Selecting the optimal cardiac stress test

INTRODUCTION — Cardiac stress testing is an important diagnostic and prognostic tool in the evaluation and management of patients with known or suspected heart disease. While stress testing can be performed in a variety of ways, the most commonly used and widely available stress testing modalities are exercise electrocardiography (ECG; non-imaging) and exercise or pharmacologic stress combined with imaging (stress echocardiography or stress radionuclide myocardial perfusion imaging [MPI]). A main objective of stress testing is to assess the functional or physiological consequences of anatomic coronary artery disease (CAD). The traditional gold standard test for the diagnosis of CAD is invasive coronary angiography via cardiac catheterization. Anatomic CAD may also be assessed noninvasively with cardiac CT. (See 'Anatomic assessment of coronary artery disease' below and "Cardiac imaging with computed tomography and magnetic resonance in the adult" and "Coronary artery calcium scoring (CAC): Overview and clinical utilization".)

The choice of stress testing modality depends on many factors, including but not limited to:

●Ability to perform adequate exercise

●Resting ECG

●Clinical indication for performing the test

●Patient's body habitus

●History of prior coronary revascularization

The majority of this topic will review the indications for stress testing and the choice of stress testing modality with emphasis on considerations for the type of stress (exercise versus pharmacologic) and the assessment of response (ECG, echocardiography, or radionuclide imaging). The technique and efficacy of these procedures, as well as cardiopulmonary exercise testing for other indications, are discussed in detail separately. There is also a brief discussion on cardiac CT for anatomic evaluation of CAD. (See "Overview of stress radionuclide myocardial perfusion imaging" and "Stress testing for the diagnosis of obstructive coronary artery disease" and "Prognostic features of stress testing in patients with known or suspected coronary disease".)

INDICATIONS FOR STRESS TESTING — In patients with symptoms suggesting coronary heart disease (CHD), cardiac stress testing is most often indicated to aid in making the diagnosis of and assessing risk related to CHD. In some patients with known CHD and prior coronary revascularization or a change in clinical status, stress testing is indicated for the diagnosis of new or progressive disease and/or for risk stratification. In addition to symptomatic patients with known or suspected CHD, patients with heart failure, cardiomyopathy, valvular heart disease, or planned non-cardiac surgery may be candidates for stress testing. In contrast, cardiac stress testing as a screening test for CHD in asymptomatic patients is rarely indicated.

Guidelines for stress testing have been proposed by several professional societies, and our approach is generally consistent with these guidelines [1-5].

●Patients with symptoms suggesting angina – Patients who have symptoms suggestive of angina and who have an intermediate or high pre-test likelihood of CHD are generally appropriate for stress testing. One exception to this is patients with ongoing or unstable symptoms, in which case stress testing should not be performed prior to relief of symptoms.

●Patients with acute chest pain – Patients presenting with acute chest pain or suspected acute coronary syndrome (ACS) may also undergo stress testing for the diagnosis of possible CHD. Stress testing in such patients should only be performed following the relief of symptoms and following the evaluation for ACS or infarction.

●Patients with a recent ACS – In patients with a prior ACS who were treated conservatively without coronary angiography, or in patients with incomplete revascularization at the time of ACS, stress testing may be used for risk assessment within three months post-ACS, assuming that the patient is stable without further symptoms [1,2,6].

●Patients with known CHD and new or worsening symptoms – Cardiac stress testing may be appropriate for patients with known CHD if there has been a clinical change (ie, new or worsening symptoms) [7].

●Patients with prior coronary revascularization – In the absence of new or changing symptoms <5 years after coronary artery bypass graft (CABG) or <2 years after percutaneous coronary intervention (PCI), stress testing is rarely appropriate. However, for patients ≥5 years after CABG or ≥2 years after PCI, stress testing may be appropriate on a one-time basis for the asymptomatic patient [7].

●Patients with valvular heart disease – Stress echocardiography may be performed to evaluate valvular heart disease, such as severe mitral stenosis without symptoms, moderate mitral stenosis with symptoms, severe mitral or aortic regurgitation (when left ventricular size and function do not meet surgical criteria), and equivocal aortic stenosis in the setting of low-cardiac output or left ventricular systolic dysfunction [3]. The exercise electrocardiography (ECG) without imaging may also be used to assess exercise capacity and need for valvular intervention in patients with asymptomatic severe aortic stenosis. (See "Overview of stress echocardiography", section on 'Indications'.)

●Patients with newly diagnosed heart failure or cardiomyopathy – Stress testing is indicated and appropriate to evaluate for ischemic heart disease as the cause for heart failure or a cardiomyopathy of uncertain etiology, assuming that coronary angiography has not already been planned or performed. Even if angiography has already been performed, stress testing may still be indicated to determine whether the myocardium is viable and to plan the revascularization.

●Patients with chronic left ventricular dysfunction and CHD who are candidates for revascularization – Stress testing with imaging can identify myocardial ischemia and regions of viable myocardium. This information may be helpful in the discussion of planned revascularization and may help predict contractile recovery and outcomes following revascularization. (See "Evaluation of hibernating myocardium" and "Assessment of myocardial viability by nuclear imaging in coronary heart disease".)

●Patients with select arrhythmias – Exercise stress testing can be helpful in the identification of chronotropic incompetence, determining the appropriate setting in patients with rate-adaptive pacemakers, evaluation of patients with congenital complete heart block considering increased physical activity, evaluation of patients with known or suspected exercise-induced arrhythmia (eg, congenital long QT syndrome and other channelopathies), and evaluation of the efficacy of therapy in patients with exercise-induced arrhythmia (table 1) [1].

●Patients undergoing non-cardiac surgery – Patients requiring emergency noncardiac surgery should undergo surgery without delay, and postoperative risk stratification and management should be performed. For preoperative evaluation of patients prior to elective noncardiac surgery, patients with active cardiac conditions should undergo evaluation and treatment prior to the planned surgery [6]. The approach to stress testing and risk assessment prior to noncardiac surgery is discussed in greater detail separately. (See "Evaluation of cardiac risk prior to noncardiac surgery".)

In contrast to its use in the above symptomatic patients, cardiac stress testing for screening of asymptomatic low-risk patients is generally not indicated or appropriate. Rare exceptions are patients with multiple risk factors and those in high-risk occupations (eg, airline pilots). (See "Screening for coronary heart disease".)

OUR APPROACH TO CHOOSING THE OPTIMAL STRESS TEST — For most patients in whom a stress test is indicated, more than one type of stress test may provide clinically useful information (algorithm 1). Our approach to arriving at the optimal stress test for an individual patient is as follows:

Clinical factors to consider — 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.

●Can the patient exercise to a satisfactory workload? – The ability to exercise directly impacts the choice of stress modality. In addition to being able to exercise, patients should be able to exercise to an adequate workload as defined by one or more of several possible variables, including exercise duration, peak heart rate, peak double product, and/or symptoms.

There is not consensus on what constitutes a "satisfactory workload" using individual dichotomous variables for peak exercise heart rate, peak double product, exercise duration, or subjective measures such as perceived exertion and symptoms. In addition, what may constitute a satisfactory workload can differ on the basis of using the exercise test as a diagnostic or prognostic tool in the evaluation of CHD. The most well-recognized stress test value for constituting a satisfactory workload or exercise test end point has been 85 percent of the age-predicted maximum heart rate; however, using this target heart rate approach has significant limitations given the wide variability of an individual's true maximal heart rate, including those with intrinsic heart rate impairment, the use of AV nodal blocking agents, and conversely those with an exaggerated heart rate response to exercise. Our approach has been to perform a symptom-limited study paying close attention to exertional symptoms and perceived exertion (ideally at least a 17 on the Borg scale), while integrating the purpose of the study with objective findings, such as exercise duration and peak heart rate.      

•Nearly all patients who are anticipated to exercise to a satisfactory workload should undergo an exercise stress test rather than a pharmacologic stress test. However, patients who can exercise may also benefit from an imaging modality depending on the clinical scenario. (See 'Patient can exercise and has a normal ECG' below and 'Patient can exercise and has abnormal baseline ECG (except LBBB or ventricular pacing)' below.)

•Patients who are unable to exercise to a satisfactory workload should undergo a pharmacologic stress test with imaging. (See 'Patient cannot exercise to a satisfactory workload' below.)

●Does the patient have an abnormal baseline ECG? – For patients who are anticipated to exercise to a satisfactory workload, significant abnormalities on the baseline electrocardiogram (ECG) can render the stress ECG nondiagnostic. ECG abnormalities that interfere with the ECG diagnosis of ischemia include (see "Exercise ECG testing: Performing the test and interpreting the ECG results", section on 'Limitations to exercise ECG testing'):

•Ventricular preexcitation (Wolff-Parkinson-White pattern)

•Ventricular paced rhythm

•Left bundle branch block (LBBB)

•Greater than 1 mm ST depression at rest

•Digoxin use with associated ST-T abnormalities

•Left ventricular hypertrophy with ST-T abnormalities

●Does the patient need an assessment of myocardial viability? – Patients with documented significant multivessel coronary heart disease and previous myocardial infarction (MI), in whom a revascularization strategy is being developed, may require an assessment of myocardial viability to determine the optimal approach to revascularization. (See "Evaluation of hibernating myocardium".)

●Systems considerations and patient preferences – In addition to the assessment of anticipated exercise capacity, baseline ECG abnormalities, and the need to assess myocardial viability, systems considerations and patient preferences can also impact the choice of a stress test. As examples:

•Patients who require a stress test with imaging may not have access to all imaging modalities (ie, stress radionuclide myocardial perfusion imaging or stress echocardiography not offered locally). In such cases, the best available stress test option should be chosen.

•Patients or laboratories may have time constraints that favor one test over another (stress echocardiography or stress-only radionuclide myocardial perfusion imaging rather than same-day rest-stress or stress-rest radionuclide myocardial perfusion imaging).

•Patients may have a desire or need to avoid radiation exposure (thereby opting for stress echocardiography).

The information obtained from this assessment should allow clinicians to choose from one of the following options to optimize the value of the stress test in a particular patient.

Patient cannot exercise to a satisfactory workload — Patients who are unable to exercise to a satisfactory workload should undergo pharmacologic stress testing with myocardial imaging. With rare exceptions, either stress radionuclide myocardial perfusion imaging or stress echocardiography is acceptable in this circumstance.

●Patients who have a baseline LBBB or right ventricular pacing can undergo either stress radionuclide myocardial perfusion imaging or stress echocardiography, although patients with a marked asynchronous left ventricular contraction pattern at rest may be better suited for a vasodilator stress radionuclide myocardial perfusion imaging since this approach does not rely on assessment of regional wall motion for ischemia detection.

●For patients who have marked obesity, in whom body habitus may limit the interpretation of both stress radionuclide myocardial perfusion imaging (with single-photon emission computed tomography [SPECT]) and stress echocardiography, stress radionuclide myocardial perfusion imaging with positron emission tomography (PET) should be performed if locally available. (See "Overview of stress radionuclide myocardial perfusion imaging", section on 'PET imaging'.)

●For patients who require an assessment of myocardial viability, radionuclide myocardial perfusion imaging with PET or cardiac magnetic resonance (CMR) imaging should be performed if locally available. If these studies are not available, either stress radionuclide myocardial perfusion imaging (SPECT) or stress echocardiography is an acceptable alternative. (See "Assessment of myocardial viability by nuclear imaging in coronary heart disease" and "Evaluation of hibernating myocardium".)

Patient can exercise and has a normal ECG — Patients who are able to exercise to a satisfactory workload should undergo exercise stress testing with ECG recordings. For most such patients, exercise stress testing with ECG alone is the optimal initial stress test. However, there are some patients for whom there are exceptions to this approach:

●For patients with known coronary heart disease (CHD) and prior revascularization, we often perform exercise stress testing with imaging with either stress radionuclide myocardial perfusion imaging or stress echocardiography to localize ischemia and determine its extent.

●For patients with known angiographic CHD of uncertain hemodynamic significance, exercise stress testing with imaging allows for functional assessment of the stenotic lesion(s) with identification and localization of ischemia.

●For patients with known CHD and prior MI who require an assessment of myocardial viability, radionuclide myocardial perfusion imaging with PET or CMR imaging should be performed if locally available. If these studies are not available, either stress radionuclide myocardial perfusion imaging or stress echocardiography is an acceptable alternative. (See "Assessment of myocardial viability by nuclear imaging in coronary heart disease" and "Evaluation of hibernating myocardium".)

●For patients with an intermediate or high pretest probability of CHD, exercise stress testing with imaging has a higher sensitivity and specificity for the diagnosis of obstructive CHD.

Patient can exercise and has LBBB or ventricular pacing on baseline ECG — During exercise radionuclide myocardial perfusion imaging, the presence of LBBB or ventricular pacing on baseline ECG is known to reduce specificity of radionuclide myocardial perfusion imaging. As such, patients with a baseline LBBB or ventricular pacing should undergo stress echocardiography or vasodilator stress radionuclide myocardial perfusion imaging, which has higher specificity.

Patient can exercise and has abnormal baseline ECG (except LBBB or ventricular pacing) — Patients who are able to exercise to a satisfactory workload, but who have a baseline ECG abnormality that obscures the interpretation of ischemic ST segment changes (ie, ventricular preexcitation, greater than 1 mm resting ST segment depression, left ventricular hypertrophy with ST-T abnormalities, digoxin use with associated ST-T abnormalities), should undergo exercise stress testing with imaging. Either stress radionuclide myocardial perfusion imaging or stress echocardiography is acceptable in this circumstance.

STRESS MODALITIES — Symptom-limited exercise testing is generally the preferred form of stress for patients who can exercise and achieve an adequate cardiac workload and heart rate (algorithm 1). Pharmacologic stress testing is typically performed when a patient is unable to exercise [1].

Exercise — Symptom-limited exercise is the preferred form of stress for patients who can attain an adequate level of exercise because it provides the most information concerning symptoms and the hemodynamic response during exercise. (See 'Clinical factors to consider' above.)

A patient's capacity to exercise is often predicted in an informal manner on the basis of his or her reported activity level; however, standard activity or exercise questionnaires are available to aid in determining the metabolic equivalents achieved by exercise testing. Given the availability of modified protocols that begin at lower levels of exertion, there is no predefined level of exercise that a patient has to complete in order to attempt exercise stress testing, although if a person can walk for more than five minutes on flat ground or up one to two flights of stairs without needing to stop, that person most likely can achieve an adequate workload during exercise stress testing.

Valuable prognostic information can be obtained during exercise stress testing. Exercise variables that have been shown to predict outcomes include exercise duration, ST segment response, chronotropic incompetence, heart rate recovery, and exercise-induced hypotension [8,9]. The inability to perform an exercise test in itself is a marker of increased risk in patients with coronary heart disease (CHD) [1]. (See 'Pharmacologic' below and "Exercise ECG testing: Performing the test and interpreting the ECG results".)

Many prognostic scores have been developed and subsequently validated using combinations of the variables described above. A frequently used score is the Duke Treadmill Score, which stratifies patients into low risk (score ≥+5), intermediate risk (score +4 to -10), or high risk (score <-10) categories [1,10,11] based on exercise duration, symptoms, and electrocardiogram (ECG) changes. Data on the prognostic value of the Duke Treadmill Score are discussed in greater detail elsewhere. (See "Prognostic features of stress testing in patients with known or suspected coronary disease", section on 'Duke treadmill score'.)

Contraindications to exercise testing — Although rare, exercise testing is not without potential risks. The absolute and relative contraindications for exercise testing (table 2) are discussed in detail elsewhere. (See "Exercise ECG testing: Performing the test and interpreting the ECG results", section on 'Contraindications'.)

Pharmacologic — Pharmacologic stress testing is typically performed when a patient is unable to exercise, but it is also frequently used in patients with left bundle branch block or ventricular paced rhythm (exercise may also be performed in these patients, but the electrocardiogram will not be interpretable for ischemia). (See 'Exercise ECG testing' below and "Stress testing in patients with left bundle branch block or a paced ventricular rhythm".)

Pharmacologic stress testing can be performed using a vasodilator or a drug with positive inotropic/chronotropic effects. The choice of pharmacologic stress agents is dependent upon patient characteristics and the stress imaging study being performed, as well as institutional and/or provider preference. Because the sensitivity of the stress ECG alone in patients who undergo pharmacologic stress is very low, pharmacologic stress always combines ECG analysis with an imaging modality. (See "Stress testing for the diagnosis of obstructive coronary artery disease".)

Vasodilators — The vasodilator stress agents (adenosine; dipyridamole; and the selective A2A receptor agonists including regadenoson, binodenoson, and apadenoson) increase coronary blood flow through their effects on adenosine A2A receptors. Vasodilators are the preferred pharmacologic stress agent for radionuclide myocardial perfusion imaging (MPI) studies and can be combined with low-level exercise. Each of these vasodilator stress agents is discussed in detail elsewhere. (See "Overview of stress radionuclide myocardial perfusion imaging".)

There are clinical circumstances and/or patient characteristics for which vasodilator agents are not recommended or are contraindicated. In brief, adenosine, dipyridamole, and A2A receptor agonists are absolutely or relatively contraindicated in patients with:

●Pronounced active bronchospastic airway disease (since these drugs may stimulate adenosine A2B receptors, which cause bronchospasm)

●Significant hypotension (since these drugs lower the blood pressure)

●Sinus node dysfunction and high-degree atrioventricular block (since these drugs may worsen preexisting conduction disease) without a functioning pacemaker

●Unstable or complicated acute coronary syndrome (an increased risk for ischemic events is present with all stress modalities)

Theophylline and caffeine should be withheld 48 and 12 hours before vasodilator stress, respectively, since these agents can decrease the effectiveness of vasodilators. (See "Overview of stress radionuclide myocardial perfusion imaging", section on 'Contraindications'.)

Inotropes and/or chronotropes — Dobutamine is a synthetic catecholamine that stimulates beta1-adrenergic receptors with the effect of increasing the heart rate (chronotropic effect) and myocardial contractility (inotropic effect). Dobutamine is the preferred pharmacologic stress agent for stress echocardiography and is the second-line pharmacologic stress agent for stress radionuclide MPI studies. The coronary hyperemia achieved with dobutamine is less than that achieved with vasodilators [12].

Contraindications to dobutamine include:

●Sustained or frequent ventricular arrhythmias and atrial fibrillation with rapid ventricular response

●Recent MI (within one to three days) or unstable angina (contraindicated for all stress modalities)

●Hemodynamically significant left ventricular outflow tract obstruction

●Aortic dissection

●Moderate to severe systemic hypertension (resting systolic blood pressure >180 mmHg)

Atropine is often used in concert with dobutamine in patients who do not achieve target heart rate given its blockade of acetylcholine at parasympathetic sites in smooth muscle. The combined use of dobutamine and atropine results in near maximal coronary vasodilatation, with a significant increase in myocardial blood flow comparable to that caused by dipyridamole in young healthy volunteers [13]. The protocols for and safety of dobutamine stress testing are described elsewhere. (See "Overview of stress echocardiography", section on 'Dobutamine stress echocardiography'.)

SHOULD THE PATIENT HOLD ANY MEDICATIONS FOR STRESS TESTING? — The decision to continue or withhold any medications prior to stress testing is dependent upon a number of patient-specific factors, the most important being the indication for stress testing and the indication for the medication, and it should be made on an individual basis. An extensive discussion of our approach to the management of medications around the time of stress testing is presented separately. (See "Stress testing: The effect of medications and methylxanthines", section on 'Our approach to medications and stress testing' and "Exercise ECG testing: Performing the test and interpreting the ECG results", section on 'Pre-test instructions'.)

Prior to scheduling a cardiac stress test, a comprehensive list of medications and supplements should be obtained from each patient as many medications and supplements can interfere with the optimal performance and interpretation of cardiac stress tests. If a pharmacologic stress test is anticipated, a quick review of medications and supplements with instructions for the patient regarding when to withhold these is critical to performance of the test. As examples, dobutamine is less effective in increasing the heart rate in the presence of a beta blocker, and certain vasodilators will not adequately increase blood flow in the presence of theophylline or caffeine. (See 'Vasodilators' above and 'Inotropes and/or chronotropes' above.)

EXERCISE ECG ALONE OR IN COMBINATION WITH AN IMAGING MODALITY? — Exercise stress testing with electrocardiographic (ECG) monitoring should be the initial test for the majority of patients who can exercise and who have an interpretable ECG (algorithm 1). While exercise stress testing with imaging has several advantages over the standard exercise ECG treadmill test (table 3), there is insufficient evidence to recommend exercise stress testing with imaging in all patients. (See 'Exercise ECG testing' below.)

When patients are unable to exercise, pharmacologic stress is recommended. Because the sensitivity of the stress ECG alone in patients who undergo pharmacologic stress is very low, pharmacologic stress always combines ECG analysis with an imaging modality.

There are also additional circumstances and patient characteristics besides the ability to exercise and resting ECG findings that determine whether a patient should undergo exercise alone or exercise with imaging. These include ischemia localization, viability assessment, prior revascularization, hemodynamic assessment for valvular disease, digoxin use, and prior equivocal exercise ECG findings.

Exercise ECG testing — Exercise ECG testing can effectively risk stratify patients with suspected or known coronary heart disease (CHD) who have a normal resting ECG. Several studies have demonstrated that annual event rates in patients with a low-risk exercise treadmill score are well below 1 percent [10]. However, in the patient with significant abnormalities on the resting ECG, the stress ECG is nondiagnostic, and stress imaging is recommended. (See "Exercise ECG testing: Performing the test and interpreting the ECG results", section on 'Limitations to exercise ECG testing'.)

Despite the lower prevalence of CHD in women and concerns with the diagnostic accuracy of exercise ECG in women, the exercise ECG is still a reasonable first stress test in most women, and there is insufficient evidence to recommend stress imaging in all women considered appropriate for stress testing. (See "Stress testing for the diagnosis of obstructive coronary artery disease", section on 'Challenges in women'.)

In patients who are on digoxin, the specificity of exercise ECG testing may also be reduced, and exercise testing with imaging is preferred because of the impracticalities of discontinuing digoxin for two weeks to allow washout before the exercise study. Similarly, the specificity of the exercise ECG is reduced in the presence of left ventricular hypertrophy with repolarization abnormalities on the resting ECG, and exercise testing with imaging is preferred in these patients. (See "Exercise ECG testing: Performing the test and interpreting the ECG results", section on 'Limitations to exercise ECG testing'.)

Advantages of the ECG exercise treadmill test over stress imaging studies include its wide availability and lower cost. In many patients undergoing an evaluation for CHD who have a normal or near normal ECG and can exercise, the initial use of an exercise treadmill test is more cost-effective than performing an initial stress imaging study in all patients. The table provides a comparison of the advantages of the exercise ECG versus stress imaging (table 3).

Stress imaging modalities

Radionuclide stress myocardial perfusion imaging (MPI) — Exercise or pharmacologic stress radionuclide MPI using single photon emission computed tomography (SPECT) and positron emission tomography (PET) are widely accepted and commonly used techniques in the diagnosis, risk stratification, and guidance of therapy in patients with suspected or known CHD. Because of the short physical half-lives of PET tracers, pharmacologic vasodilators are the preferred stress method over exercise for PET MPI studies. The most commonly used SPECT MPI agents are technetium-99m based (Tc-99m sestamibi and Tc-99m tetrofosmin) and, less commonly, thallium-201 alone or in combination with Tc-99m-based tracers (dual-isotope protocol), while PET MPI agents include rubidium-82 andN13-ammonia. Details on stress myocardial perfusion agents, testing methodologies, safety, assessment of myocardial viability, as well as the diagnosis of and prognosis in CHD are discussed separately. (See "Basic properties of myocardial perfusion agents" and "Stress testing for the diagnosis of obstructive coronary artery disease" and "Overview of stress radionuclide myocardial perfusion imaging" and "Assessment of myocardial viability by nuclear imaging in coronary heart disease".)

The basic tenet of stress radionuclide MPI is the visual assessment of relative myocardial blood flow or perfusion (via the radioactive tracer) between the resting and stressed states. Myocardial segments that demonstrate preserved myocardial perfusion at rest but decreased myocardial perfusion during stress are considered to be indicative of ischemia; whereas a matched reduction in perfusion between the rest and stress images is suggestive of a myocardial infarction.

Information on cardiac size and function can be obtained in addition to the assessment of myocardial perfusion and viability. The use of ECG-gating during SPECT or PET image acquisition allows for quantification of left ventricular volume and ejection fraction, as well as assessment of regional wall motion and thickening. The advantages of PET over SPECT include the lower radiation patient exposure (due to the shorter physical half-lives of PET perfusion tracers) and more robust attenuation correction (leading to higher diagnostic accuracy in women and patients with larger body habitus) [14].

Stress echocardiography — Similar to radionuclide stress myocardial perfusion imaging, stress (exercise or pharmacologic) transthoracic echocardiography is used to detect hemodynamically significant CHD, localize ischemia in patients with known CHD, risk stratify patients, and assess for valvular disease and myocardial viability [4,15]. The basic concept of stress echocardiography is the detection of ischemia through the development of new regional wall motion abnormalities or worsening of preexisting regional wall motion abnormalities. Decrease of global left ventricular ejection fraction, and/or increased left ventricular end-systolic volume, suggests the presence of severe obstructive coronary arterial disease such as flow-limiting left main stenosis or severe multi-vessel coronary artery disease. (See "Overview of stress echocardiography".)

Stress echocardiography has the ability to provide insight regarding hemodynamics during stress. Exercise parameters of diastolic function, systolic pulmonary artery pressure responses, and valvular heart disease can be obtained as part of a hemodynamic stress echocardiogram study. In addition, findings of the resting echocardiogram (prior to stress) may provide a prompt diagnosis of the mechanism for symptoms. As an example, the presence of a pericardial effusion may be identified, which may suggest underlying pericarditis as a cause of chest pain. Details on stress echocardiography indications, safety, assessment of myocardial viability, myocardial contrast echocardiography, as well as the diagnosis of and prognosis in coronary artery disease (CAD) are discussed separately. (See "Overview of stress echocardiography" and "Dobutamine stress echocardiography in the evaluation of hibernating myocardium" and "Contrast echocardiography: Clinical applications".)

Stress cardiovascular magnetic resonance imaging — Cardiovascular magnetic resonance (CMR) imaging can fulfill many roles in the evaluation of ischemic heart disease, given its ability to provide information on cardiac structure; global and regional left and right ventricular function; infarct size, location, and transmurality; and myocardial perfusion through pharmacologic stress. Pharmacologic stress CMR can be performed using either a vasodilator stress agent or dobutamine. The use and availability of CMR for stress imaging is growing; among a cohort of 9151 patients (mean age 63 years; 55 percent male) who underwent stress CMR at one of seven centers with median follow-up of five years, abnormal stress CMR was associated with greater risk of mortality (HR 1.80 in two different models) [16]. However, there are limited data comparing stress CMR to other stress imaging modalities, and the availability of stress CMR is still more limited than that of stress radionuclide MPI and stress echocardiography. (See "Clinical utility of cardiovascular magnetic resonance imaging".)

Comparison of different imaging techniques — In general, stress radionuclide MPI using SPECT has slightly higher sensitivity, and stress echocardiography has slightly higher specificity for the detection of coronary artery disease; however, they have similar overall diagnostic accuracy [17,18]. Stress radionuclide MPI using PET has both high sensitivity and specificity, but the diagnostic literature of PET MPI is more limited compared with those of stress SPECT and stress echocardiography, and the technique is less widely available. Both radionuclide MPI and stress echocardiography have better performance than exercise ECG testing [17]. The clinician's ultimate choice of imaging modality must take into account other factors such as local expertise and experience with each test, availability, and cost.

A meta-analysis compared the test performance in patients with an intermediate pretest risk of CHD (25 to 75 percent) of the following tests: exercise ECG testing, planar thallium imaging, SPECT perfusion imaging, stress echocardiography, and positron emission tomography (PET), each of which was followed by coronary angiography if the test was positive [18]. Not surprisingly, much more data were available about exercise ECG testing. The following values for sensitivity and specificity were noted:

●Exercise ECG testing – 68 and 77 percent in 132 studies of over 24,000 patients [19]

●Planar thallium rMPI – 79 and 73 percent in six studies of 510 patients

●SPECT rMPI – 88 and 77 percent in 10 studies of 1174 patients

●Stress echocardiography – 76 and 88 percent in six studies of 510 patients

●PET scanning – 91 and 82 percent in three studies of 206 patients

In the presence of left bundle branch block (LBBB) or ventricular pacing, there is an increased prevalence of reversible or fixed perfusion defects (classically in the septum) in the absence of angiographic CHD when exercise stress testing with radionuclide MPI is performed. The specificity of exercise radionuclide MPI using SPECT in these conditions is lower compared with vasodilator radionuclide MPI with SPECT. Although randomized studies have not been performed, vasodilator radionuclide MPI with SPECT or radionuclide MPI with PET is preferred in LBBB or ventricular pacing, even if the patient can exercise. However, stress echocardiography is also an option for this population, though it is less well studied than stress radionuclide MPI.

For the assessment of myocardial viability, radionuclide MPI with PET perfusion combined with F-18 fluorodeoxyglucose (FDG) metabolic imaging is considered the gold standard noninvasive technique for the identification of hibernating myocardium because PET has the highest sensitivity and negative predictive value among the noninvasive techniques for this purpose [20]. The assessment of myocardial viability is discussed in greater detail separately. (See "Assessment of myocardial viability by nuclear imaging in coronary heart disease".)

Anatomic assessment of coronary artery disease — While the stress testing modalities aim to assess the functional or physiological consequences of CAD, anatomic assessment of CAD may also be performed with cardiac CT in patients with suspected coronary artery disease (CAD). Two main approaches to this are coronary artery calcium scoring (CACS) and coronary CT angiography (CCTA).

CACS — The presence and extent of CAC can predict the presence of coronary artery stenoses, but in general CAC is a better marker of the extent of atherosclerosis and the risk of cardiovascular events than the severity of coronary artery stenosis. In both men and women, CAC detected by CT is highly sensitive for the presence of >50 percent angiographic stenosis but only moderately specific, especially in individuals over 60 years of age. In a review of 16 studies, the sensitivity and specificity of CAC were 91 and 49 percent, respectively [21]. CAC is also present in most patients with myocardial ischemia, both symptomatic and asymptomatic. However, CAC may also be present, although less prevalent in patients without stress-induced ischemia.

A number of studies in asymptomatic patients have shown the prognostic value of CAC, especially those at intermediate risk. CAC also has prognostic value in symptomatic patients [22,23]. However, in symptomatic patients, a CAC score of 0 does not carry the same high negative predictive value as it does in asymptomatic patients. Measurement of CAC for cardiovascular risk assessment in selected asymptomatic adults at intermediate risk (10 to 20 percent, 10-year risk) by the Framingham risk score and modified Framingham/ATP risk scores may lead to a change in management based upon reclassification to a lower or higher risk group. CAC measurement is not recommended in patients at low (<10 percent, 10-year risk) or high (>20 percent, 10-year) CHD risk as established by the Framingham risk score and modified Framingham/ATP risk scores. (See "Coronary artery calcium scoring (CAC): Overview and clinical utilization".)

CCTA — Coronary CT angiography (CCTA) is widely available and is also appropriate as the initial or second test for evaluating patients with suspected CAD, in the absence of a history of allergy to iodinated contrast medium, a high risk for contrast nephropathy, and/or patient-related factors that may interfere with the diagnostic quality of CCTA images, including heart rate greater than 60 to 70 beats per minute, irregular rhythm, inability to sustain a breath hold for at least five seconds, and prominent coronary artery calcification or the presence of coronary artery stents. Segments with a diameter <1.5 mm can usually not be assessed for stenosis. In patients able to undergo CCTA, it detects >50 percent stenosis in coronary arteries with a diameter greater than 1.5 mm with high accuracy. A major strength of CCTA is its high sensitivity and negative predictive value. With the exception of the SCOT-HEART trial (described below), the majority of studies comparing CCTA with functional testing have demonstrated significantly greater utilization of invasive coronary angiography and significant higher rate of revascularization with CCTA as compared to functional testing.

CCTA and stress testing with imaging (cardiac SPECT or echocardiography) are associated with comparable long-term clinical outcomes (ie, mortality, MI, major adverse cardiac events) . However, CCTA may result in better outcomes when added to standard care (contemporary medical therapy with a diagnostic strategy based primarily on stress ECG alone). CCTA leads to higher rates of cardiac catheterization and revascularization over the short term (<90 days) but does decrease the length of emergency department and hospital stays [24-28].

●A randomized trial studying outpatient testing for CAD found that initial CCTA versus initial stress testing (67 percent stress nuclear, 23 percent stress echocardiography, and 10 percent stress ECG alone) yielded similar clinical outcomes over a median follow-up of two years [24]. The Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) randomly assigned 10,003 symptomatic outpatients requiring evaluation for suspected CAD to either CCTA or functional stress testing (exercise ECG, nuclear stress testing, or stress echocardiography). Median follow-up was 25 months.

●In the prospective SCOT-HEART trial, 4146 patients with stable chest pain referred for cardiology evaluation were randomly assigned to standard care (which included contemporary medical therapy and diagnostic testing at the discretion of the treating physician) or standard care plus CCTA. Eighty-five percent of patients underwent stress ECG, with 9 percent undergoing a stress test with imaging [29]. Compared with standard care alone, patients randomized to CCTA and standard care had a significant reduction in the primary end point of CAD death or non-fatal MI (48 [2.3 percent] versus 81 patients [3.9 percent]) over an average follow-up of 4.8 years, with similar rates of invasive angiography and coronary revascularization. Imaging with CCTA was associated with greater preventive therapy, as patients in the CCTA group were significantly more likely to receive aspirin and a statin. However, this difference was likely related to trial design which specified preventive therapy following a positive CCTA and no preventive therapy recommendation following standard care positive test results. There were no significant between-group differences in deaths from any cause.

In patients with suspected CAD, a combination of coronary calcium scoring for risk stratification followed by CCTA may be used to select patients for coronary angiography [30,31]. In the CRESCENT-II study of 268 patients with stable angina, this combination was more effective than functional testing with exercise ECG at reducing subsequent testing and long-term cardiac events (3 percent versus 10 percent for functional testing), albeit with small numbers of patients and events [31].

Cardiovascular MR (CMR) for imaging of the coronary arteries can also be performed in patients with suspected CAD but limitations include decreased spatial resolution, and more limited literature compared CCTA with lower diagnostic accuracy for native noncongenital CAD for CMR. (See "Clinical utility of cardiovascular magnetic resonance imaging", section on 'Pharmacologic stress CMR'.)

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: Multimodality cardiovascular imaging appropriate use criteria" and "Society guideline links: Stress testing and cardiopulmonary exercise testing".)

SUMMARY AND RECOMMENDATIONS

●Cardiac stress testing is an important diagnostic and prognostic tool in the evaluation and management of patients with known or suspected coronary heart disease (CHD). While stress testing can be performed in a variety of ways, the most commonly used and widely available stress testing modalities are exercise electrocardiography (ECG; non-imaging) and stress imaging with echocardiography or radionuclide myocardial perfusion imaging (MPI). (See 'Introduction' above.)

●In patients with symptoms suggesting CHD, cardiac stress testing is most often indicated to aid in making the diagnosis of CHD and for risk stratification. In some patients with known CHD and prior coronary revascularization or a change in clinical status, cardiac stress testing can be indicated for the diagnosis of new or progressive disease and/or for risk stratification. In addition to symptomatic patients with known or suspected CHD, patients with heart failure, cardiomyopathy, valvular heart disease, or planned non-cardiac surgery may be candidates for stress testing. (See 'Indications for stress testing' above.)

●Symptom-limited exercise is generally the preferred form of stress for patients who can exercise because it provides the most information concerning symptoms, exercise capacity, and the hemodynamic response during exercise. Pharmacologic stress testing is typically performed when a patient is unable to exercise. (See 'Exercise' above and 'Pharmacologic' above.)

●Exercise electrocardiogram (ECG) should be the initial test for the majority of patients who can exercise adequately (algorithm 1), who have an interpretable ECG, and who do not have certain conditions (eg, left bundle branch block, paced ventricular rhythm, ventricular pre-excitation, etc). While stress testing with imaging has several advantages over the standard exercise ECG treadmill test, there is insufficient evidence to recommend stress testing with imaging in all patients. (See 'Our approach to choosing the optimal stress test' above.)