An acute coronary syndrome (ACS) is comprised of biomarker-positive ST-segment elevation myocardial infarction (STEMI), non–ST-segment elevation myocardial infarction (NSTEMI), and biomarker-negative unstable angina (UA; Fig. 13-1 ). The most common pathology that causes an ACS is disruption of a vulnerable coronary artery plaque and subsequent luminal thrombotic obstruction. Less common causes are coronary vasospasm, spontaneous dissection, and severe demand-induced ischemic processes, such as marked tachycardia or severe hypotension. The treatment strategy for STEMI involves immediate percutaneous coronary intervention (PCI) or fibrinolysis when feasible and appropriate, whereas for NSTEMI-UA (NSTE-ACS) an immediate (early) or selective invasive (conservative) approach is recommended, depending on prognostic indicators during the index event. In this chapter, noninvasive risk stratification for patients who present to the emergency room with chest pain and stabilized ACS patients at or around the time of hospital discharge will be discussed, with emphasis on patients admitted for NSTE-ACS syndromes caused by total or partial thrombotic occlusion on a vulnerable ruptured plaque. It should be noted that risk stratification for ACS patients is an ongoing process that starts when the patient first presents to the health care system and continues for several months after hospital discharge. The reader is referred to other sections in this text for a more detailed description of ACS patient management in the emergency room and the first 24 to 48 hours of hospitalization.
Chest Pain Evaluation in the Emergency Department
A major goal in the evaluation of patients with nontraumatic chest pain in the emergency department (ED) is to rule out an acute myocardial ischemic event. The initial evaluation requires an assessment of the likelihood that the chest pain or chest pain equivalent (e.g., dyspnea, excessive fatigue) is caused by an ACS and, if so, whether the patient is at low, intermediate, or high risk of an early adverse outcome. Of more than 5,000,000 patients presenting to the ED in the United States annually with chest pain, most (>90% to 95%) do not have electrocardiographic evidence of STEMI, and only a minority (∼20%) will rule in for an NSTE-ACS. Among patients discharged with a diagnosis of ACS, the initial ED ECG will show findings suggestive of myocardial ischemia in approximately 40% to 50% of cases. To enhance the sensitivity of the 12-lead electrocardiogram (ECG), serial or continuous electrocardiographic monitoring, and the use of nonstandard lead systems that include posterior and right ventricular leads, can be helpful when the suspicion for ACS is high and the initial ECG is nondiagnostic, with unremarkable cardiac biomarkers. The cost-effectiveness of this strategy for all patients presenting with chest pain to the ED has not been determined, but is not likely to be cost-effective. Clinically low-risk patients with chest pain, who present with stable symptoms and a normal or nondiagnostic ECG, can usually be managed by an accelerated diagnostic protocol that includes 6 to 12 hours of clinical and electrocardiographic monitoring and serial cardiac biomarkers.
Methamphetamine or cocaine-related chest pain is a common problem in the United States, leading to more than 500,000 visits to the emergency department annually; 40% of these patients complain of chest pain. Distinguishing a patient with an ACS who has recently used cocaine can present a diagnostic problem in the ED. Cocaine use causes an acute dose-dependent increase in heart rate, systolic blood pressure, and contractility by blocking catecholamine uptake and constricting coronary arteries, and may be associated with a hypercoagulable state. In one series of 4568 patients evaluated in a chest pain unit in Sacramento, California, the prevalence of coronary disease in patients with a positive drug screen was similar to those with a negative result. Thus, the risk stratification process in a patient with chest pain associated with cocaine abuse should follow standard established processes for ACS as detailed below.
Rest and Dynamic Electrocardiographic Changes
Baseline demographics and the rest and dynamic ECGs (e.g., Holter, telemetry, monitoring devices) contain important prognostic information that can be used to establish an ACS diagnosis as well as an immediate treatment strategy. Electrocardiographic abnormalities of myocardial ischemia or infarction may be inscribed in the PR segment, QRS complex, and ST segment or T waves. The earliest manifestations of myocardial ischemia are typical T waves and ST-segment changes. Increased hyperacute T-wave amplitude with prominent symmetric T waves in at least two contiguous leads is an early sign that may precede the elevation of the ST segment. Increased R-wave amplitude and width (giant R wave with S-wave diminution) are often seen in leads exhibiting ST elevation and tall T waves, reflecting conduction delay in the ischemic myocardium. Transient Q waves may be observed during an episode of acute ischemia or, rarely, during acute myocardial infarction with successful reperfusion. Q waves indicating prior myocardial infarction almost always confirms the diagnosis of coronary disease and new ST-segment depression ≥0.05 mV in at least two contiguous leads, or T-wave inversion ≥0.01 mV in at least two contiguous leads, with a prominent R wave, is consistent with myocardial ischemia during or after a chest pain episode with ST-segment elevation or depression associated with a worse mortality outcome than T-wave changes ( Fig. 13-2 ). The presence of a new conduction disturbance (e.g., left bundle branch block), or frequent or complex ventricular ectopy, is also associated with an increased likelihood of coronary disease and adverse outcomes. Table 13-1 summarizes studies on the prognostic value of ST-T–wave abnormalities in NSTE-ACS. Table 13-2 illustrates that the cardiac event rate increases with increasing magnitude of ST-segment depression; excessive risk is observed with ST-segment depression (STD) ≥0.05 mV. Although more severe STD is a marker of increased short- and long-term mortality, it is also associated with higher risk clinical features and biomarkers. In the GRACE registry, after adjustment for clinically important predictors, the magnitude of STD does not provide incremental prognostic value beyond simple dichotomous evaluation for the presence of STD.
| Study (Year) | Sample Size | ST-T Criteria on Admission ECG (Prevalence) | Major Findings | Significant Covariate Predictors |
|---|---|---|---|---|
| ST-T Abnormalities as Univariate Predictor | ||||
| Cohen et al (1991) | 90 † | ST deviation ≥ 1 mm in two or more leads (63%) | Higher 3-mo rates of death, MI, recurrent ischemia, revascularization in the presence of ST changes (77% vs. 36% without ST changes) | N/A |
| Lee et al (1993) | 136 ‡ | ST depression ≥ 1 mm in any lead (100%) | Mortality gradient at 1 yr according to degree of baseline ST depression: 14% (1 mm) vs. 39% (2 mm) vs. 30% (≥3 mm) | N/A |
| Nyman et al (1993) | 911 § | ST depression (± T↓) ≥ 1 mm in any lead (24%); isolated T↓ (31%) | Death, MI at 1 yr—7.6% (no ST-T changes) vs. 13.6% (isolated T↓) vs. 18.1% (ST depression) | N/A |
| ST-T Abnormalities as Multivariate Predictor | ||||
| Hyde et al (1999) | 367 § | ST depression ≥ 0.5 mm in any lead (47%); isolated T↓ ≥ 1 mm in any lead (16%) | ST depression ≥ 0.5 mm but not isolated T↓ significantly predicted lower 4-yr survival | Age, CHF, revascularization |
| Cannon et al (1997) | 1416 § | ST deviation ≥ 0.5 mm in any lead (27%); isolated T↓ ≥ 1 mm in any lead (22%) | ST deviation ≥ 0.5 mm but not isolated T↓ significantly predicted death, MI at 1 yr | Age, fibrinolysis within past week, nitrate within past week, LBBB, other major illnesses, poor compliance with follow-up |
| Kaul et al (2001) | 1588 ‡ | ST depression ≥ 1 mm in any lead (43%) | Mortality gradient at 1 yr according to degree of baseline ST depression: 2% (no depression) vs. 7.8% (1 mm) vs. 13.4% (≥2 mm) cerebrovascular disease | Age, COPD, previous MI, CHF, PVD diabetes, previous PTCA, cerebrovascular disease |
| Antman et al (2000) | 1957 † | ST deviation ≥ 0.5 mm in any lead (72%) | Risk of death, MI, or urgent revascularization in the presence of ST deviation 1.5 times higher than that without ST deviation | Age, three or more cardiac risk factors, prior CAD, ≥50% stenosis, two or more anginal events in prior 24 hr, use of aspirin in prior week, elevated biomarkers ‖ |
| Diderholm et al (2002) | 2457 † | ST depression ≥ 0.5 mm in any lead (46%); isolated T↓ ≥ 1 mm in any lead (36%) | ST depression ≥ 0.5 mm but not isolated T↓ significantly predicted higher death, MI at 1 yr | Age, diabetes, two or more antianginal medications, TnT ≥ 0.06 mg/L, CHF (or LVEF < 45%), early invasive strategy |
| Savonitto et al (1999) | 6986 ‡ | ST depression ≥ 0.5 mm in any lead (35%); isolated T↓ ≥ 1 mm in any lead (22%) | Death, MI at 6 mo—3.4% (isolated T↓) vs. 8.9% (ST depression), P < .02 | Age, Killip class, tachycardia, PVD diabetes, previous angina, hypertension, elevated CK on admission |
| Boersma et al (2000) | 9461 † | ST depression ≥ 0.5 mm in any lead (50%); isolated T↓ ≥ 1 mm in any lead | ST depression but not T↓ associated with near-doubling of 30-day mortality | Age, heart rate, systolic BP, CHF, elevated CK on admission, prior CABG, diabetes, CCS III/VI angina in past 6 wk, region of enrollment, prior use of beta blocker or CCB |
* NSTE ACS encompasses the clinical syndromes of UA and NSTEMI. ST-T changes are described in individual footnotes.
† Part of composite inclusion criteria.
‡ Necessary inclusion criteria.
| Parameter | ST-Segment Depression | ||
|---|---|---|---|
| None | 1 mm | ≥2 mm | |
| Enrollment MI (%) | 28.2 | 38.8 | 55.1 |
| Death (%) | |||
| 30 days | 0.7 | 2.8 | 6.3 |
| 6 mo | 1.1 | 6.2 | 12.0 |
| Reinfarction (%) | |||
| 30 days | 6.8 | 11.2 | 14.1 |
| 6 mo | 8.4 | 14.1 | 16.3 |
| Death, re-infarction (%) | |||
| 30 days | 7.2 | 12.1 | 17.1 |
| 6 mo | 9.2 | 16.7 | 23.9 |
Dynamic electrocardiographic monitoring early in the course of a STEMI is useful to determine the likelihood of reperfusion. , When ST-segment elevation (STE) recurs after the ST segment has trended toward normal, reocclusion of the infarct-related vessel should be suspected. It is recommended that an ECG be obtained during any chest pain episodes that occur after the index event because symptomatic and silent ECG changes (e.g., STD or STE) are associated with a significantly increased risk of reinfarction and death, and is an indication for further investigation and treatment ( Fig. 13-3 ).
Noninvasive Testing in the Emergency Department
An accelerated diagnostic protocol in a patient with suspect ACS stratified to low-intermediate clinical risk may include early exercise testing and/or imaging procedures for risk stratification to determine the need for hospital admission or more intensive monitoring (e.g., cardiac care unit [CCU] admission).
Exercise Testing
The use of exercise testing is relatively safe and can identify patients at very low risk for cardiac events. Box 13-1 provides indications and contraindications for exercise testing in an ED or chest pain unit. In one series of 1000 clinically low-risk patients presenting to the ED with chest pain between 1993 and 1998, Amsterdam and colleagues performed exercise testing using a modified Bruce protocol and reported that 13%, 64%, and 23% of the exercise tests were normal, abnormal, or nondiagnostic, respectively. There were no deaths in the next 30 days regardless of the exercise test results and those with a normal exercise test were discharged directly from the ED. Of the 640, 125, and 235 patients who had a negative, positive, or nondiagnostic test, a myocardial infarction was diagnosed in 1, 4 and 0 patients, respectively. Similar results have been reported by others and are summarized in an AHA statement on the role of exercise testing for chest pain evaluation in the ED.
BOX 13-1 Requirements before exercise ECG testing that should be considered in the emergency department setting:
- •
Two sets of cardiac enzymes at 4-hr intervals—should be normal
- •
ECG at the time of presentation and pre-exercise 12-lead ECG shows no significant change
- •
Absence of rest electrocardiographic abnormalities that would preclude accurate assessment of the exercise ECG
- •
From admission to the time results are available from the second set of cardiac enzymes—patient asymptomatic, lessening chest pain symptoms, or persistent atypical symptoms
- •
Absence of ischemic chest pain at the time of exercise testing
Contraindications to exercise electrocardiographic testing in the ED setting
- •
New or evolving electrocardiographic abnormalities on the rest tracing
- •
Abnormal cardiac enzyme levels
- •
Worsening or persistent ischemic chest pain symptoms from admission to the time of exercise testing
- •
Clinical risk profiling indicating imminent coronary angiography is likely
Imaging Procedures
Approximately 30% of low-risk patients presenting with chest pain are not candidates for an exercise test. In this setting, stress echocardiography, stress myocardial scintigraphy, or coronary computed tomography (CT) imaging can be used for risk stratification. The addition of left ventricular ejection fraction into risk stratification models improves prognostic accuracy in chest pain patients to predict mortality. In the PRISM-PLUS trial, the C statistic was increased from 0.67 to 0.73 by adding ejection fraction to the TIMI risk score in 1104 patients admitted for ACS. The use of a hand-held echocardiographic device to assess left ventricular function was examined by Weston and associates in 150 patients who presented to the ED with suspected ACS. The 30-day incidence of acute myocardial infarction was 2.5% in those with a normal examination and 20% in those with an abnormal test ( P = .002). Although the hand-held device provides useful information, dobutamine echocardiography is a more robust technique because it is able to induce wall motion abnormalities during stress as well as provide an estimate of resting left ventricular function; it is not as dependent on fortuitously capturing a transient wall motion abnormality if the patient is not ischemic at the time of a rest imaging study. Myocardial perfusion imaging provides similar information as dobutamine echocardiography but is more expensive and results in radiation exposure. Therefore, perfusion imaging should be considered when dobutamine echocardiography is not possible because of poor acoustic windows, technically suboptimal images, or a contraindication to dobutamine.
Computed Tomography Coronary Angiography
EBCT (ultrafast CT) is a highly sensitive technique to detect and quantify coronary artery calcification and has been used to triage patients presenting to the ED for chest pain. Absence of coronary calcification is associated with a low 30-day risk of major cardiac events (<1%). In general, the higher the calcification score, the greater the atherosclerotic burden and likelihood of cardiac events compared with patients without calcification. Limitations of imaging for coronary calcification only are the following: (1) patients with known coronary artery disease usually have coronary calcification and the incremental value of the test in this clinical setting is unlikely to aid in the risk stratification process; (2) EBCT cannot detect vulnerable plaques that do not contain calcium; and (3) approximately 10% of patients with ACS have no calcium detected on imaging. The radiation exposure to patients undergoing EBCT is small.
Contrast-Enhanced Computed Tomography
Contrast-enhanced CT imaging multidetector CT (MDCT) using more than 64-slice scanners have stimulated considerable interest in the ED evaluation of patients presenting with chest pain because the technique provides information on important noncoronary causes of chest pain, such as aortic dissection, pulmonary embolism, and pericardial disease, as well as coronary anatomy and graft patency. The images are acquired at a relatively low heart rate (<65 to 70 beats/min). Atrial fibrillation or frequent ectopy diminishes resolution and may result in suboptimal images. The contrast load is at least 60 to 120 mL and may be a relative contraindication in patients with compromised renal function. Radiation exposure can exceed that acquired during coronary angiography. In a relatively small series of clinically low-risk chest pain patients evaluated in the ED or chest pain unit, Goldstein and coworkers have randomized 197 patients to MDCT or a standard diagnostic evaluation. MDCT immediately excluded or identified coronary disease as the source of chest pain in 75% of patients, 67 of whom had normal coronary arteries and 8 of whom had severe disease requiring revascularization. The remaining 25% of the cohort required stress testing for either intermediate lesions or nondiagnostic scans. Diagnostic workup time and cost were significantly decreased using the MDCT approach. In a different series of 92 low-risk chest pain patients, Gallagher and colleagues prospectively studied 30-day event rates using MDCT and myocardial perfusion imaging. Seven (8%) were excluded because of suboptimal MDCT scans. Of the 85 remaining patients, 7 (8%) had important coronary disease, but none had a major cardiac event. The sensitivity for stress nuclear imaging and MDCT were 71% and 86% of patients, respectively, and specificity was 90% and 92%, respectively, in this small series.
The scientific value of MDCT imaging and its place in the noninvasive evaluation of patients with chest pain in the emergency room is an area of active research. Nevertheless, the number of MDCT procedures performed in the ED to evaluate patients with chest pain has increased rapidly. The MDCT test provides anatomic information but, unlike noninvasive stress test procedures, does not provide a functional assessment of coronary vascular reserve.
Establishing Pretest Risk in Acute Coronary Syndrome Patients
The pretest risk of a stabilized ACS patient needs to be assessed prior to noninvasive testing to optimize post-test diagnostic and prognostic risk statements. The use of Bayesian principles when applying the results of noninvasive tests to estimate risk is well established. In general, early mortality is greatest in patients who have sustained a STEMI and lowest in those with UA. , Figure 13-4 illustrates 6-month survival rates for the three different types of ACS in 43,810 patients enrolled in the GRACE registry from 1999 to 2005.
In addition to the type of ACS, numerous demographic characteristics independently predict risk and are incorporated into the different clinical scoring systems used to estimate mortality after an ACS. Thus, the 5-year prognostic estimate of mortality for exercise-induced ST-segment depression or an imaging defect at a workload of 5 metabolic equivalent tests (METs) will be different in an older STEMI patient with two prior myocardial infarctions and compensated heart failure (e.g., three-vessel disease and an ejection fraction of 30%) than in a younger patient with no prior cardiac history who presents for the first time with UA (e.g., single-vessel disease and ejection fraction >50%).
The TIMI risk score for STEMI is shown in Figure 13-5 (more information is available at http://www.TIMI.org ). Using this risk model, a 65-year-old obese man with anterior ST-segment elevation, a prior history of hypertension and angina but no diabetes, with a normal blood pressure and heart rate and was Killip class lower than 2 at presentation, treated less than 4 hours after symptom onset, would have a risk score of 5 and an estimated 30-day mortality of 12.4%. The pretest risk may be modified lower or higher, depending on the results of noninvasive testing. This concept will be discussed further later in the chapter.
Non–ST-Segment Elevation–Acute Coronary Syndrome Risk Scores
Risk scores to stratify NSTE-ACS have been developed by the TIMI, PURSUIT, GRACE, and FRISC groups and by others ( Table 13-3 ). Goncalves and colleagues studied 460 consecutive Portuguese patients admitted to their CCU for NSTE-ACS from 1999 to 2001 and prospectively tested the predictive accuracy of the TIMI, PURSUIT, and GRACE scores for the composite end point of death or death-MI after 1 year. In their report, each scoring method was effective in identifying low-, intermediate-, and high-risk patients. High-risk patients were classified in 36.7%, 28.7%, and 57.8% of the population using the GRACE, PURSUIT, and TIMI risk scores, respectively. However, receiver operating characteristic (ROC) has analysis determined that the GRACE score has the greatest predictive accuracy in estimating 1-year death-MI. The TIMI and GRACE scores include both the ECG and biomarkers in the model, whereas PURSUIT excludes biomarkers. The FRISC score differs from the other scoring methods by including inflammatory markers in the prediction model (e.g., interleukin-6 or C- reactive protein). An important distinction between the GRACE and other scoring methods is the variable derivation from a registry of consecutive ACS patients rather than a randomized trial that had specific inclusion-exclusion criteria and the inclusion of renal function, a variable known to affect long-term prognosis. , The validated GRACE prediction model predicts a 6-month mortality risk after hospital discharge in an international registry for all forms of ACS ( Fig. 13-6 ).
| Study | Score ( Separate Points for Enrollment Diagnosis ) |
|---|---|
| PURSUIT (0-18) | |
| Age, decade (UA [MI]) | |
| 50 | 8 (11) |
| 60 | 9 (12) |
| 70 | 11 (13) |
| 80 | 12 (14) |
| Gender | |
| Male | 1 |
| Female | 0 |
| Worst CCS class in previous 6 wk | |
| No angina or CCS class I or II | 0 |
| CCS class III or IV | 2 |
| Signs of heart failure | 2 |
| ST depression on presenting ECG | 1 |
| TIMI (0-7) | |
| Age ≥ 65 yr | 1 |
| Three or more risk factors for CAD | 1 |
| Use of aspirin (last 7 days) | 1 |
| Known CAD (stenosis ≥ 50%) | 1 |
| More than one episode rest angina in <24 hr | 1 |
| ST-segment deviation | 1 |
| Elevated cardiac markers | 1 |
| GRACE (0-258) | |
| Age (yr) | |
| <40 | 0 |
| 40-49 | 18 |
| 50-59 | 36 |
| 60-69 | 55 |
| 70-79 | 73 |
| ≥80 | 91 |
| Heart rate (beats/min) | |
| <70 | 0 |
| 70-89 | 7 |
| 90-109 | 13 |
| 110-149 | 23 |
| 150-199 | 36 |
| >200 | 46 |
| Systolic BP (mm Hg) | |
| <80 | 63 |
| 80-99 | 58 |
| 100-119 | 47 |
| 120-139 | 37 |
| 140-159 | 26 |
| 160-199 | 11 |
| >200 | 0 |
| Creatinine (mg/dL) | |
| 0-0.39 | 2 |
| 0.4-0.79 | 5 |
| 0.8-1.19 | 8 |
| 1.2-1.59 | 11 |
| 1.6-1.99 | 14 |
| 2-3.99 | 23 |
| >4 | 31 |
| Killip class | |
| I | 0 |
| II | 21 |
| III | 43 |
| IV | 64 |
| Cardiac arrest at admission | 43 |
| Elevated cardiac markers | 15 |
| ST-segment deviation | 30 |
Thus, higher risk patients can be identified early who might benefit from early coronary angiography and revascularization when clinically and technically appropriate or more intensive medical therapy during admission for the index event. For example, patients with important spontaneous silent or symptomatic ischemia after hospital admission, hemodynamic or arrhythmic instability, and severe left ventricular dysfunction (e.g., left ventricular ejection fraction ≤ 40%) are usually referred for early coronary angiography before noninvasive testing is considered. This means that many patients (but not all) referred for noninvasive testing at or around the time of hospital discharge will be at less than high risk of future cardiac events because higher risk patients are removed early for coronary revascularization. Note that it is the role of the noninvasive test procedures to identify the subset of these patients at lower risk for whom coronary angiography would not be indicated, or the higher risk patients for whom angiography and revascularization or more intensive medical therapy would be indicated to improve life expectancy. Noninvasive testing should not be ordered if the results will not be used to affect subsequent treatment.
The data base for noninvasive testing after MI is robust but the available results and prognostic estimates span several decades in which different treatment regimens and definitions for ACS have been used ( Table 13-4 ). This temporal issue affects the ability to extrapolate from earlier studies to contemporary medicine. For example, among the 44,372 patients in the ACS GRACE registry, the 6-month mortality declined from 4.9% in 1999 to 3.3% in 2005 and the recurrent infarction rate from 3% to 1.7%. During this same interval, there was an increased use of aspirin, beta blockers, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), statins, thienopyridines, and coronary revascularization. This means that post-test estimates of recurrent events will be lower currently than what would have been expected from papers published a decade ago. This is because the highest risk patients have been selected out for procedures that improve life expectancy based on the results of the noninvasive tests (post-test referral bias) and the availability of post-test long-term pharmacologic therapy now reduces cardiac event rates more than at an earlier time (see Table 13-4 ).
| Study (Year) | Inclusion Criteria | Exclusion Criteria | Type of Test | Timing After MI | Results of Abnormal Noninvasive Testing | Length of Follow-Up | Outcomes |
|---|---|---|---|---|---|---|---|
| Theroux et al (1979) | All pts who ruled in based on MI diagnosis criteria | ST elevation on ECG | Treadmill, Naughton protocol | 11 days (7-20 days) | Abnormal; angina; horizontal STD ≥ 1 mm; test results did not lead to cath, intervention | 1 yr | 2.1% mortality with no STD; 27% mortality with STD ( N = 210) |
| Wilcox et al (1991) | All pts admitted to CCU with UA; not scheduled for PCI or CABG | ≥70 yr of age; history of MI in prior mo; CP in prior 3 days; uninterpretable ECG | Treadmill, modified Naughton | 3 days after UA | Abnormal; ≥0.1 mV horizontal or downsloping STD; ≥0.15 mV slow upsloping STD; >0.1 mV additional STD in pts with ≥0.1 mV STD or ≥0.1 mV STE at rest; three pts with positive stress tests went to cath (results unknown) | 1 yr | Low-risk ECG associated with lower risk of MACE at 12 mo ( N = 149) |
| Nyman et al (1993) | Men <70 yr of age with UA | STE or QS development in two consecutive leads; previous CABG; CK peak >15 ukat/L; uninterpretable ECG; current treatment with aspirin or anticoagulation; persistent CP | Bicycle | 3-14 days after admission | Low risk—performed >140 W; 0 leads with ≥0.05 mV STD; high risk—performed <100 W; two or more leads with ≥0.05 mV of STD; no cath for high-risk pts | 1 yr | High-risk pts had 1-yr mortality of 3.6% and 1-yr event rate of MI or death of 15.4% compared with low-risk pts with event rate of 0% and 3.9%, respectively ( N = 855) |
| Lindahl et al (1997) | Pts > 40 yr of age with chest pain and changes in ECG (STD ≥ 0.1 mV or T-wave inversion) | Premenopausal women; STEMI; LBBB; pacemaker; myocarditis, pericarditis; significant AV disease; cardiomyopathy; severe systemic illness; planned PCI or CABG | Bicycle, symptom- limited | 5 days | Low risk—normal maximal workload (>90 W for men and >70 W for women); no STD of ≥0.1 mV in three or more leads; high risk—low maximal workload (<90 W in men and <70 W in women); STD of ≥0.1 mV in three or more leads; no cath in high-risk pts | 5 mo | High-risk stress test leads to higher event rates; death or MI occurred in 5% of low-risk stress test pts vs. 29% of high-risk stress test pts ( N = 766) |
| Safstrom et al (1998) | Postmenopausal women admitted to CCU with typical CP and changes in ECG (STD ≥ 0.1 mV or TWI) | LBBB; LVH; pacemaker; myocarditis, endocarditis; cardiomypathy; significant AV disease; planned PCI or CABG; severe systemic disease | Bicycle, symptom- limited | 5-8 days | ≥0.1 mV of downsloping or horizontal STD; cath on all pts within 60 days | 3 mo | STD has positive predictive value of 91% for angiographically significant CAD (no prognostic data) ( N = 176) |
| TIMI IIIB (1994) | Pts 21-79 yr with ischemic chest pain associated with ≥0.1 mV of ST elevation <30 min; STD ≥ 0.1 mV or TWI; documented CAD by cath or positive nuclear test | MI in previous 21 days; angio in previous 30 days; PTCA ≤ 30 days; CABG; pulmonary edema; SBP > 180 or DBP > 100 mm Hg; contraindication to thrombolytics; severe systemic illness; LBBB; oral anticoagulants; women who could be pregnant | Treadmill, modified Bruce protocol | Prior to discharge | Pts went to cath if prior to completing stage II they had ischemic chest pain, ≥0.2 mV of ST deviation, or decrease in SBP > 10 mm Hg; two or more areas of reversible defect on nuclear imaging; increased LHR and one area of reversible defect on nuclear imaging; chest pain ≥ 5 min with ≥0.2 mV of ST deviation in two contiguous leads; >20 min of ≥0.1 mV ST deviation on 24-hr Holter | 6 weeks to 1 year | Primary end point death, MI, unsatisfactory ETT at 6 wk; early invasive test met primary end point at 16.2% compared with selectively invasive group at 18.1%; at 1 yr, no difference between death or recurrent MI ( N = 1473) |
| Boden et al (1998) | CK-MB > 1.5 × ULN | New Q waves; serious coexisting conditions; ischemic complications mandating cath | Symptom- limited Bruce protocol; treadmill with thallium dipyridamole if METs < 5 | Prior to discharge | STD of 2 mm at peak exercise; pts with redistribution defect in one or two vascular territories and increased lung uptake went for cath | 23 months | Angio, 30 days, revasc, 30 days, one end point: invasive, 96%, 44%, 30% respectively; noninvasive, 48%, 33%, 27%, respectively; primary end point, death or nonfatal MI at 23 mo ( N = 920) |
| FRISC-II (1999) | Pts with symptoms consistent with ischemia, changes in ECG, and positive cardiac enzymes | Increased risk of bleeding, anemia; thrombolytics; PCI within 6 mo; planned PCI or CABG; renal or hepatic insufficiency; severe systemic disease | Bicycle, symptom- limited | Prior to discharge | Pts went to cath if predischarge stress test showed severe ischemia | 1 yr | Angio, 7 days; angio, 12 mo; PCI, 12 mo: invasive, 96%, 99%, 44%, respectively; noninvasive, 7%, 52%, 21%, respectively; 1.7% absolute reduction in mortality in invasive group at 12 mo; 5-yr follow-up shows 4.6% absolute risk reduction of primary composite end point of death or MI in invasive group ( N = 2457) |
| Cannon et al (2001) | >18 yr of age with anginal chest pain and STD ≥ 0.05 mV, transient STE ≥ 0.1 mV, T-wave inversion = 0.3 mV, increased cardiac enzymes, or history of CAD by cath; history of revascularization or of MI | Persistent STE; PCI or CABG in previous 6 mo; increased risk of bleeding; LBBB; paced rhythm; warfarin; clopidogrel or ticlopidine for more than 3 days prior to enrollment; severe systemic disease | Treadmill, Bruce protocol, (83% with nuclear or echo imaging) | Prior to discharge | Angina and STD ≥ 0.1 mV; STD ≥ 0.2 mV without symptoms; drop in SBP = 10 mm Hg; one large or two small areas of perfusion defect on nuclear imaging; new wall motion abnormality on echo | 6 mo | Angio in hospital, angio 6 mo, PCI 6 mo, one end point: invasive, 97%, 98%, 42%, 15.9%, respectively; noninvasive, 51%, 61%, 29%, 19.4%, respectively; primary end point defined as death, nonfatal MI, rehospitalization; decreased risk of primary end point at 6 mo with early invasive strategy ( N = 2220) |
| Spacek et al (2002) | Rest ischemic chest pain > 20 min; STD ≥ 0.1 mm or TWI in two contiguous leads; CK-MB > 2× ULN or positive troponin | Unstable chest CP despite medical therapy; cardiogenic shock; acute LBBB, RBBB, or STE; QWMI or thrombolysis in the last month; PCI or CABG < 6 mo; severe systemic disease | Bicycle, symptom- limited | 30 days | CP with STD of 2 mm at peak exercise; perfusion defect of at least one vascular territory in pts who could not exercise and had a dipyridamole nuclear stress test | 6 mo | Angio, 6 mo, revasc, 6 mo, one end point: invasive, 100%, 73%, 6.3%, respectively; noninvasive, 55%, 39%, 22.4%, respectively; primary end point, death or nonfatal MI ( N = 131) |
| Hirsch et al (2007) | Symptoms of ischemia; elevated troponin T ≥ 0.03 µg/L; ischemic changes on ECG or history of CAD | Age < 18 or > 80 yr; STEMI in the last 48 hr; hemodynamic instability; CHF; increased risk of bleeding | Exercise | Prior to discharge | Pts went for angiography if they had refractory angina (51%), hemodynamic or rhythm instability (8%), or ischemia on an exercise stress test prior to discharge (41%) | 3 yr | Angio, 3 yr, revasc, 3 yr, one end point: invasive, 99%, 81%, 30%, respectively; noninvasive, 70%, 58%, 26%, respectively; primary end point, death, nonfatal MI, or rehospitalization for angina ( N = 1200) |
| Ekstrand et al (1997) | 25% NST; 75% STE/Q wave | Decompensated CHF; severe arrhythmia; unable to exercise | Bicycle, submax | 11 days | Abnormal exercise ECG with STD ≥ 1 mm | 9 yr | Increased risk of mortality with angina and/or STD > 1 mm on submaximal exercise ECG ( N = 1098) |
| Madsen et al (1997) | ≤69 yr of age with AMI CK-MB 2× ULN, ST deviation or T-wave changes; and/or new Q waves; patients had to be treated with thrombolytics <12 hr after onset of symptoms and angina; or exercise-induced ischemia | Previous MI, PTCA, CABG; received <50% thrombolytic dose; required immediate intervention; drop in SBP with exercise; LBBB or PPM; unable to exercise; systemic illness | Bicycle, symptom- limited | Prior to discharge | Abnormal if STD ≥ 0.1 mV in any lead or STE ≥ 2.0 mV in any lead without Q waves; cath only performed if there was SBP drop; looking at follow-up in those with positive stress and/or angina treated with antianginal agents vs. cath | 2.4 yr median | Mortality, reinfarct, UA: invasive, 3.6%, 5.6%, 17.9%, respectively; noninvasive, 4.4%, 10.5%, 29.5%, respectively ( N = 1008) |
| Al-Khalili et al (2007) | Women <66 yr of age admitted with MI or UA, 48% Q-wave MI and 52% NQWMI | Unable to exercise; LBBB; ST segment could not be assessed because of RBBB or digitalis effect | Bicycle, symptom- limited | 3-6 mo | Abnormal exercise ECG with horizontal STD ≥ 1 mm | 9 yr | Decreased exercise tolerance predictor of increased mortality ( N = 273) |
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