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As with any cardiac test, patient selection is critical and patient safety of foremost concern. In their seminal 1971 study of 170,000 exercise tests, Rochmis and Blackburn observed a mortality rate of approximately 1 in 10,000 exercise tests.15 Eight subsequent studies summarized in 1993 found the mortality rate had decreased to 0 to 0.5 per 10,000 tests.16 The clinician supervising the test, be it a physician, nurse, exercise physiologist, or another professional, should be very comfortable in his or her ability to interpret a rest and exercise electrocardiogram (ECG) for ischemia and arrhythmia, recognize exercise-induced symptoms of ischemia and cardiac failure, and handle an exercise-induced emergency. Given the significant potential for harm in patients with valvular heart disease, particularly severe aortic stenosis, the supervising clinician should also be skilled in cardiac auscultation, to be performed prior to exercise testing.
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Qualifications of Testing Clinicians
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In the United States, exercise testing is increasingly supervised by nonphysicians. As reviewed by Myers and colleagues,17 the AHA stated in 1979 that an experienced nonphysician could conduct exercise testing, although a physician must be immediately available during testing.18 In 1990, a multispecialty task force of the ACC, AHA, and American College of Physicians recommended specific clinical competencies for physicians and nonphysicians in order to perform exercise testing.19 Subsequent statements by these organizations, as well as the American College of Sports Medicine and American Association of Cardiovascular and Pulmonary Medicine, further defined the level of supervision during which patients can be safely tested by nonphysician providers and the detailed training required. Central to these recommendations are the risk stratification of patients prior to exercise testing and the immediate availability of a physician during patient testing. Personal supervision by a physician in the room is recommended for high-risk patients as listed in the bullets below, which have been adapted from Myers and colleagues.17 These patients should be identified by careful pretest evaluation and good clinical judgment.
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Moderate to severe aortic or mitral valve stenosis with or without symptoms
Hypertrophic cardiomyopathy: risk stratification and exercise gradient assessment
History of malignant or exertional arrhythmias, sudden cardiac death
History of exertional syncope or presyncope
Intracardiac shunts
Genetic channelopathies
Within 7 days of myocardial infarction or acute coronary syndrome
New York Heart Association class III heart failure
Severe left ventricular dysfunction
Severe pulmonary arterial hypertension
In the broader context of potential instability resulting from noncardiovascular comorbidities, (eg, frailty, dehydration, orthopedic limitations, chronic obstructive lung disease)
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All exercise laboratory staff assisting in exercise testing should be credentialed in basic life support. Supervising nonphysicians should be certified in Advanced Cardiac Life Support. If supervising physicians are not certified in Advanced Cardiac Life Support, they should be competent in identifying and handling such emergencies based on past and continued training and experience. Given a dearth of comprehensive continuing education pathways to achieve expertise in exercise testing, the training of nonphysicians, such as registered nurses, nurse practitioners, and physician assistants can be challenging. Previous cardiac experience can be leveraged with available continuing medical education courses, textbooks, and articles, as well as extensive on the job training and supervision to develop competence. Both nonphysicians and physicians should perform a minimum of 200 exercise tests during training to meet the level 1 Core Cardiology Training Symposium standard established by the ACC in 2008.20 In general, a minimum of 50 tests should be performed annually to maintain and enhance competency. With substantial experience, nonphysicians may perform basic interpretation of the exercise test with the final responsibility for the report resting with the physician. Any physician supervising and ultimately responsible for the exercise test should meet ACC level 1 guidelines.20 Physicians who are immediately available during testing by nonphysicians should either meet these guidelines or be skilled in emergency medicine.17
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Exercise testing can be performed with bicycle ergometry or treadmill testing. The latter is much preferred if space in the exercise laboratory allows, because higher workloads can be obtained with treadmill compared to bicycle exercise given the greater muscle mass involved.
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Given the low but finite risk of prolonged myocardial ischemia, infarction, or arrhythmia, and of cardiac arrest, a “crash cart” should be immediately available, and supervising clinicians should have the knowledge to use the medications therein. A defibrillator should also be immediately available, and staff should be trained in its use. Laboratory staff should be well versed in the laboratory’s predefined plan to respond to an emergency. In an outpatient facility, this includes an understanding of who will directly attend to the patient, who will record unfolding events, and who will call for emergency medical transport personnel. When an event does occur, a postevent debriefing presents the opportunity to discuss opportunities for improvement.
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Patient preparation is key and should begin on test scheduling. The patient should be provided with digital or printed information on what to expect. They should be advised to wear clothes and shoes fit for exercising. Because caffeine is a competitive antagonist of adenosine receptors and thus blocks the effect of dipyridamole, adenosine, and regadenoson, it should be withheld for at least 12 hours if there is a possibility of the patient undergoing vasodilator stress the same day. However, we are unaware of investigative data on the impact of caffeine on stand-alone exercise testing. Because the vast majority of persons consume caffeine regularly, testing caffeinated patients would be akin to testing them in their typical physiologic state. If there is little or no chance that a patient would undergo vasodilator stress the same day as an exercise test, prohibition against caffeine use prior to exercise testing is not required. We have also found that a light meal prior to the exercise test, if desired, does not present problems.
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Tobacco has traditionally been prohibited for 3 hours prior to testing. Tobacco can potentiate vasospasm, which can result in a positive exercise test in the absence of obstructive CAD. However, if the patient smokes regularly, a test without a tobacco prohibition would reflect their day-to-day natural state. The prohibition can be implemented or relaxed depending on the clinical question to be answered.
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Avoiding vigorous exercise on the day of exercise testing is appropriate to enhance the patient’s ability to achieve maximum exercise on the test.
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If the exercise test is being performed to determine if a patient has CAD and consequent ischemia, antianginal medications should be held to minimize their anti-ischemic impact. As best observed in studies of patients undergoing SPECT imaging, beta-blockers, nitrates, and calcium channel blockers can all turn a test from ischemic to nonischemic.21,22 A practical approach to discontinuing medications for diagnostic testing is to hold beta-blockers for 24 hours and hold nitrates and calcium channel blockers the day of the study. Patients should be instructed to bring these medications to the test and to take them following the treadmill test. This is ideally accomplished while the patient is still in the exercise laboratory in order to facilitate compliance in restarting their medication.
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Holding medications is particularly important when using exercise testing for patients being evaluated from the emergency department for chest pain. If a patient is already on antianginal therapy on arrival for exercise testing from the emergency department or elsewhere, sensitivity will be decreased. If the test is negative for ischemia, the reporting clinician may consider noting in the report either that test sensitivity may be decreased by the patient’s medical regimen or that ischemia was not seen at the level of exertion or double product achieved. If the test is being performed for prognostic reasons—that is, if CAD is known to be present and the clinician wishes to determine if the patient is having ischemia on their current medical regimen—medications need not be withheld.
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On arrival, staff should review the test protocol and obtain informed consent by informing the patient of the risks and benefits. Instructions should be provided on vocalizing if chest pain or other ischemic symptoms occur prior to, during, or after exercise.
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Exercise Protocols and Testing
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The most commonly used multistage treadmill protocols in the United States are those developed by Bruce and Ellestad, often regarded as the founders of exercise treadmill testing in the United States. Both protocols begin with what they regarded as a warm-up stage (stage 1), 1.7 miles/hour at 10% grade. For patients with limited ability to exercise, the Bruce protocol can be modified to include a stage 0 in which the patient exercises at 1.7 miles/hour at 0% grade for 3 minutes prior to moving into stage 1 of the standard Bruce protocol. Ideally, a protocol should be used such that patients exercise for 5 to 6 minutes or more.23 A comparison of Bruce and Ellestad treadmill protocols is shown in Fig. 13–2.24 Pollock and colleagues compared the physiologic parameters of these two protocols in a study of 51 men who underwent both tests.24 Peak VO2max, METs, heart rate, and systolic and diastolic blood pressures obtained were similar. As with other multistage treadmill protocols, VO2max correlated directly with exercise duration (Fig. 13–3). Time to achieving peak exercise was about 1 minute sooner with the Ellestad protocol, likely secondary to its 2-minute stages following stage 1 compared to the 3-minute stages of the Bruce protocol.25 Other protocols are available, including those by Naughton and Balke. Exercise duration correlates with VO2max in each and achieves similar results.
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A brief cardiac examination, including auscultation of the heart and lungs, should be performed prior to testing, and the patient should be questioned to determine the reason for the test and any symptoms that may have prompted the referral. Particularly important are any symptoms the patient may have been experiencing that could be cardiac in nature. If the symptoms being evaluated clinically appear consistent with ischemia and the patient develops these during exercise, test termination is generally indicated. Likewise, if the patient describes symptoms prior to exercise testing that are consistent with new onset unstable angina, which have not resolved, invasive coronary angiography or computed tomography (CT) coronary angiography will often be a safer choice than exercise testing. A careful history and clinical judgment are a prerequisite to the safe execution of exercise testing.
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ECG lead placement should ensure proper contact in order to minimize artifacts, which can obfuscate the ability to interpret ischemia. The Mason-Likar “torso” ECG used for exercise testing distorts the axis rightward, which can result in a loss of inferior Q waves masking a previous inferior myocardial infarction (MI).23 Nevertheless, this is the ECG that will be used as the comparator to the exercise ECG and should be reviewed prior to exercise testing. Ideally, a standard 12-lead ECG with electrodes placed on the limbs should be performed prior to exercise testing. Previous records, often accessed via an electronic medical record system, should be reviewed for pertinent symptoms and history, including past exercise testing and a recent resting ECG. Electrocardiographic tracings from the most recent exercise test allow a direct comparison of the timing of onset and extent of previous ECG changes. Comparing exercise duration between the previous and current test is particularly helpful. For example, if a patient undergoes a follow-up exercise test and the clinician performing and/or interpreting the test has expended the effort to review the patient’s previous exercise duration and electrocardiographic response and finds them either unchanged or to have changed between the two tests, this information will be particularly helpful and appreciated by the referring clinician.
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During this review, the patient and records should be carefully interrogated for clinical conditions in which the risk of exercise testing outweighs the benefits and is contraindicated (Table 13–2).2,6 Relative contraindications are listed in Table 13–3.2,26 Indications for the test should be assessed and directly matched to the most recent societal Appropriate Use Criteria.27 If exercise testing does not appear to be indicated to address the patient’s clinical condition, the ordering physician should be contacted to discuss their understanding of the clinical situation and potential alternatives to exercise testing.
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The patient’s usual level of activity should also be assessed to determine if the patient would be expected to achieve ≥ 85% of maximum predicted heart rate (MPHR) and if so, to determine whether to modify the planned protocol. Unfortunately, laboratories are increasingly using pharmacologic rather than exercise stress as the stressor for MPI. As American Society of Nuclear Cardiology guidelines recommend, pharmacologic stress is only appropriate if the patient is unable to achieve ≥ 85% MPHR and five METs.28 Although pharmacologic MPI provides adequate perfusion images to assess ischemia, MPI performed with exercise provides key additional opportunities to assess ischemia, including exercise duration, assessment of symptoms, and electrocardiographic changes. With exercise, the expense and risks of the pharmacologic stress agent is also not incurred.
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A review of the resting ECG should include an evaluation for ischemia, conduction defects, and arrhythmias, and it should be compared to prior tracings if they are available. Obtaining an ECG during hyperventilation should be avoided before testing. Subjects with and without CAD can exhibit ST-segment changes with hyperventilation; therefore, hyperventilation to identify false-positive responders is no longer considered helpful.
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Once exercise is initiated, the technologist handling the treadmill and the supervising clinician should focus on the patient, the ECG tracings on the monitor, the intermittent 12-lead ECG obtained at the end of each stage, and the patient’s symptoms and appearance. If changes suggestive of ischemia develop on the continuous monitor, a 12-lead ECG should be immediately performed. Electrocardiographic changes should also elicit a question to the patient about any associated symptoms.
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For a stand-alone exercise test, if a patient develops convincing evidence of ischemia by ECG, symptoms, or both, the test can be terminated, because the question of the presence of ischemia has been answered.3 If ischemia is not convincingly observed, the patient should continue until they can safely or comfortably go no further. A Borg-perceived exertion scale of 6 to 20 (Table 13–4) posted in the patient’s view allows the patient to quantitate their level of exertion.29 This is particularly useful during nuclear stress testing when judging how much more time the patient can exercise in order to gauge when to inject the radioisotope. A Borg scale of ≥ 15 suggests the anaerobic threshold has been met and > 18 generally indicates maximal exercise.23 In many patients, particularly those younger and not on medication, a zero can be added to the Borg score to estimate the patient’s exertional heart rate. This is by design.29
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The clinician should talk intermittently to patients during the test, reassuring them as to their progress and asking how they feel. Toward the end of each stage, patients should be informed of the upcoming increase in treadmill speed and incline and asked if they can continue. Conversation during the test is reassuring, particularly for those undergoing testing for the first time.
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Although age-adjusted MPHR has been assessed since the early years of treadmill testing, it has proved too variable among individuals to serve as a suitable end point to terminate an exercise test. If safe, patients should be encouraged to exercise as long as they are safely able. Exercise testing is meant to be symptom limited, not terminated by an arbitrary age-related heart rate of 85% or 100% of predicted maximum. Stopping exercise prematurely once 85% of an estimated maximal heart rate is achieved decreases exercise testing sensitivity and minimizes the opportunity to assess ischemia electrocardiographically and with adjunctive imaging.30
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Obtaining a heart rate of at least 85% of MPHR is particularly relevant for exercise testing with nuclear or echocardiographic testing. Bairey and coworkers compared patients undergoing exercise MPI with a normal perfusion scan relative to whether they achieved 85% of MPHR. The annual event rate of death, nonfatal MI, or late revascularization was 1.9% for those who reached ≥ 85% MPHR compared to 8.6% for those who achieved < 85%.31 In those who had not achieved 85% MPHR, the predictive value of MPI was minimized as a normal MPI study in the setting of a submaximal heart rate failed to adequately detect ischemia and thus failed to serve as an adequate risk stratifier. Iskandrian and colleagues found MPI sensitivity to be about 20% less among patients who achieved a heart rate < 85% of MPHR compared to those who achieved ≥ 85% MPHR or who stopped on reaching an ischemic end point. Given that ischemia as assessed by MPI is heart rate dependent, ischemia detection by ECG should be heart rate dependent as well.32,33 Cumming demonstrated this concept in his comparison of submaximal to maximal bicycle exercise testing in 63 subjects who had an abnormal ECG response during maximal exercise or during recovery from maximal exercise.34 Although all were ischemic by ECG at maximum exercise or in recovery, ischemic ECG changes were present at heart rates of 85% or less of MPHR in only 46% of subjects.
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Noting that 40% of 100 consecutive laboratories applying for nuclear cardiology accreditation used 85% MPHR as their primary termination criteria for ending an exercise test, Jain and colleagues evaluated 232 of their own patients who had ischemic ECG changes at peak exercise and who exercised for more than 1 minute beyond the time at which they achieved ≥ 85% MPHR.30 At 85% MPHR, the ECG was ischemic in only 144 (62%) patients. Mean ST-segment depression was 1.2 and 2.3 mm at 85% MPHR and peak exercise, respectively. They thus emphasized the admonition of Bruce and colleagues in the first description of Bruce’s multistage treadmill protocol in 1963, that the patient should exercise until “exhausted by fatigue.”35 Achieving either maximum effort or an ischemic end point is key for exercise testing performed with or without imaging.
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An anecdote of how the commonly used, easy-to-remember 220 – age formula was created to estimate MPHR is both interesting and highlights its limitations. On a plane to a medical convention in 1970, Haskell and Fox realized that in about 10 studies of young and middle-aged men undergoing exercise testing, maximum heart rate achieved could be roughly estimated by the formula 220 – age.36 The paper in which they define the formula describes its use not to estimate MPHR on an exercise test but to develop a patient’s exercise prescription.30,37 Formulas with a greater evidence base are recommended to estimate MPHR. Tanaka and colleagues, for example, found that 220 – age results in an underestimation of maximum heart rate, particularly in older patients.38 In a meta-analysis of 351 studies involving 18,712 patients, the empirically derived formula of 208 – 0.7 × age best predicted the maximum heart rate. The formula was predictive in men and women and independent of habitual activity level. They then tested the formula prospectively in 514 subjects, finding excellent prediction of maximum heart rate. Evidence-based tables of age-related maximum heart rates can also be found in Sheffield39 and Ellestad.40 Of these examples, the formula of Tanaka and colleagues is preferred.
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Walking on the Treadmill
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Once exercise has started, patients should use the side rails of the treadmill for balance and safety but not to minimize exertional effort by a tight hold. Some patients will need to be briefly supported by the laboratory team as they start exercising to be certain they are comfortable walking on the belt of the treadmill. In patients unfamiliar with walking on a treadmill, the clinician will often need to ask that they stand erect, lengthen their stride, and move toward the front of the treadmill. This is illustrated in Fig. 13–4.
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Symptoms should be carefully solicited and recorded. Chest pain that is intermittent and of only a few seconds’ duration is far less suggestive of ischemia than chest pain that increases with exercise. If premature ventricular contractions or premature atrial contractions occur during exercise or recovery, patients should be asked if they feel them. In this case, patients can be informed of the cause of the feeling and likely reassured.
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The clinician and assisting staff member should work to obtain artifact-free ECGs during exercise and recovery. This is particularly important for ECGs at peak exercise and in immediate recovery. Additionally, obtaining diagnostic and artifact-free ECGs during exercise may require obtaining ECGs more frequently than at the end of each stage. Blood pressure should be measured toward the end of each stage and when patients report or acknowledge symptoms. Although automated sphygmomanometers are available, manual blood pressure measurement is the most reliable method. It is often difficult to obtain an accurate blood pressure when patients are walking or jogging at speeds of greater than 4 mph on the treadmill. If this is the case, the general appearance of patients—their skin color and the apparent strength and vigor of their walk—will provide clues to the adequacy of their hemodynamic response.
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Two common protocol options exist for the recovery period: an immediate stop after peak exercise or a short cool-down period of 1 to 2 minutes of walking. An immediate stop provides the opportunity to obtain an artifact-free immediate postexercise ECG while the patient is still standing on the treadmill. The patient is then immediately laid supine or semirecumbent on a gurney or its equivalent. The cool-down option of slowing the patient down over 1 to 2 minutes can delay41 or eliminate the appearance of ST-segment depression in recovery. The act of placing a patient supine immediately postexercise enhances ischemic electrocardiographic abnormalities in recovery, likely as a result of the supine position increasing venous return resulting higher left ventricular end-diastolic pressure and thus higher wall tension and oxygen consumption of the myocardium. A representative series of ECG tracings from a patient instructed to move from sitting to laying down at various times during recovery serves as an example of inducing worsening ST-segment depression with the supine position (Fig. 13–5).2 Given the advantages of an immediate stop and a swift move to the supine position, this recovery protocol is recommended for most patients undergoing stand-alone exercise testing.
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A rapid stop may occasionally induce a vagal response. This occurs particularly in young persons exercising to exhaustion and may result in lightheadedness or presyncope. The alternative recovery protocol, a 1- to 2-minute slow cool-down walk, minimizes the vagal response and may be better tolerated. In patients undergoing stress echocardiography, the immediate stop protocol facilitates the patient quickly coming to the echocardiography machine. The immediate-recovery ECG can be performed immediately on the patient laying down for post–stress echocardiography. For patients undergoing MPI, the slow walking cool-down protocol is appropriate because some radioisotope will still be circulating and can be taken up by the myocardium during a slow walking recovery.
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Recovery should last 6 or more minutes and include monitoring of the ECG and symptoms throughout with a 12-lead ECG and blood pressure obtained every minute. If any of these parameters remains abnormal, monitoring should continue until a return to normal and until any symptoms resolve. A markedly abnormal exercise test merits a prompt call to the referring physician and consideration of further care in an acute care setting.
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Indications for Termination of Exercise
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The patient should be continuously observed during exercise testing. The patient should stop exercising when they can go no further or are close to exhaustion, or if their ECG, symptoms, heart rhythm, or hemodynamics warrant stopping because of demonstration of ischemia or concern for safety. As adapted from those outlined in Ellestad2 and by Gibbons and colleagues in the 2002 ACC/AHA guidelines,6 exercise should be terminated when:
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Anginal pain increases to moderate severity. This is a decision based on clinical judgment and consideration of the chronicity of symptoms and the clinical situation. In many patients, the development of mild angina can answer the question at hand and further exercise is not needed.
ST-segment depression has become moderate, generally ≥ 2 mm.
ST-segment depression is present at rest and there is a progressive increase in ST-segment depression with modest exercise or ST-segment depression increases by ≥ 2 mm.
ST-segment elevation is ≥ 1 mm in precordial (anterior) or inferior leads that do not have a resting Q wave.
Atrial tachycardia, atrial fibrillation, or atrial flutter supervenes.
There is onset of Mobitz type 1 or 2 second-degree or third-degree heart block.
Premature ventricular contractions occur in pairs with increasing frequency as exercise increases, or when at least three-beat ventricular tachycardia occurs. Termination secondary to increasing ventricular arrhythmia should be influenced “by the company it keeps.” If associated with ischemic electrocardiographic changes, termination would be prudent with increasing ventricular arrhythmia. If the test is being performed specifically to evaluate for induction of arrhythmia and is not associated with other markers of ischemia, more tolerance can be given.
Systolic blood pressure drops progressively in the face of continuing exercise, particularly if accompanied by another indication of ischemia.
The patient is unable to continue because of dyspnea, fatigue, or lightheadedness.
Musculoskeletal pain becomes moderate, such as that which might occur with arthritis or claudication.
The patient looks vasoconstricted—pale and clammy.
Systolic blood pressure becomes greater than 250 mm Hg or diastolic blood pressure becomes greater than 115 mm Hg.
The patient has reached or exceeded MPHR. As stated, if the patient is able and wishes to go further, he or she can do so in the absence of other indications for termination.
Equipment problems occur, such as loss of the ECG on the monitor.
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Electrocardiographic Patterns and Their Significance
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ST-Segment Depression
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The most common manifestation of ischemia during exercise testing is ST-segment depression. By convention, the magnitude of ST segment is measured 0.08 seconds (80 milliseconds; two boxes on a standard ECG tracing) after the J point of the QRS, which represents the end of the QRS complex and the beginning of the ST segment. The deviation of the ST segment is measured against the location on the ECG in millivolts (mV) at the beginning of the QRS complex (the PQ junction in mV). It is measured here because as the heart rate increases, the segment between the T wave and the P wave often shortens to the point where it is no longer interpretable.42 One millivolt on the ECG corresponds to 1 mm and one box on the ECG. Two mm of ST-segment depression was the initial criterion for an abnormal exercise test and was soon changed to 1.5 mm as the criteria for being abnormal.2 However, studies using outcome or coronary angiography as the gold standard demonstrated that 1.0 to 1.5 mm of ST-segment depression also predicted adverse outcomes or one or more stenoses of 50% or more on angiography.43,44
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Studies as long ago as 1941, as well as more recently, observed either adverse clinical outcomes or angiographic coronary disease in individuals exhibiting ST-segment depression of 0.5 to 1.0 mm.45,46 Although lowering the cut point (threshold) to characterize an exercise study with 0.5 to 1.0 mm of ST-segment depression as abnormal increased sensitivity, specificity decreased to such a degree that a consensus developed to accept at least 1.0 mm of ST-segment depression as the standard cut point for ischemia. However, if patients exhibit other signs of ischemia, those with 0.5 to 1.0 mm of ST-segment depression are likely to have angiographically significant CAD.
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The ST-segment depression discussed immediately above refers to horizontal or downsloping ST-segment depression. Figure 13–6 compares the normal ECG response to different categories of ST-segment depression: J point, also called rapid upsloping, slow upsloping, horizontal, and downsloping.
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Downsloping ST-segment depression is most predictive of angiographic CAD whether it occurs during exercise or recovery, the latter termed “ischemic evolution” and highly specific for CAD.3 Horizontal ST-segment depression is also predictive of angiographic CAD, although less so than if downsloping. More controversial is ST-segment depression that is upsloping but remains 1 mm or more 0.08 seconds after the J point (slow upsloping ST-segment depression). ST-segment depression at the J point that slopes up rapidly such that the ST-segment depression is < 1 mm at 0.08 seconds after the J point of the QRS is commonly observed and is not indicative of ischemia.47
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Slow Upsloping ST Depression
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In a 6-year outcome study by Stuart and Ellestad of 2700 patients undergoing exercise testing between 1964 and 1975, 438 had 2 mm or more of ST-segment depression when evaluated in immediate recovery.48 (When exercise treadmill testing was initially performed, ECGs were performed during recovery rather than during exercise and recovery.) Using a composite end point of cardiac death, nonfatal MI, and the onset or progression of angina, patients whose ST-segment depression was downsloping had the worst prognosis, followed by those with ST-segment depression that was either horizontal or slow upsloping (Fig. 13–7). Those with no or < 2 mm of ST-segment depression experienced a favorable prognosis. In a separate group of patients in the same study who underwent coronary angiography and whose antecedent exercise test demonstrated at least 1 mm of ST-segment depression, those whose ST-segment depression was downsloping included numerically more subjects with two- or three-vessel CAD of at least 50% stenosis (62%) than those with horizontal (60%) or upsloping (57%) ST-segment depression. This cohort of patients from several generations ago had substantially more CAD than patients currently undergoing exercise testing in the United States today,49 resulting in increased test sensitivity.
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Contemporary with the study of Stuart and Ellestad,48 Brody,50 Goldschlager,3 and Kurita and colleagues51 found 1.5 mm of upsloping ST-segment depression to be highly predictive of angiographically significant CAD. Using 2 mm of upsloping ST-segment depression as their threshold for a positive test, Rijneke and associates found improved sensitivity in men and women when adding upsloping ST-segment depression to horizontal and downsloping ST-segment depression.32 Other investigators studying a more recent patient cohort found upsloping ST-segment depression to predict CAD, but with specificity progressively decreasing if ≥ 2, ≥ 1.5, or ≥ 1 mm of upsloping ST-segment depression was used as the threshold for positivity.52
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Recommended Criteria for an Abnormal Electrocardiographic Response to Exercise
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The criteria for an abnormal ST-segment response of horizontal or downsloping ST-segment depression of 1 mm or more was recommended by the AHA in a 2001 statement adding that slow upsloping ST-segment depression of 2 mm or more was a borderline response.23 In the ACC/AHA 2002 exercise testing guidelines, only at least 1 mm of horizontal or downsloping ST-segment depression is characterized as abnormal.6 Using only ST-segment depression that is horizontal or downsloping diminishes the sensitivity of exercise testing. In their 2013 AHA scientific statement on exercise standards for testing and training, Fletcher and coauthors characterize ≥ 1 mm of slow upsloping as equivocal. If exercise testing is used to “screen” a population of normal individuals, disease prevalence is low enough to exclude slow upsloping ST-segment depression as a criterion for positivity, as the positive predictive value would be too low. In patients referred for exercise testing, however, we recommend that slow upsloping ST-segment depression of ≥ 1.5 mm be included as a criterion for a positive exercise test in addition to the conventional criterion of ≥ 1.0 mm of horizontal or downsloping ST-segment depression.40 The addition of ≥ 1.5 mm of slow upsloping ST-segment depression facilitates opportune test sensitivity in an era of diminished CAD severity and allows a better use of exercise testing in patients actually referred for exercise testing.
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In order to be reliable, the ST-segment depression being measured should be present in multiple consecutive beats in at least one ECG lead. T-wave changes during exercise, such as the development of T-wave inversion with exercise or pseudonormalization, an inverted T wave at rest that becomes upright with exercise, are nonspecific findings.2
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Onset of ST-segment Depression
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The earlier during exercise that ST-segment depression occurs and the lower the rate pressure product of this depression, as well as the longer it lasts during recovery, the more severe the CAD as manifested by the incidence of multivessel and left main disease of coronary angiography.3,12
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Although ST-segment depression during exercise often persists into recovery, it may not manifest until exercise has been terminated. In a study of 214 subjects without known CAD who had asymptomatic ST-segment depression during exercise testing, Rywik and colleagues observed ST-segment depression only during recovery in 29% of patients. Over the ensuing 6 years, the development of angina, nonfatal MI or cardiac death was 2.5 times greater in those with ST-segment depression regardless of whether it occurred during exercise or recovery (Fig. 13–8).53
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In a study of 168 men with ST-segment depression during exercise testing who underwent subsequent coronary angiography, Lachterman and coworkers found that 15% demonstrated ST-segment depression only during recovery. Recovery-only ST-segment depression had the same predictive power of angiographic CAD as ST-segment depression occurring during exercise.54 The work of Goldschlager and colleagues in a group of 330 patients undergoing exercise testing and coronary angiography emphasizes the importance of a careful review of the ECGs obtained during every minute of recovery. They found ST-segment depression to occur more frequently and be more abnormal during the first 3 minutes of recovery than during exercise itself. For example, in the 90 patients who developed ≥ 2 mm of slow upsloping ST-segment depression during exercise, 63% developed horizontal or downsloping ST-segment depression of ≥ 1 mm during recovery, indicative of ischemic evolution.
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Location of ST-segment Depression
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ST-segment depression during exercise testing in the precordial leads is more predictive of CAD than in the inferior leads, potentially because of atrial depolarization affecting the ST segment in the inferior leads. Location of ST-segment depression does not predict the artery/region of myocardium involved.43
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ST-segment elevation occurring during exercise in contiguous leads without Q waves is a particularly ominous sign of ischemia and poor outcomes, often consistent with a high-grade proximal coronary lesion. It is also arrhythmogenic and is frequently accompanied by peaked T waves in the same leads, not unlike the ECG of a ST-segment elevation MI. Unlike ST-segment depression during exercise testing, ST-segment elevation during exercise in contiguous leads with an R wave localizes to the coronary artery involved.55 Although ST-segment depression is consistent with subendocardial ischemia, ST-segment elevation is most consistent with transmural ischemia. Exercise is best terminated if ≥ 1 mm of ST-segment elevation occurs during exercise testing; continuing exercise in the face of ST-segment elevation in leads without Q waves creates substantial risk to the patient. If ST-segment elevation in leads without Q waves is associated with angina or other high-risk features during exercise, coronary angiography should be considered, often urgently.2 ST-segment elevation present at rest in the setting of Q waves from a previous MI may result in an increase in ST-segment elevation with exercise that is generally not indicative of ischemia.
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Lead aVR is often unnecessarily neglected during exercise testing. On Einthoven’s classic triangle, aVR represents current going toward –150 degrees, which is roughly opposite to the left ventricular apex. Thus, the ST segment responds in a reciprocal fashion, becoming elevated in the setting of subendocardial apical ischemia. Thus, ST-segment depression in V2 to V6 or leads 2 and 3 is often reflected as ST-segment elevation in aVR. At times, diffuse ischemia from three vessel or left main disease results in cancelling out ST-segment deviation in other leads but ST-segment elevation in aVR often remains.2,56 Monitoring and evaluation of aVR with exercise is now endorsed within the 2013 AHA scientific statement on exercise standards for testing.42