99Pain: Pathophysiology and Management CHAPTER 13

typically lasting just hours after the cessation of the infusion. The

oral lidocaine congener mexiletine is poorly tolerated, producing

frequent gastrointestinal adverse effects. There is no consensus on

which class of drug should be used as a first-line treatment for any

chronically painful condition. However, because relatively high

doses of anticonvulsants are required for pain relief, sedation is not

uncommon. Sedation is also a problem with TCAs but is much less

of a problem with serotonin/norepinephrine reuptake inhibitors

(SNRIs; e.g., venlafaxine and duloxetine). Thus, in the elderly or

in patients whose daily activities require high-level mental activity,

these drugs should be considered the first line. In contrast, opioid

medications should be used as a second- or third-line drug class.

Although highly effective for many painful conditions, opioids are

sedating, and their effect tends to lessen over time, leading to dose

escalation and, occasionally, a worsening of pain. A couple of interesting alternatives to pure opioids are two drugs with mixed opioid

and norepinephrine reuptake action: tramadol and tapentadol.

Tramadol is a relatively weak opioid but is sometimes effective for

pain unresponsive to nonopioid analgesics. Tapentadol is a stronger

opioid, but its analgesic action is apparently enhanced by the norepinephrine reuptake blockade. Similarly, drugs of different classes

can be used in combination to optimize pain control. Repeated

injection of botulinum toxin is an emerging approach that is showing some promise in treating focal neuropathic pain, particularly

post-herpetic, trigeminal, and post-traumatic neuralgias.

It is worth emphasizing that many patients, especially those with

chronic pain, seek medical attention primarily because they are

suffering and because only physicians can provide the medications

required for pain relief. A primary responsibility of all physicians

is to minimize the physical and emotional discomfort of their

patients. Familiarity with pain mechanisms and analgesic medications is an important step toward accomplishing this aim.

■ FURTHER READING

De Vita MJ et al: Association of cannabinoid administration with

experimental pain in healthy adults a systematic review and

meta-analysis. JAMA Psychiatry 75:1118, 2018.

Dowell D et al: CDC guideline for prescribing opioids for chronic

pain—United States, 2016. JAMA 315:1624, 2016.

Finnerup NB et al: Pharmacotherapy for neuropathic pain in adults:

A systematic review and meta-analysis. Lancet Neurol 14:162, 2015.

Sun EC et al: Incidence of and risk factors for chronic opioid use

among opioid-naive patients in the postoperative period. JAMA

Intern Med 176:1286, 2016.

U.S. Department of Health and Human Services: Pain management best practices inter-agency task force report: Updates, gaps,

inconsistencies, and recommendations. May 2019. https://www.hhs.

gov/ash/advisory-committees/pain/reports/index.html.

TABLE 13-3 Guidelines for Selecting and Monitoring Patients

Receiving Chronic Opioid Therapy (COT) for the Treatment of

Chronic, Noncancer Pain

Patient Selection

• Conduct a history, physical examination, and appropriate testing, including an

assessment of risk of substance abuse, misuse, or addiction.

• Consider a trial of COT if pain is moderate or severe, pain is having an adverse

impact on function or quality of life, and potential therapeutic benefits

outweigh potential harms.

• A benefit-to-harm evaluation, including a history, physical examination, and

appropriate diagnostic testing, should be performed and documented before

and on an ongoing basis during COT.

Informed Consent and Use of Management Plans

• Informed consent should be obtained. A continuing discussion with the

patient regarding COT should include goals, expectations, potential risks, and

alternatives to COT.

• Consider using a written COT management plan to document patient and

clinician responsibilities and expectations and assist in patient education.

Initiation and Titration

• Initial treatment with opioids should be considered as a therapeutic trial to

determine whether COT is appropriate.

• Opioid selection, initial dosing, and titration should be individualized according

to the patient’s health status, previous exposure to opioids, attainment of

therapeutic goals, and predicted or observed harms.

Monitoring

• Reassess patients on COT periodically and as warranted by changing

circumstances. Monitoring should include documentation of pain intensity and

level of functioning, assessments of progress toward achieving therapeutic

goals, presence of adverse events, and adherence to prescribed therapies.

• In patients on COT who are at high risk or who have engaged in aberrant drugrelated behaviors, clinicians should periodically obtain urine drug screens or

other information to confirm adherence to the COT plan of care.

• In patients on COT not at high risk and not known to have engaged in aberrant

drug-related behaviors, clinicians should consider periodically obtaining urine

drug screens or other information to confirm adherence to the COT plan of

care.

Source: Adapted with permission from R Chou et al: Clinical guidelines for the use

of chronic opioid therapy in chronic noncancer pain. J Pain 10:113, 2009.

TABLE 13-4 Centers for Disease Control and Prevention Checklist for

Prescribing Opioids for Chronic Pain

For Primary Care Providers Treating Adults (18+) with Chronic Pain

≥3 months, Excluding Cancer, Palliative, and End-of-Life Care

CHECKLIST

WHEN CONSIDERING LONG-TERM OPIOID THERAPY

• Set realistic goals for pain and function based on diagnosis (e.g., walk around

the block).

• Check that nonopioid therapies tried and optimized.

• Discuss benefits and risks (e.g., addiction, overdose) with patient.

• Evaluate risk of harm or misuse.

• Discuss risk factors with patient.

• Check prescription drug monitoring program (PDMP) data.

• Check urine drug screen.

• Set criteria for stopping or continuing opioids.

• Assess baseline pain and function (e.g., Pain, Enjoyment, General Activity

[PEG] scale).

• Schedule initial reassessment within 1–4 weeks.

• Prescribe short-acting opioids using lowest dosage on product labeling;

match duration to scheduled reassessment.

IF RENEWING WITHOUT A PATIENT VISIT

• Check that return visit is scheduled ≤3 months from last visit.

WHEN REASSESSING AT A PATIENT VISIT

• Continue opioids only after confirming clinically meaningful improvements in

pain and function without significant risks or harm.

• Assess pain and function (e.g., PEG); compare results to baseline.

• Evaluate risk of harm or misuse:

• Observe patient for signs of oversedation or overdose risk. If yes: Taper

dose.

• Check PDMP.

• Check for opioid use disorder if indicated (e.g., difficulty controlling use). If

yes: Refer for treatment.

• Check that nonopioid therapies optimized. Determine whether to continue,

adjust, taper, or stop opioids.

• Calculate opioid dosage morphine milligram equivalent (MME).

• If ≥50 MME/day total (≥50 mg hydrocodone; ≥33 mg oxycodone), increase

frequency of follow-up; consider offering naloxone.

• Avoid ≥90 MME/day total (≥90 mg hydrocodone; ≥60 mg oxycodone), or

carefully justify; consider specialist referral.

• Schedule reassessment at regular intervals (≤3 months).

Source: Centers for Disease Control and Prevention, available at: https://stacks.cdc.

gov/view/cdc/38025. Accessed May 25, 2017 (Public Domain).

100 PART 2 Cardinal Manifestations and Presentation of Diseases

Chest discomfort is among the most common reasons for which

patients present for medical attention at either an emergency department (ED) or an outpatient clinic. The evaluation of nontraumatic

chest discomfort is inherently challenging owing to the broad variety

of possible causes, a minority of which are life-threatening conditions

that should not be missed. It is helpful to frame the initial diagnostic

assessment and triage of patients with acute chest discomfort around

three categories: (1) myocardial ischemia; (2) other cardiopulmonary

causes (myopericardial disease, aortic emergencies, and pulmonary

conditions); and (3) noncardiopulmonary causes. Although rapid

identification of high-risk conditions is a priority of the initial assessment, strategies that incorporate routine liberal use of testing carry the

potential for adverse effects of unnecessary investigations.

EPIDEMIOLOGY AND NATURAL HISTORY

Chest discomfort is one of the three most common reason for visits to

the ED in the United States, resulting in 6 to 7 million emergency visits

each year. More than 60% of patients with this presentation are hospitalized for further testing, and most of the remainder undergo additional investigation in the ED. Fewer than 15% of evaluated patients are

eventually diagnosed with acute coronary syndrome (ACS), with rates

of 10–20% in most series of unselected populations, and a rate as low as

5% in some studies. The most common diagnoses are gastrointestinal

causes (Fig. 14-1), and as few as 5% are other life-threatening cardiopulmonary conditions. In a large proportion of patients with transient

acute chest discomfort, ACS or another acute cardiopulmonary cause is

excluded but the cause is not determined. Therefore, the resources and

time devoted to the evaluation of chest discomfort in the absence of a

severe cause are substantial. Nevertheless, historically, a disconcerting

2–6% of patients with chest discomfort of presumed nonischemic etiology who are discharged from the ED were later deemed to have had a

missed myocardial infarction (MI). Patients with a missed diagnosis of

MI have a 30-day risk of death that is double that of their counterparts

who are hospitalized.

The natural histories of ACS, myocarditis, acute pericardial diseases, pulmonary embolism, and aortic emergencies are discussed in

Chaps. 270, 273, 274, 275, 279, and 280, respectively. In a study of more

than 350,000 patients with unspecified presumed noncardiopulmonary

chest discomfort, the mortality rate 1 year after discharge was <2% and

did not differ significantly from age-adjusted mortality in the general

14 Chest Discomfort

David A. Morrow

population. The estimated rate of major cardiovascular events through

30 days in patients with acute chest pain who had been stratified as low

risk was 2.5% in a large population-based study that excluded patients

with ST-segment elevation or definite noncardiac chest pain.

CAUSES OF CHEST DISCOMFORT

The major etiologies of chest discomfort are discussed in this section

and summarized in Table 14-1. Additional elements of the history,

physical examination, and diagnostic testing that aid in distinguishing these causes are discussed in a later section (see “Approach to the

Patient”).

■ MYOCARDIAL ISCHEMIA/INJURY

Myocardial ischemia causing chest discomfort, termed angina pectoris, is a primary clinical concern in patients presenting with chest

symptoms. Myocardial ischemia is precipitated by an imbalance

between myocardial oxygen requirements and myocardial oxygen

supply, resulting in insufficient delivery of oxygen to meet the heart’s

metabolic demands. Myocardial oxygen consumption may be elevated

by increases in heart rate, ventricular wall stress, and myocardial contractility, whereas myocardial oxygen supply is determined by coronary

blood flow and coronary arterial oxygen content. When myocardial

ischemia is sufficiently severe and prolonged in duration (as little as

20 min), irreversible cellular injury occurs, resulting in MI.

Ischemic heart disease is most commonly caused by atheromatous

plaque that obstructs one or more of the epicardial coronary arteries.

Stable ischemic heart disease (Chap. 273) usually results from the

gradual atherosclerotic narrowing of the coronary arteries. Stable

angina is characterized by ischemic episodes that are typically precipitated by a superimposed increase in oxygen demand during physical

exertion and relieved upon resting. Ischemic heart disease becomes

unstable, manifest by ischemia at rest or with an escalating pattern,

most commonly when rupture or erosion of one or more atherosclerotic lesions triggers coronary thrombosis. Unstable ischemic heart

disease is further classified clinically by the presence or absence of

detectable acute myocardial injury and the presence or absence of

ST-segment elevation on the patient’s electrocardiogram (ECG). When

acute coronary atherothrombosis occurs, the intracoronary thrombus

may be partially obstructive, generally leading to myocardial ischemia

in the absence of ST-segment elevation. Unstable ischemic heart disease is classified as unstable angina when there is no detectable acute

myocardial injury and as non–ST elevation MI (NSTEMI) when there is

evidence of acute myocardial necrosis (Chap. 274). When the coronary

thrombus is acutely and completely occlusive, transmural myocardial

ischemia usually ensues, with ST-segment elevation on the ECG and

myocardial necrosis leading to a diagnosis of ST elevation MI (STEMI;

see Chap. 275).

Gastrointestinal 42%

Ischemic heart disease 31%

Chest wall syndrome 28%

Pericarditis 4%

Pleuritis 2%

Pulmonary embolism 2%

Lung cancer 1.5%

Aortic aneurysm 1%

Aortic stenosis 1%

Herpes zoster 1%

FIGURE 14-1 Distribution of final discharge diagnoses in patients with nontraumatic acute chest pain. (Figure prepared from data in P Fruergaard et al: Eur Heart J 17:1028,

1996.)

101Chest Discomfort CHAPTER 14

TABLE 14-1 Typical Clinical Features of Major Causes of Acute Chest Discomfort

SYSTEM CONDITION ONSET/DURATION QUALITY LOCATION ASSOCIATED FEATURES

Cardiopulmonary

Cardiac Myocardial ischemia Stable angina:

Precipitated by exertion,

cold, or stress; 2–10 min

Unstable angina:

Increasing pattern or

at rest

Myocardial infarction:

Usually >30 min

Pressure, tightness,

squeezing, heaviness,

burning

Retrosternal; often

radiation to neck, jaw,

shoulders, or arms;

sometimes epigastric

S4

 gallop or mitral regurgitation

murmur (rare) during pain; S3

or rales if severe ischemia or

complication of myocardial

infarction

Pericarditis Variable; hours to days;

may be episodic

Pleuritic, sharp Retrosternal or toward

cardiac apex; may radiate

to left shoulder

May be relieved by sitting up

and leaning forward; pericardial

friction rub

Vascular Acute aortic syndrome Sudden onset of

unrelenting pain

Tearing or ripping;

knifelike

Anterior chest, often

radiating to back,

between shoulder blades

Associated with hypertension

and/or underlying connective

tissue disorder; murmur of aortic

insufficiency; loss of peripheral

pulses

Pulmonary embolism Sudden onset Pleuritic; may manifest as

heaviness with massive

pulmonary embolism

Often lateral, on the side

of the embolism

Dyspnea, tachypnea, tachycardia,

and hypotension

Pulmonary hypertension Variable; often exertional Pressure Substernal Dyspnea, signs of increased

venous pressure

Pulmonary Pneumonia or pleuritis Variable Pleuritic Unilateral, often localized Dyspnea, cough, fever, rales,

occasional rub

Spontaneous

pneumothorax

Sudden onset Pleuritic Lateral to side of

pneumothorax

Dyspnea, decreased breath

sounds on side of pneumothorax

Noncardiopulmonary

Gastrointestinal Esophageal reflux 10–60 min Burning Substernal, epigastric Worsened by postprandial

recumbency; relieved by antacids

Esophageal spasm 2–30 min Pressure, tightness,

burning

Retrosternal Can closely mimic angina

Peptic ulcer Prolonged; 60–90 min

after meals

Burning Epigastric, substernal Relieved with food or antacids

Gallbladder disease Prolonged Aching or colicky Epigastric, right upper

quadrant; sometimes to

the back

May follow meal

Neuromuscular Costochondritis Variable Aching Sternal Sometimes swollen, tender, warm

over joint; may be reproduced

by localized pressure on

examination

Cervical disk disease Variable; may be sudden Aching; may include

numbness

Arms and shoulders May be exacerbated by

movement of neck

Trauma or strain Usually constant Aching Localized to area of strain Reproduced by movement or

palpation

Herpes zoster Usually prolonged Sharp or burning Dermatomal distribution Vesicular rash in area of

discomfort

Psychological Emotional and psychiatric

conditions

Variable; may be fleeting

or prolonged

Variable; often manifests

as tightness and dyspnea

with feeling of panic or

doom

Variable; may be

retrosternal

Situational factors may

precipitate symptoms; history of

panic attacks, depression

Clinicians should be aware that unstable ischemic symptoms may

also occur predominantly because of increased myocardial oxygen

demand (e.g., during intense psychological stress or fever) or because

of decreased oxygen delivery due to anemia, hypoxia, or hypotension.

However, the term acute coronary syndrome, which encompasses unstable angina, NSTEMI, and STEMI, is in general reserved for ischemia

precipitated by acute coronary atherothrombosis. In order to guide therapeutic strategies, a standardized system for classification of MI has been

expanded to discriminate MI resulting from acute coronary thrombosis

(type 1 MI) from MI occurring secondary to other imbalances of myocardial oxygen supply and demand (type 2 MI; see Chap. 274). These

conditions are additionally distinguished from nonischemic causes of

acute myocardial injury, such as myocarditis.

Other contributors to stable and unstable ischemic heart disease,

such as endothelial dysfunction, microvascular disease, and vasospasm, may exist alone or in combination with coronary atherosclerosis and may be the dominant cause of myocardial ischemia in some

patients. Moreover, nonatherosclerotic processes, including congenital

abnormalities of the coronary vessels, myocardial bridging, coronary

arteritis, and radiation-induced coronary disease, can lead to coronary

obstruction. In addition, conditions associated with extreme myocardial oxygen demand and impaired endocardial blood flow, such

as aortic valve disease (Chap. 280), hypertrophic cardiomyopathy, or

idiopathic dilated cardiomyopathy (Chap. 259), can precipitate myocardial ischemia in patients with or without underlying obstructive

atherosclerosis.

102 PART 2 Cardinal Manifestations and Presentation of Diseases

Characteristics of Ischemic Chest Discomfort The clinical

characteristics of angina pectoris, often referred to simply as “angina,”

are highly similar whether the ischemic discomfort is a manifestation

of stable ischemic heart disease, unstable angina, or MI; the exceptions

are differences in the pattern and duration of symptoms associated

with these syndromes (Table 14-1). Heberden initially described

angina as a sense of “strangling and anxiety.” Chest discomfort characteristic of myocardial ischemia is typically described as aching, heavy,

squeezing, crushing, or constricting. However, in a substantial minority of patients, the quality of discomfort is extremely vague and may be

described as a mild tightness, or merely an uncomfortable feeling, that

sometimes is experienced as numbness or a burning sensation. The

site of the discomfort is usually retrosternal, but radiation is common

and generally occurs down the ulnar surface of the left arm; the right

arm, both arms, neck, jaw, or shoulders may also be involved. These

and other characteristics of ischemic chest discomfort pertinent to

discrimination from other causes of chest pain are discussed later in

this chapter (see “Approach to the Patient”).

Stable angina usually begins gradually and reaches its maximal

intensity over a period of minutes before dissipating within several

minutes with rest or with nitroglycerin. The discomfort typically

occurs predictably at a characteristic level of exertion or psychological stress. By definition, unstable angina is manifest by anginal chest

discomfort that occurs with progressively lower intensity of physical

activity or even at rest. Chest discomfort associated with MI is commonly more severe, is prolonged (usually lasting ≥30 min), and is not

relieved by rest.

Mechanisms of Cardiac Pain The neural pathways involved in

ischemic cardiac pain are poorly understood. Ischemic episodes are

thought to excite local chemosensitive and mechanoreceptive receptors

that, in turn, stimulate release of adenosine, bradykinin, and other substances that activate the sensory ends of sympathetic and vagal afferent

fibers. The afferent fibers traverse the nerves that connect to the upper

five thoracic sympathetic ganglia and upper five distal thoracic roots of

the spinal cord. From there, impulses are transmitted to the thalamus.

Within the spinal cord, cardiac sympathetic afferent impulses may

converge with impulses from somatic thoracic structures, and this

convergence may be the basis for referred cardiac pain. In addition,

cardiac vagal afferent fibers synapse in the nucleus tractus solitarius

of the medulla and then descend to the upper cervical spinothalamic

tract, and this route may contribute to anginal pain experienced in the

neck and jaw.

■ OTHER CARDIOPULMONARY CAUSES

Pericardial and Other Myocardial Diseases (See also Chap. 270)

Inflammation of the pericardium due to infectious or noninfectious

causes can be responsible for acute or chronic chest discomfort. The

visceral surface and most of the parietal surface of the pericardium

are insensitive to pain. Therefore, the pain of pericarditis is thought

to arise principally from associated pleural inflammation. Because

of this pleural association, the discomfort of pericarditis is usually

pleuritic pain that is exacerbated by breathing, coughing, or changes

in position. Moreover, owing to the overlapping sensory supply of the

central diaphragm via the phrenic nerve with somatic sensory fibers

originating in the third to fifth cervical segments, the pain of pleural

and pericardial inflammation is often referred to the shoulder and

neck. Involvement of the pleural surface of the lateral diaphragm can

lead to pain in the upper abdomen.

Acute inflammatory and other nonischemic myocardial diseases

can also produce chest discomfort. The symptoms of acute myocarditis are highly varied. Chest discomfort may either originate with

inflammatory injury of the myocardium or be due to severe increases

in wall stress related to poor ventricular performance. The symptoms

of Takotsubo (stress-related) cardiomyopathy often start abruptly with

chest pain and shortness of breath. This form of cardiomyopathy, in its

most recognizable form, is triggered by an emotionally or physically

stressful event and may mimic acute MI because of its commonly

associated ECG abnormalities, including ST-segment elevation, and

elevated biomarkers of myocardial injury. Observational studies support a predilection for women >50 years of age.

Diseases of the Aorta (See also Chap. 280) Acute aortic dissection (Fig. 14-1) is a less common cause of chest discomfort but is

important because of the catastrophic natural history of certain subsets

of cases when recognized late or left untreated. Acute aortic syndromes

encompass a spectrum of acute aortic diseases related to disruption

of the media of the aortic wall. Aortic dissection involves a tear in the

aortic intima, resulting in separation of the media and creation of a

separate “false” lumen. A penetrating ulcer has been described as ulceration of an aortic atheromatous plaque that extends through the intima

and into the aortic media, with the potential to initiate an intramedial

dissection or rupture into the adventitia. Intramural hematoma is an

aortic wall hematoma with no demonstrable intimal flap, no radiologically apparent intimal tear, and no false lumen. Intramural hematoma

can occur due to either rupture of the vasa vasorum or, less commonly,

a penetrating ulcer.

Each of these subtypes of acute aortic syndrome typically presents

with chest discomfort that is often severe, sudden in onset, and

sometimes described as “tearing” in quality. Acute aortic syndromes

involving the ascending aorta tend to cause pain in the midline of

the anterior chest, whereas descending aortic syndromes most often

present with pain in the back. Therefore, dissections that begin in the

ascending aorta and extend to the descending aorta tend to cause pain

in the front of the chest that extends toward the back, between the

shoulder blades. Proximal aortic dissections that involve the ascending

aorta (type A in the Stanford nomenclature) are at high risk for major

complications that may influence the clinical presentation, including

(1) compromise of the aortic ostia of the coronary arteries, resulting

in MI; (2) disruption of the aortic valve, causing acute aortic insufficiency; and (3) rupture of the hematoma into the pericardial space,

leading to pericardial tamponade.

Knowledge of the epidemiology of acute aortic syndromes can be

helpful in maintaining awareness of this relatively uncommon group

of disorders (estimated annual incidence, 3 cases per 100,000 population). Nontraumatic aortic dissections are very rare in the absence of

hypertension or conditions associated with deterioration of the elastic

or muscular components of the aortic media, including pregnancy,

bicuspid aortic disease, or inherited connective tissue diseases, such as

Marfan and Ehlers-Danlos syndromes.

Although aortic aneurysms are most often asymptomatic, thoracic

aortic aneurysms can cause chest pain and other symptoms by compressing adjacent structures. This pain tends to be steady, deep, and

occasionally severe. Aortitis, whether of noninfectious or infectious

etiology, in the absence of aortic dissection is a rare cause of chest or

back discomfort.

Pulmonary Conditions Pulmonary and pulmonary-vascular

conditions that cause chest discomfort usually do so in conjunction

with dyspnea and often produce symptoms that have a pleuritic nature.

PULMONARY EMBOLISM (SEE ALSO CHAP. 279) Pulmonary emboli

(annual incidence, ~1 per 1000) can produce dyspnea and chest discomfort that is sudden in onset. Typically pleuritic in pattern, the chest

discomfort associated with pulmonary embolism may result from

(1) involvement of the pleural surface of the lung adjacent to a resultant pulmonary infarction; (2) distention of the pulmonary artery; or

(3) possibly, right ventricular wall stress and/or subendocardial ischemia related to acute pulmonary hypertension. The pain associated with

small pulmonary emboli is often lateral and pleuritic and is believed to

be related to the first of these three possible mechanisms. In contrast,

massive pulmonary emboli may cause severe substernal pain that may

mimic an MI and that is plausibly attributed to the second and third

of these potential mechanisms. Massive or submassive pulmonary

embolism may also be associated with syncope, hypotension, and signs

of right heart failure. Other typical characteristics that aid in the recognition of pulmonary embolism are discussed later in this chapter (see

“Approach to the Patient”).

103Chest Discomfort CHAPTER 14

TABLE 14-2 Considerations in the Assessment of the Patient with

Chest Discomfort

1. Could the chest discomfort be due to an acute, potentially

life-threatening condition that warrants urgent evaluation and

management?

Unstable ischemic

heart disease

Aortic dissection Pneumothorax Pulmonary

embolism

2. If not, could the discomfort be due to a chronic condition likely to

lead to serious complications?

Stable angina Aortic stenosis Pulmonary

hypertension

3. If not, could the discomfort be due to an acute condition that warrants

specific treatment?

Pericarditis Pneumonia/

pleuritis

Herpes zoster

4. If not, could the discomfort be due to another treatable chronic

condition?

Esophageal reflux Cervical disk disease

Esophageal spasm Arthritis of the shoulder or spine

Peptic ulcer disease Costochondritis

Gallbladder disease Other musculoskeletal disorders

Other gastrointestinal conditions Anxiety state

Source: Developed by Dr. Thomas H. Lee for the 18th edition of Harrison’s Principles

of Internal Medicine.

PNEUMOTHORAX (SEE ALSO CHAP. 294) Primary spontaneous pneumothorax is a rare cause of chest discomfort, with an estimated annual

incidence in the United States of 7 per 100,000 among men and

<2 per 100,000 among women. Risk factors include male sex, smoking,

family history, and Marfan syndrome. The symptoms are usually sudden in onset, and dyspnea may be mild; thus, presentation to medical

attention is sometimes delayed. Secondary spontaneous pneumothorax

may occur in patients with underlying lung disorders, such as chronic

obstructive pulmonary disease, asthma, or cystic fibrosis, and usually

produces symptoms that are more severe. Tension pneumothorax is a

medical emergency caused by trapped intrathoracic air that precipitates hemodynamic collapse.

Other Pulmonary Parenchymal, Pleural, or Vascular Disease

(See also Chaps. 283, 284, and 294) Most pulmonary diseases

that produce chest pain, including pneumonia and malignancy, do

so because of involvement of the pleura or surrounding structures.

Pleurisy is typically described as a knifelike pain that is worsened by

inspiration or coughing. In contrast, chronic pulmonary hypertension

can manifest as chest pain that may be very similar to angina in its

characteristics, suggesting right ventricular myocardial ischemia in

some cases. Reactive airways diseases similarly can cause chest tightness associated with breathlessness rather than pleurisy.

■ NONCARDIOPULMONARY CAUSES

Gastrointestinal Conditions (See also Chap. 321) Gastrointestinal disorders are the most common cause of nontraumatic chest

discomfort and often produce symptoms that are difficult to discern

from more serious causes of chest pain, including myocardial ischemia.

Esophageal disorders, in particular, may simulate angina in the character and location of the pain. Gastroesophageal reflux and disorders of

esophageal motility are common and should be considered in the differential diagnosis of chest pain (Fig. 14-1 and Table 14-1). The pain of

esophageal spasm is commonly an intense, squeezing discomfort that

is retrosternal in location and, like angina, may be relieved by nitroglycerin or dihydropyridine calcium channel antagonists. Chest pain

can also result from injury to the esophagus, such as a Mallory-Weiss

tear or even an esophageal rupture (Boerhaave’s syndrome) caused by

severe vomiting. Peptic ulcer disease is most commonly epigastric in

location but can radiate into the chest (Table 14-1).

Hepatobiliary disorders, including cholecystitis and biliary colic,

may mimic acute cardiopulmonary diseases. Although the pain arising

from these disorders usually localizes to the right upper quadrant of the

abdomen, it is variable and may be felt in the epigastrium and radiate

to the back and lower chest. This discomfort is sometimes referred

to the scapula or may in rare cases be felt in the shoulder, suggesting

diaphragmatic irritation. The pain is steady, usually lasts several hours,

and subsides spontaneously, without symptoms between attacks. Pain

resulting from pancreatitis is typically aching epigastric pain that radiates to the back.

Musculoskeletal and Other Causes (See also Chap. 360)

Chest discomfort can be produced by any musculoskeletal disorder

involving the chest wall or the nerves of the chest wall, neck, or upper

limbs. Costochondritis causing tenderness of the costochondral junctions (Tietze’s syndrome) is relatively common. Cervical radiculitis may

manifest as a prolonged or constant aching discomfort in the upper

chest and limbs. The pain may be exacerbated by motion of the neck.

Occasionally, chest pain can be caused by compression of the brachial

plexus by the cervical ribs, and tendinitis or bursitis involving the left

shoulder may mimic the radiation of angina. Pain in a dermatomal

distribution can also be caused by cramping of intercostal muscles or

by herpes zoster (Chap. 193).

Emotional and Psychiatric Conditions As many as 10% of

patients who present to EDs with acute chest discomfort have a panic

disorder or related condition (Table 14-1). The symptoms may include

chest tightness or aching that is associated with a sense of anxiety and

difficulty breathing. The symptoms may be prolonged or fleeting.

APPROACH TO THE PATIENT

Chest Discomfort

Given the broad set of potential causes and the heterogeneous

risk of serious complications in patients who present with acute

nontraumatic chest discomfort, the priorities of the initial clinical

encounter include assessment of (1) the patient’s clinical stability

and (2) the probability that the patient has an underlying cause of

the discomfort that may be life-threatening. The high-risk conditions of principal concern are acute cardiopulmonary processes,

including ACS, acute aortic syndrome, pulmonary embolism, tension pneumothorax, and pericarditis with tamponade. Fulminant

myocarditis also carries a poor prognosis but is usually also manifest

by heart failure symptoms. Among noncardiopulmonary causes of

chest pain, esophageal rupture likely holds the greatest urgency for

diagnosis. Patients with these conditions may deteriorate rapidly

despite initially appearing well. The remaining population with noncardiopulmonary conditions has a more favorable prognosis during

completion of the diagnostic workup. A rapid targeted assessment

for a serious cardiopulmonary cause is of particular relevance for

patients with acute ongoing pain who have presented for emergency

evaluation. Among patients presenting in the outpatient setting

with chronic pain or pain that has resolved, a general diagnostic

assessment is reasonably undertaken (see “Outpatient Evaluation of

Chest Discomfort,” below). A series of questions that can be used to

structure the clinical evaluation of patients with chest discomfort is

shown in Table 14-2.

HISTORY

The evaluation of nontraumatic chest discomfort relies heavily on

the clinical history and physical examination to direct subsequent

diagnostic testing. The evaluating clinician should assess the quality, location (including radiation), and pattern (including onset and

duration) of the pain as well as any provoking or alleviating factors.

The presence of associated symptoms may also be useful in establishing a diagnosis.

Quality of Pain The quality of chest discomfort alone is never

sufficient to establish a diagnosis. However, the characteristics of

the pain are pivotal in formulating an initial clinical impression

and assessing the likelihood of a serious cardiopulmonary process

104 PART 2 Cardinal Manifestations and Presentation of Diseases

Radiation to right arm or shoulder

Radiation to both arms or shoulders

Associated with exertion

Radiation to left arm

Associated with diaphoresis

Associated with nausea or vomiting

Worse than previous angina

or similar to previous MI

Described as pressure

Inframammary location

Reproducible with palpation

Described as sharp

Described as positional

Described as pleuritic

Likelihood ratio for AMI

0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5

INCREASED LIKELIHOOD OF AMI

DECREASED LIKELIHOOD OF AMI

FIGURE 14-2 Association of chest pain characteristics with the probability of acute myocardial infarction (AMI). Note that a subsequent larger study showed a

nonsignificant association with radiation to the right arm. (Figure prepared from data in CJ Swap, JT Nagurney: JAMA 294:2623, 2005.)

(Table 14-1), including ACS in particular (Fig. 14-2). Pressure or

tightness is consistent with a typical presentation of myocardial

ischemic pain. Nevertheless, the clinician must remember that some

patients with ischemic chest symptoms deny any “pain” but rather

complain of dyspnea or a vague sense of anxiety. The severity of the

discomfort has poor diagnostic accuracy. It is often helpful to ask

about the similarity of the discomfort to previous definite ischemic

symptoms. It is unusual for angina to be sharp, as in knifelike, stabbing, or pleuritic; however, patients sometimes use the word “sharp”

to convey the intensity of discomfort rather than the quality. Pleuritic

discomfort is suggestive of a process involving the pleura, including

pericarditis, pulmonary embolism, or pulmonary parenchymal

processes. Less frequently, the pain of pericarditis or massive pulmonary embolism is a steady severe pressure or aching that can be

difficult to discriminate from myocardial ischemia. “Tearing” or

“ripping” pain is often described by patients with acute aortic dissection. However, acute aortic emergencies also present commonly

with knifelike pain. A burning quality can suggest acid reflux or

peptic ulcer disease but may also occur with myocardial ischemia.

Esophageal pain, particularly with spasm, can be a severe squeezing

discomfort identical to angina.

Location of Discomfort A substernal location with radiation to

the neck, jaw, shoulder, or arms is typical of myocardial ischemic

discomfort. Radiation to both arms has a particularly high association with MI as the etiology. Some patients present with aching in

sites of radiated pain as their only symptoms of ischemia. However,

pain that is highly localized—e.g., that which can be demarcated by

the tip of one finger—is highly unusual for angina. A retrosternal

location should prompt consideration of esophageal pain; however,

other gastrointestinal conditions usually present with pain that is

most intense in the abdomen or epigastrium, with possible radiation into the chest. Angina may also occur in an epigastric location.

Pain that occurs solely above the mandible or below the epigastrium

is rarely angina. Severe pain radiating to the back, particularly

between the shoulder blades, should prompt consideration of an

acute aortic syndrome. Radiation to the trapezius ridge is characteristic of pericardial pain and does not usually occur with angina.

Pattern Myocardial ischemic discomfort usually builds over minutes and is exacerbated by activity and mitigated by rest. In contrast,

pain that reaches its peak intensity immediately is more suggestive

of aortic dissection, pulmonary embolism, or spontaneous pneumothorax. Pain that is fleeting (lasting only a few seconds) is rarely

ischemic in origin. Similarly, pain that is constant in intensity for

a prolonged period (many hours to days) is unlikely to represent

myocardial ischemia if it occurs in the absence of other clinical consequences, such as abnormalities of the ECG, elevation of cardiac

biomarkers, or clinical sequelae (e.g., heart failure or hypotension).

Both myocardial ischemia and acid reflux may have their onset in

the morning.

Provoking and Alleviating Factors Patients with myocardial

ischemic pain usually prefer to rest, sit, or stop walking. However,

clinicians should be aware of the phenomenon of “warm-up angina”

in which some patients experience relief of angina as they continue

at the same or even a greater level of exertion (Chap. 273). Alterations in the intensity of pain with changes in position or movement

of the upper extremities and neck are less likely with myocardial

ischemia and suggest a musculoskeletal etiology. The pain of pericarditis, however, often is worse in the supine position and relieved

by sitting upright and leaning forward. Gastroesophageal reflux

may be exacerbated by alcohol, some foods, or a reclined position.

Relief can occur with sitting.

Exacerbation by eating suggests a gastrointestinal etiology such

as peptic ulcer disease, cholecystitis, or pancreatitis. Peptic ulcer

disease tends to become symptomatic 60–90 min after meals. However, in the setting of severe coronary atherosclerosis, redistribution

of blood flow to the splanchnic vasculature after eating can trigger

postprandial angina. The discomfort of acid reflux and peptic ulcer

disease is usually diminished promptly by acid-reducing therapies.

In contrast with its impact in some patients with angina, physical

exertion is very unlikely to alter symptoms from gastrointestinal

causes of chest pain. Relief of chest discomfort within minutes

after administration of nitroglycerin is suggestive of but not sufficiently sensitive or specific for a definitive diagnosis of myocardial

ischemia. Esophageal spasm may also be relieved promptly with

105Chest Discomfort CHAPTER 14

nitroglycerin. A delay of >10 min before relief is obtained after

nitroglycerin suggests that the symptoms either are not caused by

ischemia or are caused by severe ischemia, such as during acute MI.

Associated Symptoms Symptoms that accompany myocardial

ischemia may include diaphoresis, dyspnea, nausea, fatigue, faintness, and eructations. In addition, these symptoms may exist in isolation as anginal equivalents (i.e., symptoms of myocardial ischemia

other than typical angina), particularly in women and the elderly.

Dyspnea may occur with multiple conditions considered in the differential diagnosis of chest pain and thus is not discriminative, but

the presence of dyspnea is important because it suggests a cardiopulmonary etiology. Sudden onset of significant respiratory distress

should lead to consideration of pulmonary embolism and spontaneous pneumothorax. Hemoptysis may occur with pulmonary

embolism or as blood-tinged frothy sputum in severe heart failure

but usually points toward a pulmonary parenchymal etiology of

chest symptoms. Presentation with syncope or presyncope should

prompt consideration of hemodynamically significant pulmonary

embolism or aortic dissection as well as ischemic arrhythmias.

Although nausea and vomiting suggest a gastrointestinal disorder,

these symptoms may occur in the setting of MI (more commonly

inferior MI), presumably because of activation of the vagal reflex

or stimulation of left ventricular receptors as part of the BezoldJarisch reflex.

Past Medical History The past medical history is useful in assessing the patient for risk factors for coronary atherosclerosis and

venous thromboembolism (Chap. 279) as well as for conditions

that may predispose the patient to specific disorders. For example,

a history of connective tissue diseases such as Marfan syndrome

should heighten the clinician’s suspicion of an acute aortic syndrome or spontaneous pneumothorax. A careful history may elicit

clues about depression or prior panic attacks.

PHYSICAL EXAMINATION

In addition to providing an initial assessment of the patient’s clinical

stability, the physical examination of patients with chest discomfort

can provide direct evidence of specific etiologies of chest pain

(e.g., unilateral absence of lung sounds) and can identify potential

precipitants of acute cardiopulmonary causes of chest pain (e.g.,

uncontrolled hypertension), relevant comorbid conditions (e.g.,

obstructive pulmonary disease), and complications of the presenting syndrome (e.g., heart failure). However, because the findings

on physical examination may be normal in patients with unstable

ischemic heart disease, an unremarkable physical exam is not definitively reassuring.

General The patient’s general appearance is helpful in establishing an initial impression of the severity of illness. Patients with

acute MI or other acute cardiopulmonary disorders often appear

anxious, uncomfortable, pale, cyanotic, or diaphoretic. Patients

who are massaging or clutching their chests may describe their

pain with a clenched fist held against the sternum (Levine’s sign).

Occasionally, body habitus is helpful—e.g., in patients with Marfan

syndrome or the prototypical young, tall, thin man with spontaneous pneumothorax.

Vital Signs Significant tachycardia and hypotension are indicative

of important hemodynamic consequences of the underlying cause

of chest discomfort and should prompt a rapid survey for the most

severe conditions, such as acute MI with cardiogenic shock, massive pulmonary embolism, pericarditis with tamponade, or tension

pneumothorax. Acute aortic emergencies usually present with

severe hypertension but may be associated with profound hypotension when there is coronary arterial compromise or dissection into

the pericardium. Sinus tachycardia is an important manifestation of

submassive pulmonary embolism. Tachypnea and hypoxemia point

toward a pulmonary cause. The presence of low-grade fever is nonspecific because it may occur with MI and with thromboembolism

in addition to infection.

Pulmonary Examination of the lungs may localize a primary

pulmonary cause of chest discomfort, as in cases of pneumonia,

asthma, or pneumothorax. Left ventricular dysfunction from severe

ischemia/infarction as well as acute valvular complications of MI or

aortic dissection can lead to pulmonary edema, which is an indicator of high risk.

Cardiac The jugular venous pulse is often normal in patients with

acute myocardial ischemia but may reveal characteristic patterns

with pericardial tamponade or acute right ventricular dysfunction

(Chaps. 239 and 270). Cardiac auscultation may reveal a third or,

more commonly, a fourth heart sound, reflecting myocardial systolic or diastolic dysfunction. Murmurs of mitral regurgitation or a

ventricular-septal defect may indicate mechanical complications of

STEMI. A murmur of aortic insufficiency may be a complication of

ascending aortic dissection. Other murmurs may reveal underlying

cardiac disorders contributory to ischemia (e.g., aortic stenosis or

hypertrophic cardiomyopathy). Pericardial friction rubs reflect

pericardial inflammation.

Abdominal Localizing tenderness on the abdominal exam is

useful in identifying a gastrointestinal cause of the presenting

syndrome. Abdominal findings are infrequent with purely acute

cardiopulmonary problems, except in the case of right-sided heart

failure leading to hepatic congestion.

Extremities Vascular pulse deficits may reflect underlying chronic

atherosclerosis, which increases the likelihood of coronary artery disease. However, evidence of acute limb ischemia with loss of the pulse

and pallor, particularly in the upper extremities, can indicate catastrophic consequences of aortic dissection. Unilateral lower-extremity

swelling should raise suspicion about venous thromboembolism.

Musculoskeletal Pain arising from the costochondral and chondrosternal articulations may be associated with localized swelling,

redness, or marked localized tenderness. Pain on palpation of these

joints is usually well localized and is a useful clinical sign, although

deep palpation may elicit pain in the absence of costochondritis.

Although palpation of the chest wall often elicits pain in patients

with various musculoskeletal conditions, it should be appreciated

that chest wall tenderness does not exclude myocardial ischemia.

Sensory deficits in the upper extremities may be indicative of cervical disk disease.

ELECTROCARDIOGRAPHY

Electrocardiography is crucial in the evaluation of nontraumatic

chest discomfort. The ECG is pivotal for identifying patients with

ongoing ischemia as the principal reason for their presentation as

well as secondary cardiac complications of other disorders. Professional society guidelines recommend that an ECG be obtained

within 10 min of presentation, with the primary goal of identifying patients with ST-segment elevation diagnostic of MI who

are candidates for immediate interventions to restore flow in the

occluded coronary artery. ST-segment depression and symmetric

T-wave inversions at least 0.2 mV in depth are useful for detecting

myocardial ischemia in the absence of STEMI and are also indicative of higher risk of death or recurrent ischemia. Serial performance of ECGs (every 30–60 min) is recommended in the ED

evaluation of suspected ACS. In addition, an ECG with right-sided

lead placement should be considered in patients with clinically

suspected ischemia and a nondiagnostic standard 12-lead ECG.

Despite the value of the resting ECG, its sensitivity for ischemia is

poor—as low as 20% in some studies.

Abnormalities of the ST segment and T wave may occur in a

variety of conditions, including pulmonary embolism, ventricular

hypertrophy, acute and chronic pericarditis, myocarditis, electrolyte imbalance, and metabolic disorders. Notably, hyperventilation

associated with panic disorder can also lead to nonspecific ST and

T-wave abnormalities. Pulmonary embolism is most often associated with sinus tachycardia but can also lead to rightward shift of

the ECG axis, manifesting as an S-wave in lead I, with a Q-wave

106 PART 2 Cardinal Manifestations and Presentation of Diseases

Elevated cTn Concentration

Dynamic cTn (significant rise or fall)

Ischemia

Myocardial

infarction

Acute

myocardial

injury

Chronic

myocardial

Type 1 injury

MI

Type 2

MI

No ischemia

Stable cTn

FIGURE 14-3 Clinical classification of patients with elevated cardiac troponin

(cTn). MI, myocardial infarction.

and T-wave in lead III (Chaps. 240 and 279). In patients with

ST-segment elevation, the presence of diffuse lead involvement not

corresponding to a specific coronary anatomic distribution and

PR-segment depression can aid in distinguishing pericarditis from

acute MI.

CHEST RADIOGRAPHY

(See Chap. A12) Plain radiography of the chest is performed

routinely when patients present with acute chest discomfort and

selectively when individuals who are being evaluated as outpatients

have subacute or chronic pain. The chest radiograph is most useful

for identifying pulmonary processes, such as pneumonia or pneumothorax. Findings are often unremarkable in patients with ACS,

but pulmonary edema may be evident. Other specific findings

include widening of the mediastinum in some patients with aortic

dissection, Hampton’s hump or Westermark’s sign in patients with

pulmonary embolism (Chaps. 279 and A12), or pericardial calcification in chronic pericarditis.

CARDIAC BIOMARKERS

Laboratory testing in patients with acute chest pain is focused on

the detection of myocardial injury. Such injury can be detected by

the presence of circulating proteins released from damaged cardiomyocytes. Owing to the time necessary for this release, initial

biomarkers of injury may be in the normal range, even in patients

with STEMI. Cardiac troponin is the preferred biomarker for the

diagnosis of MI and should be measured in all patients with suspected ACS. It is not necessary or advisable to measure troponin

in patients without suspicion of ACS unless this test is being used

specifically for risk stratification (e.g., in pulmonary embolism or

heart failure).

The development of cardiac troponin assays with progressively

greater analytical sensitivity has facilitated detection of substantially

lower blood concentrations of troponin than was previously possible. This evolution permits earlier detection of myocardial injury

and more reliable discrimination of changing values, enhances the

overall accuracy of a diagnosis of MI, and improves risk stratification in suspected ACS. For these reasons, high-sensitivity assays

are generally preferred over prior generation troponin assays. The

greater negative predictive value of a negative troponin result with

high-sensitivity assays is an advantage in the evaluation of chest

pain in the ED. Rapid rule-out protocols that use serial testing

and changes in troponin concentration over as short a period as

1–2 h appear to perform well for diagnosis of ACS when using a

high-sensitivity troponin assay. Troponin should be measured at

presentation and repeated at 1–3 h using high-sensitivity troponin

and 3–6 h using conventional troponin assays. Additional troponin

measurements may be warranted beyond 3–6 h when the clinical

condition still suggests possible ACS or if there is diagnostic uncertainty. In patients presenting more than 2–3 h after symptom onset,

a concentration of cardiac troponin, at the time of hospital presentation, below the limit of detection using a high-sensitivity assay may

be sufficient to exclude MI with a negative predictive value >99%.

With the use of high-sensitivity assays for troponin, myocardial

injury is detected in a larger proportion of patients who have nonACS cardiopulmonary conditions than with previous, less sensitive

assays. Therefore, other aspects of the clinical evaluation are critical to the practitioner’s determination of the probability that the

symptoms represent ACS. In addition, observation of a change in

cardiac troponin concentration between serial samples is necessary

for discriminating acute causes of myocardial injury from chronic

elevation due to underlying structural heart disease, end-stage renal

disease, or the rare presence of interfering antibodies. The diagnosis of MI is reserved for acute myocardial injury that is marked by

a rising and/or falling pattern—with at least one value exceeding

the 99th percentile reference limit—and that is caused by ischemia.

Other nonischemic insults, such as myocarditis, may result in acute

myocardial injury but should not be labeled MI (Fig. 14-3).

Other laboratory assessments may include the D-dimer test to

aid in exclusion of pulmonary embolism (Chap. 279). Measurement of a B-type natriuretic peptide is useful when considered in

conjunction with the clinical history and exam for the diagnosis of

heart failure. B-type natriuretic peptides also provide prognostic

information among patients with ACS and those with pulmonary

embolism.

INTEGRATIVE DECISION-AIDS

Multiple clinical algorithms have been developed to aid in decisionmaking during the evaluation and disposition of patients with acute

nontraumatic chest pain. Such decision-aids estimate either of two

closely related but not identical probabilities: (1) the probability of

a final diagnosis of ACS and (2) the probability of major cardiac

events during short-term follow-up. Such decision-aids are used

most commonly to identify patients with a low clinical probability

of ACS who are candidates for discharge from the ED, with or

without additional noninvasive testing. Goldman and Lee developed one of the first such decision-aids, using only the ECG and

risk indicators—hypotension, pulmonary rales, and known ischemic heart disease—to categorize patients into four risk categories

ranging from a <1% to a >16% probability of a major cardiovascular complication. Decision-aids used more commonly in current

practice are shown in Fig. 14-4. Elements common across multiple

risk stratification tools are (1) symptoms typical for ACS; (2) older

age; (3) risk factors for or known atherosclerosis; (4) ischemic ECG

abnormalities; and (5) elevated cardiac troponin level. Although,

because of very low specificity, the overall diagnostic performance

of such decision-aids is poor (area under the receiver operating

curve, 0.55–0.65), in conjunction with the ECG and serial highsensitivity cardiac troponin, they can help identify patients with

a very low probability of ACS (e.g., <1%) or adverse cardiovascular events (<2% at 30 days). Clinical application of such integrated decision-aids or “accelerated diagnostic protocols” has been

reported to achieve overall “miss rates” for ACS of <0.5% and may

be useful for identifying patients who may be discharged without

the need for additional cardiac testing.

Clinicians should differentiate between the algorithms discussed

above and risk scores derived for stratification of prognosis (e.g., the

TIMI and GRACE risk scores, Chap. 275) in patients who already

have an established diagnosis of ACS. The latter risk scores were not

designed to be used for diagnostic assessment.

CORONARY AND MYOCARDIAL STRESS IMAGING

Among patients for whom other life-threatening causes of chest

pain have been reasonably excluded and serial biomarker and

clinical assessment have determined the patient to remain eligible

for further testing because of intermediate or undetermined risk,

diagnostic coronary imaging with coronary computed tomographic

(CT) angiography or functional testing, preferably with nuclear or

echocardiographic imaging, is recommended. Patient characteristics (e.g., body habitus and renal function), prior cardiac testing,

107Chest Discomfort CHAPTER 14

history of known coronary artery disease, existing contraindications for a given test modality, and patient preferences are considerations when choosing among these diagnostic tests (Chaps. 241

and A9).

CT Angiography (See Chap. 241) CT angiography has emerged as

a preferred modality for the evaluation of patients with acute chest

discomfort who are candidates for further testing after biomarker

and clinical risk assessment. Coronary CT angiography is a sensitive technique for detection of obstructive coronary disease. CT

appears to enhance the speed to disposition of patients with a

low-intermediate probability for ACS, with its major strength being

the negative predictive value of a finding of no significant stenosis

or coronary plaque. In addition, contrast-enhanced CT can detect

focal areas of myocardial injury in the acute setting. At the same

time, CT angiography can exclude aortic dissection, pericardial

effusion, and pulmonary embolism.

Stress Nuclear Perfusion Imaging or Stress Echocardiography

(See Chaps. 241 and A9) Functional testing with stress nuclear

perfusion imaging and stress echocardiography are alternatives for

the evaluation of patients with acute chest pain who are candidates

for further testing and are preferred over coronary CT angiography

in patients with known obstructive epicardial disease. The selection

of stress test modality may depend on institutional availability

and expertise. Stress testing with myocardial imaging, either with

nuclear perfusion imaging or echocardiography, offers superior

diagnostic performance over exercise ECG. In patients selected for

stress myocardial imaging who are able to exercise, exercise stress

is preferred over pharmacologic testing. When available, positron

emission tomography offers advantages of improved diagnostic

performance and fewer nondiagnostic studies than single-photon

emission CT.

Although functional testing is generally contraindicated in

patients with ongoing chest pain, in selected patients with persistent

pain and nondiagnostic ECG and biomarker data, resting myocardial perfusion images can be obtained; the absence of any perfusion

abnormality substantially reduces the likelihood of coronary artery

disease. In such a strategy, used in some centers, those with abnormal

rest perfusion imaging, which cannot discriminate between old or

new myocardial defects, usually must undergo additional evaluation.

EXERCISE ELECTROCARDIOGRAPHY

Exercise electrocardiography has historically been commonly

employed for completion of risk stratification of patients who have

undergone an initial evaluation that has not revealed a specific

cause of chest discomfort and has identified a low risk of ACS.

Early exercise testing is safe in patients without ongoing chest pain

or high-risk findings and may assist in refining their prognostic

assessment. However, for patients with chest pain for whom both

cardiac troponin and clinical risk stratification have determined the

patient to have low probability of ACS, there is insufficient evidence

that stress testing or cardiac imaging improves their outcomes.

This evolution in evidence supports a change from past practice in

which outpatient stress testing within 72 hours was broadly used for

patients with acute chest pain.

OTHER NONINVASIVE STUDIES

Other noninvasive imaging studies of the chest can be used selectively to provide additional diagnostic and prognostic information

on patients with chest discomfort.

HEART Score (without cTn)

History Highly suspicious

Moderately suspicious

Slightly suspicious

2

1

0

ECG Significant ST depression

Nonspecific abnormality

Normal

2

1

0

Age ≥65 y

45–<65 y

<45 y

2

1

0

Risk

factors

≥3 risk factors

1–2 risk factors

None

2

1

0

TOTAL

Low risk: 0–3

Not low risk: ≥4

EDACS Score

Age 86+ y

81–85 y

76–80 y

Step down by 5-y increments

46–50 y

18–45 y

20

18

16

(–2)

4

2

Known

CAD or

risk

factors

Known CAD (prior MI, PCI,

or CABG) or ≥3 cardiac risk

factors in patient aged ≤50 y

4

Sex Male

Female

6

0

Symptoms Radiation to arm, shoulder,

neck, or jaw

Diaphoresis

Pain with inspiration

Reproduced by palpation

5

3

–4

–6

TOTAL

Low risk: 0–15

Not low risk: ≥16

NPV

Captured as

low risk (%)

99.55

51.8

99.49

60.6

AND cardiac troponin < the limit of quantification.*

FIGURE 14-4 Examples of decision-aids used in conjunction with serial measurement of cardiac troponin (cTn) for evaluation of acute chest pain. The HEART score

was modified by the authors in the presented study and omitting the assignment of 0, 1, or 2 points based on troponin. The negative predictive value (NPV) reported

is for the composite endpoint of myocardial infarction (MI), cardiogenic shock, cardiac arrest, and all-cause mortality by 60 days. *Limit of quantification is the lowest

analyte concentration that can be quantitatively detected with a total imprecision of ≤20%. CABG, coronary artery bypass graft; CAD, coronary artery disease; ECG,

electrocardiogram; PCI, percutaneous coronary intervention. (Figure prepared from data in DG Mark et al: J Am Coll Cardiol 13:606, 2018.)