The exercise test continues to have an integral place in cardiovascular medicine because of its high yield of diagnostic, prognostic and functional information.
In the clinical setting, the major indications for exercise testing are the diagnosis and prognostication of heart disease.
The determination of exercise capacity is helpful in quantifying disability, estimating prognosis and monitoring the disease state of patients with chronic heart disease and known coronary heart disease.
The major emphasis is on the analysis of the electrocardiogram (ECG) in the majority of clinical tests.
The reproduction of symptoms such an angina or presyncope is vital for clinical purposes.
My seminar reviews the development of exercise ECG, gives a brief review of the pathophysiologic basis for exercise induced ST segment depression, provides detailed information on the performance, interpretation and applications of the exercise tolerance test and address the controversies and future directions in exercise ECG.
Exercise is a common physiological stress used to elicit cardiovascular abnormalities not present at rest and to determine the adequacy of cardiac function. Exercise electrocardiography (ECG) is one of the most frequent noninvasive modalities used to assess patients with suspected or proven cardiovascular disease.
The test is mainly used to estimate prognosis and to determine functional capacity, the likelihood and extent of coronary artery diseases (CAD), and the effects of therapy. Hemodynamic and ECG measurements combined with ancillary techniques such as metabolic gas analysis, radionuclide imaging, and echocardiography enhance the information content of exercise testing in selected patients. Anticipation of dynamic exercise results in an acceleration of ventricular rate due to vagal withdrawal, increase in alveolar ventilation, and increased venous return primarily as a result of sympathetic venoconstriction. In normal persons, the net effect is to increase resting cardiac output before the start of exercise. The magnitude of hemodynamic response during exercise depends on the severity of the exercise and the amount of muscle mass involved.
In the early phases of exercise in the upright position, cardiac output is increased by an augmentation in stroke volume mediated through the use of the Frank-Starling mechanism and heart rate; the increase in cardiac output in the latter phases of exercise is primarily due to a sympathetic-mediated increase in ventricular rate. At fixed submaximal workloads below anaerobic threshold, steady-state conditions are usually reached after the second minute of exercise, following which heart rate, cardiac output, blood pressure, and pulmonary ventilation are maintained at reasonably constant levels. During strenuous exertion, sympathetic discharge is maximal and parasympathetic stimulation is withdrawn, resulting in vasoconstriction of most circulatory body systems, except for that in exercising muscle and in the cerebral and coronary circulations. Venous and arterial norepinephrine release from sympathetic postganglionic nerve endings, as well as plasma renin levels, are increased; the catecholamine release enhances ventricular contractility.
As exercise progresses, skeletal muscle blood flow is increased, oxygen extraction increases by as much as threefold, total calculated peripheral resistance decreases, and systolic blood pressure, mean arterial pressure, and pulse pressure usually increase. Diastolic blood pressure does not change significantly. The pulmonary vascular bed can accommodate as much as a sixfold increase in cardiac output with only modest increases in pulmonary artery pressure, pulmonary capillary wedge pressure, and right atrial pressure; in normal individuals, this is not a limiting determinant of peak exercise capacity. Cardiac output increases by four- to sixfold above basal levels during strenuous exertion in the upright position, depending on genetic endowment and level of training. The maximum heart rate and cardiac output are decreased in older individuals, partly because of decreased beta-adrenergic responsivity.
Maximum heart rate can be estimated from the formula 220 - age in years, with a standard deviation of 10 to 12 beats per minute. The age-predicted maximum heart rate is a useful measurement for safety reasons. However, the wide standard deviation in the various regression equations used and the impact of drug therapy limit the usefulness of this parameter in estimating the exact age-predicted maximum for an individual patient. In the postexercise phase, hemodynamics return to baseline within minutes of termination of exercise. Vagal reactivation is an important cardiac deceleration mechanism after' exercise and is accelerated in welltrained athletes but blunted in patients with chronic heart failure (see also section on heart rate). Intense physical work or significant cardiorespiratory impairment may interfere with achievement of a steady state, and an oxygen deficit occurs during exercise. The total oxygen uptake in excess of the resting oxygen uptake during the recovery period is the oxygen debt.
Patient position At rest, the cardiac output and stroke volume are higher when the person is in the supine position than when the person is in the upright position. With exercise in normal supine persons, the elevation of cardiac output results almost entirely from an increase in heart rate, with little augmentation of stroke volume. In the upright posture, the increase in cardiac output in normal individuals results from a combination of elevations in stroke volume and heart rate. A change from supine to upright posture causes a decrease in venous return left ventricular end-diastolic volume and pressure, stroke volume, and cardiac index. Renin and norepinephrine levels are increased. End-systolic volume and ejection fraction are not significantly changed. The net effect on exercise performance is an approximate 10 percent increase in exercise time cardiac index, heart rate, and rate pressure product at peak exercise in the upright as compared with the supine position.
Cardiopulmonary Exercise Testing Cardiopulmonary exercise testing involves measurements of respiratory oxygen uptake (VO 2 ), carbon dioxide production (VCO 2 ), and ventilatory parameters during a symptom-limited exercise test. VO 2 max is the product of maximal arterial-venous oxygen difference and cardiac output and represents the largest amount of oxygen a person can use while performing dynamic exercise involving a large part of total muscle mass. The VO 2 max decreases with age, is usually less in women than in men, and can vary among individuals as a result of genetic factors. VO 2 max is diminished by degree of cardiovascular impairment and by physical inactivity. Peak exercise capacity is decreased when the ratio of measured to predicted VO2 max is less than 85 to 90 percent.
Oximetry, performed noninvasively, can be used to monitor arterial oxygen saturation, and the value normally does not decrease by more than 5 percent during exercise. Estimates of oxygen saturation during strenuous exercise using pulse oximetry can be unreliable in some patients.
Anaerobic threshold is a theoretical point during dynamic exercise when muscle tissue switches over to anaerobic metabolism as an additional energy source. Lactic acid begins to accumulate when a healthy untrained subject reaches about 50 to 60 percent of the maximal capacity for aerobic metabolism. Above the anaerobic threshold, carbon dioxide is produced in excess of oxygen consumption.
The anaerobic threshold is a useful parameter because work below this level encompasses most activities of daily living. Anaerobic threshold is often reduced in patients with significant cardiovascular disease.
Changes in anaerobic threshold and peak VO 2 with repeat testing can be used to assess disease progression, response to medical therapy, and improvement in cardiovascular fitness with training.
The respiratory exchange ratio represents the amount of carbon dioxide produced divided by the amount of oxygen consumed. The respiratory exchange ratio ranges from 0.7 to 0.85 at rest and is partly dependent on the predominant fuel used for cellular metabolism (e.g., the respiratory exchange rate for predominant carbohydrate use is 1.0, whereas the respiratory exchange ratio for predominant fatty acid use is 0.7).
At high exercise levels, carbon dioxide production exceeds VO 2 , and a respiratory exchange ratio greater than 1.1 often indicates that the subject has performed at maximal effort. METABOLIC EQUIVALENT In current use, the term metabolic equivalent (MET) refers to a unit of oxygen uptake in a sitting, resting person; 1 MET is equivalent to 3.5 ml 02/kg/min of body weight. Measured VO 2 in ml 02/min/kg divided by 3.5 ml 02/kg/min determines the number of METs associated with activity. Work activities can be calculated in multiples of METs; this measurement is useful to determine exercise prescriptions, assess disability, and standardize the reporting of submaximal and peak exercise workloads when different protocols are used.
The measurements obtained with cardiopulmonary exercise testing are useful in understanding an individual patient’s response to exercise and can be useful in the diagnostic evaluation of a patient with dyspnea.
General concerns prior to performing an exercise test include –
Besides emergency equipment, the safety and accuracy of testing equipment should be considered.
The treadmill should have front and side rails for subjects to steady themselves.
It should be calibrated monthly.
An emergency stop button should be readily available to the staff only.
A small plateform or stepping area at the level of belt is advisable so that the subject can start the test by “pedaling” the belt with one foot prior to stepping on.
Although numerous clever devices have been developed to automate blood pressure measurement during exercise, none can be recommended. The time proven method of holding the subject’s arm with a stethoscope placed over the brachial artery remains most reliable.
Exercise test should be performed under the supervision of a physician who has been trained to conduct exercise tests. An ACC/AHA clinical competence statement in exercise testing published in 2000 describes a “majority opinion” of its authors that supervising physician should participate in at least 50 exercise test procedure during training and perform at least 25 exercise test per year”.
The degree of supervision required is primarily dependent on the type of patient being tested and can range from direct performance of the test for patients who are at higher risk of complications (e.g. those who have unstable angina after stabilization, who have congestive heart failure or who have high risk of arrhythmias) to assigning the performance of the test to an appropriately trained exercise physiologist or a specialist in patients at lower risk. In all cases a physician should be immediately available during the exercise test.
During the pretest evaluation, the physician should establish and understanding of any patterns of cardiopulmonary compromise associated with exercise and the patient’s usual level of exercise tolerance.
The patient should be asked whether he or she has ever become light headed or fainted while exercising and whether anyone in the family has died suddenly during exercise.
The physician should also ask about family history and general medical history, making note of any considerations that may increase the risk of sudden death.
A brief physical examination should always be performed prior to testing to rule out significant outflow obstruction.
If abnormal findings occur at levels of exercise that the patient usually performs, then it may not be necessary to stop the test because of them.
Preparation for exercise testing include the following –
The subject should be instructed not to eat or smoke atleast 2 hours prior to the test and to come in loose fitting clothes.
Unusual physical exertion should be avoided before testing.
A brief history physical examination (particularly noting systolic murmurs) should be accomplished to rule out any contraindications to testing.
Specific questioning should determine which drugs are being taken, and potential electrolyte abnormalities should be considered. The labeled medication bottles should be brought along so that medications can be identified and recorded. Because of a greater potential for cardiac events with the sudden cessation of -blockers , they should not be automatically stopped prior to testing but done so gradually under physician guidance, only after consideration of the purpose of the test. Many post infarct patients referred for exercise testing have been prescribed beta-adrenergic blocking agents and angiotensin converting enzyme inhibitors.
Although beta-adrenergic blocking drugs may attenuate the ischemic, they do not interfere with poor functional capacity as a marker of adverse prognosis and should be continued in patients referred for testing. (BRAUNDWALD PAGE 167).
Pretest standard 12 lead ECG are necessary in both the supine and standing positions.
Good skin preparations must cause some discomfort but is necessary for good conductance and to avoid artifacts.
Patients should continue antihypertensive drug therapy on the day of testing.
Hyperventilation is not necessary prior to testing. Subjects both with or without disease may or may not exhibit ST segment changes with hyperventilation, the value of this procedure in lessening the number of false positive responders is no longer considered useful. (HURST PAGE 462)
Most problems can be avoided by having an experienced physician standing next to the subject, measuring blood pressure and assessing appearance during the test.
Subjects should be reminded not to grasp the front or side rails because this decreases the work performed and create noise in the ECG. Hanging on increases exercise time resulting in an over estimation of exercise capacity.
The AHA published standards for performance of exercise testing in 2001 which define absolute and relative contraindications to exercise testing, these recommendations were slightly modified in ACC/AHA guidelines published in 2002.
Relative contraindications are those that can be superseded if clinicians believe that the benefits of testing outweigh the risk of exercise.
Exercise Protocols The main types of exercise are isotonic or dynamic exercise, isometric or static exercise, and resistive (combined isometric and isotonic) exercise. Dynamic protocols most frequently are used to assess cardiovascular reserve, and those suitable for clinical testing should include a low intensity warm-up phase. In general, 6 to 12 minutes of continuous progressive exercise during which the myocardial oxygen demand is elevated to the patient's maximal level is optimal for diagnostic and prognostic purposes. The protocol should include a suitable recovery or cool-down period. If the protocol is too strenuous for an individual patient, the test must be terminated early, and there is no opportunity to observe clinically important responses. If the exercise protocol is too easy for an individual patient, the prolonged procedure tests endurance and not aerobic capacity.
Thus, exercise protocols should be individualized to accommodate a patient’s limitations. Protocols may be set up at a fixed duration of exercise for a certain intensity to meet minimal qualifications for certain industrial tasks or sports programs. TREADMILL PROTOCOL The treadmill protocol should be consistent with the patient’s physical capacity and the purpose of the test. In healthy individuals, the standard Bruce protocol is popular, and a large diagnostic and prognostic data base has been published using this protocol. The Bruce multistage maximal treadmill protocol has 3-minute periods to allow achievement of a steady state before workload is increased. In older individuals or those whose exercise capacity is limited by cardiac disease, the protocol can be modified by two 3-minute warm up stages at 1.7 mph and 0 percent grade and 1.7 mph and 5 percent grade.
A limitation of the Bruce protocol is the relatively large increase in VO 2 between stages and the additional energy cost of running as compared with walking at stages in excess of Bruce’s stage III. It is important to encourage patients not to grasp the handrails of the treadmill during exercise, particularly the front handrails. Functional capacity can be overestimated by as much as 20 percent in tests in which handrail support is permitted, and VO 2 is decreased. Because the degree of handrail support is difficult to quantify from one test to another, more consistent results can be obtained during serial testing when handrail support is not permitted. The 6-Minute Walk Test The 6-minute walk test can be used for patients who have marked left ventricular dysfunction or peripheral arterial occlusive disease and who cannot perform bicycle or treadmill exercise.
Patients are instructed to walk down a 100-foot corridor at their own pace, attempting to cover as much ground as possible in 6 minutes. At the end of the 6-minute interval, the total distance walked is determined and the symptoms experienced by the patient are recorded. The 6-minute walk test as a clinical measure of ambulatory function requires highly skilled personnel following a rigid protocol to elicit reproducible and reliable results. The coefficient of variation for distance walked during two 6-minute walk tests was 10 percent in one series of patients with peripheral arterial occlusive disease.
Estimated oxygen cost of bicycle ergometer and selected treadmill protocols. The standard Bruce protocol starts at 1.7 mph and 10 percent grade (5 METs), with a larger increment between stages than protocols such as the Naughton, ACIP, and Weber, which start at less than 2 METs at 2mph and increase by 1- to 1.5-MET increments between stages. The Bruce protocol can be modified by two 3-minute warm-up stages at 1.7mph and 0 percent grade and 1.7mph and 5 percent grade. METs = metabolic equivalents. (Adapted from Fletcher GF, Balady G, Amsterdam EA, et al: Exercise Standards for Testing and Training. A statement for healthcare professionals from the American Heart Association. Circulation 104:1694, 2001.
Electrocardiographic Measurements LEAD SYSTEMS. The Mason-Likar modification of the standard 12-lead ECG requires that the extremity electrodes be moved to the torso to reduce motion artifact. The arm electrodes should be located in the most lateral aspects of the infraclavicular fossae, and the leg electrodes should be in a stable position above the anterior iliac crest and below the rib cage. The Mason-Likar modification results in a right-axis shift and increased voltage in the inferior leads and may produce a loss of inferior Q waves and the development of new Q waves in lead aV 1 . Thus, the body torso limb lead positions cannot be used to interpret a diagnostic resting 12-1ead ECG. The more cephalad the leg electrodes are placed, the greater is the degree of change and the greater is the augmentation of R wave amplitude.
Types of ST Segment Displacement In normal persons, the PR, QRS, and QT intervals shorten as heart rate increases. P amplitude increases, and the PR segment becomes progressively more downsloping in the inferior leads. J point, or junctional, depression is a normal finding during exercise.
J point depression of 2 to 3 mm in leads V 4 to V 6 with rapid upsloping ST segments depressed approximately 1mm 80msec after the J point. The ST segment slope in leads V 4 and V 5 is 3.0mV/sec. This response should not be considered abnormal.
In patients with myocardial ischemia, however, the ST segment usually becomes more horizontal (flattens) as the severity of the ischemic response worsens. With progressive exercise, the depth of ST segment depression may increase, involving more ECG leads, and the patient may develop angina. In the immediate post recovery phase, the ST segment displacement may persist, with downsloping ST segments and T wave inversion, gradually returning to baseline after 5 to 10 minutes.
Bruce protocol. lead V 4 , the exercise electrocardiographic (ECG) result is abnormal early in the test, reaching 0.3mV (3mm) of horizontal ST segment depression at the end of exercise. The ischemic changes persist for at least 1 minute and 30 seconds into the recovery phase. The right panel provides a continuous plot of the J point, ST slope, and ST segment displacement at 80msec after the J point (ST level) during exercise and in the recovery phase. Exercise ends at the vertical line at 4.5 minutes (red arrow). The computer trends permit a more precise identification of initial onset and offset of ischemic ST segment depression. This type of ECG pattern, with early onset of ischemic ST segment depression, reaching more than 3mm of horizontal ST segment displacement and persisting several minutes into the recovery phase, is consistent with a severe ischemic response.
Bruce protocol. In this type of ischemic pattern, the J point at peak exertion is depressed 2.5mm, the ST segment slope is 1.5mV/sec, and the ST segment level at 80msec after the J point is depressed 1.6mm. This “ slow upsloping” ST segment at peak exercise indicates an ischemic pattern in patients with a high pretest prevalence of coronary disease. A typical ischemic pattern is seen at 3 minutes of the recovery phase when the ST segment is horizontal and 5 minutes after exertion when the ST segment is downsloping. Exercise is discontinued at the vertical line in the right panels at 7.5 minutes.
Ischemic ST segment displacement may be seen only during exercise, emphasizing the importance of adequate skin preparation and electrode placement to capture high~ quality recordings during maximum exertion. In about 10 percent of patients, the ischemic response may appear only in the recovery phase. This is a relevant finding, and the prevalence of reversible perfusion defects by singlephoton emission computed tomography criteria are comparable to those observed when the ischemic ST segment response occurs both during and after exercise. Patients should not leave the exercise laboratory area until the postexercise ECG has returned to baseline.
Bruce protocol. The exercise electrocardiographic (ECG) result is not yet abnormal at 8:50 minutes but becomes abnormal at 9:30 minutes (horizontal arrows, right ) of a 12-minute exercise test and resolves in the immediate recovery phase. This ECG pattern in which the ST segment becomes abnormal only at high exercise workloads and returns to baseline in the immediate recovery phase may indicate a false-positive result in an asymptomatic individual without atherosclerotic risk factors. Exercise myocardial imaging would provide more diagnostic and prognostic information if this were an older person with several atherosclerotic risk factors. Vertical arrow indicates termination of exercise.
Illustration of eight typical exercise electrocardiographic (ECG) patterns at rest and at peak exertion. The computer-processed incrementally averaged beat corresponds with the raw data taken at the same time point during exercise and is illustrated in the last column. The patterns represent worsening ECG responses during exercise. In the column of computer-averaged beats, ST 80 displacement (top number) indicates the magnitude of ST segment displacement 80 msec after the J point relative to the PQ junction or E point. ST segment slope measurement (bottom number) indicates the ST segment slope at a fixed time point after the J point to the ST 80 measurement. At least three noncomputer average complexes with a stable baseline should meet criteria for abnormality before the exercise ECG result can be considered abnormal (see Fig. 10-9). The normal and rapid upsloping ST segment responses are normal responses to exercise. J point depression with rapid upsloping ST segments is a common response in an older, apparently healthy population. Minor ST depression can occur occasionally at submaximal workloads in patients with coronary disease; in this illustration, the ST segment is depressed 0.09mV (0.9mm) 80msec after the J point. The slow upsloping ST segment pattern often demonstrates an ischemic response in patients with known coronary disease or those with a high pretest clinical risk of coronary disease. Criteria for slow upsloping ST segment depression include J point and ST 80 depression of 0.15mV or more and ST segment slope of more than 1.0mV/sec. Classic criteria for myocardial ischemia include horizontal ST segment depression observed when both the J point and ST 80 depression are 0.1mV or more and ST segment slope is within the range of 1.0mV/sec. Downsloping ST segment depression occurs when the J point and ST 80 depression are 0.1mV and ST segment slope is − 1.0mV/sec. ST segment elevation in a non-Q wave noninfarct lead occurs when the J point and ST 60 are 1.0mV or greater and represents a severe ischemic response. ST segment elevation in an infarct territory (Q wave lead) indicates a severe wall motion abnormality and in most cases is not considered an ischemic response.
Measurement of ST Segment Displacement For purposes of interpretation, the PQ junction is usually chosen as the isoelectric point. The TP segment represents a true isoelectric point but is an impractical choice for most routine clinical measurements. The development of 0.10 mV (1 mm) or greater of J point depression measured from the PQ junction, with a relatively flat ST segment slope (e.g., <0.7 to 1 mV/sec), depressed 0.10 mV or more 80 msec after the J point (ST 80) in three consecutive beats with a stable baseline is considered to be an abnormal response. When the ST 80 measurement is difficult to determine at rapid heart rates (e.g., >130 beats/min), the ST 60 measurement should be used. The ST segment at rest may occasionally be depressed. When this occurs, the J point and ST 60 or ST 80 measurements should be depressed an additional 0.10 mV or greater to be considered abnormal.
Magnified ischemic exercise– induced electrocardiographic pattern. Three consecutive complexes with a relatively stable baseline are selected. The PQ junction (1) and J point (2) are determined; the ST 80 (3) is determined at 80 msec after the J point. In this example, average J point displacement is 0.2mV (2mm) and ST 80 is 0.24mV (24mm). The average slope measurement from the J point to ST 80 is −1.1 mV/sec.
When the degree of resting ST segment depression is 0.1 mV or greater, the exercise ECG becomes less specific, and myocardial imaging modalities should be considered. In patients with early repolarization and resting ST segment elevation, return to the PQ junction is normal. Therefore, the magnitude of exercise-induced ST segment depression in a patient with early repolarization should be determined from the PQ junction and not from the elevated position of the J point before exercise. Exercise-induced ST segment depression does not localize the site of myocardial ischemia, nor does it provide a clue about which coronary artery is involved. For example, it is not unusual for patients with isolated right CAD to exhibit exercise-induced ST segment depression only in leads V 4 to V 6 , nor is it unusual for patients with disease of the left anterior descending coronary artery to exhibit exercise-induced ST segment displacements in leads II, III, and aVf,
Exercise-induced ST segment elevation is relatively specific for the territory of myocardial ischemia and the coronary artery involved. UPSLOPING ST SEGMENTS. Junctional or J point depression is a normal finding during maximal exercise, and a rapid upsloping ST segment (>1 mV/sec) depressed less than 0.15 mV (1.5 mm) after the J point should be considered to be normal. Occasionally, however, the ST segment is depressed 0.15 mV (1.5 mm) or greater at 80 msec after the J point. This type of slow upsloping ST segment may be the only ECG finding in patients with well-defined obstructive CAD and may depend on the lead set used. In patient subsets with a high CAD prevalence, a slow upsloping ST segment depressed 0.15 mV or greater at 80 msec after the J point should be considered abnormal. The importance of this finding in asymptomatic individuals or those with a low CAD prevalence is less certain.
Increasing the degree of ST segment depression at 80 msec after the J point to 0.20 mV (2.0 mm) or greater in patients with a slow upsloping ST segment increases specificity but decreases sensitivity. ST SEGMENT ELEVATION. Exercise-induced ST segment elevation may occur in an infarct territory where Q waves are present or in a noninfarct territory. The development of 0.10 mV (1 mm) or greater of J point elevation, persistently elevated greater than 0.10 mV at 60 msec after the J point in three consecutive beats with a stable baseline, is considered an abnormal response. This finding occurs in approximately 30 percent of patients with anterior myocardial infarctions and 15 percent of those with inferior ones tested early (within 2 weeks) after the index event and decreases in frequency by 6 weeks.
As a group, postinfarct patients with exercise-induced ST segment elevation have a lower ejection fraction than those without, a greater severity of resting wall motion abnormalities, and a worse prognosis. Exercise-induced ST segment elevation in leads with abnormal Q waves is not a marker of more extensive CAD and rarely indicates myocardial ischemia. Exercise-induced ST segment elevation may occasionally occur in a patient who has regenerated embryonic R waves after an acute myocardial infarction; the clinical significance of this finding is similar to that observed when Q waves are present. When ST segment elevation develops during exercise in a non-Q wave lead in a patient without a previous myocardial infarction, the finding should be considered as likely evidence of transmural myocardial ischemia caused by coronary vasospasm or a high-grade coronary narrowing. This finding is relatively uncommon, occurring in approximately 1 percent of patients with obstructive CAD.
The ECG site of ST segment elevation is relatively specific for the coronary artery involved, and myocardial perfusion scintigraphy usually reveals a defect in the territory involved.
A 48-year-old man with several atherosclerotic risk factors and a normal resting electrocardiographic (ECG) result developed marked ST segment elevation (4 mm [arrows]) in leads V 2 and V 3 with lesser degrees of ST segment elevation in leads V 1 and V 4 and J point depression with upsloping ST segments in lead II, associated with angina. This type of ECG pattern is usually associated with a full-thickness, reversible myocardial perfusion defect in the corresponding left ventricular myocardial segments and high-grade intraluminal narrowing at coronary angiography. Rarely, coronary vasospasm produces this result in the absence of significant intraluminal atherosclerotic narrowing. HR = heart rate; METs = metabolic equivalents; SBP = systolic blood pressure.
T WAVE CHANGES. The morphology of the T wave is influenced by body position, respiration, hyperventilation, drug therapy, and myocardial ischemia/necrosis. In patient populations with a low CAD prevalence, pseudonormalization of T waves (inverted at rest and becoming upright with exercise) is a nondiagnostic finding. In rare instances, this finding may be a marker for myocardial ischemia in a patient with documented CAD, although it would need to be substantiated by an ancillary technique, such as the concomitant finding of a reversible myocardial perfusion defect.
Pseudonormalization of T waves in a 49-year-old man referred for exercise testing. The patient had previously been seen for typical angina. The resting electrocardiogram in this patient with coronary artery disease shows inferior and anterolateral T wave inversion, an adverse long-term prognosticator. The patient exercised to 8 METs, reaching a peak heart rate of 142 beats/min and a peak systolic blood pressure of 248 mm Hg. At that point, the test was stopped because of hypertension. During exercise, pseudonormalization of T waves occurs, and it returns to baseline (inverted T wave) in the postexercise phase. The patient denied chest discomfort, and no arrhythmia or ST segment displacement was noted. Transient conversion of a negative T wave at rest to a positive T wave during exercise is a nonspecific finding in patients without prior myocardial infarction and does not enhance the diagnostic or prognostic content of the test; however, the ability to exercise to 8 METs without ischemic changes in the ST segment places this patient into a subset of lower risk. HR = heart rate; METs = metabolic equivalents; SBP = systolic blood pressure.
OTHER ELECTROCARDIOGRAPHIC MARKERS. Changes in R wave amplitude during exercise are relatively nonspecific and are related to the level of exercise performed. When the R wave amplitude meets voltage criteria for left ventricular hypertrophy, the ST segment response cannot be used reliably to diagnose CAD, even in the absence of a left ventricular strain pattern. U wave inversion can occasionally be seen in the precordial leads at heart rates of 120 beats/min. Although this finding is relatively specific for CAD, it is relatively insensitive. COMPUTER-ASSISTED ANALYSIS When the raw ECG data are of high quality, the computer can filter and average or select median complexes from which the degree of J point displacement, ST segment slope, and ST displacement 60 to 80 msec after the J point (ST 60 to 80) can be measured. The selection of ST 60 or ST 80 depends on the heart rate response.
At ventricular rates greater than 130 beats/min, the ST 80 measurement may fall on the upslope of the T wave, and the ST 60 measurement should be used instead. In some computerized systems, the PQ junction or isoelectric interval is detected by scanning before the R wave for the 10-msec interval with the least slope. J point, ST slope, and ST levels are determined; the ST integral can be calculated from the area below the isoelectric line from the J point to ST 60 or ST 80. ST/HEART RATE SLOPE MEASUREMENTS. Heart rate adjustment of ST segment depression appears to improve the sensitivity of the exercise test, particularly the prediction of multivessel CAD. The ST/heart rate slope depends on the type of exercise performed, number and location of monitoring electrodes, method of measuring ST segment depression, and clinical characteristics of the study population.
Calculation of maximal 5ST/heart rate slope in mV/beats/min is performed by linear regression analysis relating the measured amount of ST segment depression in individual leads to the heart rate at the end of each stage of exercise, starting at the end of exercise. An ST/heart rate slope of 2.4 mV/beats/min is considered abnormal, and values that exceed 6 mV/beats/min are suggestive evidence of three-vessel CAD. The use of this measurement requires modification of the exercise protocol such that increments in heart rate are gradual, as in the Cornell protocol, as opposed to more abrupt increases in heart rate between stages, as in the Bruce or Ellestad protocols, which limit the ability to calculate statistically valid ST segment heart rate slopes. The measurement is not accurate in the early postinfarction phase. A modification of the ST segment/heart rate slope method is the ST segment/heart rate index calculation, which represents the average change of ST segment depression with heart rate throughout the course of the exercise test.
The ST/heart rate index measurements are less than the ST/heart rate slope measurements, and a ST/heart rate index of 1.6 is defined as abnormal. Mechanism of ST Segment Displacement PATHOPHYSIOLOGY OF THE MYOCARDIAL ISCHEMIC RESPONSE. Myocardial oxygen consumption (MO 2 ) is determined by heart rate, systolic blood pressure, left ventricular end-diastolic volume, wall thickness, and contractility. The rate-pressure or double product (heart rate × systolic blood pressure) increases progressively with increasing work and can be used to estimate the myocardial perfusion requirement in normal persons and in many patients with coronary artery disease. The heart is an aerobic organ with little capacity to generate energy through anaerobic metabolism. Oxygen extraction in the coronary circulation is nearly maximal at rest.
The only significant mechanism available to the heart to increase oxygen consumption is to increase perfusion, and there is a direct linear relationship between MO 2 and coronary blood flow in normal individuals. The principal mechanism for increasing coronary blood flow during exercise is to decrease resistance at the coronary arteriolar level. In patients with progressive atherosclerotic narrowing of the epicardial vessels, an ischemic threshold occurs, and exercise beyond this threshold can produce abnormalities in diastolic and systolic ventricular function, ECG changes, and chest pain. The subendocardium is more susceptible to myocardial ischemia than the subepicardium because of increased wall tension; causing a relative increase in myocardial oxygen demand in the subendocardium.
Dynamic changes in coronary artery tone at the site of an atherosclerotic plaque may result in diminished coronary flow during static or dynamic exercise instead of the expected increase that normally occurs from coronary vasodilation in a normal vessel; that is, perfusion pressure distal to the stenotic plaque actually falls as during exercise, resulting in reduced subendocardial blood flow. Thus, regional left ventricular myocardial ischemia may result not only from an increase in myocardial oxygen demand during exercise but also from a limitation of coronary flow as a result of coronary vasoconstriction, or inability of vessels to sufficiently vasodilate at or near the site of an atherosclerotic plaque. Increased myocardial oxygen demand associated with a failure to increase or an actual decrease in regional coronary blood flow usually causes ST segment depression; ST segment elevation may occasionally occur in patients with more severe coronary flow reduction.
The ECG is only one part of the exercise response and abnormal hemodynamics or functional capacity is just as important as, if not more important then ST segment displacement.
1) Blood pressure
The normal exercise response is to increase systolic blood pressure progressively with increasing workloads to a peak response ranging from 160 to 200mmHg with the higher range of the scale in older patients with less compliant vascular systems.
Failure to increase systolic blood pressure beyond 120mmHg, a sustained decrease greater than 10mmHg repeatable within 15 seconds or a fall in systolic blood pressure below standing resting values during progressive exercise.
when the blood pressure has otherwise been increasing appropriately is abnormal and reflects either inadequate elevation of cardiac output because of left ventricular systolic pump dysfunction or an excessive reduction in systemic vascular resistance.
Exertional hypotension ranges from 3 to 9 percent and is higher in patients with three vessel or left main CAD.
Conditions other than myocardial ischemia that have been associated with a failure to increase or an actual decrease in systolic blood pressures during progressive exercise are cardiomyopathy, cardiac arrythmias, vasovagal reaction. Left ventricular outflow tract obstruction, ingestion of antihypertensive drugs, hypovolumia and prolonged vigorous exercise.
An abnormal hypertensive blood pressure response in patients with a high prevalence of CAD is associated with more extensive CAD and more extensive myocardial perfusion defects.
In normal persons, the diastolic blood pressure does not usually change significantly.
(2) MAXIMAL WORK CAPACITY
Maximal work capacity in normal individuals is influenced by familiarization with exercise test equipment, level of training, and environmental conditions at the time of testing.
In patients with known or suspected CAD, a limited exercise capacity is associated with an increased risk of cardiac events and in general the more severe the limitation, the worse the CAD extent and prognoses.
In estimating functional capacity the amount of work performed (or exercise stage achieved) expressed in METs and not the number of minutes of exercise, should be the parameter measured.
Major reduction in exercise capacity indicates significant worsening of cardiovascular status.
The interpretation of exercise tests results for diagnostic and prognostic purposes requires consideration of maximal work capacity.
When a patient is unable to complete moderate levels of exercise or reach at least 85 to 90% of age predicted maximum, the level of exercise performed may be inadequate to test cardiac reserve. Thus ischemic ECG, scientigraphic, or ventriculographic abnormalities may not be evoked and the test may be non diagnostic.
Non diagnostic test results are more common in patients with peripheral vascular disease, orthopedic limitation or neurological impairment and in patients with poor motivation. Pharmacological stress imaging studies should be considered in this settings.
The sinus rate increases progressively with exercise mediated in part through sympathetic innervation of SA node and circulating catecholamine.
An inappropriate increase in heart rate at low exercise workloads may occur in patients who are in atrial fibrillation, physically disconditioned, hypovolumic or anaemic or who have marginal left ventricular function, this increase may persist for several minutes in recovery phase.
In some patients, heart rate (HR) fails to increase appropriately with exercise and is associated with an adverse prognosis.
Chronotropic incompetence is determined by decreased heart rate sensitivity to the normal increase in sympathetic tone during exercise and is defined as inability to increase hart rate to atleast 85 percent of age predicted maximum or as an abnormal heart rate reserve.
Heart rate reserve is calculated as follows –
% HRR used = (HR peak - HR res ) / (220-age-HR res )
Abnormal heart rate recovery refers to a relatively slow deceleration of heart rate following exercise cessation. This type of response reflects decreased vagal tone and is associated with increased mortality.
The heart rate systolic blood pressure product an indirect measure of myocardial oxygen demand, increases progressively with exercise and the peak rate pressure product can be used to characterize cardiovascular performance.
Most normal individuals develop a peak rate pressure product of 20 to 35mmHg×beats/min×10 -3 .
(6) CHEST DISCOMFORT
Characterization of chest pain during exercise can be useful diagnostic finding, particularly when the symptom complex is compatible with typical angina pectoris.
In some patients, however chest discomfort may be the only signal that obstructive CAD is present.
The new development of an S 3 , holosystolic apical murmur or basilar rales in the early recovery phase of exercise enhances the diagnostic accuracy of test.
It is helpful to grade exercise induced chest discomfort on a 1 to 4 scale, with 1 indicating initial onset of chest discomfort and 4 of the most severe chest pain the patient has ever experienced.
The physician should note the onset of grade 1 chest discomfort on the work sheet and the test should be stopped when the patient reports grade 3 chest pain.
In the absence of symptoms, it is prudent to stop exercise when a patient demonstrates 0.3mvV (3mm) or greater of ischemic ST segment depression or 0.1mV (1mm) or greater of ST segment elevation in a non-infarct lead without an abnormal Q-wave.
Significant worsening of ambient ventricular ectopy during exercise or the unsuspected appearance of VT is an indication to terminate exercise.
A progressive, reproducible decrease in systolic blood pressure of 10mmHg or more may indicate transient left ventricular dysfunction or an inappropriate decrease in systemic vascular resistance and is an indication to terminate exercise.
The test should be stopped if the arterial blood pressure is 250-270/120 to 130 mmHg or higher.
Relative indications for termination of testing are those that can be supersided when the clinician considers the benefit of continued exercise to exceed the risk.
Indications of TMT Clearly indicated Diagnosis of CAD in men with atypical symptoms . Patient has known CAD; assess prognosis and functional capacity Symptomatic, recurrent, exercise-induced arrhythmias Patient has experienced an uncomplicated myocardial infarction; evaluate prognosis and functional capacity Patient has undergone coronary artery revascularization; evaluation recommended Possibly indicated Diagnosis of CAD in woman with typical or atypical angina Diagnosis of CAD in patient taking digitalis Diagnosis of CAD in patient with complete right bundle branch block
Patient has CAD or heart failure; evaluate functional capacity and response to therapy Patient has variant angina; evaluation recommended . Patient has known CAD; serial evaluation recommended Asymptomatic man who is older than 40 yr and in a high-risk occupation, who has-two or more risk factors for CAD, or who is sedentary and plans to begin a vigoi'ous exercise program; evaluation recommended Asymptomatic patient after coronary revascularization; annual evaluation recommended Selected patients with valvular heart disease; evaluate functional capacity Probably not indicated Asymptomatic patient with isolated ventricular ectopy; evaluation recommended
Patient is enrolled in a cardiac rehabilitation program; serial evaluation recommended Diagnosis of CAD in patient with left bundle branch block or ventricular preexcitation (Wolff Parkinson-White) syndrome on resting electrocardiography Asymptomatic man or woman; evaluation recommended Man or woman with chest pain of noncardiac etiology; evaluation recommended Diagnostic Use of Exercise Testing Approximately 75 to 80 percent of the diagnostic information on exercise-induced ST segment depression in patients with a normal resting ECG is contained in leads V 4 to V 6 Exercise ECG is less specific when patients in whom false-positive results are more common are included, such as those with valvular heart disease, left ventricular hypertrophy, marked resting ST segment depression, or digitalis therapy.
Exercise Testing in Determining Prognosis Exercise testing provides not only diagnostic information but also, more importantly, prognostic data. The value of exercise testing to estimate prognosis must be considered in light of what is already known about a patient’s risk status. Left ventricular dysfunction, CAD extent, electrical instability, and noncoronary comorbid conditions must be taken into consideration when estimating long-term outcome. ASYMPTOMATIC POPULATION. The prevalence of an abnormal exercise ECG result in middle-aged asymptomatic men ranges from 5 to 12 percent. The future risk of cardiac events is greatest if the test result is strongly positive or if an asymptomatic subject has atherosclerotic risk factors such as diabetes, hypertension, hypercholesterolemia, smoking history, or familial history of premature coronary disease.
Serial change of a negative exercise ECG result to a positive one in an asymptomatic person carries the same prognostic importance as an initially abnormal test result. However, when an asymptomatic individual with an initially abnormal test result has significant worsening of the ECG abnormalities at lower exercise workloads, this finding may indicate significant CAD progression and warrants a more aggressive diagnostic work-up. In general , the prognostic value of an ST segment shift in women is less than in men. SYMPTOMATIC PATIENTS. Exercise testing should be routinely performed (unless this is not feasible or unless there are contraindications) before coronary angiography in patients with chronic ischemic heart disease. Patients who have excellent exercise tolerance (e.g., >10 METs) usually have an excellent prognosis regardless of the anatomical extent of CAD.
Mark and colleagues developed a treadmill score based on 2842 consecutive patients with chest pain in the Duke data bank; these patients underwent treadmill testing using the Bruce protocol and cardiac catheterization. Patients with left bundle branch block (LBBB) or those with exercise induced ST elevation in a Q wave lead were excluded. The treadmill (TM) score is calculated as follows: TM score = exercise time - (5 × ST deviation) - (4 × treadmill angina index) Angina index was assigned a value of 0 if angina was absent, 1 if typical angina occurred during exercise, and 2 if angina was the reason the patient stopped exercising. ST deviation was defined as the largest net ST displacement in any lead.
The 13 percent of patients with a treadmill score of -11 or less had a 5-year survival rate of 72 percent, as compared with a 97 percent survival rate among the 34 percent of patients at low risk with a treadmill score of +5 or greater. The score worked equally well in men and women, although women had a lower overall risk than men for similar scores. SILENT MYOCARDIAL ISCHEMIA In patients with documented CAD, the presence of exerciseinduced ischemic ST segment depression confers increased risk of subsequent cardiac events regardless of whether angina occurs during the test. ACUTE CORONARY SYNDROMES The prognostic risk assessment after an acute coronary syndrome should incorporate findings from the history, physical examination, resting 12-lead ECG, and level of serum markers to optimize mortality and morbidity estimates and to categorize patients into low- intermediate, and high-risk groups.
Exercise testing should be considered in the outpatient evaluation of low-risk patients with unstable angina (biomarker negative) who are free of active ischemic symptoms for a minimum of 8 to 12 hours, and in hospitalized low- to intermediate-risk ambulatory patients who are free of angina or heart failure symptoms for at least 48 hours. In many intermediate or high-risk patients, coronary angiography will have been performed during the acute phase of the illness; coronary disease extent, left ventricular function, and degree of coronary revascularization, if performed, should then be incorporated with the exercise test data to determine the overall predischarge prognostic risk estimate.
MYOCARDIAL INFARCTION Exercise testing after myocardial infarction (both non-ST and ST elevation) is useful to determine (1) risk stratification and assessment of prognosis, (2) functional capacity for activity prescription after hospital discharge, and (3) assessment of adequacy of medical therapy and need to use supplemental diagnostic or treatment options. A low-level exercise test (achievement of 5 to 6 METs or 70 to 80 percent of age-predicted maximum) is frequently performed before hospital discharge to establish the hemodynamic response and functional capacity. The ability to complete 5 to 6 METs of exercise or 70 to 80 percent of age-predicted maximum in the absence of abnormal ECG or blood pressure is associated with a I-year mortality rate of 1 to 2 percent and may help guide the timing of early hospital discharge.
Parameters associated with increased risk include inability to perform or complete the low-level predischarge exercise test, poor exercise capacity, inability to increase or a decrease in exercise systolic blood pressure, and angina or exercise-induced ST segment depression at low workloads. Many postinfarct patients referred for exercise testing have been prescribed beta-adrenergic blocking agents and angiotensinconverting enzyme inhibitors. Although beta-adrenergic blocking drugs may attenuate the ischemic response, they do not interfere with poor functional capacity as a marker of adverse prognosis and should be continued in patients referred for testing. The relative prognostic value of a 3- to 6-week postdischarge exercise test is minimal once clinical variables and the results of the low-level predischarge test are adjusted for.
For this reason, the timing of the exercise test after the infarct event favors predischarge exercise testing to allow implementation of a definitive treatment plan in patients in whom coronary anatomy is known as well as risk stratification of patients in whom coronary anatomy has not yet been determined. There is a trend toward early predischarge exercise testing (within 3 to 5 days) in uncomplicated cases after acute myocardial infarction. A 3 to 6-week test is useful in clearing patients to return to work in occupations involving physical labor in which the MET expenditure is likely to be greater than that performed on a predischarge test. In patients with negative T waves after infarction, stress-induced normalization of the T waves may also indicate higher coronary flow reserve than in patients unable to normalize their T waves.
Nomogram of prognostic relations using the Duke treadmill score, which incorporates duration of exercise (in minutes) – (5 × maximal ST segment deviation during or after exercise) (in mm)–(4 × treadmill angina index). Treadmill angina index is 0 for no angina, 1 for nonlimiting angina, and 2 for exercise-limiting angina. The nomogram can be used to assess the prognosis of ambulatory outpatients referred for exercise testing. In this example, the observed amount of exercise-induced ST segment deviation (minus resting changes) is marked on the line for ST segment deviation during exercise (1). The degree of angina during exercise is plotted (2), and the points are connected. The point of intersection on the ischemic reading line is noted (3). The number of METs (or minutes of exercise if the Bruce protocol is used) is marked on the exercise duration line (4). The marks on the ischemia reading line and duration of exercise line are connected, and the intersection on the prognosis line determines 5-year survival rate and average annual mortality for patients with these selected specific variables. In this example, the 5-year prognosis is estimated at 78 percent in this patient with exercise-induced 2-mm ST depression, nonlimiting exercise angina, and peak exercise workload of 5 METs. MET = metabolic equivalent.