Stress Echocardiography: Protocols and Interpretation

Definition and Pathophysiology

Stress echocardiography is a functional cardiac imaging technique used primarily to identify inducible myocardial ischaemia and to estimate prognosis in patients with suspected or established coronary artery disease (CAD). It combines echocardiographic assessment of left ventricular (LV) structure and function with exercise or pharmacological stress.

The physiological basis is an imbalance between myocardial oxygen demand and coronary blood supply. Stress increases myocardial oxygen requirements, principally through increased heart rate and contractility. In the presence of a flow-limiting coronary stenosis, supply cannot increase adequately. Ischaemia begins in the subendocardium, which contributes substantially to systolic wall thickening; consequently, inducible regional systolic wall-thickening abnormalities may develop in the myocardial territory supplied by the narrowed artery.

The principal diagnostic endpoint is a new or worsening regional wall-motion abnormality (RWMA) during stress. A fixed abnormality that remains unchanged with stress generally indicates previous infarction. Extensive ischaemia may produce a reduction in global LVEF and transient LV cavity dilatation during stress.

Stress echocardiography can also provide information beyond regional wall motion, including:

• Global and regional LV systolic function

• LV contractile reserve

• Valve function and stress-related haemodynamic changes

• Diastolic function

• Pulmonary hypertension

• Coronary flow velocity reserve (CFVR)

• Pulmonary congestion detected by B-lines on lung ultrasound

• Myocardial perfusion when ultrasound contrast agents are used

The technique is particularly useful because it is rapid, can be performed at the bedside, avoids ionizing radiation, and can be repeated. It is, however, operator-dependent and its diagnostic performance is influenced by image quality and local expertise.

Clinical Presentation and Indications

Stress echocardiography is used in patients with suspected or known CAD when the clinical question concerns the presence, extent, severity, or location of inducible ischaemia. It is particularly appropriate when:

• The pre-test likelihood of obstructive CAD is moderate or high, generally greater than 15% and less than 85%

• Baseline ECG abnormalities make exercise ECG interpretation unreliable

• The patient cannot perform an adequate treadmill test but can undergo pharmacological stress

• Local expertise and adequate echocardiographic facilities are available

• Risk stratification is required in established or suspected CAD

• The extent or location of ischaemia needs to be defined before revascularization

• Residual ischaemia must be assessed after initiation of medical treatment

• LV function requires evaluation in the setting of suspected ischaemia or previous infarction

• Dyspnoea requires assessment of dynamic LV function, valve disease, pulmonary pressure, or haemodynamics

Stress imaging is not recommended in patients undergoing urgent non-cardiac surgery or those with an unstable clinical condition. In patients with suspected or established non-ST-segment elevation acute coronary syndrome, stress testing may be considered after at least 24 hours of stabilization, provided that active ischaemia and haemodynamic or electrical instability are absent.

A resting transthoracic echocardiogram is useful before stress testing when previous echocardiographic information is unavailable. It may identify significant valve disease, cardiomyopathy, hypertrophy, LV dysfunction, or other pathology that could affect the safety or interpretation of the examination.

Evaluation and Physical Examination

Before stress echocardiography, clinical assessment should establish:

• The nature and stability of symptoms

• Exercise capacity

• The presence of active chest pain or other evidence of ongoing ischaemia

• Symptoms suggesting haemodynamic compromise, such as near-syncope or poor perfusion

• Known arrhythmia or electrical instability

• The presence of severe hypertension or hypotension

• Conditions that may impair exercise performance or image acquisition

The pre-test likelihood of CAD should be considered when interpreting the result. False-positive findings are more consequential when the likelihood of disease is low, whereas a negative examination is most useful when the test is technically adequate and the target stress level has been reached.

A brief baseline echocardiographic survey should assess the cardiac chambers, valves, aortic root, LV size, wall thickness, systolic function, and pre-existing regional wall motion abnormalities. This survey helps identify contraindications or important structural disease and provides a reference for comparison with stress images.

During the test, symptoms, heart rate, rhythm, blood pressure, ECG, and echocardiographic findings are monitored. Stress is generally continued until exercise-limiting symptoms occur or the target heart rate is reached.

Diagnostic Modalities and Protocols

Exercise Stress Echocardiography

Exercise may be performed on a treadmill or stationary bicycle.

Treadmill protocol

The standard treadmill approach uses the Bruce protocol. Echocardiographic images are obtained:

• At rest, before exercise

• During or immediately after peak exercise

• During early recovery, as close to peak stress as possible

The endpoint is usually exercise-limiting symptoms or completion of the protocol, with a target of at least 85% of the age-predicted maximal heart rate.

Bicycle protocol

With an upright or supine bicycle, workload is increased by 25 W every 2 or 3 minutes. The ability to image continuously permits acquisition at peak stress and assessment of the response throughout increasing workloads.

Exercise stress testing is terminated for absolute indications such as:

• Moderate-to-severe angina

• ST-segment elevation

• Sustained ventricular tachycardia

• Near-syncope or evidence of poor perfusion

• A fall in systolic blood pressure of more than 10 mmHg from baseline when accompanied by another sign of ischaemia

• The patient’s request to stop because of intolerable symptoms

Relative indications include a hypertensive response, defined in the source material as systolic blood pressure greater than 220 mmHg and/or diastolic blood pressure greater than 120 mmHg.

Dobutamine Stress Echocardiography

Dobutamine is used when the patient cannot exercise adequately. It increases myocardial oxygen demand through increased heart rate and myocardial contractility. A graded infusion may be administered up to 40 µg/kg/min. Atropine may be added if necessary to achieve the target heart rate.

Dobutamine stress is less physiological than exercise but generally produces a smaller increase in blood pressure and allows imaging precisely at peak pharmacological stress. It is particularly useful when baseline conduction abnormalities, such as left bundle branch block or pacing-related septal dyssynchrony, make exercise-induced septal motion difficult to interpret.

Vasodilator Stress

Vasodilator stress may be produced with adenosine, dipyridamole, or regadenoson. Atropine may be combined with vasodilator stress to increase heart rate when necessary.

When vasodilator stress echocardiography is not combined with myocardial contrast perfusion, the test remains dependent on stress-induced wall-motion abnormalities. This differs from nuclear vasodilator testing, which evaluates flow redistribution.

Vasodilator stress is less widely used than exercise or dobutamine stress echocardiography.

Pacing Stress

Pacing stress can be performed through a pre-existing permanent pacemaker or a transoesophageal pacing catheter. It is possible but less commonly used.

Image Acquisition

The standard examination acquires LV images from:

• Parasternal long-axis views

• Parasternal short-axis views

• Apical windows

Images are ECG-gated and displayed side by side for comparison between rest and stress. Assessment is performed using the standard 17-segment model. Each segment is graded as:

• Normal

• Hyperkinetic

• Hypokinetic

• Akinetic

• Dyskinetic

The resting study evaluates LV size, wall thickness, global systolic function, and baseline regional abnormalities. During stress, a normal ventricle becomes hypercontractile and its cavity becomes smaller.

Use of Ultrasound Contrast Agents

Ultrasound contrast agents consist of microbubbles that pass through the pulmonary microcirculation and opacify the left-sided cardiac chambers. They improve endocardial border definition and therefore the accuracy of regional wall-motion assessment.

Contrast should be used when two or more contiguous myocardial segments are not visualized. It is particularly valuable in patients with obesity, chronic obstructive pulmonary disease, or poor baseline acoustic windows. If inadequate endocardial visualization is already evident at baseline, contrast should be used to ensure that all segments can be assessed during stress.

Contrast-enhanced imaging can also assess myocardial perfusion simultaneously with wall motion. This may improve detection of single-vessel and microvascular disease and may refine risk stratification beyond wall-motion analysis alone. Rare anaphylactic reactions have been reported, although ultrasound contrast agents are generally considered safe.

Additional Stress Echocardiographic Parameters

Coronary flow velocity reserve

CFVR can be measured, most reliably in the left anterior descending artery, using Doppler transthoracic echocardiography at rest and during vasodilator stress with adenosine or dipyridamole. A value below approximately 1.9–2.0 in the LAD territory correlates with angiographic stenosis greater than 70% and predicts future adverse cardiac events.

Reduced CFVR may provide information about coronary microcirculatory dysfunction beyond that obtained from regional wall motion.

Lung ultrasound

B-lines may be counted across several chest segments to identify pulmonary congestion during stress. Stress-related pulmonary congestion, particularly when accompanied by reduced CFVR, abnormal LV contractile reserve, or inducible wall-motion abnormalities, may provide additional prognostic information.

Carotid ultrasound

Carotid ultrasound may be performed during the same session to assess extracoronary atherosclerosis. It does not confirm chronic coronary syndrome itself but may add prognostic information beyond the assessment of myocardial ischaemia.

Interpretation of Findings

Normal Response

A normal resting study demonstrates:

• Normal LV size

• Normal wall thickness

• LVEF ≥50%

• No focal wall-motion abnormalities

• A wall-motion score index of 1.0

With adequate stress, the normal ventricle becomes hypercontractile and the LV cavity decreases in size.

A normal stress echocardiogram in a patient who has achieved good exercise capacity or the target heart rate is associated with a very low subsequent cardiac event rate. The source material reports a risk below 1% per year after a normal exercise stress echocardiogram and below 2% per year after a normal pharmacological study.

Inducible Regional Wall-Motion Abnormality

A new or worsening abnormality in one or more segments indicates inducible ischaemia in the distribution of the supplying coronary artery. The abnormality may appear as reduced wall thickening, hypokinesis, akinesis, or dyskinesis.

The number and distribution of affected segments are clinically important. Extensive ischaemia, particularly involving four or more LV segments, is associated with substantially increased risk of cardiac death or myocardial infarction. A stress-induced failure of LVEF to increase, or a fall in LVEF, also indicates a higher-risk response.

Fixed Wall-Motion Abnormality

A resting abnormality that remains unchanged during stress is consistent with previous infarction. Interpretation is more difficult when a previous infarct is present and no earlier study is available, because it may be difficult to distinguish pre-existing abnormalities from new ischaemia.

Extensive Ischaemia and Transient LV Dilatation

Large ischaemic territories, such as those associated with left main or multivessel disease, may result in:

• Diminished global LVEF during stress

• Stress-induced LV chamber dilatation

• Multiple new regional abnormalities

• A failure of the ventricle to become hypercontractile

Transient ischaemic LV dilatation is therefore a marker of extensive myocardial ischaemia.

Myocardial Perfusion

When contrast agents are used, myocardial perfusion can be assessed in addition to regional wall motion. The combination may improve sensitivity for single-vessel and microvascular disease and may provide risk information beyond RWMA alone.

Stress echocardiography based solely on wall motion may underestimate ischaemia in microvascular disease, particularly in patients with angina or ischaemia and non-obstructive coronary arteries, because microvascular abnormalities may not produce subendocardial dysfunction sufficient to cause a visible RWMA.

Diagnostic Performance

Stress echocardiography has diagnostic accuracy comparable to stress radionuclide perfusion imaging and is superior to exercise ECG alone for detecting CAD.

Reported diagnostic performance for significant CAD, generally defined as more than 50% coronary artery stenosis on angiography, includes:

Other reported ranges place sensitivity at approximately 85–90% and specificity at approximately 80–95%, depending on the population, protocol, image quality, and reference standard.

Adequate images can generally be obtained in more than 85% of patients, and harmonic imaging may provide diagnostic-quality images in at least 90% of patients. Performance is best in experienced laboratories.

Stress echocardiography may have higher specificity than nuclear imaging for left main and three-vessel CAD. It is less expensive than nuclear perfusion imaging, although it is more expensive and less widely available than exercise ECG.

Electrocardiography and Stress ECG

A resting 12-lead ECG remains an essential component of the initial assessment of chest pain and suspected chronic coronary syndrome. It may be normal despite disease, but can show:

• Pathological Q or R waves indicating previous myocardial infarction

• ST-segment or T-wave abnormalities

• Left bundle branch block

• Abnormal atrioventricular conduction

• Atrial fibrillation

Dynamic ST-segment changes during ongoing angina may identify transient myocardial ischaemia. Transient ST-segment elevation or depression with U-wave changes during rest pain should raise suspicion of vasospastic angina.

Exercise ECG is less useful when baseline abnormalities preclude interpretation, including significant resting ST-segment depression, left bundle branch block, ventricular pacing, pre-excitation, conduction disturbances, ventricular hypertrophy, or repolarization abnormalities. In these situations, stress imaging is preferred.

The standard exercise ECG is considered positive when there is flat or downsloping ST-segment depression exceeding 0.1 mV below baseline and lasting longer than 0.08 seconds. A test that fails to reach 85% of the age-predicted maximal heart rate is considered nondiagnostic. Exercise ECG has an overall sensitivity of approximately 75%, so a negative result does not exclude CAD.

Ambulatory ECG monitoring can be considered in selected patients with episodic symptoms unrelated to physical activity and may reveal silent ischaemia. However, strategies directed specifically at ambulatory ECG evidence of silent ischaemia have not demonstrated clear survival benefit.

Biomarkers and Laboratory Findings

Laboratory blood testing may identify contributors to ischaemia, cardiovascular risk factors, and prognostic comorbidity. Relevant assessments include:

• Blood testing for severe anaemia

• Thyroid assessment when hyperthyroidism is suspected

• Lipid measurement

• Fasting glucose

• Glycated haemoglobin

• Oral glucose tolerance testing when fasting glucose and HbA1c are inconclusive

• Renal function

• Markers of inflammation

Cardiac troponin and high-sensitivity cardiac troponin are important in the evaluation of suspected acute coronary syndrome, particularly when deciding whether non-invasive testing such as coronary CT angiography or stress imaging is appropriate. The source material does not provide a stress-echocardiography-specific biomarker threshold or dosing strategy.

Safety and Contraindications

The risks of exercise and dobutamine stress echocardiography are low. The most frequent serious complications are:

• Acute myocardial infarction

• Ventricular tachycardia

• Ventricular fibrillation

Reported life-threatening event rates are approximately 1 per 1000 examinations overall, with rates of 0.015% for exercise and 0.18% for dobutamine studies.

The study should be performed with appropriate monitoring and the capacity to respond to serious arrhythmia or haemodynamic deterioration. Patient symptoms and requests must be respected as valid reasons to terminate the test.

Exercise stress testing is contraindicated or inappropriate in settings including:

• Rest angina within the preceding 48 hours

• Unstable rhythm

• Severe aortic stenosis

• Acute myocarditis

• Uncontrolled heart failure

• Severe pulmonary hypertension

• Active infective endocarditis

• Unstable clinical conditions or urgent surgery when stress imaging is being considered for peri-operative risk assessment

Limitations and Sources of Error

False-negative studies

Important causes of a false-negative result include:

• Failure to achieve an adequate stress level

• Limited exercise capacity

• Beta-blocker therapy

• Poor image quality

• A small ischaemic territory

• Single-vessel disease

• Left circumflex disease

• Marked LV hypertrophy

• A hyperdynamic state

• Microvascular disease without adequate subendocardial dysfunction

Ischaemia involving less than approximately 10% of the myocardium may not generate a detectable regional wall-motion abnormality. Mild atherosclerotic disease and some single-vessel lesions may therefore be missed.

False-positive studies

False-positive results are more likely when the pre-test probability of CAD is low. Other contributors include:

• Pre-existing wall-motion abnormalities

• Abnormal septal motion

• Left bundle branch block

• Ventricular pacing

• Postoperative septal dyssynchrony

• Severe hypertension

• Hypertrophic cardiomyopathy

• Other cardiomyopathies with impaired microvascular perfusion reserve

In patients with left bundle branch block or pacing-related dyssynchrony, exercise may exaggerate septal motion and impair interpretation. Dobutamine stress is recommended in this setting, and emphasis on wall thickening rather than endocardial excursion may be helpful.

Image quality

Obesity and chronic obstructive pulmonary disease are important causes of poor acoustic windows. Poor endocardial definition can be mitigated by:

• Ultrasound contrast agents

• Harmonic imaging

• Three-dimensional imaging

• Strain-rate echocardiography

Operator acquisition and interpretation skills also affect reproducibility.

Interpretation in prior infarction

When a previous infarct is present, distinguishing fixed abnormalities from new ischaemia may be difficult without a prior echocardiogram. Side-by-side comparison with earlier images is therefore valuable.

Guideline Recommendations

The source material supports the following recommendations:

Stress imaging is appropriate for risk assessment in patients with clinical risk factors and poor functional capacity when the clinical condition is stable. The choice among stress imaging modalities should reflect local expertise, test availability, patient characteristics, and image quality.

In patients with suspected non-ST-segment elevation acute coronary syndrome who have non-elevated or uncertain high-sensitivity troponin, no ischaemic ECG changes, and no recurrent ischaemic symptoms, coronary CT angiography or non-invasive stress imaging may be considered as part of the initial evaluation. High-risk stress findings—such as severe ischaemia, hypotension, ventricular tachyarrhythmia, or new or worsening LV dysfunction—should prompt rapid consideration of coronary angiography and revascularization.

Prognosis and Follow-up

Stress echocardiography provides prognostic information beyond the resting echocardiogram. Prognosis is influenced by:

• Exercise capacity

• Achievement of the target heart rate

• Extent of resting wall-motion abnormalities

• Extent of inducible ischaemia

• Number of affected LV segments

• Stress-induced change in LVEF

• Development of transient LV dilatation

• Stress-induced pulmonary congestion

• CFVR

• Associated valve disease and pulmonary hypertension

A normal, technically adequate exercise stress echocardiogram with good exercise capacity is associated with a very low risk of future cardiac events, reported as less than 1% per person-year. Normal pharmacological studies also identify a low-risk group, although the reported event rate is somewhat higher, at less than 2% per year.

Conversely, an increase in wall-motion score index, involvement of four or more LV segments, or failure of LVEF to increase—or a decrease in LVEF—with stress is associated with at least a fourfold higher risk of cardiac death or myocardial infarction.

Follow-up should be determined by symptoms, test findings, LV function, the extent of inducible ischaemia, and the need for further anatomical assessment or revascularization. The source material does not specify routine repeat-testing intervals.