M.W. Luong, MD, FRCPC, M. Ignaszewski, MD, C.M. Taylor, MD, FRCPC

Stress testing: A contribution from Dr Robert A. Bruce, father of exercise cardiology

The exercise treadmill test known as the Bruce protocol continues to play an important role in diagnosing in intermediate-risk patients.

ABSTRACT: Recognizing the im- hour and a 22% grade. The aim of r Robert Arthur Bruce was portant physiological relationship testing is to detect the presence of born in Somerville, Massa- between the and exercise, coronary artery disease by looking D chusetts, on 20 November Dr Robert Arthur Bruce undertook for electro­cardiogram changes dur- 1916. He graduated from Boston research that revolutionized the ing times of stress. The sensitivity Uni­versity with a bachelor of science way physicians approach cardiac of exercise treadmill testing is esti- degree and went on to finish his medi- disease. His contributions to exer- mated to be 70% and the specific- cal studies at the University of Roch- cise physiology and cardiology have ity to be 80%. These values range ester School of Medicine in 1943. In shaped many concepts used today broadly depending on multiple fac- 1950, at the age of 34, Dr Bruce was in clinical practice. He is best known tors, including the definition of a appointed as the first chief of cardiol- for developing a protocol for the ex- positive test result. The strongest ogy at the University of Washington ercise treadmill test known as the predictor of survival found on ex- School of Medicine, where he served Bruce protocol. Because of its uni- ercise treadmill testing is exercise as director for 21 years and co-direc- versality, reproducibility, and prac- capacity. Treadmill testing can also tor for another 10 years.1,2 ticality, the protocol remains one of be combined with imaging modali- During his time at the University the most widely used methods for ties to further increase sensitivity of Washington, Dr Bruce contributed diagnosing ischemic heart disease. and specificity, making it one of the to the evolution of the exercise tread- Patients commonly start exercising first tests considered when coro- mill test (ETT) from a single-stage on a treadmill set at 1.7 miles per nary artery disease is suspected in to a multistage hour and a 10% grade, and increase a patient. examination called the Bruce proto- to a maximum speed of 6.0 miles per col, which involved increasing both speed and incline while monitoring a patient’s cardiovascular response using electrodes. Before the devel- opment of the Bruce protocol, physi- cians had been using the Master two-

Dr Luong is a cardiology resident in the Divi- sion of Cardiology at the University of Brit- ish Columbia. Dr Ignaszewski is a medical resident at the State University of New York Upstate Medical University. Dr Taylor is a staff cardiologist in the Division of Cardiol- This article has been peer reviewed. ogy at the University of British Columbia.

70 bc medical journal vol. 58 no. 2, march 2016 bcmj.org Stress testing: A contribution from Dr Robert A. Bruce, father of exercise cardiology

step exercise test, which involves the Association of University Cardi- gen demand is from skeletal muscle, obtaining an electrocardiogram ologists in 1969.2,6 where oxygen extraction increases by (ECG) after a patient has repeatedly As a believer in practising his up to threefold. As exercise intensity climbed up onto and down from a own medicine, Dr Bruce enjoyed a increases, the increase in cardiac out- small platform,3,4 a test that can be too healthy lifestyle and walked a mile put by up to sixfold is due mainly to an strenuous for some patients. along the waterfront with his wife increased as stroke volume In 1963, when Dr Bruce described almost daily until his passing. Every plateaus. In addition, total peripheral the stress test in print, he identi- bit the gentleman, he donned a sport resistance and diastolic blood pres- fied as the development of coat and tie at a celebration of his life sure (DBP) decreases, while systolic chest pain with exercise due to either and career with his closest family, blood pressure (SBP) and pulse pres- underlying coronary artery disease friends, and colleagues on 11 Febru- sure increases.10 (CAD), a previous myocardial infarc- ary 2004 in Seattle, Washington.2,6 The heart rate increase during ex- tion (MI), or a ventricular .5 He passed away the next day at age ercise is due to decreased vagal tone The ETT remains a well-proven tool 87 after a 13-year battle with chronic followed by increased sympathetic for diagnosing underlying CAD and lymphocytic leukemia. His discover- tone. As people age, beta-receptor for determining a patient’s maximal ies in exercise physiology and cardi- responsiveness decreases, leading to functional aerobic capacity, a term ology have altered the way cardiolo- a lower maximum heart rate and car- that Dr Bruce himself coined. gy is practised. Dr Bruce’s name will diac output in the elderly. A common Dr Bruce was also one of the remain synonymous with one of the and simplified method of estimating founders of the Seattle Heart Watch most extensively used screening and a person’s maximum heart rate is 220 program in 1971, which led to the diagnostic tools for detecting signs of minus age. To take into account indi- development of a database including CAD, and he will forever be known vidual variability, it is common prac- results from more than 10 000 indi- as the father of exercise cardiology tice to conclude that patients reach viduals who completed his treadmill because of this. their target heart rate at 85% of this test over a 10-year span. Using ambu- calculated maximum value.11 After latory cardiac patients and healthy Exercise treadmill testing exercise, the increased vagal tone will individuals as test subjects, the pro- Exercise treadmill testing to identify rapidly reduce the heart rate in the gram proved that the Bruce protocol CAD is now a widely available and first 30 seconds, followed by a more was both a reproducible and verifiable relatively low-cost examination that gradual decline back to baseline. method for diagnosing underlying has been used for more than 60 years.7 Another value that can be obtained heart disease. It is with this very data- The use of the ETT has expanded to from an ETT is a patient’s myocardi- base that Dr Bruce created the stan- include testing for functional capac- al oxygen uptake. This value is esti- dards we use when assessing today’s ity, chronotropic incompetence, car- mated by the product of heart rate patients.1,4 diac rehabilitation, valvular heart dis- and SBP. This rate-pressure product Publishing well over 300 articles, ease, hypertrophic cardiomyopathy, is important since myocardial oxy- Dr Bruce was an innovator above all, arrhythmias, and pacemaker evalua- gen uptake and coronary perfusion and was one of the first physicians tion.8-10 In addition, exercise testing are directly correlated. Since coro- to contemplate the benefit of throm- has been combined with other modal- nary flow can increase by up to five- bolysis in acute coronary syndrome. ities such as radionuclide imaging fold above baseline with exercise, a Moreover, his merging of cardiology and to elicit infor- patient who has obstructed coronary with technology inspired him to suc- mation that may be required in select arteries cannot meet this increased cessfully measure QRS and ST seg- patients. demand and ischemia results. In gen- ments during exercise.1 The ETT can reveal cardiovas- eral, a rate-pressure product 25 000 Dr Bruce is truly a giant of car- cular abnormalities that are not seen or higher indicates that a patient has diovascular medicine, whose inquisi- at rest by taking measurements that achieved an adequate workload.10 The tive nature led him to research that unmask these during aerobic exer- rate-pressure product can also be used advanced the field. He held many cise, when the heart responds to the to estimate when ischemia occurs and leadership positions throughout his body’s demand for more oxygen by is a better predictor of when ischemia illustrious career, including founding increasing heart rate, stroke volume, will develop than the exercise testing and serving as the second president of and cardiac output. Much of this oxy- stage.12

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Maximal oxygen uptake (VO2 Table 1. Absolute contraindications for exercise testing.10 max) is an additional accurate repre- sentation of a person’s cardiovascu- Acute , within 2 days lar fitness and exercise capacity, and Ongoing unstable angina is estimated from the peak workload Uncontrolled cardiac arrhythmia with hemodynamic compromise achieved on an ETT. This is usually Active endocarditis expressed in terms of a metabolic Symptomatic severe aortic stenosis equivalent task (MET), where 1 MET Decompensated heart failure is equal to 3.5 mL O2 per kg per min. The VO2 max value is affected by Acute pulmonary embolism, pulmonary infarction, or deep vein thrombosis age, gender, baseline exercise capac- Acute myocarditis or pericarditis ity and genetics.10 Metabolic equiva- Acute aortic dissection lent tasks (METs) can be estimated Physical disability that precludes safe and adequate testing based on the protocol used for an ETT. Table 2. Relative contraindications for exercise testing.10 Patient selection Exercise stress testing to diagnose Known obstructive left main coronary artery stenosis CAD is considered appropriate in an Moderate to severe aortic stenosis with uncertain relation to symptoms adult patient who is able to exercise Tachyarrhythmias with uncontrolled ventricular rates and who has an intermediate pretest Acquired advanced or complete heart block probability of CAD with an interpre- Hypertrophic obstructive cardiomyopathy with severe resting gradient table ECG. Patients with more than 1 mm of resting ST depression, left Recent stroke or transient ischemic attack bundle branch block (LBBB), ven- Mental impairment with limited ability to cooperate tricular paced rhythm, or pre-excita- Resting hypertension with SBP > 200 mm Hg or DBP > 110 mm Hg tion syndrome (e.g., Wolff-Parkinson- Uncorrected medical conditions, such as significant anemia, important electrolyte imbalance, White syndrome) will not have an and hyperthyroidism interpretable ECG and should not be referred for the purpose of diagnosing based on patient abilities and the rea- the Bruce protocol but with an initial CAD. Additional absolute contraindi- son for examination. The most com- grade of 0%. The Cornell, Naugh- cations and relative contraindications mon protocol used is the Bruce proto- ton, and Balke protocols use a more for exercise testing are described in col whereby patients start exercising gradual increase in workload and are Table 1 and Table 2 . at 1.7 miles per hour on a 10% grade. reasonable options for patients who Every 3 minutes the speed and grade are unable to ambulate comfortably.13 Test preparation increase to a maximum of 6.0 miles Ramp protocols also exist whereby Patients arriving for the test should per hour and 22% grade. The Bruce patients start off with no incline and be dressed comfortably in appropriate protocol is used commonly and is well at a low speed. The incline and speed exercising attire. They should not have described in many studies involving are then gradually and progressively eaten in the preceding 3 hours, but exercise testing. increased according to the patient’s may have taken regular medications When patients have ambulation functional abilities.10 with sips of water. When assessing for difficulties, the large increments in After an appropriate protocol has CAD, medications that may dampen a workload between stages may lead been selected for a patient and the test patient’s heart rate and blood pressure to premature discontinuation of the is proceeding, it is important to recog- response to exercise should be held ETT and an underestimation of the nize when stress testing should stop. the morning of the ETT. This applies patient’s true workload capacity. The current recommendations for ter- especially to beta blockers. Modifications have been made to the minating an exercise test are listed in Bruce protocol and other protocols Table 3 and Table 4 . Test protocols to overcome these potential limita- Once the ETT has been complet- There are several protocols that can tions.10 The modified Bruce proto- ed, there is an obligatory cool-down be used for an ETT and these are col starts off at the same speed as period. Patients are typically moni-

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tored for 6 to 8 minutes after test Table 3. Absolute indications to terminate exercise test.10 completion but may require addition- al monitoring of blood pressure, heart ST elevation > 1 mm in leads without pre-exisiting Q waves because of prior MI (other than leads rate, or ST segments if they have not aVR, aVL, and V1) normalized or if they remain symp- Drop in SBP > 10 mm Hg, despite an increase in workload, when accompanied by other evidence of ischemia tomatic. Additionally, ST segment Moderate-to-severe angina deviation, a relatively poor prognos- tic factor, may only occur during the Central nervous system symptoms (dizziness, near syncope, ataxia) postexercise period.10 Signs of poor perfusion (cyanosis or pallor) Sustained ventricular tachycardia or other arrhythmia that interferes with normal maintenance of cardiac output during exercise, such as second- or third-degree atrioventricular block Monitoring It is important to monitor patients for Technical difficulties in monitoring the electrocardiogram or SBP the development of symptoms during Subject’s desire to stop and after the test. Particular attention 10 should be paid to the presence of an- Table 4. Relative indications to terminate exercise test. gina and dyspnea. Exercise-limiting Marked ST segment depression > 2 mm measured 60 to 80 milliseconds after the J point in a angina is especially important be- patient with suspected ischemia cause it indicates a poorer progno- Drop in SBP > 10 mm Hg, despite an increase in workload, in the absence of other evidence of sis according to the Duke treadmill ischemia score (DTS). The DTS is a validated Increasing chest pain tool that provides both prognostic and Fatigue, shortness of breath, wheezing, leg cramps, or claudication diagnostic information in evaluating Arrhythmias other than ventricular tachycardia that have the potential to become more complex patients with suspected CAD14 (see or affect hemodynamic stability, such as multifocal ectopy, ventricular triplets, supraventricular more about this below). In addition, tachycardia, or bradyarrhythmias exercise-limiting dyspnea independ- Development of bundle branch block that cannot be immediately distinguished from ventricular tachycardia ent of angina has also been recog- Exaggerated hypertensive response with SBP > 250 mm Hg or DBP > 115 mm Hg nized as a worrisome ETT finding.15 Exercise capacity on an ETT has long been touted as a predictor of car- patients are able to achieve as a per- dium, which can be detected subse- diovascular risk. In a meta-analysis centage of their predicted abilities.10 quently on the surface ECG. A pattern by Kodama and colleagues, there was of characteristic alterations known as a decrease in cardiovascular events ECG changes the ischemic cascade develops with of approximately 15% with every The aim of exercise treadmill testing reduced left ventricular compliance 1-MET increase in aerobic exercise is to detect CAD by identifying ECG followed by localized wall motion capacity. Kodama also found that changes during times of stress, when abnormalities, increased left ven- subjects who were able to exercise there is an imbalance between myo- tricular end-diastolic pressure, ST to a level beyond 7.9 METs had a cardial oxygen supply and demand. segment changes, and lastly angina significantly better cardiovascular At increasing levels of stress, pro- ( Figure 1 ). It is these last two find- prognosis than those who did not.16 duction of adenosine triphosphate is ings that can be assessed on a stan- A patient’s predicted exercise abil- decreased and production of lactate dard ETT.10 ity can be estimated based on sex and is increased, ultimately affecting the Close attention to ECG changes is age, making it important to note what electrical properties of the myocar- needed to identify signs of ischemia.

Reduced left Increased left Wall motion ST segment ventricular ventricular end- Angina abnormalities deviation compliance diastolic pressure

Figure 1. The ischemic cascade.

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When looking for exercise-induced ECG changes, such as T wave and they are less well studied and have ischemia, the ST segment has long ST segment deviations, that normal- not been duplicated. These possible been the focus and is measured rel- ize with exercise due to elimination of signs of ischemia include increases in ative to the end of the PR segment. electric forces that are directed against P wave duration, particularly in lead The baseline should be stable to deter- each other, a phenomenon termed V1, increases in R wave amplitude at mine any significant ST segment de- ischemic counterpoise. Furthermore, peak exercise, absent QRS shorten- viations, and three or more consecu- ST changes in leads with existing Q ing, increases in T wave amplitude, tive beats should be used to detect ST waves may represent ongoing isch- exercise-induced U wave inversions, changes. The ST segment tangential emia in the territory or wall motion and absent QT interval shortening.10 direction should be measured at 60 abnormalities from prior infarcts.10 In to 80 milliseconds after the J point. patients with underlying conduction Arrhythmias A positive test for ischemia shows at abnormalities, interpretation of the Exercise increases sympathetic tone least 1 mm ST depression that is either ETT is more difficult. With underly- and increases myocardial demand, horizontal or downsloping ( Figure 2 ). ing left bundle branch block the ETT which are both potential mechanisms Upsloping ST depression, however, cannot be interpreted, but this is not for inducing supraventricular and can be seen in up to 20% of the nor- the case in patients with underlying ventricular arrhythmias. These ar- mal population and is therefore not right bundle branch block (RBBB). rhythmias are potentially dangerous diagnostic for ischemia. If more than The ECG of a patient with underlying in the postexercise period, when cat- 1 mm upsloping ST depression is RBBB can still demonstrate ischemia echolamine levels are high while the identified, the test is deemed equivo- in all leads other than V1 to V3. In patient is still vasodilated.10 cal.10 It is important to note that ST RBBB, the anterior precordial leads Ectopic atrial arrhythmias may changes identified on ETT do not re- will usually have baseline ST depres- occur in subjects with underlying car- liably predict the coronary artery af- sion that worsens with exercise; diac disease, such as rheumatic heart fected. The main exception to this is these changes are not associated with disease or Wolff-Parkinson-White in rare cases where ST elevation de- underlying CAD. syndrome, but may also be seen in velops in leads without pre-existing ECG changes other than ST seg- subjects with no identified abnormali- Q waves.10 ment deviations have also been impli- ties. Atrial fibrillation and flutter may Some subjects may have resting cated as signs of ischemia, though transiently occur in less than 1% of ETTs. Generally, these transient ar- rhythmias are not related to underly- ing ischemic heart disease. This is in No STST depressiondepression Negative stressstress test test contrast to ventricular arrhythmias, which are the most frequent arrhyth- mia seen during exercise. Premature ventricular beats are more concerning Upsloping ST Equivocal stresss test t Upsloping ST Equivocal tress est when accompanied by a family histo- depression (>1mm) (≥1mm) ry of sudden cardiac death, previous myocardial ischemia, or existing car- diomyopathy. Studies have suggested Horizontal ST ST Positive stressstress test test that ventricular ectopy, particularly in depression (>1mm) depression (≥1mm) the recovery period after an ETT, may be associated with an increased risk of death.17

Downsloping ST The development of atrioventric- depression (≥1mm) ular (AV) block is relatively uncom- Downsloping ST mon during ETT, particularly since depression (>1mm) vagal tone is decreased during exer- cise. When AV block develops, it may be related to medications, CAD, or Figure 2. ST segment depression with exercise. aortic stenosis.10 Rate-related con-

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duction abnormalities can develop specificity can be lowered if an ETT affected by the type of protocol used, in patients while exercising, but the is done on a subject with resting ECG and universal agreement on the exact development of LBBB or RBBB with abnormalities that are more likely to heart rate decline is lacking.10 exercise is not necessarily related to lead to false-positive results. Simi- Hypotension during exercise may underlying CAD. However, LBBB larly, the predictive value of an ETT indicate left ventricular outflow tract during exercise may be an indepen- is influenced by the prevalence of obstruction, severe left ventricular dent risk factor for death and major CAD in the population, which can be dysfunction, and significant CAD, cardiac events.18 Developing RBBB predicted by the patient’s underlying and is a marker of an increased risk during exercise is less common than risk factors. As such, exercise testing of cardiac events.20 During exercise, it developing LBBB, but may occur to identify CAD is inappropriate for a is abnormal to see the SBP dip below more commonly in patients with low-risk, asymptomatic patient.10 the resting value or drop 10 mm underlying CAD than in patients with Hg or more after an initial increase. LBBB.10 Prognostic value of ETT However, the most common reason Looking at ETT results, the stron- for hypotension during exercise is Alternatives to ETT gest predictor of survival is exercise the use of antihypertensive medica- When patients are physically unable capacity, which is how much exercise tions, making it important to review to exercise on a treadmill, alterna- a patient can sustain. One caveat is a patient’s medication profile before tives to the ETT are available. ECG that an ETT is often terminated when testing. Blood pressure can also rise changes can be recorded during phar- patients reach their target heart rate, excessively during exercise and this macological stress testing with adren- so merely noting the time it takes for too has been shown to predict mortali- ergic agents such as dobutamine or a patient to reach this stage does not ty. A hypertensive response is defined vasodilating agents such as adenos- indicate how much longer they would by a rise of SBP to 210 mm Hg and ine. These agents are often used in otherwise have been able to contin- beyond for men and to 190 mm Hg conjunction with nuclear myocar- ue exercising. Furthermore, exercise and beyond for women.20 Further- dial perfusion imaging with single- capacity is best assessed by calculat- more, a rise in DBP of more than 10 photon emission computed tomog- ing a patient’s workload in METs as mm Hg or a rise to an absolute val- raphy (SPECT), which increases opposed to simply indicating how ue beyond 90 mm Hg may also be a both the sensitivity and specificity of many minutes the patient exercised. sign of CAD.21 These hypertensive detecting CAD. Stress echocardio- There are no simple numbers of responses may predict an increased grams can also be performed to look METs one must reach to be consid- risk of developing hypertension, left for wall motion abnormalities, which ered to have high exercise capacity ventricular hypertrophy, and cardiac are seen earlier than ST segment because this number varies with age events.20 deviations as part of the ischemic and gender.10 Perhaps the most popular prog- cascade. Lastly, magnetic resonance Chronotropic incompetence is nostic risk score used for the ETT is imaging (MRI) and computed tomog- another prognostically important the Duke treadmill score. The DTS raphy (CT) scans are also being used variable defined by the failure to is calculated by subtracting 5 times increasingly to detect CAD.10 reach 85% of the maximum predict- the ST depression (measured in mm) ed heart rate. Heart rate response is and 4 times the angina score (no an- Sensitivity and important during exertion because it gina=0, non-limiting angina=1, and specificity of ETT is a measure of how well the patient’s test-limiting angina=2) from the total The sensitivity of ETT is estimat- cardiac output matches metabolic exercise duration (measured in min- ed to be 70% and the specificity is demands, and an impaired response utes) on the standard Bruce protocol. estimated to be 80%.19 These values predicts cardiac events and overall Subjects are considered low risk if range broadly depending on multiple mortality. they score 5 or above, intermediate factors, including the definition of a Abnormal heart rate response is risk if they score between 4 and -10, positive ETT, prevalence of disease, also prognostically important, and is and high risk if they score -11 and underlying cardiomyopathies, and defined as a decline during recovery below. Subjects with a high-risk DTS resting ECG abnormalities. For exam- of less than 12 beats per minute after are much more likely to have triple- ple, the sensitivity of a test increases ETT termination while the patient is vessel or left main CAD, and have a with multivessel CAD, while the still upright. However, this value is reduced 5-year survival rate of 65%.14

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Summary 7. Kligfield P. Historical notes: The early evo- Lippincott Williams & Wilkins; 2000. Dr Bruce will forever be known as the lution of the exercise electrocardiogram. 14. Shaw LJ, Peterson ED, Shaw LK, et al. father of exercise cardiology. The easy, In: Schalij MJ, Janse MJ, van Oosterom Use of a prognostic treadmill score in iden- relatively low-cost test he developed A, van der Wall EE, Wellens HJJ (eds). tifying diagnostic coronary disease sub- continues to play an important role Einthoven 2002: 100 years of electrocardi- groups. Circulation 1998;98:1622-1630. in diagnosing CAD in intermediate- ography. Leiden, Netherlands: Einthoven 15. Abidov A, Rozanski A, Hachamovitch R, et risk patients. The Bruce protocol al- Foundation; 2002. al. Prognostic significance of dyspnea in lows patients to exercise on a treadmill 8. Morise A. Exercise testing in nonathero- patients referred for cardiac stress test- according to their baseline functional sclerotic heart disease: Hypertrophic ing. N Engl J Med 2005;353:1889-1898. status, and is used to determine a pa- cardiomyopathy, , 16. Kodama S, Saito K, Tanaka S, et al. Cardio- tient’s exercise capacity, predict over- and arrhythmias. Circulation 2011;123: respiratory fitness as a quantitative pre- all mortality, and stratify patient risk, 216-225. dictor of all-cause mortality and cardio- irrespective of the presence of CAD. 9. Rajala J, Taylor CM, Kamossi N, et al. Car- vascular events in healthy men and Today exercise treadmill testing diac rehabilitation in BC: An approach women: A meta-analysis. JAMA 2009; is also being combined with imaging based on Dr Hellerstein’s model. BCMJ 301:2024-2035. modalities to increase sensitivity and 2013;53:153-158. 17. Frolkis JP, Pothier CE, Blackstone EH, et specificity for CAD, making the ETT 10. Fletcher GF, Ades PA, Kligfield P, et al.; al. Frequent ventricular ectopy after exer- a flexible test that is often used first American Heart Association Exercise, cise as a predictor of death. N Engl J Med when CAD is suspected in a patient. Cardiac Rehabilitation, and Prevention 2003;348:781-790. Committee of the Council on Clinical 18. Grady TA, Chiu AC, Snader CE, et al. Prog- Competing interests Cardiology, Council on Nutrition, Physical nostic significance of exercise-induced None declared. Activity and Metabolism, Council on left bundle-branch block. JAMA 1998; Cardiovascular and Stroke Nursing, and 279:153-156. References Council on Epidemiology and Prevention. 19. Gianrossi R, Detrano R, Mulvihill D, et al. 1. Kennedy JW, Cobb LA, Samson WE. Rob- Exercise standards for testing and train- Exercise-induced ST depression in the ert Arthur Bruce, MD. Circulation 2005: ing: A scientific statement from the diagnosis of coronary artery disease. A 111;2410-2412. American Heart Association. Circulation meta-analysis. Circulation 1989;80:87-98. 2. Wenger NK, Froelicher E. In memoriam: 2013;128:873-934. 20. Le VV, Mitiku T, Sungar G, et al. The blood Robert A. Bruce, MD scientist, clinician, 11. Pinkstaff S, Peberdy MA, Kontos MC, et pressure response to dynamic exercise teacher, mentor, and friend. J Cardiopulm al. Quantifying exertion level during exer- testing: A systematic review. Prog Cardio- Rehabil 2004;24:216-217. cise stress testing using percentage of vasc Dis 2008;51:135-160. 3. Shah BN. On the 50th Anniversary of the age predicted maximal heart rate, rate 21. Ha JW, Juracan EM, Mahoney DW, et al. first description of a multistage exercise pressure product, and perceived exertion. Hypertensive response to exercise: A po- treadmill test: Re-visiting the birth of the Mayo Clin Proc 2010;85:1095-1100. tential cause for new wall motion abnor- “Bruce Protocol.” Heart 2013;99:1793- 12. Balady GJ, Arena R, Sietsema K, et al.; mality in the absence of coronary artery 1794. American Heart Association Exercise, disease. J Am Coll Cardiol 2002;39: 4. Wood S. Father of exercise testing, Cardiac Rehabilitation, and Prevention 323-327. Dr Robert A Bruce, dies at age 87. 16 Committee of the Council on Clinical February 2004. Accessed 21 February Cardiology; Council on Epidemiology and 2015. www.medscape.com/viewarticle/ Prevention; Council on Peripheral Vascu- 784880. lar Disease; and Interdisciplinary Council 5. Bruce RA, Blackmon JR, Jones JW, et al. on Quality of Care and Outcomes Re- Exercise testing in adult normal subjects search. Clinician’s guide to cardiopulmon- and cardiac patients. Pediatrics 1963; ary exercise testing in adults: A scientific 32:742-756. statement from the American Heart As- 6. Oliver M. Robert Bruce, 87; researcher sociation. Circulation 2010;122:191-225. developed treadmill stress test. Los An- 13. Franklin BA, Whaley MH, Howley ET, et geles Times. 16 February 2004. Accessed al.; American College of Sports Medicine. 24 February 2015. http://articles.latimes ACSM’s guidelines for exercise testing .com/2004/feb/16/local/me-bruce16. and prescription. 6th ed. Baltimore, MD:

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