Testing for Coronary Artery Disease

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´╗┐John L. Tan, MD, PhD North Texas Heart Center Presbyterian Hospital of Dallas Testing for Coronary Artery Disease

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Cardiovascular Disease Mortality Trends United States: 1979-2002 Deaths in Thousands Year Source: CDC/NCHS.

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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 Alzheimer's Disease Source: CDC/NCHS

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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. 353:89

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Growing Prevalence of CAD Larger pool Population is becoming more seasoned Greater Risks Increasing occurrence of Obesity Diabetes Metabolic Syndrome Hypertension

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Who Are at Risk? By what method Can We Identify Them?

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The Framingham Score for Risk Prediction Risk: Low <10% Intermediate 10-20% High >20% 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 12 10% (Intermediate)

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Framingham Risk Score 45 year-old lady 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 normal development. Source: Circulation 2004;110:1245-50.

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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? "Dread of God" Modify Risk Factors Further Risk Stratify

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Available Tests to Detect CAD Stress ECG Stress Imaging Study Ultra-quick 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 (distinct) (1) Substernal mid-section distress with a trademark quality and length that is (2) incited by effort or passionate anxiety and (3) soothed by rest or nitroglycerin Atypical Angina (plausible) Meets 2 of the above attributes Noncardiac Chest Pain Meets one or none of the run of the mill angina attributes ACC/AHA ACP-ASIM Guidelines for Chronic Stable Angina, 1999

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Pretest Likelihood of CAD in Symptomatic Patients: Percent with noteworthy CAD on catheterization Nonanginal Chest Pain Atypical Angina Typical Angina Age, yrs Men Women Men Women Men Women 30-39 4 2 34 12 76 26 40-49 13 3 51 22 87 55 50-59 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 action level (3.5 ml O2 comsumed/Kg/min < 5 METs Associated with a poor forecast in patients <65 y/o 5 METs Marks the farthest point of ADLs, common utmost prompt post MI 10 METs Considered normal level of wellness In patients with angina, no mortality advantage CABG versus therapeutic Rx 13 METs Good guess regardless of any strange practice test reaction 18 METs Aerobic ace athelete 22 METs Achieved by all around prepared focused 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. Span of ETT <6.5 METS (<5 METS for ladies) 2. Exercise HR <120 bpm off b - blockers 3. Ischemic ST portion change at HR <120 bpm or <6.5 METS 4. ST fragment wretchedness >2 mm, particularly in different leads 5. ST portion sorrow for >6 min in recuperation 6. Diminish in BP amid work out

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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-investigation of Exercise Testing Number of Sensitivity Specificity Predictive Grouping Studies (%) (%) Accuracy (%) Standard practice test 147 68 77 73 Without MI 58 67 72 69 Without workup predisposition 3 50 90 69 With ST depression 22 69 70 69 Without ST melancholy 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 MVO 2 Diastolic Dysfunction Time

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Stress Imaging

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Exercise Dobutamine Adenosine (Persantine) Echocardiography Perfusion Imaging Nuclear Scan Thallium Scan Sestamibi Scan Hybrid Scan MRI Stress Imaging Studies Stress Modalities Imaging Modalities

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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. 344:1840

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Advantages of Stress Echocardiography 1. Higher specificity 2. Versatility: more broad assessment of cardiac life systems and capacity 3. More noteworthy comfort/viability/accessibility 4. Bring down cost

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Advantages of Stress Myocardial Perfusion Imaging 1. Higher specialized achievement rate 2. Higher affectability, particularly for one-vessel infection 3. Better exactness in assessing conceivable ischemia when various rest LV divider movement variations from the norm are available 4. More broad distributed database, particularly in assessment of anticipation

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Patients without Symptoms High Grade Stenoses Diabetics Non-stream 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. 27:1954) B Rajagopalan et al. (Rajagopalan et al. 2005. J Am Coll Cardiol. 45:43) C Cedars-Sinai Group (Zellweger et al. 2004. Eur Heart. 25:543)

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Yield of High-Risk Scans in Asymtomatic Diabetics Q waves on ECG 43% Abnormal ECG 26% Peripheral Vascular Disease 28% LDL >100 mg/dl 20% at least two hazard factors 17% Subgroup High-chance Scans Rajagopalan et al. 2005. J Am Coll Cardiol. 45:43

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Screening of CAD: ADA Recommendations In asymptomatic diabetic patients with: Abnormal resting ECG (MI or ischemia) Peripheral vascular malady at least two extra CAD chance variables

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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. 336:1276 Myocardial Infarctions (%) 2/3 1/6 1/6 Plaque Severity

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Outcomes with Mild CAD TIMI Trials Meta-investigation % Death or Non-lethal MI 1-year development

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5-Year Incidence of Coronary Death % n=763 n=274 n=377 MONICA Belgian Substudy Stenosis by Angiography

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Available Tests to Detect CAD Stress ECG Stress Imaging Study Ultra-quick 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 cuts per gantry turn (presently 64 cuts) Faster gantry speed (330 ms/revolution) bringing about: better spatial determination (0.4 mm) better transient determination (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. 46:1209

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Coronary Angiography with MDCT Raff, et al. J Am Coll Cardiol. 2005. 46:552

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64-Slice CT Angiography: Per Segment Analysis Sensitivity (%) Specificity (%) PPV (%) NPV (%) Leschka, et al 94 9

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