Basics of Stress Testing

Basics of Stress Testing Kelley R. Branch, MD, MS Department of Cardiology University of Washington

Case 50 yo male with HTN, dyslipidemia with chest pain x 1 week. Burning, mid chest, worse with exercise and bending over,?better with rest. PMH: HTN, dyslipidemia, prior gout on chlorthalidone SH: No tobacco, 1-2 glasses wine daily FH: No premature CAD Medications: Losartan 50 mg daily ASA 81 mg daily Allopurinol 100 mg daily

Case 1: Continued Physical Examination: BP 126/80, HR 72, RR 12, Pox 99% Normal pulses, no bruits. Normal chest/cv examination. No edema. JVP normal.

Case 1 Question: Which of the following is correct? A.This patient has typical angina. B.Patient is low risk and no further testing is required. C.ECG is needed to select appropriate testing. D.Order echocardiogram.

Case 1: ECG to plan stress testing Baseline ECG changes decreases exercise ECG specificity Increases false positive rate Baseline ECG changes include: >1 mm ST depression in 2 consecutive leads Left bundle branch block Ventricular pacing (which causes LBBB) Pre-excitation (Wolf-Parkinson-White pattern) CAVEAT: 50% of normal resting ECG have significant CAD LBBB=Left bundle branch block

ECG Interpretation: NSR, HR 75, no significant ST changes

Case 1: Choices 1. Reassurance and send home 2. Invasive cardiac catheterization 3. Cardiology consultation 4. Stress testing

Indications for Stress Testing in Symptomatic Adults Diagnosis of CAD Estimating the probability of obstructive CAD Risk Stratification in known or suspected CAD (Estimating the risk of death or non-fatal MI) Low risk < 1% per year Intermediate risk 1-3% per year High risk > 3% per year CAD coronary artery disease Gibbons RJ, et al. J Am Coll Cardiol. 1997;30:260-311.

Clinical Classification of Chest Pain Typical angina (definite) Substernal chest discomfort with a characteristic quality and duration that is... Provoked by exertion or emotional stress Relieved by rest or nitroglycerin Atypical angina (probable) meets 2 of the of characteristics Noncardiac chest pain meets 1 of the typical angina characteristics J Am Coll Cardiol. 1983;1:574, Letter

Pretest Likelihood of CAD in Symptomatic Patients (Combined Diamond/Forrester and CASS Data) Nonanginal Age Chest Pain Atypical Angina Typical (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 *Each value represents the percent with significant CAD on catheterization

Pretest Likelihood of CAD in Symptomatic Patients (Combined Diamond/Forrester and CASS Data) Nonanginal Age Chest Pain Atypical Angina Typical (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 *Each value represents the percent with significant CAD on catheterization

Case Question 1: Which of the following is a correct statement? A. This patient has typical angina. B. Patient is low risk and no further testing is required. C.ECG is needed to select appropriate testing. D. Order echocardiogram. Why the others are incorrect Atypical angina Intermediate to high risk Murmur III/VI or greater or concerning findings/symptoms

Modern CAD Imaging Catheterization Imaging for Atherosclerosis SPECT/PET Cardiac CT Echocardiography Cardiac MRI

Coronary Flow (ml/m/g) Coronary Stenosis Flow Physiology 5 4 3 2 Maximal Stress Baseline 1 0 0 10 20 30 40 50 60 70 80 90 100 Artery Percent Diameter Stenosis

Effect Manifestations of Ischemia Perfusion Abnormalities Wall Motion Abnormalities ECG Changes Angina, MI, Death Chest Pain Ischemia Electrical Transit Abnormalities Regional Systolic Dysfunction Diastolic Dysfunction Increasing Degree and Duration of Ischemia

Non invasive Cardiac Testing Modalities for Diagnosis and Prognosis Exercise stress without imaging Treadmill, Bicycle Stress Nuclear myocardial perfusion imaging (MPI) with SPECT or PET Exercise Stress, Pharmacologic Stress Stress Echocardiogaphy Exercise Stress, Pharmacologic Stress CT Coronary Angiography Stress MRI MRI - magnetic resonance imaging; CT - computed tomography Higgins JP, Higgins JA. Int J Cardiol. 2007;116:285-299.

Type of Stress Test: Questions to Ask 1. Can patient exercise? If so, EXERCISE! Can achieve 85% maximal predicted heart rate (220 age)? Limitations to exercise (e.g., arthritis, pulmonary disease) to < 5 METS (2 blocks, 2 flights of stairs)? 2. Asthma or reactive airway disease or second degree heart block? Avoid vasodilators 3. Inducible arrhythmia or significant baseline HTN? Avoid dobutamine 4. Least expensive, least invasive for board testing!!

Stress Testing Algorithm No Able to Exercise? (> 5 METS or 2 flights Stairs) Yes Prior coronary revascularization, Digoxin therapy, LBBB, Paced rhythm, WPW, >1 mm ST No Yes Stress : Pharmacologic Imaging : Nuclear, echo Stress : Treadmill Imaging : None Stress : Treadmill Imaging : Nuclear, echo Echo = echocardiogram; LBBB=Left bundle branch block; WPW=preexcitation (Wolf-Parkinson-White)

Selection of the Correct Test Treadmill Low risk, diagnosis/prognosis, localization not important Echocardiography Good windows, localization, cardiac/valve function (bonus), soft tissue issues, experienced interpreters needed Nuclear Most patients, best for prognosis, localization, infarction PET Best for viability, quantifiable, not readily available, not for prime time MRI Interesting, technically complex, quantitation possible

Stress Agents: Comparison Test Diagnosis Prognosis Available Cardiac Fxn Time Required Cost Stress ECG (ETT) + + +++ - 30 min + Stress echo ++ ++ ++ ++ 30 min/ 1.5 hr ++ Stress MPI ++ +++ ++ ++ 2-4 hr +++ CT/CAC ++ ++ + +*/- 15 min ++ PET +++ ++ +/- ++ 1-2 hr ++++

Diagnostic Exercise Measurements ST changes Exercise duration Hemodynamic stability/instability Symptom reproduction

ETT Indicators of Adverse Prognosis <6 METs of exercise Failure to increase SBP to 120 mm Hg Decrease in BP of 10 mm Hg during exercise Downsloping ST segment 2 mm at <6 METs involving 5 leads, persisting 5 min into recovery ST segment elevation Angina at low exercise workloads Sustained (>30 sec) or symptomatic VT MET metabolic equivalent (unit of measurement); VT ventricular tachycardia Morrow K, et al. Ann Intern Med. 1993:118(9):689-695,

Advantages Treadmill ECG Testing Available in most cardiology offices and all hospitals Best stress test with best physiologic information Prognostic Inexpensive Relatively easy to interpret Disadvantages Uses ST changes to measure ischemia (high on ischemia cascade) Worst diagnostic accuracy of all stress tests No localization of ischemia not used with known CAD May not achieve diagnostic study ( heart rate response) No other cardiac information (heart structure, valves)

Sensitivity and Specificity of Treadmill Stress Test for CAD *Compared to observed CAD with cardiac catheterization 80 Ex. ECG 77 75 % 70 68 65 60 Sensitivity* Specificity/Normalcy* Lee TH, et al. N Engl J Med. 2001;344:1840-1845.

Exercise stress test: Key Point Best physiologic testing Good prognostic data Use when possible Worst diagnostic accuracy

Case 1 Exercised 8 minutes, stopped due to fatigue. Questionable chest pain ECG normal Normal hemodynamic response Returns with continued chest pain despite PPI, acetaminophen Refer for stress testing with imaging

To Stress or Not to Stress or when to refer to Cardiology Stress Low or intermediate probability of CAD Atypical or not convincing angina No rest angina Refer Without Stress Classic angina (or anginal equivalent) and/or with high probability of CAD Resting angina (CCS IV) Worrisome symptoms (syncope, CHF, VT)

Stress Testing with Imaging Stress Modalities Exercise Pharmacologic: Vasodilators (dipyridamole, Adenosine, Regadenoson) Nuclear only Dobutamine Nuclear Tracers Tc-99m-based tracers (Tc-99m sestamibi and Tc-99m tetrofosmin) Thallium-201 MIBI - Methoxy-IsoButyl-Isonitrile Beller GA. Adv Intern Med. 1997;42:139-201.

Nuclear Medicine

SPECT Cardiac Imaging Advantages Available in many cardiology offices and all hospitals Localization of in myocardium ischemia Can obtain images in most patients Evaluation of myocardial morphology and EF Large diagnostic, prognostic data basis Disadvantages Radiation from radiotracers Attenuation common in women, obese Relatively low spatial resolution Need area of normal perfusion

Stress Perfusion Imaging RESTING FLOW Coronary artery Radiotracer Radiotracer 75% stenosis Short axis heart image

Stress Perfusion Imaging STRESS FLOW Coronary artery Radiotracer Radiotracer 75% stenosis Flow to path of least resistance Heterogeneity of flow shows ischemia!!! Short axis heart image

100 80 Sensitivity and Specificity of Non-Invasive Tests for CAD *Compared to observed CAD with cardiac catheterization 92 90 Ex. ECG Ex. SPECT TI Ex. SPECT Tc 93 84 77 68 % 60 40 20 0 Sensitivity* Specificity/Normalcy* ECG electrocardiogram; SPECT single-photon emission computed tomography; CAD coronary artery disease. Lee TH, et al. N Engl J Med. 2001;344:1840-1845.

anterior wall apex inferior wall anterior wall septum lateral wall inferior wall Pt:Be.

Patient Preparation NPO 6 hours prior to injection of radiotracer WHY??? No caffeine 24 hrs prior to vasodilator study Hold beta blockers or anti-anginals if attempting to diagnosis ischemia

Sensitivity (%) Effect of Antianginals on MPI 100% 90% 80% 70% * * None Anti-anginals 60% 50% * *p<0.05 p=0.000003 40% Sharir. JACC 1998:31:1540-6 LAD LCx RCA Overall

Case 1 6 min ETT, some CP HR 86 -> 127 BP 135/80 -> 185/72 ECG 1-1.5 mm horiz. ST diffusely

Stress or Dobutamine Echocardiography

Stress Echocardiography Advantages Available in many cardiology offices and all hospitals Allows evaluation of valvular function and myocardial morphology Exercise or dobutamine Prognostic Better sensitivity (lower false positive) than nuclear Disadvantages Operator dependent Image quality suboptimal in significant number of patients Ischemic wall motion abnormalities do not persist after exercise termination

100 80 Sensitivity and Specificity of Non-Invasive Tests for CAD *Compared to observed CAD with cardiac catheterization 92 90 68 81 Ex. ECG Ex. SPECT TI Ex. SPECT Tc 93 Ex. Echo 84 77 87 % 60 40 20 0 Sensitivity* Specificity/Normalcy* ECG electrocardiogram; SPECT single-photon emission computed tomography; CAD coronary artery disease. Lee TH, et al. N Engl J Med. 2001;344:1840-1845.

Selection of Stress SPECT vs. Echo SPECT Baseline wall motion abnormalities Poor acoustic windows (COPD, obese) Irregular heart rate Echocardiogram Young, radiation risk Left bundle branch block Infarct vs. hibernating myocardium Similar diagnosis, prognosis USE WHAT IS BEST IN YOUR AREA

Stress Testing: Prognosis Negative stress imaging = <1% risk of cardiac event per year Higher burden of ischemia = higher risk Generally refer to angiography for moderate to high risk

MRI Stress Stress Perfusion Theoretic benefit with excellent functional images, good perfusion Dobutamine vs. vasodilator Not available in all centers MRI expertise required Rest Perfusion Courtesy of Peter Cawley, MD

Coronary Angiography Invasive coronary angiography (ICA) and cardiac CT

Cardiac CT Advantages: Very rapid (<1 sec for imaging) 3D data set -> manipulating images anytime Highest diagnostic sensitivity Non-invasive Limitations: Visualization if calcium present Iodinated contrast needed Relatively low specificity No measure of ischemia Operator expertise

Cardiac CT

Sensitivity and Specificity of Non- Invasive Tests for CAD 100 80 60 40 20 Key Point: No test is perfect, but some are worse than others Ex. ECG Ex. Echo Ex. SPECT Tl Ex. SPECT Tc PET CT 0 Sensitivity* Specificity/Normalcy* *Compared to observed CAD with cardiac catheterization Adapted from Zaret & Beller, 1999

Coronary angiography Left Coronary Artery Right Coronary Artery

Invasive Coronary angiography Cardiac catheterization Advantages: Imaging gold standard for coronary atherosclerosis Combined diagnosis and possible treatment in single study Widely used Low complication rate, but not zero Limitations: Invasive Bleeding, stroke, MI, dissection possible Iodinated contrast and radiation given Expensive Facilities and operator expertise required No routine measure of ischemia

Catheterization LAD LCx

Survival free of all cause mortality, MI COURAGE: Primary Outcome No Difference for Medical Treatment vs. Revascularization in Myocardial Ischemia 1.0 0.9 0.8 HR 1.05 (0.87-1.27) P = 0.62* 0.7 0.6 Medical Tx PCI + Medical Tx 0.5 0 0 1 2 3 4 5 6 7 Years No. at risk Medical therapy 1138 1017 959 834 638 408 192 30 PCI *Unadjusted 1149 1013 952 833 637 417 200 35 Boden WE et al. N Engl J Med. 2007;356:1503-16.

Angina-free (%) COURAGE: Lower Angina with Revascularization 80 70 PCI + medical therapy Medical therapy P < 0.001 P = 0.02 P=NS 60 50 40 30 20 P=NS 10 0 Baseline 1 year 3 years 5 years Boden WE et al. N Engl J Med. 2007;356:1503-16.

Summary: Stress Testing Low/intermediate risk stress or CT. High risk stress or invasive angiography Exercise stress whenever possible >2 blocks or flights of stairs, 85% maximal predicted heart rate Add imaging with ECG changes, known CAD, pharmacologic stress

Thank You! Kelley Branch, MD, MSc kbranch@u.washington.edu