Ischemic Heart Disease

Patients with ischemic heart disease (IHD) fall into 2 groups: stable angina secondary to ischemic heart disease (coronary artery disease or CAD) and acute coronary syndromes (ACS). ACS is further grouped into acute myocardial infarction (AMI) and unstable angina (UA). CAD is the leading cause of death in the U.S.

Epidemiology

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

Risk Factors

Hypertension
Hyperlipidemia
Diabetes mellitus
Tobacco use
Family history
Obesity (including metabolic syndrome)
Physical inactivity
Increasing age

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 AMI or UA from other conditions such as gastroesophageal reflux disease (GERD)
CAD
- May be asymptomatic
- May present with symptoms like ACS or AMI
Sudden death event
- Caused by ventricular fibrillation, ventricular tachycardia, electromechanical dissociation and bradycardias
- Most patients have underlying CAD or structural heart disease
- High fatality rate associated with this event

Treatment

Early recognition of ACS is important to prevent complications
Use established guidelines for specific treatment strategies from the American Heart Association

Prevention

Aggressive management of risk factors

Indications for Testing

Patient presenting with chest pain who also has risk factors suggesting CAD
Clinical history and risk factor assessment

Laboratory Testing

Cardiac markers testing

Cardiac Markers Testing
Troponins Useful to distinguish AMI from UA Cardiac-specific troponins have amino acid sequences different from skeletal muscle forms and therefore are highly specific for cardiac injury Preferred markers for the diagnosis of AMI – use in conjunction with EKG and clinical picture Negative predictive value is 97-99%; low sensitivity in myocardial infarction (MI) <6 hours old Should always be used in conjunction with clinical assessment Elevated troponins indicate cardiac injury Obtain blood sample at presentation and again after 6-9 hours – rising troponins confirm cardiac injury Guideline* recommendation for diagnosis – maximal concentration >99th percentile of a reference control group in the first 24 hours Guidelines* also recommend troponins be 5 times the 99th percentile during the first 72 hours following coronary artery bypass graft (CABG) to confirm CAD or related MI Troponins can remain elevated 10-14 days after an event CK-MB (creatine kinase-MB isoenzyme) Acceptable marker when troponins not available Guideline* recommendation for 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 Impaired use in organ injury (acute or chronic muscle, intestines, diaphragm, uterus and prostate damage) Due to nonspecific elevations Low sensitivity in early MI (<6 hours); late MI (>36 hours); minor damage MI Myoglobin Not recommended as a stand-alone test Very low specificity; high sensitivity in early detection of MI 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 relaxers Elevated in conditions characterized by wall stretch, ventricular dilation or increased pressure Most frequently used to diagnose heart failure Most guidelines* recommend serial sampling of cardiac markers and repeated EKG tracings over 24 hours to rule out AMI
*Guidelines include European Society of Cardiology, American College of Cardiology Foundation, American Heart Association, National Academy of Clinical Biochemistry, ESC/American College of Cardiology

Cardiac Markers Testing

Troponins

Useful to distinguish AMI from UA
Cardiac-specific troponins have amino acid sequences different from skeletal muscle forms and therefore are highly specific for cardiac injury
Preferred markers for the diagnosis of AMI – use in conjunction with EKG and clinical picture
- Negative predictive value is 97-99%; low sensitivity in myocardial infarction (MI) <6 hours old
- Should always be used in conjunction with clinical assessment
Elevated troponins indicate cardiac injury
Obtain blood sample at presentation and again after 6-9 hours – rising troponins confirm cardiac injury
- Guideline* recommendation for diagnosis – maximal concentration >99th percentile of a reference control group in the first 24 hours
- Guidelines* also recommend troponins be 5 times the 99th percentile during the first 72 hours following coronary artery bypass graft (CABG) to confirm CAD or related MI
Troponins can remain elevated 10-14 days after an event

CK-MB (creatine kinase-MB isoenzyme)

Acceptable marker when troponins not available
Guideline* recommendation for 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
Impaired use in organ injury (acute or chronic muscle, intestines, diaphragm, uterus and prostate damage)
- Due to nonspecific elevations
Low sensitivity in early MI (<6 hours); late MI (>36 hours); minor damage MI

Myoglobin

Not recommended as a stand-alone test
Very low specificity; high sensitivity in early detection of MI

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 relaxers
Elevated in conditions characterized by wall stretch, ventricular dilation or increased pressure
Most frequently used to diagnose heart failure

Most guidelines* recommend serial sampling of cardiac markers and repeated EKG tracings over 24 hours to rule out AMI

*Guidelines include European Society of Cardiology, American College of Cardiology Foundation, American Heart Association, National Academy of Clinical Biochemistry, ESC/American College of Cardiology

BNP measures may give additional prognostic information about mortality during first cardiovascular events
Newer markers (diagnostic significance not proven)
- Oxidative stress – lipoprotein-associated phospholipase A2, myeloperoxidase
- Tissue necrosis – CRP, interleukin 6, other interleukins, fatty acid binding proteins, free fatty acid unbound to albumin

Imaging Studies

Stress testing
Echocardiography – wall motion abnormalities suggest AMI

Other Testing

Electrocardiogram (EKG) – may have false negatives
- Typically demonstrates ST elevation, but not always (posterior MI, right ventricular infarction)

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
  - >2 anginal events in preceding 24 hours
  - ASA (acetylsalicylic acid) treatment in previous 7 days
  - Increased cardiac markers (troponins preferred)
  - Prior AMI, 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

Nonischemic cardiovascular
- Aortic dissection
- Myocarditis/pericarditis
- Hypertrophic cardiomyopathy
- Cardiac injury/rhabdomyolysis
- Cardiac arrhythmias
- Infiltrative cardiac disease
- Congestive heart failure
Chest wall/musculoskeletal
- Cervical disk disease
- Costochondritis
- Herpes zoster
- Neuropathic pain
- Rib fracture
Pulmonary
- Pulmonary embolism
- Pneumonia
- Tension pneumothorax
- Pleurisy
Gastrointestinal
- Esophageal reflux
- Cholecystitis
- Peptic ulcer disease
- Esophageal spasm
- Pancreatitis
- Esophageal rupture
Other
- Sepsis/shock
- Burns (>30% of body)
Psychiatric
- Depression
- Panic attack
- Somatization with psychogenic pain disorder

U.S. Preventative Services Task Force states EKG, exercise treadmill and electron beam computerized tomography may provide prognostic information about future events, but screening of asymptomatic patients is not recommended

Tests generally appear in the order most useful for common clinical situations

Test name: Troponin I

ARUP #: 0090613

Methodology: Chemiluminescent Immunoassay

Use:

Determine if injury has occurred to heart muscle

Determine etiology of chest pain

First-line laboratory test for myocardial injury

Limitations:

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

Test name: Troponin T

ARUP #: 0098803

Methodology: Quantitative Electrochemiluminescent Immunoassay

Use:

Determine if injury has occurred to heart muscle

Determine etiology of chest pain

First-line laboratory test for myocardial injury

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

Test name: Creatine Kinase, MB

ARUP #: 0080480

Methodology: Chemiluminescent Immunoassay

Use:

Cardiac injury marker when troponins are not available

Limitations:

Troponins preferred

Additional Tests Available

Test name: Creatine Kinase, Total, Serum or Plasma

ARUP #: 0020010

Methodology: Quantitative Enzymatic

Comments:

Test name: Myoglobin, Serum

ARUP #: 0020224

Methodology: Quantitative Electrochemiluminescent Immunoassay

Comments:

May be used selectively by clinicians to evaluate causes of non-cardiac muscle injury

Test name: B-Type Natriuretic Peptide

ARUP #: 0030191

Methodology: Quantitative Chemiluminescent Immunoassay

Comments:

Test name: proBrain Natriuretic Peptide, NT

ARUP #: 0050083

Methodology: Quantitative Electrochemiluminescent Immunoassay

Comments:

Test name: Lipoprotein-Associated Phospholipase A₂ (PLAC™Test)

ARUP #: 0081055

Methodology: Quantitative Enzyme-Linked Immunosorbent Assay

Comments:

Test name: C-Reactive Protein

ARUP #: 0050180

Methodology: Quantitative Immunoturbidimetric

Comments:

Test name: Interleukin 6 by MAFD

ARUP #: 0051537

Methodology: Quantitative Multi-Analyte Fluorescent Detection

Comments:

Guidelines

General

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) :606-609.PubMed

Comprehensive Review: January 2011
Last Update: January 2011

Cardiovascular Disease (Non-traditional Risk Markers)

Cardiovascular Disease (Traditional Risk Markers)