Version May 2024
INTRODUCTION — Many patients who are evaluated for acute chest pain are felt to be at low to intermediate pre-test risk of an acute coronary syndrome (ACS) if they have resolution of symptoms, normal or nonischemic/nondiagnostic electrocardiograms, and initial troponin value(s) that are not diagnostic for myocardial infarction (MI). Ultimately, these individuals may have unstable angina, non-ischemic cardiac pain, or non-cardiac pain. Evaluation of these patients generally occurs in a hospital emergency department or observation unit.
Noninvasive cardiovascular testing can be used to further risk stratify those patients for whom the diagnosis of myocardial ischemia is still a concern, despite the initial absence of definitive proof of MI, and for whom discharge without exclusion of the diagnosis may be risky [1]. The use of noninvasive cardiovascular testing generally helps determine further management decisions, such as discharge, the need for invasive coronary angiography, or evaluation for other causes of symptoms. (See "Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department", section on 'Impact of missed diagnosis'.)
The use of noninvasive cardiovascular testing to assess the likelihood of an ACS is discussed here. The initial evaluation of patients with chest pain at low to intermediate risk for ACS, including determination of whether noninvasive imaging during rest and/or provocative stress testing is indicated, is discussed separately. (See "Evaluation of emergency department patients with chest pain at low or intermediate risk for acute coronary syndrome", section on 'Noninvasive evaluation'.)
AVAILABLE TESTS — The various noninvasive cardiovascular diagnostic tests are broadly grouped into two categories: those acquired during the resting state or those requiring provocative stress testing.
Rest imaging — Diagnostic imaging tests that do not stress the heart are termed "rest tests." These are often performed on actively symptomatic patients. Three major rest imaging modalities are available to evaluate patients presenting to the emergency department (ED) with possible acute coronary syndrome (ACS), including radionuclide myocardial perfusion imaging (rMPI), echocardiography, and coronary computed tomographic angiography. We do not recommend the use of the coronary artery calcium score to evaluate chest pain in the ED, since absence of coronary artery calcium does not exclude an ACS [2]. (See "Coronary artery calcium scoring (CAC): Overview and clinical utilization".)
Provocative (stress) testing — Provocative (stress) testing, with or without an imaging modality, is chosen for clinically stable (after resolution of symptoms) patients. Such patients generally have no or minimal symptoms at rest or symptoms that have resolved, stable hemodynamics, a normal or nondiagnostic electrocardiogram and serial troponin results that are not elevated. Available tests include a traditional treadmill exercise tolerance test or stress (exercise or pharmacologic) imaging with nuclear/positron emission tomography imaging, echocardiography, and cardiac magnetic resonance imaging.
PATIENTS WITH ONGOING SYMPTOMS — For hemodynamically unstable patients, we often refer them for diagnostic coronary angiography rather than performing noninvasive testing.
For hemodynamically stable patients with ongoing chest pain, a nonischemic electrocardiogram, and troponin values that are not elevated, unstable angina (or an unusual presentation of stable angina) remains a diagnostic possibility. (See "Diagnosis of acute myocardial infarction" and "Diagnosis of acute myocardial infarction", section on 'Definitions'.)
We also refer many of these patients with possible unstable angina for coronary angiography, particularly if we think the likelihood of unstable angina is high. Patients with established cardiovascular disease or chest pain characteristic for angina pectoris fall into this group.
Rest (no stress) cardiac imaging (see 'Rest imaging' above) may be useful. However, rest imaging has not been widely adopted. If rest imaging is to be performed, the choice of test depends on local expertise and availability.
The rationale for rest imaging derives from the pathophysiologic events that follow the onset of myocardial ischemia [3]:
●When myocardial oxygen demand exceeds supply (due to either increased oxygen demand or reduced supply), the first abnormality detected is regional myocardial blood flow heterogeneity between the vascular beds supplied by normal and stenosed coronary arteries. This manifests as a regional perfusion defect on myocardial perfusion imaging.
●Regional systolic dysfunction (manifest as regional wall motion abnormalities) is highly specific for regional ischemia in patients without prior abnormality. Regional systolic dysfunction may be seen on 2D echocardiography.
Since regional flow heterogeneity and systolic dysfunction precede chest pain in the ischemic cascade, the absence of these phenomena (ie, a normal rest study) in a patient with ongoing chest pain is reliable evidence of the nonischemic nature of the chest pain. Noninvasive imaging studies have demonstrated that regional flow heterogeneity has a higher sensitivity for acute coronary syndrome (ACS) while regional systolic dysfunction has a higher specificity. It should be kept in mind that an ACS may be present despite a noninvasive study with no wall motion abnormalities (WMA) and that a noninvasive study WMA may represent old infarction.
Rest imaging for patients with suspected ACS in the emergency department (ED) is among the most rigorously studied areas in terms of evidence for the use of imaging, with numerous randomized controlled trials involving many of the modalities. Large trials have been performed using rMPI and substantial observational data exist for 2D echocardiography, which can also offer insights about nonischemic causes of chest pain. Cardiovascular magnetic resonance (CMR) imaging requires provocative stress testing and placing the patient with active chest pain in the scanner for a prolonged period of time is not appropriate.
The utility of testing varies across these tests in relation to whether symptoms are ongoing or have resolved. The longer the interval between the end of symptoms and the test, the lower the sensitivity of the test [4,5]. Assessment of wall motion abnormalities appears to require ongoing symptoms for optimal sensitivity (unless infarction has occurred). Perfusion or anatomic changes may persist for several hours or more despite resolution of symptoms. In general, we do not evaluate the patient with these rest studies if the patient has been pain free for more than two to three hours, but instead wait for a final troponin results and plan for stress testing.
Radionuclide myocardial perfusion imaging — Multiple studies have validated the benefit from the use of acute rest single photon emission computed tomography (SPECT) rMPI in the evaluation of patients with chest pain and a non-diagnostic electrocardiograph (ECG). During rest rMPI with technetium (Tc)-99m sestamibi or Tc-99m tetrofosmin, the radiolabeled tracers accumulate in myocardial tissue in a degree proportional to myocardial blood flow [6-11]. If these agents are injected during or shortly after resolution of chest pain, areas of ischemic myocardium demonstrate reduced radioactive counts (image 1). Because there is minimal redistribution of these agents over three to four hours, imaging can provide accurate information about myocardial perfusion at the time of injection even if the scintigraphy is delayed for a few hours after the injection. (See "Basic properties of myocardial perfusion agents".)
It must be emphasized that the lowest event rates are associated with scans that are completely normal. Equivocal scans are associated with event rates that are intermediate between those associated with normal and clearly abnormal scans (table 1). Thus, the interpretation of rMPI in ED patients should be geared towards obtaining maximum sensitivity and negative predictive value for potential disease by identifying and reporting any abnormality as significant.
Multiple studies have shown that patients with chest pain and normal images on acute rest rMPI can be safely discharged from the ED:
●The efficacy of this approach was evaluated in a randomized controlled trial in which 2475 patients with suggestive chest pain within the previous three hours, a non-diagnostic ECG, and no prior MI were studied [11]. The patients were randomly assigned to resting technetium-99m SPECT or to routine ED assessment. An ACS was subsequently confirmed in 329 patients (13 percent). Patients with negative serial enzymes, no evolutionary changes on serial ECGs, and a negative follow-up stress test were considered to have noncardiac chest pain. There was no difference in the appropriate admission rate between the SPECT group and the controls (97 versus 96 percent for acute MI and 83 versus 81 percent for unstable angina). However, among patients confirmed to have noncardiac chest pain, the erroneous admission rate was significantly lower for the SPECT group (42 versus 52 percent).
●The value of acute rest rMPI was evaluated in 532 consecutive patients presenting to an ED with a nondiagnostic ECG and a low to intermediate probability of an ACS [8]. A positive rMPI was present in 32 percent and was the only multivariable predictor of MI and was the most important independent predictor of MI or revascularization (figure 1). The sensitivity of a positive scan for MI and for MI or revascularization was 93 and 81 percent, respectively; the negative predictive values were 99 and 95 percent, respectively.
●The value of rest imaging in identifying patients with ischemia was confirmed in a multicenter prospective trial in which Tc-99m tetrofosmin SPECT rMPI was performed in 357 patients who were admitted from the ED with symptoms suggestive of myocardial ischemia but with a normal or nondiagnostic ECG [9]. Among 20 patients who subsequently had an acute MI, 18 had an abnormal scan (sensitivity 90 percent); the specificity was 60 percent. The reduced specificity was in part due to patients with positive scans who had coronary disease but no acute MI. Because so few patients had an MI, the positive predictive value was only 12 percent; however, the negative predictive value was 99 percent (figure 2).
Two-dimensional echocardiography — Two-dimensional echocardiography is an accurate, noninvasive test that is able to detect evidence of myocardial ischemia or infarction in patients with ongoing chest pain. Severe ischemia produces regional wall motion abnormalities (RWMA) that can be visualized echocardiographically within seconds of coronary artery occlusion (12±5 and 19±8 seconds in two series of patients evaluated during transient coronary occlusions induced by angioplasty) [12,13]. These changes occur prior to the onset of ECG changes or the development of symptoms (figure 3) [14]. The RWMA reflects a localized decrease in the amplitude and rate of myocardial excursion, as well as a blunted degree of myocardial thickening and local remodeling.
Since ischemic RWMA develop prior to symptoms, chest pain in the absence of RWMA is likely not to be due to active myocardial ischemia. However, the converse is not true; the presence of RWMA does not establish the diagnosis of ischemia. There are a number of other causes of resting RWMA, including a prior infarction, focal myocarditis, prior surgery, and cardiomyopathy.
Thus, echocardiography for an ACS has a high sensitivity but a relatively lower specificity. These predictions were confirmed in a study of 180 patients with chest pain in the ED. The following findings were noted [15]:
●RWMA were present in 27 of 29 patients with an acute MI (sensitivity 93 percent as two non-ST elevation MIs were not apparent).
●RWMA were indicative of acute MI in only 31 percent of 87 patients.
●Among the 88 patients without RWMA, only two (2.2 percent) subsequently "ruled in" for a non-ST elevation MI by cardiac enzymes.
It may be impossible to distinguish RWMA due to acute ischemia from those due to a previous MI. One clue, the preservation of normal wall thickness and normal reflectivity, suggests an acute event, while a thin akinetic reflective segment suggests chronicity. Some authorities recommend utilization of left-sided contrast for better delineation of the endocardial border when standard views are difficult to interpret [16].
Two-dimensional, resting transthoracic echocardiography has been shown to have high sensitivity for the diagnosis of acute MI (93 percent) and ACS (88 percent), and moderate specificity for acute MI (78 percent) and ACS (53 percent) using regional dysfunction as the criteria for abnormality [15,17-20]. The performance characteristics of echocardiography are less optimal for the detection of ACS compared with acute MI, while the ED physician faced with a decision on patient disposition is interested in identifying all ACS including unstable angina as well as acute MI.
The predictive value of resting echocardiography within four hours of ED presentation was demonstrated in a study of 260 patients presenting to the ED with possible ACS found that rest echocardiography predicted cardiac events (including acute MI and revascularization) with 91 percent sensitivity and 75 percent specificity [19]. When patients with abnormal ECGs were excluded, the sensitivity and specificity of rest echocardiography for predicting cardiac events was similar (85 and 74 percent, respectively). Other studies indicate that echocardiography performed after resolution of symptoms is unlikely to predict cardiac events [21].
The use of contrast agents can enhance endocardial detection for assessment of regional wall motion. Use of contrast agents to assess myocardial perfusion has also been investigated and found to be useful but expertise is not widely available, especially in the emergency setting. Additionally, echo contrast agents have not been approved for perfusion imaging. (See "Contrast echocardiography: Clinical applications".)
A potential advantage of use of echocardiography in the ED setting is its ability to detect complications of MI as well as evidence of other causes of acute chest pain such as proximal aortic dissection, acute pericarditis, stress-induced cardiomyopathy, and pulmonary embolism, which may manifest echocardiographically as dilated and hypokinetic right ventricle and increased pulmonary artery pressure. Limitations of this approach include the fact that many patients become asymptomatic by the time of the test, thus decreasing its sensitivity; a normal test does not exclude important CAD.
rMPI versus echocardiography — Both rMPI and echocardiography may be useful for the patient with ongoing symptoms. The strength of evidence supporting a management strategy of potential ED discharge with a normal resting study may be higher with rMPI, based on the larger populations that have been reported and the consistently high negative predictive value compared with rest echo.
The choice between these two should be made based on local expertise, availability, and cooperation among the various stakeholder groups, including ED physicians, cardiologists, and imaging specialists. We believe that echocardiography is less useful in patients whose symptoms have resolved. Another advantage for rMPI is that imaging can be deferred for up to four hours after the injection of a Tc-99m tracer, making test logistics easier in busy departments.
Few studies directly compare rMPI and echocardiography in patients with ongoing chest pain. A study of 470 patients classified as having low to intermediate risk of ACS found that rest rMPI and rest echocardiography had similar sensitivities and specificities for prediction (ie, prognosis) of acute MI or coronary intervention (sensitivity 100 percent for both, specificity 89 percent for rMPI, and 86 percent for echocardiography) [22]. Rest rMPI and rest echocardiography also performed similarly for prediction of acute MI, significant coronary artery stenosis, or positive stress rMPI (sensitivity 75 percent for both, specificity 88 percent for echocardiography, and 90 percent for rMPI).
Cardiac computed tomographic angiography — Cardiac computed tomographic angiography (CCTA) should not be performed in patients with ongoing chest pain who may have ACS since transporting them is unsafe and radiology suites are generally not equipped to deal potentially unstable patients. CCTA is discussed elsewhere. (See "Cardiac imaging with computed tomography and magnetic resonance in the adult", section on 'Cardiac CT'.)
Cardiovascular magnetic resonance imaging — CMR imaging is another potential MR method for identifying coronary artery disease (CAD) in patients with chest pain. We see no advantage of preferring this test in patients who can have 2D echocardiography or acute rest SPECT rMPI performed. While CMR can provide comprehensive information, the literature on its use in ED chest pain patients emanates from a small number of expert centers. In most centers it is likely that rMPI or echo would be more readily available on short notice, and that expertise is more likely present. The test requires transfer of the patient from the ED, which we are reluctant to perform in some cases.
CMR imaging may be helpful in diagnosing particular cases, such as suspected myocarditis, though this is often suspected after ACS due to CAD is ruled out. (See "Clinical manifestations and diagnosis of myocarditis in adults", section on 'Cardiovascular magnetic resonance'.)
Limitations of rest testing — There are significant limitations to the use of rest imaging with either echocardiography or acute rest SPECT rMPI in patients with ongoing chest pain:
●Rest imaging is less helpful in diagnosing ACS in patients with prior MI since the age of abnormalities may be uncertain unless a significant new defect is present and a prior study is available for comparison.
●Acute rest rMPI can miss small areas of ischemia or infarction, especially in the inferior wall [9].
●The sensitivity for ACS is highest when the test is performed during active symptoms and progressively diminishes after symptom resolution. This is an important consideration in evaluation of ED patients who frequently present when symptoms have resolved. Evidence suggests that while regional dysfunction frequently resolves within minutes after resolution of ischemic symptoms, perfusion abnormalities may persist longer [7,23]. We recommend that rest tests not be performed if the patient has been pain free for more than three hours, although there may be instances in which a longer duration is acceptable. One example is a patient whose troponin has returned as equivocal for MI.
●Another limitation of rMPI is the confounding influence of soft tissue attenuation artifacts. In the ED setting in which only one set of images is acquired, gating is less useful to differentiate attenuation artifacts from true perfusion defects. However, use of gated images for assessment of left ventricular function with rest rMPI improved its predictive power [24].
PATIENTS WHOSE SYMPTOMS HAVE RESOLVED — For patients who have become and remain symptom free, noninvasive cardiac stress (provocative) testing, with or without imaging, is performed on those for whom there remains a suspicion of an acute coronary syndrome (ACS) despite normal or nondiagnostic electrocardiography and two normal sensitive (conventional) troponin values (algorithm 1). The definitions of sensitive and highly sensitive troponin are found elsewhere. (See "Troponin testing: Analytical considerations".)
Safe performance of provocative stress testing requires careful screening to assure that the patient is symptom-free at rest and lacks evidence of myocardial necrosis or resting ischemia by serial biomarkers and electrocardiograms (ECGs).
At institutions where 64-slice (or better) cardiac computed tomography (CT) scanner are available, rest imaging (no stress) with cardiac CT angiography (CCTA) can be used in symptom-free patients with nonischemic electrocardiograms (ECGs) and one initial conventional troponin negative. (See 'Limitations of rest testing' above.)
Our approach — For hemodynamically stable, symptom-free patients with nonischemic ECGs and two normal troponins in whom there remains a concern for myocardial ischemia as the cause of the presenting symptom, a noninvasive testing strategy can further evaluate the patient (algorithm 1). The selection of the test is based primarily on whether the patient can exercise and whether the ECG will be interpretable for new ischemic changes. (See 'Imaging or no imaging' below and "Selecting the optimal cardiac stress test", section on 'Our approach to choosing the optimal stress test'.)
As discussed below, the choice of test should also be influenced by factors such as local expertise and availability.
●For patients who are likely to be able to exercise maximally and who have an interpretable ECG, we send the patient for exercise (stress) testing without imaging. We generally perform this prior to discharge.
●For patients who are likely to be able to exercise maximally and whose exercise ECG is not likely to be valuable for risk prediction, we send the patient for exercise testing with imaging. We prefer echocardiography or radionuclide myocardial perfusion imaging. The choice between the two depends on local expertise and availability.
●For patients who are not likely to be able to exercise maximally, we send the patient for pharmacologic stress testing with imaging.
At institutions where 64-slice cardiac CT scanner or better and local expertise are available, rest imaging with CCTA can be used in symptom-free patients with nonischemic ECGs and one initial conventional troponin negative. Since CCTA is performed when patients are in the resting state, serial troponins are not necessary and one negative initial troponin would suffice.
Inpatient or outpatient — In patients with low risk of ACS, stress testing prior to discharge from the emergency department (ED) or observation unit is often preferred to discharge with early outpatient testing (algorithm 1). However, early (within 72 hours) outpatient testing is an option in selected patients. An early outpatient stress test evaluation is a reasonable alternative to inpatient testing for the reliable and adherent patient with a low to intermediate pre-test probability for ACS due to coronary artery disease (CAD) (table 2) with low-risk features (table 3), provided the patients has at least two sets of negative cardiac biomarkers, has no ECG evidence of ischemia on serial ECGs, has physician follow-up, and has an outpatient stress test to be performed within 72 hours, which is scheduled prior to ED discharge [25-27].
One study supporting this approach included 971 patients ≥40 years old with chest pain with low risk for CAD who underwent outpatient stress testing within 72 hours [27]. Compliance with outpatient stress testing was 92 percent; no cardiac events (death, MI, or coronary intervention) were observed among those who were not compliant. Among 871 patients with six-month follow-up, 2 percent required coronary intervention, 0.2 percent had a myocardial infarction (MI), 0.7 percent had normal stress test results after discharge but later required cardiac catheterization, and 0.6 percent returned to the ED for ongoing chest pain. Hospital admission rates decreased significantly from 31 to 26 percent after initiation of the protocol.
Outpatient stress testing should not be offered to patients at risk for poor compliance since such a strategy may lead to an increased rate of adverse cardiac events [28].
Choice of stress type — Exercise or pharmacologic agents can be used to stress (provocation) patients. The choice of the stress method depends upon the patient's ability to exercise. (See "Selecting the optimal cardiac stress test".) Pharmacologic stress agents include vasodilators (eg, adenosine, dipyridamole, and the newer adenosine A2A-agonist regadenoson and dobutamine with atropine). In the United States, vasodilators are generally used in conjunction with radionuclide myocardial perfusion imaging (rMPI) and dobutamine plus atropine is generally used in conjunction with echocardiography. In Europe, vasodilator echocardiography is also performed.
●For patients who are able to exercise maximally, exercise stress testing (exercise/supine bike echocardiography) has the ability to assess the patient’s functional capacity.
●For patients who are able to exercise submaximally, conversion to pharmacologic stress testing should be considered if ischemic changes are not present by end of the submaximal test.
●For patients who are unable to exercise, pharmacologic stress testing (adenosine, dipyridamole, regadenoson, dobutamine) with imaging (nuclear/positron emission tomography [PET], echo, or cardiovascular magnetic resonance [CMR]) should be considered.
Studies have demonstrated the safety and utility of symptom-limited treadmill exercise ECG testing after 8 to 12 hours of evaluation in ED patients with low to intermediate risk for CAD [29-31]. A negative exercise stress test makes severe obstructive coronary artery stenosis highly unlikely given the pre-test probability, particularly if the patient is able to exercise to a good functional capacity. An abnormal exercise treadmill test would warrant admission to the hospital and further workup.
Imaging or no imaging — For patients who are able to maximally exercise and have resting ECGs that are interpretable for ST-segment changes, exercise ECG stress testing does not require the addition of imaging. Exercise can be performed using a standard treadmill or supine bike protocol. (See "Exercise ECG testing: Performing the test and interpreting the ECG results".)
For patients who are able to exercise maximally but whose exercise ECG is uninterpretable for ischemia, adding imaging allows for assessment of ischemic changes. Baseline ECG abnormalities that preclude ECG stress test interpretation include pre-excitation (Wolff-Parkinson-White) syndrome, a paced ventricular rhythm, more than 1 mm of ST depression at rest, complete left bundle branch block, and patients taking digoxin or with ECG criteria for left ventricular hypertrophy, even if they have less than 1 mm of baseline ST depression. In patients with such abnormalities, an imaging stress test is helpful for diagnosis and prognosis. (See "Exercise ECG testing: Performing the test and interpreting the ECG results".)
Choice of imaging modality — For patients who require imaging in addition to stress, the choice of stress imaging technique depends upon patient characteristics as well as local expertise and availability. (See "Selecting the optimal cardiac stress test".)
Stress imaging modalities that have been evaluated include radionuclide myocardial perfusion imaging (single photon emission CT [SPECT] and PET), echocardiography, and CMR.
Stress radionuclide myocardial perfusion imaging — Stress radionuclide myocardial perfusion imaging with either SPECT (image 1) or PET offers a significantly higher sensitivity for detection of CAD than exercise ECG testing without imaging [32,33]. In a study of 151 low-risk ED patients with chest pain, the sensitivity of exercise rMPI (95 percent) was higher than that of exercise ECG (28 percent); the specificities were 83 and 95 percent [32]. A limitation of SPECT or PET is that they both require ionizing radiation. (See "Prognostic features of stress testing in patients with known or suspected coronary disease".)
A prospective observational study of 2074 chest pain patients evaluated by an accelerated protocol including two-hour delta serum creatine kinase-MB and troponin I levels, serial ECGs, and rest and stress rMPI in those with a negative two-hour evaluation demonstrated high sensitivity (99 percent) and specificity (87 percent) for 30-day ACS [34].
In low-risk patients who can exercise, a selective stress-only (also called a "stress-first") strategy preferably with attenuation correction may be employed to obviate the need for a rest study when the stress portion is normal, and thus, facilitate early discharge, improve patient comfort, and reduce radiation dose [35].
Stress rMPI as a component of initial evaluation of acute chest pain may reduce the rate of return chest pain visits. Such a benefit was suggested by a study of 1195 ED chest pain patients with normal or nondiagnostic ECG and at least three negative serial troponin levels [36]. Patients with normal stress rMPI had a lower return visit rate at three months (4 percent) compared with those with abnormal rMPI studies (19 percent), or those with no initial diagnostic evaluation (stress test or cardiac catheterization) (15 percent). In addition, patients who underwent initial diagnostic evaluation had a lower rate of acute MI or death in the three-month follow-up period.
The majority of studies of stress MPI in acute chest pain patients have used SPECT. Despite some advantages, including more robust attenuation correction and improved performance characteristics in obese patients, the application of PET MPI in this population is limited by lack of wide availability, and the inability to perform PET MPI using available tracers in conjunction with exercise stress.
Stress echocardiography — Stress echocardiography is an alternative to stress rMPI in this setting [37-39]. It is usually performed with either treadmill exercise or dobutamine.
Dobutamine stress echocardiography (DSE) is helpful for risk stratification in patients who are unable to exercise. In a study of 377 low-risk ED patients with negative work-up who underwent pre-discharge DSE, patients with a positive DSE had more than 10-fold risk of cardiac death, MI, rehospitalization for unstable angina, or revascularization as compared with patients with a negative DSE [40].
The use of ultrasound contrast agents can enhance endocardial detection for assessment of regional wall motion. Use of contrast agents to assess myocardial perfusion has also been investigated but not routinely used. (See "Contrast echocardiography: Clinical applications" and "Contrast echocardiography: Contrast agents, safety, and imaging technique".)
Stress CMR — Pharmacologic (adenosine, dipyridamole, or dobutamine) CMR stress testing has also been used to detect ischemia from CAD with first pass perfusion defects, regional wall motion abnormalities on cine images, and delayed hyperenhancement pattern after gadolinium administration [41,42]. (See "Clinical utility of cardiovascular magnetic resonance imaging", section on 'Pharmacologic stress CMR'.)
Limitations of this procedure include the absence of widespread expertise and facilities to perform comprehensive examinations, length of scan times (up to one hour), a contraindication in patients with MR-incompatible pacemakers, or implantable cardioverter-defibrillators. Additionally, gadolinium is contraindicated for renal impaired or end-stage renal patients (eGFR <30) due to the potential risk of the rare but irreversible nephrogenic systemic sclerosis.
CMR may be helpful in diagnosing particular cases, such as suspected myocarditis, though this is often suspected after ACS due to CAD is ruled out. (See "Clinical manifestations and diagnosis of myocarditis in adults", section on 'Cardiovascular magnetic resonance'.)
Although multicenter studies have evaluated the accuracy of CMR imaging to identify CAD in patients referred for elective invasive coronary arteriography, data are not sufficient to support clinical CMR imaging for the routine identification of coronary artery stenoses in patients with chest pain at this time [41-44].
Coronary computed tomography angiography — An alternate approach to functional imaging is direct visualization of the coronary artery tree to detect obstructive CAD (anatomy) by noninvasive coronary imaging using CCTA with 64-slice cardiac CT scanner (or better capabilities) (image 2). With this approach, the absence of obstructive CAD in a patient with chest pain is used to exclude ACS.
The principle limitation of CCTA is that a positive study (the presence of coronary artery stenoses) does not guarantee that unstable angina is the diagnosis. In patients with chest pain and known CAD, or in chest pain patients found to have intermediate degrees of coronary stenosis, functional testing may be required to establish or exclude myocardial ischemia as the cause of symptoms. The strength of CCTA is its near perfect negative predictive value of a normal CCTA, which would effectively eliminate ACS as the cause of chest pain in approximately 50 percent of low- to intermediate-risk acute chest pain patients. (See "Cardiac imaging with computed tomography and magnetic resonance in the adult".)
Other potential limitations of the use of CCTA in this setting include:
●Need for heart rate lowering agents such as beta blocker or calcium channel blockers to slow the heart rate for motion-free coronary images (newer higher temporal resolution CT scanner such as the dual-source CT scanner does not require stringent heart rate control).
●It is not recommended in patients with impaired renal function (creatinine elevation or reduced estimate glomerular filtration rate).
●It is not recommended in the presence of significant arrhythmia or atrial fibrillation with slower temporal resolution scanners such as the 64-slice single-source CT scanners. Newer generation CT scanners with faster temporal resolution are able to produce motion-free images despite arrhythmia or rate-controlled atrial fibrillation.
●Imaging quality is reduced in patients with heavy coronary artery calcification (eg, the elderly).
●Radiation exposure. (See "Radiation dose and risk of malignancy from cardiovascular imaging" and "Cardiac imaging with computed tomography and magnetic resonance in the adult".)
CCTA was evaluated in a 2013 meta-analysis of four randomized controlled trials [45-48] with 3266 low- to intermediate-risk patients that compared 64-slice CCTA to usual care triage of acute chest pain in the ED [49]. The ACRIN PA and ROMICAT II trials were the largest studies included in the above meta-analysis. Patients were followed for six months in two trials [45,46] and for one month in two trials [47,48]. Average length of stay was significantly reduced with CCTA compared with usual care in all four studies. In the ROMICAT II trial, patients were referred for CCTA after return of the first negative troponin.
An earlier meta-analysis of nine observational studies with a total of 1559 low- to intermediate-risk patients presenting with possible ACS evaluated the accuracy of 64-slice coronary CT in predicting major adverse cardiac events (MACE; defined as MI, coronary revascularization, cardiac arrest, or death from an ACS) at 30 days [50]. A positive CCTA (at least 50 percent coronary stenosis) was identified in 14.8 percent of patients. The overall sensitivity and specificity of CCTA for prediction of MACE were 93.3 percent and 89.9 percent. The positive predictive value was 48.1 percent and the negative predictive value was 99.3 percent.
Patient cooperation is particularly crucial for CCTA, since motion or breathing artifacts can invalidate a study that generally cannot be readily reacquired due to contrast and radiation dose considerations. With rMPI, an acquisition affected by patient motion can generally be repeated without additional tracer or radiation burden. Scanner technology (dual-source CT) and algorithms have been developed to perform CCTA in patients with atrial fibrillation or uncontrolled tachycardia who cannot be effectively imaged with single-source CT [51].
CT-derived fractional flow reserve (FFRCT) has become available at certain institutions and has been studied in the setting of acute chest pain [52,53]. FFRCT has the ability to determine lesion-specific ischemia. In a single-center study of 555 patients in the emergency department, FFRCT was feasible, and a negative FFRCT result was deemed safe for deferral of revascularization and was associated with higher nonobstructive disease by invasive coronary angiography [53].
In summary, CCTA has strong negative predictive value in excluding risk of MACE, can facilitate triage decisions, and reduce lengths of stay [54,55].
Comparison of tests — When considering which imaging test to choose for symptom-free patients at low to intermediate risk of ACS after two negative troponin values have been secured, several factors that should be taken into account: local expertise, availability, portability (use at the bedside), radiation dose, ease of applicability to the ED chest pain population, and cost (table 4). In most patients who will be referred for stress imaging, we perform either rMPI or echocardiography.
In addition, body habitus may influence decision making. rMPI is more tolerant of variations in body habitus (eg, obesity or chronic obstructive pulmonary disease) than echocardiography.
A potential advantage of echocardiography and CMR is that these methods may identify other thoracic causes of chest pain when ACS has been excluded.
The diagnostic accuracy of stress echocardiography was evaluated in a study of 503 acute chest pain patients who underwent both exercise stress echocardiography and exercise rMPI for detection of CAD. CAD was defined as >50 percent coronary artery stenosis on angiography or cardiac events (sudden death, nonfatal MI, revascularization) within six months. Stress echocardiography demonstrated similar sensitivity to stress rMPI (85 versus 86 percent), with slightly but significantly greater specificity (95 versus 90 percent) [56]. The sensitivity of exercise ECG was significantly lower (43 percent), although specificity was similar to that for stress echocardiography (95 percent).
RECOMMENDATIONS OF OTHERS — The most relevant documents are the 2015 ACR/ACC/AHA/AATS/ACEP/ASNC/NASSCI/SAEM/SACCT/SCMR/SCPC/SNMMI/STR/STS Appropriate Utilization of Cardiovascular Imaging in Emergency Department Patients With Chest Pain, the 2013 ACCF/AHA/ASE/ASNC/HFSA/HRS/SCAI/SCCT/SCMR/STS multimodality appropriate use criteria for the detection and risk assessment of stable ischemic heart disease, and the Coronary Artery Disease - Reporting and Data System (CAD-RADS): An Expert Consensus Document of SCCT, ACR and NASCI: Endorsed by the ACC [55,57,58].
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)".)
SUMMARY AND RECOMMENDATIONS
●Many patients with low-to-intermediate probability of acute coronary syndrome (ACS) (table 2) are candidates for assessment by noninvasive cardiac testing (algorithm 1). These patients may either have ongoing symptoms or may be symptom free.
●For patients with ongoing chest pain who need further diagnostic testing, we recommend rest imaging with either two-dimensional echocardiography or radionuclide myocardial perfusion imaging (rMPI). For rest echocardiography, intravenous ultrasonic contrast agent should be used to optimize endocardial border detection if all segments are not well visualized. (See 'Patients with ongoing symptoms' above.)
●For patients who are symptom free, stress testing is recommended for those individuals (table 3) without recurrent ischemic discomfort after at least six to eight hours of observation and follow-up 12-lead electrocardiogram (ECG) is normal or unchanged from previous tracings and two troponin levels at least six hours apart are normal. (See 'Provocative (stress) testing' above.)
•Patients with the above characteristic with an ECG that is interpretable for ischemic changes should undergo exercise ECG test rather than pharmacologic stress testing (See 'Patients whose symptoms have resolved' above and 'Choice of stress type' above.)
•Patients who have an uninterpretable ECG for ischemia (eg, left bundle branch block, ventricular paced rhythm, left ventricular hypertrophy with strain pattern, or digoxin therapy) should undergo exercise stress testing with imaging (either rMPI or echocardiography). Stress perfusion cardiovascular magnetic resonance (CMR) is another option. (See 'Choice of imaging modality' above.)
•Patients who are unable to exercise should undergo pharmacologic stress testing combined with imaging (vasodilator stress rMPI or dobutamine stress echocardiography).
•Outpatient stress testing is a reasonable alternative for appropriately screened patients with low probability of ACS due to coronary artery disease (table 2) who are compliant and reliable and have proper instructions with close follow-up with an outpatient stress test scheduled to be performed within 72 hours of emergency department discharge. (See 'Inpatient or outpatient' above.)
●CMR is not recommended for routine risk stratification of possible ACS at this time. However, CMR may be helpful to establish a diagnosis in individual cases (eg, for suspected myocarditis) during the inpatient workup. (See 'Cardiovascular magnetic resonance imaging' above.)
●Further evaluation, which may include cardiology consultation and coronary angiography, is recommended in patients with stress or imaging tests that reveal ongoing or inducible ischemia, significant coronary artery stenosis, or indeterminate results. Consultation may also be considered for patients with a known history of coronary artery disease, as their tests are more difficult to interpret. (See "Evaluation of emergency department patients with chest pain at low or intermediate risk for acute coronary syndrome", section on 'Indications for consultation'.)
ACKNOWLEDGMENT — The UpToDate editorial staff thank Dr. Christopher P. Cannon for his contributions as a section editor to prior versions of this topic review.
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