Screening for CAD: What Test to Order for Which Situation John L. Tan, MD, PhD Presbyterian Hospital of Dallas

Estimated Annual Incidence of CV Disease Cardiovascular Diseases 70 million Silent Ischemia ? 3 million Chest Pain 6 million Stroke 0.5 million Not Admitted 2 million Heart Attack 1.5 million Stroke Deaths 150,000 Unstable Angina 1 million Wrongful Discharge 30,000 AMI Deaths 500,000

Available Tests Stress ECG Stress Imaging Study Ultra-fast CT (EBCT) CT Angiography Stress Cardiac MRI/MRA Coronary Angiography

Initial Considerations Symptomatic versus Asymptomatic Diagnosis versus Prognosis Assessment of Risk for CV mortality

Patients with Symptoms

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

Pretest Likelihood of CAD in Symptomatic Patients: Percent with significant 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

Kaplan-Meier Survival in Risk Stratified Patients Shaw, et al, AJC, 2000

Diagnosis and Risk Stratification of Patients with Chest Pain ACC/AHA ACP-ASIM Guidelines for Chronic Stable Angina, 1999 Yes Contraindications to stress testing? No Symptoms or clinical findings warranting angiography? Yes Consider coronary angiography No No Patient able to exercise? Pharmacologic imaging study Yes Yes Exercise imaging study Previous coronary revascularization? No No Resting ECG interpretable? Yes Perform exercise test

Exercise Testing

Indications for Stress Testing without an Imaging Modality 1. Patients with an intermediate probability of CAD, including those with RBBB or <1 mm resting ST- segment changes (Class I) 2. Patients with suspected vasospastic angina (Class IIa) 3. Patients with a high or low probability of CAD (Class IIb) 4. Annual TMT in asymptomatic patients with estimated annual mortality rate >1% ACC/AHA ACP-ASIM Guidelines for Chronic Stable Angina, 1999

Four-year Mortality Rates with Abnormal ETT: Effects of Severity of CAD Weiner, et al, JACC, 1984

Four-year Mortality Rates with Abnormal ETT: Effects of Exercise Capacity Weiner, et al, JACC, 1984

Clinically Useful Bench Marks of Exercise Capacity 1 MET Basal activity level (3.5 ml O2 comsumed/Kg/min < 5 METs Associated with a poor prognosis in patients <65 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

Exercise Parameters Associated with Advanced CAD or Poor Prognosis 1. Duration of ETT <6.5 METS (<5 METS for women) 2. Exercise HR <120 bpm off b-blockers 3. Ischemic ST segment change at HR <120 bpm or <6.5 METS 4. ST segment depression >2 mm, especially in multiple leads 5. ST segment depression for >6 min in recovery 6. Decrease in BP during exercise

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

Special Populations Elderly Persons (Age > 65 ) Women

Exercise Testing of the Elderly Few elderly persons were included in studies validating the use of exercise testing (mean age in Duke Treadmill Score studies was 49 years old) The elderly have greater prevalence and severity of disease more co-morbid diseases increasingly sedentary lifestyle

Prognostic Value of Treadmill Exercise Testing in the Elderly Two variables are associated with cardiac events in the elderly 1. Angina with exercise 2. Workload achieved After workload was taken into account, neither abnormal ST-segment changes or exercise-induced angina was independently related to time to cardiac event Ann Intern Med 132:862-870, June 2000

The Problem with Women . . . Almost half the women younger than 65 year old with anginal symptoms in CASS had normal coronary arteriograms More women with inability to exercise to maximum aerobic capacity

More Problems with Women . . . Exercise-induced ST-segment depression is less sensitive in women than men due to lower prevalence of severe CAD (22-42% of women vs 13-29% of men with CAD have one-vessel disease) Exercise ECG may also be less specific (72 vs 79%, with a PPVof 62 vs 85%)

. . .But it may not be that Bad

Probability of Significant Disease Across Duke TM Scores Alexander, et al, JACC, 1998

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

The “Ischemic Ladder” MVO2 Time Angina ECG Changes Systolic Dysfunction MVO2 Diastolic Dysfunction Time

Stress Imaging

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

Indications for Stress Imaging for Diagnosis 1. Abnormal resting ECG Wolff-Parkinson-White syndrome > 1mm resting ST-segment depression LBBB V-paced rhythm 2. Previous non-diagnostic TMT 3. Inability to perform TMT ACC/AHA ACP-ASIM Guidelines for Chronic Stable Angina, 1999

Indications for Stress Imaging for Diagnosis 4. Prior re-vascularization including percutaneous interventions or CABG 5. Increased likelihood of a false-positive TMT Digoxin use Left ventricular hypertrophy 6. As the initial stress test in patients with a normal resting ECG ACC/AHA ACP-ASIM Guidelines for Chronic Stable Angina, 1999

Further indications for Stress Imaging for Risk Stratification 1. To identify the extent, severity, and location of ischemia to determine - ischemic burden - functional significance of lesions 2. To assess post-MI prognosis ACC/AHA ACP-ASIM Guidelines for Chronic Stable Angina, 1999

Of Note Adenosine/dipyridamole perfusion imaging preferred in patients able to exercise with a V-paced rhythm or underlying LBBB (Class I vs IIb for stress echocardiography) ACC/AHA ACP-ASIM Guidelines for Chronic Stable Angina, 1999

Comparing Stress Echo to Perfusion Imaging Myocardial Perfusion Imaging Normal Ischemic Fixed Total Normal 137 10 7 154 Ischemic 4 47 3 54 Fixed 13 30 38 81 Total 154 87 48 289 Echocardiography 137 + 47 + 38 = 222/289 77% Agreement SPECT vs Echo 87 vs 54 Ischemic regions 48 vs 81 Fixed regions Quinones and Zoghbi

Sensitivity and Specificity of Stress Studies Procedure Sensitivity (%) Specificity (%) Exercise Test 68 77 Stress Echo 76 88 SPECT 88 77

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

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

Prognostic Value of a Normal Perfusion Scan Number Mean Annual of Patients Study Type follow-up mortality (%) 3594 Meta-analysis 29 months 0.9 473 Retrospective 30 +/- 16 months 0.2 5183 Prospective 642 +/- 226 day <0.5 8411 Prospective 2.5 +/- 1.5 years <0.4 In contrast, patients with an abnormal scan have a 5-7% annualized serious adverse event rate

Myocardial Perfusion Imaging Normal Study

Myocardial Perfusion Imaging Abnormal Study post-CABG

Cardiac Imaging Echo MRI

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

Testing in Symptomatic Patients Stress Perfusion Scan Higher pre-test probability population Cardiac MRI When above unhelpful and expertise is available

Testing in Symptomatic Patients 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

Patients without Symptoms

Estimated Annual Incidence of CV Disease Cardiovascular Diseases 70 million Silent Ischemia ? 3 million Chest Pain 6 million Stroke 0.5 million Not Admitted 2 million Heart Attack 1.5 million Stroke Deaths 150,000 Unstable Angina 1 million Wrongful Discharge 30,000 AMI Deaths 500,000

The Framingham Score for Risk Prediction Greenland and Gaziano, NEJM, 2003

Elevated hs-CRP as an Independent Risk Factor Ridker et al, NEJM, 2004

Elevated hs-CRP as an Independent Risk Factor Ridker et al, NEJM, 2004

Available Tests Stress ECG Stress Imaging Study Ultra-fast CT (EBCT) CT Angiography Stress Cardiac MRI/MRA Coronary Angiography

Coronary Calcium Scoring Greenland and Gaziano, NEJM, 2003

Coronary Calcium Scoring Meta-analysis: Sensitivity of 80-92% Specificity of 40-51% High prevalence of unexpected, incidental noncardiac findings

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

Incremental Value of Non-invasive Testing to Risk Assessment Low Risk <10% Interm Risk 10-20% High Risk >20% Greenland and Gaziano, NEJM, 2003

Incremental Value of Coronary Calcium Scoring to Risk Assessment Greenland et al, JAMA, 2004

Greenland and Gaziano, NEJM, 2003