagnostic superiority and improved cost-effectiveness
compared with physician decision making alone, these instruments have not been
embraced by clinicians. Among the barriers cited to acceptance of decision aids into
clinical practice are medicolegal concerns, slow adoption of new technology, and
physicians' fear of losing autonomy. Thus, additional work in this area must now focus
on physician behavior and the interface between human and machine.
Approach to Low Probability of Ischemia
Patients identified as having ST-segment elevation MI or recognized as having a high
potential for an ACS are addressed as discussed in Chap. 50. Other patients may be
classified as having a very low, low, or moderate probability of acute ischemia based on
clinical information available within the initial hours of their ED visit. Many
investigators now recommend the use of a five-subgroup classification scheme for this
initial risk stratification (Table 49-3). However, there is still no consensus regarding
optimal risk subgroupings, criteria for such stratification, or agreement as to the most
effective evaluation and treatment protocols after initial categorization. There is
consensus on two issues regarding lower-risk patients: history alone is inadequate to
exclude the presence of acute ischemia, and the goal should always be "zero tolerance"
for missed AMI. It is also accepted that some form of systematic approach based on
objective data is required to accurately and efficiently pursue further diagnostic
evaluation to an appropriate end point in each patient (Figure 49-2).10
Table 49-3 Prognosis-Based Classification System for ED Chest Pain Patients*
I. Acute myocardial infarction: immediate revascularization candidate
II. Probable acute ischemia: high risk for adverse events
Any of the following
Evidence of clinical instability (i.e., pulmonary edema, hypotension, arrhythmia)
Ongoing pain thought to be ischemic
Pain at rest associated with ischemic ECG changes
One or more positive myocardial marker measurements
Positive perfusion imaging study
III. Possible acute ischemia: intermediate risk for adverse events
History suggestive of ischemia with any of the following
Rest pain, now resolved
New onset of pain
Crescendo pattern of pain
Ischemic pattern on ECG not associated with pain
IV. A. Probably not ischemia: low risk for adverse events
Requires all of the following
History not strongly suggestive of ischemia
ECG normal, unchanged from previous, or nonspecific changes
Negative myocardial marker measurement
B. Stable angina pectoris: low risk for adverse events
Requires all of the following
More than 2 wk of unchanged symptom pattern or longstanding symptoms with only
mild change in exertional pain threshold
ECG normal, unchanged from previous, or nonspecific changes
Negative initial myocardial marker measurement
V. Definitely not ischemia: very low risk for adverse events
Requires all of the following
Clear objective evidence of non-ischemic symptom etiology
ECG normal, unchanged from previous, or nonspecific changes
Negative initial myocardial marker mesurement
*Authors' analyses from multiple sources.
Abbreviation: ECG = electrocardiogram.
Fig. 49-2.
Algorithm for risk-based decision-making. Abbreviation: PCI = percutaneous coronary
intervention.
Interpretation of the many diagnostic tests now available to assist in diagnosis and risk
stratification of ED patients with possible ACS increasingly has become the
responsibility of the emergency physician.
Common Diagnostic Tests Used in Emergency Cardiac Care
ECG-Based (Standard) Exercise Stress Testing
In the ED setting, exercise testing has been recommended for patients applied as the final
component of a chest pain observation protocol after the exclusion of AMI or, in selected
low-risk patients, soon after presentation as an alternative to an extended observation
period.24
Many variations exist in the equipment, procedures, and interpretive algorithms used.
Treadmills are used more commonly in the United States, because many patients cannot
reach the desired point of maximum oxygen uptake by using cycles or other devices. In
appropriate patients, stress testing is safe: dysrhythmia, AMI, and death occur at rates of
4.8, 3.6, and 0.5 per 10,000 tests, respectively.
No consensus exists on the preferred protocol, although the Bruce protocol is the most
common and best studied. Depending on the protocol followed, exercise is terminated
when the subject reaches a predetermined percentage of predicted maximum heart rate
(i.e., 85 percent) or when another defined end point is reached. The most commonly used
definition of a positive exercise test result from an ECG standpoint is greater than or
equal to 1 mm of horizontal or downsloping ST-segment depression or elevation for at
least 60 to 80 ms after the end of the QRS complex.
Exercise stress testing may be contraindicated for various reasons (Table 49-4). If the
patient has physical limitations preventing exercise but no other contraindications, a
pharmacologic stress test using a chronotropic drug (i.e., dobutamine) may be
appropriate. Exercise testing may not be safe for patients at high risk for acute ischemia
or those with other uncontrolled cardiovascular or pulmonary pathologies. Further,
patients with an abnormal baseline ECG, such as those with left ventricular hypertrophy,
bundle-branch block, or digoxin effect, are less likely to benefit from standard exercise
testing owing to difficulties in interpretation of exercise-induced ECG changes.
Table 49-4 Contraindications to Exercise Testing
Absolute
Acute myocardial infarction (within 2 d)
Unstable angina not previously stabilized by medical therapy
Uncontrolled cardiac dysrhythmias causing symptoms or hemodynamic compromise
Symptomatic severe aortic stenosis
Uncontrolled symptomatic heart failure
Acute pulmonary embolus or pulmonary infarction
Acute myocarditis or pericarditis
Acute aortic dissection
Relative*
Left main coronary stenosis
Moderate stenotic valvular heart disease
Electrolyte abnormalities
Severe arterial hypertension
Tachydysrhythmias or bradydysrhythmias
Hypertrophic cardiomyopathy and other forms of outflow tract obstruction
Mental or physical impairment leading to inability to exercise adequately
High-degree atrioventricular block
*Relative contraindications can be superseded if the benefits of exercise outweigh the
risks.
In the absence of definitive evidence, the AHA committee suggests systolic blood
pressure of >200 mm Hg and/or diastolic blood pressure of >110 mm Hg.
Source: Fletcher GF, Balady G, Froelicher VF, et al: Exercise standards: A statement for
healthcare professionals from the American Heart Association Writing Group. Special
Report. Circulation 91:580, 1995.
The clinical utility of ED stress testing depends on the test result's ability to modify the
pretest probability of the diagnosis and to change treatment and disposition. Emergency
department stress testing is particularly difficult to quantify, because test sensitivity and
specificity are greatly influenced by the population being tested. As the pretest
probability of significant CAD increases, the likelihood of a false-negative test also
increases. Conversely, when a population with a very low pretest probability of disease is
tested, the likelihood of a false-positive result increases. Therefore, based on current data,
diagnostic stress testing is recommended for patients with a low pretest probability of
CAD but is unlikely to be helpful in those at very low risk (<5 percent) or moderate to
high risk (>30 percent). The pretest probability of disease can be determined
semiquantitatively based on demographic, historical, and ECG data with any of the
validated decision aids previously described.
Emergency department stress testing may be of further value when applied to a broader
range of patients, if the goal of testing is to predict prognosis rather than diagnosis. Many
studies have confirmed that ED stress testing of selected patients can reliably predict
short-term (<1 y) prognosis.
Myocardial Imaging
Echocardiography
Advantages of echocardiography include its noninvasive, dynamic nature, its lack of
radioactive materials, and that even sophisticated machines can be used at the bedside in
the ED.24 Further, it can assess the potential for other etiologies of chest pain, including
aortic dissection, pericardial pathology, valvular disease, and possibly PE (see Chap. 61).
The value of echocardiography in evaluating ischemic heart disease is based largely on
the experimental finding in animal and human studies that acute myocardial ischemia
reliably and rapidly results in observable wall motion abnormalities. Thus, theoretically, a
normal echocardiogram during chest pain should exclude the presence of ischemia.
Unfortunately, this finding is limited by several factors. Because the effects of adjacent
wall segments commonly lead to false-positive and false-negative interpretations of wall
motion abnormalities, systolic wall thickening is used as a more specific indicator of
ischemia. However, detection of wall-thickening abnormalities is highly dependent on
imaging technique and interpretative skills, with up to 10 percent of tests being
technically inadequate. Further, the echocardiogram cannot distinguish between
myocardial ischemia and acute infarction, cannot reliably detect subendocardial ischemia,
and may be falsely interpreted as positive in the presence of several conditions
(conduction disturbances, volume overload, heart surgery, or trauma). Timing of the test
relative to the onset of symptoms is critical, because transient wall motion abnormalities
may resolve within minutes of an ischemic episode. Indeed, one prospective study of ED
patients found that resting echo within 12 h of ED arrival does not provide additional
predictive value for MI over myocardial markers alone. Thus, a normal resting
echocardiogram in the ED should not be used to exclude ACS.25
Stress echocardiography combines a standard ECG stress test with cardiac imaging at rest
and after exercise (or during pharmacologically induced tachycardia). Thus, it is superior
to standard stress testing. When evaluated among low-risk ED patients, three studies have
reported negative predictive values for subsequent cardiac events to be 97 to 100 percent,
comparable to that of stress testing using nuclear imaging techniques.25
Contrast echocardiography using physiologically safe microbubbles is a newer technique
that holds future promise but is not routinely used in clinical practice. Studies have
suggested that this technique significantly improves the detection of regional wall motion
abnormalities and wall thickening as compared with conventional sonography. In one
study, 28 percent of standard stress echoes performed were inconclusive due to
difficulties in interpretation but were decisively normal or abnormal with the use of
contrast. In the future, contrast echocardiography may be able to directly assess coronary
vessel patency, even at the microvascular level, with sensitivity similar to or greater than
that of nuclear perfusion imaging.25
Perfusion Imaging
Myocardial perfusion imaging uses an intravenously injected radioactive tracer that is
distributed throughout the coronary circulation (see Chap. 61). Local myocardial uptake
and, subsequently, myocardial imaging therefore are dependent on adequate regional
coronary flow and myocardial cell integrity. Tracer uptake occurs in direct proportion to
regional myocardial blood flow.24
Thallium 201 is the oldest and most studied tracer in common use today. Thallium is
rapidly redistributed after initial uptake. The image represents blood flow at the moment
of imaging. Areas of positive uptake reflect adequate coronary flow and viable
myocardium, whereas areas without uptake represent infarcted or ischemic myocardium.
On repeat imaging several hours later, continued lack of perfusion ("irreversible defect")
indicates an area of infarction, whereas areas with tracer uptake only on delayed images
("reversible defect") represent previously ischemic myocardium. Combined with
conventional ECG-based stress testing, thallium imaging offers improved sensitivity and
specificity for detection of significant CAD over ECG-based testing alone. Further,
thallium testing (or other perfusion imaging) is likely to be of value in patients who
would not otherwise benefit from stress testing due to a confounding or potentially
masking abnormal baseline ECG.
There are several limitations of thallium testing. Imaging must be performed soon after
injection, making it impractical for use in patients with ongoing chest pain. Moreover,
because of a long half-life, the injected dose of thallium must be kept low to avoid
excessive radiation exposure. This and other properties of the tracer result in a relatively
poor image quality and the frequent occurrence of artifactual perfusion defects (false
positives) due to overlying tissue attenuation. This is particularly common in women and
obese patients. Due to these limitations and the lack of ED-based efficacy studies,
thallium-201 imaging alone is not an ideal agent for use in the ED.
Myocardial perfusion imaging using technetium 99m (99mTc)-labeled agents such as
sestamibi offers advantages over thallium for ED use. Because the half-life of 99mTc is
much shorter than that of thallium (6 vs. 73 h), a larger dosage can be injected without
harm to the patient. This results in the superior image quality, decreased tissue
attenuation-related artifacts, and higher specificity for sestamibi imaging. Newer 99mTc
agents being introduced continue to improve image quality. In addition, in contrast to
thallium, the initial distribution of 99mTc agents is stable for several hours. Therefore,
accurate imaging can occur up to 3 h after injection. The image represents the blood flow
at the moment of injection. By using "gated" image acquisition technology, sestamibi
scanning can yield an accurate estimation of ejection fraction. As with thallium, resting
and stress (exercise or pharmacologic) images can be compared to yield additional data.
Dual isotope stress testing using thallium and sestamibi is an increasingly common
component of ED ACS evaluation protocols. In this technique, a resting thallium scan is
first performed. Those patients without resting defects can then immediately undergo
stress testing with sestamibi imaging, thereby avoiding the delay usually required for
isotope "washout" in single isotope techniques. In a recent prospective study, a strategy
using this method reliably identified or excluded ACS among 1775 low-risk ED
patients.26
The use of electron-beam computed tomography for the detection of coronary artery
calcification has shown promise as a noninvasive alternative for the diagnosis of CAD. A
"calcium score" is generated and is directly related to the likelihood of having CAD
(within a given demographic group). Electron-beam computed tomography has a number
of limitations. It cannot identify the minority of plaques that do not contain calcium, and
it does not demonstrate microvascular or vasospastic disease. Although this technique
shows promise as an alternative to the previously discussed imaging techniques, its role
in ED evaluation remains undefined.27
Low-Risk Patient Protocols
Inpatient Admission
In settings where extended observation and definitive diagnostic testing are not available
in the ED, all patients whose presentations suggest a reasonable plausibility of an acute
ischemic event should be admitted to an inpatient bed. Once the need for inpatient
admission has been determined, further stratification based on assessment of the patient's
short-term risk of morbidity or mortality can be made based on the patient's history and
physical examination, initial ECG, and early myocardial marker measurement. Patients
with a prior history of CAD, evidence of congestive heart failure on physical
examination, recurrent chest pain in the ED, or new or presumed new ischemic ECG
changes are at higher short-term risk and may be more appropriately managed in an
intermediate-care (step-down) unit. Conversely, patients whose initial ED ECG is normal
or unchanged from a previous ECG have a very low risk of adverse events and can safely
be evaluated on a monitored floor or telemetry bed. Those with nonspecific changes on
the initial ECG represent an intermediate-risk group. A single myocardial marker
measurement soon after ED presentation also can identify those patients at greater risk
from among those with atypical presentations.
ED Observation/Monitoring
In 1991, the Multicenter Chest Pain Study Group reported that the diagnosis of infarction
could have been safely excluded within a 12-h observation period among a subgroup of
patients admitted for chest pain but identified at presentation as having a low probability
of AMI.28 The investigators also suggested routine predischarge stress testing of these
patients to reduce the risk of discharging patients with unstable coronary syndromes
prematurely. Gibler and colleagues later refined this approach.29 Patients with symptoms
consistent but weakly suggestive of acute ischemia were observed for 9 h with
continuous 12-lead ST-segment ECG monitoring and serial CK-MB testing at 0, 3, 6, and
9 h after presentation. Those who completed a negative 9-h evaluation subsequently
underwent echocardiography followed by graded exercise stress testing in the ED before
discharge. With this approach, 82.1 percent of patients were released home from the
cardiac evaluation unit.29
Although there is no consensus on the best approach, many studies have documented
clinical safety and efficacy and cost savings associated with use of an ED-based Cardiac
Evaluation Unit protocol compared with traditional inpatient admission, and their use has
continued to expand.
Normal serial ECGs and myocardial marker measurements do not preclude the presence
of other ACSs (i.e., unstable angina), which may still put the patient at high risk for a
subsequent adverse event. Therefore, further evaluation is generally recommended before
discharge (Figure 49-3). The various forms of stress testing (with or without myocardial
imaging) currently offer the best noninvasive method to predict the presence of CAD and
assess prognosis. Over the past decade, numerous published reports have confirmed the
safety, clinical utility, and cost-effectiveness of various versions of this accelerated MI
rule-out/early risk stratification concept, and this strategy has been incorporated into the
ACC/AHA 2002 guideline update for the management of patients with unstable angina
and non-ST-segment elevation MI.10
Fig. 49-3.
Alternative risk stratification protocols for low-risk patients.
Disposition
The assessment of acute chest pain patients is difficult, and the processes and approaches
discussed in this chapter are not perfect. This is best illustrated in AMI, where the "miss"
rate for AMI in patients evaluated in the emergency department using history, physical
examination, ECG, and serum markers is currently about 2 percent; these patients were
discharged and upon follow-up were determined to have sustained an AMI. The good
news is that the use of serial marker measurements, evaluation or observation units,
myocardial imaging studies, and stress testing has the potential to reduce this "missedMI" rate to close to zero. Unfortunately, UA sometimes remains an elusive and difficult
diagnosis. There is little information on the ED "miss rate" for the important diagnoses of
aortic dissection and pulmonary embolism. Despite advances in serum marker technology
and imaging studies, the physician must still exercise clinical judgment when evaluating
acute chest pain patients. To make the best possible decisions, clinicians should collect
adequate information first before exercising their judgment. The ability to make good
decisions when faced with incomplete or uncertain information is an important skill.
The disposition of patients who have a defined diagnosis as the cause of their chest pain
is relatively straightforward. Those patients without a specific diagnosis—so-called
atypical chest pain—pose more of a problem. A useful principle in these patients with
atypical chest pain is the use of a composite picture to assign patients to a category where
the potential for ACS or other serious causes of chest pain is vanishingly small, and such
patients can be safely discharged. These patients often have pain described as sharp; well
localized; reproducible by position, breathing, or palpation; and have no prior diagnosis
of angina or AMI. The pretest probability of ACS or other serious conditions is so low
that ancillary testing is usually not indicated and patients can be discharged after the
history and physical examination. Conversely, patients with unexplained visceral chest
pain should not be discharged unless potentially serious conditions have been excluded
using appropriate ancillary testing.
Discharged patients should receive appropriate instructions regarding medications and
follow-up directions. They should also be instructed to seek prompt attention or return for
recurrent or worsening chest pain or other serious symptoms. Some institutions have
instituted chest pain clinics to ensure that patients receive appropriate follow-up after
their discharge from the ED.
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