31 CHEST PAIN
BRETT E. FENSTER, MD • TEOFILO L. LEE-CHIONG, JR., MD • G.F. GEBHART, PhD •
RICHARD A. MATTHAY, MD
INTRODUCTION Cardiovascular Disorders
EPIDEMIOLOGY NONCARDIAC CHEST PAIN
NEUROBIOLOGY OF PAIN Musculoskeletal Disorders
Somatic Pain Gastrointestinal Disorders
Visceral Pain Psychological Factors
HYPERALGESIA Miscellaneous Causes of Chest Pain
MEASURING PAIN EVALUATION AND TREATMENT OF
CHEST PAIN SYNDROMES CHEST PAIN
Pleuropulmonary Disorders Cardiac Ischemia
Tracheobronchitis Pulmonary Embolism
Inflammation or Trauma of the Chest Pericardial Disease
Wall Cardiac Tamponade
INTRODUCTION
Pain is a complex subjective experience that varies from
person to person in its quality, intensity, duration, location,
frequency, and associated features. Its perception is influ-
enced by a subject’s culture, emotional and cognitive
contributions, socioeconomic status, familial background,
prevailing psychological factors, anticipation and previous
experience, and the clinical context.
Chest pain is characterized by an unpleasant sensation
that is either localized to the thorax or believed to originate
from structures located there. It may announce the pres-
ence of severe, occasionally life-threatening, disease. Diag-
nosis of chest pain is often complicated by the vague
presentations and indistinct anatomic localization of many
of its causes.
EPIDEMIOLOGY
There are uncertainties about the exact prevalence of chest
pain. In a study of 500 randomly selected households in
Burlington, Canada, 16% of 827 respondents reported
experiencing pain within the 2 weeks preceding the survey.1
Persistent pain was approximately twice as common as
temporary pain, and chest pain was the fifth most common
type of temporary pain. In studies of acute pain that was
sufficient to warrant medical attention, chest pain is always
an important factor.
A survey of 1016 randomly selected enrollees of a health
care plan in Seattle, Washington, revealed that they reported
a high incidence of pain lasting a whole day or more several
times during the previous 6 months2; the most common
complaint was back pain, followed by headache, abdominal
pain, facial pain, and chest pain. Chest pain accounted for
12% of the reported cases but was the most common site
of pain that prompted respondents (35%) to seek medical
attention. Pain is also a common reason for persons to visit
hospital emergency departments. In a survey of 36,271
random evaluations, stomach pain, other abdominal pain,
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Pulmonary Arterial Hypertension
Thoracic Aortic Dissection
Pneumothorax
Tension Pneumothorax
Pancoast Tumors
Chest Trauma
Gastroesophageal Reflux
Pancreatitis
and chest pain were the most often cited reasons; they pre-
sented with almost equal frequency and, together, accounted
for 10.7% of all emergency department visits.3
NEUROBIOLOGY OF PAIN
Pain is not a simple sensation. The neurobiologic and
functional components of the sensory channels for pain
are neither fixed nor immutable. The nervous system, from
the level of the nociceptor (the receptor that responds to
noxious stimuli) to the supraspinal sites of integration, is
characterized by its dynamic response (plasticity) to tissue
insult.
Pain arising from visceral organs (e.g., heart or gastroin-
testinal tract) differs in many ways from that arising from
somatic structures, such as the skin. Visceral pain is difficult
to localize, is diffuse in character, and is typically referred to
somatic structures. In addition, it is often associated with
greater autonomic and motor responses than is somatic
pain. These differences between visceral and somatic pain
are associated with characteristic features of sensory inner-
vations that are unique to the viscera.
SOMATIC PAIN
Somatic structures, such as the skin, are invested with a
wide variety of nociceptors, each with selective sensitivities
to mechanical, thermal, or chemical stimuli, in addition
to the polymodal nociceptor that responds to multiple
modalities of noxious stimuli.4,5 Cutaneous nociceptors are
characterized by very infrequent or no spontaneous dis-
charges, an ability to encode stimulus intensities in the
noxious (but not innocuous) range, and most importantly,
sensitization. Sensitization refers to an increase in the mag-
nitude of response after tissue insult, sometimes associated
with an increase in spontaneous activity as well as a de­­
crease in response threshold. This attribute of nociceptors
contributes to development of hyperalgesia, or an increased
response to a stimulus that is normally painful.
515
516 PART 3  •  Clinical Respiratory Medicine
When a tissue is injured, a host of sensitizing chemicals
are synthesized at the site of injury or released from circu-
lating cells that are attracted to the site of injury. These
include amines (e.g., histamine and serotonin), peptides
(e.g., substance P and calcitonin gene—related peptide),
kinins (e.g., bradykinin), neurotrophins, cytokines, prosta-
glandins, leukotrienes, excitatory amino acids (e.g., gluta-
mate), and free radicals. However, it is unlikely that any one
putative chemical mediator is responsible for nociceptor
sensitization. Although substance P, for example, is con-
tained in most nociceptor cell bodies, it is also present in a
significant number of non-nociceptor cell bodies. Similarly,
other neuropeptides, such as calcitonin gene—related
peptide, somatostatin, and galanin, are found more com-
monly in small- to intermediate-sized dorsal root ganglion
cell bodies.
VISCERAL PAIN
Input to the central nervous system from aortic barorecep-
tors, gastric chemoreceptors, and pulmonary stretch recep-
tors is rarely perceived. Nevertheless, it is evident that
visceral afferents possess many of the characteristics of
nociceptors.
All viscera possess a dual innervation. Organs of the tho-
racic cavity are innervated by vagal afferent fibers with cell
bodies in the nodose and jugular ganglia as well as by spinal
afferent fibers with cell bodies in thoracic dorsal root
ganglia. Unlike their somatic counterpart, spinal visceral
afferent fibers typically traverse either or both prevertebral
and paravertebral ganglia en route to the spinal cord. Thus,
in contrast to somatic input to the central nervous system,
which has a single, usually spinal, destination, input to the
central nervous system from organs in the thoracic cavity
arrives at two locations, namely the brain-stem nucleus
tractus solitarii (vagal afferent input) and the thoracic
spinal cord. Accordingly, the potential exists for interaction
in the central nervous system of inputs from the same
thoracic organ. The esophagus and heart also possess an
intrinsic nervous system with cell bodies in the organ wall
or in ganglia in the epicardial fat.6
Further differences between somatic and visceral inner-
vation relate to the density of innervation and spinal
pattern of termination. In general, the number of visceral
afferent fibers is disproportionately less than the number of
somatic afferent fibers, although the rostrocaudal spread of
visceral afferent fiber terminals in the spinal cord is consid-
erably greater than the spread of central terminals from
somatic afferent fibers. Although this means that there are
fewer central visceral terminals in the spinal cord, visceral
afferent fiber terminals have many more terminal swellings
(suggestive of synapses) than somatic nociceptor terminals
and they spread over several spinal cord segments.7 The
obvious consequence of the low number of visceral affer-
ents and greater intraspinal spread is loss of spatial dis-
crimination, consistent with the diffuse, difficult-to-localize,
nature of visceral pain.
The axons of visceral sensory neurons are, with rare
exception, either thin, myelinated Αδ fibers or unmyelin-
ated C fibers. In general, Αδ fibers, having some myelin,
carry moderately fast impulses, usually of acute or sharp
pain but also temperature. C fibers, without myelin, carry
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slow impulses, usually of burning pain. Generally the pro-
portion of Αδ fibers in visceral sensory nerves is less than
the proportion of C fibers. In addition, Αδ fibers are fibers
with a low threshold for response to mechanical stimula-
tion, whereas C fibers have high thresholds; however, this is
not universal.
Unlike tissue-damaging stimuli that produce pain in
somatic structures, tissue injury is not required for produc-
tion of pain in the viscera. For the lower airways, irritants
contained in smoke, ammonia, and other inhaled sub-
stances are capable of producing discomfort and pain. For
the heart and mesentery, ischemia can be an adequate
stimulus.8 For hollow organs of the gastrointestinal tract,
distention of the lumen of the organ, which activates
stretch and tension receptors in the smooth muscles, is typi-
cally adequate.
Hollow viscera, including the esophagus, are innervated
by two populations of mechanosensitive afferent fibers,
namely a larger group (70% to 80%) of fibers that have low
thresholds for response (i.e., within the physiologic range),
and a smaller group (20% to 30%) of fibers that have
thresholds for response that fall in the noxious range.9 All
mechanosensitive visceral afferent fibers may function in
some circumstances as nociceptors, and low- and high-
threshold mechanosensitive fibers contribute to discomfort
and pain that arise from the viscera.
Silent nociceptors, a relatively new category of receptor/
afferent fibers, may also contribute to altered sensations
from visceral structures.10 Silent nociceptors, more appro-
priately termed “mechanically insensitive afferents” have
no spontaneous activity and do not respond to acute, high-
intensity mechanical stimulation in normal circumstances.
After tissue insult, mechanically insensitive afferents typi-
cally begin to discharge spontaneously and acquire sensitiv-
ity to mechanical stimulation. However, the contribution of
such “silent” or “sleeping” afferent fibers to altered sensa-
tions that arise from the viscera is uncertain at present.11,12
HYPERALGESIA
Some individuals are uniformly more sensitive (i.e., have
lowered thresholds for stimulus-produced pain) than others.
Hyperalgesia, the enhanced response to a stimulus that
is normally noxious, consists of primary and secondary
components. Primary hyperalgesia refers to enhanced sensi-
tivity to stimuli applied at the site of tissue injury (e.g., an
incision). Secondary hyperalgesia, conversely, pertains to
enhanced sensitivity to stimuli applied to uninjured tissue
adjacent to and occasionally distant from the site of injury.
Peripheral mechanisms (sensitization of nociceptors and
afferent fibers innervating the insulted tissue) and central
mechanisms (changes in the excitability of spinal and
supraspinal neurons) contribute to primary and secondary
hyperalgesia, respectively. Afferent fibers that innervate the
pelvic viscera have been shown to sensitize when organs are
experimentally inflamed. After inflammation, both low-
threshold and high-threshold mechanosensitive afferent
fibers in the pelvic nerve exhibit exaggerated responses
to distention relative to responses of the same afferent
fibers before inflammation. This change in neuron excit-
ability is believed to arise principally through the action of

glutamate at the N-methyl-D-aspartate receptor. Contribu-
tions of non–N-methyl-D-aspartate receptors, AMPA or
kainate, and of the receptor at which substance P acts (neu-
rokinin 1 receptor) are also likely.13 Glutamate and sub-
stance P are co-contained in many small-diameter dorsal
root ganglion cells and presumably are concurrently
released in the spinal dorsal horn, where N-methyl-D-
aspartate receptors on nociceptor terminals may act as
autoreceptors to facilitate the further release of both gluta-
mate and substance P.14 In addition, there is evidence that
substance P can act synergistically with glutamate to
enhance the responses of spinal neurons.15
Virtually all spinal cord neurons that receive a visceral
input also receive input from somatic structures, including
the skin, muscle, and joints. This convergence of inputs in
the spinal dorsal horn includes both viscerosomatic and
viscerovisceral pathways and is believed to be the basis of
the referred sensation that characterizes visceral pain. Such
convergence suggests that injury to somatic tissue could
lead to visceral hyperalgesia and, conversely, that injury to
a viscus could lead to somatic hyperalgesia.
Spinal nociceptive transmission can be modulated by
electrical or chemical stimulation in the midbrain or
medulla.16 Both facilitatory and inhibitory influences on
spinal nociceptive transmission are present and likely play
an important role in the maintenance of secondary hyper-
algesia.17 Electrical activation of vagal afferent fibers
similarly engages descending facilitatory and inhibitory
modulation of spinal nociceptive transmission. Responses
of neurons in the thoracic dorsal horn to either esophageal
distention18 or lower airway irritation caused by ammonia
or smoke19 are altered when the cervical spinal cord is
blocked or transected or when the vagi are cut. Responses
to esophageal or respiratory stimulation would be expected
to increase when the cervical spinal cord was blocked
because tonic descending inhibitory influences are usually
present; unexpectedly, responses were more commonly
reduced, suggesting the presence of a descending facilita-
tory influence that is associated with vagal input to the
brain stem. In a related work, both vagal afferent input and
spinal cardiac nerve afferent inputs contribute to the sensa-
tion of cardiac pain, particularly referral of such pain to the
neck and jaw.20
MEASURING PAIN
Pain has proved to be both hard to define and difficult to
measure. Because pain can be quantified only indirectly, it
has been difficult to determine the optimal measuring tool
for all types of pain sensations. Two widely used techniques,
namely rating scales and questionnaires, are often used in
clinical and epidemiologic studies of chest pain.
Rating scales constitute the simplest measurement of
pain. One of the easiest to use is the quantification of pain
intensity by a graded rating scale, such as the popular
visual analogue scale.21 However, the sensation of pain has
many more components than just its intensity; thus a
single-dimensional rating scale leaves many aspects of the
sensation undocumented.
To address the multidimensional qualities of pain, ques-
tionnaires have been developed.22 The McGill Pain Ques-
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31  •  Chest Pain 517
tionnaire, the most widely used method in the English
language for studying the epidemiology of pain, was devel-
oped in the 1970s23 and has been shown to be reliable and
useful.24 Although questionnaires are a powerful way of
obtaining data on both the qualitative and the quantitative
aspects of pain, it is not always possible to compare the
results of studies with the same questionnaire because of
differences in the way they have been employed.
CHEST PAIN SYNDROMES
Pain arising from the various viscera in the thoracic cavity
and from the chest wall is often qualitatively similar and
exhibits overlapping patterns of referral, localization, and
quality, given the proximity of the various organs and the
vagaries of perception of pain of visceral origin. This leads
to difficulty in the differential diagnosis of chest pain (Table
31-1). Nevertheless, many chest pain syndromes are suffi-
ciently distinctive clinically that diagnostic efforts often rely
on accurate description of the characteristic pattern of
pain. The importance of the medical history in unraveling
the various causes of chest pain cannot be overemphasized.
The locations to which various pain syndromes are referred
in the chest are illustrated in Figure 31-1.
PLEUROPULMONARY DISORDERS
Although the lung parenchyma and visceral pleura are
considered to be insensitive to ordinary noxious stimuli,
immunohistochemical studies from vagal denervation and
talc-pleurodesis animal models indicate the presence of
nerve fibers in the visceral pleura that may be capable of
conducting pain stimuli.25,26 Pain does arise from stimula-
tion of the mucosa of the trachea and main bronchi.25 The
lungs and bronchi are innervated with mechanoreceptors
that respond to stretch (inflation or deflation of the lungs)
as well as chemoreceptors called J receptors that respond to
a variety of pain-inducing chemicals, including bradykinin,
prostaglandins, serotonin, and capsaicin.27,28 Inhalation of
irritant substances, such as ammonia, can trigger a cough
reflex and can produce a sense of rawness, tightness in the
chest, and pain. In addition, rapidly adapting mechanore-
ceptors that respond to lung deflation are also “irritant
receptors” and signal respiratory pain. J receptors have
been proposed to contribute to discomfort and pain that
accompanies breathlessness.27-29
These receptors are, in turn, innervated by vagal and
spinal splanchnic afferent fibers. Nerve fibers that travel in
the vagus nerves, including myelinated axons that carry
impulses from slowly adapting stretch receptors in the con-
ducting airways, myelinated axons that lead from rapidly
adapting irritant cough receptors in the trachea and
bronchi, and unmyelinated axons that subserve the exten-
sive network of C fiber receptors (e.g., “pulmonary” J recep-
tors and “bronchial” C fibers), are most important.30
The pulmonary causes of chest pain may be related to
the pleural tissue, pulmonary vessels, or lung parenchyma.
Causes of chest pain related to the lung parenchyma include
infection, cancer, or chronic diseases such as sarcoidosis.
These are discussed in more detail elsewhere in the
textbook.
518 PART 3  •  Clinical Respiratory Medicine

Table 31-1  Common Causes of Chest Pain contiguous inflammation), the resulting pain is referred to
the ipsilateral shoulder or neck. This pain referral likely
PLEUROPULMONARY DISORDERS arises because visceral afferent input carried by the phrenic
Pleurisy nerve converges with somatic input carried by the supracla-
Infection
Pulmonary embolism
vicular nerves that innervate the skin of the shoulder onto
Spontaneous pneumothorax C3-5 spinal dorsal horn neurons (i.e., viscerosomatic con-
Collagen vascular disease vergence, a common feature of visceral pain leading to
Sickle cell disease referred sensations). Thus, when this portion of the dia-
Familial Mediterranean fever phragm is stimulated (e.g., by contiguous inflammation),
Malignancy (e.g., mesothelioma)
Pulmonary hypertension the resulting pain is referred to the ipsilateral shoulder
Pulmonary embolism or neck.
Primary pulmonary hypertension Because of the somatic innervation of the parietal pleura,
Eisenmenger syndrome as well as the localization of most diseases of the lungs or
TRACHEOBRONCHITIS chest wall to one hemithorax or the other, pleuritic pain
Infection tends to be limited to the affected region rather than be
Inhalation of irritants diffuse, with the exception of referral to the ipsilateral neck
Malignancy or shoulder. Pain may be variously described as “sharp,”
INFLAMMATION OR TRAUMA OF THE CHEST WALL “dull,” “achy,” “burning,” or simply a “catch.” There is a
Rib fracture distinctive and unmistakable relationship to breathing
Muscle injury (myalgia) movements, and taking a deep breath typically aggravates
Infection pleuritic pain.31 Coughing and sneezing can cause intense
Malignancy
Sickle cell disease
distress. Movements of the trunk, such as bending, stoop-
Neuritis-radiculitis ing, or turning in bed, worsen pleuritic pain, so much so
Herpes zoster infection that patients often prefer the body position in which motion
CARDIOVASCULAR DISORDERS of the affected region is least.
Angina pectoris
An immediate onset of pleuritic pain suggests traumatic
Variant angina injuries or spontaneous pneumothorax. A sudden onset,
Myocardial infarction often associated with dyspnea and tachypnea, also charac-
Aortic valve disease terizes the clinical presentation of pulmonary embolism.32
Mitral valve prolapse A slower but still acute onset over minutes to a few hours
Hypertrophic cardiomyopathy
Pericarditis often heralds the development of community-acquired bac-
Cocaine toxicity terial (typically pneumococcal) pneumonia, especially when
DISORDERS OF THE AORTA
accompanied by fever and chills. Recurrent acute pleuritic
pain is a feature of familial Mediterranean fever.33 Finally, a
Aortic dissection
gradual onset over days or weeks, often associated with fea-
GASTROINTESTINAL DISORDERS tures of chronic illness, such as low-grade fever, weakness,
Reflux esophagitis and weight loss, suggests tuberculosis or malignancy.
Esophageal motility disorders
Cholecystitis Pulmonary Hypertension
Peptic ulcer disease
Pancreatitis Persons with pulmonary hypertension may experience
Disorders of intestinal motility crushing or constricting substernal pain that at times radi-
MISCELLANEOUS CAUSES OF CHEST PAIN ates to the neck or arms, thus resembling the pain of myo-
Thoracic outlet obstruction cardial ischemia.34 Pain from pulmonary hypertension has
Mediastinal emphysema been reported in patients with conditions that are acute
Iatrogenic (e.g., multiple or massive pulmonary emboli) and chronic
(e.g., Eisenmenger syndrome, pulmonary vasculitis, or
mitral stenosis). In addition, approximately half of the
Pleurisy patients with primary pulmonary hypertension may have
Pleurisy results from inflammation of the parietal pleura. precordial chest pain.35
Inflammatory processes in the periphery of the lung that In acute pulmonary hypertension resulting from massive
involve the overlying visceral pleura (e.g., pneumonia) fre- pulmonary embolism, the pain may be caused by sudden
quently cause inflammation of the adjacent parietal pleura distention of the main pulmonary artery and stimulation
that, in turn, provokes pleuritic pain conveyed by somatic of mechanoreceptors.
nerves. The parietal pleura that lines the interior of the rib In primary pulmonary hypertension, chest pain may be
cage and covers the outer portion of each hemidiaphragm related to either (1) right ventricular ischemia because cor-
is innervated by the neighboring intercostal nerves; when onary blood flow is unable to meet the metabolic needs of
pain fibers in these regions are stimulated, pleuritic pain is the overloaded right ventricular muscle mass as the latter
localized to the cutaneous distributions of the involved strives to maintain sufficient systolic and diastolic pulmo-
neurons over the chest wall. In contrast, the parietal pleura nary arterial pressures36 or (2) compression of the left main
that lines the central region of each hemidiaphragm is coronary artery by the dilated pulmonary artery trunk.37
innervated by fibers that travel with the phrenic nerves; Although precordial pain related to the sudden onset of
when this portion of the diaphragm is stimulated (e.g., by pulmonary hypertension can develop in cases of acute

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 31  •  Chest Pain 519

Front
Shoulder
Shoulder Acute coronary syndrome
Diaphragmatic inflammation Aortic dissection
Perforated viscus Acute pericarditis
Thoracic outlet syndrome Diaphragmatic inflammation
Acromial bursitis Perforated viscus
Acromial bursitis
Thoracic outlet syndrome
Chest
Acute coronary syndrome
Aortic dissection Left arm
Spontaneous Acute coronary
pneumothorax syndrome
Cocaine toxicity
Acute/chronic pulmonary
hypertension (including
pulmonary embolism)
Pneumonia
Acute pericarditis
Valvular heart disease Abdomen
Tracheobronchitis Acute coronary syndrome
Esophageal disorders Perforated viscus
Costochondritis
Intercostal muscle cramps
Pectus deformity Back

Pericarditis

Acute coronary syndrome

Aortic dissection
Esophageal disorders
Figure 31-1  Sites of referred pain in the chest. Some conditions are shown that should be considered as sources of referred pain in certain locations
of the chest. Potential sources are listed in order of severity. Referred pain is generally due to viscerosomatic convergence, in which spinal cord neurons
receive input from both visceral and somatic sources so that visceral pain can be interpreted as coming from a somatic source. Not shown are psychologi-
cal causes of pain, which may constitute one of the most common entities, although it should remain a diagnosis only after considering and excluding
these sources of pain.

pulmonary embolism, embolism-associated pain is much
more likely to be pleuritic in character, whether or not there
is pulmonary infarction.38
Pulmonary artery stenosis may also cause substernal
pain, presumably by the same pressure-overload mecha-
nism through which pulmonary hypertension with right
ventricular hypertrophy provokes pain.39
or “achy,” and exaggerated by deep breathing. This type of
discomfort usually denotes the presence of viral or bacterial
tracheobronchitis or, less often, a malignancy but can also
be experienced during exposure to noxious gases. Tracheo-
bronchial pain is thought to be mediated by bronchial C
fibers. Experimentally induced tracheal pain can be abol-
ished by vagal blockade41 or by vagotomy.42

TRACHEOBRONCHITIS INFLAMMATION OR TRAUMA OF THE CHEST

Pain of tracheal origin is generally felt in the midline, ante-
riorly, from the larynx to the xyphoid. Conversely, pain from
either main bronchus is felt in the ipsilateral anterior chest
near the sternum or in the anterior neck near the midline.40
Whatever its origin, pain related to tracheobronchitis is
typically described as “raw” or “burning” but may be “dull”
WALL (see Chapter 98)
Inflammation of, or trauma to, the joints, muscles, carti-
lages, bones, and fasciae that constitute the thoracic cage
can cause chest pain.43-45 Fibromyalgia, fibrositis, and other
rheumatologic disorders of the thoracic cage, such as anky-
losing spondylitis, are known to cause pain and discomfort

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520 PART 3  •  Clinical Respiratory Medicine
in the chest.46 Acute or chronic inflammation of the xiphoid
process (xiphodynia)47 and superficial thrombophlebitis of
the chest wall (Mondor syndrome)48 may also be uncom-
mon sources of chest pain. Occasionally pain related to res-
piration may be experienced along the costal margins after
vigorous exercise.49 In addition, metastatic malignancy
may present as painful lesions of the chest wall, sometimes
with spontaneous rib fractures. Another confusing source
of chest pain is infectious arthritis of the sternoclavicular
joint or costochondral junctions, which is an increasing
problem among injection drug users.50
With costochondritis, chest wall pain arises from the cos-
tochondral cartilaginous junctions. It is usually described
as “dull with a gnawing, aching quality.” There is little, if
any, relationship to respiratory or other body movements.
Tenderness to palpation is clearly localized to one or more
of the costal cartilages.51 There may be redness, swelling,
and enlargement of the costal cartilages (Tietze syndrome).
The most common sites of costosternal perichondritis are
the second, third, and fourth cartilages, but any part of the
large cartilaginous shield along the central and lower por-
tions of the anterior thoracic cage may be involved.
The pain of intercostal neuritis or radiculitis, which often
originates from disorders of the cervicodorsal spine or nerve
roots, is usually perceived in the rib cage. The superficial,
spontaneous lancinating or electric shock–like pain of
intercostal neuritis is typically felt over the cutaneous dis-
tribution of the involved nerves and may be worsened by
taking deep breaths, coughing, and sneezing. Unlike pleu-
risy, neuritic pain is usually not aggravated by ordinary
breathing; the diagnosis is supported by the presence of
hyperalgesia or anesthesia on examination of the skin. In
some patients with neuritis/radiculitis, the diagnosis
becomes evident 2 or 3 days later with the development of
the characteristic vesicular rash of herpes zoster over the
involved dermatome. Painful radiculitis is also recognized
as an important early manifestation of Lyme disease.52
Injuries to the ribs (fracture) and thoracic cage muscles
(strain, tears, or hematoma) are common causes of local-
ized chest pain. The relationship of the pain to trauma is
obvious in most instances, but diagnosis may be elusive,
particularly if the inciting event is relatively minor (e.g.,
unnoticed episode of coughing) or when the onset of pain
is delayed.
CARDIOVASCULAR DISORDERS
Mechanosensitive and chemosensitive afferent fibers are
present in the myocardium.27,53 Chemical stimuli are
believed to be the most important causes of cardiac pain,
but mechanical distention or distortion may also play a
role.54 Sensory fibers travel from the heart to the spinal cord
through the several cardiac nerves, the upper five thoracic
sympathetic ganglia, and finally, the upper five thoracic
dorsal roots; afferent fibers also reach the brain through the
vagus nerves.55 Cardiac pain is likely associated with activ-
ity in afferent fibers contained in the spinal afferent inner-
vation of the heart.
Acute Coronary Syndrome
Acute coronary syndrome includes all conditions with myo-
cardial ischemia caused by obstruction to coronary blood
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flow. Angina pectoris due to myocardial ischemia is typically
described as severe “pressure,” “squeezing,” or “constric-
tion” with maximal intensity retrosternally or over the left
parasternal border. Radiation to the neck, jaw, shoulder, or
down the inner aspect of one or both arms may be present.
It is usually induced by exercise but may be provoked by
heavy meals, excitement, or extreme emotion. Pain tends to
recur with repeated provocation, although its severity may
vary. Pain usually subsides within 2 to 10 minutes with
rest, and relief is accelerated by treatment with sublingual
nitroglycerin.56 A majority of patients with stable angina
pectoris have significant reduction of at least one major
coronary artery.57 Prinzmetal or variant angina is similar
in quality and location to typical angina pectoris but
appears at rest rather than during exercise or increased
myocardial oxygen needs.58 In this syndrome the imbalance
between myocardial oxygen supply and demand is postu-
lated to arise from epicardial coronary artery vasospasm,
usually superimposed on noncritical atheromatous vessel
narrowing. Pain does not always accompany myocardial
ischemia, and many electrocardiographically detectable
episodes of ischemia in patients with stable angina pectoris
are asymptomatic (“silent” ischemia).59 Conversely, many
individuals with angina-like chest pain have normal or
nearly normal coronary arteries when studied by arteriog-
raphy. As many as 30% of these noncoronary cases are
classified as “syndrome X,”60 with the development of chest
pain attributed to either coronary microvascular spasm or
heightened pain perception.60,61
The pain of acute myocardial infarction is similar in loca-
tion to that of angina pectoris but is typically much more
severe in intensity, is not relieved by rest or nitroglycerin,
often requires large doses of opiates for control, and is fre-
quently associated with profuse sweating, nausea, dyspnea,
and profound weakness.56 During episodes of myocardial
ischemia, the involved myocardium stiffens; when severe,
this decrease in compliance may increase left ventricular
end-diastolic filling pressure sufficiently to raise left atrial
and pulmonary vascular pressures and cause pulmonary
edema. Massive myocardial infarction may also lead to
intractable hypotension and shock. Acute myocardial
infarction may also be silent,62 especially in patients with
diabetes mellitus.63
Valvular Heart Disease
Chest pain can also arise from other non–coronary artery
disorders, including mitral valve prolapse, myocarditis,56
pericarditis, and hypertrophic cardiomyopathy.64 It can also
be related to cocaine use.
Patients with aortic stenosis may complain of angina-like
pain on exertion. The frequency of chest pain is higher with
aortic stenosis than with any other valvular heart disease
and is found in two thirds of patients with severe disease.56
Whenever a patient presents with progressive angina,
dyspnea, or syncope, aortic stenosis should be considered.
In contrast, patients with mitral stenosis or pulmonic
stenosis infrequently experience chest pain.
Pericarditis
The pain of pericarditis is most commonly pleuritic and
arises from spread of the inflammatory process across the
pericardium to the adjacent parietal pleura. Typically pain

is worse in the recumbent position and while lying on the
left side and is partially or completely relieved by sitting
up, leaning forward, or lying on the right side. Occasionally,
pericardial pain may be confused with anginal pain, but
radiation to the arms is uncommon. Although there are
few nociceptors in the pericardium, there appear to be
nociceptors in the diaphragmatic portion of its parietal
layer, which is innervated by sensory axons that travel in
the phrenic nerves.65 Stimulation of these fibers causes
pain that may be sharp and steady and referred to the
margins (ridge) of the trapezius muscles. Pain in this
location is claimed to be specific for pericarditis because
other diseases seldom cause discomfort in that area56 (see
Figure 31-1).
Pericardial friction rubs, presumably indicating underly-
ing pericarditis, are more common than pericardial pain
during the first few days after acute myocardial infarction
and with worsening uremia.56,66 Other causes of pericardi-
tis, usually associated with pericardial pain, are infections,
often viral but also bacterial,67 and connective tissue dis-
eases (e.g., lupus erythematosus). Pericarditis, usually with
fever, also can develop after open heart surgery (post-
pericardiotomy syndrome) and after myocardial infarction
(Dressler syndrome), both of which are considered to be
autoimmune disorders.68 Often, no diagnosis can be made,
and pericarditis is considered idiopathic.
Cocaine Toxicity
Cocaine toxicity is associated with more visits to the emer-
gency department for adverse reactions than any other
illicit drug, and chief among the presenting complaints
is chest pain.69 Cocaine-associated chest pains typically
begin approximately 60 minutes after injection or inhala-
tion of the substance and last for 120 minutes.70 The pain
is most frequently substernal in location and pressure-like
in character; it may be accompanied by shortness of
breath and diaphoresis. Interestingly, clinical presentation
may not differ among persons who develop myocardial
infarction documented by biochemical markers and those
who do not.
Cocaine-induced chest pain is undoubtedly provoked by
the combined effects of an increase in myocardial oxygen
demand owing to an increase in heart rate and in systolic
and mean arterial pressures and a decrease in myocardial
oxygen supply due to vasoconstriction of the epicardial
coronary arteries.71
Despite the widespread use of cocaine and the frequent
causal association (even among casual users) with chest
pain, patients with chest pain who are seeking medical assis-
tance are seldom queried about recent use of cocaine. Con-
sequently, in the setting of cardiac symptoms, identification
of cocaine exposure is a legitimate goal of cardiovascular
history taking. In addition, this is an important question
to ask because there is consensus that β-adrenergic block-
ing agents, which are indicated in acute coronary artery
syndromes, may aggravate cocaine-induced myocardial
ischemia by leaving the α-adrenergic system unopposed
and potentially aggravating hypertension and coronary
vasoconstriction. Thus, for cocaine-induced chest pain,
nitroglycerin and calcium-channel blocking drugs (e.g.,
verapamil) constitute the treatments of choice. Cessation of
cocaine use is essential for secondary prevention.
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31  •  Chest Pain 521
Disorders of the Aorta
Dissection of the aorta is usually associated with pain that is
nearly always sudden and extremely severe at onset. Pain
may be described, aptly, as “tearing” or “ripping” and often
spreads widely, to the neck, throat, jaw, back, or abdomen,
as the dissection extends from its point of origin.72 Frequent
associated features are drenching sweats, nausea and vom-
iting, and light-headedness. Angina-like chest pain can also
arise secondary to reduced coronary artery blood flow as a
result of syphilitic aortitis or Takayasu vasculitis.
NONCARDIAC CHEST PAIN
The term noncardiac chest pain is used to describe an entity
resembling angina. Noncardiac chest pain in the United
States has an estimated annual incidence as high as
450,000 cases and causes considerable long-term morbid-
ity as well as health care utilization. There are three main
categories of extracardiac disease that cause angina-like
chest pain: (1) musculoskeletal disorders of the chest wall,
which may account for 10% to 20% of cases; (2) a variety
of esophageal disorders, particularly gastroesophageal
reflux, which may cause 30% to 40%; and (3) psychological
factors, which may explain up to 50% of the total.
MUSCULOSKELETAL DISORDERS
Of the musculoskeletal causes of chest pain, the ones most
commonly confused with angina are cervical neck disease,
costochondritis, subacromial bursitis, intercostal muscle
cramps, or congenital malformations such as pectus exca-
vatum or carinatum. The best way to distinguish musculo-
skeletal pain from true angina is by reproduction of the pain
with palpation or manipulation of the affected area. A
history of recent trauma, chest infection, or cough can also
support this diagnosis.
GASTROINTESTINAL DISORDERS
Receptors are present in the esophagus and may cause pain
when activated by mechanical (spasm), chemical (acid
reflux), or thermal (hot liquids) stimuli. Afferent nerves
travel in both vagal and spinal (T3-12) pathways.73 Pain
originating from the esophagus is usually referred to midline
structures, such as the throat, neck, and sternal regions but
may involve the arms as well. Stimulation of the distal end
of the esophagus can cause pain directly over the heart.
Chest pain may arise either from esophageal reflux (the
most common identifiable esophageal cause of chest pain)
or from disorders of esophageal motility, such as diffuse
esophageal spasm, achalasia, hyperactive lower esophageal
sphincter, or nutcracker esophagus (a dysmotility disorder
with high peristaltic pressures).74,75 Esophageal pain may
mimic angina pectoris by its radiation to the neck and arms
as well as relief by nitroglycerin.56 Chest discomfort that
lasts an hour or more, that leaves a residual dull achy dis-
comfort, or that is associated with heartburn, odynophagia,
or dysphagia should suggest pain of esophageal origin.
Clinical history alone, however, cannot reliably distinguish
pain originating from the esophagus from cardiac pain.
522 PART 3  •  Clinical Respiratory Medicine
Lastly, other gastrointestinal disorders, such as cholecys-
titis, peptic ulcer disease, and acute pancreatitis, may
present with pain that is perceived in the lower thorax.65
PSYCHOLOGICAL FACTORS
Many patients experience chest pain for which no cause is
ever found even after careful and thorough evaluation. Psy-
chological factors clearly affect each person’s interpretation
of bodily sensations, and a psychiatric cause should be
excluded in undiagnosed cases of chest pain.
An association between noncardiac chest pain and
anxiety disorders, particularly panic disorder, has been
reported. This is particularly well described in patients
with mitral valve prolapse.76 Patients with demonstrable
heart disease may also have panic attacks. Alternatively,
persons with chest pain may have psychological distress
that is related to the panic syndrome and not the cardiac
condition.
MISCELLANEOUS CAUSES OF CHEST PAIN
Obstructive lesions at the thoracic outlet may compress the
brachial plexus and subclavian artery and can cause pain
in the anterior chest and arms. Thoracic outlet syndrome is
usually caused by compression of the neurovascular bundle
by a cervical rib or a structural abnormality of the 1st rib
or clavicle. Associated neuronal abnormalities have been
described,77 and electrophysiologic studies are useful not
only to assist with the diagnosis but also to define which
patients will respond to surgical decompression.78 Chest
pain may also arise from iatrogenic causes, such as pneumo-
thorax following bronchoscopy or central venous catheter
malposition.79
EVALUATION AND TREATMENT
OF CHEST PAIN
Given the wide variety of causes and seriousness of chest
pain, considerable clinical judgment is required to decide
which patients should be thoroughly evaluated and which
tests should be used in the workup. In many instances,
empirical therapy may need to be initiated even as evalua-
tion proceeds, with subsequent readjustments in treatment
protocols as more information is obtained that clarifies the
clinical picture.
The evaluation of chest pain begins with a complete
medical interview. The history may reveal nuances in the
quality, location, duration, provoking events, and relieving
measures, which serve to focus the subsequent evaluation.
However, with few exceptions, such as evident injury to the
chest wall, a specific diagnosis cannot be made with com-
plete confidence from the clinical history alone. Physical
examination may reveal evidence of pleural, lung paren-
chymal, or airway disease; localized chest wall involvement;
or signs of mitral valve prolapse, aortic valve stenosis, or
other cardiac abnormalities.
For adults who present to the emergency department
with new-onset chest pain, the immediate concern is
to identify and characterize potentially life-threatening
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conditions, such as myocardial infarction, acute pulmo-
nary embolism, or tension pneumothorax, requiring urgent
management. Some diagnostic features are listed in
Table 31-2.
A standard 12-lead electrocardiogram (ECG), appropriate
chest imaging, measurement of oxygen saturation and
arterial blood gas levels, and blood chemistry profiles (e.g.,
troponin, D-dimer) often provide important data. In the
appropriate clinical setting, some patients may require
echocardiography or pulmonary function testing. Many
other noninvasive or invasive tests are available for the
evaluation of pain believed to be of respiratory, cardiac, or
gastrointestinal origin. If the diagnosis remains uncertain,
admission to chest pain observation units that offer a safe
and effective means of care for patients with possible unsta-
ble angina who are considered to be at intermediate risk for
cardiovascular events may be considered.
The most definitive treatment of chest pain, whatever its
origin, is to find its cause and to cure it. The general prin-
ciples of therapy for respiratory, cardiac, musculoskeletal,
esophageal, and panic disorders are available, and the clini-
cian is encouraged to refer to them. Chronic noncardiac
chest pain is more difficult to manage, especially when its
trigger cannot be found. Because of the complexities and
difficulties in dealing with those few patients who have
chronic, severe, and often refractory pain, referral to special
pain centers staffed by a multidisciplinary team of special-
ists is recommended. At times, psychiatric consultation for
specific treatment may be helpful.
CARDIAC ISCHEMIA
Initial evaluation of patients with suspected acute coronary
syndrome including unstable angina or non–ST elevation
myocardial infarction should always include a 12-lead ECG.
Serial ECGs may be considered if the initial ECG is not diag-
nostic or if the patient is thought to have evolving myocar-
dial ischemia or injury. Biomarker assessment for myocardial
injury should include creatine kinase-MB, myoglobin, and
cardiac-specific troponin. Patients who are chest pain–free
and have no ischemic ECG changes or cardiac biomarker
elevation should be considered for risk stratification with a
cardiac functional study including exercise stress electro-
cardiography, stress echocardiography, or myocardial
single-photon emission computed tomography imaging.80-82
The indication for stress echocardiography has recently
been clarified and includes the evaluation of acute chest
pain and other chest pain syndromes, such as anginal
equivalent, with or without heart failure, as well as risk
assessment in symptomatic patients following revascular-
ization procedures.81,82
Acute ECG changes, such as ST segment deviations or
deep T wave inversions, positive cardiac biomarkers or stress
test results, or hemodynamic instability should prompt
admission to an intensive care unit. Hospital admission
may also be considered if the diagnosis remains uncertain
despite initial limited evaluations. Available risk stratifica-
tion models, such as the Thrombolysis in Myocardial Infarc-
tion score, may aid diagnosis and management.83 Aspirin,
preferably non–enteric-coated formulations, should be pro-
vided unless contraindicated or already taken by the patient.
Other medications that may be useful in the management
 31  •  Chest Pain 523

Table 31-2  Differential Diagnosis of Chest Pain

Diagnosis Pain Characteristics ECG CXR Associated Features
Angina pectoris Substernal, Transient, Local ST depression; Normal Relief with NTG
constricting effort-related occasional elevation
MI Substernal, Persistent, severe Local ST elevation Possible vascular Relief with opiates;
crushing or depression congestion or possible hypotension;
cardiomegaly ↑ troponin
Pulmonary Pleuritic Sudden onset with Nonspecific; Normal or opacities ± Risk factor/s for venous
embolism dyspnea occasional RV strain small pleural effusion thrombosis
Pulmonary artery Gradual onset Associated with Tall right precordial Prominent pulmonary Exclude pulmonary
hypertension dyspnea, fatigue, R waves, right axis arteries thromboembolism and
and edema deviation, RV strain interstitial lung disease
Bacterial Pleuritic Onset in minutes Normal Consolidation Fever, productive
pneumonia to hours cough
Pneumothorax Sharp, unilateral Sudden onset with Normal Collapsed lung Asthenic habitus,
dyspnea recurrence
Pericarditis Pleuritic Either side; gradual Generalized ST Possible enlarged Friction rub
onset; pain referred elevation silhouette
to trapezius
Aortic dissection Substernal, Radiation to the Nonspecific; LVH or Widened Prostration, loss of
severe back inferior MI mediastinum pulse, aortic
insufficiency
Esophageal Substernal May mimic angina; Normal or ST-T Normal Relief with NTG or
spasm/reflux burning changes antacids
Costochondritis Dull-achy, ↑ by cough or Normal Normal Localized tenderness
localized deep breath
Herpes zoster Sharp, unilateral Dysesthesia Normal Normal Vesicular rash

LVH, left ventricular hypertrophy; MI, myocardial infarction; NTG, nitroglycerin; RV, right ventricular.

of ischemic heart disease include nitroglycerin (sublingual
or intravenous), β-blockers, angiotensin-converting enzyme
inhibitors, nondihydropyridine calcium channel blockers,
morphine sulfate (for persistent chest discomfort), anti-
platelet agents (clopidogrel, prasugrel, ticagrelor, or glyco-
protein IIb/IIIa inhibitor), and anticoagulant therapy (e.g.,
unfractionated heparin, enoxaparin, or fondaparinux).84
Patients should be placed on strict bed rest, and supplemen-
tal oxygen should be provided, particularly if the patient is
in respiratory distress or if oxygen saturation is less than
90%. Every patient with acute coronary syndrome should
be evaluated for possible revascularization, preferentially
percutaneous coronary intervention.85 Management of
non–ST segment elevation acute coronary syndromes by
early invasive therapy improves long-term survival and
reduces adverse cardiovascular events (late myocardial
infarction and rehospitalization for unstable angina) com-
pared with a more conservative approach.86 Reperfusion
therapy with fibrinolytic agents should be reserved for ST
elevation myocardial infarction patients presenting to
centers without angioplasty capability when anticipated
delay to performing angioplasty is greater than 120 minutes
from first medical contact. Urgent coronary artery bypass
grafting surgery should be considered in acute coronary
syndromes or ST elevation myocardial infarctions when
primary angioplasty has failed or coronary anatomy is
not amenable to percutaneous coronary intervention
and high-risk features are present—including ongoing
symptomatic ischemia, cardiogenic shock, heart failure,
ischemic mitral regurgitation, ventricular septal defect,
ventricular free wall perforation, or life-threatening
arrythmias.87
Evaluation and management of variant or Prinzmetal
angina consists of coronary angiography in patients with
chest pain accompanied by transient ST segment elevation.
Nitrates and calcium channel blockers may be given if no
obstructive coronary artery lesions are evident on coronary
angiography, with percutaneous coronary intervention
reserved for those with significant coronary artery stenosis.
Provocative testing may be considered in cases of diagnostic
uncertainty if no contraindications exist.
For cardiac ischemic chest pain related to the use of
cocaine or methamphetamine, nitroglycerin and calcium
channel blockers may be considered as is immediate coro-
nary angiography (preferred) or fibrinolytic therapy (if cor-
onary angiography is not possible) if electrocardiographic
ST elevation (or new ST segment depression or T wave
changes) persists despite pharmacologic intervention. A
combined α- and β-blocking agent, such as labetalol, may be
helpful in patients with sinus tachycardia related to cocaine
use if a vasodilator (nitroglycerin or calcium channel
blocker) has been administered within the previous hour.
Patients with cardiovascular syndrome X may also benefit
from medical intervention with nitrates, calcium channel
blockers, and/or β-adrenergic blockers. Intracoronary
ultrasonography, coronary angiography, 24-hour ambula-
tory ECG, provocative testing, or coronary flow reserve mea-
surement may be considered to aid with diagnosis.
Risk stratification with exercise ECG (using the Bruce
protocol or Duke treadmill score), exercise perfusion
imaging, or exercise echocardiography should be consid-
ered for patients with symptomatic chronic stable angina
who are able to exercise and have no contraindications
to such testing. For those who are unable to exercise,

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524 PART 3  •  Clinical Respiratory Medicine
pharmacologic stress testing with dipyridamole, adenosine,
dobutamine, or regadenoson nuclear myocardial perfusion
imaging or dobutamine echocardiography is recommended
unless contraindications to such testing exist.88
PULMONARY EMBOLISM (see Chapter 57)
Pulmonary embolism is a life-threatening feature of venous
thromboembolism and most frequently originates from
deep venous thrombosis in the lower extremities.
Patients with acute pulmonary embolism who have ele-
vated levels of troponin are at high risk for short-term mor-
tality and adverse outcome events.89 A recent meta-analysis
of the different diagnostic strategies for suspected pulmo-
nary embolism disclosed the positive likelihood ratios for
high-probability ventilation-perfusion lung scan (18.3),
computed tomography pulmonary angiography (CTPA) (24.1),
and lower extremity venous ultrasonography (16.2).90 The
corresponding negative likelihood ratios were 0.05 for a
normal or near-normal lung scan, 0.04 for a negative result
on CTPA along with a negative result on ultrasonography,
and 0.08 for a D-dimer concentration less than 500 µg/L
by quantitative enzyme-linked immunosorbent assay. Using
these tests, patients with a moderate or high pretest prob-
ability had a posttest probability of greater than 85%, while
patients with a low or moderate pretest probability had a
5% posttest probability. Because of higher negative likeli-
hood ratios, CTPA alone, a low-probability ventilation-
perfusion lung scan, magnetic resonance angiography, a
quantitative latex D-dimer test, and hemagglutination
D-dimers can only exclude pulmonary embolism in those
with a low pretest probability.90
Patients with pulmonary embolism can be treated with
either unfractionated heparin or low-molecular-weight
heparin. Dabigatran, a direct thrombin inhibitor, was
recently shown to be noninferior to warfarin for the treat-
ment of venous thromboembolism and may be adopted
as an acceptable treatment of pulmonary embolism in
the future.91 Anticoagulation is maintained either for 3
to 6 months for events related to a transient risk factor
or for greater than 12 months for recurrent venous
thromboembolism.92
PERICARDIAL DISEASE
Acute pericarditis is often associated with a pericardial
effusion, diffuse concave ST segment elevation, and/or PR
segment depression. Therapy for acute pericarditis involves
identification and management of any underlying cause of
the condition (e.g., infection or malignancy). In constrictive
pericarditis, echocardiography can demonstrate the pres-
ence of pericardial thickening and calcification that limits
diastolic filling of the ventricles and causes a characteristic
biphasic pattern of venous return with a diastolic compo-
nent that is equal to or greater than the systolic component.
In selected patients, pericardectomy is a highly effective
treatment of constrictive pericarditis.93
CARDIAC TAMPONADE
Cardiac (or pericardial) tamponade is the presence of fluid
within the pericardial sac leading to cardiac compression.
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This, in turn, impairs ventricular diastolic filling and gives
rise to the sensation of chest pain, dyspnea, tachycardia,
falling systemic blood pressure, elevated venous pressure
(characteristic loss of the atrial Y descent with maintenance
of both the systolic atrial filling wave and the X descent),
and pulsus paradoxus (an exaggerated inspiratory decrease
in arterial systolic pressure > 10 mm Hg). Cardiac tampon-
ade should be suspected whenever a patient presents with
unexplained hypotension and/or pulsus paradoxus follow-
ing myocardial infarction, chest trauma, percutaneous
coronary intervention, or cardiac surgery. Other risk factors
include anticoagulation therapy, malignancy, or an under-
lying connective tissue disease. A pericardial rub may be
appreciated during physical examination. ECG changes
compatible with acute pericarditis may be present as is an
enlarged cardiac silhouette on chest films. Diagnosis is gen-
erally determined by two-dimensional echocardiography
that demonstrates an inspiratory increase of right ventricu-
lar dimensions and decrease of left ventricular dimensions,
compression of the right atrium, right ventricular diastolic
collapse, and a heart that swings with cardiac contractions.
Left atrial collapse is less common than right atrial collapse
but is very specific for cardiac tamponade. There is com-
monly also an abnormal inspiratory increase of blood flow
velocity through the tricuspid valve accompanied by a
decrease in mitral valve flow velocity as well as dilation of
the inferior vena cava with lack of inspiratory collapse.
Aggressive volume loading and percutaneous or surgical
pericardial fluid drainage leads to immediate relief of chest
discomfort, dyspnea, venous hypertension, and pulsus
paradoxus.93,94
PULMONARY ARTERIAL HYPERTENSION
(see Chapter 58)
Initial evaluation of suspected pulmonary arterial hyper-
tension generally consists of ECG, determination of arterial
blood gas levels, a chest radiograph, pulmonary function
testing, exercise capacity (6-minute walk test), brain natri-
uretic peptide or N-terminal brain natriuretic peptide, and
noninvasive Doppler echocardiography with and without
saline contrast.95 Chronic thromboembolic disease is evalu-
ated with ventilation-perfusion scanning and chest CTPA.
Ultimately, right heart catheterization is required both to
confirm the diagnosis and to assess the severity of the pul-
monary hypertension. Testing for connective tissue disease
or human immunodeficiency virus infection may be consid-
ered in patients with suggestive clinical histories for these
disorders.96 Acute vasoreactivity testing using inhaled nitric
oxide (or other pulmonary vasodilators, including epopros-
tenol, adenosine, or sodium nitroprusside) should be per-
formed for patients with pulmonary arterial hypertension to
guide therapy.96a Polysomnography is indicated for patients
with a clinical history suggestive of obstructive sleep apnea.
Treatment of pulmonary arterial hypertension includes
potent vasodilators such as intravenous prostacyclin and
the prostacyclin analogue treprostinil, inhaled iloprost
or treprostinil, endothelin receptor antagonists (bosentan
and ambrisentan), and cyclic guanosine monophosphate–
specific phosphodiesterase type 5 inhibitors (sildenafil and
tadalafil).96b Calcium channel blocker therapy is reserved for
those patients who demonstrate vasoreactivity at the time

of right heart catheterization. Pulmonary thromboendar-
terectomy may benefit patients with chronic thromboem-
bolic pulmonary hypertension. Lung (preferably bilateral)
transplantation or heart-lung transplantation may be con-
sidered for selected patients with New York Heart Associa-
tion functional class III and IV symptoms.97
THORACIC AORTIC DISSECTION
Rapid diagnosis and management are critical for patients
with thoracic aortic dissection. Invasive aortography for the
diagnosis of thoracic aortic dissection has been replaced by
less invasive imaging techniques, including transesopha-
geal echocardiography, contrast-enhanced chest computed
tomography (CT) scan, and magnetic resonance imaging.
All of these modalities yield clinically reliable data for both
confirming and ruling out this condition. In one review,
pooled sensitivity (98% to 100%) and specificity (95% to
98%) from 16 studies involving 1139 patients were compa-
rable for these three less invasive imaging tools.98 Pooled
positive likelihood ratio was higher for magnetic resonance
imaging than for transesophageal echocardiography or CT.
In this review if the patient had a high-risk pretest probabil-
ity (i.e., 50%), the posttest probability of thoracic aortic
dissection following a positive result for each of these
imaging tests was 93% to 96%; if the patient had a low-risk
pretest probability (i.e., 5%), the posttest probability follow-
ing a negative result from each of the imaging tests dropped
to 0.1% to 0.3%.98
PNEUMOTHORAX (see Chapter 81)
Spontaneous pneumothorax can be either primary or sec-
ondary. Patients with small primary pneumothoraces may
be observed closely for either progression or resolution if
they are clinically stable. Chest catheter or tube insertion is
indicated if the pneumothorax enlarges or if the patient’s
clinical situation deteriorates, as well as in patients with
large primary or secondary pneumothoraces. Patients with
small secondary spontaneous pneumothoraces who are
clinically stable may be either observed or managed with a
chest tube depending on clinical severity and course of the
pneumothorax.99,100
TENSION PNEUMOTHORAX
A tension pneumothorax is a life-threatening condition
that requires urgent management. High intrathoracic pres-
sures develop because of ingress of air into the pleural space
via a one-way valve process, which, in turn, prevents egress
of air; this gives rise to vena caval compression, reduction
in venous return, and diminished cardiac output. Radio-
graphically, a tension pneumothorax presents as a complete
collapse of the ipsilateral lung, depression/flattening of the
ipsilateral hemidiaphragm, and shift of the mediastinum to
the contralateral hemithorax. Therapy consists of emer-
gency percutaneous aspiration or chest tube insertion.100
PANCOAST TUMORS
Pancoast (superior sulcus) tumors require a definitive tissue
diagnosis before initiation of therapy, which may, in selected
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31  •  Chest Pain 525
patients, include resection and/or chemoradiotherapy.
Magnetic resonance imaging, both mediastinal and extra-
thoracic, is frequently performed to rule out involvement of
adjacent neurovascular structures (brachial plexus, verte-
bral column, or subclavian vessels) that will influence surgi-
cal approaches.101
CHEST TRAUMA (see Chapter 76)
Blunt and penetrating chest trauma can give rise to chest
pain related to hemothorax (bleeding into the pleural
space); pneumothorax; rib, sternal, or clavicular fractures;
or injury to the chest wall musculature.
As little as 5  mL of hemothorax can be appreciated
on a decubitus chest radiograph, but a size of approxi-
mately 200  mL is required for it to be readily identified
on an upright chest radiograph, where it will appear as
blunting or, with greater volume of bleeding, a concave
upward sloping of the fluid, in the ipsilateral costophrenic
angle. The presence of an air-fluid level indicates a hemo-
pneumothorax. Chest CT is more sensitive than chest
radiographs in detecting a small hemothorax; in addi-
tion, it may occasionally offer clues to the origin of the
bleeding.
Rib fractures may be associated with injuries to the bra-
chial plexus and subclavian veins (upper rib fractures) or
spleen and liver (lower rib fractures). A flail chest resulting
from at least two fracture sites on at least three consecutive
ribs can create regional chest wall instability and respira-
tory distress. The sternum fractures most commonly at the
body or manubrium, generally following direct trauma to
the anterior chest or from deceleration. Significant poste-
rior displacement of the sternum may be associated with
trauma to the underlying cardiovascular structures. Chest
CT is more sensitive than plain chest radiographs for detect-
ing rib and sternal fractures.100
GASTROESOPHAGEAL REFLUX (see Chapter 93)
Dyspepsia secondary to gastroesophageal reflux can be
managed with proton pump inhibitors, histamine2 receptor
antagonists, or prokinetic agents. An empirical trial with
these medications may be considered if the clinical history
strongly supports the diagnosis of gastroesophageal reflux
and if the patient is not at high risk for a gastrointestinal
malignancy. Risk factors, such as use of nonsteroidal anti-
inflammatory agents, should be investigated. Endoscopy
may be necessary in some patients with unexplained
dyspepsia and persistent symptoms. Recommendations for
eradication therapy for Helicobacter pylori–positive dyspep-
sia have been published.102
PANCREATITIS
Common causes of acute pancreatitis include gallstone
disease (approximately 50% of cases) and alcohol abuse
(20% to 25%). Patients typically complain of abdominal
pain and vomiting, but chest pain may develop as well.
Elevation of lipase has a higher sensitivity and specificity for
pancreatitis than elevation of amylase perhaps because,
compared to amylase, lipase is produced only by the pan-
creas. In addition, the half-life of lipase is longer than that
526 PART 3  •  Clinical Respiratory Medicine
of amylase. Thus measurement of lipase is preferred. Other
helpful laboratory tests include liver chemistry determina-
tions, triglyceride level, and calcium level. When diagnostic
doubt exists, abdominal imaging by contrast-enhanced CT
may be beneficial. In additional to supportive measures,
therapeutic endoscopic retrograde cholangiopancreatogra-
phy may be considered, particularly if the acute pancreati-
tis is severe, due to gallstones, or when cholangitis, jaundice,
or a dilated common bile duct is present. The presence of
cholangitis is an indication for endoscopic sphincterotomy
or duct drainage by stenting. Image-guided fine-needle aspi-
ration is recommended for patients with significant pancre-
atic necrosis, who may require débridement if infection is
present.103,104
Key Points
■ Chest pain is characterized by an unpleasant sensation
that is either localized to the thorax or believed to
originate from structures located there. It may
announce the presence of severe, occasionally life-
threatening disease.
■ Pain arising from visceral organs (e.g., heart or gastro-
intestinal tract) differs in many ways from that arising
from somatic structures, such as the skin. Visceral pain
is difficult to localize, is diffuse in character, and is typi-
cally referred to somatic structures. Visceral pain is
also often associated with greater autonomic and
motor responses than is somatic pain.
■ Visceral and somatic innervations differ in relation to
the density of innervations and spinal pattern of ter-
mination. In general, the number of visceral afferent
fibers is less than the number of somatic afferent
fibers, and the rostrocaudal spread of visceral afferent
fiber terminals in the spinal cord is considerably
greater than the spread of central terminals from
somatic afferent fibers. The low number of visceral
afferents and greater intraspinal spread is responsible
for loss of spatial discrimination, consistent with the
diffuse, difficult-to-localize nature of visceral pain.
■ Pain is both hard to define and difficult to measure.
Two widely used techniques, namely rating scales and
questionnaires, are often used in clinical and epide-
miologic studies of chest pain. Although rating scales
constitute the simplest measurement of pain, the sen-
sation of pain has many more components than just
its intensity; thus, a single-dimensional rating scale
leaves many aspects of the sensation undocumented.
■ Because of the proximity of the various organs and the
vagaries of perception of pain of visceral origin, pain
arising from the various viscera in the thoracic cavity
and from the chest wall is often qualitatively similar
and exhibits overlapping patterns of referral, localiza-
tion, and quality. This leads to difficulty in the differ-
ential diagnosis of chest pain.
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Para uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2016. Elsevier Inc. Todos los derechos reservados.
Complete reference list available at ExpertConsult.
Key Readings
Antman EM, Cohen M, Bernink PJ, et al: The TIMI risk score for unstable
angina/non–ST elevation MI: a method for prognostication and thera-
peutic decision making. JAMA 284(7):835–842, 2000.
Douglas PS, Garcia MJ, Haines DE: ACCF/ASE/AHA/ASNC/HFSA/HRS/
SCAI/SCCM/SCCT/SCMR 2011 appropriate use criteria for echocar-
diography: a report of the American College of Cardiology Foundation
Appropriate Use Criteria Task Force, American Society of Echocardiog-
raphy, American Heart Association, American Society of Nuclear Car-
diology, Heart Failure Society of America, Heart Rhythm Society, Society
for Cardiovascular Angiography and Interventions, Society of Critical
Care Medicine, Society of Cardiovascular Computed Tomography, and
Society for Cardiovascular Magnetic Resonance. J Am Coll Cardiol
57:1126–1166, 2011.
Fihn SD, Gardin JM, Abrams J, et al: ACCF/AHA/ACP/AATS/PCNA/SCAI/
STS Guideline for the diagnosis and management of patients with stable
ischemic heart disease: a report of the American College of Cardiology
Foundation/American Heart Association Task Force on Practice Guide-
lines, and the American College of Physicians, American Association for
Thoracic Surgery, Preventive Cardiovascular Nurses Association,
Society for Cardiovascular Angiography and Interventions, and Society
of Thoracic Surgeons. J Am Coll Cardiol 24:e44–e164, 2012.
Gibbons RJ, Balady GJ, Bricker JT, et al: ACC/AHA 2002 guideline update
for exercise testing: summary article. A report of the American College
of Cardiology/American Heart Association Task Force on Practice
Guidelines (Committee to Update the 1997 Exercise Testing Guidelines).
J Am Coll Cardiol 40:1531–1540, 2002.
Hendel RC, Berman DS, Di Carli MF, et al: CCF/ASNC/ACR/AHA/ASE/
SCCT/SCMR/SNM 2009 appropriate use criteria for cardiac radionu-
clide imaging: a report of the American College of Cardiology Founda-
tion Appropriate Use Criteria Task Force, the American Society of
Nuclear Cardiology, the American College of Radiology, the American
Heart Association, the American Society of Echocardiography, the
Society of Cardiovascular Computed Tomography, the Society for Car-
diovascular Magnetic Resonance, and the Society of Nuclear Medicine.
Endorsed by the American College of Emergency Physicians. J Am Coll
Cardiol 53:2201–2229, 2009.
Hillis LD, Smith PK, Anderson JL, et al: American College of Cardiology
Foundation/American Heart Association Task Force on Practice Guide-
lines, et al: 2011 ACCF/AHA guideline for coronary artery bypass graft
surgery: executive summary: a report of the American College of Car-
diology Foundation/American Heart Association Task Force on Practice
Guidelines. J Thorac Cardiovasc Surg 1:4–34, 2012.
Jneid H, Anderson JL, Wright RS, et al: 2012 ACCF/AHA Focused updated
of the guidelines for the management of patients with unstable angina/
non-ST-elevation myocardial infarction (updating the 2007 guideline
and replacing the 2011 focused update): a report of the American
College of Cardiology Foundation/American Heart Association task
force on practice guidelines. J Am Coll Cardiol 60:645–681, 2012.
Levine GN, Bates ER, Blankenship JC, et al: 2011ACCF/AHA/SCAI 2005
guideline update for percutaneous coronary intervention: a report of
the American College of Cardiology Foundation/American Heart Asso-
ciation Task Force on Practice guidelines and the Society of Cardiovas-
cular Angiography and Interventions. J Am Coll Cardiol 58:e44–e122,
2011.
McLaughlin VV, Archer SL, Badesch DB, et al: ACCF/AHA.ACCF/AHA
2009 expert consensus document on pulmonary hypertension: a report
of the American College of Cardiology Foundation Task Force on Expert
Consensus Documents and the American Heart Association: developed
in collaboration with the American College of Chest Physicians, Ameri-
can Thoracic Society, Inc., and the Pulmonary Hypertension Associa-
tion. Circulation 119:2250–2294, 2009.
Snow V, Qaseem A, Barry P, et al: Management of venous thromboembo-
lism: a clinical practice guideline from the American College of Physi-
cians and the American Academy of Family Physicians. Ann Intern Med
146:204–210, 2007.

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