INTRODUCTION — Echocardiography enables evaluation of cardiac function at rest, during pharmacologic stress, and during or immediately following dynamic exercise. Exercise two-dimensional (2D) transthoracic imaging is used primarily to detect the presence and extent of coronary artery disease by provoking regional ischemia with resulting wall motion abnormalities. The addition of exercise Doppler permits evaluation of exercise-induced changes in valvular function (eg, severity of mitral regurgitation/mitral stenosis gradient), pulmonary artery systolic pressure, left ventricular outflow tract gradient, and global left ventricular systolic and diastolic function.
Stress echocardiography can be accomplished using either exercise (treadmill or bicycle) or pharmacologic agents (predominantly dobutamine) as the stress mechanism [1-3]. Microbubble ultrasound-enhancing agents may be useful in enhancing endocardial border definition when two or more segments of the left ventricle are not well visualized. (See "Contrast echocardiography: Clinical applications" and "Contrast echocardiography: Contrast agents, safety, and imaging technique".)
An overview of the indications, contraindications, techniques, and safety of stress echocardiography will be provided here. Exercise treadmill testing and radionuclide myocardial perfusion imaging, as well as the advantages and disadvantages of stress echocardiography as compared with other stress modalities, are discussed separately. (See "Exercise ECG testing: Performing the test and interpreting the ECG results" and "Overview of stress radionuclide myocardial perfusion imaging" and "Selecting the optimal cardiac stress test".)
INDICATIONS — There are several specific indications for stress echocardiography [3-5]:
●Evaluation of patients with known or suspected coronary artery disease.
●Assessment of myocardial viability. (See "Dobutamine stress echocardiography in the evaluation of hibernating myocardium" and "Evaluation of hibernating myocardium".)
●Evaluation of dyspnea of possible cardiac origin. (See "Approach to the patient with dyspnea".)
●Evaluation for pulmonary artery hypertension, as pulmonary artery systolic pressure can be estimated at rest and post-exercise. (See "Clinical features and diagnosis of pulmonary hypertension of unclear etiology in adults".)
●Evaluation of mitral valve disease, including mitral stenosis gradient and mitral regurgitation. (See "Rheumatic mitral stenosis: Clinical manifestations and diagnosis", section on 'Exercise testing' and "Clinical manifestations and diagnosis of chronic mitral regurgitation", section on 'Stress testing'.)
●Evaluation of aortic stenosis. Stress echocardiography may be reasonable and helpful in patients with low gradient aortic stenosis. (See "Clinical manifestations and diagnosis of low gradient severe aortic stenosis".)
●Evaluation of left ventricular outflow tract gradients, mitral regurgitation, and pulmonary hypertension in patients with hypertrophic cardiomyopathy. (See "Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation", section on 'Exercise testing'.)
The baseline (resting) echocardiographic imaging performed prior to stress testing is described below. (See 'Baseline echocardiography' below.)
CONTRAINDICATIONS — Contraindications to exercise and pharmacologic stress echocardiography are the same as those for standard exercise electrocardiographic (ECG) testing. Contraindications for all stress testing modalities include the following:
●Acute coronary syndromes
●Severe cardiac arrhythmias
●Significant left ventricular outflow tract obstruction
●Symptomatic severe aortic stenosis 
Contraindications to dobutamine stress echocardiography include tachyarrhythmias and systemic hypertension . (See "Exercise ECG testing: Performing the test and interpreting the ECG results", section on 'Contraindications'.)
Some have considered abdominal aortic aneurysm to be a relative contraindication to exercise testing or dobutamine stress echocardiography [6,7]. However, there is evidence that such stress testing can be safely performed in these patients. In a review of 262 patients with an abdominal aortic aneurysm diameter >4 cm (average 5.5 cm), one patient (0.4 percent) with a 6.1 cm aneurysm had a contained rupture 12 hours after exercise, which was successfully repaired . In 98 patients with abdominal aortic aneurysms ≥4 cm who underwent dobutamine stress echocardiograms, there were no vascular complications .
Exercise two-dimensional echocardiography — Exercise stress is preferable to pharmacologic stress for patients who are capable of performing an exercise test, as exercise capacity and the hemodynamic response to exercise are important predictors of outcomes . (See "Selecting the optimal cardiac stress test" and "Exercise ECG testing: Performing the test and interpreting the ECG results".)
Protocols — The practice guidelines from the American Society of Echocardiography (ASE) recommend symptom-limited exercise according to standard protocols using either a treadmill or bicycle [2,3]. These guidelines note that if evaluation of wall motion is the main purpose of the test, then treadmill exercise is usually used, whereas if stress Doppler information is desired, supine bicycle exercise should be considered because it enables Doppler as well as wall motion evaluation during each stage of exercise [2,3]. As with any exercise stress test, exercise should be performed until the patient feels that he/she cannot exercise further due to fatigue or symptoms, although in some instances there may be appropriate endpoints determined by the provider or the protocol. (See "Exercise ECG testing: Performing the test and interpreting the ECG results", section on 'Test endpoints'.)
Treadmill — Exercise echocardiography is most commonly performed using a treadmill protocol (table 1). Echocardiographic images are acquired prior to and immediately after completion of exercise [2,3,8,9]. This method requires that the patient transfer from the treadmill into a recumbent position for imaging within a few seconds so that a complete set of images can be obtained as rapidly as possible, usually within 60 seconds after cessation of exercise. Use of digitized images permits review of multiple cardiac cycles, as well as side-by-side comparison of these images. This approach maximizes accuracy of interpretation. Continuous recording of images is also recommended as backup [2,3].
For maximal diagnostic accuracy, images should be obtained prior to the heart rate decreasing toward baseline. Early image acquisition is necessary since ischemia-induced wall motion abnormalities may resolve rapidly as the heart rate slows, causing a decrease in the sensitivity of the test, especially for single vessel disease. The experience and competence of a laboratory's clinician/sonographer team influence the reliability of this test [2,3].
Supine or upright bicycle ergometry — Some laboratories perform stress echocardiography using supine or upright bicycle ergometry. A typical symptom-limited supine bicycle protocol starts at a workload of 25 or 30 watts and increases by 25 or 30 watt increments every three minutes until an endpoint is achieved.
A major advantage of supine bicycle ergometry is that it allows for continuous monitoring of wall motion during exercise. Imaging throughout the study may permit detection of the onset of wall motion abnormalities and improve sensitivity of detection of coronary artery disease [10,11]. Moreover, acquisition of Doppler imaging during each stage of exercise is also feasible during supine bicycle exercise.
Pharmacologic stress echocardiography — Pharmacologic stress is employed in patients who are unable to perform exercise testing. In addition, it may be preferable to exercise testing for preoperative risk and myocardial viability assessment since the majority of data validating stress echocardiography for myocardial viability involved pharmacologic (largely dobutamine) stress.
Pharmacologic stress testing most commonly involves the administration of dobutamine with the addition of atropine as needed to achieve the target heart rate [2,3,12-15]. The American Society of Echocardiography (ASE) guidelines recommend dobutamine as preferable to vasodilators (eg, dipyridamole, adenosine, regadenoson) as there is greater experience using dobutamine for stress echocardiography in the United States . However, dobutamine and vasodilators are equally potent ischemic stressors for inducing wall abnormalities in the presence of a critical epicardial coronary artery stenosis [1,3]. As such, dipyridamole is a popular pharmacologic regimen for stress echocardiography in Europe [16-18].
Dobutamine stress echocardiography — The dobutamine dosage and protocols for the indications of assessment of obstructive coronary artery disease and viability are provided.
●Graded dobutamine infusion in five three-minute stages starting at 5 mcg/kg/minute, followed by 10, 20, 30, and 40 mcg/kg/minute (figure 1). Some experts start the graded infusion at a lower dosage (eg, 2.5 mcg/kg/minute) while others use an accelerated protocol of 15, 30, and 45 mcg/kg/minute. Some experts omit the first low-dose stage when no viability evaluation is sought.
●Atropine, in divided doses of 0.5 mg each to a total of 2 mg, should be administered as needed to achieve target heart rate. Atropine increases the sensitivity of dobutamine echocardiography in patients receiving beta-blockers and in those with single-vessel disease [19-21]. Some laboratories also use a sustained isometric hand grip or a low-level dynamic foot exercise (with or without atropine) in the late stages of the dobutamine protocol as a supplemental maneuver to achieve peak heart rate. (See 'Handgrip exercise' below.)
During dobutamine stress echocardiography, echocardiographic images are acquired prior to the start of the dobutamine infusion, at the completion of each stage, and during recovery.
Variations from the standard dobutamine protocol have been proposed. Some laboratories use a sixth dose of 50 mcg/kg/minute; others, based on pharmacokinetic data, extend the 40 mcg infusion to five minutes. Some omit the first low-dose (5 mcg/kg/min) stage when no viability evaluation is sought. Accelerated dobutamine protocols have been described [22,23].
The standard endpoint for dobutamine stress echocardiography is the achievement of target heart rate, defined as at least 85 percent of the age-predicted maximum heart rate. However, the test may also be terminated following the development of significant symptoms, new or worsening wall motion abnormalities of moderate degree, significant arrhythmias, hypotension (systolic blood pressure less than 90 mmHg), or severe hypertension . (See "Exercise ECG testing: Performing the test and interpreting the ECG results", section on 'Test endpoints'.)
Viability assessment — A dobutamine stress echocardiogram can assess myocardial viability and contractile reserve. (See "Dobutamine stress echocardiography in the evaluation of hibernating myocardium" and "Evaluation of hibernating myocardium".)
Dobutamine dosing for viability assessment starts at a lower initial dose than for assessment of coronary artery disease. We use the following dosing:
●Continuous dobutamine infusion initiated at 2.5 mcg/kg/minute, and increasing at five-minute intervals in 2.5 mcg/kg/minute increments until a contractile response is noted, up to a maximum dose of 10 mcg/kg/minute [2,24,25].
Effect of beta blocker therapy — Use of beta-blockers may attenuate heart rate response as well as evidence of myocardial ischemia during dobutamine stress echocardiography [18,26]. However, the effect of beta-blockers on heart rate response to dobutamine can usually be overcome by the administration of atropine . Moreover, performing the stress echocardiogram while the patient stays on all medications, including beta-blockers, may be useful for assessment of treatment efficacy. Some stress echocardiography laboratories recommend withholding beta-blockers prior to the test while others typically recommend continuation of beta-blockers and all cardiac medications prior to stress echocardiograms . While the safety and prognostic value of dobutamine stress echocardiography for patients who continue taking their home medication is well established, the referring care provider may decide to withhold beta-blockers in certain circumstances (eg, to maximize the sensitivity of the test for the initial diagnosis of coronary heart disease) [28-31].
Vasodilator stress echocardiography — Dipyridamole is administered at up to 0.84 mg/kg in two separate infusions: 0.56 mg/kg over four minutes ("standard dose"), followed by four minutes of no dose and, if an adequate physiologic response is not achieved, then an additional 0.28 mg/kg is given over two minutes. If no endpoint is reached following the second infusion (total of 0.84 mg/kg), then atropine (doses of 0.25 mg, up to a maximum of 1 mg) may be administered .
Adenosine is typically infused at a maximum dose of 140 mcg/kg/minute over six minutes . Imaging is performed prior to and after starting adenosine infusion. Adenosine is a shorter-acting agent employed for myocardial perfusion contrast echocardiography and, to a lesser extent, to detect stress-induced changes in wall motion, but this method has not been in wide clinical use. Vasodilator stress may be better suited for perfusion than wall motion analysis .
Pacing — In selected patients with a permanent pacemaker, increasing the pacing rate to facilitate achievement of target heart rate may be used; this stress method is combined with dobutamine infusion  , starting with dobutamine infusion following the usual protocol and then holding the infusion at 20 mcg. At this dose of dobutamine, we start a stepwise increase of the heart rate by increase pacing rate until achievement of the target heart rate. During recovery the pacing rate is progressively reduced at one-minute intervals.
Handgrip exercise — Handgrip may be used as an adjunct to exercise or dobutamine stress echocardiography [32,33]. During the last stage of exercise or dobutamine infusion and 30 seconds before acquiring the peak exercise images, patients are asked to exert a sustained grip on a tennis ball. The hand grip response reliably raises blood pressure at least 10 mmHg and usually also increases heart rate; superimposed on the maximum achieved levels, this augmentation results in a "bonus" increment in rate pressure product.
Baseline echocardiography — The baseline (resting) echocardiogram obtained prior to stress testing should include a screening assessment of ventricular function, chamber sizes, left ventricular wall thicknesses, aortic root diameter, pericardial effusions, and gross valvular structure and function, including an estimate of pulmonary arterial systolic pressure using the peak tricuspid regurgitation velocity. Baseline and stress images are acquired in a variety of standard echocardiographic windows, including apical (four-chamber, long axis, and two-chamber), and parasternal (long and short axis) [34-39]. Rest imaging allows screening and prompt identification of potential etiologies for cardiac symptoms . It also allows the diagnosis of ancillary conditions in the setting of coronary artery disease, such as intracavitary thrombus or ischemic mitral regurgitation. (See "Transthoracic echocardiography: Normal cardiac anatomy and tomographic views".)
Two-dimensional imaging — When stress echocardiography is performed to evaluate coronary heart disease, the main goal of two-dimensional (2D) imaging is side-by-side comparison of images for assessment of global and regional left ventricular systolic function at rest and immediately after stress. Images are also compared with pre-peak and peak stress, during pharmacologic stress or with bicycle exercise. With stress, the normal left ventricle becomes hypercontractile, cavity size is reduced, and ejection fraction increases [2,3]. Various professional society recommendations for chamber quantification have suggested either a 16- or 17-segment model for left ventricular regional wall motion analysis (figure 2 and figure 3) [3,40,41]. Function in each segment is graded (normal, hyperdynamic, hypokinetic, akinetic, dyskinetic, or aneurysmal) at rest and with stress. In addition, global left ventricular systolic function and cavity size are evaluated. (See "Transthoracic echocardiography: Normal cardiac anatomy and tomographic views".)
Detection of segmental left ventricular dysfunction is useful in diagnosing and localizing obstructive coronary artery disease (figure 2 and figure 4). The development of new or worsening segmental wall motion with stress suggests presence of hemodynamically significant coronary artery stenoses supplying the abnormal segments. Decrease of global left ventricular ejection fraction, and/or increased left ventricular end-systolic volume, suggest presence of severe obstructive coronary arterial disease such as flow-limiting left main stenosis or severe multivessel coronary artery disease.
Low-dose dobutamine stress echocardiography enables identification of dysfunctional but viable myocardial segments. In segments that have resting dysfunction but are viable (hibernating or stunned), low-dose dobutamine infusion leads to improved contractility . As the dobutamine dose is increased, a biphasic response is detected with the segmental motion improving at low-dose and then deteriorating at a higher dose to a level of dysfunction that is worse than it was at rest [12,13,42-44]. Such a response is highly specific for identifying a dysfunctional hibernating segment that is served by a stenotic coronary artery. The highest sensitivity for viability detection is obtained by identification of improvement with low-dose dobutamine; highest specificity is achieved when a biphasic response occurs. (See "Dobutamine stress echocardiography in the evaluation of hibernating myocardium" and "Evaluation of hibernating myocardium".)
Doppler imaging — Doppler echocardiography enables measurement of flow velocities and pressure gradients. Because Doppler recordings display instantaneous changes in these parameters, this is an excellent technique for the study of hemodynamic response to exercise or pharmacologic stress.
Doppler examination following stress should be individualized based on the findings from the baseline (resting) echocardiogram as well as the indications for the study. The common potential targets for Doppler examination following stress testing include:
●Mitral valve – Changes in mitral stenosis gradient or mitral regurgitation following stress
●Aortic valve – Evaluation of aortic valvular gradients in suspected low-flow, low-gradient aortic stenosis
●Tricuspid valve – Assessment of tricuspid regurgitation velocity for estimation of pulmonary artery systolic pressure in patients with suspected pulmonary hypertension
●Left ventricular outflow tract (LVOT) – Evaluation for inducible or worsening LVOT gradient in suspected or known hypertrophic cardiomyopathy
Use of microbubble ultrasound-enhancing agents — Microbubble ultrasound-enhancing agents improve left ventricular endocardial border definition during stress echocardiography. Though the administration of an ultrasound-enhancing agent requires intravenous access, use of these agents increases the number of interpretable left ventricular wall segments, improves the accuracy of less experienced readers, enhances diagnostic confidence, and reduces the need for additional noninvasive tests [45-48].
Indications for ultrasound-enhancing agents — Ultrasound-enhancing agents should be used when two or more contiguous segments cannot be visualized with resting native imaging, coronary artery territory cannot be completely visualized, or Doppler signals are inadequately recorded [3,49].
Clinical characteristics suggesting the need for ultrasound-enhancing agents during stress echocardiography include older age, male sex, smoking, presence of multiple coronary artery disease risk factors, higher body mass index, chronic lung disease, referral for dobutamine stress, history of coronary artery disease, and abnormal baseline electrocardiogram . (See "Contrast echocardiography: Clinical applications".)
In addition to enhancement of endocardial border definition, ultrasound-enhancing agents can be helpful for augmenting Doppler signals . Technically suboptimal right heart Doppler signals can usually be improved by intravenous agitated saline. In selected cases, technically suboptimal left heart Doppler signals could be improved by the use of intravenous injection of microbubble ultrasound contrast agents .
General concerns — There are no known adverse effects from diagnostic ultrasound at clinical imaging frequencies, so the addition of echocardiographic imaging to stress testing (either exercise or pharmacologic) does not alter the underlying risk of the stress test. (See "Echocardiography essentials: Physics and instrumentation", section on 'Bioeffects and safety'.)
As with any stress test, the patient's electrocardiogram, heart rate, and blood pressure should be monitored throughout the test and during recovery, and the patient should be frequently queried about the development of symptoms. The monitoring of the patient during stress testing and the interpretation of the results are discussed in greater detail elsewhere. (See "Exercise ECG testing: Performing the test and interpreting the ECG results".)
The risks of exercise or dobutamine stress echocardiography testing are low. In one cohort of more than 60,000 stress echocardiograms (including more than 25,000 exercise and more than 35,000 dobutamine), life-threatening complications were very rare (0.015 percent of exercise stress echocardiograms and 0.18 percent of dobutamine stress echocardiograms) .
Safety of dobutamine administration — Dobutamine is generally safe and well tolerated when used in stress testing [28,52,53]. While both cardiac (eg, arrhythmias, chest pain, left ventricular outflow tract obstruction, etc) and noncardiac side effects can occur, serious complications, such as ventricular fibrillation or myocardial infarction, are rare, occurring in approximately 1 of every 2000 studies [3,52]. Atropine poisoning was observed in 0.12 percent of patients .
●Minor arrhythmias, predominantly ventricular and/or premature atrial complex (also referred to a premature atrial beat, premature supraventricular complex, or premature supraventricular beat), occur in up to 30 percent of dobutamine stress studies [52,53].
●Atrial fibrillation and nonsustained ventricular tachyarrhythmias occur in 1 and 3 percent of studies, respectively; these arrhythmias are generally well tolerated and spontaneously resolve [52,53].
●Sustained ventricular tachycardia is rare, occurring in approximately 0.1 to 0.3 percent of studies, and the risk may be associated with left ventricular dysfunction and/or coronary artery disease .
●Although chest pain has been reported in up to 11 percent of patients receiving dobutamine for stress testing, serious complications from myocardial ischemia are very uncommon. In a review of more than 4000 patients, there was only one case of nonfatal myocardial infarction . Symptomatic ischemia is effectively treated with discontinuation of dobutamine and sublingual nitroglycerin and/or intravenous beta-blocker.
There are a number of minor noncardiac side effects including nausea, anxiety, headache, tremor, and urinary urgency, which can lead to test termination in approximately 3 percent of cases (table 2) .
Ultrasound-enhancing agent safety — Ultrasound-enhancing agents are generally safe to use for the evaluation of endocardial borders and wall motion [58,59]. The safety of these agents is discussed in detail separately. (See "Contrast echocardiography: Contrast agents, safety, and imaging technique", section on 'Second-generation contrast safety'.)
As examples of the safety of ultrasound-enhancing agents during stress echocardiography:
●In a retrospective analysis of a multicenter cohort including more than 40,000 patients, rates of death and myocardial infarction were not significantly different between patients receiving ultrasound-enhancing agents and those not receiving these agents .
●Patients with pulmonary hypertension have been thought to have a higher risk of adverse reactions receiving ultrasound-enhancing agents, but an evaluation of more than 25,000 patients showed that right ventricular systolic pressure had no impact on adverse outcomes after receiving ultrasound-enhancing agents .
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
●Indications – Similar to other modalities of stress testing (eg, exercise treadmill testing without imaging, radionuclide myocardial perfusion imaging, etc), the majority of stress echocardiograms are performed to evaluate for known or suspected coronary heart disease (CHD). Stress echocardiography is useful for the assessment of myocardial viability. In addition, because of its ability to assess hemodynamics, stress echocardiography can be useful in a variety of other non-CHD conditions (eg, valvular heart disease, hypertrophic cardiomyopathy, etc). (See 'Indications' above.)
●Stress techniques – Stress echocardiography can be accomplished using either exercise (treadmill or bicycle) or pharmacologic agents (predominantly dobutamine) as the mechanism of stress. (See 'Introduction' above.)
•Exercise stress is preferred to pharmacologic stress for patients who can perform an exercise test. Exercise echocardiography is most commonly performed using a treadmill protocol, with echocardiographic images acquired prior to and immediately after the peak treadmill exercise. However, supine and upright bicycle ergometry are other well validated methods of exercise echocardiography, with the major advantage of allowing for monitoring of wall motion and Doppler parameters during exercise. (See 'Exercise two-dimensional echocardiography' above.)
•Pharmacologic stress is employed in patients who are unable to perform exercise testing. In addition, it may be preferred to exercise testing for preoperative risk and myocardial viability assessment since the majority of data validating stress echocardiography for this indication involved pharmacologic (largely dobutamine) stress. During dobutamine echocardiography, echocardiographic images are acquired prior to the start of the dobutamine infusion, at the completion of each stage, at peak stress, and during recovery. (See 'Pharmacologic stress echocardiography' above.)
●Patients on beta-blocker therapy – Use of beta blockers may attenuate heart rate response as well as evidence of myocardial ischemia during dobutamine stress echocardiography. However, the effect of beta-blockers on heart rate response to dobutamine can usually be overcome by the administration of atropine. (See 'Effect of beta blocker therapy' above.)
●Imaging techniques – The baseline (resting) echocardiogram obtained prior to stress testing should include a screening assessment of ventricular function, chamber sizes, left ventricular wall thicknesses, aortic root diameter, pericardial effusion, and gross valvular structure and function. The echocardiographic imaging protocol that is chosen for stress imaging should be tailored to the indication for the test. (See 'Imaging techniques' above.)
Use of ultrasound-enhancing agents – Clinical characteristics suggesting the need for ultrasound-enhancing agents during stress echocardiography include older age, male sex, smoking, presence of multiple coronary artery disease risk factors, higher body mass index, chronic lung disease, referral for dobutamine stress, history of coronary artery disease, and abnormal baseline electrocardiogram.
●Safety – There are no known adverse effects from diagnostic ultrasound at clinical imaging frequencies, so the addition of echocardiographic imaging to stress testing (either exercise or pharmacologic) does not alter the underlying risk of the stress test. As with any stress test, the patient's electrocardiogram, heart rate, and blood pressure should be monitored throughout the test and during recovery, and the patient should be frequently queried about the development of any symptoms. (See 'Safety' above and "Exercise ECG testing: Performing the test and interpreting the ECG results".)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Dr. Nelson Schiller, Dr. Xiushui Ren, and Dr. Bryan Ristow, who contributed to an earlier version of this topic review.
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