Treadmill Stress Testing Periprocedural Care
- Author: David Akinpelu, MD, FACP; Chief Editor: Eric H Yang, MD more...
Planning for exercise testing varies, depending on whether the procedure is being considered for diagnosis of coronary artery disease (CAD), for prognostic or risk assessment in patients who are symptomatic or are known to have CAD, for evaluation of patients who have experienced a myocardial infarction (MI), for cardiopulmonary exercise testing, or for other purposes.
Diagnosis of obstructive CAD
Exercise stress testing can be useful in establishing the diagnosis of significant obstructive CAD when the diagnosis is in question. Although other clinical findings (eg, dyspnea on exertion, resting electrocardiographic [ECG] tracing abnormalities, or multiple risk factors for atherosclerosis) may suggest the possibility of CAD, the most important clinical finding is a history of chest discomfort or pain. Myocardial ischemia is the most important cause of chest discomfort or pain and is most commonly a consequence of underlying CAD.
For proper assessment of the risk-to-benefit ratio of exercise testing in patients thought to have CAD, these patients should be categorized in terms of the American College of Cardiology (ACC)/American Heart Association (AHA) guidelines (see Technical considerations).
Class I patients include the following:
Adult patients (including those with complete right bundle branch block or less than 1 mm of resting ST depression [at the ST80 point]) with an intermediate pretest probability of CAD on the basis of on sex, age, and symptoms; specific exceptions are noted in the descriptions of classes II and III
Class IIa patients include the following:
Patients with vasospastic angina
Class IIb patients include the following:
Patients with a high pretest probability of CAD on the basis of age, symptoms, and sex
Patients with a low pretest probability of CAD on the basis of age, symptoms, and sex
Patients with less than 1 mm of baseline ST depression who are taking digoxin
Patients with ECG criteria for left ventricular hypertrophy (LVH) and less than 1 mm of baseline ST depression
Class III patients include the following:
Patients with the following baseline ECG abnormalities: preexcitation syndrome (Wolff-Parkinson-White [WPW] syndrome), electronically paced ventricular rhythm, greater than 1 mm of resting ST depression, or complete left bundle branch block
Patients with a documented MI or prior coronary angiography findings demonstrating significant disease who have an established diagnosis of CAD – Testing can help determine ischemia and risk
The clinician’s estimation of the pretest probability of CAD is primarily based on the patient’s history. The most predictive parameters are the description of chest pain, sex, and age. The pretest probability of CAD on the basis of these parameters is applied in the Bayes theorem. According to this theorem, the diagnostic power of exercise testing results is maximal when the pretest probability of CAD is intermediate (30-70%).
The usefulness of exercise testing for the diagnosis of CAD is most commonly expressed in terms of sensitivity and specificity. Sensitivity ranges from 61% to 73%, as reported by various analysts, and specificity ranges from 59% to 81%, depending on the study or article referenced. Results of correlative studies have been divided with respect to the use of exercise stress testing in patients with 50% or 70% luminal diameter occlusion.
A meta-analysis of 58 consecutively published reports involving 11,691 patients without prior MI who underwent coronary angiography and exercise testing revealed wide variances in sensitivity and specificity. Mean sensitivity was 67%; mean specificity was 72%. In the 3 studies where workup bias was avoided by having the patients undergo both coronary angiography and exercise testing, the approximate sensitivity and specificity of 1 mm of horizontal or downsloping ST depression for diagnosing CAD were 50% and 90%, respectively.
The true diagnostic value of the exercise ECG findings apparently lies in their relatively high specificity. The wide variability in test performance apparent from this meta-analysis demonstrates the importance of using proper methods for testing and analysis. Consider up-sloping ST depression as a borderline positive test result or as a result possibly warranting further diagnostic testing.
The standard exercise test remains the first option in the evaluation of possible CAD in patients with an indeterminate pretest probability, though resting ST depression of less than 1 mm reduces its specificity somewhat. LVH with less than 1 mm of ST depression (at the ST80 point) and the use of digoxin with less than 1 mm of depression also lower specificity, but the standard exercise test remains a reasonable option in such patients.
In contrast, other baseline ECG abnormalities (eg, preexcitation, ventricular pacing, more than 1 mm of ST depression at the ST80 point at rest, and complete left bundle branch block) greatly affect the diagnostic performance of the exercise test results. Imaging modalities are preferred in the subset of patients with other baseline ECG abnormalities.
Whereas computer processing of the exercise ECG can be helpful, it can also result in a false-positive depiction of ST depression. To avoid this problem, the ordering clinician should always be provided with recordings of the raw unprocessed ECG data for comparison with any averages the exercise test monitor generates.
New pretest probability considerations
In the update to the original ACC/AHA guidelines, other clinical scores were formulated that could better predict the pretest probability of CAD. These mathematical equations, or scores, developed from multivariable analysis of clinical and exercise test variables and provide better discrimination than the ST segment response alone in the diagnosis of CAD. Such scores can provide probabilities of CAD that are more accurate than ST measurements alone.
Detailed nomograms are available that incorporate the effects of a history of prior MI, Q waves, ST- and T-wave changes, diabetes, smoking, and hypercholesterolemia. History and ECG evidence of prior infarction dramatically affect pretest probability. The Duke treadmill prognostic score has been shown to be better than ST depression alone for diagnosing angiographic CAD.
The variability of the reported diagnostic accuracy of the exercise ECG has been studied by meta-analysis. Despite workup bias, such analysis provides the best description of the diagnostic accuracy of the exercise stress test.
The usefulness of Bayes theorem in the diagnosis of CAD was subject to analysis in 147 patients who had exercise stress testing, with nuclear imaging using thallium-201 and coronary angiography. Of those analyzed, 89 patients had typical anginal chest discomfort and 58 had atypical chest pain. The sensitivity and specificity of the tests and prevalence of CAD at each level of testing were compared with the results generated from the Bayes theorem. The sensitivity of ECG stress was higher in patients with multivessel CAD than in patients with single-vessel CAD.
According to the report, sensitivity, but not specificity, of each test was dependent, in part, on the result of the other test. The calculated results from Bayes theorem when used for sequential testing were remarkably close to the tabulated data. Thus, Bayes theorem is useful clinically despite some evidence of test dependence. Sequential test analysis by Bayes theorem is most useful in establishing or ruling out a diagnosis when the pretest prevalence is approximately 50% and when the 2 tests are concordant.
Confounders of exercise stress testing
Confounders of exercise stress testing include the following:
Resting ST depression
Left bundle branch block
Atrial repolarization waves are opposite to P waves in direction and may extend into the ST segment and T wave. Exaggerated atrial repolarization waves during exercise can cause downsloping ST depression in the absence of ischemia. Patients with false-positive exercise test results based on this finding have a high peak exercise heart rate, an absence of exercise-induced chest pain, and markedly downsloping PR segments in the inferior leads.
Right-side chest leads
Michaelides et al examined 245 patients who underwent exercise testing with standard 12 leads, right ventricular leads, and thallium-201 scintigraphy, reporting sensitivities of 66%, 92%, and 93% and specificities of 88%, 88%, and 82%, respectively, for the detection of CAD based on angiography (ie, results comparable with those of perfusion scanning) when right-side leads were added.
However, this study was performed in a population with an abnormally high prevalence of CAD, and the committee would not recommend clinical use of right-side chest leads until these results are confirmed by others.
ST–heart rate adjustment
Several methods of heart rate adjustment have been proposed to increase the diagnostic accuracy of the exercise ECG. The maximal slope of the ST segment relative to heart rate is derived either manually or by computer. A second technique, termed the ST–heart rate (ST/HR) index, divides the difference in ST depression at peak exercise by the exercise-induced increase in heart rate. ST/HR adjustment has been the subject of several reviews since the last publication of the ACC/AHA guidelines.
Major studies of this approach to diagnostic testing include Morise’s report of 1358 individuals undergoing exercise testing (only 152 with catheterization data) and the report by Okin et al considering heart rate reserve (238 controls and 337 patients with CAD). Viik et al considered the maximum value of the ST/HR hysteresis over a different number of leads for the detection of CAD. The study population consisted of 127 patients with CAD and 220 patients with a low likelihood of CAD who were referred for an exercise test.
Neither the study by Okin et al nor the one by Viik et al considered consecutive patients with chest pain, and both studies had limited challenge. Limited challenge favors the ST/HR index because healthy patients have relatively high heart rates and sick patients have low heart rates. Because this leads to a lower ST/HR index in those without disease and a higher index in sicker patients, the enrollment of relatively healthy patients in these studies presents a limited challenge to the ST/HR index.
Likewise, the Morise study had a small number of patients who underwent angiography. The only study with neither of these limitations was QUEXTA. This large, multicenter study followed a protocol to reduce workup bias and was analyzed by independent statisticians. The ST/HR slope or index was not found to be more accurate than simple measurement of the ST segment.
Although some studies in asymptomatic individuals (who are very unlikely to have CAD) have demonstrated additional prognostic value with the ST/HR adjustment, these data are not directly applicable to the issue of diagnosis in symptomatic patients. Nevertheless, one could take the perspective that the ST/HR approach in symptomatic patients has at least equivalent accuracy to the standard approach.
Although not yet validated, this approach could prove useful in some situations, such as in rendering a judgment concerning certain borderline or equivocal ST responses (eg, ST-segment depression associated with a very high exercise heart rate). The initial promising reports notwithstanding, neither meta-analysis nor a subsequent study found convincing evidence of benefit. In the interpretation of exercise tests, exercise capacity is more important to consider than exercise heart rate.
Although computer processing of the exercise ECG can be helpful, it can result in a false-positive indication of ST depression. To avoid this problem, the ordering clinician should always be provided with ECG recordings of the raw, unprocessed ECG data for comparison with any averages the exercise test monitor generates. Preferably, averages should always be contiguously preceded by the raw ECG data.
The degree of filtering and preprocessing should always be presented along with the ECG recordings and should be compared with the AHA recommendations (0-100 Hz with notched power line frequency filters). Preferably, the AHA standards should be the default setting.
All averages should be carefully labeled and explained, particularly those that simulate raw data. Simulation of raw data with averaged data should be avoided. Obvious breaks should be inserted between averaged ECG complexes. Averages should be marked to indicate the PR isoelectric line and the ST measurement points.
None of the computerized scores or measurements have been validated sufficiently to warrant recommending their widespread use. At least 1 study in which these shortcomings have been addressed showed that computerized measurements are comparable with visual measurements and that they can provide excellent test characteristics when combined with scores.
Risk assessment and prognosis of symptomatic patients or those with CAD
For proper evaluation, risk assessment, and prognosis in symptomatic patients or those with CAD, these patients should be categorized in terms of the ACC/AHA guidelines (see Technical considerations).
Class I patients include the following:
Patients undergoing initial evaluation with possible or known CAD, including those with complete right bundle branch block or less than 1 mm of resting ST depression; specific exceptions are noted in the description of class IIb
Patients with possible or known CAD who were previously evaluated and are now presenting with a significant change in clinical status
Low-risk patients with unstable angina 8-12 hours after presentation who have been free of active ischemic or heart failure symptoms (level of evidence: B)
Intermediate-risk patients with unstable angina 2-3 days after presentation who have been free of active ischemic or heart failure symptoms (level of evidence: B)
Class IIa patients include the following:
Intermediate-risk patients with unstable angina who have normal initial cardiac markers, a repeat ECG without significant change, normal cardiac markers 6-12 hours after the onset of symptoms, and no other evidence of ischemia during observation (level of evidence: B)
Class IIb patients include the following:
Patients with the following resting ECG abnormalities: preexcitation syndrome (WPW syndrome), electronically paced ventricular rhythm, resting ST depression greater than 1 mm, complete left bundle branch block, or any interventricular conduction defect with a QRS duration greater than 120 msec
Patients with a stable clinical course who undergo periodic monitoring to guide treatment
Class III patients include the following:
Patients with severe comorbidity likely to limit life expectancy, candidacy for revascularization, or both
High-risk patients with unstable angina (level of evidence: C)
Patients with possible or known CAD and new or changing symptoms that suggest ischemia should generally undergo exercise testing (only if cardiac catheterization is not indicated) to assess their risk for future cardiac events.
Documentation of exercise or stress-induced ischemia is desirable for most patients undergoing evaluation for revascularization, according to the ACC/AHA guidelines for percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG).
When determining the initial stress test modality, evaluate the patient’s resting ECG findings, physical ability to exercise, and local expertise and technologies. For risk assessment, the exercise test should be the standard initial mode of stress testing used in patients at the provider’s institution who have normal ECG tracings and are not taking digoxin.
In patients who are unable to exercise because of physical limitations (eg, arthritis, amputations, severe peripheral vascular disease, severe chronic obstructive pulmonary disease [COPD], or general debility), pharmacologic stress testing in combination with imaging is recommended.
Exercise testing may be useful for prognostic assessment of patients taking digoxin or patients with abnormal resting ECG findings, but its usefulness is less well established in this setting. Patients with preexcitation, ventricular-paced rhythm, widespread ST depression (≥1 mm), or complete left bundle branch block (QRS duration >120 msec) should usually be tested with an imaging modality. Exercise testing may provide prognostic information (particularly exercise capacity) in patients with nondiagnostic ECG changes but cannot be used to identify ischemia.
One of the strongest and most consistent prognostic markers identified in exercise testing is maximum exercise capacity, which is at least partly influenced by the extent of resting left ventricular dysfunction and the amount of increased left ventricular dysfunction induced by exercise.
It is very important to consider exercise capacity when interpreting an exercise test result. This may be achieved with one of several markers of exercise capacity, including maximal exercise duration, maximal metabolic equivalent of task (MET) level achieved, maximum workload achieved, or maximum heart rate and heart rate–blood pressure product.
A second group of prognostic markers identified from the exercise test relates to exercise-induced ischemia and includes exercise-induced ST deviation (elevation and depression) and exercise-induced angina.
The Duke treadmill score incorporates both groups of prognostic markers (exercise capacity and exercise-induced ischemia). This score was originally developed on the basis of data from 2842 inpatients with known or possible CAD who underwent exercise testing before diagnostic angiography and had no prior revascularization or recent MI. The score applies equally well in males and females but has not been evaluated extensively in elderly patients.
Risk assessment also may be appropriate in certain patients with unstable angina. Guidelines for the diagnosis and treatment of unstable angina endorsed by the ACC and the AHA stratify risk assessment as being low, moderate, or high on the basis of patient history, physical examination findings, and initial resting ECG tracings.[16, 17, 18]
In low-risk patients with unstable angina who are evaluated in an outpatient setting, exercise or pharmacologic stress testing should generally be performed within 72 hours of presentation. In low- or intermediate-risk patients with unstable angina who have been hospitalized for evaluation, exercise or pharmacologic stress testing should generally be performed unless cardiac catheterization is indicated.
Testing can be performed when patients have been free of active ischemic or heart failure symptoms for a minimum of 8-12 hours. Intermediate-risk patients can be tested after 2-3 days, but selected patients can be evaluated earlier as part of a carefully constructed chest pain management protocol (see Chest pain centers). In general, as with patients with stable angina, the treadmill test should be the standard stress test for patients with normal resting ECG tracings who are not taking digoxin.
Most patients with unstable angina have an underlying ruptured plaque and significant CAD. Some have a ruptured plaque without significant lesions in any coronary segment as determined by angiography. Still others have no evidence of a ruptured plaque or atherosclerotic coronary lesions.
Very little evidence exists with which to define the safety of early exercise testing in unstable angina. A review of this area found 3 studies covering 632 patients with stabilized unstable angina who had a 0.5% rate of death or MI within 24 hours of their exercise test. In addition, many available studies contain both patients with unstable angina and those who have experienced MI.
The limited evidence available supports exercise testing in patients with acute coronary syndrome who have appropriate indications once they are clinically stable. A study comparing a symptom-limited predischarge exercise test with a test performed at 1 month in patients with unstable angina or non–Q-wave infarction found that the 2 tests had similar prognostic value, but the earlier test identified additional patients who would experience events during the initial 1 month (these earlier events represented one half of all events occurring during the first year).
The Research on Instability in Coronary Artery Disease (RISC) study group examined the use of predischarge symptom-limited bicycle exercise testing in 740 men admitted with unstable angina (51%) or non–Q-wave MI (49%). The major independent predictors of 1-year infarction-free survival in multivariable regression analysis were the number of leads with ischemic ST-segment depression and the peak exercise workload achieved.
In 766 patients with unstable angina enrolled in the Fragmin During Instability in Coronary Artery Disease (FRISC) study between 1992 and 1994 who had both a troponin T level and a predischarge exercise test, the combination of a positive troponin T level and exercise-induced ST depression stratified patients into groups with a risk of death or MI that ranged from 1% to 20%.
In 395 women enrolled in FRISC I with stabilized unstable angina who underwent a symptom-limited stress test at days 5-8, risk for cardiac events in the next 6 months could be stratified from 1% to 19%. Important exercise variables included not only ischemic parameters such as ST depression and chest pain but also parameters that reflected cardiac workload.
Chest pain centers
Over the past decade, increasing experience has been gained with the use of exercise testing in emergency department (ED) chest pain centers. The goal of a chest pain center is to provide rapid and efficient risk stratification and treatment for patients with chest pain who may have acute coronary disease.
Various physical and administrative setups have been used for chest pain centers in medical centers across the country; review of these details is beyond the scope of this article. In most of the published series, exercise testing has been reserved for the investigation of patients who are determined to be at low risk on the basis of history and physical examination, 12-lead ECG, and serum markers.
In a study by Gibler et al that evaluated 1010 patients with clinical examination, 9 hours of continuous ST monitoring, serial 12-lead ECG, serial measurement of creatine kinase-MB levels, resting echocardiography, and (in patients without high-risk markers) a symptom-limited Bruce exercise ECG test, no adverse events were reported from the testing, and the authors estimated a 5% prevalence of CAD in the tested population.
These results are generally consistent with the results in the approximately 2100 patients with chest pain who have undergone exercise testing as part of a chest pain center protocol report. The prevalence of CAD is extremely low in such patients, and the risk of adverse events with testing is correspondingly low.
Farkouh et al, examining the use of exercise testing in 424 intermediate-risk patients with unstable angina as part of a randomized trial of admission to a chest pain unit versus standard hospital admission, reported that event rates (ie, rates of death, MI, and congestive heart failure [CHF]) did not significantly differ between the 212 patients in the hospital admission group and the 212 patients in the chest pain unit group.
Of the total chest pain unit group, 60 patients met the criteria for hospitalization before stress testing, 55 had an indeterminate or high-risk test result, and 97 had negative stress test findings. No complications were directly attributable to the performance of a stress test in these patients.
These results demonstrate that exercise testing is safe in low-risk patients with chest pain who present to the ED. In addition, testing appears safe in carefully selected intermediate-risk patients. Early exercise testing in ED chest pain centers improves the efficiency of treatment (and may lower costs) without compromising safety. However, exercise testing in this setting should be performed only as part of a carefully constructed management protocol and only after patients have been screened for high-risk features or other indications for admission.
Exercise testing after myocardial infarction
When exercise stress testing after MI is under consideration, it is important to consider the appropriate time frame with regard to the risks and benefits of the test before it is performed. This is done in accordance with the AHA/ACC guidelines.
Class I applications of post-MI exercise testing are as follows:
Before discharge for prognostic assessment, activity prescription, or evaluation of medical therapy (submaximal at approximately 4-7 days); exceptions are noted in the descriptions of classes IIb and III
Early after discharge for prognostic assessment, activity prescription, evaluation of medical therapy, and cardiac rehabilitation if the predischarge exercise test was not performed (symptom-limited at approximately 14-21 days); exceptions are noted in the descriptions of classes IIb and III
Late after discharge for prognostic assessment, activity prescription, evaluation of medical therapy, and cardiac rehabilitation if the early exercise test was submaximal (symptom-limited at approximately 3-6 weeks); exceptions are noted in the descriptions of classes IIb and III
Class IIa applications are as follows:
After discharge for activity counseling or exercise training as part of cardiac rehabilitation in patients who have undergone coronary revascularization
Class IIb applications are as follows:
Before discharge in patients who have undergone cardiac catheterization to identify ischemia in the distribution of a coronary lesion of borderline severity
In patients with the following ECG abnormalities: complete left bundle branch block, preexcitation syndrome, LVH, digoxin therapy, more than 1 mm of resting ST-segment depression, and electronically paced ventricular rhythm
Periodic monitoring in patients who continue to participate in exercise training or cardiac rehabilitation
Class III applications are as follows:
In cases involving severe comorbidity likely to limit life expectancy, candidacy for revascularization, or both
At any time, to evaluate patients with acute MI who have uncompensated CHF, cardiac arrhythmia, or noncardiac conditions that severely limit their ability to exercise (level of evidence: C)
Before discharge, to evaluate patients who have already been selected for, or have undergone, cardiac catheterization; although a stress test may be useful before or after catheterization to evaluate or identify ischemia in the distribution of a coronary lesion of borderline severity, stress imaging tests are recommended (level of evidence: C)
Current guidelines for the treatment of patients with acute MI include medical therapy, thrombolytic agents, and coronary revascularization. These interventions have led to a marked improvement in prognosis for post-MI patients, particularly those who have been treated with reperfusion, and mortality has been low among patients who have received thrombolytic agents or direct angioplasty.
Patients who are unable to perform an exercise test have a much higher rate of adverse events than those who are able to perform an exercise test. Symptomatic ischemic ST depression with exercise testing after thrombolytic therapy increases the risk of cardiac mortality 2-fold, but the absolute risk rate remains low (1.7% at 6 months).
Exercise testing after MI is generally safe. Submaximal testing can be performed at 4-7 days, and a symptom-limited test can be performed 3-6 weeks later. Some experts feel that symptom-limited tests can be conducted early after discharge, at approximately 14-21 days.
Exercise testing is useful in activity counseling after discharge from the hospital, and it is also an important tool in exercise training, as part of comprehensive cardiac rehabilitation for assessing the patient’s response to the exercise training program.
Cardiopulmonary exercise testing
Cardiopulmonary exercise testing (CPET) combines exercise testing with ventilation gas analysis. Like post-MI exercise testing, it is performed in accordance with ACC/AHA guidelines.
Class I applications of CPET are as follows:
For evaluation of exercise capacity and response to therapy in patients with heart failure who are being considered for heart transplantation
For assistance in differentiating cardiac limitations from pulmonary limitations as a cause of exercise-induced dyspnea or impaired exercise capacity when the cause is uncertain
Class IIa applications are as follows:
For evaluation of exercise capacity when indicated for medical reasons in patients with unreliable estimates of exercise capacity from exercise test time or work rate
Class IIb applications are as follows:
For evaluation of the patient’s response to specific therapeutic interventions in which improvement of exercise tolerance is an important goal or end point
For determination of the intensity for exercise training as part of comprehensive cardiac rehabilitation
Class III applications are as follows:
For routine use to evaluate exercise capacity
CPET is a useful adjunctive tool for the assessment of patients with cardiovascular and pulmonary disease. It involves measurements of gas exchange, primarily oxygen uptake (ie, VO2), carbon dioxide output (VCO2), minute ventilation, and anaerobic (lactic acid) threshold. Patients usually wear a nose clip and breathe through a nonrebreathing valve that separates expired air from room air.
VO2 at maximal exercise (peak VO2) is considered the best index of aerobic capacity and cardiorespiratory function. Estimation of maximal aerobic capacity by using published formulas based on exercise time or work rate without direct measurement is limited by physiologic and methodologic inaccuracies.
According to data acquired from patients with heart failure who have undergone cardiopulmonary stress testing with this method, subsequent analysis is reliable and important and has been shown to benefit this subgroup of patients the most.
Such data are only partly influenced by resting left ventricular dysfunction. Maximal exercise capacity does not necessarily reflect the daily activities of patients with heart failure. Use of this technique to stratify patients with ambulatory heart failure has improved the clinician’s ability to identify those with the poorest prognosis, who should be considered for heart transplantation.
Abnormal ventilatory and chronotropic responses to exercise are also predictors of outcome in patients with heart failure. In addition, evaluation of the rate of VO2 decline during exercise recovery (VO2 kinetics) may provide additional information regarding the functional state in patients with heart failure. Compared with normal oxygen kinetics, prolonged recovery time of VO2 has been correlated with poorer exercise tolerance, lower peak VO2, and a lower cardiac index.
Most investigators conclude that measurement of peak VO2 yields the best prognostic information in patients with heart failure. Evaluation of submaximal and recovery ventilatory responses may be particularly useful when exercise to near-maximal levels (respiratory exchange ratio greater than 1) is not achieved.
Diagnosis of CAD in special populations
The utility of exercise ECG for the diagnosis of CAD in women is limited. Exercise-induced ST depression is less sensitive in women than in men, reflecting a lower prevalence of severe CAD and the inability of many women to exercise to maximum aerobic capacity. Exercise ECG findings are also commonly viewed as less specific in women than in men, though careful review of the published data demonstrates that this finding certainly has not been uniform.
Studies reporting lower specificity in women have cited lower disease prevalence, non-Bayesian factors, and possible hormonal differences. It is important to be cognizant of the decrease in sensitivity that occurs when women do not exercise to maximum aerobic capacity. Patients likely to exercise submaximally should be considered for pharmacologic stress testing. Concern about false-positive ST-segment responses may be addressed through careful assessment of posttest probability and selective use of stress imaging tests before angiography.
Although the optimal strategy for circumventing false-positive test results for the diagnosis of CAD in women remains to be defined, the data are insufficient to justify routine stress imaging tests as the initial test for the diagnosis of CAD in women.
CAD is highly prevalent in symptomatic elderly patients (> 65 years). Pharmacologic stress testing is required more often in elderly patients because of their inability to exercise adequately.
Interpretation of exercise test results from elderly patients differs somewhat from that in younger patients. Resting ECG abnormalities may compromise the accuracy of diagnostic data from the ECG. Nonetheless, the application of standard ST-segment response criteria to elderly subjects does not appear to be associated with a significant difference in accuracy from that of younger patients.
Because of the greater prevalence of severe CAD, exercise testing in this group is reported to have a slightly higher sensitivity than in younger patients. A slightly lower specificity has also been reported, which may reflect the coexistence of LVH due to valvular disease and hypertension. Although the risk of coronary angiography may be greater in elderly patients and the justification for coronary intervention less, the results of exercise testing in elderly patients remain important because medical therapy may carry substantial risks for this group.
Exercise testing in asymptomatic persons without known CAD
Exercise testing in asymptomatic persons without known CAD or risk factors is assessed in the light of the ACC/AHA guidelines.
No class I applications of exercise testing in this population exist. Class IIa applications are as follows:
For evaluation of asymptomatic persons with diabetes mellitus who plan to start vigorous exercise (level of evidence: C)
Class IIb applications are as follows:
For evaluation of persons with multiple risk factors (as a guide to risk-reduction therapy; see below)
For evaluation of asymptomatic men older than 45 years and women older than 55 years, including those who plan to begin vigorous exercise (especially if previously sedentary), those with occupations in which impairment might impact public safety, and those who are at high risk for CAD due to other diseases (eg, chronic renal failure and peripheral vascular disease)
Class III applications are as follows:
For routine screening of asymptomatic men or women
The goal of screening for possible CAD in asymptomatic patients is either to prolong life or to improve quality of life. This goal has been supported by data from the Coronary Artery Surgery Study and the Asymptomatic Cardiac Ischemia Pilot (ACIP) study in asymptomatic patients with severe CAD, which suggests that performing revascularization may prolong life.
Although current clinical guidelines suggest risk reduction factors in all people, the detection of ischemia after stress testing results indicate that functional impairment may further motivate patients to be more compliant with a program of risk factor modification.
Prediction of MI and death are considered the most important endpoints in the screening of asymptomatic patients. In general, the relative risk of a subsequent event is increased in patients with a positive exercise test result, though the absolute risk of a cardiac event in an asymptomatic patient remains low. The annual rate of MI and death in such patients is approximately 1%, even when ST-segment changes are associated with risk factors.
A positive exercise test result is a better predictor of the subsequent development of angina than the occurrence of a major event is. Even when subsequent angina is considered an event, a minority of patients with a positive test result experience cardiac events. Unfortunately, patients with positive test results may be labeled as being at risk.
For example, general population screening programs attempting to identify young patients with early disease are limited, in that severe CAD requiring intervention in asymptomatic patients is exceedingly rare. Although the physical risks of exercise testing are negligible, false-positive test results may (1) engender inappropriate anxiety, (2) have serious adverse consequences related to work and insurance coverage, and (3) lead to complications from further diagnostic testing. For these reasons, exercise testing in healthy, asymptomatic persons is not recommended.
Selected patients with multiple risk factors for CAD are at greater absolute risk for subsequent MI and death. Screening may potentially be helpful in patients who are at moderate risk, as defined by the available prognostic data from asymptomatic persons in the Framingham study.
For these purposes, define risk factors very strictly. Multiple risk factors are defined as hypercholesterolemia (cholesterol >240 mg/dL), hypertension (systolic blood pressure [SBP] >140 mm Hg or diastolic blood pressure [DBP] >90 mm Hg), smoking, diabetes, and family history of heart attack or sudden cardiac death in a first-degree relative younger than 60 years.
An alternative approach might be to select patients with a Framingham risk score consistent with at least a moderate risk of serious cardiac events within 5 years. Attempts to extend screening to persons with lower degrees of risk are not recommended because screening is extremely unlikely to improve patient outcome.
In a study of 6578 asymptomatic individuals who performed Bruce treadmill tests and were observed for 20 years to assess the risk of cardiovascular death, Weiss et al determined that elevated exercise blood pressure in asymptomatic individuals was associated with a higher risk of cardiovascular death, but the risk become nonsignificant after resting blood pressure was accounted for.
In this study, Bruce stage 2 blood pressure 180/90 mm Hg identified those without hypertension who were at high risk for cardiovascular death. Good blood pressure control in individuals with asymptomatic hypertension is always desirable for overall long-term good prognosis.
Exercise testing in patients with valvular heart disease
According to the ACC/AHA guidelines, no recommendations exist for routine exercise testing of patients with valvular heart disease. The current recommendations for the application of exercise testing in patients with valvular heart disease are as follows:
Class I – None
Class IIb – For evaluation of exercise capacity of patients with valvular heart disease – The presence of symptomatic, severe aortic stenosis is a contraindication to exercise testing
Class III – For diagnosis of CAD in patients with valvular heart disease
In symptomatic patients with documented valvular disease, the course of treatment is usually clear, and exercise testing is not required. Furthermore, the expanding use of Doppler echocardiography has greatly increased the number of asymptomatic patients with well-defined valvular abnormalities, the etiology of which may be nonischemic (eg, congenital abnormalities).
The primary value of exercise testing in persons with valvular heart disease lies in its ability to assess atypical symptoms, exercise capacity, and the extent of disability objectively—all of which may have implications for clinical decision making. Assessment is particularly important in elderly patients, who may not have symptoms because of limited activity. Use of the exercise ECG for diagnosis of CAD in these situations is limited by false-positive responses due to LVH and baseline ECG changes.
In patients with aortic stenosis, a clinician familiar with the patient’s condition should supervise the test directly, and exercise should be terminated for inappropriate blood pressure augmentation, slowing of the heart rate with increasing exercise, or premature beats.
Because the major indication for surgery in mitral stenosis is symptom status, exercise testing is most valuable when a patient is thought to be asymptomatic because of inactivity or when a discrepancy exists between the patient’s symptoms and the valve area.
Because ejection fraction is a reliable index of left ventricular function in aortic regurgitation, decisions regarding surgery are likely to be based on resting ejection fraction values, and exercise testing is not commonly required unless symptoms are ambiguous.
Resting ejection fraction is a poor guide to ventricular function in patients with mitral regurgitation; thus, combinations of exercise and assessment of left ventricular function may be of value in documenting occult dysfunction.
Exercise testing before and after revascularization
Exercise testing in patients undergoing revascularization constitutes an important part of treatment of these patients because the risks of undergoing major surgery must be carefully measured against the expected benefits and because proper assessment is essential for optimal results. The decision to employ such testing is made in accordance with ACC/AHA guidelines.
Class I applications of exercise testing in patients undergoing revascularization are as follows:
For demonstration of proof of ischemia before revascularization
For evaluation of patients with recurrent symptoms suggesting ischemia after revascularization
Class IIa applications are as follows:
After discharge for activity counseling and/or exercise training as part of cardiac rehabilitation in patients who have undergone coronary revascularization
Class IIb applications are as follows:
For detection of restenosis in selected, high-risk, asymptomatic patients within the first months after angioplasty
For periodic monitoring of selected high-risk, asymptomatic patients for restenosis, graft occlusion, or disease progression
Class III applications are as follows:
For localization of ischemia to determine the site of intervention
For routine periodic monitoring of asymptomatic patients after PTCA or CABG without specific indications
Current guidelines do not recommend routine testing within 2 years for patients who have undergone coronary revascularization procedures. However, a study has shown that 12% of these patients who visit their physician at least 3 months after the procedure undergo stress testing within 30 days of the visit. The study shows that discretionary stress testing is performed more frequently by physicians who bill for technical and professional fees than by those who do not, possibly as a way to recoup upfront costs for imaging equipment.
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