Testing for Coronary Artery Disease

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Testing for Coronary Artery Disease

• John L. Tan, MD, PhD
• North Texas Heart Center
• Presbyterian Hospital of Dallas

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Cardiovascular Disease Mortality Trends United
States 1979-2002
Deaths in Thousands
Year
Source CDC/NCHS.
3
Leading Causes of Death United States 2002
Deaths in Thousands
A Total CVD (Preliminary) B Cancer C
Accidents
D Chronic Lower Respiratory Diseases E Diabetes
Mellitus F Alzheimers Disease
Source CDC/NCHS
4
Rate of Myocardial Infarctions
Number (Annual)
Myocardial Infarction
Heart and Stroke Statistical Update. 2002.
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Lifetime Risk of CAD
Lifetime Risk ()
Age (Years)
Lloyd-Jones, DM et al. 1999. Lancet. 35389
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Growing Prevalence of CAD

• Larger pool
• Population is growing older
• Greater Risks
• Increasing incidence of
• Obesity
• Diabetes
• Metabolic Syndrome
• Hypertension

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Who Are at Risk?
How Can We Identify Them?
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The Framingham Score for Risk Prediction
Risk Low lt10 Intermediate 10-20 High
gt20
Greenland and Gaziano, NEJM, 2003
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Framingham Risk Score

• 50 year-old man
• Total cholesterol 240
• Non-smoker
• HDL 40
• SBP 140 mm Hg
• Framingham Risk Score
• 10-year Risk

6
4
0
1
1
12
10 (Intermediate)
10
Framingham Risk Score

• 45 year-old woman
• Total cholesterol 240
• Smoker
• HDL 50
• SBP 140 mm Hg
• Framingham Risk Score
• 10-year Risk

3
8
7
0
3
21
14 (Intermediate)
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Limitations of the Framingham Risk Score

• Family History of Premature CAD
• CRP Levels
• Metabolic Syndrome

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Elevated hs-CRP as an Independent Risk Factor
Ridker et al, NEJM, 2004
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Mortality Rates in Adults with Metabolic
Syndrome NHANES II 1976-80 Follow-up Study
13 years average follow-up.
Source Circulation 20041101245-50.
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Initial Assessment

• Framingham Risk Score
• Family History of Premature CAD
• CRP Levels
• Presence of the Metabolic Syndrome
• (High triglycerides, Glucose Intolerance,
  Central Adiposity)
• Presence of Diabetes

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Now What?
Fear of God
Modify Risk Factors
Further Risk Stratify
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Available Tests to Detect CAD

• Stress ECG
• Stress Imaging Study
• Ultra-fast CT (EBCT)
• CT Angiography
• Coronary Angiography

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Initial Considerations

• Symptomatic versus Asymptomatic
• Diagnosis versus Prognosis
• Assessment of Risk for CV mortality
• Physiological/Functional versus Anatomical

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Patients with Symptoms
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Clinical Classification of Chest Pain
Typical Angina (definite)
(1) Substernal chest discomfort with a
characteristic quality and duration that is (2)
provoked by exertion or emotional stress and (3)
relieved by rest or nitroglycerin
Atypical Angina (probable)
Meets 2 of the above characteristics
Noncardiac Chest Pain
Meets one or none of the typical angina
characteristics
ACC/AHA ACP-ASIM Guidelines for Chronic Stable
Angina, 1999
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Pretest Likelihood of CAD in Symptomatic
Patients Percent with significant CAD on
catheterization
Nonanginal Chest Pain
Atypical Angina
Typical Angina
Age, yrs
Men
Men
Women
Men
Women
Women
30-39 4 2 34 12 76 26 40-49 13 3 51 22 87 55 5
0-59 20 7 65 31 93 73 60-69 27 14 72 51 94 86
ACC/AHA ACP-ASIM Guidelines for Chronic Stable
Angina, 1999
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Kaplan-Meier Survival in Risk Stratified Patients
Shaw, et al, AJC, 2000
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Exercise Testing
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Clinically Useful Bench Marks of Exercise Capacity

• 1 MET Basal activity level (3.5 ml
  O2 comsumed/Kg/min
• lt 5 METs Associated with a poor prognosis
  in patients lt65 y/o
• 5 METs Marks the limit of ADLs, usual
  limit immediate post MI
• 10 METs Considered average level of
  fitness
• In patients with angina, no
  mortality benefit CABG vs
• medical Rx
• 13 METs Good prognosis in spite of any
  abnormal exercise test
• response
• 18 METs Aerobic master athelete
• 22 METs Achieved by well-trained
  competitive atheletes

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Four-year Mortality Rates with Abnormal ETT
Effects of Exercise Capacity
4-year Mortality Rates ()
Weiner, et al, JACC, 1984
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Exercise Parameters Associated with Advanced CAD
or Poor Prognosis

• 1. Duration of ETT lt6.5 METS (lt5 METS for
  women)
• 2. Exercise HR lt120 bpm off b-blockers
• 3. Ischemic ST segment change at HR lt120 bpm or
  lt6.5
• METS
• 4. ST segment depression gt2 mm, especially in
  multiple
• leads
• 5. ST segment depression for gt6 min in
  recovery
• 6. Decrease in BP during exercise

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Probability of Significant Disease Across Duke TM
Scores
Alexander, et al, JACC, 1998
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Survival According to Risk Groups Based on Duke
TM Scores
Risk Group, Score of Total Survival
Mortality,
Low (5 or greater) 62 0.99 0.25 Moderate
(-10 to 4) 34 0.95 1.25 High (-10 or
less) 4 0.79 5.0
Duke TM Score Exercise time - (5 x ST
deviation) - (4 x Treadmill angina)
ACC/AHA ACP-ASIM Guidelines for Chronic Stable
Angina, 1999
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Meta-analysis of Exercise Testing
Number of
Sensitivity Specificity Predictive
Grouping Studies ()
() Accuracy ()
Standard exercise test 147 68
77 73 Without MI 58
67 72
69 Without workup bias 3
50 90 69 With ST depression
22 69 70
69 Without ST depression 3
67 84 75 With digoxin
15 68 74
71 Without digoxin 9
72 69 70 With LVH
15 68 69 68 Without LVH
10 72 77
74 Overall 70 80
ACC/AHA Guidelines for Exercise Testing, 1997
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The Ischemic Ladder
Angina
ECG Changes
Systolic Dysfunction
MVO2
Diastolic Dysfunction
Time
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Stress Imaging
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Stress Imaging Studies
Stress Modalities
Imaging Modalities

• Echocardiography
• Perfusion Imaging
• Nuclear Scan
• Thallium Scan
• Sestamibi Scan
• Hybrid Scan
• MRI

• Exercise
• Dobutamine
• Adenosine
• (Persantine)

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Sensitivity and Specificity of CAD Studies
Procedure Sensitivity () Specificity ()
Exercise Test 68 77 Stress Echo
76 88 SPECT 88 77
Lee and Boucher. 2001. NEJM. 3441840
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Advantages of Stress Echocardiography

• 1. Higher specificity
• 2. Versatility more extensive evaluation of
• cardiac anatomy and function
• 3. Greater convenience/efficacy/availability
• 4. Lower cost

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Advantages of Stress Myocardial Perfusion Imaging

• 1. Higher technical success rate
• 2. Higher sensitivity, especially for
  one-vessel disease
• 3. Better accuracy in evaluating possible
  ischemia
• when multiple rest LV wall motion
• abnormalities are present
• 4. More extensive published database,
  especially in
• evaluation of prognosis

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Patients without Symptoms
High Grade Stenoses
Diabetics
Non-flow Limiting Disease
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Abnormal Perfusion Scans in Asymptomatic Diabetics
Abnormal Stress Perfusion Scan
A DIAD Study (Wackers et al. 2004. Diabetes
Care. 271954) B Rajagopalan et al.
(Rajagopalan et al. 2005. J Am Coll Cardiol.
4543) C Cedars-Sinai Group (Zellweger et al.
2004. Eur Heart. 25543)
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Yield of High-Risk Scans in Asymtomatic Diabetics
Subgroup
High-risk Scans

• Q waves on ECG 43
• Abnormal ECG 26
• Peripheral Vascular Disease 28
• LDL gt100 mg/dl 20
• Two or more risk factors 17

Rajagopalan et al. 2005. J Am Coll Cardiol.
4543
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Screening of CAD ADA Recommendations

• In asymptomatic diabetic patients with
• Abnormal resting ECG (MI or ischemia)
• Peripheral vascular disease
• Two or more additional CAD risk factors

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Patients without Symptoms
Mild CAD Not Detectable by Stress Testing
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Myocardial Infarctions and Plaque Severity
Burke et al. NEJM. 1997. 3361276
Myocardial Infarctions ()
2/3
1/6
1/6
Plaque Severity
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Outcomes with Mild CAD
TIMI Trials Meta-analysis
Death or Non-fatal MI
1-year follow-up
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5-Year Incidence of Coronary Death

n763
n274
n377
MONICA Belgian Substudy
Stenosis by Angiography
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Available Tests to Detect CAD

• Stress ECG
• Stress Imaging Study
• Ultra-fast CT (EBCT)
• CT Angiography
• Coronary Angiography

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Coronary Calcium Scoring
Greenland and Gaziano, NEJM, 2003
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Incremental Value of Coronary Calcium Scoring to
Risk Assessment
Greenland et al, JAMA, 2004
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Sensitivity and Specificity of CAD Studies
Procedure Sensitivity () Specificity ()
Exercise Test 68 77 Stress Echo
76 88 SPECT 88 77 EBCT
80-90 40-50
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Population versus Individual Risk
Treating the Herd
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Multi-Detector Computer Tomography (MDCT)
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Multi-Detector Computed Tomography (MDCT)

• Increased slices per gantry rotation
• (currently 64 slices)
• Faster gantry speed (330 ms/rotation)
• resulting in
• better spatial resolution (0.4 mm)
• better temporal resolution (165 ms)

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MDCT Capabilities
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Coronary Angiography with MDCT
Fuster V, et al. J Am Coll Cardiol. 2005.
461209
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Coronary Angiography with MDCT
Raff, et al. J Am Coll Cardiol. 2005. 46552
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64-Slice CT Angiography Per Segment Analysis
Sensitivity () Specificity () PPV ()
NPV ()
Leschka, et al 94
97 87 99 Leber,
et al 80 97 NR
NR Raff, et al 86
95 66 98 Pugliese,
et al 99 96 78
99 Mollet, et al 99
95 76 99
NR Not Reported
Leschka, et al. Eur Heart J. 2005. 261482
Leber, etl al. J Am Coll Cardiol 2005.
46147 Raff, et al. J Am Coll Cardiol. 2005.
46552 Pugliese, et al. Eur Radiol. 2005 161
Mollet, et al. Circulation 2005. 112(15)2318
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64-Slice CT Angiography Per Patient Analysis
Sensitivity () Specificity () PPV ()
NPV ()
Raff, et al 86
95 66 98 Pugliese, et
al 100 90 96
100
Raff, et al. J Am Coll Cardiol. 2005. 46552
Pugliese, et al. Eur Radiol. 2005 161
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Detection of Soft Plaque by CT Angiography
Fuster V, et al. J Am Coll Cardiol. 2005.
461209
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Indications for MDCT Angiography of the Heart

1. Facilitation of the diagnostic cardiac evaluation
   of a patient with chest pain syndrome (e.g. chest
   pains, anginal equivalent, angina). Depending on
   the clinical presentation, the MDCT for coronary
   artery evaluation may precede a perfusion stress
   test, or it may be used to clarify a perfusion
   stress test that is non-diagnostic, equivocal, or
   is inadequate in explaining the patients
   symptoms.
2. Facilitation of the management decision of a
   symptomatic patient with known coronary artery
   disease. (e.g. post-stent, post CABG) when the
   results of the MDCT may guide the decision for
   repeat invasive intervention.
3. Assessment of suspected congenital anomalies of
   coronary circulation or great vessels.

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Radiation Exposure of CAD Studies
Dose (mSv)
Background (per year) 3.5 Chest
X-ray 0.1 CT of Chest 5-7 Procedure
EBCT 1 Perfusion Imaging 10 CT
Angiography 10 Coronary Angiography 2-3
Conti, CR. Clin. Cardiol. 2005. 28450 Morin
RL, et. al. Circulation. 2003. 107917
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Sensitivity and Specificity of CAD Studies
Procedure Sensitivity () Specificity ()
Exercise Test 68 77 Stress Echo
76 88 SPECT 88 77 (40-60 of patients
have attenuation defects) EBCT 80-90
40-50 MDCT (per
patient analysis) 16-Slice 85-100
75-86 64-Slice
86-100 90-95
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Invasive Coronary Angiography

• 25 of angiograms performed annually in the US
  are normal
• 8 million angiograms are performed annually in
  the US at a cost of 4,000 per procedure

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Invasive Coronary Angiography

• Therefore, there are 2 million angiograms
  performed annually on patients with normal
  coronary arteries
• These procedures expose patients to the inherent
  risks of invasive coronary angiography at a cost
  of 4 billion per year

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Summary

• The incidence and prevalence of CAD is
• growing due to aging of the population
• and to increases in risk factors.
• Global clinical assessment, CRP levels,
• and calcium scoring may help to further
• stratify individual risks.

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Summary

• Stress testing currently remains the
• standard for assessing symptoms.
• Although a negative stress study most
• likely excludes the presence of flow-
• limiting disease (stenosis of gt70), it
• does not exclude the presence of mild to
• moderate disease.

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Summary

• Mild to moderate disease still confers an
• increase in coronary deaths and
• infarctions.
• Invasive coronary arteriography has been
• the only method of identifying patients
• with mild to moderate disease up to now.

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Summary

• CT angiography will allow for the non-
• invasive identification of at-risk patients
• as having (or not having) underlying
• coronary atherosclerosis.

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Summary

• Exercise Test
• Probable more than we do
• Stress Echocardiogram
• Lower pre-test probablility population
• Valvular or other structural heart disease

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Summary

• Stress Perfusion Scan
• Higher pre-test probability population
• Cardiac MRI
• When above unhelpful and expertise is available

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Summary

• Ultra-fast CT (EBCT)
• No role in symptomatic patients
• CT Angiography
• Will play larger role with ability to image
  coronaries (Triple Rule Out)
• Coronary Angiography
• When stress testing is potentially dangerous

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