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Stress testing in pre-discharge risk stratification of patients with non-ST elevation acute coronary syndrome

Stress testing in pre-discharge risk stratification of patients with non-ST elevation acute coronary syndrome
Literature review current through: Aug 2023.
This topic last updated: Oct 11, 2022.

INTRODUCTION — Patients with non-ST elevation acute coronary syndrome (NSTEACS) are treated with anti-ischemic, antiplatelet, and anticoagulant agents to provide immediate relief of ischemia and prevent further myocardial damage. In addition to aggressive medical therapy, two pathways of NSTEACS treatment have emerged: the early invasive strategy and the early conservative strategy. In the early invasive strategy, the more common approach in the modern treatment of NSTEACS, patients with high-risk features and without contraindications undergo coronary angiography and revascularization as deemed appropriate. Alternatively, there is a smaller group of patients with NSTEACS, generally those with low-risk features or at higher risk of complications from invasive angiography, who can be treated with an early conservative approach. In such conservatively treated patients, an ischemia-guided management strategy, dictated by stress test findings, results in outcomes similar to the early invasive strategy.

The role of stress testing in pre- and early post-discharge risk stratification of patients with NSTEACS will be reviewed here. The comprehensive risk stratification of patients with NSTEACS, as well as the approach to treatment, is discussed separately. (See "Risk stratification after non-ST elevation acute coronary syndrome" and "Overview of the acute management of non-ST-elevation acute coronary syndromes" and "Overview of the nonacute management of unstable angina and non-ST-elevation myocardial infarction".)

WHO NEEDS A STRESS TEST AND WHEN SHOULD IT BE PERFORMED — Our approach to the use of noninvasive stress testing following conservative treatment of patients with NSTEACS treated medically is consistent with the American Heart Association/American College of Cardiology guidelines for the management of patients with NSTEACS [1]. The primary role of stress testing is to distinguish between higher-risk subjects with severe and/or extensive ischemia who would have improved outcomes with revascularization, and lower-risk subjects with no or limited ischemia who would have comparable outcomes with medical therapy alone. Stress test findings also provide prognostic information, guide activity prescription, and assess the effectiveness of therapy. In subjects with extensive myocardial injury, stress testing may also provide information on the presence and extent of myocardial viability.

Patients with recent NSTEACS may safely undergo a stress test provided they have been asymptomatic and clinically stable at least 12 to 24 hours for those with unstable angina and two to five days for those with non-ST elevation myocardial infarction [2]. The longer delay prior to stress testing (two to five days) may also be warranted in some patients with high-risk features such as advanced age, left ventricular (LV) systolic dysfunction, and peripheral vascular disease. (See "Acute coronary syndrome: Terminology and classification".)

Most patients who require a stress test post-NSTEACS will undergo the test prior to discharge. However, early post-discharge testing may be considered in lower-risk patients including those who have been revascularized (culprit lesion) and those who have remained asymptomatic with normal levels of physical activity during hospitalization. Post-discharge testing may also be considered in stable patients who will transition to an intermediate care setting that provides ongoing monitoring and medical treatment of the patient’s cardiac problems and medical comorbidities.

Pre-discharge stress testing — Pre-discharge exercise and dobutamine stress studies performed within 48 to 72 hours of infarction have typically utilized submaximal levels of stress to arbitrary end points such as 70 percent of age-predicted maximal heart rate or heart rate of 130 beats/min. The safety and short-term prognostic value of testing using these end points have been documented [3].

Patients who would benefit from a pre-discharge stress test include:

Patients with higher-risk NSTEACS features who would ordinarily undergo an early invasive strategy but have current contraindications or comorbidities that increase the risk of invasive procedures. This group includes patients with renal insufficiency or increased risk of bleeding including those with recent noncardiac surgery. The demonstration of significant ischemia identifies those who may benefit from coronary angiography and revascularization (or additional intensification of medical therapy in subjects who do not proceed with an invasive approach). (See "Risk stratification after non-ST elevation acute coronary syndrome".)

Patients treated with an early conservative strategy (usually with fewer high-risk features and an uncomplicated NSTEACS). The demonstration of significant ischemia identifies those who may benefit from coronary angiography and revascularization prior to discharge.

The Invasive Versus Conservative Treatment in Unstable Coronary Syndromes (ICTUS) trial randomly assigned 1200 patients with ACS to an early invasive strategy or a conservative strategy and found no significant differences between the groups at one and three years in the rates of death, myocardial infarction, or rehospitalization for angina [4].

Early post-discharge stress testing — In patients who are expected to regain the capacity to perform maximal exercise, deferral of stress testing to the post-discharge period is reasonable. Post-discharge maximal exercise testing provides better long-term risk stratification information versus submaximal pre-discharge testing.

Patients who would benefit from an early post-discharge stress test include:

Patients who underwent an early invasive strategy with culprit vessel revascularization but who have residual disease of uncertain functional significance in one or more remaining vessels.

Selected patients who have been fully revascularized and are planning to enroll in cardiac rehabilitation, such as those with LV systolic dysfunction or patients with peri-infarction ventricular arrhythmia. Stress testing can establish baseline exercise capacity, evaluate for residual myocardial viability, assess the hemodynamic response to exercise, and guide activity prescription.

Stable patients with post-infarction mitral regurgitation or dyspnea who can exercise. Exercise echocardiography can provide information on changes in mitral regurgitation and LV filling pressures that may contribute to exertional dyspnea.

Patients identified as low-risk from NSTEACS, such as those with limited extent of injury and normal global LV systolic function, who have remained asymptomatic with normal daily activities during hospitalization.

Low-risk patients with biomarker elevation likely not due to ACS (eg, due to anemia, sepsis, hypoxemia, etc) but who have risk factors for coronary artery disease (CAD), or in whom obstructive CAD is felt to be a possible contributor to biomarker elevation (type 2 NSTEACS with possible underlying CAD). Stress testing is considered for both risk stratification and diagnostic purposes to determine the presence or absence of obstructive CAD. (See "Acute coronary syndrome: Terminology and classification", section on 'Definition of myocardial infarction'.)

WHO DOES NOT NEED A STRESS TEST? — Stress testing is usually not needed in the following groups of patients (see 'Who needs a stress test and when should it be performed' above):

Patients who have been completely revascularized.

Patients with limited life expectancy due to medical comorbidities.

Patients who are not candidates for revascularization, based on comorbidities or results of coronary angiography showing anatomy that is not amenable to revascularization. In selected patients in this group, stress testing may be of value in determining if ischemia is the cause of symptoms and in guiding medical therapy.

CONTRAINDICATIONS TO STRESS TESTING — Stress testing is not without potential risks or discomfort to the patient, although the procedure is generally quite safe for most patients. Serious complications such as myocardial infarction (MI), cardiac arrest, or death are rare, although the risk in the post-MI population is potentially higher given the increased prevalence of obstructive coronary artery disease in these subjects. Contraindications to stress testing, both absolute and relative, are listed in a table (table 1) [5]. The benefits of stress testing may outweigh the risks in some subjects with a relative contraindication to testing, in whom the potential information gained by assessment of exercise capacity, blood pressure response to exercise, symptoms, and ischemia may outweigh the small risk of complications. (See "Exercise ECG testing: Performing the test and interpreting the ECG results", section on 'Contraindications'.)

WHICH STRESS TEST IS PREFERRED? — The decision to choose a particular stress test over other testing options should be made by incorporating clinical data, potential side effects, costs, and test availability. The choice of an imaging modality, when indicated, also depends on a variety of factors, including local availability, local expertise, cost, the patient's body habitus (eg, morbid obesity), limited acoustic windows for echocardiography (only if neither traditional nor contrast-enhanced echocardiographic imaging is adequate), radiation exposure, and the need for concomitant assessment of hemodynamics or valvular disease. The available modalities include exercise electrocardiography (ECG), exercise or vasodilator radionuclide myocardial perfusion imaging using positron emission tomography (PET) or single-photon emission computed tomography (SPECT), exercise or pharmacologic (dobutamine or dipyridamole) stress echocardiography, and pharmacologic stress magnetic resonance imaging (MRI). (See "Selecting the optimal cardiac stress test", section on 'Our approach to choosing the optimal stress test'.)

Nearly all patients who are anticipated to exercise to a satisfactory workload should undergo an exercise stress test rather than a pharmacologic stress test. Exercise is the preferred method of stress because of the information gained on functional capacity and the presence or absence of symptoms with physical activity [6]. In modern practice, an increasing proportion of post-myocardial infarction (MI) patients undergo exercise stress testing with imaging or pharmacologic stress testing because of perceived intermediate or higher risk or factors that prevent or limit their ability to perform adequate exercise. This is particularly true for those referred for pre-discharge testing. (See "Stress testing for the diagnosis of obstructive coronary heart disease", section on 'Challenges in women'.)

For decades, exercise ECG testing was the standard method for post-MI stress testing. When performed to an end point of symptoms or maximal exercise capacity, exercise ECG testing has moderate sensitivity and specificity for diagnosing obstructive coronary artery disease. However, many post-MI patients have ECGs that are uninterpretable which lowers the sensitivity of exercise ECG testing. Stress testing with some form of cardiac imaging has been shown to increase the accuracy and incremental prognostic value compared with exercise ECG testing without imaging [7-9]. As such, in modern practice, nearly all post-MI stress testing employs some form of imaging, with SPECT radionuclide myocardial perfusion imaging and stress echocardiography being the two most commonly used modalities. (See "Stress testing for the diagnosis of obstructive coronary heart disease" and "Selecting the optimal cardiac stress test", section on 'Comparison of different imaging techniques'.)

Each stress modality has particular advantages and disadvantages, and there is some variability in the diagnostic and prognostic information provided. In general, our approach for choosing a specific stress testing modality is presented in the table (table 2). For example, a postinfarction patient with unexplained exertional dyspnea may be best evaluated using exercise echocardiography. The presence of mitral regurgitation, pulmonary hypertension, and elevated left ventricular filling pressure can be assessed prior to exercise, and worsening of these conditions as causes of dyspnea can be assessed during bicycle exercise or immediately post-treadmill exercise [10].

The general approach to selecting the optimal stress imaging modality is discussed in more detail separately. (See "Selecting the optimal cardiac stress test".)

INTERPRETING THE STRESS TEST RESULTS — Risk assessment of an individual patient should incorporate clinical risk factors, the hospital course, and response to medical therapy, in addition to the results of the stress electrocardiogram and imaging studies. A number of parameters derived by rest and stress echocardiography and nuclear perfusion imaging can be used for postinfarction risk stratification (table 3 and table 4 and table 5) [11,12]. (See "Exercise ECG testing: Performing the test and interpreting the ECG results" and "Prognostic features of stress testing in patients with known or suspected coronary disease".)

Patients undergoing stress echocardiography with normal left ventricular ejection fraction (LVEF), no resting wall motion abnormalities/perfusion defects, no stress-induced ischemia, and who have good exercise capacity for age and gender have excellent prognosis over the next several years with annualized recurrent myocardial infarction (MI) and cardiac death rates <1 percent (very low risk group) [13].

Patients with normal resting echocardiograms, no perfusion defect, and no ischemia who undergo pharmacologic stress or who have suboptimal exercise capacity are considered at low risk but have slightly higher risk than those who can exercise to higher levels of stress (<2 percent annual mortality). Patients with normal LVEF and limited infarct size (≤2 segments) with no stress-induced ischemia also remain at relatively low risk.

Intermediate-risk patients include those with mildly reduced LV systolic function (LVEF >35 percent but <50 percent), limited infarct size (≤2 segments), or limited peri-infarction ischemia (≤2 segments) at a high level of stress.

High-risk patients include those with moderate to severely reduced LVEF (<35 percent), extensive infarct size (≥5 segments), ischemia in a coronary territory separate from the infarction zone, extensive ischemia (≥5 segments), or ischemia occurring at a low stress level. Additional high-risk findings include dilatation of the LV cavity with stress (single-photon emission computed tomography and stress echocardiogram) and reduction of global systolic function from rest to stress (stress echocardiogram).

MANAGEMENT FOLLOWING STRESS TESTING — Based on the provocative test findings, we propose the following three groups of patients:

Patients with large ischemic burden or a high-risk treadmill score are usually referred for coronary angiography with revascularization as deemed appropriate. (See "Non-ST-elevation acute coronary syndromes: Selecting an approach to revascularization" and "Revascularization in patients with stable coronary artery disease: Coronary artery bypass graft surgery versus percutaneous coronary intervention".)

Patients with moderate ischemic burden or an intermediate treadmill score are referred for coronary angiography as long as they have no contraindications and their expected risk from an invasive procedure is low. Conversely, in patients at increased risk of complications from coronary angiography, or for patients who are interested in pursuing a less invasive approach or are averse to invasive procedures, we attempt initial aggressive medical treatment and reserve the invasive approach for those with recurrent ischemia despite maximal medical therapy. (See "Non-ST-elevation acute coronary syndromes: Selecting an approach to revascularization" and "Revascularization in patients with stable coronary artery disease: Coronary artery bypass graft surgery versus percutaneous coronary intervention" and "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk".)

Patients with limited or no ischemic burden and a low treadmill score have excellent long-term outcomes on appropriate medical therapy and generally do not require coronary angiography. (See "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Non-ST-elevation acute coronary syndromes (non-ST-elevation myocardial infarction)" and "Society guideline links: Multimodality cardiovascular imaging appropriate use criteria" and "Society guideline links: Stress testing and cardiopulmonary exercise testing".)

SUMMARY AND RECOMMENDATIONS

Early invasive versus ischemia-guided management strategies – In the modern treatment of non-ST elevation acute coronary syndrome (NSTEACS), patients with high-risk features and without contraindications undergo coronary angiography and revascularization as deemed appropriate. Alternatively, there is a smaller group of patients with NSTEACS, generally those with low-risk features or at higher risk of complications from invasive angiography, who can be treated with an early conservative approach. In such conservatively treated patients, an ischemia-guided management strategy dictated by stress testing results in outcomes similar to the early invasive strategy. (See 'Introduction' above.)

Who needs a stress test and timing of the test – Patients with recent NSTEACS may safely undergo a stress test provided they have been asymptomatic and clinically stable at least 12 to 24 hours for those with unstable angina and two to five days for those with non-ST elevation myocardial infarction. Most patients who require a stress test post-NSTEACS will undergo the test prior to discharge. However, early post-discharge testing may be considered in lower-risk patients including those who have been revascularized (culprit lesion), those who have remained asymptomatic with normal levels of physical activity during hospitalization, and patients who will transition to an intermediate care setting that provides ongoing monitoring. (See 'Who needs a stress test and when should it be performed' above.)

Who does not need a stress test? – Stress testing is usually not needed in patients who have been completely revascularized, patients with limited life expectancy due to medical comorbidities, and patients who are not candidates for revascularization, based on comorbidities or results of coronary angiography showing anatomy that is not amenable to revascularization. (See 'Who does not need a stress test?' above.)

Which stress test is preferred? – The decision to choose a particular stress test over other testing options should be made by incorporating clinical data, potential side effects, costs, and test availability. Nearly all patients who are anticipated to exercise to a satisfactory workload should undergo an exercise stress test rather than a pharmacologic stress test. The choice of an imaging modality, when indicated, also depends on a variety of factors, including local availability, local expertise, cost, the patient's body habitus (eg, morbid obesity), limited acoustic windows for echocardiography (only if neither traditional nor contrast-enhanced echocardiographic imaging is adequate), radiation exposure, and the need for concomitant assessment of hemodynamics or valvular disease. (See 'Which stress test is preferred?' above.)

Management based on stress test results – Based on the provocative test findings, patients can generally be stratified into high, intermediate, and low risk, with subsequent management according to the identified risk (table 3 and table 4 and table 5).

Patients with high-risk stress test findings – Patients with moderate to large or multiple areas of reversible ischemia or who have a high treadmill score are usually referred for coronary angiography and, if necessary, revascularization.

Patients with low-risk stress test findings – Those with no ischemia on stress test and a low treadmill score have excellent long-term outcomes and generally do not require coronary angiography. (See 'Management following stress testing' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Rabih Azar, MD, who contributed to an earlier version of this topic review.

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