Exercise Treadmill Testing Prognostication in Coronary Artery Disease Dr. Peter Krampl 11 October 2001

Introduction 300,000 ER visits per year acute non traumatic chest pain Only apx. 25% have clear positive, Unstable coronary disease Angiography Image studies Acute myocardial infarction or negative diagnosis of coronary syndromes

Introduction Current ED Modalities Reviewed in EM Clinics February 2001 History / Physical Mair. Chest. 1995. 110 patients; non traumatic chest pain Using NPV as most used indicator for admission PPV 53% NPV 75% for acute cardiac ischemia

Introduction Current ED Modalities ECG Rovan, American Journal Cardiology. 1989. Multicentre Chest Pain Trial Sensitivity 61% Specificity 90% for ischemia Current ST, Q, LBBB criteria Variable Specific Addition of T wave abnormality Sensitivity increases to 95% Specificity may decreases to 23% Current computer algorithms tend to higher sensitivity

Introduction Current ED Modalities Cardiac Markers Hedges et al. Acad EM. (CK-MB) 1042 patients; CK-MB at presentation and serial investigated Sensitivity 19-31% Specificity 95-96% Hamm et al. NEJM. 1997 (TnT) 776 patients Prospective study looking at prognosis of TnT and TnI and 30 day cardiac event rate Negative values of T and I gave annual event rates of 1.1 and 0.3% respectively Sensitivity 31% Specificity 98%

Introduction Are We Satisfied With Those Numbers? How Do We Further Risk Stratify Coronary Patients? Treadmill Testing Observation Units / Time Radionuclear Imaging +/- Exercise Echocardiography +/- Exercise Angiography

Introduction In ED, old chart or patient notes: What do those mean? I was on treadmill for 8 minutes. A negative treadmill. I did not have pain on the treadmill. What do those mean? Can we use those simple guides to further stratify these patients?

What Use Has The Exercise Stress Test?

Outline Introduction Treadmill Testing Review of Current Literature Indications Procedures Results Notable Studies Exercise Modalities Conclusions Questions

Treadmill Testing: Introduction Froelicher. Hdbk of Exercise Testing. 1996 Goals Diagnosis CAD Prognosis CAD Evaluation of Medical Therapy Evaluation of Exercise Capacity

Treadmill Testing: Indications When to use…. AHA / CPSA guidelines advise to use only up to intermediate pre test probability cases Kuntz et al. Ann Int Med. 1999. Exercise stress test or rest echo most cost effective (mild-mod) Life expectancy Cost Incremental Cost Effectiveness over other modalities For high risk, immediate coronary angio most cost beneficial. Other stress modalities supplement to Exercise Treadmill

Treadmill Testing: Indications Braunwald et al. High / Intermediate / Low Risk / Pretest Probability Guidelines published by AHA 1995. Reviewed by Primary Care Clinics. 2001 Example: Low Risk Chest pain by history classified as “probable not or definitely not angina normal ECG New onset angina 2 months No change in previous 2 months T wave flattening or inversion <1 mm in leads with dominant R waves One risk factor other than diabetes

Treadmill Testing: Indications Majority of tests done on referral basis Advent of chest pain units in United States… Studies by Zalenski. Ann EM. 1997. Low and Intermediate Risk. Safety at 4-12 hours Mikhail. Ann EM. 1997. Intermediate risk. Safety at 12 to 24 hours Lewis. Am J Card. 1994. Low risk. Safety at 1-2 hours Kirk. Ann EM. 1998. Low risk. CP Observation Units have adopted 6 hours as Industry standard for exercise port work up and stabilization

Treadmill Testing: Indications Froelicher / Annals of EM Clear (Class 1) Evaluation of male patients with atypical symptoms Functional capacity testing Evaluation of exercise related dizziness, syncope, palpitations Evaluation of Recurrent exercise induced Arrhythmias

Treadmill Testing: Indications Probable Benefit (Class 2) Evaluation of Women with atypical symptoms Evaluation of Variant Angina All those in Class one with baseline ECG changes other than LBBB Evaluation of patients on digitalis or RBBB

Treadmill Testing: Indications Not Indicated (Class 3) Assymptomatic young men / women with no risk factors and high suspicion non cardiac chest discomfort Evaluation of patients with LBBB Evaluation of Patients with Pre-excitation Syndromes

Treadmill Testing: Indications Contraindications AHA Guidelines Absolute AMI within 3-5 days Unstable angina not stabilized by medical therapy Aortic dissection Endo, Myo, or pericarditis PE Lower Extremity Thrombosis Uncontrolled symptomatic cardiac arrhythmias Severe aortic stenosis Symptomatic severe and terminal heart failure

Treadmill Testing: Indications Contraindications Relative High degree AV block Moderate stenotic valvular disease DBP >200 or DBP > 110 Bradyarrythmias Known left main coronary stenosis Mental / physical incapacity

Treadmill Testing: Indications Complications Brady / Tachyarrythmias AMI / Sudden Death CHF / Shock MSK Trauma / Fatigue / Malaise

Treadmill Testing: Procedures Important Concepts VO2 max : maximum oxygen uptake Amt of O2 transported for cellular metabolism Useful to express in multiples of METS CO X (arteriovenous oxygen difference) METS used to standardize protocols MO2 : myocardial O2 uptake wall tension, thickness, contractility and HR Estimated by double product (HR X BP) Angina usually occurs at the same double product

Treadmill Testing: Procedures Physiology Exercise creates increase CO Four to six fold increase from rest at peak CO increase by increase HR and PB and decreased vagal tone HR affected by Age, sex, motivation, habitus, blood volume, health SBP increases with exercise DBP stays same or slightly decreases Hypotension ominous sign Outflow obstruction, ventricular dysfunction or ischemia

Treadmill Testing: Procedures Equipment Treadmill or cycle ergometer Cycle has major pitfall of rapid fatigue of quadriceps in older patients Most studies use treadmill Handrails, Rest Area Assistant, Supervisor Resuscitation Equipment

Treadmill Testing: Procedures Preparation Fast 3 hours prior / dress appropriately… footwear Medications reviewed by physician prior History and physical prior regarding change in disease CHF; valvular disease; onset of unstable angina; bronchospasm Consent Baseline supine and upright ECG

Treadmill Testing: Procedures Protocols Most diagnostic and prognostic studies based on Bruce protocol Seven phases Change in grade and speed every 3 minutes Correlation with METS Large incremental stages Not correlated for height / weight / stride Ideal protocol lasts 6-12 minutes and adjusts for patients ability Others include Naughton, McHenry, USAF, Blake

Treadmill Testing:Procedures Borg Scale Borg. Sports and Exercise. 1982. Correlation of scale to actual fatigue 6-20 grade scale for exertion 10 grade scale for exertion now adopted 0 – nothing 9 – very strong 10 – very, very strong Continues to be a clinical assessment of fatigue by technician (skilled) and supervisor Mainly used as repetitive assessment tool in rehab

Treadmill Testing: Procedures Measurements ST depression / elevation (60-80 ms; J point changes) ST slope (downsloping worse than horizontal) Duration of changes into recovery Exercise induced arrhythmias Peak HR / BP Total Duration Exertional hypotension Angina Other exercise induced symptoms

Treadmill Testing: Procedures Termination Absolute Drop of SPB > 10 Anginal Pain (other than non-limiting / known pain) CNS symptoms Signs of poor perfusion Serious Arrhythmias (runs of VT > 3; multiform) Technical Difficulties in monitoring Subject Request

Treadmill Testing: Procedures Termination Relative Maintenance of SBP well into protocol Excessive ST / QRS changes Fatigue, SOB, Wheeze, Cramps, Claudication SVT Development of BBB Observation Important !! Case 77 y.o. male; level one indications; no contraindications; stable angina Maintenance of SBP into Phase 2

Treadmill Testing: Results Diagnostic Exercise Treadmill (ST response only) Sens 66% Spec 84% Froelicher et al. Exercise. 1993. Sens 70% Spec 75% Gianrossi. Meta-analysis. Circulation. 1989. Using Bayes rules of pretest probability, these numbers may only be applied to intermediate cases at best. Original Duke University Investigators showed repeated studies of poor specificity and positive predictive value

Treadmill Testing: Results Diagnostic Lehmann and Froelicher. Veteran’s Study Group. QUEXTA. Ann Int Med. 1998. 814 patients 400 selected for decreased work-up bias Only 40% Stress test ‘positive’ ST changes correlated to > minimal luminal CAD Overall sensitivity 45% specificity 85%

Treadmill Testing: Results Prognostic Giagnoni. NEJM. 1983 Prospective following of 135 men with ST changes vs. 379 controls Angina, MI, sudden death endpoints 5.55 percent risk increase Suggested that ECG positive ST changes should be independent coronary risk factor

Treadmill Testing: Results Prognostic Mark et al. Duke University. Ann Int Med 1987; Validation Mark et al. NEJM. 1991. Developed score based on 613 patients (1983-85) Validated on further 1420 patients Simple score to prognosticate patients Associated score > 5 with annual mortality of 0.25 % outpatients 0.6 % inpatients

Treadmill Testing: Results Prognostic Duke Score Time in minutes ST depression in mm Type of pain 0 - none 1 – typical anginal pain limited by time / fatigue / other 2 – limiting anginal pain

Treadmill Testing: Results Duke Score = Time(m) – 4X Angina – 5X depression(mm) Score: 5 & above low risk 4 to –9 intermediate risk -10 & below high risk

Treadmill Testing: Results Kowk et al. JAMA. 1999. Revisited Duke Score 2405 patients 939 had ST segment changes on stress test Found 97 % seven year survival based on score Duke > 5 These studies have solidified the prognostic benefits of the treadmill test

Treadmill Testing: Results Duke score Low Risk Less than 1% per year acute coronary syndrome Optimize Medical Rx; reassess in one year Intermediate Risk 1 to 5 % per year Optimize Medical Rx; nuclear studies non-urgent High Risk Greater than 5 % per year Urgent referral for further risk stratification

Treadmill Testing: Results Other prognostic indices: Morrow & Froelicher. Ann IM. 1993. Veteran’s Score Exercise duration ST depression Rate of change of systolic BP during exercise History of CHF, digoxin use Low risk groups stratified with 2% annual mortality

Treadmill Testing: Results Exercise Capacity AHA Guidelines Carliner et al. Am J Card. 1985 Reasonable to Use exercise testing for Surgical patients recovering from Congenital repair Valvular replacement Cardiac transplant CHF DM CRF Chronic Lung Disease No exercise induced symptoms

Treadmill Testing: Results Exercise Capacity and Prognostication Lauer and Fletcher. Circulation. 1996. 1575 men; mean age 43 Failure to achieve 85 % of age predicted maximum heart rate associated with increase in death of 1.84 Extrapolation techniques used

Treadmill Testing: Results AHA Guidelines Evaluation of Medical Therapy Look for improvement of exercise capacity to previous before angina or ST depression Evaluation of Valvular Disease Strict guideline for evaluation of AS Evaluation of Dysrrythmias PVC, Sick sinus Syndrome Pre-operative Anesthetists 2nd largest user of stress test for evaluation of patient for non cardiac surgery

Notable Studies Exercise Hypotension Dubach et al. Circulation. 1989 Looking at SBP drop with exercise Looked at 0, 10, 20 drop of SBP Drop of 20 associated with increased PPV of at least 50% Left Main or Triple Vessel Disease

Notable Studies Variables Prakash et al. Am Heart J. 2001 3974 men Kaplan-Meier regression Four variables predict mortality within 5 year Rate of change of rate-pressure product Age > 65 Maximum MET <5 LVH on ECG

Notable Studies METS Ramamurthy et al. Chest. 1999. Found that sensitivity increases if MET >7 Also found that METS achieved may be a stronger variable than rate-pressure product High heart rate at low MET (<5) level carries adverse prognosis

Notable Studies Risk Factors Am J Cardiol. MRFIT. 1985. Multiple Risk Factor Intervention Trial 12,866 participants Those with ST changes on Stress Treadmill benefit to greater degree with risk factor modification than controls.

Notable Studies Women Large number of false positives Mitral valve prolapse; Higher incidence atypical chest pain Hormonal, esp. estrogen mimickery of digoxin Ventilation Responses and Metabolic Alkalosis Curzen. Heart. 1998. 205 women Compared with coronary angiography 42 false positives & 31 false negatives (36 % of total) Increase false positives correlated with Increasing age to 52 Increasing coronary risks to 3

Notable Studies Early Stress Testing Polanczyk. Am J Card. 1998. 276 low risk patients Stress test within 48 hours Similar prognostication numbers 0.5 % event rate Additional variables over 6 months 15% less ED visits 30% fewer admission

Exercise Modalities Stress Echocardiography Evaluate rest / stress changes in wall motion. Dobutamine given to stimulate beta-1 Advantages: Readily available; little equipment; transportable Disadvantages: poor images in up to 10%; user dependant; hard in presence of previous abnormalities

Exercise Modalities Thallium 201 Older agent; Replaces potassium in cells Advantages Able to calculate lung heart ratios Disadvantages Immediate imaging Poor in obese patients and large breasted women Maddahi. Am J Coll Card. 1989 Increases sensitivity from 60-70% of treadmill test to 90% overall with addition of perfusion studies but 70% with single vessel disease

Exercise Modalities Technetium-99m sestamibi Deposited into mitochondria Advantages Longer half life Better images Improved estimates of ejection fraction Disadvantage Poor extraction from blood at high blood flow Hachamovitch et al. Circulation. 1996. 834 patients; treadmill, Tc-99m and catheterization 78% of the listed 0.6% mortality from Duke Low Treadmill prognostication caught as severe perfusion scans.

Exercise Modalities Two schools of thought: EM Clinics Feb 2001 “as useful as exercise testing is, it has the limitations of suboptimal sensitivity and specificity…. Imaging is a necessity, not an optional component of stress testing” vs. “exercise testing alone is a useful first step.” Froelicher. Primary Care. 2001. Quotes George Bernard Shaw “the doctor does the test he is paid the most for” to stress our need for continued evaluation of present modalities

Conclusions Prognosis Common Sense Appropriate population in step wise work-up Common Sense 55 y.o male; 6 minutes; no angina; no ST changes; no change in systolic BP…. In helping to risk stratify patients after initial (ED) work-up, do exercise treadmills meet our need? Set indications & structure Understand what the test does and doesn’t tell us Calgary / Rural Centres / Emergency Departments Ongoing Studies…

Resources Staff, Division of Nuclear Medicine, FMC Dr. Stone, C-Plus Clinic Froelicher. Handbook of Exercise Testing. 1996. Reviews (individual studies plus) Primary Care Clinics. 2001. EM Clinics. 1998, 2001. Froelicher et al. Chest. 1999 (Pitfalls) ACC / AHA Cardiology Guidelines. 1995. Updated with review 1997. CPSA Guidelines. 2000.