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Cardiovascular Disease: Chest Pain: Cardiac or Not
Cardiovascular Disease: Chest Pain: Cardiac or Not
Cardiovascular Disease
CHAPTER
52
The management of the patient with chest pain is a diagnostic and therapeutic challenge of critical importance. Three key chapters in this textbook discuss the identification of acute presentations of ischemic cardiac
disease and its differentiation from other life-threatening disorders: the
current chapter, Chapter 53, Acute Coronary Syndrome: Acute Myocardial Infarction and Unstable Angina and Chapter 55, Low Probability
Acute Coronary Syndrome. The current chapter covers the assessment of
acute chest pain with emphasis on identification of patients with potentially serious disorders and differentiating cardiac disease from noncardiac disease. The Acute Coronary Syndromes chapter discusses ST-segment
elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), and
unstable angina. The Low Probability Acute Coronary Syndrome chapter
discusses the identification and management of the remainder of patients
who do not meet criteria for acute coronary syndrome (ACS), yet require
further evaluation beyond the immediate ED period.
OVERVIEW
DEFINITIONS
ACS is a constellation of signs and symptoms resulting from an imbalance between myocardial oxygen supply and demand. There are three
general classifications: unstable angina, NSTEMI, and STEMI. Unstable
angina is a type of ACS with no elevation of biomarkers and no pathologic
ST-segment elevation. NSTEMI is characterized by biomarker elevation
and no pathologic ST segment elevation. Acute myocardial infarction
(AMI) is characterized by ST elevation and biomarker elevation (STEMI).
The phrase acute chest pain, commonly used in emergency medicine,
deserves discussion. The term acute means of sudden or recent onset. Although there is no precise time period defined, most studies of acute chest
pain patients in the ED limit entry to those with symptoms of <24-hours
duration. In common practice, acute means that the patient stops his or
her usual activity to seek medical attention, typically within minutes to
hours. The term chest in this context refers to a location described by the
patient on the anterior thorax, between xiphoid and suprasternal notch
and between the right and left midaxillary lines. As the major serious thoracic disorders typically manifest symptoms within these regions, thoracic pain localized to the back, between the base of the neck and the lumbar
region, is approached differently (see Chapter 276, Neck and Back Pain).
Occasional patients with serious and life-threatening intrathoracic disorders will describe the location of their pain outside the anterior thoracic
boundaries noted above. Some patients will have migratory pain that is
no longer perceived to be in the chest by the time the patient reaches medical attention. Therefore, include significant intrathoracic disorders in the
differential diagnosis whenever patients describe symptoms in adjacent
regions (e.g., epigastric, neck, jaw, shoulder, and arm). The term pain describes a noxious, uncomfortable sensation. However, pain perception
and description vary widely, and patients may use terms such as pressure,
heaviness, ache, or discomfort. Be attuned to variation in the patients description of the perceived sensation. In summary, acute chest pain is pain
(1) of recent onset, typically <24 hours, which causes the patient to seek
prompt medical attention; (2) with location on the anterior thorax; and
(3) with a sensation distressing to the patient.
INITIAL APPROACH
The recommended initial approach to acute chest pain takes into account that some causes are serious and life-threatening, and prompt
medical attention may prevent death and limit morbidity. Therefore, all
patients should be triaged promptly. Patients with visceral-type chest
pain (described above in Definitions), abnormal vital signs, significant
vascular disease risks, and those with dyspnea should be placed into a
treatment bed, a cardiac monitor initiated, an IV line established, oxygen
administered, and an ECG performed. Other, less well-defined patients
may simply appear ill; this 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 patients 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
to follow response to therapy.
If immediate life threats are not detected or have already been addressed, a more extensive evaluation can be performed. This secondary
survey consists of a more comprehensive history and physical examination and appropriate laboratory and diagnostic testing. This evaluation
should focus on those variables that will aid in establishing a tentative diagnosis and ruling out immediate life threats. The physical examination
during this phase should complete those body systems not evaluated initially as well as rechecking abnormalities noted earlier. 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. Although such structured records
may be helpful to less experienced physicians, they should never preempt sound clinical judgment. After consideration of a broad differential diagnosis, further diagnostic testing is then directed by history and
7-1
7-2
physical findings toward the goal of systematic exclusion and/or confirmation of serious pathology.
TABLE 52-2
Pain Descriptor
Study
No. of
Patients
Studied
Described as pleuritic
Described as positional
Described as sharp
Reproducible with palpation
Inframammary location
Not associated with exertion
Chun et al.7
Chun et al.7
Chun et al.7
Chun et al.7
Everts et al.8
Goodacre et al.6
8822
8330
1088
8822
903
893
HISTORY
A thorough history will provide data useful for both diagnosis and risk
stratification. Routine questions should determine the quality, location,
area of distribution, radiation, intensity, frequency, duration, first occurrence, associated symptoms, and precipitating factors of chest pain. Although open-ended queries should be used initially, patients who have
difficulty explaining symptoms in a narrative fashion should be asked directed questions. Pain intensity is commonly graded on a scale of 1 to 10,
with 10 representing the worst pain the patient can imagine and zero being no discomfort whatsoever. The frequency, severity, and duration of
pain episodes should be assessed over a continuum of the past weeks to
better determine whether the condition might represent a stable or unstable symptom pattern. Precipitating factors, such as symptom changes
with inspiration, movement, palpation, or exertion and during sleep or
rest should also be identified.
The classic description of angina pectoris is a retrosternal left anterior
chest or epigastric discomfort described as crushing, tightening, squeezing, or a pressurelike sensation. Conversely, patients whose pain is described as stabbing, positional, or pleuritic do have a reduced likelihood of
ACS as a cause of chest pain. The presence of certain associated symptoms
during chest paindyspnea, diaphoresis, nausea, and/or vomitingis
common and does indicate a twofold higher risk of ischemia. Discomfort
radiating from the chest to either shoulder, arm, hand, or jaw also indicates a significantly increased probability of ACS.35 However, lack of
such radiation does not exclude ischemia. Anginal pain (or other anginal
symptoms) is typically described as lasting from 2 to 20 minutes and pain
from an uncomplicated AMI lasting up to 2 hours. In contrast, chest pain
that is described as lasting a split second or only a few seconds is more
likely to be due to another cause. This is also true for constant, unremitting pain lasting 12 to 24 hours or more. Anginal pain is often brought on
by exertion and relieved by rest, although pain worsened by body movement or body position is suggestive (but certainly not diagnostic) of another etiology. Angina may also occur at rest, either due to destabilization
of a preexisting coronary lesion or to coronary artery spasm with or without underlying atherosclerotic lesions. Most important, although the
emergency physician can begin to estimate the risk of AMI based on
symptoms alone, it must be recognized that in ACS, atypical characteristics are the rule rather than the exception. For example, up to 22% of patients with AMI describe symptoms as being sharp or stabbing in
character, and up to 6% describe pain that is pleuritic.3 Tables 52-1 and
52-2 list factors that can be used to risk stratify patients based on clinical
TABLE 52-1
Pain Descriptor
Study
No. of
Patients
Studied
Positive
Likelihood
Ratio (95% CI)
Chun et al.7
770
4.7 (1.912.0)
Goodacre et al.6
893
4.1 (2.56.5)
Goodacre et al.6
Panju et al.3
Panju et al.3
Panju et al.3
893
278
8426
970
2.4 (1.53.8)
2.3 (1.73.1)
2.0 (1.92.2)
1.9 (1.72.3)
Chun et al.7
7734
1.8 (1.62.0)
Chun et al.6
11,504
1.3 (1.21.5)
Positive
Likelihood
Ratio (95% CI)
0.2 (0.10.3)
0.3 (0.20.5)
0.3 (0.20.5)
0.3 (0.20.4)
0.8 (0.70.9)
0.8 (0.60.9)
criteria, combining the data from four studies that assessed the clinical
predictors of myocardial infarction (MI).3,4,68 Despite the existence of
this information from studies, there is no identifiable symptom complex
that allows for the safe discharge of the undifferentiated chest pain patient
without objective testing.
Atypical presentations of ACS occur more frequently in women, nonwhite minorities, diabetics, the elderly, and patients with psychiatric disease or altered mental status, compared with white males.911 In addition,
disorders such as vasospastic and microvascular angina (also known as
Syndrome X) and mitral valve prolapse are more common in women. Ischemia also produces different patterns of pain in women with known
coronary artery disease compared with men. For example, chest pain at
rest but not during exercise does not decrease the likelihood of disease in
women as it does in men, and women with stable angina are more likely
than men to have pain during rest, sleep, or stress. Other features that
have been particularly associated with atypical presentations of ischemia
in women include pain relieved by antacids, pain unrelated to exercise,
pain not relieved with rest or nitroglycerin, palpitations without chest
pain, and fatigue as a chief compliant.12 This may partly explain the observation that women, along with the elderly, take a longer time to seek
care once their symptoms begin and have further delays in evaluation
once they reach the ED. One study showed that although men presenting
with AMI were more likely to have chest pain, this was explained by their
younger age and delayed development of diabetes mellitus when compared with women. The associated symptoms more commonly found in
women were nausea, emesis, jaw pain, neck pain, and back pain, although
diaphoresis was more commonly found in men.12
All patients should also be questioned regarding the presence of cardiac risk factors, although these risks are valid only for predicting the
presence of coronary artery disease within a given population and are
not predictive of the presence or absence of acute ischemia in an individual patient.13 Major risk factors identified by large epidemiologic studies
include age >40 years old, male or postmenopausal female, hypertension, cigarette smoking, hypercholesterolemia, diabetes, truncal obesity,
family history, and sedentary lifestyle.7,8 Cocaine use is associated with
AMI even in young people with minimal or no coronary artery disease.
Chronic cocaine use has also been associated with accelerated atherosclerosis and severe coronary artery disease.
The patients medical record should be reviewed, and any previous
ECGs should always be compared with current tracings. Results of prior
stress testing, echocardiograms, catheterizations, or radionuclide scans
should be reviewed, if available, and the present symptoms interpreted
in light of those results. For a more detailed discussion of the evaluation
of patients with prior studies, see Chapter 55, Low Probability Acute
Coronary Syndrome.
ISCHEMIC EQUIVALENTS
Because of the visceral afferent innervation of the myocardium as well as
the many confounding factors affecting the perception of ischemia,
many patients with ACS will not experience chest discomfort. In fact,
among 434,877 MI patients entered into the National Registry of Myocardial Infarction 2, 33% did not have chest pain upon presentation to
SPECIAL POPULATIONS
There are a number of interrelated and unquantifiable factors that influence how a patient perceives, interprets, and communicates symptoms.
These factors span the physiologic, psychological, and cultural differences between peoples and individuals.14 Physiologically, there are true differences in pain signal propagation and mediation related to gender, age,
and race as well as permanent or transient metabolic influences.15 It is
well understood that the elderly patient is more likely to present with
atypical symptoms of myocardial ischemia, and the diabetic patient may
not be able to accurately sense or describe pain, making the diagnosis
more difficult. The presence of multiple prescription medications, drugs,
and alcohol will also alter the patients ability to perceive discomfort.
There are gender and cultural differences in the perception and interpretation of pain, and the patients communication of symptoms and the
clinicians interpretation is affected by several filters that represent a
wide spectrum of social, cultural, and personal biases of both parties.14,16
For example, the term sharp in some cultures is interpreted to mean
severe, rather than knife-like.4 Therefore, to rapidly and effectively
identify the minority of patients with life-threatening illness from the
majority with less serious pathology, consistently use a thorough and
systematic approach.
PHYSICAL EXAMINATION
The physical examination of patients with the pain of ACS is often normal. Abnormalities in vital signs may include hyper- or hypotension, sinus tachycardia, or bradycardia. Tachycardia often results from increased
sympathetic tone and decreased left ventricular stroke volume, although
bradycardia may represent inferior wall ischemia. Patients with acute ischemia have a higher incidence of abnormal heart sounds, such as a di-
7-3
CLINICAL FEATURES
During the initial assessment of patients with chest pain, the diagnosis of
ACS should be considered in concert with other life-threatening conditions. These conditions include aortic dissection, pulmonary embolism,
pneumothorax, pericarditis, pericardial tamponade, pneumonia, and
esophageal rupture (Table 52-3). Other significant causes of chest pain
include mitral valve prolapse, aortic stenosis, and GI conditions, such as
perforated ulcer and cholecystitis. Table 52-4 contrasts the classic symptoms of life-threatening causes of acute chest pain. Although atypical presentations are common with all listed disorders, the classic symptoms are
included here to stimulate the process of differential decision making.
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. In theory, the pain
associated with a pulmonary embolism occurs when inflammation of the
parietal pleura overlying the infarction causes chest pain that is generally
sharp and related to respiration; however, most patients with pulmonary
embolism and pleuritic chest pain have no radiographic evidence of pulmonary infarction. The discomfort of massive pulmonary embolism (such
as saddle embolism) is described using more visceral terms such as a heaviness and tightness. Dyspnea, fever, cough, and/or hemoptysis also may be
present, and the chest wall may be tender to palpation. Patients with massive pulmonary embolism often present with unstable vital signs and chest
pain and dyspnea associated with tachypnea, tachycardia, and hypoxemia.
Criteria can be used to determine the need for diagnostic testing in the
evaluation for pulmonary embolism18 and to guide the intensity of the
investigation19 (see Chapter 60, Thromboembolism).
Risk factors for aortic dissection include atherosclerosis, uncontrolled
hypertension, coarctation of the aorta, bicuspid aortic valves, aortic stenosis, Marfan syndrome, Ehlers-Danlos syndrome, and pregnancy (see
Chapter 62, Aortic Dissection and Related Aortic Syndromes). 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
TABLE 52-3
Pleuritic Pain
Visceral Pain
Costosternal syndrome
Costochondritis (Tietze
syndrome)
Precordial catch syndrome
Slipping rib syndrome
Xiphodynia
Radicular syndromes
Intercostal nerve
syndromes
Pulmonary embolism
Pneumonia
Spontaneous
pneumothorax
Pericarditis
Pleurisy
Fibromyalgia
Aortic dissection
Pericarditis
Esophageal reflux or
spasm
Esophageal rupture
Mitral valve prolapse
7-4
TABLE 52-4
Disorder
Pain (Location)
Pain (Character)
Angina pectoris
Retrosternal or epigastric
Whole chest
Substernal
Pericarditis
Pneumonia
Perforated peptic ulcer
Substernal
Focal chest
Epigastric
Pain (Radiation)
Pleuritic
Ripping, tearing
Sudden, sharp, lancinating,
pleuritic
Sudden, sharp, after forceful
vomiting
Sharp, constant or pleuritic
Sharp, pleuritic
Severe, sharp
None
Intrascapular area of back
Shoulder, back
Back
Back, neck, shoulder
None
Back, up into chest
Associated Symptoms
Dyspnea, diaphoresis, nausea
Dyspnea, unstable vital signs, feeling of
impending doom
Tachycardia, tachypnea
Secondary arterial branch occlusion
Dyspnea
Dyspnea, diaphoresis, may see signs of
sepsis
Fever, pericardial friction rub
Fever, may see signs of sepsis
Acute distress, diaphoresis
back. Typically, the pain is at its worst at symptom onset and is often felt
above and below the diaphragm. Secondary symptoms resulting from arterial branch occlusions include stroke, AMI, or limb ischemia, and may
overshadow the clinical presentation. 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.20
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 Chapter 71, Spontaneous and Iatrogenic
Pneumothorax). 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 hyper-resonance
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 lifethreatening 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 Chapter 80, Esophageal Emergencies, Gastoesophageal Reflux Disease, and Swallowed Foreign Bodies). 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 Chapter 59, The Cardiomyopathies, Myocarditis, and Pericardial Disease). 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 Chapter 68, Community-Acquired Pneumonia, Aspiration Pneumonia, and Noninfectious Pulmonary Infiltrates). 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 is the most frequently diagnosed cardiac valvular
abnormality and is more commonly diagnosed in women than in men.
The discomfort of mitral valve prolapse often occurs at rest, is atypical
for myocardial ischemia, and can be associated with dizziness, hyperventilation, anxiety, depression, palpitations, and fatigue (see Chapter 58,
Valvular Emergencies). 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 mitral valve prolapse.
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 pulmonary embolism 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 minutes near the cardiac
apex associated with inspiration and poor posture and inactivity.
GI 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 Chapter 81,
Peptic Ulcer Disease and Gastritis). 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 Chapter 80,
Esophageal Emergencies, Gastoesophageal Reflux Disease, and Swallowed Foreign Bodies). The pain may disappear with the administration
of sublingual nitroglycerin, typically with a slight delay.
Peptic ulcer disease is classically characterized as a postprandial, dull,
boring pain in the midepigastric region (see Chapter 81, Peptic Ulcer Disease and Gastritis). 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.
ANCILLARY TESTING
Ancillary testing in acute chest pain applies electrocardiography, laboratory testing, and imaging studies within the context of a focused, evidencebased approach to initially screen for, and subsequently distinguish, those
with dangerous intrathoracic pathology from those with more benign
conditions. Although the specific studies are chosen according to individual clinical circumstances, ACS is by far the most common serious cause
of acute chest pain. Treatment is time dependent, and its presence cannot
be excluded by history and exam alone. Accordingly, consensus guidelines
and common practice direct the early, routine application of ECG and
myocardial marker measurements for the early detection of ACS.
The remainder of this chapter focuses on the indications, interpretations, and synthesis of ancillary testing during the initial assessment of
undifferentiated chest pain in the ED. The subsequent application of either serial or continuous ECG monitoring, serial myocardial marker
measurements, advanced imaging techniques and/or stress testing to definitively diagnose or exclude ACS or for risk stratification is the focus of
Chapter 55, Low Probability Acute Coronary Syndrome.
The chest radiograph is of limited value in the evaluation of ACS, but
aids in detection and exclusion of a variety of other serious diagnoses.
The appropriate utilization and interpretation of radiography and other
diagnostic modalities in the evaluation of specific pathologic conditions
(i.e., pulmonary embolism, aortic dissection, etc.) are discussed in detail
in their respective chapters.
ECG
Patients with chest pain or other symptoms suggestive of ACS should receive a 12-lead ECG upon ED presentation. The 2007 American College
of Cardiology/American Heart Association Guidelines for Management
of Patients with Unstable Angina/Non ST-Elevation MI recommend
that an ECG be performed and shown to an experienced emergency
physician as soon as possible after ED arrival, with a goal of within 10
minutes of ED arrival for all patients with chest discomfort or other
symptoms suggestive of ACS.23 Although complete compliance with
this guideline may be challenging in the resource-constrained environments of many high-volume EDs, delay in identification of high-risk
ECG findings has been associated with increased inhospital mortality.24
ED systems that reduce delays to ST-elevation AMI identification improve guideline compliance and patient outcomes.25
About half (range, 13% to 69%) of patients with AMI have diagnostic changes on the initial ECG (new ST-segment elevation >1 mm in
two contiguous leads),26 whereas another 20% to 30% have new ST-seg-
7-5
100
cTnT
50
cTnI
15
MLC
Myoglobin
creatine kinase, subunits muscle and brain (CK-MB) and myoglobin, clinicians must maintain an accurate understanding of appropriate applications, proper results interpretation, and assay limitations.
When highly sensitive assays are used, both troponin I and troponin
T may be detectable in serum as early as 2 hours after AMI but are not
reliably elevated in all patients until 6 to 12 hours. Levels reach their
peak at 12 hours and remain elevated for 7 to 10 days, making troponin
a uniquely useful test for patients with delayed presentations. However,
the diagnosis of reinfarction or infarct extension must then be based
upon an alternative marker (i.e., CK-MB) or recognition of a newly increasing pattern of troponin elevation. As troponin has greater cardiac
specificity than CK-MB, either troponin I or troponin T is also a preferred marker in the setting of possible skeletal muscle injury, recent surgery, trauma, skeletal muscle disease, or cocaine use.
Elevation of either troponin is associated with a higher risk of subsequent cardiovascular complications and mortality compared with those
with a negative troponin test, independent of CK-MB and the ECG.32 Accordingly, the European College of Cardiology/American College of Cardiology Consensus Document on redefinition of MI declared that (when
utilizing recent generations of troponin assays) there is no discernible
threshold below which an elevated value of cardiac troponin would be
deemed harmless.33 However, although it should never be ignored, an
elevated troponin must always be considered within the clinical context
of the patients presentation. Considered alone, an elevated troponin level
does not diagnose the presence of coronary artery disease or identify any
particular etiology of cell death. Indeed, elevated troponin levels have
been documented in many clinical conditions in the absence of coronary
artery disease, including, but not limited to, tachyarrhythmias, left ventricular hypertrophy, myocarditis, pericarditis, heart failure, pulmonary
embolism, and sepsis (Table 52-5).34,35 Recognizing this, 2007 consensus guidelines recommends the term myocardial necrosis be applied to
any patient with an elevation of troponin above the 99th percentile of
normal while reserving the diagnosis of MI for those with troponin elevation and at least one of the following additional criteria: ischemic
symptoms, new ST and T-wave changes, new left bundle-branch block,
new Q-waves, or imaging evidence of a new loss of viable myocardium
or new regional wall motion abnormality.32,34
In the ED, the clinical utility of troponin I and troponin T assays can
generally be considered equivalent, although there are a few notable differences. Although only one troponin T assay exists, various manufacturers produce assays based on antibodies to several different troponin I
fragments, resulting in significant heterogeneity in troponin I assay performance. In addition, the two tests perform differently in the setting of
renal failure. Among patients with end-stage renal disease, a greater proportion will have an elevated troponin T (15% to 50%) compared with
troponin I (<10%), and, after dialysis, serum levels of troponin T generally
increase while troponin I levels decrease.36 The reasons for this paradox is
not completely clear but likely relates to protein fractionation and differential clearance as well as other factors. Despite this, renal failure patients
with a positive test for either troponin I or troponin T have been repeatedly and consistently shown to be at significantly higher risk for death and
other adverse events compared with those with a negative test regardless
of symptoms and across the entire spectrum of renal dysfunction. Thus,
similar to patients with normal renal function, a positive troponin test in
the setting of renal failure may or may not indicate the presence of coronary obstruction and must be considered within the individual patients
clinical context but should never be dismissed as a false positive test.
Creatine Kinase, Subunits, and Myoglobin Creatine kinase (CK; ATP creatine N-phosphotransferase) is an intracellular enzyme involved in the
transfer of high-energy phosphate groups from ATP to creatine. The enzyme is a dimer of two subunits, which may be of the M (muscle) or the
B (brain) type, thus creating three distinct isoenzymes: CK-BB, predominant in brain; CK-MM, mostly in skeletal muscle, and CK-MB. The
cardiac isoenzyme, CK-MB is found in greater proportion in cardiac
muscle but accounts for only 14% to 42 % of total cardiac muscle activity.
Thus, the predominant enzyme in the heart is also CK-MM. CK levels
become elevated within 4 to 8 hours after coronary artery occlusion,
7-6
10
CK-MB
LD1
5
Reference interval
10
FIGURE 52-1. Typical pattern of serum marker elevation after acute myocardial
infarction (AMI). CK-MB = creatine kinase-MB isoenzyme; cTnI = cardiac troponin I;
cTnT = cardiac troponin T; LD1 = lactate dehydrogenase isoenzyme 1; MLC = myosin light chain.
Common
Uncommon
Unclear
Congestive heart
failure
Acromegaly
Hypothermia
Rocky Mountain
spotted fever
Typhoid fever
Chronic bronchitis
Lumbago
Febrile disorder
Isolated rare case
in normal person
Cardiomyopathies
Circulatory failure and shock
Cardiac surgery
Cardiac trauma
Skeletal muscle trauma
(severe)
Dermatomyositis,
polymyositis
Muscular dystrophy,
especially Duchenne
Extreme exercise
Malignant hyperthermia
Reye syndrome
Rhabdomyolysis of any cause
Delirium tremens
Ethanol poisoning (chronic)
hours, peak at 4 to 9 hours (Figure 52-1), and, with normal kidney function, return to baseline within 24 hours. False positive results are common because myoglobin found in myocardium is indistinguishable from
that found in skeletal muscle, and false negatives may occur if the test is performed after myoglobin has already been cleared from serum. Although
still useful for rapid diagnosis of AMI among patients presenting soon after
symptom onset, the improved sensitivity of successive generations of
troponin assays reduces the need for routine use of this early marker.
Natriuretic Peptides and Other Laboratory Markers B-type natriuretic peptide (BNP) is a neurohormone that rapidly and reproducibly appears in
blood in response to increased ventricular wall tension and pressure overload. It is initially released by ventricular myocytes as the precursor molecule, pro-BNP, which is then enzymatically cleaved in an equimolar ratio
into the 76 amino acid N-terminal pro-BNP (NTproBNP) and the 32 amino acid BNP. Physiologically, BNP decreases blood volume through natriuresis and decreases peripheral resistance through vasodilation, having
the net effect of decreasing afterload on the heart. The half-life of BNP is
approximately 20 minutes, and its clearance mechanism is believed to be
by natriuretic receptor internalization and enzymatic degradation by a
neutral endopeptidase in the blood stream. NTproBNP, conversely, has a
plasma half-life of approximately 90 minutes, and is excreted by the kidneys.37 Although initially adopted into routine ED use as highly sensitive
diagnostic and prognostic markers of heart failure, BNP and NTproBNP
have also each been shown to have high diagnostic and prognostic sensitivity among ED patients with possible ACS.37 However, in this clinical
context, both tests have limited specificity, resulting in many false positives for each additional true positive patient detected. Therefore, although of great value in the evaluation of dyspnea, these assays are not be
recommended for routine use among ED chest pain patients either as a replacement for or a supplement to troponin testing.38
7-7
REFERENCES
The complete reference list is available on the included DVD or online
at www.placeholderurl.com