Unstable Angina Differential Diagnoses

  • Author: Walter A Tan, MD, MS; Chief Editor: Eric H Yang, MD   more...
 
Updated: Dec 7, 2011
 
 

Diagnostic Considerations

Patients in whom the diagnosis of myocardial infarction or unstable angina has been missed and those who are sent home from the emergency department have, respectively, a 2- and 1.7-fold increased risk of death compared with those who were admitted to the hospital. This a public health issue, and up to 20% of the millions of dollars awarded in malpractice suits against emergency department practitioners is for missed acute coronary syndrome.

As shown in one study, 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, with rates of 0-10% across different academic centers. Even more disturbing, the presence of a well-established chest pain unit was not related to lower rates of missed diagnosis.

Although eliminating missed diagnoses of acute ischemic syndromes is impossible without undue hospitalization rates and costs, this problem could be minimized by the following means:

  • Addressing factors or preconceptions that obscure correct diagnosis in women and nonwhite patients, subgroups that are at higher risk for missed diagnosis
  • Recognition of angina equivalents, particularly in elderly patients
  • More careful history taking to account for recent changes in the character or course of anginal symptoms
  • Use of confirmatory point-of-care cardiac enzyme assays that have a high negative predictive value in patients with nonspecific or normal electrocardiographic findings
  • Predischarge stress testing in stable patients at low risk who have a moderate likelihood of coronary artery disease
  • Awareness that absence of ECG or early cardiac enzyme elevation does not automatically preclude the possibility of acute ischemia, because these are merely snapshots in time of a dynamic process

Observation and serial or further testing should be considered for patients who have coronary risk factors or a suspicious history.

Be aware that unstable angina or acute myocardial infarction 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-PCI) reocclusion or coronary stent thrombosis
  • Congestive heart failure in association with positive cardiac enzymes

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–blocker therapy.

The differential diagnoses for unstable angina fall into the following categories:

  • Cardiac
  • Vascular
  • Pulmonary
  • Gastrointestinal
  • Musculoskeletal
  • Other

Differential Diagnoses

Proceed to Workup
 
 
Contributor Information and Disclosures
Author

Walter A Tan, MD, MS  Associate Professor of Medicine, Clinical Associate Professor of Surgery, Director of Stroke Interventions, Associate Director of Cardiac Catheterization, Department of Cardiovascular Sciences, Brody School of Medicine, East Carolina University

Walter A 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 and Biology, and Society of Interventional Radiology

Disclosure: Gilead Honoraria Other

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, American College of Physicians, American Heart Association, American Medical Association, Association of Professors of Cardiology, and European Society of Cardiology

Disclosure: Nothing to disclose.

George A Stouffer III, MD  Henry A Foscue Distinguished Professor of Medicine and Cardiology, Director of Interventional Cardiology, Cardiac Catheterization Laboratory, Chief of Clinical Cardiology, Division of Cardiology, University of North Carolina Medical Center

George A Stouffer III, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Cardiology, American College of Physicians, American Heart Association, Phi Beta Kappa, and Society for Cardiac Angiography and Interventions

Disclosure: Nothing to disclose.

Josh W Todd, MD  Fellow in Interventional Cardiology, University of North Carolina at Chapel Hill

Josh W Todd, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Cardiology, American College of Physicians, and American Heart Association

Disclosure: Nothing to disclose.

Specialty Editor Board

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

Karlheinz Peter, MD, PhD  Professor of Medicine, Monash University; Head of Centre of Thrombosis and Myocardial Infarction, Head of Division of Atherothrombosis and Vascular Biology, Associate Director, Baker Heart Research Institute; Interventional Cardiologist, The Alfred Hospital, Australia

Karlheinz Peter, MD, PhD is a member of the following medical societies: American Heart Association, Cardiac Society of Australia and New Zealand, and German Cardiac Society

Disclosure: Nothing to disclose.

Chief Editor

Eric H Yang, MD  Associate Professor of Medicine, Director of Interventional Cardiology Fellowship Program, Henry Ford Hospital

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

Disclosure: Nothing to disclose.

Additional Contributors

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors Steven James Filby, MD, Robert Vincent Kelly, MD, Jeb Burchenal, MD, James Maddux, MD, and Jorge Davalos, MD, to the development and writing of the source articles.

References

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Pathogenesis of acute coronary syndromes.
Thrombolysis in Myocardial Infarction (TIMI) Risk Score correlates with major adverse outcome and the effect of therapy with low molecular weight heparin.
Algorithm for Initial Invasive Strategy (Adapted from 2007 ACC/AHA UA/NSTEMI Guidelines).
Algorithm for Initial Conservative Strategy (Adapted from 2007 ACC/AHA UA/NSTEMI Guidelines).
Rate and timing of revascularization for patients with unstable angina using an invasive versus a conservative approach (Fragmin during instability in coronary artery disease [FRISC II]).
Time course of elevations of serum markers after acute myocardial infarction.
Table 1. Patient Characteristics, GUARANTEE Versus CRUSADE
GUARANTEE, 1995-96CRUSADE, 2001-06
Mean age62 years69 years
Patients older than 65 years44%
Female39%40%
Hypertension60%73%
Diabetes mellitus26%33%
Current smoker25%
Hypercholesterolemia43%50%
Previous stroke9%
Previous myocardial infarction36%30%
Previous angina66%
Congestive heart failure14%18%
Previous coronary intervention23%21%
Previous coronary bypass surgery25%19%
Table 2. Demographic Characteristics of Patients in the International OASIS-2 Registry
CharacteristicsAustraliaBrazilCanadaHungaryPolandUnited States
GeneralNumber of patients1899147816269311135918
Mean age (y)656266656366
Women (%)374237454037
ClinicalNQMI presentation (%)7714221716
Abnormal electrocardiogram (ECG)( %)749182959787
Select treatmentsBeta-blocker (%)675373675957
Calcium blocker (%)595153524359
Invasive procedures (index hospitalization)Cardiac catheterization (%)24694320758
Percutaneous coronary intervention (PCI) (%)7191650.424
Coronary artery bypass graft (CABG) (%)4201070.417
Table 3. Thirty-Day Clinical Outcome in Patients With Acute Coronary Syndromes in Clinical Trials
StudyYearNumber of PatientsDeath (%)Myocardial infarction (%)Major Bleed (%)
TIMI-3*19941,4732.59.00.3
GUSTO-IIb † 19978,0113.86.01.0
ESSENCE ‡ 19983,1713.34.51.1
PARAGON-A § 19982,2823.210.34.0
PRISM || 19983,2323.04.20.4
PRISM-PLUS ¶ 19981,9154.48.11.1
PURSUIT#199810,9483.612.92.1
TIMI-11B**19993,9103.96.01.3
PARAGON-B †† 20005,2253.19.31.1
Pooled40,1673.58.51.5
* TIMI-3: Thrombolysis in Myocardial Infarction Clinical Trial 3



† GUSTO-IIb: Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries.



‡ ESSENCE: Efficacy and Safety of Subcutaneous Enoxaparin in Non–Q-wave Coronary Events.



§ PARAGON-A: 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.



†† PARAGON-B: Platelet IIb/IIIa Antagonism (lamifiban) for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network



Table 4. Braunwald Classification of Unstable Angina
CharacteristicClass/CategoryDetails
SeverityISymptoms with exertion
IISubacute symptoms at rest (2-30 d prior)
IIIAcute symptoms at rest (within prior 48 h)
Clinical precipitating factorASecondary
BPrimary
CPostinfarction
Therapy during symptoms1No treatment
2Usual angina therapy
3Maximal therapy
Table 5. AHA/ACC Recommendations for a Preferred Invasive Strategy
Preferred StrategyPatient Characteristics
InvasiveRecurrent angina/ischemia at rest or with low-level activities despite intensive medical therapy
Elevated cardiac biomarkers (TnT or TnI)
New or presumably new ST-segment depression
Signs or symptoms of heart failure or new or worsening mitral regurgitation
High-risk findings on noninvasive stress testing
High-risk score (eg, TIMI, GRACE)
Reduced LV systolic function (LVEF less than 40%)
Hemodynamic instability
Sustained ventricular tachycardia
PCI within 6 months
Previous CABG
ConservativeLow-risk score (eg, TIMI, GRACE)
Patient or physician preference in the absence of high-risk features
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