STRESS ECG AND STRESS ECHOCARDIOGRAPHY Giuseppe Biondi Zoccai Division of Cardiology, University of Turin, Turin, Italy Meta-analysis and Evidence-based medicine Training in Cardiology (METCARDIO), Ospedaletti, Italy

LEARNING GOALS Scope of the problem Stress ECG Stress echocardiography Reconciling the evidence

LEARNING GOALS Scope of the problem Stress ECG Stress echocardiography Reconciling the evidence

FINDING AN APPROPRIATE DIAGNOSTIC LEVEL

FINDING AN APPROPRIATE PROGNOSTIC LEVEL

DIAGNOSTIC AND PROGNOSTIC WORK-UP OF SUSPECTED CORONARY HEART DISEASE Clinical history Physical examination Resting ECG Resting echocardiography Stress ECG Stress echocardiography Stress nuclear scan Coronary CT Coronary angiography ….

EFFECTIVE RADIATION DOSES Picano, Am J Med 2003

CORONARY STEAL PHENOMENON Picano, Circ 1998

CORONARY STEAL PHENOMENON Picano, Circ 1998

THREE STATES OF THE SODIUM CHANNEL AND THE NORMAL SODIUM CURRENT (INa) Late INA Slides from CVT CARE Meeting in Miami 4/20/2017 THREE STATES OF THE SODIUM CHANNEL AND THE NORMAL SODIUM CURRENT (INa) Sodium Current Late Na+ Na+ Na+ Peak Resting Closed Activated Inactivated out Na+ Na+ in [Na] 140 mM Na+ Na+ ~ 10mM Na+ Na+ Ca++ Ca++ in Ca++ Ca++ Na+ Ca++ Ca++ out Na+/Ca++ Exchanger Na+ Ca++ Confidential, Please Do Not Copy and/or Distribute

ISCHEMIA INDUCED EFFECTS ON LATE INa AND INTRACELLULAR CALCIUM Excess Calcium: Electrical instability Contractile dysfunction ECG changes Sodium Current Late Na+ Impaired Inactivation Peak Na+ Na+ out Na+ Na+ Na+ Na+ Na+ Ca++ in Na+ Na+ Na+ Na+ Ca++ Ca++ Ca++ Ca++ Ca++ Ca++ Ca++ in Ca++ Ca++ Ca++ Na+ Ca++ Ca++ Ca++ Ca++ out Na+/Ca++ Exchanger Na+ Ca++

THE ISCHEMIC CASCADE

LEARNING GOALS Scope of the problem Stress ECG Stress echocardiography Reconciling the evidence

TREADMILL STRESS TEST

KEY ACCESSORY

EQUIPMENT FOR STRESS TESTING Treadmill or bicycle or steps ECG machine Blood pressure cuff Computer is a ‘nice to have’ ACLS certification Defibrillation/intubation cart Exit strategy Good help* (it takes two to test)

PROTOCOLS

TYPICAL BRUCE OR RAMP STRESS WORK WORK TIME TIME

WHY USE A BIKE ERGOMETER? 1. Accurate measurement of POWER. 2. Ramping protocols allow for assessment of physiologic function across all work levels. 3. Independent of patient’s weight. 4. Less danger of fall and injury to patient. 5. Easier to take accurate B/P at high work rates. 6. Patient can stop at anytime. 7. Holding handle bars does not effect test (Holding treadmill handrails can significantly effect results). 8. Fits into smaller space and is portable. 9. Patients with knee or hip problems tend to perform better and report being more comfortable on the bike.

WHY USE A BIKE ERGOMETER? 10. Bike ramp protocols are designed to last 6-10 minutes, resulting in less fatigue (yet peak work is maximized). 11. HR, Work, and VO2 (Cardiac Output) are linearly related. Bike ramp protocols produce linear increases in Work, thereby mimicking the expected physiologic response in health and disease. 12. Determination of the Anaerobic Threshold (AT) by the most popular methods (V-slope and VE/VO2 nadir) were developed and proven through the use of bike ramp protocols. To use another method means to lose AT detection accuracy. 13. Bike ramp protocols are used by many of the leading clinical and research cardiopulmonary exercise testing labs (UCLA, Duke, Mayo, Stanford, Bowman-Gray, Johns Hopkins, UAB, Temple to name a few). Recently, treadmills capable of performing ramp protocols have been developed.

MY VIEW: TREADMILL IS BEST

INDICATIONS TO STRESS TEST Diagnosis of coronary artery disease Risk-stratification of coronary artery disease Risk-stratification in cardiac valve disease Appraisal of rate response Appraisal of pressure response to stress Appraisal of functional capacity

Exercise duration/tolerance Reproducibility of symptoms with activity INFORMATION OBTAINED FROM EXERCISE STRESS BUT NOT AVAILABLE WITH PHARMACOLOGICAL TEST Exercise duration/tolerance Reproducibility of symptoms with activity Heart rate response to exercise Blood Pressure response Detection of stress induced arrhythmias Assess control of angina with medical therapy Prognosis

KEY ASPECTS Exercise duration and work-load (minutes, METs, Watts) Maximum blood pressure Maximum heart rate (given that predicted for age) Rate-pressure product Baseline ECG ST-segment changes T-wave changes Q waves Duke treadmill score Heart rate recovery

ABNORMAL RESPONSE TO STRESS TESTING Heart rate fails to rise above 120 or unable to attain target heart rate of 85% of max Blood pressure shows a drop in systolic Patient physically unable to complete test Marked hypertension, >260/115 Chest Pain and/or unusual shortness of breath

NORMAL RESPONSE OF ECG TO STRESS TESTING ECG Changes QRS complex decreases in size J point depresses, resulting in up sloping of ST segment ST segment returns to baseline by 80 milliseconds PR segment may down slope – thus baseline is defined as PQ junction R amplitude may decrease at rates that go above 130 T wave decreases

ABNORMAL RESPONSE OF ECG TO STRESS TESTING ECG Changes Horizontal or down sloping ST segments ST segment depressed or elevated ST segment does not return to baseline by 80 milliseconds U or T wave inversion Dysrhythmias – rate dependent blocks above first degree, WPW appears, Atrial fib/flutter, multiform and/or increasing PVC’s, V-tach occurs

ECG CHANGES

ECG CHANGES

RISK

CRITERIA DIAGNOSTIC FOR ISCHEMIA Horizontal or down sloping ST segment with depression of 1 or greater mm. Horizontal, up or down sloping ST segment with elevation of 1 or greater mm. Up sloping ST depression greater than 1.5 mm at J+80 msec.

CRITERIA DIAGNOSTIC FOR ISCHEMIA Horizontal or down sloping ST segment with depression of 1 or greater mm. Horizontal, up or down sloping ST segment with elevation of 1 or greater mm. Up sloping ST depression greater than 1.5 mm at J+80 msec.

CRITERIA SUGGESTIVE FOR ISCHEMIA Horizontal or down sloping ST segment with depression greater than 0.5mm but <1 mm. Up sloping ST depression between 0.7 and 1.5mm at J+80 msec. Chest pain or fall in Blood pressure or persistent HTN in recovery or new S3 or murmur at peak exercise. (<1 mm)

SYMPTOM-SIGN LIMITED TESTING ENDPOINTS – WHEN TO STOP! Dyspnea, fatigue, chest pain Systolic blood pressure drop ECG--ST changes, arrhythmias Physician Assessment Borg Scale (17 or greater)

PREDICTED MAXIMUM HEART RATE

WHAT IS A MET? Metabolic Equivalent Term 1 MET = "Basal" aerobic oxygen consumption to stay alive = 3.5 ml O2 /Kg/min Actually differs with thyroid status, post exercise, obesity, disease states But by convention just divide ml O2/Kg/min by 3.5

MAJOR DETERMINANTS OF MYOCARDIAL OXYGEN CONSUMPTION Picano, Circ 1998

PROGNOSTIC ROLE OF METs Myers et al, New Engl J Med 2002

PREDICTING CARDIAC DEATH Marcus et al, Chest 1995

DUKE TREADMILL SCORE

BAYES THEOREM If P(B) ≠ ), then P(A/B) = “ P(B/A)P(A) “ P(B/A)P(A) + P(B/not A)P (not A)

CONTINUOUS OF RISK

TYPICAL REPORT Treadmill stress test stopped at the end of the 3rd standard Bruce stage for fatigue (max BP 200/100 mm Hg, max HR 140 bpm, RPP 28,000). No symptoms. No arrhythmias. No abnormalities in the baseline ECG. In the 2nd stage development of ST depression, which becomes diagnostic in the 3rd stage (max 1.5 mm in V5 at the peak), with quick recovery after the stress. Duke treadmill score: 1 (<-11 high risk; >4 low risk). Heart rate recovery: 10 (valore di riferimento >12). Positive stress test for myocardial ischemia at mid-to-high work-load.

GUIDELINES Gibbons et al, Circ 2002

GUIDELINES: RECOMMENDATIONS Gibbons et al, Circ 2002

GUIDELINES: RECOMMENDATIONS Gibbons et al, Circ 2002

STRESS EKG IS NOT A SLAM DUNK 5/10,000 result in serious cardiovascular event 1/10,000 result in death Results are based on Bayes Theorem Requires proper selection, preparation, and execution Not the GOLD standard

LEARNING GOALS Scope of the problem Stress ECG Stress echocardiography Reconciling the evidence

STRESS ECHOCARDIOGRAPHY

BASIC PRINCIPLE OF STRESS ECHO

BASIC PRINCIPLE OF STRESS ECHO

WALL MOTION RESPONSES Sicari et al, Eur Heart J 2009

CARDIAC SEGMENTS

WALL SEGMENTS AND CORONARY DISTRIBUTION

CURRENT STRESS PROTOCOLS ECG ECHO NUCLEAR Exercise: Tread Post-Tread Tread Bicycle Bicycle Pharmacologic: Catecholamines: Dobutamine Dobutamine Vasodilators: Dipyridamole Dipyridamole Dipyridamole Adenosine Adenosine Vasospastic: Ergonovine Ergonovine Adjuncts: Atropine Handgrip

INDICATIONS TO STRESS ECHOCARDIOGRAPHY Diagnosis of coronary artery disease Risk-stratification of coronary artery disease Risk-stratification in cardiac valve disease Appraisal of myocardial viability Patients unable to ambulate

PREPARATION Avoid smoking Avoid food/beverages Take all medications unless instructed otherwise Wear comfortable clothes and shoes

KEY PHARMACOLOGICAL TESTS Picano, Circ 1998

DOBUTAMINE PROTOCOL Sicari et al, Eur Heart J 2009

DIPYRIDAMOLE PROTOCOL Sicari et al, Eur Heart J 2009

FURTHER APPLICATIONS Sicari et al, Eur Heart J 2009

LEARNING GOALS Scope of the problem Stress ECG Stress echocardiography Reconciling the evidence

PATIENTS APPROPRIATE FOR ROUTINE ECG STRESS TEST WITHOUT IMAGING Patient can exercise for 6 or more minutes Normal baseline ECG No history of diabetes No history of coronary revascularization No history of myocardial infarction

ABSOLUTE CONTRAINDICATIONS Within 24 hours of troponin positive ACS Within 7 days for high dose DSE after STEMI Left ventricular failure with symptoms at rest (in tertiary centres viability may be assessed using low dose dobutamine stress). Recent history (within the last week) of life threatening arrhythmias. Severe dynamic or fixed left ventricular outflow tract obstruction although low dose DSE may be useful. BP >220/120 Recent pulmonary embolism or infarction. Thrombophlebitis or active deep vein thrombosis. Known hypokalaemia (particularly for Dobutamine stress) Active endocarditis, myocarditis, or pericarditis.

POSSIBLE CONTRAINDICATIONS TO STRESS TESTING BASED ON RESTING ECG ST-segment changes 1 mm or greater, either depression or elevation Ventricular strain patterns or hypertrophy T-wave inversions Left bundle branch block Right bundle branch block, if significant Prolonged QT interval

ABSOLUTE CONTRAINDICATIONS TO DOBUTAMINE STRESS ECHO Suspected or known severe bronchospasm 2nd or 3rd degree AV block without pacemaker Sick sinus syndrome without pacemaker BP <90mmHg systolic Xanthines taken in the last 12 hours, or dipyridamole use in the last 24 hours

FIRST THINGS FIRST: DIAGNOSTIC PERFORMACE OF DIFFERENT TESTS

Heijenbrok-Kal et al, Am Heart J 2007 CHOOSING YOUR TEST Heijenbrok-Kal et al, Am Heart J 2007

CHOOSING YOUR TEST Froelicher et al, Chest 1999

CARDIAC STRESS IMAGING Picano, Am J Med 2003

ADVANTAGES OF STRESS ECHOCARDIOGRAPHY COMPARED TO NUCLEAR STRESS TESTING Higher Specificity Visualization of cardiac valves Evaluate for presence of pericardial effusion Ability to measure RV Systolic Pressure More accurate assessment of LV ejection fraction Doppler interrogation to determine Diastolic Function Lower Cost Lack of Radiation Exposure

TAKE HOME MESSAGES Stress testing, by either stress ECG, stress nuclear scan, dipyrididamol/dobutamine nuclear scan, stress echocardiography, dipyrididamol/dobutamine echocardiography, is crucial in the diagnostic work-up of patients with suspected coronary heart disease These tests are also useful in the prognostic work-up of patients with established coronary heart disease Given financial and logistic constraints, stress ECG should be performed in most suitable subjects as 1st line test, followed/substituted by imaging tests in all the other cases

Thank you for your attention For any correspondence: gbiondizoccai@gmail.com For these and further slides on these topics feel free to visit the metcardio.org website: http://www.metcardio.org/slides.html