1. STRESS TESTING Indications, modalities and patient selection Dr. Kalyana Sundaram

2. Stress Testing When? – Indications What type? – Modalities Who? – Patient selection How often? – Frequency How much? – Cost

3. Diagnostic Testing Testing threshold Testing threshold Diagnostic uncertainty Diagnostic uncertainty Treating threshold Treating threshold

4. The 2 x 2 (or 4 x 4) table Test TestDiseasePositiveNegative PresentACSeA/(A+C) AbsentBDSpD/(B+D) PPVA/(A+B)NPVD/(C+D)Acc (A+D)/tot al

5. How “normal” is the normal curve?

6. The norm isn’t always the norm…

7. Which test is more accurate? An exercise treadmill test (Se 80%, Sp 90%) in a population of post-CABG patients with worsening angina? An exercise treadmill test (Se 80%, Sp 90%) in a population of post-CABG patients with worsening angina?or The same test (Se 80%, Sp 90%) in a population of young, healthy women without family history of CAD? The same test (Se 80%, Sp 90%) in a population of young, healthy women without family history of CAD?

8. Statistics can be tricky… 1 P 40% 1000 +- CAD32060 No CAD 80540 2 P 5% 1000 +- CAD4095 No CAD 10855 Accuracy 86% vs. 89.5%

9. If there is one thing you should think about before ordering ANY test… LIKELIHOOD RATIO

12. Stress Testing: Who? Adults with intermediate (10-90%) pre-test probability of CAD AgeSexTypicalAtypicalNon-anginalAsymp 30-39 MaleIntermediate LowVery low FemaleIntermediateVery LowVery low 40-49 MaleHighIntermediate Low FemaleIntermediateLowVery low 50-59 MaleHighIntermediate Low FemaleIntermediate LowVery low 60-69 MaleHighIntermediate Low FemaleHighIntermediate Low

13. Angina Precordial (retro-sternal) chest pain that… Is triggered by physical or emotional stress Is triggered by physical or emotional stress Is relieved by rest or SL NTG Is relieved by rest or SL NTG Lasts for 15-20 minutes each episode Lasts for 15-20 minutes each episode

14. For those of you who like history… First described in 1772 by the English physician William Heberden in 20 patients who suffered from "a painful and most disagreeable sensation in the breast, which seems as if it would extinguish life, if it were to increase or to continue." Such patients, he wrote, "are seized while they are walking (more especially if it be uphill, and soon after eating). But the moment they stand still, all this uneasiness vanishes." First described in 1772 by the English physician William Heberden in 20 patients who suffered from "a painful and most disagreeable sensation in the breast, which seems as if it would extinguish life, if it were to increase or to continue." Such patients, he wrote, "are seized while they are walking (more especially if it be uphill, and soon after eating). But the moment they stand still, all this uneasiness vanishes." Sir William Heberden, 1710-1801

15. Back to contemporary times… Classic anginal features: Is triggered by physical or emotional stress Is triggered by physical or emotional stress Is relieved by rest or SL NTG Is relieved by rest or SL NTG Lasts for 15-20 minutes each episode Lasts for 15-20 minutes each episode 2-3/3: typical angina 1/3: atypical angina 0/3: likely non-cardiac chest pain

16. Importance of typicality Jones et al. Prognostic importance of presenting symptoms in patients undergoing exercise testing for evaluation of known or suspected coronary disease. Am J Med 2004. 560 patients presenting for exercise tolerance testing (treadmill) Prospective follow-up over 5.8 years

17. Stress Testing: Who? Patients with symptoms or prior history of CAD Patients with symptoms or prior history of CAD Initial evaluation with suspected or known CADInitial evaluation with suspected or known CAD Known CAD with change in status (crescendo)Known CAD with change in status (crescendo) Low risk, unstable angina 8-12 hours after presentation free of symptoms (“rule out time”)Low risk, unstable angina 8-12 hours after presentation free of symptoms (“rule out time”) Intermediate risk, unstable angina, 2-3 days free of active ischemiaIntermediate risk, unstable angina, 2-3 days free of active ischemia

18. Stress Testing: Who? Post-MI Post-MI Prognostic assessmentPrognostic assessment Activity prescriptionActivity prescription Evaluation of medical therapyEvaluation of medical therapy Before beginning cardiac rehabilitationBefore beginning cardiac rehabilitation

19. Stress Testing: Who? Special Groups Special Groups WomenWomen Lower sensitivity, similar specificity Lower sensitivity, similar specificity Elderly (>75 years of age)Elderly (>75 years of age) Other evaluated endpoints include chronotropic response, exercise-induced arrhythmias, and assessment of exercise capacity Other evaluated endpoints include chronotropic response, exercise-induced arrhythmias, and assessment of exercise capacity

20. Chronotropic response

21. Stress Testing: Who? Asymptomatic patients Asymptomatic patients Diabetics planning to start exerciseDiabetics planning to start exercise Guide to risk reduction therapy in a patient with multiple risk factors*Guide to risk reduction therapy in a patient with multiple risk factors* Men > 45 and women > 55Men > 45 and women > 55 Starting exercise Starting exercise Impact public safety Impact public safety High risk due to concomitant disease (PVD, CRF) High risk due to concomitant disease (PVD, CRF)

22. Stress Testing: Absolutely Who Not! Acute MI Acute MI High risk unstable angina High risk unstable angina Uncontrolled arrhythmias with symptoms Uncontrolled arrhythmias with symptoms Symptomatic, severe aortic stenosis* Symptomatic, severe aortic stenosis* Uncontrolled, symptomatic heart failure Uncontrolled, symptomatic heart failure Acute PE Acute PE Acute myocarditis or pericarditis Acute myocarditis or pericarditis Acute aortic dissection Acute aortic dissection

23. Stress Testing: Maybe Who Not?* Left main coronary stenosis Left main coronary stenosis Moderate stenotic valvular heart disease Moderate stenotic valvular heart disease Electrolyte abnormalities Electrolyte abnormalities Severe hypertension (SBP > 200, DBP > 110) Severe hypertension (SBP > 200, DBP > 110) Tachy or bradyarrhythmias Tachy or bradyarrhythmias Outflow tract obstruction (HCM) Outflow tract obstruction (HCM) Mental or physical impairment (unsafe) Mental or physical impairment (unsafe) High-degree AV block High-degree AV block

24. Stress Testing: When? Patients with chest pain Patients with chest pain Change in clinical statusChange in clinical status Acute coronary syndromes Acute coronary syndromes Low, intermediate, high risk (H&P, ECG, markers – TIMI risk score)Low, intermediate, high risk (H&P, ECG, markers – TIMI risk score) Low: 8-12 h symptom-freeLow: 8-12 h symptom-free Intermediate: 2-3 days symptom-free*Intermediate: 2-3 days symptom-free* High: consider chemical imaging study versus coronary angiography*High: consider chemical imaging study versus coronary angiography*

25. Stress Testing: When? Post-MI Post-MI Pre-discharge* Pre-discharge* Submaximal (<70% MPHR) Submaximal (<70% MPHR) Early after discharge* (14-21 days)Early after discharge* (14-21 days) Symptom limited (85% MPHR) Symptom limited (85% MPHR) Late after discharge* (3-6 weeks if early test was submaximal)Late after discharge* (3-6 weeks if early test was submaximal) Symptom limited (85% MPHR) Symptom limited (85% MPHR)

26. Stress Testing: When? Before and after revascularization* Before and after revascularization* Demonstration of ischemiaDemonstration of ischemia Evaluation of post-procedure chest painEvaluation of post-procedure chest pain Evaluation of territory at riskEvaluation of territory at risk Evaluation of restenosisEvaluation of restenosis Post-bypass surgery – useful later not earlyPost-bypass surgery – useful later not early

27. Stress Testing: How Often? Change in clinical symptom pattern Change in clinical symptom pattern Prognostication: Prognostication: There is no absolute guaranteeThere is no absolute guarantee Progression of testing modality to higher sensitivity and specificity Progression of testing modality to higher sensitivity and specificity Depends on risk factors, their degree of control and intensity of modification Depends on risk factors, their degree of control and intensity of modification

28. Two Components Each cardiac imaging modality has two components: Each cardiac imaging modality has two components: Stressing agent: treadmill, dobutamine, or adenosineStressing agent: treadmill, dobutamine, or adenosine Imaging agent: EKG, echo, or radionuclide tracer (thallium or technetium)Imaging agent: EKG, echo, or radionuclide tracer (thallium or technetium)

29. Stress Testing: What Type? Exercise modality Exercise modality TreadmillTreadmill Bruce, Modified Bruce, Branching, Naughton… Bruce, Modified Bruce, Branching, Naughton… Bicycle (recumbent)Bicycle (recumbent) Chemical/PharmacologicChemical/Pharmacologic Dipyridamole (Persantine®) Dipyridamole (Persantine®) Adenosine (Adenoscan®) Adenosine (Adenoscan®) Dobutamine Dobutamine

30. The Bruce protocol Developed in 1949 by Robert A. Bruce, considered the “father of exercise physiology”. Developed in 1949 by Robert A. Bruce, considered the “father of exercise physiology”. Published as a standardized protocol in 1963. Published as a standardized protocol in 1963. Remains the gold- standard for detection of myocardial ischemia when risk stratification is necessary. Remains the gold- standard for detection of myocardial ischemia when risk stratification is necessary.

31. Protocol description StageTime (min)km/hrSlope 102.7410% 234.0212% 365.4714% 496.7616% 5128.0518% 6158.8520% 7189.6522% 82110.4624% 92411.2626% 102712.0728%

32. Stress Testing: What Type? Non-imaging versus imaging Non-imaging versus imaging Consideration of imagingConsideration of imaging Resting ST depression (<1 mm) Resting ST depression (<1 mm) Digoxin Digoxin LVH LVH Women Women

33. Stress Testing: What Type? Non-imaging vs. Imaging Non-imaging vs. Imaging Require imagingRequire imaging Intermediate risk non-imaging exercise test Intermediate risk non-imaging exercise test Pre-excitation Pre-excitation Paced rhythm Paced rhythm LBBB or QRS > 120 ms LBBB or QRS > 120 ms > 1 mm resting ST depression > 1 mm resting ST depression Vessel localization Vessel localization Improved prognostic information Improved prognostic information

34. Sensitivity and Specificity SensitivitySpecificity Exercise EKG 68%77% Stress Echo 76%88% Nuclear Imaging 79-92%73-88%

35. Normal Myocardial Perfusion

36. Myocardial Ischemia

37. Myocardial Infarction

38. Stress Testing: What Type? Choice of imaging modality is multi-factorial Choice of imaging modality is multi-factorial Body habitus – attenuation, COPD, etc.Body habitus – attenuation, COPD, etc. Local expertiseLocal expertise ClaustrophobiaClaustrophobia Understanding of sensitivity and specificityUnderstanding of sensitivity and specificity Coincident information:Coincident information: Ejection fraction Ejection fraction Valvular structure Valvular structure Exercise capacity Exercise capacity

39. Stressing Agents StressorProCon TreadmillPhysiologic, simple, less expensive, good for patient who can walk DobutamineNo exercise needed Caution in patients with arrhythmias Adenosine or dipyridamole (used with nuclear) No exercise needed; uncomfortable sensation of “heart stoppage” Adenosine may induce bronchospasm – caution in COPD and asthma!

40. Imaging Agents StressorProCon EKGSimple, less expensive Less information. May not be able to localize the lesion. Can not use if there are baseline EKG abnormalities i.e. LBBB with ST changes EchocardiogramGood if patient has pre-existing EKG abnormalities. More info than EKG. Less expensive than nuclear. Operator dependent to some extent. May have poor windows due to body habitus. Pre-existing wall motion abnormalities may make interpretation more challenging. Thallium or technetiumLocalizes ischemia and infarcted tissue. Expensive

41. Sensitivity and Specificity SensitivitySpecificity Exercise EKG 68%77% Stress Echo 76%88% Nuclear Imaging 79-92%73-88%

43. Exercise Testing: Contraindications Unstable Angina Unstable Angina Decompensated CHF Decompensated CHF Uncontrolled hypertension (blood pressure > 200/115 mmHg) Uncontrolled hypertension (blood pressure > 200/115 mmHg) Acute myocardial infarction within last 2 to 3 days Acute myocardial infarction within last 2 to 3 days Severe pulmonary hypertension Severe pulmonary hypertension Relative contraindications (AS, HCM…) Relative contraindications (AS, HCM…)

44. Last but not least… cost TEST COST - done Hospital Office ETT $ 637 $ 239 STRESS ECHO $ 1600 $657 NUCLEARSCAN $ 3000- $4400 $937

45. Case Question A 60yo man is evaluated for chest pain of 4 months’ duration. He describes the pain as sharp, located in the left chest, with no radiation or associated symptoms, that occurred with walking one to two blocks and resolves with rest. Occasionally, the pain improves with continued walking or occurs during the evening hours. He has hypertension. Family history does not include cardiovascular disease in any first- degree relatives. His only medication is amlodipine. On physical examination, he is afebrile, blood pressure is 130/80mHg, pulse rate is 72/min, and respiration rate is 12/min. BMI is 28. No carotid bruits are present, and a normal S1 and S2 with no murmurs are heard. Lung fields are clear, and distal pulses are normal. EKG showed normal sinus rhythm.

46. Case Question Which of the following is the most appropriate diagnostic test to perform next? Which of the following is the most appropriate diagnostic test to perform next? a.Adenosine nuclear perfusion stress test. b.Coronary angiography c.Echocardiography d.Exercise treadmill

47. Take Home Points Stress testing is indicated for patients with intermediate pre-test probability Stress testing is indicated for patients with intermediate pre-test probability Each stress test has two components: an imaging modality and stress modality Each stress test has two components: an imaging modality and stress modality When determining which stress test to order, keep in mind their ability to exercise, whether any contraindications are present, cost by LOCATION, body weight and specificity and sensitivity When determining which stress test to order, keep in mind their ability to exercise, whether any contraindications are present, cost by LOCATION, body weight and specificity and sensitivity