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A. Risk Factors For CAD navigator

  1. Typical Anginal Symptoms [3]
    1. Sensation in chest of squeezing, heaviness, pressure, weight, tightness, aching
    2. Radiation to shoulder, neck, jaw, inner arm, epigastrium, band like-discomfort
    3. Relatively predictable onset with exertion (stable angina) or at rest (unstable angina)
    4. Stable angina with pain at rest is well document and due to high grade stenosis
    5. Abates when stressor is gone or nitroglycerin is taken
  2. Clinical History
    1. Previous Myocardial Infarction
    2. Left Ventricular Hypertrophy (LVH)
    3. Diabetes Mellitus
    4. Smoking - Mortality reduction 36% in patients with CAD who quit smoking [40]
    5. Hypertension (HTN)
    6. Male age >45 or Female age >55 years
    7. Sedentary Lifestyle
    8. Obesity
    9. Family History
    10. Cocaine abuse
  3. Laboratory
    1. Hypercholesterolemia - elevated total cholesterol (Chol)
    2. Elevated low density lipoprotein (LDL) Chol
    3. Low high density lipoprotein (HDL) Chol: <35mg/dL
    4. C-reactive protein (CRP) level [27,39] - marker for inflammation, better single predictor for CAD than LDL Chol [35] and clearly additive to standard lipid markers [18]
    5. Adding apolipoproteins A1 and B100 to total and HDL chol levels adds no cardiovascular prognostic value in women [18]
    6. CRP levels do add cardiovascular prognostic value to standard lipids in women [18]
    7. Elevated N-terminal-BMP associated with increase MI and death risk in CAD patients, independent of usual clinical risk factors [4]
    8. Elevated serum homocysteine
    9. Coagulation Factor V "Leiden" (1691A) or prothrombin 20210A mutations [19]
    10. Anti-cardiolipin antibodies (in patients with systemic lupus)
    11. A large number of partially validated risk factors have been identified
  4. Atypical Chest Pain [3,24]
    1. Includes pleuritic, sharp, prickling or knife-like
    2. Involves chest wall, is positional, tender to palpation, variable response to nitroglycerin
    3. Rule out cardiac causes and then evaluate for reflux esophagitis (GERD)
    4. Omeprazole (proton pump inhibitor, PPI) Challenge Test is probably most cost effective
    5. Empiric trial of omeprazole 60mg per day x 7 days (or other PPI) with symptom evaluation
    6. Patients with good reduction / elimination of symptoms are very likely to GERD
  5. Depression [41]
    1. Prominent finding in ~20% of CAD patients
    2. Depressive symptoms strongly associated with quality of life
    3. Detection and treatment of depression is key component of care
  6. Severity of Angina [3]
    1. Class I: no angina with ordinary physical activity; angina with strenous or plonged exertion
    2. Class II: early-onset limitation of ordinary activity, or with emotional stress
    3. Class III: marked limitation of ordinary activity
    4. Class IV: inability to carrout any physical activity without chest discomfort; angina at rest

B. Evaluation of Stable CAD [1,3] navigator

  1. Medical History
    [Figure] "Evaluation of Angina"
    1. Most important part of evaluation is patient's history and cardiac risk factors
    2. This provides a pre-test probability of CAD
    3. Angina: level, frequency, inducers, reducers
    4. Concommitant risk factors - (above), such as HTN, smoking
    5. Tests are done to rule out CAD and avoid unnecessary cardiac angiography
  2. Electrocardiogram (ECG)
  3. Laboratory
    1. Cholesterol panel
    2. CRP
    3. Homocysteine
    4. Renal function
  4. Exercise Treadmill Test (ETT) - recommended initial evaluation [1,13,30]
  5. Radiographic Evaluation of CAD
    1. Exercise or dobutamine echocardiography - assess for wall motion abnormalities
    2. Exercise or pharmacologic myocardial perfusion (SPECT) - shows specific perfusion defects
    3. Coronary computed tomography (CT) - more selective for intermediate risk patients [14]
    4. Electron Beam CT - mainly calcium score; may signify high grade stenoses [2,45]
    5. Multidetector CT is has high sensitivity, negative predictive value, but ~30% non-evaluable segments for detection of CAD [20,22]
    6. Electron beam or multidetector CT to determine calcium score as a strong predictor of cardiac events across racial and ethnic groups, independent of other risk factors [45]
    7. Contrast magnetic resonance images (CMR) may detect smaller subendocardial MI's than dual isotope SPECT [37]
    8. Magnetic Resonance Angiography (MRA) to rule out left main or 3-vessel CAD [31]
  6. Relief of chest pain after nitroglycerin does not distinguish coronary from other causes [44]
  7. Cardiac catheterization for high risk patients who are candidates for PCI or cardiac surgery
  8. Prediction of Overall Cardiac and Mortality Risk
    1. Strong inverse relationship between a patient's red blood cell glutathione peroxidase (GPO) levels and risk of subsequent cardiovascular (CV) events [42]
    2. Elevated levels of N-terminal-pro-B-type natriuretic protein (NT-pro-BNP) associated with independent 2.4X increased risk for death from any cause (top-bottom quartiles) [17]
    3. Single serum myeloperoxidase level predicts risk for subsequent CV events over 1 and 6 months [43]

C. Evaluation of Prolonged Chest Pain [3] navigator

  1. In patients presenting to emergency room, full "rule-out" MI protocol should be done [5,16]
    1. Usually consists of history (risk factors), physical exam (especially for murmers)
    2. ECG with comparison to (asymptomatic) baseline is essential in rule-out MI protocol
    3. Troponin T or I levels allows rule-out MI in 6 hours rather than 12 hours
    4. Serum myeloperoxidase (MPO) are probably the most sensitive marker fo ruling out MI [43]
    5. Single MPO level also predicts risk for subsequent CV events over 1 and 6 months [43]
    6. Serial creatinine kinase (CK) MB fractions every 4-6 hours for 12 hours was previously the standard rule-out protocol [3]
    7. Real-time Tc-99m SPECT imaging for perfusion can help rule-out MI within 1-2 hours [36]
    8. Patients with initial negative evaluation should further evaluation
  2. Further Evaluation in Patients with Chest Pain but no MI
    1. Serum MPO and red blood cell GPO levels predict risk for recurrent CV events [42,43]
    2. Exercise treadmill testing (ETT) is standard further evaluation
    3. This protocol has a 98% negative predictive value (so effectively rules out ischemia)
    4. Positive predictive value is still only 16% for true CAD (by angiography)
    5. Newer tests use single photon computed tomography to assess cardiac blood flow
  3. Hybernating Myocardium [5,31]
    1. Chronically ischemic, non-scarred, dysfunctional cardiac muscle with functional potential
    2. Under normal conditions, hybernating myocardium does not contract but is viable
    3. Improving perfusion to these areas improves contractility and overall cardiac function
    4. Therefore, identification of hypernating myocardium is critical for revascularization
    5. Hypokinetic, akinetic and/or dyskinetic areas may be seen on echocardiography
    6. Chronically stunned myocardium may be a component of hypernating myocardium
    7. Stimulation with vasodilators (dobutamine) or with epinephrine can induce contraction
    8. Revascularization (CABG, PTCA) can return function to hybernating myocardium

D. Diagnostic Methods for Anatomic Localization [1,3]navigator

  1. ETT with ECG is standard evaluation for stable CAD
  2. For unstable angina (acute coronary syndromes), angiography is generally recommended
  3. Indications for Use of New Diagnostic Methods in Initial Evaluation
    1. Complete left bundle branch block (LBBB)
    2. Electronically paced ventricular rhythm
    3. Preexcitation (Wolff-Parkinson-White) Syndrome
    4. More than 1mm of ST-segment depression at rest
    5. Inability to exercise to level high enough to give meaningful results with ETT
    6. Anginga and a history of revascularization
  4. Newer Diagnostic Methods [26]
    1. Exercise or pharmacologic echocardiography (more sensitive than ETT)
    2. Electron-beam CT or spiral CT
    3. Magnetic resonance imaging, angiography, and contrast MRI (CMR)
    4. Dual isotope single-photon emission computed tomography (SPECT)
    5. CT and MRI/MRA are much more expensive and not substantially superior to ETT
  5. Elevated CRP is a risk factor for cardiovascular death in both men and women [27,39]

E. ECG Changes navigator

  1. Reversible ST segment depression
    1. Down-sloping depression most specific
    2. Horizontal depression is less specific
    3. Up-sloping (with J point) is most likely a normal variant
    4. Patients may have abnormal (CAD) or normal (Syndrome X) Coronary Arteriograms
  2. Variant Angina (Prinzmetal's)
    1. ST segment elevation
    2. Vasospasm induced, relieved when spasm stops
    3. May be due to underlying plaque / thrombus which is variably lodged / dislodged
    4. Overall good prognosis; related to tobacco use
    5. Other vasospastic diseases are commonly found (eg. migraine, Raynaud's Disease)
  3. In general, any ST segment or T wave changes from baseline ECG with symptoms should be fully evaluated
  4. Nonspecific ST abnormalities at baseline ECG in symptomatic patients may be evaluated accurately with exercise treadmill testing (ETT) and Duke criteria [23]
  5. ECG-gated single photon emission computed tomography (GSPECT) can be used in patients with chest pain to rule out cardiac cause (99m-Tc-based perfusion test)

F. Exercise Treadmill Testing (ETT) [3,6,30]navigator

  1. Good predictive accuracy of any of the non-invasive CAD tests
    1. Overall 20-30% false positives and false negatives
    2. Women have higher rates of both false positives and negatives
    3. Coronary angiography is often used to resolve disparate results
  2. ETT is better predictor than ANY other clinical or laboratory predictor in "healthy" men referred for ETT for clinical reasons [34]
  3. Goal of ETT is to increase myocardial workload to identify potentially ischemic regions
    1. Walking or jogging (or arm) ergometry to increase myocardial workload
    2. Workload includes increased heart rate, blood pressure, and myocardial vessel dilation
    3. Usually expressed in METs, or metabolic equivalents
    4. METs are derived from standard tables relating protocol and duration to individual
    5. Workload is the most important parameter derived from ETT in any age patient [28]
    6. In general, attempt to achieve >90% of maximal heart rate: maximal HR ~ 220 - Age
  4. Monitor symptoms and ECG for specific changes
    1. ST depressions most specific for ischemia:
    2. Horizontal or downsloping ST-segment depression at least 1mm (60 msec after J point)
    3. Upsloping ST segment with depression of at least 1.5mm (80msec after J point)
    4. If ST segment depression at rest, additional 2mm of ST segment depression
    5. ST segment elevation of at least 1mm at J point versus baseline rest ECG
    6. Nonspecific ST abnormalities at rest require careful interpretation on ETT using Duke Criteria [23]
  5. Test is evaluated in context of subject's Rate Pressure Product (RPP)
    1. RPP = maximal systolic blood pressure (SBP) x maximal heart rate (HR)
    2. A "good" (interpretable) test usually has RPP > 20,000
    3. Combination with thallium or technicium (MIBI) improves specificity and sensitivity
    4. Addition of right precordial leads to standard ETT increases sensitivity to ~90% [7]
  6. Patients with the following abnormal results have high risk for CAD:
    1. Decrease in or no change in blood pressure during test
    2. Global ischemia
    3. Lung uptake (thallium)
    4. Reversible cavity dilatation
    5. Excercise induced left bundle branch block (LBBB) has >2.5 fold increased risk for subsequent primary cardiovascular events over 4 years [8]
    6. Therefore, it is reasonable to evaluate persons with exercise induced LBBB further
  7. ETT Test Characteristics [7]
    1. Overall sensitivity ~45-66% and specificity ~85% for ETT in a moderate probability cohort which had undergone minimal previous testing [6,7]
    2. Meta-analysis showed sensitivity 50-68% and specificity 72-90% [30]
    3. Workload evaluated by ETT was the only useful parameter for evaluation in age >65 [28]
    4. Sensitivity for single vessel disease is <35-61%
    5. Sensitivity for two vessel disease <70% and three vessel disease 83%
    6. Adding nuclear medicine scans to ETT improves characteristics (see below)
    7. Strongly advocate adding V3R, V4R, and V5R right precordial leads to ECG
    8. Increases overall sensitivity from 66% to 92% [7]
    9. Evaluation of right sided leads for ischemic changes similar to that for left sided
    10. Peak exercise capacity on ETT was best overall best predictor mortality in men [34]
  8. Nuclear Medicine Scans with Stress Testing [31]
    1. Specific radioisotopes are retained in myocardial tissue in proportion to blood flow
    2. Radionuclide tracer distributions under stress versus rest can show perfusion problems
    3. Analysis using SPECT (single proton emission computerized tomography) is performed
    4. Most commonly used is the potassium (K+) analog Thallium-201 (Tl-201)
    5. Tl-201 is taken up avidly by myocardial cells (slow washout exchange with K+)
    6. Tl-201 is used for evaluating myocardial blood flow due its high extraction rate (85%)
    7. 99mTc-sestamibi or 99mTc-tetrofosmin have less myocardial extraction (60-65%)
    8. These agents are more useful for assessing viable versus non-viable myocardium
    9. Stress myocardial SPECT imaging has sensitivity 87% and specificity 76%
    10. Thallium and ETT predict 3 fold increased major event risk post-CABG in asymptomatic patients [11]
  9. ETT in Women and Other Groups [9]
    1. ETT may be less accurate in women and in persons with poor exercise tolerance
    2. Women have increased number of false positive ETT compared with men
    3. Nuclear tests often show large number of false positives in low risk patients as well
    4. In women and patients with baseline ECG anomalies, especially LBBB, nuclear studies or dobutamine (stress) echocardiography should strongly be considered
    5. Use of Duke Treadmill Score (DTS) in women improves accuracy of ETT
    6. DTS evaluation of ETT in men and women gave approximately equivalent accuracy
    7. In patients with normal ECG, nuclear scans add cost but no useful information [10]
  10. Inadequate Exercise Capacity
    1. An increasing number of patients cannot tolerate or achieve exercise goals
    2. In these cases, a "pharmacological" stress agent is used instead of exercise
    3. These agents are (fairly) specific coronary vasodilators
    4. Dipyridamole (Persantine®) can be given intravenously to dilate coronary arteries
    5. Adenosine (Adenoscan®) is approved for CAD evaluation as an adjunct to 201-Thalium imaging
    6. Regadenoson (Lexiscan®), an adenosine A2A receptor agonist, is approved for CAD evaluation
  11. Myocardial Perfusion Scanning to Rule-Out MI [36]
    1. Technetium-99m sestamibi (Tc99m) SPECT imaging may help rule-out cardiac ischemia
    2. Real-time emergency room assessment of cardiac perfusion
    3. Can reduce unnecessary hospitalizations for "rule-out MI" patients
    4. However, troponin testing (in addition to creatinine kinase) is typically used for rule-out MI
  12. Heart Rate Recovery after Exercise [25,29]
    1. Increase in heart rate during exercise due to increased sympathetic (adrenergic) drive
    2. Also due to reduction in vagal (parasympathetic) tone
    3. Recovery of heart rate after exercise is a function of vagal reactivation
    4. Reduction in vagal activity is a risk factor for death (likely cardiac sudden death)
    5. A delayed decrease in heart rate during first minute after graded exercise incresaes overall risk of death of 2-4 fold over 6 years [25]
    6. Heart rate recovery is independent of treadmill excercise score for prognosis [29]
  13. Frequent ventricular ectopy during recovery after exercise is better predictor for increased risk of death than ventricular ectopy only during exercise [38]

G. Echocardiography [9] navigator

  1. Wall motion abnormalities (WMA) evaluated
  2. For interpretation, baseline echocardiogram should be available
    1. Comparison of new WMA to old echo
    2. Useful for posterior wall (Circumflex disease) abnormalities (often not seen on ECG)
  3. Dobutamine echocardiography not used in setting of acute ischemia / infarction
  4. However, dobutamine echocardiography may be useful for evaluating stable angina

H. Stress-Echocardiography [12]navigator

  1. Assessment of wall motion abnormalities (implies ischemia) at high cardiac work
  2. Similar sensitivity and specificity as other pharmacologic stress tests
  3. Various Drugs are used to increase cardiac work
    1. Dobutamine (10-40µg/kg/min) is most commonly used
    2. Atropine (0.25-1mg iv) may be added to increase heart rate to >90% predicted
    3. Arbutamine (GenESA®) is a potent intravenous non-specific ß agonist drug [13]
    4. Arbutamine is FDA approved with special computer system for evaluation
    5. No clear clinical advantage of arbutamine over dobutamine (with atropine)
  4. Cardiac Ultrasound (echocardiogram)
    1. Used to detect work-induced wall motion abnormalities
    2. Wall motion abnormalities usually occur prior to development of ischemic symptoms
    3. Test is useful for evaluation of chest pain to rule out myocardial source
    4. Extremely useful in peroperative assessment in patients who cannot exercise
    5. Negative predictive value for late cardiac events ~87% in patients with suspected coronary disease
    6. Positive predictive value ~25%; therefore, best used to rule out cardiac ischemia
  5. Stress echocardiograms are highly predictive of hybernating myocardium [5]

I. Magnetic Resonance Imaging (MRI) navigator

  1. Coronary Magnetic Resonance Angiography (MRA) [31]
    1. Real time coronary MRA with breathing is now possible
    2. Permits noninvasive, noncontrast assessment of proximal and middle segments
    3. Mid-diastolic images combined to create 3-dimensional reconstruction
    4. Reliably identifies left main or 3 vessel CAD
    5. Standard protocols for obtaining these images are available
  2. Contrast-Enhanced MRI [32,33]
    1. MRI gives excellent spacial resolution and can identify dysfunctional myocardium
    2. Regions of MI show 10-fold hyperintensity with gadolinium enhanced MRI (gad-MRI)
    3. Highly hyperintense regions represent dead (versus hybernating) myocardial tissue
    4. Reversible myocardial dysfunction (hybernating myocardium) can be identified with gad-MRI
    5. At least as sensitive and specific as other techniques [32]
    6. Superior to other techniques for quantitation of hypernating regions of myocardium

J. Ambulatory ECG Monitoring navigator

  1. Mainly to assess ST segment changes during daily activities
  2. Hypothesis is that patients at risk for serious cardiac events have ST changes
  3. Acute cardiac events are not predicted by ambulatory ST segment changes [15]
  4. This is likely because acute events occur in areas of "new" atherosclerotic lesions
  5. Older lesions, responsible for stable ischemia, contribute less to acute coronary events

Resources navigator

calcDuke Score

References navigator

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