Clinical Evaluation of CAD Diagnostic Testing for Ischaemia and Chest Pain Evaluation

1. Continuing Medical Implementation .. .bridging the care gap Clinical Evaluation of CAD Diagnostic Testing for Ischaemia Clinical Evaluation of CAD Diagnostic Testing for Ischaemia Joel Niznick MD FRCPC

2. Continuing Medical Implementation .. .bridging the care gap Chest Pain Evaluation Chest Pain Evaluation 1. Approach to diagnosis of CAD 2. Classification of chest pain 3. Pre-test likelihood CAD 4. Algorithm for chest pain evaluation in women 5. Indications for stress testing 6. High risk indicators- stress testing 7. Indications for myocardial perfusion imaging (MPI) 8. High risk indicators-MPI 9. Coronary Distribution- Polar Map 10. Comparing Perfusion Agents 11. Sensitivity and specificity of cardiac testing

3. Continuing Medical Implementation .. .bridging the care gap Approach to diagnosis CAD -1- Approach to diagnosis CAD -1- Confirm or deny presence of CAD with TMT High false positive rate in pre-menopausal females (up to 50%) or low pre-test likelihood CAD Exclude false positives with perfusion imaging Assess extent of CAD with perfusion imaging

4. Continuing Medical Implementation .. .bridging the care gap Approach to diagnosis CAD -2- Approach to diagnosis CAD -2- Assess prognosis combining extent of CAD with severity of LV dysfunction:echo/MUGA Cardiac Cath:adverse prognostic indicators; refractory symptoms;3VCAD/2VCAD(prox.LAD) plus LV dysfunction (echo or MUGA),AP post MI

5. Continuing Medical Implementation .. .bridging the care gap Classification of Chest Pain Classification of Chest Pain Typical angina 1. Steady retrosternal component 2. Provoked by exertion or stress 3. Relieved by rest or NTG Atypical angina 2 of 3 criteria Non-anginal chest pain 1 of 3 criteria

6. Continuing Medical Implementation .. .bridging the care gap Prevalence of CAD (%) in Symptomatic Patients According to Age and Sex Prevalence of CAD (%) in Symptomatic Patients According to Age and Sex Typical angina Atypical angina Non anginal chest pain AGE Men Women Men Women Men Women 30-39 69.7 25.8 21.8 4.2 5.2 0.8 40-49 87.3 55.2 46.1 13.3 14.1 2.8 50-59 92.0 79.4 58.9 32.4 21.5 8.4 60-69 94.3 90.6 90.6 54.6 28.1 18.6 3 of 3 criteria 2 of 3 criteria 1 of 3 criteria 1) Retrosternal discomfort.2) Provoked by exercise or stress.3) Relieved by rest or NTG

7. Continuing Medical Implementation .. .bridging the care gap Indications for Stress Testing Indications for Stress Testing Objective confirmation of ischaemia Assessing extent of ischaemia Documenting exercise capacity Functional assessment of known CAD Determining risk and prognosis Determining need for angiography High risk cut points Assessing response to treatment

8. Continuing Medical Implementation .. .bridging the care gap Contraindications for stress testing Contraindications for stress testing Acute myocardial infarction (within two days) Unstable angina pectoris Uncontrolled arrhythmias causing symptoms of hemodynamic compromise Symptomatic severe aortic stenosis Uncontrolled symptomatic heart failure Active endocarditis or acute myocarditis or pericarditis Acute aortic dissection Acute pulmonary or systemic embolism Acute noncardiac disorders that may affect exercise performance or may be aggravated by exercise

9. Continuing Medical Implementation .. .bridging the care gap Stress Testing Options Stress Testing Options Exercise stress alone (usually Bruce protocol) Exercise stress with nuclear myocardial perfusion imaging (MPI) Pharmacologic stress nuclear myocardial perfusion imaging (MPI) Exercise stress echo Pharmacologic stress echo

10. Continuing Medical Implementation .. .bridging the care gap Sensitivity and Specificity of Non-invasive Tests for the Diagnosis of CAD* Sensitivity and Specificity of Non-invasive Tests for the Diagnosis of CAD* Diagnostic Test Sensitivity % (range) Specificity % (range) # Studies # Patients TMT 68 77 132 24,027 Planar MPI 79 (70-94) 73 (43-97) 6 510 SPECT 88 (73-98) 77 (53-96) 8 628 Stress echo 76 (40-100) 88 (80-95) 10 1174 * NEJM Vol. 344, No. 24 June 14, 2001

11. Continuing Medical Implementation .. .bridging the care gap Exercise stress testing Exercise stress testing Treadmill or bicycle ergometer Protocols vary - symptom limited Bruce most popular 8 stages Incline and speed increment every 3 minutes Target 85-100% maximum age predicted HR Achieve at least 6 METS for diagnostic accuracy

12. ECG Patterns Indicative of Myocardial Ischaemia ECG Patterns Not Indicative of Myocardial Ischaemia

13. Continuing Medical Implementation .. .bridging the care gap High Risk Indicators Exercise Stress Testing High Risk Indicators Exercise Stress Testing Early positive-stage I: Mortality >5%/year Strongly positive > 2.5 mm ST depression ST elevation > 1 mm in leads without Q waves Fall in SBP >10 mm HG Early onset ventricular arrhythmia's Chronotropic incompetence Ex HR <120/min not due to drugs Prolonged Ischaemic changes in recovery > 2mm lasting > 6 minutes in multiple leads

14. Continuing Medical Implementation .. .bridging the care gap Indications for Myocardial Perfusion Imaging (Exercise or Pharmacologic Stress) Indications for Myocardial Perfusion Imaging (Exercise or Pharmacologic Stress) Suspected false +ve or-ve TMT Resting ST changes LBBB,RBBB,LVH, digitalis,pre-excitation or pacemaker Women with +ve TMT and low or intermediate probability CAD Inability to exercise Prognosis of known CAD Detecting post PTCA or CABG ischaemia Assessing myocardial viability Risk evaluation in non- cardiac surgery patients Assessment functional significance of documented coronary stenosis

15. Continuing Medical Implementation .. .bridging the care gap Myocardial Perfusion Imaging Myocardial Perfusion Imaging Exercise Stress Treadmill Bicycle ergometer Pharmacologic Stress Persantine (dipyridamole) Adenosine Dobutamine Isotopes Thallium 201 Technesium 99m Sestamibi MIBI (Cardiolyte) Tetrofosmin (Myoview) PET Rubidium 82 (flow agent) FDG (viability)

16. Continuing Medical Implementation .. .bridging the care gap Persantine (dipyridamole) Persantine (dipyridamole) Coronary vasodilator With coronary stenosis differential dilatation results in differential flow hence differential uptake of isotope Side effects Chest pain 20% Dizziness12% Headache 12% Dyspnea & flushing 5%

17. Continuing Medical Implementation .. .bridging the care gap Persantine (dipyridamole) Persantine (dipyridamole) 4 minute infusion Maximum vasodilatation at 3 minutes post infusion Circulatory effects peak 7-12 minutes post infusion Isotope injected at 7 minutes Antidote aminophylline given for side effects False negatives with recent caffeine intake

18. Continuing Medical Implementation .. .bridging the care gap Persantine (dipyridamole) contra-indications Persantine (dipyridamole) contra-indications Recent MI within 72 hours Unstable angina Severe lung disease or asthma Heart failure/severe systolic dysfunction 2 nd or 3 rd degree heart block Resting hypotension

19. Continuing Medical Implementation .. .bridging the care gap Comparing Perfusion Agents Comparing Perfusion Agents Thallium-201 K analogue uptake proportional to blood flow washes out slowly from myocardium-redistribution phase defect normalizes = ischaemia defect unchanged = scar Tl lung uptake- indicates ischaemic LV dysfunction ischaemic LV dilatation on post exercise scan = high risk indicator Tc 99m-Sestamibi uptake proportional to blood flow tissue uptake is fixed true perfusion agent higher energy/better tissue penetration and images tissue fixation permits gated LV Angiogram wall motion ejection fraction

20. Continuing Medical Implementation .. .bridging the care gap Scanning Scanning

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22. Continuing Medical Implementation .. .bridging the care gap High Risk Indicators Myocardial Perfusion Imaging High Risk Indicators Myocardial Perfusion Imaging Increased pulmonary thallium uptake indicating low CO or elevated LVEDP Ischaemic LV dilatation (TID) Multiple perfusion defects Large perfusion defects

23. Continuing Medical Implementation .. .bridging the care gap Coronary Territories Coronary Territories

24. Continuing Medical Implementation .. .bridging the care gap Normal Study Normal Study

25. Continuing Medical Implementation .. .bridging the care gap Reversible LAD Ischaemia Reversible LAD Ischaemia

26. Continuing Medical Implementation .. .bridging the care gap SVD - RCA SVD - RCA

27. Continuing Medical Implementation .. .bridging the care gap SVD-RCA SVD-RCA

28. Continuing Medical Implementation .. .bridging the care gap 2 Vessel Disease LAD & RCA 2 Vessel Disease LAD & RCA

29. Continuing Medical Implementation .. .bridging the care gap 2 Vessel Disease LAD & RCA 2 Vessel Disease LAD & RCA

30. Continuing Medical Implementation .. .bridging the care gap Left Main Disease Left Main Disease

31. Continuing Medical Implementation .. .bridging the care gap Triple Vessel CAD Triple Vessel CAD

32. Continuing Medical Implementation .. .bridging the care gap Global Ischaemia Global Ischaemia

33. Continuing Medical Implementation .. .bridging the care gap Stress Echo Stress Echo Based on principle that ischaemic myocardium becomes hypokinetic Baseline echo to identify regional LV function Exercise or pharmacologic stress Immediate echo to look for changes n wall motion

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36. Continuing Medical Implementation .. .bridging the care gap Stress Echo Stress Echo Indicated to increase sensitivity and specificity of stress testing Pharmacologic stress-usually dobutamine if exercise no possible Indicated in women with intermediate probability CAD, LBBB, LVH, resting ST changes

37. Continuing Medical Implementation .. .bridging the care gap Stress Echo Limitations Stress Echo Limitations Technical quality of images COPD Obesity Timing of acquisition of images Learning curve Operator dependent Reproducibility

38. Continuing Medical Implementation .. .bridging the care gap Dobutamine Stress Echo Dobutamine Stress Echo Positive inotrope and chronotrope Given in incremental doses 5-10 g/kg/min up to 30-40 g/kg/min to simulate exercise Induces ischaemia via Increased HR, BP & contractility Preferred agent if Persantine or aggrenox on board History of asthma or COPD Critical carotid stenosis

39. Continuing Medical Implementation .. .bridging the care gap Dobutamine Echo contraindications Dobutamine Echo contraindications Ventricular arrhythmias Recent myocardial infarction (one to three days) Unstable angina Hemodynamically significant left ventricular outflow tract obstruction Severe aortic stenosis Aortic aneurysm or aortic dissection Systemic hypertension

40. Continuing Medical Implementation .. .bridging the care gap Dobutamine Stress Echo Dobutamine Stress Echo Half life 2 minutes/steady state 10 minutes Atropine needed concurrently to increase HR 36% of time Side effects Palpitation 35% Chest pain 19% Nausea 8% Anxiety 6%

41. Continuing Medical Implementation .. .bridging the care gap Dobutamine Stress Echo Dobutamine Stress Echo Development of new wall motion abnormalities indicates ischaemia Improvement of existing wall motion abnormalities indicates viable myocardium Wall motion may worsen at higher doses with onset of ischaemia

42. Continuing Medical Implementation .. .bridging the care gap Prognostic value of stress echo compared with stress thallium in patients evaluated for CAD Prognostic value of stress echo compared with stress thallium in patients evaluated for CAD 248 patients, age 56 12yrs, simultaneous treadmill stress echo and SPECT thallium studies Follow up 3.7 2.0 years Outcome: death, MI, revascularization, hospitalization for congestive heart failure or unstable angina Olmos, L.I. et al Circulation 1998;98: 2679-86 Olmos, L.I. et al Circulation 1998;98: 2679-86

43. Continuing Medical Implementation .. .bridging the care gap Baseline Characteristics of the Initial Study Population Prognostic value of stress echo compared with stress thallium in patients evaluated for CAD Prognostic value of stress echo compared with stress thallium in patients evaluated for CAD Male 189 76 Chest pain 77 31 History of myocardial infarction 86 35 Diabetes mellitus 43 17 Hypertension 97 39 Hypercholesterolemia 100 40 Smoking 109 44 Obesity 41 17 Prior revascularization 57 23 Age (mean SD) was 56.3 12 y. n=248 Olmos, L.I. et al Circulation 1998;98: 2679-86 n %

44. Continuing Medical Implementation .. .bridging the care gap Prognostic value of stress echo compared with stress thallium in patients evaluated for CAD Prognostic value of stress echo compared with stress thallium in patients evaluated for CAD Event-free survival curves for total cardiac events with use of exercise 201 TI SPECT and exercise echocardiography (echo). WMA indicates wall motion abnormality. Olmos, L.I. et al Circulation 1998;98: 2679-86 Olmos, L.I. et al Circulation 1998;98: 2679-86

45. Continuing Medical Implementation .. .bridging the care gap Comparison of AUCs of 4 models tested in predicting all cardiac events. Clin (clinical parameters) Ex (exercise) Echo (echocardiography) Olmos, L.I. et al Circulation 1998;98: 2679-86 0.85 0.80 0.75 0.70 0.65 0.60 NS P < 0.05 NS Area Under the Curve Clin + Ex ECG Clin + Ex ECG + Rest Echo Clin + Ex ECG + Ex 201 TI Clin + Ex ECG + Ex Echo Prognostic value of stress echo compared with stress thallium in patients evaluated for CAD Prognostic value of stress echo compared with stress thallium in patients evaluated for CAD

46. Continuing Medical Implementation .. .bridging the care gap Prognostic value of stress echo compared with stress thallium in patients evaluated for CAD Prognostic value of stress echo compared with stress thallium in patients evaluated for CAD Conclusions: In patient evaluated for CAD, both exercise echo and SPECT thallium significantly improve the prognostic power of clinical variables including stress ECG and provide comparable prognostic information. The choice of imaging modality in a particular setting depends on several factors including availability, feasibility, expertise and cost considerations. Olmos, L.I. et al Circulation 1998;98: 2679-86

47. Continuing Medical Implementation .. .bridging the care gap Prognostic implications of stress echo in women Prognostic implications of stress echo in women Heupler, J. et al J Am Coll Cardiol 1997;30: 414-20 Heupler, J. et al J Am Coll Cardiol 1997;30: 414-20 Event-free survival of patients with normal results on exercise echocardiograms, ischemia, infarction and ischemia with infarction. Event-free survival according to the presence (+) or absence (-) of ischemia by exercise echocardiography (ExE) or exercise ECG

48. Continuing Medical Implementation .. .bridging the care gap Prognostic implications of stress echo in women Prognostic implications of stress echo in women Heupler, J. et al J Am Coll Cardiol 1997;30: 414-20 Heupler, J. et al J Am Coll Cardiol 1997;30: 414-20 Incremental value of exercise testing (ExECG) and exercise echocardiography (ExE) to clinical data (Clin), illustrated by the global chi-square of sequential Cox models incorporating clinical, exercise testing and echocardiographic data . Global chi-square Global chi-square Subanalysis to examine the incremental value of exercise testing (ExECG) and exercise echocardiography (ExE) to clinical data (Clin) in patients with (white bar) and without (black bars) a history of known CAD .

49. Continuing Medical Implementation .. .bridging the care gap Algorithm for Chest Pain Evaluation in Women Algorithm for Chest Pain Evaluation in Women Low Probability of CAD (< 20 %) Consider no test High likelihood false + result Intermediate Probability of CAD (20-80%) Perfusion imaging or stress echo High Risk Probability of CAD (> 80%) Perfusion imaging or stress echo Consider direct angiography

50. Continuing Medical Implementation .. .bridging the care gap Comparison of Non-invasive Modalities in the Diagnosis of CAD in Women Comparison of Non-invasive Modalities in the Diagnosis of CAD in Women Sensitivity % Specificity % TMT 61 70 Stress Thallium 78 64 SPECT MIBI 86 80 Stress Echo 86 70 Dobutamine Echo 80 (SVD) 91 (MVD) 79 Rubidium PET 91 90 Meta-analysis of exercise testing to detect coronary artery disease in women Kwok Y. Kim C. et al Am J Cardiol 1999. Mar 1:83(5); 660-6.

51. Continuing Medical Implementation .. .bridging the care gap Indications for Coronary Angiography Indications for Coronary Angiography High risk stress test ECG Hemodynamic High risk perfusion study Multiple defects Severe perfusion defects TID Ongoing symptoms Unstable angina Post MI angina CHF Vocational indication Pilots Truck/bus drivers Diagnostic uncertainty

52. Continuing Medical Implementation .. .bridging the care gap See CVD in Women Slideshow See CVD in Women Slideshow