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.^[23]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 (post−percutaneous 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

Workup

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Media Gallery

Unstable Angina. Pathogenesis of acute coronary syndromes.
Unstable Angina. Thrombolysis in Myocardial Infarction (TIMI) Risk Score correlates with major adverse outcome and effect of therapy with low-molecular-weight heparin. ARD = absolute risk difference; ESSENCE = Efficacy and Safety of Subcutaneous Enoxaparin in Non–Q-wave Coronary Events; No. = number; NNT = number needed to treat.
Unstable Angina. Algorithm for initial invasive strategy. ASA = acetylsalicylic acid (aspirin); GP IIb/IIIa= glycoprotein IIb/IIIa; IV = intravenous; LOE = level of evidence; UA/NSTEMI = unstable angina/non–ST-segment elevation myocardial infarction; UFH = unfractionated heparin. (Adapted from 2007 ACC/AHA UA/NSTEMI Guidelines.)
Unstable Angina. Algorithm for initial conservative strategy. ASA = acetylsalicylic acid (aspirin); EF = ejection fraction; GP IIb/IIIa= glycoprotein IIb/IIIa; IV = intravenous; LOE = level of evidence; LVEF = left ventricular ejection fraction; UA/NSTEMI = unstable angina/non–ST-segment elevation myocardial infarction. (Adapted from 2007 ACC/AHA UA/NSTEMI Guidelines.)
Unstable Angina. Rate and timing of revascularization for patients with unstable angina using invasive versus conservative approach (FRagmin during InStability in Coronary artery disease [FRISC] II).
Unstable Angina. Time course of elevations of serum markers after acute myocardial infarction. CK = creatine kinase; CK-MB = creatine kinase MB fraction; LDH = lactate dehydrogenase.

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Table 1. Patient Characteristics, GUARANTEE Versus CRUSADE Trials

Characteristics	GUARANTEE, 1995-96 ^[12]	CRUSADE, 2001-06 ^[13]
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 (%)	9	–
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.

Table 2. Demographic Characteristics of Patients in International OASIS-2 Registry

Characteristics ^[15]		Australia	Brazil	Canada	Hungary	Poland	United States
General	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
Clinical	NQMI presentation (%)	7	7	14	22	17	16
Clinical	Abnormal ECG (%)	74	91	82	95	97	87
Select treatments	Beta blocker (%)	67	53	73	67	59	57
Select treatments	Calcium blocker (%)	59	51	53	52	43	59
Invasive procedures (index hospitalization)	Cardiac catheterization (%)	24	69	43	20	7	58
	PCI (%)	7	19	16	5	0.4	24
	CABG (%)	4	20	10	7	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.

Table 3. Thirty-Day Clinical Outcome in Patients With Acute Coronary Syndromes in Clinical Trials

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
Pooled		40,167	3.5	8.5	1.5
ESSENCE = Efficacy and Safety of Subcutaneous Enoxaparin in Non–Q-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; PRISM-PLUS = 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.

Table 4. Braunwald Classification of Unstable Angina

Characteristic	Class/Category	Details
Severity	I	Symptoms with exertion
	II	Subacute symptoms at rest (2-30 days prior)
	III	Acute symptoms at rest (within prior 48 hr)
Clinical precipitating factor	A	Secondary
	B	Primary
	C	Postinfarction
Therapy during symptoms	1	No treatment
	2	Usual angina therapy
	3	Maximal therapy

Table 5. Recommendations for Selection of Preferred Management Strategy

Preferred Strategy	Patient Characteristic/Clinical Risk
Immediate Invasive Strategy (< 2 hours)	Refractory angina
	Signs/symptoms of heart failure or new or worsening mitral regurgitation
	Hemodynamic instability or cardiogenic shock
	Recurrent angina/ischemia at rest or with low-level activities despite intensive medical therapy
	Sustained ventricular tachycardia or ventricular fibrillation
Ischemia-Guided Strategy	Low-risk score (eg, TIMI 0 or 1, GRACE < 109)
	Low-risk Tn-negative female
	Patient or physician preference in the absence of high-risk features
Early Invasive Strategy (< 24 hours)	GRACE score >140
	Rise or fall in Tn compatible with myocardial infarction
	New or presumably new ST-segment depression
Delayed Invasive Strategy (24-72 hours)	Diabetes mellitus
	Renal insufficiency (GFR < 60 mL/min/1.73m²)
	Reduced LV systolic function (LVEF < 40%)
	Early postinfarction angina
	PCI within 6 months
	Prior CABG
	GRACE score 109-140; TIMI Score ≥2
ACC/AHA = American College of Cardiology/American Heart Association; CABG = coronary artery bypass grafting; GFR = glomerular filtration rate; GRACE = Global Registry of Acute Coronary Events; LV = left ventricle; LVEF = left ventricular ejection fraction; PCI = percutaneous coronary intervention; TIMI = Thrombolysis in Myocardial Infarction Clinical Trial; Tn = troponin.

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Author

Walter Tan, MD, MS Associate Professor of Medicine, Wake Forest University School of Medicine; Director of Cardiac Cath Labs, Wake Forest Baptist Medical Center

Walter Tan, MD, MS is a member of the following medical societies: American Association for the Advancement of Science, American College of Cardiology, American Heart Association, American Stroke Association, National Stroke Association, Society for Vascular Medicine, Society of Interventional Radiology

Disclosure: Nothing to disclose.

Coauthor(s)

David J Moliterno, MD Professor of Medicine, Jefferson Morris Gill Professor of Cardiology, Chief, Division of Cardiovascular Medicine, University of Kentucky; Vice Chairman of Internal Medicine, Chandler Medical Center; Medical Director, Gill Heart Institute

David J Moliterno, MD is a member of the following medical societies: American College of Cardiology, European Society of Cardiology, Association of Professors of Cardiology, American College of Physicians, American Heart Association, American Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Richard A Lange, MD, MBA President, Texas Tech University Health Sciences Center, Dean, Paul L Foster School of Medicine

Richard A Lange, MD, MBA is a member of the following medical societies: Alpha Omega Alpha, American College of Cardiology, American Heart Association, Association of Subspecialty Professors

Disclosure: Nothing to disclose.

Chief Editor

Eric H Yang, MD Associate Professor of Medicine, Director of Cardiac Catherization Laboratory and Interventional Cardiology, Mayo Clinic ArizonA

Eric H Yang, MD is a member of the following medical societies: Alpha Omega Alpha

Disclosure: Nothing to disclose.

Acknowledgements

Steven James Filby, MD Fellow in Interventional Cardiology, The Cleveland Clinic Foundation

Disclosure: Nothing to disclose.

Justin D Pearlman, MD, ME, PhD, FACC, MA Chief, Division of Cardiology, Director of Cardiology Consultative Service, Director of Cardiology Clinic Service, Director of Cardiology Non-Invasive Laboratory, Director of Cardiology Quality Program KMC, Dartmouth-Hitchcock Medical Center, Dartmouth Medical School

Justin D Pearlman, MD, ME, PhD, FACC, MA is a member of the following medical societies: American College of Cardiology, American College of Physicians, American Federation for Medical Research, International Society for Magnetic Resonance in Medicine, and Radiological Society of North America

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment