Practice Essentials

Unstable angina belongs to the spectrum of clinical presentations referred to collectively as

acute coronary syndromes (ACSs), which range from ST-segment elevation myocardial
infarction (STEMI) to non-STEMI (NSTEMI). Unstable angina is considered to be an ACS in
which there is no detectable release of the enzymes and biomarkers of myocardial necrosis.

Essential update: New AHA-ACC guidelines for managing non-ST-elevation ACS

The 2014 guidelines from the American Heart Association and the American College of
Cardiology on the management of patients with nonST-elevation ACSs contain revisions of
their 2007 guidelines.[1, 2, 3] Updates include the following:

Because unstable angina and NSTEMI are on a pathophysiologic continuum and are
often indistinguishable, they are considered together in the 2014 guidelines
Cardiac troponin assays, not yet available in the United States, may improve the
diagnosis of myocardial necrosis
High-intensity statins should be used in patients with overt cardiovascular disease
Risk stratification tools in these patients include the Thrombolysis in Myocardial
Infarction (TIMI) risk score and the Global Registry of Acute Coronary Events (GRACE) risk
score
After discharge, referral to a cardiac rehabilitation program should be made
Signs and symptoms
Symptoms of unstable angina are similar to those of myocardial infarction (MI) and include the
following:

Chest pain or pressure

Sweating
Dyspnea
Nausea, vomiting
Dizziness or sudden weakness
Fatigue
Pain or pressure in the back, neck, jaw, abdomen, or shoulders or arms
Symptoms that occur at rest; become suddenly more frequent, severe, or prolonged; are
a change from the usual pattern of angina; and do not respond to rest or nitroglycerin[4]
The patients history and diagnostic testing are generally more sensitive and specific for
unstable angina than the physical examination, which may be unremarkable. Evaluate the
patients vital signs and perform a cardiac evaluation, which includes resting 12-lead
electrocardiography (ECG).
Examination in a patient with unstable angina may yield the following findings:

Diaphoresis
Tachycardia or bradycardia
Transient myocardial dysfunction (eg, systolic blood pressure < 100 mm Hg or overt
hypotension, elevated jugular venous pressure, dyskinetic apex, reverse splitting of S2,
presence of S3 or S4, new or worsening apical systolic murmur, or rales or crackles)
Peripheral arterial occlusive disease (eg, carotid bruit, supraclavicular or femoral bruits,
or diminished peripheral pulses or blood pressure)

Any sign of congestive heart failure, including isolated sinus tachycardia, particularly in
physiologically vulnerable populations (eg, very elderly patients), should trigger expeditious
workup, treatment, or consultation with a cardiologist. Such patients can deteriorate rapidly.
See Presentation for more detail.

Diagnosis
The following laboratory studies are recommended within the first 24 hours in the evaluation of a
patient with unstable angina:

Serial cardiac biomarker assays (eg, creatine kinase MB isoenzyme [CK-MB], troponins,
C-reactive protein [CRP], and brain natriuretic peptide [BNP])

Complete blood count (CBC) with hemoglobin level

Serum chemistry panel (including magnesium and potassium)

Lipid panel
Other tests that may be used to assess patients include the following:

Creatinine level
Exercise testing when patients are stable
The following imaging studies may be used to assess patients with suspected unstable angina:

Chest radiography
Echocardiography
Computed tomography angiography
Magnetic resonance angiography
Single-photon emission computed tomography
Magnetic resonance imaging
Myocardial perfusion imaging
See Workup for more detail.

Management
Patients with unstable angina require admission to the hospital for bed rest with continuous
telemetry monitoring. Obtain intravenous (IV) access, and provide supplemental oxygen. The
course of unstable angina is highly variable and potentially life-threatening; therefore, quickly
determine whether the initial treatment approach should use an invasive (surgical management)
or a conservative (medical management) strategy.
The following medications are used in the management of unstable angina:

Antiplatelet agents (eg, aspirin and clopidogrel)

Lipid-lowering statin agents (eg, simvastatin, atorvastatin, pitavastatin, and pravastatin)
Cardiovascular antiplatelet agents (eg, tirofiban, eptifibatide, and abciximab)
Beta blockers (eg, atenolol, metoprolol, esmolol, nadolol, and propranolol)
Anticoagulants (eg, heparin)
Low-molecular-weight heparins (eg, enoxaparin, dalteparin, and tinzaparin)
Thrombin inhibitors (eg, bivalirudin, lepirudin, desirudin, and argatroban)
Angina nitrates (eg, nitroglycerin IV)
Angiotensin-converting enzyme inhibitors (eg, captopril, lisinopril, enalapril, and ramipril)
Surgical intervention in unstable angina may include the following:

Cardiac catheterization
Revascularization

Pathophysiology
Factors involved in the pathophysiology of unstable angina include the following:

Supply-demand mismatch
Plaque disruption or rupture
Thrombosis
Vasoconstriction
Cyclical flow

Supply-demand mismatch
The myocardial ischemia of unstable angina, like all tissue ischemia, results from excessive demand or
inadequate supply of oxygen, glucose, and free fatty acids.
Increased myocardial oxygen demand may be caused by the following:

Fever
Tachyarrhythmias (eg, atrial fibrillation or flutter)
Malignant hypertension
Thyrotoxicosis
Pheochromocytoma
Cocaine use
Amphetamine use
Aortic stenosis
Supravalvular aortic stenosis
Obstructive cardiomyopathy
Aortovenous shunts
High-output states
Congestive heart failure (CHF)
Decreased oxygen supply may be caused by the following:

Anemia
Hypoxemia
Polycythemia
Hypotension
The above causes must be investigated because a number of them are reversible. For example, anemia
from chronic gastrointestinal (GI) bleeding is not uncommon in elderly patients. This can coexist
with coronary artery disease (CAD). However, patients may not benefit from or may be harmed by
treatments such as anticoagulants and antiplatelet drugs. Avoidance or treatment of the underlying
condition is paramount.
Excess demand from increased myocardial workload (the product of heart rate and systolic blood
pressure) or wall stress is responsible for nearly all cases of stable angina and perhaps one third of all
episodes of unstable angina.

Plaque disruption
Accumulation of lipid-laden macrophages and smooth muscle cells, so-called foam cells, occurs within
atherosclerotic plaques. The oxidized low-density lipoprotein cholesterol (LDL-C) in foam cells is
cytotoxic, procoagulant, and chemotactic. As the atherosclerotic plaque grows, production of macrophage

proteases and neutrophil elastases within the plaque can cause thinning of the fibromuscular cap that
covers the lipid core.
Increasing plaque instability, coupled with blood-flow shear and circumferential wall stress, leads to
plaque fissuring or rupture (see the image below), especially at the junction of the cap and the vessel
wall. (See Vulnerable Plaque Pathology.)

Pathogenesis of acute coronary syndromes.

The degree and consequences of plaque disruption cover a wide spectrum. Minor fissuring is typically
nonocclusive and hence clinically silent, and repeat occult episodes of plaque ulceration and healing with
a gradual growth of plaque volume have been histologically documented. Moderate-to-large plaque
disruptions commonly result in unstable angina or acute infarction.
As many as 50% of MIs are due to lesions that are angiographically considered functionally insignificant.
[5]
Angiographically mild lesions can still be dangerous because they have an unstable thin-cap
fibroatheroma (TCFA). This means that focal treatments such as percutaneous coronary
intervention (PCI) are incomplete and that medical therapy to protect the entire vascular tree is
complementary and crucial, particularly in patients with a history of ACS.

Vasoconstriction and thrombosis

Most patients with ACS have recurrent transient reduction in coronary blood supply because of
vasoconstriction and thrombus formation at the site of atherosclerotic plaque rupture. These events occur
as consequences of episodic platelet aggregation and complex interactions among the vascular wall,
leukocytes, platelets, and atherogenic lipoproteins.
Exposure of subendothelial components provokes platelet adhesion and activation. Platelets then
aggregate in response to exposed vessel wall collagen or local aggregates (eg, thromboxane and
adenosine diphosphate). Platelets also release substances that promote vasoconstriction and production
of thrombin. In a reciprocating fashion, thrombin is a potent agonist for further platelet activation, and it
stabilizes thrombi by converting fibrinogen to fibrin.
ACS may involve a clot in flux (ie, forming and enlarging, chipping off and embolizing). Over time, this
dynamic clot formation or lysis, in conjunction with coronary vasoreactivity and resistance in the
microvascular bed, causes intermittent and alternating (or cyclical) occlusion and flow.
The nonocclusive thrombus of unstable angina can become transiently or persistently occlusive.
Depending on the duration of the occlusion, the presence of collateral vessels, and the area of
myocardium perfused, recurrent unstable angina, non-Q-wave MI (NQMI), or Q-wave MI can result.
[#IntroductionEpidemiology] Genetics
Although the etiology of cardiovascular disease is strongly linked to modifiable environmental factors, it is
known that genetics also play a significant part in the development of CAD and unstable angina. Much of
the literature regarding the genetics of cardiovascular disease concerns MI and the development of CAD;
however, there is a growing body of literature concerning unstable angina itself.

A number of genetic contributions are known to play a part in unstable angina. Genome-wide association
studies (GWAS) have found linkage with unstable angina at chromosome 2q36-q37.3, chromosome
3q26-q27, and chromosome 20q11-13.[6]A polymorphism in glycoprotein Ia was associated with an
increased time before platelet aggregation occurs in heterozygotes for the polymorphism in a Chinese
population[7] ; it was postulated that the difference in platelet aggregation affected the pathogenesis of
unstable angina.
Polymorphisms in several matrix metalloproteinase (MMP) genes have also been described. A guanine
insertion in MMP1 is associated with smaller and more stable plaques, whereas the presence of more
than 22 CA microsatellite repeats in MMP9 is associated with a worse prognosis for unstable angina. [8, 9]
Polymorphisms of interleukin (IL)-1 receptor antagonist (IL-1Ra) are suspected of having a role in the
development of unstable angina. Studies conducted to date suggest that persons with allele-2 of IL-2Ra
have increased inflammation, as measured by C-reactive protein (CRP) levels. There was an increased
frequency of younger presentation in one study,[10] but a clear association between this polymorphism and
an increased risk for unstable angina has not been found.
Apolipoprotein E (ApoE) polymorphisms also may play a pathogenetic role. In a study assessing the
relation of ApoE4 to serum IL-10 levels, IL-10 levels were found to be lower in patients with at least 1
copy of ApoE4.[11] Higher IL-10 levels are believed to be cardioprotective, further suggesting that ApoE4 is
associated with increased risk for unstable angina.[11] Ultimately, the genetics of unstable angina appear to
be most closely linked with markers of inflammation and mediated by their effects on the risk of plaque
rupture.[12]

Epidemiology
In the United States, the incidence of unstable angina is increasing, and each year, nearly 1
million hospitalized patients have a primary diagnosis of unstable angina. A similar number of
unstable angina episodes likely occur outside the hospital and either go unrecognized or are
managed in the outpatient setting. However, even with heightened public awareness, improved
survival after MI, and an aging population, the incidence of unstable angina should continue to
rise despite primary and secondary prevention measures.

United States demographics

Reasonably representative statistical estimates for unstable angina can be obtained from 2
registries, the GUARANTEE (Global Unstable Angina Registry and Treatment Evaluation)
registry[13] and the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress
ADverse outcomes with Early implementation) registry of the American College of Cardiology
(ACC) and the American Heart Association (AHA).[14, 15] (See Table 1 below.)
Table 1. Patient Characteristics, GUARANTEE Versus CRUSADE Trials (Open Table in a new
window)
Characteristics

GUARANTEE, 1995-96[13]

CRUSADE, 2001-06[14]

Mean age (y)

62

69

Patients >65 y (%)

44

Female (%)

39

40

Hypertension (%)

60

73

Diabetes mellitus (%)

26

33

Current smoker (%)

25

Hypercholesterolemia (%)

43

50

Previous stroke (%)

Previous MI (%)

36

30

Previous angina (%)

66

CHF (%)

14

18

Previous coronary intervention (%)

23

21

Previous coronary bypass surgery (%)

25

19

CHF = congestive heart failure; CRUSADE = Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early
implementation of the American College of Cardiology/American Heart Association guidelines; GUARANTEE = Global Unstable Angina Registry and
Treatment Evaluation; MI = myocardial infarction.

GUARANTEE involved 3000 consecutive hospital admissions for unstable angina in 35 US

hospitals in 6 geographic regions (Northeast, Mideast, Midwest, Southeast, Southwest,
Northwest) from September 1995 to August 1996.
CRUSADE registered more than 180,000 US patients with NSTEMI from 2001 to 2006,
targeting high-risk patients with unstable angina or NSTEMI according to the following inclusion
criteria, either separately or in combination[14, 15] :

Chest pain or anginal equivalent at rest, more than 10 minutes in duration

Ischemic electrocardiographic (ECG) changes (ST-segment depression >0.5 mm,
transient ST-segment elevation 0.5-1.0 mm lasting for < 10 minutes); or

Elevated markers of myocardial necrosis (CK-MB or troponin I or T exceeding the upper

limit of normal for the local laboratory assay used at each institution)
International demographics
The best international demographic data available are from the OASIS-2 (Organization to
Assess Strategies for Ischemic Syndromes) registry (see Table 2 below).[16]
Table 2. Demographic Characteristics of Patients in International OASIS-2 Registry(Open Table
in a new window)
Characteristics[16]

General

Clinical

Select treatments

Australia

Brazil

Canada

Hungary

Poland

United States

Number of patients

1899

1478

1626

931

1135

918

Mean age (y)

65

62

66

65

63

66

Women (%)

37

42

37

45

40

37

NQMI presentation (%)

14

22

17

16

Abnormal ECG (%)

74

91

82

95

97

87

Beta blocker (%)

67

53

73

67

59

57

Calcium blocker (%)

59

51

53

52

43

59

Invasive procedures (index hospitalization)

Cardiac catheterization (%)

24

69

43

20

58

PCI (%)

19

16

0.4

24

CABG (%)

20

10

0.4

17

CABG = coronary artery bypass grafting; ECG = electrocardiographic; NQMI = non-Q wave myocardial infarction; OASIS = Organization to Assess Strategies for Ischemic Syndromes; PCI = percutaneous coronary intervention.

Because unstable angina is intimately linked to the incidence of coronary events, an

approximation of international trends might be found in the MONICA (Monitoring Trends and
Determinants in Cardiovascular Diseases) registry sponsored by the World Health Organization
(WHO).[17] This large project monitored more than 7 million people aged 35-64 years from 30
populations in 21 countries from the mid-1980s.
In the study, the highest average rates of heart disease were found in Glasgow and Belfast,
United Kingdom; North Karelia and Kuopio, Finland; Newcastle, Australia; and Warsaw, Poland.
[17]
The lowest average MI rates, and presumably the lowest average unstable angina rates, were
observed in Beijing, China; Toulouse, France; Catalonia, Spain; Vaud-Fribourg, Switzerland; and
Brianza, Italy.
The GRACE (Global Registry of Acute Coronary Events) registry (http://www.outcomesumassmed.org/grace/) is prospectively tracking contemporary ACS treatment and outcome
across 30 countries and has accumulated more than 100,000 patients.[18]

Age-related demographics
The mean age of presentation with unstable angina is 62 years (range, 23-100 years). To put
this in perspective, the mean age is 60 years for patients in clinical trials for MI, about 67 years
for carotid artery stenosis, and 63 years for congestive heart failure. On average, women with
unstable angina are 5 years older than men on presentation, with approximately half of women
older than 65 years, as opposed to only about one third of men. Black individuals tend to
present at a slightly younger age than people of other races do.

Sex-related demographics
Women with unstable angina are older and have a higher prevalence of hypertension, diabetes
mellitus, CHF, and family history of CAD than men. Men tend to have a higher previous
incidence of MI and revascularization, a higher proportion of positive cardiac enzymes on
admission, and higher rates of catheterization and revascularization. However, outcome is
related more to the severity of the illness than to sex.

Race-related demographics
Disparities in outcome and risk-factor prevalence among different ethnic groups have been
widely reported. For instance, as a group, black persons exhibit a higher prevalence of
atherosclerotic risk factors (eg, hypertension, diabetes mellitus, and smoking), greater left
ventricular mass, and decreased peripheral vasodilatory response. Relative to white persons,
MI more frequently results in death in black individuals at young ages.
Fewer myocardial events but more cerebral complications have also been observed in black
patients with unstable angina in randomized clinical trials of heparin versus hirudin (the Global
Utilization of Streptokinase and TPA [tissue plasminogen activator] for Occluded coronary

arteries II [GUSTO II] trial) or eptifibatide versus placebo (the Platelet glycoprotein IIb/IIIa in
Unstable angina: Receptor Suppression Using Integrilin Therapy [PURSUIT] trial), possibly
because of enhanced fibrinolytic activity and a higher prevalence of hypertension.
Racial differences also exist with regard to the delivery and response to medical care. White
individuals have a higher rate of catheterization, angioplasty, and bypass surgery than
individuals from other racial groups do.
Studies have shown equivalent short-term (30-day) mortality figures from unstable angina
(including NQMI) for black individuals, but over the long term, persistent worse outcomes have
been demonstrated.

Prognosis
The risk of MI, complications, and death in unstable angina varies because of the broad clinical
spectrum that is covered by the term unstable angina. The aggressiveness of the therapeutic
approach should be commensurate with the individualized estimated risk.
Patients who present with new ST-segment deviation (1 mm) have a 1-year death or MI rate of
11%, compared with a rate of only 6.8% in patients with isolated T-wave inversion.[19]
The current standard for cross-comparing studies is the 30-day event rate. The aggregate data
for the more than 40,000 patients with ACSs (excluding STEMI), as derived from studies using
contemporary treatments (albeit in varying degrees), indicate improving outcomes (see Table 3
below). The 30-day MI and death rates are currently around 8.5% and 3.5%, respectively,
despite increased disease complexity and an aging cohort.
Table 3. Thirty-Day Clinical Outcome in Patients With Acute Coronary Syndromes in Clinical
Trials (Open Table in a new window)
Study

Year

Number of Patients

Death (%)

Myocardial Infarction (%)

Major Bleed (%)

TIMI-3

1994

1,473

2.5

9.0

0.3

GUSTO-IIb

1997

8,011

3.8

6.0

1.0

ESSENCE

1998

3,171

3.3

4.5

1.1

PARAGON-A

1998

2,282

3.2

10.3

4.0

PRISM

1998

3,232

3.0

4.2

0.4

PRISM-PLUS

1998

1,915

4.4

8.1

1.1

PURSUIT

1998

10,948

3.6

12.9

2.1

TIMI-11B

1999

3,910

3.9

6.0

1.3

PARAGON-B

2000

5,225

3.1

9.3

1.1

40,167

3.5

8.5

1.5

Pooled

ESSENCE = Efficacy and Safety of Subcutaneous Enoxaparin in NonQ-wave Coronary Events; GUSTO-IIb = Global Utilization of Streptokinase and
TPA (tissue plasminogen activator) for Occluded Coronary Arteries; PARAGON-A = Platelet IIb/IIIa Antagonism (lamifiban) for the Reduction of Acute

Coronary Syndrome Events in a Global Organization Network; PARAGON-B = Platelet IIb/IIIa Antagonism (lamifiban) for the Reduction of Acute
Coronary Syndrome Events in a Global Organization Network; PRISM = Platelet Receptor Inhibition in Ischemic Syndrome Management; PRISMPLUS = Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Angina Signs and Symptoms; PURSUIT =
Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy; TIMI-11B = Thrombolysis in Myocardial Infarction
Clinical Trial 11B; TIMI-3 = Thrombolysis in Myocardial Infarction Clinical Trial 3.

The RESCATE (Recursos Empleados en el Sindrome Coronario Agudo y Tiempos de Espera)

investigators from Spain reported a 1.8% death rate and a 5.1% MI rate at 28 days (consecutive
series, 1992-1994; early revascularization rate, ~6%) in 791 patients with unstable angina.
[20]
Compared with the rates in the North American studies listed earlier (see Epidemiology),
these seem lower, probably because of the healthier case-mix; this illustrates the difficulties of
direct outcome comparisons between institutions, countries, and trials.
A contemporary large clinical trial with centrally adjudicated outcomes showed that an ACS
portends more adverse events in the year to come.[21] The following are the 12-month event
rates for the ACS patients (final diagnosis of unstable angina, 16.6%; NSTEMI, 42.9%; STEMI,
37.5%), whose median age was 62 years, 25% of whom were diabetic, and fewer than 1% of
whom were classified as above Killip class 2[21] :

Death from vascular causes - 4.3%

Death from nonvascular causes - 0.6%
MI - 5.9%
Stroke - 1.2%
These findings present an opportunity for secondary prevention of such adverse events.

Prognostic indicators
Of note, studies have shown that the following are significant prognosticators for poor outcome
in patients with unstable angina:

Ongoing CHF
Presence or history of poor left ventricular ejection fraction (LVEF)
Hemodynamic instability
Recurrent angina despite intensive anti-ischemic therapy
New or worsening mitral regurgitation
Sustained ventricular tachycardia
Although these factors were not evaluated in the Thrombolysis in Myocardial Infarction (TIMI)
Risk Score model (see Physical Examination), they should be taken into consideration when the
level of care is decided.
Other predictors of worse long-term outcome in unstable angina include underlying left
ventricular systolic dysfunction and more widespread extent of CAD.
The level of troponin positivity correlates with intermediate-term death in a dose-dependent
fashion (range, 1.0-7.5% at 6 weeks) independent of age, creatine kinase MB isoenzyme (CKMB) levels, and ST-segment deviation.

Presentation
Patients with unstable angina represent a heterogeneous population. Therefore, the
clinician must obtain a focused history of the patients symptoms and coronary risk

factors and immediately review the electrocardiogram (ECG) to develop an early risk
stratification. (See Prognosis.)
Initially, obtain a history to determine whether any evidence of angina is present, then
aim to identify whether it is stable or unstable.
Unstable angina differs from stable angina in that the discomfort is usually more intense
and easily provoked, and ST-segment depression or elevation on ECG may occur.
Otherwise, the manifestations of unstable angina are similar to those of other conditions
of myocardial ischemia, such as chronic stable angina and myocardial infarction (MI).
Angina can take many forms, and inquiry should be directed at eliciting not only chest
pain but also any associated discomfort and its frequency, location, radiation pattern,
and precipitating and alleviating factors.
Ischemic pain can manifest as heaviness, tightness, aching, fullness, or burning of the
chest, epigastrium, or arm or forearm (usually the left). These sensations less typically
involve the lower jaw, neck, or shoulder. Important associated symptoms may be
dyspnea, generalized fatigue, diaphoresis, nausea and vomiting, flulike symptoms, and,
less commonly, lightheadedness or abdominal pain. The intensity of pain on a 1-10 scale
does not correlate with diagnosis or prognosis.
Elderly and female patients are more likely to present with atypical signs and symptoms.

Diagnostic Considerations
Observation and serial or further testing should be considered for patients who have coronary
risk factors or a suspicious history. In one study, the unintentional failure to recognize or
hospitalize patients with myocardial infarction or unstable angina occurred in an average of 2.2
per 100 patients presenting to the emergency department with a chest pain syndrome.[22] The
rates were 0-10% across different academic centers.
Be aware that unstable angina can infrequently coexist or concurrently present with the
following:

Aortic dissection with involvement of the right coronary artery ostium

Infective endocarditis with embolus into a coronary artery
Periprocedural (postpercutaneous coronary intervention) reocclusion or coronary stent
thrombosis

Congestive heart failure

Also consider cocaine-induced coronary spasm, which can be indistinguishable from acute
coronary syndromes. (Nitroglycerin and calcium-channel antagonists are the drugs of choice;

beta blockers may exacerbate cocaine-induced coronary vasoconstriction.) In patients with

persistent ST elevation, coronary angiography should be performed. If this cannot be carried out
immediately, consider empiric fibrinolytic therapy.
Variant (Prinzmetal) angina is characterized by transient ST-segment elevation and can involve
multiple coronary arterial territories. Patients typically respond to nitroglycerin and high-dose,
and sometimes even dual, calcium channel blockers.
The differential diagnoses for unstable angina fall into the following categories:

Cardiac (eg, acute myocarditis and right ventricular strain due to severe pulmonary
hypertension)
Vascular (eg, microvascular disease [syndrome X])
Pulmonary (eg, pneumonia, pneumothorax, pulmonary hypertension, and
tracheobronchitis)
Gastrointestinal (eg, Mallory-Weiss tear, pancreatitis, and peptic ulcer disease)
Musculoskeletal (eg, arthritis of the shoulder or spine, cervical disk disease, interscalene
or hyperabduction syndromes, subacromial bursitis, and intercostal muscle cramps)
Other (eg, mediastinitis, disorders of the breast, and tumors of the chest wall)

Differential Diagnoses

Anxiety Disorders
Aortic Dissection
Aortic Stenosis
Biliary Disease
Costochondritis
Esophageal Reflux
Esophageal Spasm
Herpes zoster
Hypertrophic obstructive cardiomyopathy
Pericarditis
Pulmonary Embolism
Pulmonary hypertension