http://chestjournal.chestpubs.org/content/119/3/907.full.htmlservices can be found online on the World Wide Web at:The online version of this article, along with updated information and
written permission of the copyright holder.this article or PDF may be reproduced or distributed without the priorDundee Road, Northbrook, IL 60062. All rights reserved. No part ofCopyright2001by the American College of Chest Physicians, 3300Physicians. It has been published monthly since 1935.
is the official journal of the American College of ChestChest
T he stress test combined with ECG was originally used primarily for the detection of ST changes
secondary to myocardial ischemia. Modern exercisetesting, however, is not limited to observation of these changes. Important information is derivedfrom exercise capacity, BP response, development of arrhythmias, and whether or not symptoms such aschest pain develop during exercise. This allows forassessment of presence and severity of ischemia,prognosis, overall functional capacity, and efficacy of therapeutic interventions. Although stress testing isoften combined with radionuclide or echocardio-graphic imaging, I shall focus primarily on the ECGcomponent. The proper selection of stress tests inclinical evaluation will also be discussed.
The major indications for performing a stress testare summarized in Table 1. Table 2 lists the gener-ally accepted contraindications for such testing, asadapted from the guidelines provided by the Amer-ican College of Cardiology/American Heart Associa-tion Task Force in 1997.1
Safety of the Exercise Test
Stress testing is a relatively safe procedure. Before
1980, an overall mortality rate of 1 in 20,000 tests was observed. In the contemporary era, however,this frequency has been found to be even lower,generally 1 in 50,000.2 Nonfatal complications,such as myocardial infarction, occur at the rate of
4 per 10,000 tests.2 In subjects with histories of ventricular tachycardia or fibrillation, serious butnonfatal arrhythmias occurred during 2.3% of thetests.3 In the absence of such a history, the incidenceof such complications is approximately 0.05%.
Types of Stress Tests
The most commonly performed stress test is thegraded exercise test, using either the treadmill orcycle ergometer. The patient is generally subjectedto increasing workloads at 2- or 3-min intervals. Thetest is stopped for any of the reasons listed in Table3. The ECG is monitored not only during exercisebut also afterward, for 5 to 11% of patients withabnormal responses may not display such findingsuntil reaching the recovery period4,5 (see below).
The protocol used for treadmill testing variesamong different institutions. One of the most widely used is that of Bruce and Hornsten,6 but the proce-dure may be customized to allow for 6 to 12 min ofexercise.7 A modified version of this protocol isdetailed in Table 4 and is especially useful because itfacilitates extrapolation from maximum treadmillperformance to levels of work and recreational ac-tivity. It also allows for estimation of severity ofcardiac decompensation (New York Heart Associa-tion classes). The estimated workload is reported inmetabolic equivalents (METs), a unit that facilitatescomparison of different exercise protocols as well asallowing for comparison with work or recreationaleffort requirements. This term actually representsthe energy cost of activity in multiples of restingoxygen consumption (1 MET 3.5 mL/kg/min). In-asmuch as oxygen consumption is determined pri-marily by cardiac output in the absence of pulmonary or skeletal limitations, this information allows forrough estimates of cardiac function. Although oxygenuptake is not actually measured in most clinicallaboratories, one can estimate these approximate values simply by consulting published informationderived from the various treadmill workloads. In-
* From the Indiana Heart Institute, Care Group, Inc, and theDepartment of Medicine, Indiana University School of Medicine,Indianapolis, IN.Manuscript received March 16, 2000; revision accepted July 5,2000.Correspondence to: Morton E. Tavel, MD, FCCP, 8333 Naab Rd,Suite 200, Indianapolis, IN 46260; e-mail: [email protected]
creasing age and deconditioning reduce normal max-imum values.8 In some clinics, the test is stopped atan arbitrary target point of 85% of the predictedmaximal heart rate for the subject’s age. This maxi-mal rate is estimated by subtracting the subject’s agefrom 220. This practice is no longer recommended infavor of stressing individuals to the point of exhaus-tion or the development of warning signs or symp-toms (Table 3).1 If the subject can continue, I usually
terminate the test on reaching 100% of the expectedmaximum heart rate for age.The ECG and BP are monitored throughout
exercise and for several minutes thereafter. In mostinstances, the test may be conducted by a properly trained nonphysician,2 especially with subjects at lowrisk for cardiac events. In subjects at high risk,ie, with chest pain suggestive of angina pectoris or withknown heart disease, a physician should be in atten-
dance or in close proximity during the test. In allinstances, a physician should be near enough to bereadily available should there be an emergent need.
BP Response to Exercise
In response to the increased stroke volume andsystolic contractile force, the systolic BP normally rises progressively with increasing workloads, reach-ing approximately 160 to 220 mm Hg with maximumeffort. Because exercise lowers overall peripheral vascular resistance, the diastolic pressure exhibitslittle or no change ( 10 mm Hg). If the systolic
pressure fails to rise to 130 mm Hg or falls by 10 mm Hg in response to exercise, this frequently indicates left ventricular dysfunction and often sig-nals the presence of severe coronary artery disease(CAD) associated with extensive myocardial isch-emia.9,10 However, possibly in a substantial numberof patients, myocardial ischemia may produce anabnormal fall in BP, presumably resulting from anexcessive vasodilator reflex in nonexercising vascularbeds.11 In this instance, cardiac output actually may be increased during exercise.
An abnormal rise in exercise systolic pressure to a
level 214 mm Hg in a subject with a normalresting pressure predicts increased risk for futuresustained hypertension, estimated at approximately 10 to 26% for the next 5 to 10 years.12 This isassociated with a relatively high prevalence of left ventricular hypertrophy.13 Some investigators12 havefound a slightly greater 5- to 10-year rate of subse-quent cardiovascular events within this group, butothers14 have not observed this outcome.
Normally, the systolic pressure falls rapidly aftercessation of exercise, dropping by an average of
Table 1— Reasons for Stress Testing
1. Diagnosis of CAD in patients with chest pain that is atypicalfor myocardial ischemia.
2. Assessment of functional capacity and prognosis of patients with known CAD.
3. Assessment of prognosis and functional capacity of patients with CAD soon after an uncomplicated myocardial infarction(before hospital discharge or early after discharge).
4. Evaluation of patients with symptoms consistent withrecurrent, exercise-induced cardiac arrhythmia.
5. Assessment of functional capacity of selected patients withcongenital or valvular heart disease.
6. Evaluation of patients with rate-responsive pacemakers.7. Evaluation of asymptomatic men 40 years with special
occupations (airline pilots, bus drivers, etc).8. Evaluation of asymptomatic individuals 40 years with two or
more risk factors for CAD.9. Evaluation of sedentary individuals (men 45 years and
women 55 years) with two or more risk factors who plan toenter a vigorous exercise program.
10. Assessment of functional capacity and response to therapy inpatients with ischemic heart disease or heart failure.
11. Monitoring progress and safety in conjunction withrehabilitation after a cardiac event or surgical procedure.
Table 2— Contraindications to Stress Testing
1. Very recent acute myocardial infarction (generally 3–4 days).2. Angina pectoris, which is unstable or present at rest.3. Severe symptomatic or unstable left ventricular dysfunction.4. Potentially life-threatening cardiac dysrhythmias.5. Acute pericarditis, myocarditis, or endocarditis.6. Acute pulmonary embolus or infarction.7. Severe aortic stenosis.8. Noncardiac illness that precludes physical exertion,ie, acute
thrombophlebitis or deep vein thrombosis, serious generalillness, dissecting aneurysm, neuromuscular or arthriticconditions, and inability or lack of desire or motivation toperform the test.
Table 3— Indications for Terminating Exercise Testing
1. Drop in systolic BP of 10 mm Hg from baseline BP despitean increase in work load, especially when accompanied by symptoms or signs of ischemia.
2. Moderate-to-severe angina.3. Increasing nervous system symptoms (eg, ataxia, dizziness, or
near syncope).4. Signs of poor perfusion (cyanosis or pallor).5. Maximum fatigue or patient’s desire to stop.6. Sustained ventricular tachycardia, increasing multifocal
15% at 3 min after stopping. Myocardial ischemiamay reduce the rate at which this level falls: a 3-minpostexercise level of 90% in comparison with thepeak systolic level during exercise suggests the pres-ence of ischemia.15–17 To minimize the inaccuraciesof BP measurement at peak exercise, McHam et al17
suggested comparing pressures at 1 and 3 min afterexercise. Abnormality existed if the value at 3 minequaled or exceeded that at 1 min. Such a retardedpressure drop is an insensitive indicator of ischemia,but it is fairly specific for this disorder, reportedly exceeding 80%.17 Although the mechanism for thisabnormal pressure response is uncertain, it may result from ischemic suppression of left ventricularfunction during exercise combined with the subse-quent recovery of contractility during recovery. Thisresponse has been found usually to signal profoundand extensive ischemia, with the systolic pressureratio increasing proportionally with the number of diseased coronary arteries.16
Heart Rate Response to Exercise
In general, the heart rate rises proportionately with the intensity of the workload. Excessively rapidrises in rate result primarily from reduced left ven-tricular stroke volume, which, in turn, may be causedby physical deconditioning or cardiac disease. Undersuch circumstances, the heart rate reaches its peaklevel relatively early, and this limits maximum exer-
cise capacity. However, when the heart rate responseto exercise is excessively attenuated (in the absenceof rate-limiting drugs), this condition is termedchronotropic incompetence. Patients showing thisresponse often have significant organic heart disease,and among patients with known or suspected coro-nary disease, it is independently predictive of higherall-cause mortality.18 Unfortunately, however, defi-nitions of chronotropic incompetence vary: they range from the inability to achieve 85% of expectedmaximum heart rate, to failure to achieve 100 beats/ min at maximal exertion,19 to heart rate responses in
terms of percentage or standard deviations around amean heart rate for each stage on the treadmill.18,20
Because of such limitations, analysis of cardiac chro-notropic responses currently has limited practicalapplicability.21
The rate with which the heart rate slows in theearly recovery period can also provide informationabout ventricular function and prognosis. A recentstudy by Cole et al22 demonstrated that a drop in rateby 12 beats/min at 1 min after peak exerciseduring the cool-down phase in early recovery (while walking 1.5 mph at 2.5% grade) signaled a poor
prognosis. These subjects were found to have asubsequent 6-year mortality rate four times greaterthan those have with a more rapid fall in heart rate.The retarded heart rate drop during recovery prob-ably signifies reduced vagal tone, which is oftenassociated with decreased myocardial function andexercise capacity. An abnormal rate drop may addindependent prognostic information that extendsbeyond such factors as effort tolerance and rateresponse during the exercise period.
Cardiac Auscultatory Findings
Cardiac auscultation should be performed beforeand immediately after exercise. Resting abnormali-ties, such as murmurs and third and fourth heartsounds, should be noted and compared with postex-ercise findings. This facilitates recognition of impor-tant valvular abnormalities, such as aortic stenosis,that might preclude or modify testing. I have alsoencountered individuals with hypertrophic subaorticstenosis in whom intense systolic murmurs becamemanifest only after exercise. The appearance of a
Table 4— Relationship Between Treadmill Workloads,General Activities, and Cardiac Classification (New
York Heart Association)
TreadmillLevel
METS(Approx.)
FunctionalClass
(NYHA)Equivalent
Environmental Activities
1.7 mph0% grade
1.8 IV Minimal: wash/shave, dress,desk work, writing,sewing, piano playing,
walk 1.5 mph1.7 mph5% grade
3 III Very light: drive car,clerical and assembly work, shuffleboard,billiards, walk 3 mph
1.7 mph10% grade
5 II Light: clean windows, rake, wax floors, paint, stockshelves, light weldingand carpentry, golf,dancing (waltz), tabletennis, walk 3.5 mph
2.5 mph12% grade
7 I Moderate: light gardening,lawn mowing (level),slow stair climbing,exterior carpentry,doubles tennis,badminton, walk 4 mph
third heart sound or mid-diastolic gallop sound afterexercise is usually indicative of reduced restingsystolic function of the left ventricle, which may beassociated with cardiomyopathy or prior infarction,often associated with diabetes mellitus and left bun-dle branch-block, although extensive stress-inducedischemia is occasionally found.23
Recording Techniques
The conventional 12-lead ECG is the most widely chosen one for the graded exercise test. Almost allthe significant ST-segment changes, however, can bedemonstrated in leads I and V3 through V6 ,24 andapproximately 90% of that information is containedin lead V5 . Some investigators have suggested thatthe addition of right precordial leads,ie, leads V1Rthrough V4 R, may improve the diagnostic accuracy indetection of ischemia in general, especially in thedistribution of the right and circumflex left coronary arteries.25,26
Equipment for computer averaging of the ECGsignals is commonly available, and this providesassistance in the analysis of various changes—espe-cially ST depression. I agree with others27 who havenoted that such records often produce spuriously abnormal ST changes. Thus, the clinician shouldalways evaluate the actual ECG recording strips.
Criteria for a Positive Exercise Test:Conventional Criteria
Horizontal or Downsloping ST-Segment Depressionof 1 mm
The PR segment is the reference point with whichthe ST segment is compared (Fig 1). The criterion of
1 mm of horizontal or downsloping depression(Fig 1, D and E) is the most generally accepted.Junctional (J point) depression with slowly upslopingST segments (Fig 1C) also is generally considered tobe an abnormal response,28–30 although the defini-tion of slowly upsloping varies. Various investiga-tors31 have reported that including upsloping STresponses that remain 1 to 2 mm below the baselineat 60 to 80 ms after the J point significantly increasestest sensitivity without degrading specificity. How-ever, Sansoy et al32 noted that specificity was re-duced, especially if 1-mm depression was selected at80 ms. For this reason and until further data areavailable, in the case of upsloping ST segments, Iagree with others33 who suggest using 1.5-mm de-pression at 80 ms after the J point as a reasonablecriterion for a positive response.
The depth of ST depression caused by ischemia
appears to be influenced by the overall amplitude of the ECG signal as displayed by the R-wave height inlead V5 . Hollenberg et al34 reported that increasedR-wave amplitude might give rise to exaggerated STdepression during exercise. Accuracy was improvedby normalizing the ST depression for the R-waveamplitude. Ellestad et al35 noted that the correctionof ST depression for R-wave amplitude is especially useful in subjects with a low R wave in V5 . Thisgroup36 found that if the R wave decreases by 1mm in V5 at the end of exercise, ST depression of
0.5 mm constituted a positive ischemic responseand would thereby increase the sensitivity of the testto detect disease. Although of interest, these obser- vations require further confirmation, for Froelicheret al37 were unable to find improvement in testaccuracy by adjusting for R-wave amplitude.
ST-Segment Elevation
Although horizontal or downsloping ST-segmentdepression is the typical ischemic response in stresstesting (in all leads except aVR), some patientsexhibit ST-segment elevation of 1 mm (Fig 1F).Generally, in the absence of prior infarction, thisfinding is uncommon but implies severe transmuralischemia exceeding that associated with isolated STdepression.38 The reported incidence among pa-tients with chest pain ranges from 0.2 to 1.7%.38–42
High-grade proximal coronary stenosis is usually found, and this combination is associated with anominous prognosis.38 The correlation between thesite of the ST-segment elevation and the artery involved is generally quite good.38–43 Probably rep-resenting a variant of ST elevation, isolated transientincrease in height of T waves in the anterior leads (V1through V3) strongly suggests severe narrowing of the left anterior descending coronary artery.44
Exercise-induced ST-segment elevation is seenmost commonly in patients who have had previousmyocardial infarctions.40,41 Most studies demon-strated an incidence of 14 to 27%.40– 42,45–50 Patients with anterior myocardial infarction are more likely tohave exercise-induced ST-segment elevation thanare those with inferior myocardial infarction.49,51 TheST-segment elevation almost always occurs in theleads with abnormal Q waves.50 It also is associated with a left ventricular wall motion abnormality,either dyskinetic or akinetic, in the correspondingsite in 90% of cases.41,50–52 Overall poor left ventricular systolic function is usually found.45,52
Although some studies suggest that such ST changesdenote residual myocardial ischemia and contractilereserve within this infarct area,53,54 passive segmen-tal left ventricular wall motion abnormality (with or without aneurysm formation) is probably the under-
lying mechanism for the ST-segment elevation inmost cases.54 Findings in one study,55 however,suggested that residual viability could be found only in those instances in which ST elevation was associ-ated with reciprocal ST depression in those leadstaken from the opposite side of the heart. In thiscontext, therefore, ST depression may simply be asecondary response to remote ischemia rather than aprimary marker of ischemia in itself—as is the usualinterpretation. In the case of prior inferior myocar-dial infarction, the ST elevation found accompanyingthe Q waves in the inferior leads (II, III, and aVF)often gives rise to reciprocal ST depression in thehigh lateral leads (I and aVL).56
Ten to 30% of patients with variant angina alsomay have ST-segment elevation with exercise.51 Theleads that show ST-segment elevation are usually the
same leads that record elevation during angina at rest.All studies51,57,58 regularly report the occurrence of spasm of a major coronary artery supplying the area of the myocardium corresponding to the site of the ST-segment elevation. Most patients with variant anginaand exercise-induced ST-segment elevation, however,also have significant fixed coronary lesions.59
Transient, exercise-induced ST elevation has beenreported to occur in conjunction with acute pericar-ditis60 and may be mistaken for ischemic pain in theacute care setting. As noted previously, patients withknown pericarditis are usually not subjected to stresstesting. When the diagnosis is uncertain, however,persistence of ST elevation in response to exercisestress testing may aid in the distinction betweenpericarditis and early repolarization (a normal vari-ant) inasmuch as in the latter condition, ST elevation
Figure 1. Schematic representation of various ST-segment patterns potentially produced by exercise. A:normal; B: junctional depression that returns to baseline (level of PR segment) within 0.08 s (arrow);C: junctional depression that remains below baseline at 0.08 s;D: horizontal ST depression; E:downsloping ST depression;.F: ST elevation. See text for explanation.
returns to the isoelectric line.61 Exercise-inducedresolution of ST elevation, however, although un-common, may occur in pericarditis as well.62
Less Commonly Used or ControversialCriteria
The degree of ST-segment displacement in rela-tion to the increase in heart rate ( ST/HR index) with exercise has been suggested by some investiga-tors to be a more accurate indicator of the presenceand severity of CAD.63–67 This method requiresmeticulous or computerized measurement of STdisplacement. Other studies68–71 have not demon-strated the superiority of the ST/HR index in theprediction of CAD. The usefulness of changes of the heart rate-adjusted ST-segment depression inthe detection of CAD, therefore, remains controver-sial72 and, at best, may add only limited incrementaldiagnostic value.73 Thus, this method has not gained wide acceptance.
Transient inversion of U waves—even in theabsence of an abnormal ST-segment response—hasbeen suggested as a marker of extensive ischemia inthe anterior myocardium74 or elsewhere.75 Analo-gous to U-wave inversion, others76,77 have found thatexercise-induced increased magnitude of the U wavein the precordial leads ( 0.05 MV) was strongly suggestive of ischemia in the distribution of the leftcircumflex or right coronary arteries, presumably representing reciprocal changes from posterior U- wave inversion when myocardial ischemia occurredin this latter location. Detection of all U-wavechanges is difficult in the presence of tachycardia, afactor that limits the usefulness of these observa-tions.
Bonoris et al78 initially reported an increase in theR-wave amplitude immediately after exercise in pa-tients with severe multivessel coronary artery nar-rowing and ventricular dysfunction, presumably caused by transient ventricular dilatation. The resultsof later studies varied, some supporting and othersnot supporting the original observation.79–84 Never-theless, although the sensitivity of this finding is low, when the R-wave amplitude increases by 2 mm atpeak exercise, this has been said to strongly suggestischemia.85 In general, however, analysis of R-waveamplitude is not used in clinical practice.
Normally, the Q-wave depth in lead V5 increasesin response to exercise,86,87 presumably because of septal thickening in response to inotropic stimula-tion. A decrease or no change in this wave has beenfound with stenosis of the left anterior descendingcoronary artery, usually in association with multives-sel disease.86
The P wave shortens normally by approximately 0.02 s in response to exercise, whereas in the pres-ence of ischemia, it may lengthen slightly or remainunchanged.88 Transient elevation of atrial and left ventricular filling pressure induced by ischemia isthe assumed mechanism for such P-wave prolonga-tion. This interesting observation, if confirmed, may provide a useful secondary means to confirm thesignificance of other changes, such as ST depression.
The mean frontal plane QRS axis normally shiftstoward the right in response to exercise. Exercise-induced leftward axis shift89,90 or absence of right- ward shift89 is reported to be highly specific fornarrowing of the left anterior descending coronary artery, presumably caused by ischemia of the leftanterior fascicle. However, transient rightward axisshift to 90° is a rare occurrence, but said to behighly specific for CAD,91 presumably as a conse-quence of septal ischemia.
Exercise induction of complete right or left bundle
branch block is generally nonspecific. When foundtogether with other evidence of ischemia, however,such as angina pectoris, the conduction abnormality is said to be strongly suggestive of myocardial isch-emia, especially in the distribution of the proximalleft anterior descending coronary artery.90
The QRS duration normally remains unchanged orshortens slightly in response to exercise. In thepresence of ischemia, the QRS may lengthen slightly ( 3 to 5 ms) and this may allow detection ofischemia with greater sensitivity and specificity thanST segment changes alone,92–95 even in patients withrecent myocardial infarction.96 Michaelides et al95
found that the QRS prolongation correlated withseverity of ischemia, prolonging progressively withone (9.7 ms), two (13.6 ms), and three (16.3 ms)ischemic areas as demonstrated by nuclear scintigra-phy. When prolongation of S waves (10 to 12 ms)occurs in subjects with resting right bundle branchblock or left anterior hemiblock, this is believed to behighly suggestive of left anterior descending coro-nary artery stenosis.97 Because of the small incre-ments in duration of any of the above intervals,higher recording paper speeds or computer-aidedmeasuring techniques such as signal averaging93,95
would be generally required to achieve sufficientaccuracy.
Normally, the QT interval (corrected for heartrate) shortens with exercise. Some investigators havefound that this interval fails to shorten or lengthens when ischemia is present.98,99 Others100,101 havesuggested that abnormal exercise-induced QT dis-persion, ie, the difference between shortest andlongest QT intervals when multiple leads are com-pared, is greater in patients with ischemia. Measure-
ment of this interval, however, is difficult, especially when tachycardia is present, and this limits itspotential clinical value.
Methods to Validate the Presence ofMyocardial Ischemia
Despite its limitations, the coronary arteriogramremains the most common standard against whichthe diagnostic value (especially sensitivity) of stresstesting for CAD is measured. As noted, the use of arteriography as a standard usually suffers from thedisadvantages of referral bias,ie, a positive ECGstress test is often involved in the decision to selectthose referred for subsequent coronary arteriogra-phy. The effect of such selective referral is to raisefalsely sensitivity estimates, and, conversely, to re-duce falsely specificity values.
Noninvasive techniques (eg, stress thallium perfu-sion imaging or stress echocardiography) have alsobeen used to confirm the presence of coronary disease. When such studies are used to evaluate theperformance of stress ECG, referral bias can beminimized, and this usually results in lower sensitiv-ity but relatively high specificity values.
Accuracy of ST-Segment Depression inDetection of Ischemia
Stress-induced ST-segment depression is probably caused largely by reduction of perfusion to thesubendocardium, the zone most vulnerable to isch-emia. The sensitivity of such changes in the detectionof coronary disease varies widely in published re-ports,102–104 undoubtedly reflecting various con-founding factors such as referral bias, severity of disease in the selected population, and so forth.Overall, test sensitivity is most often found to lie inthe 60 to 70% range. In studies in which referral bias was minimized, however, lower sensitivity values arereported, falling in the range of 45 to 60%.37,105 Ingeneral, the greater the degree and extent of isch-emia, the more likely will ST depression occur, and,therefore, the higher the sensitivity of the stressECG. Most investigators have reported a sensitivity in the range of 40%, 66%, and 76% for one-, two-,and three-vessel coronary disease, respectively.106,107
We have also found that with larger nuclear perfu-sion defects in response to stress imaging, ST de-pression was more often encountered.105 Notwith-standing the results of smaller studies,108 we havealso found that larger areas of hypoperfusion alsoincreased the average depth of ST depression.105
In general, the distribution of leads manifesting
ST-segment depression does not appear to be help-ful in localizing the obstructive coronary le-sions,105,106,109 –112 for as noted, the lead V5 is mostapt to reflect this change whenever ischemia ispresent. However, some studies43,113 have noted thatST depression of lead V1—either isolated or associ-ated with other lead changes—suggests the presenceof ischemia in posterior myocardial regions,ie, inthose areas supplied by the left circumflex or rightcoronary arteries. Such depression in these leadspresumably arises as a reciprocal response to STelevation posteriorly, a location usually inaccessibleto conventional lead systems. Extending these obser- vations further, one group26 has suggested that STdeviation in the right precordial leads (V3 R and V4 R)may not only enhance the recognition of posteriorischemia, but when these changes are combined withabnormalities in the conventional lead systems, thesensitivity of ECG stress testing in general could begreatly enhanced for detection of coronary disease.They claimed a sensitivity ranging from 89% insingle-vessel involvement to as high as 95% in triple- vessel coronary disease. To enter the clinical main-stream, however, these latter observations requireconfirmation.
In contrast to the almost universal changes pro-duced in the left precordial leads (V4 through V6),myocardial ischemia seldom produces ST depressionconfined to the inferior leads (II, III, and aVF), and when one encounters such a limited distribution, thisusually denotes a false-positive test response,105,114
possibly often attributable to P-wave repolarization(see below).
In general, the myocardial location of ischemiaalso appears to play no role in the likelihood of STdepression,105,110 for we have demonstrated that thelikelihood of its appearance depends primarily on theextent of ischemia rather than its location.105
The configuration, time of onset, and duration of depressed ST segment during and after treadmillexercise have important diagnostic significance.115
Multivessel or left main coronary disease is presentin approximately 90% of patients who have changesappearing at low workloads (Bruce stage I or II) orpersisting for 8 min after exercise.116,117 Althoughsuch early and prolonged ST responses are highly specific for ischemia, some studies suggest that they correlate less well with subsequent prognosis,118 andeven arteriographic or scintigraphic severity may be variable.119 Although T-wave changes alone are nothelpful in diagnosis, the presence of deep T-waveinversion ( 5 mm) when combined with ST depres-sion has been found to be highly specific for mul-tivessel CAD with multiple severe narrowings.120
ST-segment depression occasionally begins only after cessation of exercise. The diagnostic and
prognostic significance of such a delayed responseis generally similar to those occurring during exer-cise121–123 ; however, when the onset of such a changeis delayed by 2 to 3 min into recovery, thissuggests a false-positive response.124 When STchanges during exercise are equivocal, the finding of progressively greater downsloping ST depressionduring recovery is a fairly specific sign of severeischemia and also signals a greater incidence of cardiac events in follow-up.125
The pattern of regression of ST changes in therecovery period may be useful in distinguishingischemic responses from those encountered occa-sionally in normal subjects who are falsely posi-tive.124,126 In true ischemia, the major ST depressiontends to coincide with the termination of exerciseand continues—often intensifying—for 2 to 3 minafter cessation.124 The persistence of this depressionin recovery usually parallels its onset,ie, when itbegins early at low workloads, it is more persistentduring recovery. When it reaches a maximum later inthe exercise phase, it usually regresses relatively early in recovery, but it usually continues for at least3 min after stopping. In contrast, false-positive STdepression tends to reach its maximum immediately before and at peak exertion but regresses quickly oncessation, frequently returning to normal within 1 to3 min of recovery. In this latter instance, as the heartrate slows in recovery, the depth of ST depression isless when compared with corresponding cycle lengthsduring the exercise phase, whereas those subjects withtrue ischemia usually show equal or greater ST dis-placement at comparable cycle lengths.126
The development of typical anginal chest painduring the test generally signifies fairly extensive isch-emia and thus increases the likelihood of ST changes,adding significantly to test sensitivity.105 Moreover,typical chest pain during testing is almost as predictiveof ischemia as is ST-segment depression.127
As already noted for test sensitivity, the specificity of ST depression in the evaluation of coronary ischemia has also been found to vary considerably, with a mean value derived from a meta-analysisreported to be 72%.102 Referral bias, however, prob-ably reduced these values spuriously, for when thistype of bias is minimized, these values generally approach or exceed 90%.37,128,129
Differences in results of stress tests between menand women have been the subject of considerablecontroversy. In general, women are far more likely than men to manifest a false-positive response,130–132
but the difference may be attributable to the lowerrate of CAD in the populations of women subjectedto testing. Based on Bayes theorem, the lowergeneral prevalence of CAD among women results ina relatively low predictive value of a positive test in
this group. Some investigators133 have suggested thathormonal effects, especially those of progestin,might be responsible for the production of false-positive ST responses. This effect, if present at all, would be small, for the rate of false-positive stresstests in premenopausal women is low129 and only marginally greater than that of men.
Test specificity, ie, the percentage of negativeresponders in a population known to be free of disease, is of utmost importance in clinical evalua-tion, and many mistakenly believe that this value isunacceptably low in women. For proper determina-tion of test specificity, a group must be defined thatis uniformly proven to be free of disease and in which no prior ECG tests have been performed.Coronary cineangiography is often used as the defin-itive test to rule out CAD. Unfortunately, such adesign is basically flawed because it is a rare individ-ual who has not been subjected to prior stress testingand in whom the results of this testing were notinstrumental in the decision to obtain the cineangio-graphic study. This process produces so-called refer-ral bias, ie, the inclusion of an inordinately highpercentage of positive test responders in a disease-free group selected in this manner, thus yieldingfalsely low specificity values. Such bias may producegreater distortions of test specificity in women sim-ply because, as noted above, falsely abnormal stressresponders are more plentiful in mixed populationsof women (with and without disease) from whichthese subjects are drawn. When this type of bias isminimized, however, the difference in specificity between the sexes all but disappears, with a false-positive response rate of 10% for each.128,129
Therefore, in accordance with Bayesian principles, anegative test result encountered in a subject from anunselected population of women generally carries ahigh negative predictive value and thus is useful inexcluding CAD. These data suggest that, in general,the initial evaluation of an individual woman shouldbe identical to that of a man,ie, accomplished with astandard ECG stress test. It need not involve costly nuclear or echocardiographic techniques unless theformer test result is positive—a relatively uncommonoccurrence in the absence of coronary disease.
Causes of Positive Results of ExerciseTests in the Absence of CAD
Numerous situations appear to give rise to exer-cise-induced ST depression in the absence of ob-struction to the major coronary arteries. Mechanicallesions that place a greater burden on left ventriculardynamics and oxygen requirements include suchabnormalities as mitral or aortic valvular dysfunc-
tion,134,135 pulmonary hypertension,135 pericardialconstriction,136 and left ventricular hypertro-phy.136,137 Relative coronary insufficiency is probably also the responsible mechanism in patients with left ventricular hypertrophy. The frequency of positivetest results in such cases has been found to be as highas 38%.138 Patients with increased left ventricularmass, even in the absence of standard ECG voltagecriteria for this diagnosis, may have false-positiveECG exercise responses.137,138
A wide variety of miscellaneous situations has alsobeen associated with falsely positive ST responses toexercise.139 These include digitalis administra-tion,140,141 hypokalemia,142,143 normal postprandialchanges,144 hyperventilation,145,146 postural chang-es,147 vasoregulatory abnormalities,148,149 mitral valveprolapse,150,151 pectus excavatum,152 and intraven-tricular conduction defect including left bundlebranch block and Wolff-Parkinson-White syn-drome.153–155 There is undoubtedly no commonmechanism for ST shifts in these diverse situations;however, effects brought about by electrolyte shiftsand sympathetic nervous stimulation at the cellularlevel may play an important role.
Digitalis is known to cause a false-positive exercisetest result in both normal subjects and in patients with heart disease,140,141,156 occurring as often as25% in healthy subjects,141 showing a greater prev-alence with increasing age. Hamasaki et al156 foundthat digitalis-induced ST-segment depression occursgradually as the heart rate increases in response toexercise, a pattern differing from that usually seen inmyocardial ischemia, in which the ST depressionprogresses more rapidly as peak heart rates areapproached. This might aid in distinguishing be-tween drug effect and ischemia.
Hypokalemia is often associated with abnormalexercise responses,142 and these changes can beabolished after potassium repletion. Therefore, inpatients who are taking diuretics, the results of theECG stress test should be interpreted with caution.
Food intake may induce ST-segment and T-wavechanges in the resting ECG.157 Significant ST de-pression also may develop after glucose ingestion insubjects who otherwise had normal exerciseECGs.144 For this reason, exercise testing should beproscribed until 2 h after a meal to avoid thissource of variability.
Although usually causing changes primarily con-fined to the T waves, hyperventilation is known toproduce ST-segment changes in response to exercisethat mimic those of myocardial ischemia.145,146,158 If this cause is suspected in a given individual withsuspicious stress-induced ST changes, that subjectmay be instructed to voluntarily hyperventilate for aperiod of 2 to 3 min during rest and with ECG
monitoring. If ST changes are produced by thismaneuver, they are compared with those encoun-tered during the stress test, and if similar, thissuggests a false-positive result induced by hyperven-tilation. This maneuver, however, should be selec-tively performed only after the standard stress test,for routine performance before the test is usually unnecessary and may produce dizziness and discom-fort and interfere with the proper execution of thestandard test.
A peculiar syndrome, sometimes labeled syn-drome X, is occasionally encountered, especially in young and middle-aged women, consisting of angi-nal-type chest pain and abnormal exercise ECG butnormal coronary arteriograms.159 Exercise-inducedcoronary spasm and microvascular disease160 arepossible causes of this syndrome. Therefore, in thiscontext, the abnormal ECG stress test result may notbe truly false positive.
Patients with the mitral valve prolapse and normalcoronary arteriograms may have false-positive exer-cise responses.150 This phenomenon is clinically im-portant because chest pain and vasoregulatory ab-normalities are occasionally encountered in thesepatients.
The secondary ST-segment and T-wave changes inpatients with intraventricular conduction defectssuch as left bundle branch block, ventricular pacedrhythm, and Wolff-Parkinson-White (preexcitation)syndrome interfere with proper interpretation of theexercise response.153–155,161,162 Both false-positiveand false-negative responses may be seen in patients with left bundle branch block. Studies in a limitednumber of patients, however, suggested that the exer-cise test might be useful even if this latter conductionabnormality is present.163,164 Recently, Ibrahim et al165
found that additional exercise-induced J point de-pression in leads II, aVF, and V5 was suggestive of ischemia in this group. Most useful in their study wasa change of 0.5 mm in lead II. This finding, if confirmed, would be of significant clinical value.False-positive changes are particularly common inpatients with the Wolff-Parkinson-White syn-drome,154 being observed in as many as 100% of suchcases.155
In the case of right bundle branch block, theresting anterior ST-T changes secondary to thisconduction abnormality interfere with interpretationof the exercise response. Thus, changes in leads V1through V3 often falsely suggest ischemia.166 The testis still reliable if the ST segment depression isrecorded in leads V4 through V6 . In one smallstudy,167 however, this conduction abnormality wasfound to be capable of masking the usual ischemicST depression in these latter leads, thus producingfalse-negative ST responses to stress.
Exaggerated atrial repolarization waves may pro-duce spurious depression of ST segments.168–170 Theatrial repolarization wave is directionally opposite tothe P wave and can extend well into the ST segment.Thus, with exercise-induced tachycardia, P wave andatrial repolarization wave amplitudes increase, andthe PR segment shortens, thus shifting the atrialrepolarization wave toward the ST segment. In prac-tice, this phenomenon may be suspected when ap-parent ST depression is found together with a prom-inent P wave with a short, sharply downsloping PRsegment, especially notable in the inferior leads.
Causes of False-Negative Response
Apart from the inherent limitations of sensitivity of the exercise test in the detection of myocardialischemia, certain drugs are known to limit its valueeven further. Drugs which limit the heart rateresponse to exercise ( -adrenergic blocking agents,diltiazem, and verapamil) reduce the heart rate andmaximum systolic arterial BP during exercise, thusdecreasing the left ventricular work and myocardialoxygen requirements and reducing or eliminatingthe ST-segment depression.171 In the process of increasing exercise capacity, nitrates may also pre- vent or minimize changes in exercise ECG.172 Ingeneral, if one wishes to maximize test sensitivity,treatment with any of the drugs noted above shouldbe withdrawn for a sufficient period to allow removalfrom the body before testing. Depending on theinformation desired from the test and the need forcontinued medication, however, the clinician may decide to perform the test in selected cases withoutdrug withdrawal.
Exercise Testing in Patients WithAbnormal Resting ECGs
A number of reports suggest that exercise testingmay be of value even when the resting ECG isabnormal.173–175 Most of the patients with abnormalresting ECGs show nonspecific ST-segment andT-wave changes. In general, additional ST depres-sion of 1 mm with exercise has a diagnosticaccuracy approaching that found in the absence of resting changes.173–175 Such changes also have beenfound to have similar prognostic significance as thosefound in patients with a normal resting ECG.175
In the presence of resting T-wave inversion, nor-malization of this abnormality in response to exercisemay occur in different clinical settings176–178 : it may result from regional myocardial ischemia or abnor-mal left ventricular wall motion, but may also occur
in normal subjects. Thus, in general, this finding haslittle specificity. However, if such normalization oc-curs in conjunction with an infarcted dysfunctionalmyocardial zone, it may indicate higher coronary flow reserve, and this in turn suggests better preser- vation of coronary microcirculatory function and thelikely presence of myocardial viability.176,177 Thisconcept, however, has been challenged by others.52
ST-segment elevation may be seen in the restingECGs of healthy subjects because of early repolar-ization. In such cases, the ST segment returns to theisoelectric baseline with exercise, whereas those withsignificant CAD may have horizontal ST-segmentdepression.179 Therefore, even in the presence of STelevation in the baseline ECG, the usual criteria forthe interpretation of the exercise test are probably stillapplicable. As noted above, persistent or increasing STelevation during exercise may be encountered in myo-cardial ischemia, prior infarction, or pericarditis.
Prognostic Value of Exercise Testing
When large groups of unselected individuals arescreened with stress tests, studies consistently showthat subjects manifesting abnormal ST responses areat greater risk for subsequent cardiovascular events(angina, acute myocardial infarction, or suddendeath).180–186 In general, after a follow-up period of 5 to 13 years, those with positive ECG responsesshow approximately a four- to sixfold greater inci-dence of such events in comparison with thoseresponding normally to stress. Inability to exercise
6 min on a standard Bruce protocol (approximately 6 to 7 METs) and inability to increase the heart rate to85% of age-predicted normal maximum values also were significant indicators of increased risk of coro-nary events. Individuals demonstrating high exercisetolerance ( 10 METs) generally enjoy an excellentprognosis, regardless of the ECG response and evenin the presence of known CAD.187–189
The combination of various exercise test variableshas improved the estimation of long-term progno-sis.187,190 Variables found to be independently asso-ciated with time to cardiovascular death were weighted to create an equation that calculates anumeric score. The Duke score,187 which is the most widely used and confirmed by others,175 is based onthree exercise variables: exercise tolerance in METs,the largest measured ST-segment depression duringexercise, and whether angina pectoris could be in-duced by the test. (Duke Score exercisetime 5 {exercise-induced ST depression inmillimeters} 4 treadmill angina index. Whereexercise time is in minutes of Bruce protocol; STdepression is largest stress-induced downward dis-
placement in mm, and angina index is given as thefollowing: 0 for no angina during exercise, 1 for typicalangina, and 2 for angina leading to discontinuation of exercise. The Duke score [DS] is then used to calculateannual cardiovascular mortality [CVM]: CVM
0.00018[DS]3 0.0071[DS]2 0.143[DS] 1.60.)A Long Beach Veteran’sAdministration score190 incor-porates slightly different variables but yields similarprognostic information. The use of such indexesenhances the practical value of stress testing farbeyond that obtained from simple analysis of ECGchanges alone, further emphasizing the importanceof using symptom-limited protocols for testing. Al-though patient management should be individual-ized, the projection of an annual mortality rate of
1% would usually warrant a conservative medicalapproach to management in favor of aggressiveinvasive or surgical procedures.
The induction of typical angina pectoris duringtreadmill stress signifies that the extent of ischemia is
greater than in subjects lacking this symptom,105
although diabetics are generally less likely to experi-ence pain. The subsequent survival rate decreasesincrementally in proportion to the reduction inexercise duration and effort tolerance.191 As a rule,those who have good exercise capacity (approximate-ly 10 METs) enjoy a good prognosis, experiencinga 5-year survival of 95%. However, the probability of survival is much lower in those patients who have
1 mm ST-segment depression and who are able toachieve a level of exercise equivalent to only Brucestage 1 (5 METs) or lower. Survival at 5 years in thislatter group ranges from 50 to 72%. In view of thedata cited above, one may formulate the followinggeneral strategy for the use of ECG stress testing indeciding whether and which further tests arerequired for patients with known or suspectedCAD. If an ECG stress test is negative or indicatesa low risk (yearly mortality 1%), medical man-agement with risk-factor control is generally pre-ferred. For those demonstrating high risk (project-ed mortality 5% yearly), direct intervention withcoronary cineangiocardiography should bestrongly considered. For those determined to be atintermediate risk (1 to 5% annual mortality),further stratification with nuclear imaging shouldbe considered before choosing further evaluationor treatment.192 Multiple or extensive nuclear perfu-sion abnormalities signal the need for invasive study, whereas a normal scan or one containing a smalldefect warrants a conservative approach. Obviously,initial evaluation with nuclear or echocardiographicprocedures with pharmacologic provocation is re-quired for those individuals unable to exercise or who possess disqualifying resting ECG abnormal-
ities. Moreover, other clinical features, such as ageand comorbidities, enter into these testing andmanagement decisions.
Exercise Testing After MyocardialInfarction
To assess the presence of ischemia or left ventric-ular dysfunction and to gauge future risk moreeffectively, stress testing is often used as early as 4 to7 days after an acute myocardial infarction193,194 and,more recently, 3 days after such an event.195 In thepast, it was performed typically after an interval of
2 months had elapsed.196–199 The predictive valueof early testing, especially when symptom limited, issimilar to that of testing performed 6 weeks afterinfarction.193,200,201 If performed early, exercise onthe treadmill is commonly stopped when the subjectreaches an arbitrary heart rate, which is generally 120 or 130 beats/min, or 70% of predicted maximumheart rate for age. More recently, however, severalinvestigators193–195 have found that symptom-limitedtesting could be performed early and safely in sub- jects with uncomplicated myocardial infarctions (av-erage 4 to 7 days after the event). Stress-induced STdepression after a single previous myocardial infarc-tion usually identifies those with ischemia resultingfrom multivessel coronary disease.45,48 A poor BPresponse during exercise is suggestive of reduced left ventricular function.199 With maximal testing, theability to achieve a high heart rate–systolic pressureproduct ( 21,700) implies good myocardial bloodflow and a favorable prognosis (6 months mortality,0.8% vs 2% in those failing to reach this product).202
Exercise-induced ST-segment elevation in leads pos-sessing pathologic Q waves usually is associated withgreater impairment of left ventricular function be-cause of more extensive damage rather than extent of the CAD,203 but, as noted above, whether it indicatesthe presence of viable myocardium is controversial.Combining various features of stress testing en-hances assessment of prognosis: exercise-inducedangina, ST-segment displacement, falling BP or fail-ure to increase BP to 110 mm Hg, repetitive ventricular arrhythmias, poor exercise tolerance ( 6METs), and inability to reach exercise heart rate of 120 beats/min (in the absence of -blockers) arepredictive of higher risk for future cardiac eventssuch as unstable angina, recurrent myocardial infarc-tion, and cardiac death.193,194,196,204–207 The esti-mated 1-year mortality ranges from approximately 1% if none of these features was present to 17% if three or more were present. Similar findings havebeen observed both in patients with Q-wave and inthose with non–Q-wave infarctions.193,194,208 Those
receiving thrombolytic treatment apparently enjoy abetter prognosis even when these test results arepositive.207
With the increasing popularity of various stress-imaging modalities, physicians must consider theproper strategy of patient management after a myo-cardial infarction before discharge from the hospital.In a meta-analysis,207 stress ECG was compared withmyocardial nuclear perfusion and ventricular func-tion imaging. Positive results of all forms of testing yielded relatively low positive predictive values forsubsequent events, ie, 20% chance of death orreinfarction in 1 year. In general, tests to detectreduced left ventricular function (peak stress-in-duced ejection fraction 40%) were more predic-tive of an adverse outcome, averaging from 30 to40% chance of death or reinfarction in 1 year.Those tests that disclosed myocardial perfusiondefects, such as ST depression or reversible nu-clear perfusion or wall motion abnormalities, were
less predictive of subsequent events. However,negative results of all tests were comparably andindependently predictive of lower ( 10%) eventrates at 1 year.
From these data above, one might formulate thefollowing strategy for noninvasive testing after amyocardial infarction. In patients undergoing im-mediate angiography or angioplasty, a predis-charge stress test is generally superfluous, and thistest may be deferred until 4 to 6 weeks afterhospital discharge.195 In the remainder who havesustained an uncomplicated infarction (absence of congestive heart failure, reduced resting ejectionfraction, or other adverse markers such as persis-tent chest pain, hypotension, and so forth), one would proceed first with an ECG stress test,preferably symptom-limited in type. If such pa-tients exercise to 6 METs without ECG orhemodynamic abnormalities, they are at low risk of a recurrent cardiac event during the ensuing year.Through this means, no further tests are required,costs can be minimized, and the patient can bereassured. If results of this test are abnormal or if
resting ECG abnormalities preclude assessment of stress-induced changes, I suggest stress imaging with nuclear or echocardiographic techniques. Ex-ercise is the preferable form of stress unlesslimitations of patient performance necessitatepharmacologic stimulation with agents such asdobutamine or dipyridamole. In those patients with complicated infarctions or who exhibit evi-dence of reduced resting left ventricular function,one would proceed directly to stress imaging orinvasive study.
Exercise ECG in Risk Assessment BeforeNoncardiac Surgery
Stress testing may be useful in risk assessmentbefore any type of elective surgical procedure. Theindications for testing are basically the same as notedin Table 1, especially categories 1 and 2. The fea-tures indicative of high risk for perioperative cardiacevents are, as expected, poor functional capacity,
marked exercise-induced ST-segment shift or anginaat low workloads, and a drop or an inability toincrease the BP with progressive exercise.209 Thoseshown to be at low long-term risk generally may proceed directly to surgery without further testing.Patients requiring surgical procedures, however, es-pecially for peripheral vascular disease, are oftenunable to exercise, and, therefore, evaluation mustnecessarily begin with nuclear or echocardiographicimaging with pharmacologic provocation. Selectionfor additional testing, including invasive procedures,before elective surgery is generally the same as that
described above for the general population. Thissubject has been reviewed previously by Chaitmanand Miller.209
Relationship Between Exercise Testingand Ventricular Arrhythmias
Premature ventricular beats are often induced by exercise. In studies of middle-aged or older subjects without overt heart disease, approximately 3% ormore have premature ventricular beats at rest, in-creasing by more than twofold (to as high as 50%) atpeak exercise, which often includes the new appear-ance of repetitive ventricular ectopic beats.181,210–212
The incidence of such arrhythmias appears to in-crease with age.213 In general, more arrhythmias areseen on recovery than during exercise. Although ventricular ectopy is more easily evoked in patients with CAD than in normal subjects, the considerableoverlap between those with and without ischemiaprevents this finding from possessing diagnostic value. The long-term prognosis of asymptomaticsubjects manifesting exercise-induced ventricular ar-rhythmias, including nonsustained ventricular tachy-cardia, appears to be benign.181,214
In patients with CAD, the reported incidence of exercise-induced ventricular arrhythmias rangesfrom 38 to 65%.211,212,215 In general, the survival rateof patients with CAD, including those with recentmyocardial infarction, is decreased if they haveexercise-induced complex ventricular arrhyth-mias.205,216–218 Some reports dispute such an associ-ation, however,219 at least in low-risk patients withdemonstrable stable coronary disease.220,221 Signifi-cant multivessel disease is likely to be present in
patients with angina and exercise-induced ventricu-lar arrhythmias,215,222 especially if ST-segmentchanges consistent with myocardial ischemia also arepresent.223
Thus, the appearance of ventricular arrhythmias inresponse to exercise in asymptomatic subjects has nodiagnostic or prognostic value. When they are foundin association with known CAD or with other mark-ers of ischemia, such as ST depression or anginal-type chest discomfort, they generally predict aninordinately high incidence of subsequent cardiacevents.
Selection of a Stress Test in InitialEvaluation
Authorities disagree about whether any form of exercise testing should be performed in asymptom-atic individuals.1 In this category, I believe it justifi-able to test individuals with multiple risk factors foratherosclerosis (including associated diseases such aschronic renal failure), sedentary individuals who planto start vigorous exercise, and those who are involvedin occupations in which impairment might impactpublic safety. The use of ultrafast (electron beam)CT is being used with increasing frequency inasymptomatic individuals for the detection of coro-nary artery calcification.224 The presence andamount of calcium detected by this means appear tocorrelate with the amount of atherosclerotic plaque,but they do not necessarily signal the presence of coronary arterial flow restricting disease. It may offeran earlier means to assess risk and observe responsesto therapy. The proper role of this technique, how-ever, is currently controversial and is underreview.225
In patients presenting to emergency facilities withacute chest pain syndromes, stress testing with elec-trocardiography may provide an important means fortriage and management with the attendant reductionof medical costs.226,227 In those subjects with sus-pected cardiac pain demonstrating a low or moderaterisk for immediate adverse outcomes, managementmay proceed swiftly to include the following. First,serum enzymes are assessed (total serum creatinekinase and its MB isoenzyme and troponin levels),and if these are normal, a treadmill test is performedeither immediately 225 or after a 6-h observationperiod with repeat enzyme determination.226 Indi- viduals undergoing this strategy would include those with ECGs that are normal or with only nonspecificrepolarization abnormalities, stable BP, no clinicalevidence of cardiac decompensation, and absence of prolonged chest pain associated with dynamic STchanges. A normal result of a stress test allows for
immediate hospital discharge, whereas an equivocalor positive test result is followed by hospitalization with additional study.
When given a choice among ECG and imagingmethods in evaluating patients with recurrent chestpain with intermediate or high likelihood of a cardiacorigin, the physician should opt for the most directand cost-effective means of initial evaluation—theECG stress test. Men and women should be ap-proached in the same fashion. Even though stressnuclear and echocardiographic imaging are moresensitive in the detection of ischemia, there is insuf-ficient evidence to assume that information so ob-tained can be more cost-effective or used to improveoutcomes beyond that obtained through prognosticassessment used in conjunction with stress ECGalone. If the ECG changes suggest ischemia andclinical circumstances warrant it, an imaging study may then be used. When resting ECG abnormalitiespreclude interpretation, then initial evaluation
should combine stress testing with imaging modali-ties. When patients are unable to exercise for any reason or if an unsatisfactory rate response to exerciseis anticipated (as exemplified by the inability to with-draw treatment with rate-limiting drugs), then imagingstudies with pharmacologic provocation should be con-sidered.
Concluding Remarks
Modern exercise testing with ECG monitoringremains a cornerstone of cardiovascular evaluation,providing a valuable source for several types ofinformation. (1) Changes in the ECG pattern—especially depression of the ST segment—indicatethe presence and often the severity of myocardialischemia. (2) When combined with ECG changes,symptoms of dyspnea and chest pain, limitation of maximum performance, and BP response provide valuable markers of the presence and severity of disease and its prognosis. Combined with the history and physical examination, a prognostic index indica-
tive of low risk for future cardiovascular events mayallow the clinician to avoid aggressive and costlyprocedures such as cardiac catheterization.228 (3)Maximum effort tolerance is useful in gauging workand recreational limitations and for use in monitor-ing efficacy of treatment and in prescribing a safeexercise program. (4) Diagnostic and prognostic dataderived in this way can supplement those obtainedthrough simultaneously performed imaging tech-niques, ie, stress echocardiography or nuclear perfu-sion study.
References1 Gibbons RJ, Balady GJ, Beasley JW, et al. ACC/AHA
guidelines for exercise testing: a report of the ACC/AHAtask force on practice guidelines. J Am Coll Cardiol 1997;30:260–311
2 Franklin B, Timmis GC, O’Neill WW. Is direct physiciansupervision of exercise stress testing routinely necessary?Chest 1997; 111:262–265
3 Young DZ, Lampert S, Graboys TB, et al. Safety of maximalexercise testing in patients at high risk for ventriculararrhythmia. Circulation 1984; 70:184–191
4 Martin CM, McConahay DR. Maximal treadmill exerciseelectrocardiography: correlations with coronary arteriogra-phy and cardiac hemodynamics. Circulation 1972; 46:956–962
5 Mason RE, Likar I, Biern RO, et al. Multiple-lead exerciseelectrocardiography: experience in 107 normal subjects and67 patients with angina pectoris, and comparison withcoronary cinearteriography in 84 patients. Circulation 1967;36:517–525
6 Bruce RA, Hornsten TR. Exercise stress testing in evalua-tion of patients with ischemic heart disease. Prog CardiovascDis 1969; 11:371–390
7 Myers J, Froelicher VF. Optimizing the exercise test forpharmacological investigations. Circulation 1990; 82:1839–1846
8 Fletcher GG, Froelicher VF, Hartley LH, et al. Exercisestandards: a statement for health professionals from theAmerican Heart Association. Circulation 1990; 82:2286–2322
9 Sanmarco ME, Pontius S, Selvester RH. Abnormal bloodpressure response and marked ischemic ST-segment depres-sion as predictors of severe coronary artery disease. Circu-lation 1980; 61:572–578
10 Weiner DA, McCabe CH, Cutler SS, et al. Decrease insystolic blood pressure during exercise testing: reproducibil-ity, response to coronary bypass surgery and prognosticsignificance. Am J Cardiol 1982; 49:1627–1631
11 Lele SS, Scalia G, Thomson H, et al. Mechanism of exercisehypotension in patients with ischemic heart disease. Circu-lation 1994; 90:2701–2709
12 Allison TG, Cordeiro MA, Miller TD, et al. Prognosticsignificance of exercise-induced systemic hypertension inhealthy subjects. Am J Cardiol 1999; 83:371–375
13 Molina L, Elosua R, Marrugat J, et al. Relation of maximumblood pressure during exercise and regular physical activity in normotensive men with left ventricular mass and hyper-trophy. Am J Cardiol 1999; 84:890–893
14 Campbell L, Marwick HT, Pashkow JF, et al. Usefulness of an exaggerated systolic blood pressure response to exercisein predicting myocardial perfusion defects in known orsuspected coronary artery disease. Am J Cardiol 1999;84:1304–1310
15 Taylor AJ, Beller GA. Postexercise systolic blood pressureresponse: association with the presence and extent of per-fusion abnormalities on thallium-201 scintigraphy. AmHeart J 1995; 129:227–234
16 Tsuda M, Hatano K, Hayashi H, et al. Diagnostic value of post exercise systolic blood pressure response for detectingcoronary artery disease in patients with or without hyper-tension. Am Heart J 1993; 125:718–725
17 McHam SA, Marwick TH, Pashkow FJ, et al. Delayedsystolic blood pressure recovery after graded exercise: anindependent correlate of angiographic coronary disease.J Am Coll Cardiol 1999; 34:754–759
18 Lauer MS, Francis GS, Okin PM, et al. Impaired chrono-
tropic response to exercise stress testing as a predictor of mortality. JAMA 1999; 281:524–529
19 Dreifus LS, Fisch C, Griffin JC, et al. Guidelines forimplantation of cardiac pacemakers and antiarrhythmic de- vices: a report of the ACC/AHA task force on assessment of diagnostic and therapeutic cardiovascular procedures. Cir-culation 1991; 84:455–467
20 Ellestad MH, Wan M. Predictive implications of stresstesting: follow-up of 2700 subjects after maximum treadmillstress testing. Circulation 1975; 51:363–369
21 Wilkoff BL, Miller RE. Exercise testing for chronotropicassessment. Cardiol Clin 1992; 10:705–717
22 Cole CR, Blackstone EH, Pashkow MJ, et al. Heart-raterecovery immediately after exercise as a predictor of mor-tality. N Engl J Med 1999; 341:1351
23 Tavel ME. The appearance of gallop rhythm after exercisestress testing. Clin Cardiol 1996; 19:887–891
24 Viik J, Lehtinen R, Turjanmaa V, et al. Correct utilization of exercise electrocardiographic leads in differentiation of men with coronary artery disease from patients with a lowlikelihood of coronary artery disease using peak exerciseST-segment depression. Am J Cardiol 1998; 81:964–969
25 Braat SH, Kingma JH, Brugada P, et al. Value of lead V4 Rin exercise testing to predict proximal stenosis of the rightcoronary artery. J Am Coll Cardiol 1985; 5:1308–1311
26 Michaelides AP, Psomadaki ZD, Dilaveris PE, et al. Im-proved detection of coronary artery disease by exerciseelectrocardiography with the use of right precordial leads.N Engl J Med 1990; 340:340–345
27 Miliken JA, Abdollah H, Burggraf GW. False-positive tread-mill exercise tests due to computer averaging. Am J Cardiol1990; 65:946–948
28 McHenry PL, Fisch C. Clinical applications of the treadmillexercise test. Mod Concepts Cardiovasc Dis 1977; 46:21–25
29 Rijneke AD, Ascoop CA, Talmon JL. Clinical significance ofupsloping ST segments in exercise electrocardiography.Circulation 1980; 61:671–678
30 Greenberg PS, Friscia DA, Ellestad MH. Predictive accu-racy of Q-X/Q-T ratio, Q-Tc interval, S-T depression and R
wave amplitude during stress testing. Am J Cardiol 1979;44:18–2331 Sheffield LT. Upsloping ST segments: easy to measure, hard
to agree upon. Circulation 1991; 84:426–42832 Sansoy V, Watson DD, Beller GA. Significance of slow
33 Stuart RJ, Ellestad MH. Upsloping ST segments in exercisetesting. Am J Cardiol 1976; 37:19–22
34 Hollenberg M, Go M Jr, Massie BM, et al. Influence of R-wave amplitude on exercise-induced ST depression: needfor a “gain factor” correction when interpreting stress elec-trocardiograms. Am J Cardiol 1985; 56:13–17
35 Ellestad MH, Crump R, Surber M. The significance of leadstrength on ST change during treadmill stress test. J Elec-trocardiol 1992; 25:31–34
36 Cheng S, Ellestad MH, Selvester RH. Significance of ST-segment depression with R-wave amplitude decrease onexercise testing. Am J Cardiol 1999; 83:955–959
37 Froelicher VF, Lehmann KG, Thomas R, et al. The electro-cardiographic exercise test in a population with reduced workup bias: diagnostic performance, computerized inter-pretation, and multivariable prediction. Ann Intern Med1998; 128:965–974
38 Galik DM, Mahmarian JJ, Verani MS. Therapeutic signifi-cance of exercise-induced ST-segment elevation in patients without previous myocardial infarction. Am J Cardiol 1993;72:1–7
denced by intracoronary electrogram during balloon angio-plasty. J Am Coll Cardiol 1990; 15:1007–1011
76 Chikamori T, Yamada M, Takata J, et al. Exercise-inducedprominent U waves as a marker of significant narrowing of the left circumflex or right coronary artery. Am J Cardiol1994; 74:495–499
77 Chikamori T, Takata J, Furuno T, et al. Usefulness of U-wave analysis in detecting significant narrowing limited toa single coronary artery. Am J Cardiol 1995; 75:508–511
78 Bonoris PE, Greenberg PS, Christison GW, et al. Evaluationof R wave amplitude changes versus ST-segment depressionin stress testing. Circulation 1978; 57:904–910
79 Baron DW, Ilsley C, Sheiban I, et al. R wave amplitudeduring exercise: relation to left ventricular function andcoronary artery disease. Br Heart J 1980; 44:512–517
80 Battler A, Froelicher V, Slutsky R, et al. Relationship of QRSamplitude changes during exercise to left ventricular func-tion and volumes and the diagnosis of coronary artery disease. Circulation 1979; 60:1004–1013
81 Berman JL, Wynne J, Cohn PF. Multiple-lead QRS changes with exercise testing: diagnostic value and hemodynamicimplications. Circulation 1980; 61:53–61
82 Fox K, England D, Jonathan A, et al. Inability of exercise-induced R wave changes to predict coronary artery disease.Am J Cardiol 1982; 49:674–679
83 Hopkirk JA, Uhl GS, Hickman JR, et al. Limitation of exercise-induced R wave amplitude changes in detectingcoronary artery disease in asymptomatic men. J Am CollCardiol 1984; 3:821–826
84 Wagner S, Cohn S, Selzer A. Unreliability of exercise-induced R wave changes as indexes of coronary artery disease. Am J Cardiol 1979; 44:1241–1246
85 Ellestad MH, Lerman S, Thomas L. The limitations of thediagnostic power of exercise testing. Am J NoninvasiveCardiol 1989; 3:139–146
86 Nohara R, Kambara H, Suzuki Y, et al. Septal Q wave inexercise testing: evaluation by single-photon emission com-puted tomography. Am J Cardiol 1985; 55:905–909
87 Furuse T, Mashiba H, Jordan JW, et al. Usefulness of
Q-wave response to exercise as a predictor of coronary artery disease. Am J Cardiol 1987; 59:57–6088 Pandya A, Ellestad MH, Crump R. Time course of changes
in P-wave duration during exercise. Cardiology 1996; 87:343–360
89 Shiran A, Halon DA, Merdler A, et al. Exercise-inducedleft-axis deviation of the QRS complex in left anteriordescending coronary artery disease and reversal after revas-cularization. Am J Cardiol 1994; 74:1277–1278
90 Boran KJ, Oliveros RA, Boucher CA, et al. Ischemia-associated intraventricular conduction disturbances duringexercise testing as a predictor of proximal left anteriordescending coronary artery disease. Am J Cardiol 1983;51:1098–1102
91 Madias JE, Knez P. Transient left posterior hemiblockduring myocardial ischemia-eliciting exercise treadmill test-ing. J Electrocardiol 1999; 32:57–64
92 Michaelides A, Ryan JM, VanFossen, et al. Relation betweenexercise-induced QRS prolongation and reversible myocar-dial perfusion defects in patients with coronary artery disease. Am J Noninvasive Cardiol. 1994; 8:53–57
93 Cantor A, Goldfarb B, Mai O, et al. Ischemia detection in women: the diagnostic value of exercise QRS durationchanges. J Electrocardiol 1998; 31:271–277
94 Cantor A, Goldfarb B, Aszodi A, et al. QRS prolongationmeasured by a new computerized method: a sensitivemarker for detecting exercise induced ischemia. Cardiology 1997; 88:446–452
95 Michaelides AP, Dilaveris PE, Psomadaki ZD, et al. QRSprolongation on the signal-averaged electrocardiogram ver-sus ST-segment changes on the 12-lead electrocardiogram: which is the most sensitive electrocardiographic marker of myocardial ischemia? Clin Cardiol 1999; 22:403–408
96 Cantor A, Goldfarb B, Aszodi A, et al. Ischemia detectionafter myocardial infarction. J Electrocardiol 1998; 31:9–15
97 Michaelides A, Boudoulas H, Vyssoulis GP, et al. Exercise-induced S-wave prolongation in left anterior descendingcoronary artery stenosis. Am J Cardiol 1992; 70:1407–1411
98 Macieira-Coelho E, Garcia-Alves M, Lacerda AP, et al.Postexercise changes of theQTcinterval in patientswith recentmyocardial infarction. J Electrocardiol 1993; 26:125–129
99 Egloff C, Merola P, Schiavon C, et al. Sensitivity, specificity,and predictive accuracy of the Q wave, QX/QT ratio, QTcinterval and ST depression during exercise testing in men withcoronary artery disease. Am J Cardiol 1987; 60:1006–1008
100 Koide Y, Yotsukura M, Tajino K, et al. Use of QT dispersionmeasured on treadmill exercise electrocardiograms for de-tecting restenosis after percutaneous transluminal coronary angioplasty. Clin Cardiol 1999; 22:639– 648
101 Stoletniy LN, Pai RG. Value of QT dispersion in theinterpretation of exercise stress test in women. Circulation1997; 96:904–910
102 Gianrossi R, Detrano R, Mulvihill D, et al. Exercise-inducedST depression in the diagnosis of coronary artery disease: ameta-analysis. Circulation 1989; 80:87–98
103 Detrano R, Gionrossi R, Froelicher V. The diagnosticaccuracy of the exercise electrocardiogram: a meta-analysis of 22 years of research. Prog Cardiovasc Dis 1989; 32:173–206
104 Kwok Y, Kim C, Grady D, et al. Meta-analysis of exercisetesting to detect coronary artery disease in women. Am JCardiol 1999; 83:660– 666
105 Tavel ME, Shaar C. Relation between the electrocardio-graphic stress test and degree and location of myocardialischemia. Am J Cardiol 1999; 84:119–124
106 Bartel AG, Behar VS, Peter RH, et al. Graded exercise stresstests in angiographically documented coronary artery dis-ease. Circulation 1974; 49:348–356
107 McHenry PL, Phillips JF, Knoebel SB. Correlation of computer-quantitated treadmill exercise electrocardiogram with arteriographic location of coronary artery disease. Am JCardiol 1972; 30:747–752
108 Taylor AJ, Sackett MC, Beller GA. The degree of ST-segment depression on symptom-limited exercise testing:relation to the myocardial ischemic burden as determined by thallium-201 scintigraphy. Am J Cardiol 1995; 75:228–231
109 Dunn RF, Freedman B, Bailey IK, et al. Localization of coronary artery disease with exercise electrocardiography:correlation with thallium-201 myocardial perfusion scan-ning. Am J Cardiol 1981; 48:839–843
110 Fox RM, Hakki AH, Iskandrian AS. Relation betweenelectrocardiographic and scintigraphic location of myocar-dial ischemia during exercise in one-vessel coronary artery disease. Am J Cardiol 1984; 53:1529–1531
111 Kaplan MA, Harris CM, Aronow WS, et al. Inability of thesubmaximal treadmill stress test to predict the location of coronary disease. Circulation 1973; 47:250–256
112 Mark DB, Hlatky MA, Lee KL, et al. Localizing coronary artery obstructions with the exercise treadmill test. AnnIntern Med 1987; 106:53–55
113 Michaelides A, Psomadaki ZD, Richter DJ, et al. Exercise-induced ST-segment changes in lead V1 identify the signif-icantly narrowed coronary artery in patients with single- vessel disease. J Electrocardiol 1999; 32:7–14
114 Miranda CP, Liu J, Kadar A, et al. Usefulness of exercise-induced ST-segment depression in the inferior leads during
exercise testing as a marker for coronary artery disease. Am JCardiol 1992; 69:303–307
115 Goldschlager N, Selzer A, Cohn K. Treadmill stress tests asindicators of presence and severity of coronary artery dis-ease. Ann Intern Med 1976; 85:277–286
116 Colby J, Hakki AH, Iskandrian AS, et al. Hemodynamic,angiographic and scintigraphic correlates of positive exerciseelectrocardiograms: emphasis on strongly positive exerciseelectrocardiograms. J Am Coll Cardiol 1983; 2:21–29
117 McNeer JF, Margolis JR, Lee KL, et al. The role of theexercise test in the evaluation of patients for ischemic heartdisease. Circulation 1978; 57:64–70
118 Podrid PJ, Graboys TB, Lown B. Prognosis of medically treated patients with coronary-artery disease with profoundST-segment depression during exercise testing. N EnglJ Med 1981; 305:1111–1116
119 Bogaty P, Guimond J, Robitaille NM, et al. A reappraisal of exercise electrocardiographic indexes of the severity of ischemic heart disease: angiographic and scintigraphic cor-relates. J Am Coll Cardiol 1997; 29:1497–1504
120 Chikamori T, Doi YL, Furuno T, et al. Diagnostic signifi-cance of deep T-wave inversion induced by exercise testingin patients with suspected coronary artery disease. Am JCardiol 1992; 70:403–406
121 Karnegis JN, Matts J, Tuna N, et al. Comparison of exercise-positive with recovery-positive treadmill graded exercisetest. Am J Cardiol 1987; 60:544–547
122 Rywik TM, Zink NS, Gittings NS, et al. Independentprognostic significance of ischemic ST-segment responselimited to recovery from treadmill exercise in asymptomaticsubjects. Circulation 1998; 97:2117–2122
123 Savage MP, Squires LS, Hopkins JT, et al. Usefulness of STsegment depression as a sign of coronary artery disease when confined to the recovery period. Am J Cardiol 1987;60:1405–1406
124 Barlow JB. The “false positive” exercise electrocardiogram: value of time course patterns in assessment of depressed STsegments and inverted T waves. Am Heart J 1985; 110:1328–1336
125 Rodriguez M, Moussa I, Froning J, et al. Improved exercisetest accuracy using discriminant function analysis and “re-covery ST slope.” J Electrocardiol 1993; 26:207–218
126 Okin PM, Ameisen O, Kligfield P. Recovery-phase patternsof ST segment depression in the heart rate domain. Circu-lation 1989; 80:533–541
127 Cole J, Ellestad, MG. Significance of chest pain duringtreadmill exercise. Am J Cardiol 1978; 41:227–232
128 Tavel ME. Specificity of electrocardiographic stress test in women versus men. Am J Cardiol 1992; 70:545–547
129 Morise AP, Diamond GA. Comparison of the sensitivity andspecificity of exercise electrocardiography in biased andunbiased populations of men and women. Am Heart J 1995;130:741–747
130 Sketch MH, Mohiuddin SM, Lynch JD, et al. Significant sexdifferences in the correlation of electrocardiographic exer-cise testing and coronary arteriograms. Am J Cardiol 1975;36:169–173
131 Guiteras P, Chaitman BR, Waters DD, et al. Diagnosticaccuracy of exercise ECG lead systems in clinical subsets of women. Circulation 1982; 65:1465–1474
132 Weiner DA, Ryan TJ, McCabe CH, et al. Correlationsamong history of angina: ST-segment response and preva-lence of coronary artery disease in the Coronary Artery Surgery Study (CASS). N Engl J Med 1979; 301:230–235
133 Morise AP, Dalai JN, Duval RD. Frequency of oral estrogenreplacement therapy in women with normal and abnormalexercise electrocardiograms and normal coronary arteries by
angiogram. Am J Cardiol 1993; 72:1197–1199134 Hellerstein HK, Prozan GB, Leibow IM, et al. The two-step
exercise test as a test of cardiac function in chronic rheu-matic heart disease and in arteriosclerotic heart disease withold myocardial infarction. Am J Cardiol 1961; 7:234–252
135 Mattingly TW. The postexercise electrocardiogram: its valuein the diagnosis and prognosis of coronary arterial disease.Am J Cardiol 1962; 9:395–409
136 Harris CN, Aronow WS, Parker DP, et al. Treadmill stresstest in left ventricular hypertrophy. Chest 1973; 63:353–357
137 Roitman D, Jones WB, Sheffield LT. Comparison of sub-maximal exercise ECG test with coronary cine angiocardio-gram. Ann Intern Med 1970; 72:641–647
138 Smith RH, LePetri B, Moisa RB, et al. Association of increased left ventricular mass in the absence of electrocar-diographic left ventricular hypertrophy with ST depressionduring exercise. Am J Cardiol 1995; 76:973–974
139 McHenry PL, Richmond HW, Weisenberger BL, et al.Evaluation of abnormal exercise electrocardiogram in appar-ently healthy subjects: labile repolarization (ST-T) abnor-malities as a cause of false-positive responses. Am J Cardiol1981; 47:1152–1160
140 Nordstrom-Ohrberg G. Effect of digitalis glycosides onelectrocardiogram and exercise test in healthy subjects. ActaMed Scand 1964; 24:(suppl 420):1–75
141 Sketch MH, Mooss AN, Butler ML, et al. Digoxin-inducedpositive exercise tests: their clinical and prognostic signifi-cance. Am J Cardiol 1981; 48:655–659
142 Georgopoulos AJ, Proudfit WL, Page IH. Effect of exerciseon electrocardiograms of patients with low serum potassium.Circulation 1961; 23:567–572
143 Soloff LA, Fewell JW. Abnormal electrocardiographic re-sponses in exercise in subjects with hypokalemia. Am J MedSci 1961; 242:724–728
144 Riley CP, Oberman A, Sheffield LT. Electrocardiographiceffects of glucose ingestion. Arch Intern Med 1972; 130:703–707
changes secondary to hyperventilation and exercise. AnnIntern Med 1974; 81:479–482146 Lary D, Goldschlager N. Electrocardiographic changes dur-
ing hyperventilation resembling myocardial ischemia in pa-tients with normal coronary arteriograms. Am Heart J 1974;87:383–390
147 Lachman AB, Semler HJ, Gustafson RH. Postural ST-Tchanges in the radioelectrocardiogram simulating myocar-dial ischemia. Circulation 1965; 31:557–563
148 Friesinger GC, Biern RO, Likar I, et al. Exercise electro-cardiography and vasoregulatory abnormalities. Am J Car-diol 1972; 30:733–740
149 Furberg C. Adrenergic beta-blockade and electrocardio-graphic ST-T changes. Acta Med Scand 1967; 181:21–32
150 Engel PJ, Alpert BL, Hickman JR Jr. The nature andprevalence of the abnormal exercise electrocardiogram inmitral valve prolapse. Am Heart J 1979; 98:716–724
151 Gardin JM, Isner JM, Ronan JA Jr, et al. Pseudoischemic“false positive” S-T segment changes induced by hyperven-tilation in patients with mitral valve prolapse. Am J Cardiol1980; 45:952–958
152 Kattus AA. Exercise electrocardiography: recognition of theischemic response, false positive and negative patterns. Am JCardiol 1974; 33:721–731
153 Feil H, Brofman BL. The effect of exercise on the electro-cardiogram of bundle branch block. Am Heart J 1953;45:665–669
154 Gazes PC. False-positive exercise test in the presence of the
Wolff-Parkinson-White syndrome. Am Heart J 1969; 78:13–15
155 Strasberg B, Ashley WW, Wyndham CR, et al. Treadmillexercise testing in the Wolff-Parkinson-White syndrome.Am J Cardiol 1980; 45:742–748
156 Hamasaki S, Nakano F, Arima S, et al. A new criterioncombining ST/HR slope and (ST/(HR index for detection of coronary artery disease in patients on digoxin therapy. Am JCardiol 1998; 81:1100–1104
158 McHenry PL, Cogan OJ, Elliott WC, et al. False positiveECG response to exercise secondary to hyperventilation:cineangiographic correlation. Am Heart J 1970; 79:683–687
159 Likoff W, Segal BL, Kasparian H. Paradox of normalselective coronary arteriograms in patients considered tohave unmistakable coronary heart disease. N Engl J Med1967; 276:1063–1066
160 Epstein SE, Cannon RO, Bonow RO. Exercise testing inpatients with microvascular angina. Circulation 1991;83(suppl):II-I73–II-176
161 Orzan F, Garcia E, Mathur VS, et al. Is the treadmillexercise test useful for evaluating coronary artery disease inpatients with complete left bundle branch block? Am JCardiol 1978; 42:36–40
162 Whinnery JE, Froelicher VF, Stewart AJ, et al. The electro-cardiographic response to maximal treadmill exercise inasymptomatic men with left bundle branch block. AmHeart J 1977; 94:316–324
163 Cooksey JD, Parker BM, Bahl OP. The diagnostic contribu-tion of exercise testing in left bundle branch block. AmHeart J 1974; 88:482–486
164 Lewis CM, Dagenais GR, Friesinger CG, et al. Coronary arteriographic appearance in patients with left bundlebranch block. Circulation 1970; 41:299–307
165 Ibrahim NS, Abboud G, Selvester RS, et al. Detectingexercise-induced ischemia in left bundle branch block usingthe electrocardiogram. Am J Cardiol 1998; 82:832–885
166 Tanaka T, Friedman MJ, Okada RD, et al. Diagnostic valueof exercise-induced ST segment depression in patients withright bundle branch block. Am J Cardiol 1978; 41:670–673
167 Chacko KA, Jacob A, Bhat KVR. Right bundle branch blockmasks exercise-induced ST segment depression. Am J Non-invasive Cardiol 1994; 8:391–396
168 Sapin PM, Koch GG, Blauwet MB, et al. Identification of false positive exercise tests with use of electrocardiographiccriteria: a possible role for atrial repolarization waves. J AmColl Cardiol 1991; 18:127–135
169 Sapin PM, Blauwet MB, Koch GG, et al. Exaggerated atrialrepolarization waves as a predictor of false positive exercisetests in an unselected population. J Electrocardiol 1995;28:313–321
170 Hayashi H, Okajima M, Yamada K. Atrial T (Ta) wave andatrial gradient in patients with AV block. Am Heart J 1976;91:689–698
171 Gianelli RD, Treister BL, Harrison DC. The effect of propranolol on exercise induced ischemic S-T depression.Am J Cardiol 1969; 24:161–165
172 Goldstein RF, Rosing DR, Redwood DR, et al. Clinical andcirculatory effects of isosorbide dinitrate: comparison withnitroglycerin. Circulation 1971; 43:629–640
173 Kansal S, Roitman D, Sheffield LT. Stress testing and ST-segment depression at rest. Circulation 1976; 54:636–639
174 Fearon WF, Lee DP, Froelicher VF. The effect of restingST segment depression on the diagnostic characteristics of the exercise treadmill test. J Am Coll Cardiol 2000; 35:1206–1211
175 Kwok JM, Miller TD, Christian TF, et al. Prognostic value of a treadmill exercise score in symptomatic patients withnonspecific ST-T abnormalities on resting ECG. JAMA1999; 282:1047–1053
176 Giorgetti A, Sambuceti G, Neglia D, et al. Myocardial bloodflow and perfusion reserve in infarcted patients with stress-induced normalization of previously negative T waves: a positronemission tomography study. J Nucl Cardiol 1999; 6:11–19
177 Mobilia G, Zanco P, Desideri A, et al. T wave normalizationin infarct-related electrocardiographic leads during exercisetesting for detection of residual viability. J Am Coll Cardiol1998; 32:75–82
178 Frais MA, Hoeschen RJ. Exercise-induced T wave normal-ization is not specific for myocardial ischemia detected by perfusion scintigraphy. Am Heart J 1990; 119:1225–1229
179 Alimurung BN, Gilbert CA, Felner JM, et al. The influenceof early repolarization variant on the exercise electrocardio-gram: a correlation with coronary arteriograms. Am Heart J1980; 99:739–745
180 Bruce RA, DeRouen TA, Hossack KF. Value of maximalexercise tests in risk assessment of primary coronary artery disease events in healthy men: five years’ experience of theSeattle Heart Watch Study. Am J Cardiol 1980; 46:371–378
181 Froelicher VF, Thomas MM, Pillow C, et al. Epidemiologicstudy of asymptomatic men screened by maximal treadmill
testing for latent coronary artery disease. Am J Cardiol 1974;34:770–776182 Giagnoni E, Secchi M, Wu SC, et al. Prognostic value of
exercise EKG testing in asymptomatic normotensive sub- jects: a prospective matched study. N Engl J Med 1983;309:1085–1089
183 McHenry PL, O’Donnell J, Morris SN, et al. The abnormalexercise electrocardiogram in apparently healthy men: apredictor of angina pectoris as an initial coronary eventduring long-term follow-up. Circulation 1984; 70:547–551
184 Doyle JT, Kinch SH. The prognosis of an abnormal electro-cardiographic stress test. Circulation 1970; 41:545–553
185 Ellestad MH, Wan MK. Predictive implications of stresstesting: follow-up of 2700 subjects after maximum treadmillstress testing. Circulation 1975; 51:363–369
186 Rautaharju PM, Princas RJ, Eifler WJ, et al. Prognostic value of exercise electrocardiogram in men at high risk of future coronary heart disease: Multiple Risk Factor Inter- vention Trial experience. J Am Coll Cardiol 1986; 8:1–10
187 Mark DB, Shaw L, Harrell FE Jr, et al. Prognostic value of a treadmill exercise score in outpatients with suspectedcoronary artery disease. N Engl J Med 1991; 325:849–853
188 Chatziioannou SN, Moore WH, Ford PV, et al. Prognostic value of myocardial perfusion imaging in patients with highexercise tolerance. Circulation 1999; 99:867–872
189 Roger V, Jacobsen SJ, Pellikka PA, et al. Prognostic value oftreadmill exercise testing. Circulation 1998; 98:2836–2841
190 Froelicher VF, Morrow K, Brown M, et al. Prediction of atherosclerotic cardiovascular death in men using a prognos-tic score. Am J Cardiol 1994; 73:133–138
191 Weiner DA, Ryan TJ, McCabe CH, et al. Prognosticimportance of a clinical profile and exercise test in medically treated patients with coronary artery disease. J Am CollCardiol 1984; 3:772–779
192 Hachamovitch R, Berman DS, Kiat H, et al. Exercisemyocardial perfusion SPECT in patients without knowncoronary artery disease. Circulation 1996; 93:905–914
193 Jain A, Myers GH, Sapin PM, et al. Comparison of symptom-limited and low-level exercise tolerance test early after myocar-dial infarction. J Am Coll Cardiol 1993; 22:1816–1820
194 Juneau M, Colles P, Theroux P, et al. Symptom-limited versus low level exercise testing before hospital discharge after
myocardial infarction. J Am Coll Cardiol 1992; 20:927–933195 Senaratne MPJ, Smith G, Gulamhusein SS. Feasibility and
safety of early exercise testing using the Bruce protocol afteracute myocardial infarction. J Am Coll Cardiol 2000; 35:1212–1220
196 Davidson DM, DeBusk RF. Prognostic value of a singleexercise test 3 weeks after uncomplicated myocardial infarc-tion. Circulation 1980; 61:236–242
197 Starling MR, Crawford MH, Henry RL, et al. Prognostic value of electrocardiographic exercise testing and noninva-sive assessment of left ventricular ejection fraction soon afteracute myocardial infarction. Am J Cardiol 1986; 57:532–537
198 Theroux P, Water DD, Halphen C, et al. Prognostic value of exercise testing soon after myocardial infarction. N EnglJ Med 1979; 301:341–345
199 Weld FM, Chu KL, Bigger JT Jr, et al. Risk stratification with low-level exercise testing 2 weeks after acute myocar-dial infarction. Circulation 1981; 64:306–314
200 Waters DD, Bosch X, Bouchard A, et al. Comparison of clinical variables and variables derived from a limited pre-discharge exercise test as predictors of early and late mortality after myocardial infarction. J Am Coll Cardiol 1985; 5:1–8
201 Senaratne MPJ, Hsu L, Rossall RE, et al. Exercise testingafter myocardial infarction: relative values of the low levelpredischarge and post discharge exercise test. J Am Coll
Cardiol 1988; 12:1416–1422202 Villella M, Villella A, Barlera S, et al. Prognostic significanceof double product and inadequate double product responseto maximal symptom-limited exercise stress testing aftermyocardial infarction in 6296 patients treated with throm-bolytic agents. Am Heart J 1999; 137:443–452
203 Haines DE, Beller GA, Watson DD, et al. Exercise-inducedST segment elevation 2 weeks after uncomplicated myocar-dial infarction: contributing factors and prognostic signifi-cance. Am J Coll Cardiol 1987; 9:996–1003
204 Koppes GM, Kruyer W, Beckmann CH, et al. Response toexercise early after uncomplicated acute myocardial infarc-tion in patients receiving no medication: long-term follow-up. Am J Cardiol 1980; 46:764–769
205 Krone RJ, Gillespie JA, Weld FM, et al. Low-level exercisetesting after myocardial infarction: usefulness in enhancingclinical risk stratification. Circulation 1985; 71:80–89
206 Schwartz KM, Turner JD, Sheffield LT, et al. Limitedexercise testing soon after myocardial infarction. Ann InternMed 1981; 94:727–734
207 Shaw LJ, Peterson ED, Kesler K, et al. A meta-analysis of predischarge risk stratification after acute myocardial infarction with stress electrocardiographic, myocardial perfusion, and ventricular function imaging. Am J Cardiol 1996; 78:1327–1337
208 Miranda CP, Herbert WH, Dubach P, et al. Post-myocardialinfarction exercise testing: non-Q wave versus Q wavecorrelation with coronary angiography and long-term prog-nosis. Circulation 1991; 84:2357–2365
209 Chaitman BR, Miller DD. Perioperative cardiac evaluationfor noncardiac surgery noninvasive cardiac testing. ProgCardiovasc Dis 1998; 40:405–418
210 Blackburn H, Taylor HL, Hamrell B, et al. Premature ventricular complexes induced by stress testing. Am J Car-diol 1973; 31:441–449
211 Jelinek MV, Lown B. Exercise stress testing for exposure of cardiac arrhythmia. Prog Cardiovasc Dis 1974; 16:497–522
212 McHenry PL, Morris SN, Kavalier M, et al. Comparativestudy of exercise-induced ventricular arrhythmias in normalsubjects and patients with documented coronary artery disease. Am J Cardiol 1976; 37:609–616
213 Faris JV, McHenry PL, Jordan JW, et al. Prevalence andreproducibility of exercise-induced ventricular arrhythmiasduring maximal exercise testing in normal men. Am JCardiol 1976; 37:617–622
214 Busby MJ, Shefrin EA, Fleg JL. Prevalence and long-termsignificance of exercise-induced frequent or repetitive ven-tricular ectopic beats in apparently healthy volunteers. J AmColl Cardiol 1989; 14:1659–1665
215 Goldschlager N, Cake D, Cohn K. Exercise-induced ven-tricular arrhythmias in patients with coronary artery disease:their relationship to angiographic findings. Am J Cardiol1973; 31:434–440
216 Henry RL, Kennedy GT, Crawford MH. Prognostic value of exercise-induced ventricular ectopic activity for mortality after acute myocardial infarction. Am J Cardiol 1987; 59:1251–1255
217 Califf RM, McKinnis RA, McNeer JF, et al. Prognostic valueof ventricular arrhythmias associated with treadmill exercisetesting in patients studied with cardiac catheterization forsuspected ischemic heart disease. J Am Coll Cardiol 1983;2:1060–1067
218 Margonato A, Mailhac A, Bonetti F, et al. Exercise-inducedischemic arrhythmias in patients with previous myocardialinfarction: role of perfusion and tissue viability. J Am CollCardiol 1996; 27:593–598
219 Nair CK, Aronow WS, Sketch MH, et al. Diagnostic andprognostic significance of exercise-induced premature ven-tricular complexes in men and women: a four year follow-up.J Am Coll Cardiol 1985; 5:1201–1206
220 Sami M, Chaitman B, Fisher L, et al. Significance of exercise-induced ventricular arrhythmia in stable coronary artery disease: a Coronary Artery Surgery Study project.Am J Cardiol 1984; 54:1182–1188
221 Schweikert RA, Pashkow FJ, Snader CE, et al. Association ofexercise-induced ventricular ectopic activitywith thalliummyo-cardial perfusion and angiographic coronary artery disease instable, low-risk populations. Am J Cardiol 1999; 83:530–534
222 Helfant RH, Pine R, Kabde V, et al. Exercise-related ventricular premature complexes in coronary heart disease:correlations with ischemia and angiographic severity. AnnIntern Med 1974; 80:589–592
223 Udall JA, Ellestad MH. Predictive implications of ventricu-lar premature contractions associated with treadmill stresstesting. Circulation 1977; 56:985–989
224 Wexler L, Brundage B, Crouse J, et al. Coronary artery calcification: pathophysiology, epidemiology, imaging meth-ods, and clinical implications: a statement for health profes-sionals from the American Heart Association Writing Group.Circulation 1996; 94:1175–1192
225 Gibbons RJ, Chatterjee K, Daley J, et al. ACC/AHA/ACP-ASIM guidelines for the management of patients withchronic stable angina: a report of the American College of Cardiology/American Heart Association Task Force on Prac-tice Guidelines (Committee on the Management of Patients With Chronic Stable Angina). J Am Coll Cardiol 1999;33:2092–2197
226 Lewis WR, Amsterdam EA, Turnipseed S. Immediate exer-cise testing of low risk patients with known coronary artery disease presenting to the emergency department with chestpain. J Am Coll Cardiol 1999; 33:1843–1847
227 Farkouh ME, Smars PA, Reeder GS, et al. A clinical trial of a chest-pain observation unit for patients with unstableangina. N Engl J Med 1998; 339:1992–1998
228 Marcus R, Lowe R, Froelicher, VF. The exercise test asgatekeeper. Chest 1995; 107:1442–1446
: Current Concepts With*Stress Testing in Cardiac Evaluation
February 24, 2012This information is current as of
http://chestjournal.chestpubs.org/content/119/3/907.full.htmlUpdated Information and services can be found at:
Updated Information & Services
http://chestjournal.chestpubs.org/content/119/3/907.full.html#ref-list-1This article cites 227 articles, 99 of which can be accessed free at:
References
http://chestjournal.chestpubs.org/content/119/3/907.full.html#related-urlsThis article has been cited by 4 HighWire-hosted articles:
Cited Bys
http://www.chestpubs.org/site/misc/reprints.xhtmlfound online at:Information about reproducing this article in parts (figures, tables) or in its entirety can bePermissions & Licensing
http://www.chestpubs.org/site/misc/reprints.xhtmlInformation about ordering reprints can be found online:
Reprints
"Services" link to the right of the online article.Receive free e-mail alerts when new articles cite this article. To sign up, select the
Citation Alerts
PowerPoint slide format. See any online figure for directions.articles can be downloaded for teaching purposes inCHEST Figures that appear in
