Stress Echocardiography

Stress echocardiography combines two dimensional echocardiography with a form of stress (exercise or pharmacological) to detect inducible myocardial ischaemia by wall motion abnormalities, and to assess valve disease, diastolic function and pulmonary pressure under stress.

Images are obtained at rest, during stress (or immediately after treadmill exercise) and in recovery, and compared side by side in a quad screen display for the same views (parasternal long axis and short axis, apical four chamber, two chamber and long axis).

Exercise stress (treadmill or supine or semi-supine bicycle) is preferred when the patient can exercise to 85% of the age predicted maximal heart rate (220 minus age).

Dobutamine stress is used if the patient cannot exercise adequately. The infusion starts at 5 or 10 micrograms each kilogram each minute and increases every 3 minutes to 40 micrograms each kilogram each minute. Atropine 0.25 to 1 mg is added to reach the target heart rate. Vasodilator stress (dipyridamole or adenosine) is used less often.

An ultrasound contrast agent is used when two or more contiguous segments are not seen well. The examination takes about 45 to 60 minutes, with no radiation.

Stress echocardiography is a first line functional test for the diagnosis and risk stratification of chronic coronary syndromes. Pooled sensitivity is about 80 to 85% and specificity 80 to 88% for angiographically significant coronary artery disease.

• Exercise: sensitivity 80 to 85%, specificity 84 to 86%.
• Dobutamine: sensitivity 80 to 85%, specificity 84 to 90%.

A normal stress echocardiogram predicts an annual cardiac event rate of under 1%. The diagnostic accuracy is lower in single vessel disease, mild stenosis and the circumflex territory.

Indications. Stable chest pain and intermediate pre-test probability of coronary artery disease. Known coronary artery disease with new or changed symptoms. Assessment of the functional significance of an intermediate stenosis on angiography. Risk assessment before non-cardiac surgery in patients with poor functional capacity and intermediate to high surgical risk.

Assessment of myocardial viability (low dose dobutamine, in left ventricular dysfunction before revascularisation: biphasic response). Evaluation of asymptomatic patients with prior revascularisation after a set interval where symptoms are uncertain.

Valve disease: low flow, low gradient aortic stenosis (dobutamine, to distinguish true severe from pseudo severe stenosis and assess contractile reserve), exercise assessment of asymptomatic severe aortic stenosis, dynamic mitral regurgitation, mitral stenosis (pulmonary pressure and gradient with exercise). Exercise induced pulmonary hypertension.

Dyspnoea of uncertain cause (diastolic stress test: E/e' ratio with exercise). Hypertrophic cardiomyopathy (provocable left ventricular outflow gradient). Following heart transplantation (surveillance of allograft vasculopathy). Not for acute coronary syndrome, high risk unstable angina, decompensated heart failure, or acute pulmonary embolism.

Contraindications and precautions. Absolute: acute myocardial infarction (within 2 days), unstable angina not stabilised, uncontrolled arrhythmia with haemodynamic compromise, symptomatic severe aortic stenosis (exercise), decompensated heart failure, acute pulmonary embolism or infarction, acute myocarditis, pericarditis or endocarditis, acute aortic dissection.

Specific for dobutamine: significant arrhythmias, severe hypertension (over 180/110 mmHg), left ventricular outflow obstruction in hypertrophic cardiomyopathy, and recent thromboembolic events. Atropine is avoided in narrow angle glaucoma and urinary retention.

Vasodilator agents are avoided in severe asthma and bronchospasm, second or third degree heart block, and severe hypotension, and caffeine and theophylline are stopped (24 hours). Beta blockers, nitrates and calcium channel blockers may be withdrawn for 24 to 48 hours (for diagnostic tests) if clinically safe, and are continued in patients on treatment for risk stratification.

Fasting for 3 hours is needed for dobutamine. Equipment for resuscitation, a defibrillator, and an experienced doctor and nurse must be present. Informed consent is obtained. Blood pressure, heart rate and a 12-lead electrocardiogram are monitored throughout.

Preparation and technique. Resting images are acquired, then stress is applied. During treadmill exercise (staged technique), post-exercise images are acquired within 60 to 90 seconds (in the first minute, as wall motion abnormalities resolve quickly), while bicycle exercise allows imaging at each stage and peak.

Dobutamine infusion continues in 3-minute stages with imaging at each stage. It is stopped for any of the following:

• target heart rate (85% of age predicted maximum);
• severe or extensive new wall motion abnormality;
• severe chest pain;
• ST depression of over 2 mm;
• significant arrhythmia;
• hypotension (fall in systolic blood pressure of over 20 mmHg);
• severe hypertension (over 220/120 mmHg);
• intolerable side effects.

Beta blocker (esmolol or metoprolol) is available to reverse the effects of dobutamine. The digital loops are compared at rest, low dose, peak and recovery. Segmental wall motion is scored in a 17-segment model (1 normal, 2 hypokinetic, 3 akinetic, 4 dyskinetic), with a wall motion score index (sum of scores divided by the number of segments).

Normal appearances. At rest all segments show normal wall thickening and inward motion. With stress, all segments become hyperdynamic: wall motion increases, the left ventricular cavity size falls (end systolic volume decreases by over 10 mL or the ejection fraction increases by at least 5 points), and the global ejection fraction rises.

Normal heart rate and blood pressure rise appropriately (systolic blood pressure rise over 20 mmHg with exercise). A normal study has no new wall motion abnormality, wall motion score index of 1.0 at peak, and no left ventricular dilatation. Normal exercise capacity is expressed in metabolic equivalents (7 or more) or minutes of exercise.

Right ventricular function increases under stress, and pulmonary pressure rises by under 20 mmHg in healthy people (peak tricuspid regurgitation velocity under 3.4 m each second).

Interpretation.

• Inducible ischaemia: new or worsening wall motion abnormality in one or more segments at stress compared with rest (normal to hypokinetic, akinetic or dyskinetic; hypokinetic to akinetic), with failure of the segments to become hyperdynamic.
• Other features of inducible ischaemia: reduced ejection fraction or left ventricular dilatation with stress. The abnormality localises to the coronary territory (left anterior descending: anterior wall, septum, apex; circumflex: lateral and posterior walls; right coronary artery: inferior wall and inferoseptal segments).
• Severity and extent: more segments, multiple territories, early onset (low dose or low workload), a wall motion score index over 1.7 at peak, left ventricular dilatation, drop in ejection fraction, and associated ST depression or hypotension indicate multi-vessel or left main disease and a high risk.
• Limited abnormality in one segment at peak stress suggests single vessel disease and low to moderate risk.
• Biphasic response (viability): improvement of an akinetic or hypokinetic segment at low dose dobutamine (5 to 10 micrograms each kilogram each minute), then worsening at high dose. This indicates viable, hibernating myocardium with a patent but critically stenosed artery, and predicts functional recovery after revascularisation.
• A sustained improvement indicates viable non-ischaemic myocardium. No response indicates scar (non-viable, wall thin under 6 mm and echogenic).
• Fixed wall motion abnormality: unchanged abnormality at rest and stress without improvement indicates prior infarction or scar.
• Non-ischaemic positive: dobutamine induced septal motion abnormality in left bundle branch block, paced rhythm or after cardiac surgery (abnormal septal motion with preserved thickening); hypertensive response and severe hypertension can cause false positives.
• Aortic stenosis: in low flow, low gradient stenosis with reduced ejection fraction, a rise in stroke volume of 20% or more (contractile reserve) with a peak velocity over 4 m each second and a mean gradient over 40 mmHg, and an unchanged valve area under 1.0 cm2, indicates true severe stenosis.
• A valve area that rises over 1.2 cm2 with minimal change in gradient indicates pseudo severe stenosis. Absent contractile reserve carries a higher operative risk.
• Mitral valve: exercise increases the mean gradient in mitral stenosis (over 15 mmHg), and the pulmonary systolic pressure over 60 mmHg indicates the need for intervention.
• Exercise induced increase in the severity of mitral regurgitation (an increase in the effective regurgitant orifice area of over 10 mm2) accompanies symptoms in functional mitral regurgitation.
• Pulmonary pressure: exercise induced pulmonary hypertension (tricuspid regurgitation velocity over 3.4 m each second or pulmonary systolic pressure over 50 mmHg at peak exercise) may indicate cause of exertional dyspnoea.
• Diastolic stress test: E/e' ratio over 15 at peak exercise (or an average E/e' over 14 at rest with peak tricuspid regurgitation velocity over 2.8 m each second) suggests elevated filling pressure and heart failure with preserved ejection fraction.
• Hypertrophic cardiomyopathy: provocable left ventricular outflow gradient over 50 mmHg with exercise indicates obstructive physiology (exercise is preferred to dobutamine).
• Coronary flow reserve: assessment of the left anterior descending artery flow by Doppler can be added; reserve under 2.0 suggests an abnormal microvascular or epicardial response.
• Global longitudinal strain at peak stress adds sensitivity in selected centres.

Critical values and findings needing immediate action.

• Extensive new wall motion abnormality at low workload or low dobutamine dose, left ventricular dilatation, a fall in ejection fraction or hypotension (suggesting left main or three vessel disease): stop the test. Give sublingual nitrate if blood pressure allows (and beta blocker for dobutamine effect), and arrange urgent coronary angiography.
• Ongoing ischaemic chest pain with ST elevation: stop, manage the event as an acute coronary syndrome, and emergency coronary angiography.
• Sustained ventricular tachycardia, ventricular fibrillation or symptomatic bradyarrhythmia: stop stress and start cardiac arrest management.
• Severe hypotension, syncope or a severe hypertensive response (over 250/120 mmHg): stop the test and treat.
• Symptomatic severe aortic stenosis unmasked during exercise (a fall in blood pressure, syncope, angina): stop and plan valve intervention.
• Bronchospasm with vasodilator stress: stop infusion and give aminophylline (theophylline antagonises adenosine) and bronchodilator.
• Acute pulmonary oedema during stress: stop and treat.
• High risk results (ischaemia in more than 3 segments, a wall motion score index over 1.7, ischaemia at low heart rate or low workload): angiography and revascularisation assessment.

Limitations and artefacts.

• Subjective interpretation depends heavily on observer experience (inter-observer agreement 80 to 90% in experts and lower in beginners), with a need of at least 100 to 300 supervised studies for competence.
• Contrast, digital side-by-side comparisons, and strain imaging reduce variability.
• Poor acoustic windows (obesity, lung disease) and rapid heart rates make interpretation harder; contrast is used when two or more segments are not seen.
• False negatives: inadequate stress (failure to reach 85% of the age predicted heart rate, beta blockers, chronotropic incompetence), single vessel disease, mild stenosis (under 70%) or collateralised disease.
• Further causes of false negatives: delayed post-exercise imaging (wall motion normalises within 1 to 2 minutes), balanced three vessel disease (no relative difference between segments), and poor views of the lateral wall.
• False positives: hypertensive response, left bundle branch block, microvascular disease, cardiomyopathy and left ventricular hypertrophy, and tethering of adjacent segments to an infarcted segment, or a basal inferior segment with poor views.
• The dobutamine stress test carries a risk of arrhythmias (ventricular ectopy in 10% and sustained ventricular tachycardia in about 1 in 1000), hypotension, and the complication rate is about 1 to 3 in each 1000 studies.
• Exercise stress has about 1 in 10 000 major complications.
• The study does not give coronary anatomy, and an abnormal result does not specify the culprit lesion; the result must be correlated with the clinical picture.
• Resting wall motion abnormalities complicate interpretation, and 17 segments must be compared.
• Women have lower accuracy with exercise ECG, but stress echocardiography performs similarly in both sexes.
• In the presence of anti-anginal drugs, sensitivity falls; the decision to stop them should consider the purpose of the test.
• Atropine causes dry mouth, blurred vision and urinary retention in older men.

Special groups.

• Women: stress echocardiography is preferred to exercise electrocardiography, with higher accuracy; microvascular disease is more common, and results may be false positive.
• Older adults and patients with limited mobility: dobutamine is used if exercise is not possible; carefully monitor blood pressure and arrhythmia.
• Patients with diabetes: higher prevalence of silent ischaemia and multi-vessel disease.
• Patients with left bundle branch block or a pacemaker: septal abnormality alone is not interpreted as ischaemia; the anterior wall and other segments are used.
• Patients with chronic kidney disease: no contrast nephropathy, which makes stress echocardiography a preferred test; risk is high.
• Pregnancy: exercise echocardiography at low intensity may be used for cardiac symptoms; dobutamine is avoided if possible.
• Children and congenital disease: exercise echocardiography assesses pulmonary pressure, ventricular function and outflow gradients.
• Patients after transplantation: dobutamine stress for allograft vasculopathy.
• Regions: ischaemic heart disease is increasing, and rheumatic valve disease, hypertensive heart disease, Chagas disease and cardiomyopathies are frequent, so exercise echocardiography for valve disease and pulmonary pressure is useful.
• The availability of nuclear stress imaging, CT coronary angiography and angiography is limited, and stress echocardiography is a practical, radiation free functional test.

Follow up tests. Invasive coronary angiography with fractional flow reserve for positive high risk studies or intermediate lesions, CT coronary angiography (rule out disease with a negative stress test and a persistent suspicion), myocardial perfusion imaging, stress cardiac MR, cardiac MR with late gadolinium enhancement for viability and cardiomyopathy,

resting echocardiography for valve severity, resting and ambulatory electrocardiogram, lipid profile, glucose or HbA1c, troponin if the test provokes chest pain, medical therapy optimisation and risk factor control, and referral to cardiology or cardiac surgery.