Acute Coronary Syndrome - Ischemic Heart Disease

Acute coronary syndrome (ACS), formerly referred to as ischemic heart disease, refers to a large spectrum of clinical conditions, including unstable angina and myocardial infarction (MI). ACS is caused by a sudden onset of cardiac tissue ischemia secondary to impaired blood flow. The precipitating event is blockage in the coronary arteries or a mismatch between cardiac tissue demand and supply. The resulting tissue ischemia can cause substernal chest pressure; radiation of pain to the left arm, shoulder, or jaw; shortness of breath; sweating; nausea; and changes on an electrocardiogram (ECG). ACS requires immediate diagnosis and care.

  • Diagnosis
  • Screening
  • Background
  • Lab Tests
  • References
  • Related Topics

Indications for Testing

  • Patient presenting with chest pressure or chest discomfort with risk factors for cardiovascular disease
  • Patient experiencing pain in left arm, left jaw, left shoulder, or back
  • Accompanying symptoms of shortness of breath, dizziness, nausea, and/or sweating

Laboratory Testing

  • Cardiac biomarker testing should be initiated at presentation in cases of suspected acute coronary syndrome (ACS)
  • Recommended cardiac biomarkers (European Society of Cardiology, American College of Cardiology Foundation, American Heart Association, National Academy of Clinical Biochemistry, ESC/American College of Cardiology)
  • Troponins (I or T)
    • Preferred marker for the diagnosis of ACS – use in conjunction with electrocardiogram (ECG) and clinical picture
      • Predictive of short-term risk for myocardial injury (MI) or death
    • Diagnosis
      • Measure serial troponin values for risk stratification on arrival and after at least 3 hours of observation
      • First troponin measurement used for risk stratification; measure change to confirm diagnosis
        • ACS diagnosis can be established when change in troponin value is significant in appropriate clinical setting
      • Other diagnostic testing may add value to patient evaluation – BNP, chest x-ray
    • Sensitivity/specificity
      • Sensitive and specific for MI
      • Cardiac-specific troponins have amino acid sequences different from skeletal muscle forms and are therefore highly specific for cardiac injury
      • Troponins can remain elevated for up to 7-10 days after an event
    • Limitations
      • Troponins may also be elevated by causes of cardiac injury other than ACS
  • Creatine kinase MB isoenzyme (CK MB)
    • Acceptable marker only when troponins are unavailable or if autoantibodies to troponins are known to exist
    • Diagnosis
      • Maximal concentration >99th percentile of a reference control group in two successive samples or a maximal value >twice the upper limit of normal during the first 24 hours
        • Loss of specificity after 24 hours
    • Sensitivity/specificity
      • Decreased sensitivity in
        • Organ injury (acute or chronic muscle, intestine, diaphragm, uterus, and prostate damage)
        • Nonspecific elevations
      • Low sensitivity in
        • Early acute myocardial infarction (AMI) – <6 hours
        • Late AMI – >36 hours
        • Minimal damage AMI
  • Myoglobin
    • Not recommended as a standalone test for diagnosis of AMI
    • Sensitivity/specificity
      • Low specificity, high sensitivity in AMI early detection
  • Natriuretic peptides (NP)
    • Atrial (ANP), brain or b-type (BNP), and N-terminal (Nt) metabolic peptides are released by cardiocytes
      • Release stimulated by ventricular wall stress
      • Function as powerful diuretics/natriuretics and as vascular smooth muscle relaxants
    • Elevated in conditions characterized by wall stretch, ventricular dilation, or increased pressure
    • Most frequently used to diagnose heart failure
      • BNP measures may give additional prognostic information about mortality during first cardiovascular events
  • Newer markers (diagnostic significance not proven)
    • Oxidative stress markers – lipoprotein-associated phospholipase A2, myeloperoxidase
    • Tissue necrosis markers – C-reactive protein, interleukin 6, other interleukins, fatty acid binding proteins, free fatty acid unbound to albumin

Imaging Studies

  • Coronary angiogram
    • Useful for evaluation and possible intervention when there is a  high probability of ACS
  • Stress testing (exercise or chemical)
    • Usually deferred until patient stable and ACS ruled out
  • Echocardiogram
    • Evaluate for wall motion abnormalities (suggestive of ischemic injury)
    • Helpful in ruling out differential diagnoses (eg, aortic dissection, pulmonary embolism, pericardial effusion)
  • Coronary CT
  • Cardiac MRI

Other Testing

  • Electrocardiogram (ECG)
    • Typically demonstrates ST elevation, but not typically posterior MI, right ventricular infarction
    • May have false negatives (non-ST elevated MI)

Prognosis

  • Use of TIMI (thrombolysis in myocardial infarction) risk score prognosticates 2-week, all-cause mortality in new or recurrent AMI
    • One point for each of the following
      • Age >65 years
      • History of diabetes mellitus, hypertension, angina
      • Documented coronary stenosis >50%
      • ST elevation on ECG
      • >2 anginal events in preceding 24 hours
      • Acetylsalicylic acid (ASA) treatment in previous 7 days
      • Increased cardiac markers (troponins preferred)
      • Prior AMI, congestive heart failure (CHF), bypass surgery, or percutaneous angioplasty
    • 1 point = 5%; 2 points = 8%; 3 points = 13%; 4 points = 20%; 5 points = 26%; ≥6 points = 41%

Differential Diagnosis

  • Differential diagnosis based on clinical presentation
    • Nonischemic cardiovascular
      • Aortic dissection
      • Myocarditis/pericarditis
      • Hypertrophic cardiomyopathy
      • Cardiac injury/rhabdomyolysis
      • Cardiac arrhythmias
      • Infiltrative cardiac disease
      • Congestive heart failure
      • Coronary vasospasm
      • Takotsubo cardiomyopathy
    • Chest wall/musculoskeletal
      • Cervical disk disease
      • Costochondritis
      • Herpes zoster
      • Neuropathic pain
      • Rib fracture
    • Pulmonary
    • Gastrointestinal
    • Other
      • Sepsis/shock
      • Burns (>30% of body)
    • Psychiatric
      • Depression
      • Panic attack
      • Somatization with psychogenic pain disorder
  • Differential diagnosis based on elevated troponins
    • Heart failure – acute or chronic
    • Kidney disease
    • Pulmonary embolism
    • Pericarditis/myocarditis
    • Cardiac trauma
    • Hypotension or  hypertension
    • Hypoxia
    • Anemia
    • Arrhythmias
    • Systemic inflammatory response syndrome or sepsis
    • Infiltrative cardiomyopathies
    • Cardiac dissection
    • Cardiotoxic chemotherapy
    • Heterophile antibodies
  • Individuals should be screened for coronary artery disease prior to the development of an acute syndrome and placed on appropriate lifestyle and medication management
    • Lipid profile (refer to cardiovascular risk factors, traditional and nontraditional)
    • Blood pressure checks
    • Screening for elevated sugars (number one cause of death for diabetics is cardiac disease) in at-risk individuals
    • Screening for tobacco use
  • ECG, exercise treadmill, and coronary CT
    • May provide prognostic information about future events
    • Testing is indicated only in individuals with high pretest probability
  • Screening of asymptomatic patients is not recommended (U.S. Preventive Services Task Force)

Epidemiology

  • Incidence – >1,500,000 cases of ACS annually in U.S. (AHA, 2008)
  • Age – peak onset is >50 years
  • Sex – M>F

Risk Factors

Pathophysiology

  • Atherosclerosis – disease of large- and medium-sized arteries
  • Clot formation in the coronary arteries – ACS caused by rupture or erosion of plaques
  • Rupture of plaques leads to inadequate circulation with ischemia, resulting in myocardial cell death

Clinical Presentation

  • ACS
    • Substernal chest pain, dyspnea, gastric discomfort, diaphoresis, tachycardia, or hypotension
      • Atypical pain site presentations are not uncommon – arm, back, jaw, neck
    • May auscultate S3 or S4, new murmur, pericardial friction rub, or bibasilar rales
    • May be difficult to distinguish the chest pain of acute myocardial infarction (AMI) or unstable angina from other conditions such as gastroesophageal reflux disease (GERD)
  • Coronary artery disease (CAD)
    • May be asymptomatic
    • May present with symptoms similar to ACS or AMI
Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Troponin I 0090613
Method: Chemiluminescent Immunoassay

Limitations 

False-positive results may occur in acute pulmonary embolism, acute and chronic heart failure, sepsis, stroke, renal failure

Troponin T 0098803
Method: Quantitative Electrochemiluminescent Immunoassay

Limitations 

False-positive results may occur in acute pulmonary embolism, acute and chronic heart failure, sepsis, stroke, renal failure

Lower early sensitivity than troponin I for myocardial necrosis

Creatine Kinase, MB 0080480
Method: Chemiluminescent Immunoassay

Guidelines

2012 Writing Committee Members, Jneid H, Anderson JL, Wright S, Adams CD, Bridges CR, Casey DE, Ettinger SM, Fesmire FM, Ganiats TG, Lincoff M, Peterson ED, Philippides GJ, Theroux P, Wenger NK, Zidar JP, Anderson JL, American College of Cardiology Foundation, American Heart Association Task Force on Practice Guidelines. 2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/Non-ST-elevation myocardial infarction (updating the 2007 guideline and replacing the 2011 focused update) A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2012; 126(7): 875-910. PubMed

Diagnosis and treatment of chest pain and acute coronary syndrome (ACS). Institute for Clinical Systems Improvement - Nonprofit Organization. 2004 November (Revised 2012 November). NGC: 009521

General References

Anaya P, Moliterno DJ. The evolving role of cardiac troponin in the evaluation of cardiac disorders. Curr Cardiol Rep. 2013; 15(11): 420. PubMed

Baker JO, Reinhold J, Redwood S, Marber MS. Troponins: redefining their limits. Heart. 2011; 97(6): 447-52. PubMed

Christenson E, Christenson RH. Characteristics of cardiac troponin measurements. Coron Artery Dis. 2013; 24(8): 698-704. PubMed

Christenson RH, Phillips D. Sensitive and high sensitivity next generation cardiac troponin assays: more than just a name. Pathology. 2011; 43(3): 213-9. PubMed

Keller T, Zeller T, Peetz D, Tzikas S, Roth A, Czyz E, Bickel C, Baldus S, Warnholtz A, Fröhlich M, Sinning CR, Eleftheriadis MS, Wild PS, Schnabel RB, Lubos E, Jachmann N, Genth-Zotz S, Post F, Nicaud V, Tiret L, Lackner KJ, Münzel TF, Blankenberg S. Sensitive troponin I assay in early diagnosis of acute myocardial infarction. N Engl J Med. 2009; 361(9): 868-77. PubMed

Kumar A, Cannon CP. Acute coronary syndromes: diagnosis and management, part I. Mayo Clin Proc. 2009; 84(10): 917-38. PubMed

Lee-Lewandrowski E, Januzzi JL, Grisson R, Mohammed AA, Lewandrowski G, Lewandrowski K. Evaluation of first-draw whole blood, point-of-care cardiac markers in the context of the universal definition of myocardial infarction: a comparison of a multimarker panel to troponin alone and to testing in the central laboratory. Arch Pathol Lab Med. 2011; 135(4): 459-63. PubMed

Muthu V, Kozman H, Liu K, Smulyan H, Villarreal D. Cardiac troponins: bench to bedside interpretation in cardiac disease. Am J Med Sci. 2014; 347(4): 331-7. PubMed

Senter S, Francis GS. A new, precise definition of acute myocardial infarction. Cleve Clin J Med. 2009; 76(3): 159-66. PubMed

Sherwood MW, Newby K. High-sensitivity troponin assays: evidence, indications, and reasonable use. J Am Heart Assoc. 2014; 3(1): e000403. PubMed

Tanindi A, Cemri M. Troponin elevation in conditions other than acute coronary syndromes. Vasc Health Risk Manag. 2011; 7: 597-603. PubMed

Tiwari RP, Jain A, Khan Z, Kohli V, Bharmal RN, Kartikeyan S, Bisen PS. Cardiac troponins I and T: molecular markers for early diagnosis, prognosis, and accurate triaging of patients with acute myocardial infarction. Mol Diagn Ther. 2012; 16(6): 371-81. PubMed

Twerenbold R, Jaffe A, Reichlin T, Reiter M, Mueller C. High-sensitive troponin T measurements: what do we gain and what are the challenges? Eur Heart J. 2012; 33(5): 579-86. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Knoblock RJ, Lehman CM, Smith RA, Apple FS, Roberts WL. False-positive AxSYM cardiac troponin I results in a 53-year-old woman. Arch Pathol Lab Med. 2002; 126(5): 606-9. PubMed

Medical Reviewers

Content Reviewed: 
February 2017

Last Update: October 2017