Erp 18 0068

R P Steeds et
al. Stress echo in coronary 6:2 G17–G33

disease
GUIDELINES AND RECOMMENDATIONS
Stress echocardiography in coronary artery

disease: a practical guideline from the British
Society of Echocardiography
Richard P Steeds1,*, Richard Wheeler2,*, Sanjeev Bhattacharyya3, Joseph Reiken4, Petros Nihoyannopoulos5,*,

Roxy Senior6,*, Mark J Monaghan4,* and Vishal Sharma7,*,†
1Department of Cardiology, Institute of Cardiovascular Science, University Hospital Birmingham, Birmingham, UK
2Department of Cardiology, University Hospital of Wales, Cardiff, UK
3Department of Cardiology, St Bartholomew’s Hospital, London, UK
4Department of Cardiology, Kings College Hospital, London, UK
5Department of Cardiology, National Heart Lung Institute, Hammersmith Hospital, London, UK
6Department of Cardiology, Royal Brompton Hospital, London, UK
7Department of Cardiology, Royal Liverpool and Broadgreen University Hospital, Liverpool, UK
Correspondence should be addressed to R P Steeds: rick.steeds@uhb.nhs.uk
*R P Steeds, R Wheeler, P Nihoyannopoulos, R Senior, M J Monaghan and V Sharma are members of the editorial board of Echo Research and Practice.
They were not involved in the review or editorial process for this paper, on which they are listed as authors
†(V Sharma is the Guidelines Chair)
Abstract
Stress echocardiography is an established technique for assessing coronary artery disease. Key Words
It has primarily been used for the diagnosis and assessment of patients presenting with ff stress echocardiography
chest pain in whom there is an intermediate probability of coronary artery disease. In ff coronary artery disease
addition, it is used for risk stratification and to guide revascularisation in patients with ff exercise
known ischaemic heart disease. Although cardiac computed tomography has recently been ff pharmacological stress
recommended in the United Kingdom as the first-line investigation in patients presenting ff myocardial perfusion
for the first time with atypical or typical angina, stress echocardiography continues to ff 3D echocardiography
have an important role in the assessment of patients with lesions of uncertain functional ff left ventricular
significance and patients with known ischaemic heart disease who represent with chest opacification contrast
pain. In this guideline from the British Society of Echocardiography, the indications and
recommended protocols are outlined for the assessment of ischaemic heart disease by
stress echocardiography.
Introduction
Stress echocardiography (SE) is a well-established non- the number of studies that should be performed per year
invasive technique that is most often used in the to maintain competency by individual operators (1).
assessment of coronary artery disease (CAD). A recent SE requires a high level of expertise to achieve accurate
survey by Bhattacharyya et al. highlights important themes and reproducible results, and it is recognised that
that relate to quality and consistency in performance, performing the technique requires additional training
including selection of the optimal method for stress and beyond proficiency in transthoracic echocardiography.
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R P Steeds et al. Stress echo in coronary 6:2 G18
disease
This is reflected in the recent development of a specific abnormalities on the electrocardiogram and finally
accreditation process for people undertaking SE (2). symptoms of angina (4). Although the concept of a ‘cascade’
Furthermore, echocardiography services that provide has recently been called into question, the advantage of
SE are scrutinised during departmental accreditation, SE is that it can detect each one of the abnormalities that
which requires standardised approaches to testing that make up the ischaemic ‘constellation’, whether that be
is known to improve both quality of image acquisition abnormal perfusion, diastolic dysfunction, regional wall
and reporting (3). In the light of the need for a systematic motion abnormalities, ECG changes or symptoms (4). It
approach to SE, this document sets out practical guidance is this multiparametric capability that makes exercise SE a
for the performance of SE in CAD. more attractive test to use with greater accuracy than the
The aim of this document is to provide a framework traditional exercise ECG (5, 6). Finally, contrast-enhanced
for the practical aspects of performing and reporting SE SE has a good agreement with invasive fractional flow
for diagnosis and prognosis of CAD. The focus of this reserve when used with second generation contrast agents
guideline is on 2D imaging with the assessment of changes in predicting reversible myocardial ischaemia in patients
in myocardial thickening as the marker of ischaemia. with intermediate lesions (7). This increases the utility
There is an increasing evidence base for advanced imaging of SE as a ‘gatekeeper’ to reduce unnecessary invasive
techniques in SE including myocardial perfusion, coronary coronary procedures.
flow, strain and 3D SE, which will also be discussed,
although these are not all yet in widespread clinical
practice. The role of SE in non-ischaemic indications will Indications for SE in CAD
be covered in future guidelines.
It is recognised that different stress modalities 1. The diagnosis of stable chest pain suspicious of angina
may be applicable in an individual patient and that in patients with intermediate probability of CAD. The
the choice of stress modality may depend on clinician European guidelines for the management of stable
preference, availability of equipment and experience. In CAD indicate that stress imaging is the preferred
some patients, there may be technical or clinical reasons modality for all patients with a pre-test probability
that make SE difficult or even impossible to perform. of 15–85% if the expertise is available (8). While the
Indeed, patients will receive the greatest clinical benefit National Institute for Health and Care Excellence
at the lowest risk when SE departments have access to a Clinical Guideline 95 (2010) previously recommended
wide range of other functional tests, for example, stress functional testing (including SE) for patients with
cardiovascular magnetic resonance (CMR) imaging or intermediate probability (30–60%) of CAD, this was
nuclear perfusion techniques. One of the key aims of rescinded in an update in 2016 in favour of CT coronary
this document is to explain the practical and logistical angiography (CTCA) as the first-line imaging modality
difficulties that commonly arise in performing SE so that in patients presenting with recent-onset typical or
readers will have a useful and applicable template to atypical angina (9). Although there are data to show
disseminate amongst their staff. equivalent outcomes from a functional compared to an
angiographic approach (10) and there continues to be
support for calculation of pre-test likelihood to select
Pathophysiology of ischaemia an imaging test (11), this is current NICE guidance.
2. The diagnosis of CAD in suspected acute coronary
Myocardial ischaemia results from a mismatch between syndrome with non-diagnostic ECG and negative
myocardial oxygen consumption and oxygen delivery biomarkers of low-risk ACS (12).
to the myocardium. Normally, in the setting of a 3. The assessment of the functional significance of CAD
fixed stenosis within the coronary arteries, the supply of intermediate severity on CTCA or invasive coronary
of oxygen to the myocardium is enough at rest but angiography.
results in ischaemia at times of increasing workload. 4. The diagnosis of chest pain in patients with known CAD
This is responsible for the typical presentation of (including prior percutaneous coronary intervention
exertional angina. The classical concept of ischaemia and coronary artery by-pass grafting) who present with
is that the effects alter myocardial physiology in such symptoms of angina.
a way to produce a ‘cascade’ of changes to coronary 5. The evaluation of a cardiac aetiology of dyspnoea.
perfusion, diastolic dysfunction, systolic dysfunction, Dyspnoea is defined as difficult, laboured or
disease
uncomfortable breathing, which is a non-specific on activation of a cardiac arrest call. In addition, where
symptom that can reflect several underlying diseases, SE is performed by non-medical health professionals,
including lack of physical fitness, obesity, lung a named clinician trained in SE should be available to
disease, heart failure and ischaemia. The prevalence answer queries if required.
rate of angina increases with increasing severity of
breathlessness (13), and approximately a third of
patients referred for stress testing will have a positive Patient information leaflets
test for ischaemia (14). Predictors for a positive test
include male gender, history of CAD and abnormal SE is a low-risk, but not risk-free procedure and formal
wall motion on resting echocardiography (15). written consent should be obtained (18). Contemporary
6. The assessment of prognosis in patients with known practice is for this to be obtained before the day of
CAD, e.g. risk stratification post myocardial infarction. the test with the help of a written information leaflet,
7. Stratification of risk prior to non-cardiac surgery. for patients to understand the risk involved and make
SE should be used in well-defined groups where the an informed decision whether to proceed in their
finding of an abnormal stress test will significantly own time. For example, this could be done at the time
alter the surgical and perioperative management (16). when the SE is booked or by sending out the patient
These patients will be undergoing intermediate or information leaflet sent out with the appointment, so
high-risk surgery but with poor functional capacity in that the patient has time to consider the issues involved.
addition to the presence of certain risk factors – angina, Consent before the day of the test may not always be
previous myocardial infarction, renal failure, previous practical or in the patients’ interest, for example, when
stroke or insulin requiring diabetes. SE is done on request immediately within the context
of a rapid access chest pain unit. In these circumstances,
the patient should be given as much opportunity to read
Staffing requirements for safe performance and consider the information supplied before consent
of SE is obtained. Examples of patient information leaflets
relating to exercise and pharmacological stress are
A minimum of two individuals are required for every case. available (www.bsecho.org) and should be sent with the
The first operator usually performs the echocardiography appointment letter or notification. These can be modified
and can be any health professional with the appropriate according to local practice. Patient information leaflets
skill and experience (17). The health professional should are also important to outline the preparations to be made
not only be fully trained in transthoracic echocardiography by the patient prior to attending for the test. This will
(BSE TTE Proficiency Accreditation or equivalent), but include advice on which medications to stop prior to the
it is desirable for practitioners to undergo additional test, whether they need to fast and to clarify transport
training in the acquisition of SE images, such as the BSE arrangements after the test.
Accreditation in SE or international equivalent (2). The
second operator oversees haemodynamic monitoring,
ECG acquisition and drug administration if required. This Equipment requirements
person can be a clinician, nurse, healthcare scientist or
cardiac physiologist. This will depend on whether exercise or pharmacological
Departments need to establish which operator is in stress is being used. It is expected that the designated
overall charge of the test in terms of taking responsibility room is fit for purpose and there are criteria for suitability
for decision making and maintaining patient safety. within BSE Departmental Accreditation requirements
This division of labour will vary between departments (www.bsecho.org). Space should be available during
depending on the personnel involved in SE. At least one scanning that will allow the immediate co-location of
of these individuals must have advanced life support a crash trolley or defibrillator next to the patient in the
competency. The second will have a minimum of event of an arrhythmia requiring shock. Space should
intermediate life support competency. In units where also be adequate to run an arrest scenario with the
SE is performed by non-medical health professionals full cardiac arrest team present, as well as standard
(e.g. cardiac physiologists, nurses), it is expected that a monitoring and infusion equipment necessary to perform
crash (resuscitation) team will be available immediately the test (Table 1).
disease
Table 1 Equipment requirements for stress promoting arrhythmia. Under such circumstances the
echocardiography. clinician in charge should make a judgement, following
discussion with the clinician referring the patient for the
All cases
1. Digital echocardiography machine with appropriate SE test and if necessary, consider an alternative stress test for
analysis package. example vasodilator stress with myocardial contrast SE
2. Automated blood pressure machine with manual back (20), nuclear imaging or CMR.
up if needed.
3. Continuous ECG monitoring. Baseline blood pressure, heart rate and 12-lead ECG
4. Fully equipped resuscitation trolley with defibrillator. are obtained. Continuous 12-lead ECG monitoring may
5. Oxygen supply and suction. be performed during SE but the positions of the chest leads
6. Availability of transpulmonary contrast when echo
window is suboptimal. often need to be lower than usual to avoid interfering with
7. Drugs to manage severe allergic reactions and the acoustic window. Moreover, whether using exercise or
anaphylactic shock. To include – IV/IM adrenaline 1:1000, dobutamine, the ECG data do not add to the prognostic
IV chlorpheniramine, IV hydrocortisone, salbutamol
nebuliser – in dose and preparation to meet current value of the SE result and there are no consistent data
Resuscitation UK guidelines to indicate this improves accuracy (21, 22). Although
8. Cannulation equipment the performance of 12-lead ECG monitoring during
Specific to exercise stress echo
1. Exercise treadmill and/or semi-supine bike with protocol
SE is not mandated, ECG monitoring for arrhythmia is
options. necessary. The ECG leads attached to the echo machine
Specific to dobutamine stress echo must achieve a very clear tracing of the QRS complexes
1. Dobutamine infusion and administration pump.
because well-demarcated imaging loops are critical at high
2. IV Atropine – up to 1.2 mg.
3. IV beta-blockers e.g. metoprolol. heart rates, specifically for acquisition of correctly timed
systolic images. One option can be to slave the ECG trace
from the exercise machine if this is the stressor used. Left
Setup bundle branch block and pacing present challenges in
SE due to the septal dyssynchrony seen during baseline
Patient identification is established with three key imaging and is often accentuated at peak stress, so note
identifiers – usually name, hospital or NHS number and must be made in such patients in the report (23).
date of birth. The basic history should be reassessed to Intravenous access is established for all cases of
confirm the indication and to ensure there has been no pharmacological stress and in patients undergoing
change in clinical status which may contraindicate the test exercise SE in whom the images are suboptimal to
for example crescendo angina. A list of patient medication allow administration of transpulmonary contrast (left
should be available at the time of referral specifically ventricular opacification (LVO)). A suboptimal window
mentioning rate slowing drugs. The sensitivity of detecting is typically defined as difficulty in seeing two or more
ischaemia is increased by achieving adequate workload and contiguous segments in any of the available echo windows
therefore in most patients it is sensible to stop rate slowing (24). There should be a preference for use of LVO when
drugs 48 h prior to the test (19). In some patients, however, there is a concern that image quality may not be optimal
it may be necessary to continue all drugs for example in at peak stress, particularly when exercise is used as the
problematic hypertension or when assessing ischaemia stressor due to the likelihood of translational motion with
in patients with known CAD on medical therapy, making respiration at peak (see current international guidelines
note in the report whether this would affect the sensitivity on use of LVO) (20, 24). When a patient only has one
of the SE. In other patients, for example, in assessment arm that is available for IV access and monitoring, for
of risk of cardiovascular complications during non-cardiac example, haemodialysis fistula or lymphoedema, it may
surgery, it may be preferable not to stop drugs such as be necessary to measure the blood pressure on the same
B-blockers when these would be continued through the side. During pharmacological stress, it may be easier to
proposed operation. Consideration should be given in make manual blood pressure recordings as this tends
patients who have a history of arrhythmia for example to reduce the time of cuff inflation which temporarily
paroxysmal atrial fibrillation or ventricular tachycardia. occludes the infusion.
Discontinuation of regular anti-arrhythmic medication Prior to acquisition of SE images, a baseline
may be problematic and, in some cases, potentially echocardiogram should be performed to assess ventricular
hazardous, particularly if the patient is undergoing function, chamber sizes, wall thickness, aortic root and
a dobutamine stress study, due to the potential for valves unless this assessment has already been performed
disease
within 6 months. Baseline assessment should always thickening and/or wall motion. In dobutamine SE,
consider pathology which may not have been previously administration of IV B-Blockers in recovery rapidly lowers
identified but which may be very important in the context the heart rate and acquisition of images in early recovery
of the patient’s presenting symptoms. Two examples may improve the sensitivity of detecting regional changes
include: in myocardial thickening and/or wall motion (26).
1. Significant valve disease. If this is a new diagnosis, then

further discussion with the referring clinician may be Technique
necessary to decide on the safety and indication for the
stress test, for example severe aortic stenosis. Exercise is the preferred method of stress for the assessment
2. Flow acceleration in the LVOT may occur at baseline of CAD whenever possible, as the duration of exercise is a
in association with basal septal hypertrophy, usually key marker of prognosis. Moreover, exercise SE has a better
in the elderly. This may provide the substrate for safety profile compared to pharmacological SE, although
systolic anterior motion of the mitral valve (SAM) contraindications remain (Table 2). Pharmacological
with increasing heart rates which then exacerbates the stress with dobutamine is the common alternative used
degree of LVOT obstruction. The presence of a resting in patients who are unable to exercise or when the
LVOT gradient is not an absolute contraindication to assessment of contractile reserve and viability is the key
a SE study, however, increasing LVOT gradients may clinical question. Although exercise SE is recommended,
lead to hypotension or exacerbation of ischaemia and it is recognised that pharmacological stress minimises
therefore may be a reason for terminating the test factors such as patient motion, hyperventilation and
earlier than planned. Dobutamine infusions will often chest wall movement that can degrade image quality
induce this mechanism of LVOT obstruction at higher and make it much harder to acquire the same images at
doses which are much less common with physiological each stage. Hence, a lower threshold for the use of LVO is
exercise. This needs to be considered when selecting recommended (20).
the most appropriate method of stress.
Exercise stress
There are two main techniques to achieve exercise stress

Image acquisition – (a) semi-supine bicycle exercise or (b) a conventional
treadmill test. Semi-supine bicycle is more sensitive than
The core images to obtain are at baseline and at peak stress
post-treadmill exercise (27). There are limited data to
but during both bicycle exercise and dobutamine stress,
indicate similar sensitivity of SE during treadmill exercise
it is usual to obtain additional images through the test. It
to semi-supine bicycle but this is technically difficult (28).
is important for the machine to have a preset protocol to
The aim of exercise SE is to achieve both the maximum
minimise acquisition time and to guarantee quad review.
target heart rate which is calculated (220 – age), although
Standard images at each stage as a minimum include:
sensitivity of the test does not appear to fall providing
1. Apical four chamber imaging is performed above 85% of the maximum heart
2. Apical two chamber rate and maximal exercise. If a patient fails to achieve
3. Parasternal long axis and/or apical three chamber a minimum of 85% maximum heart rate, the rate of
4. Parasternal short axis
The precise number of stages recorded varies depending Table 2 Contraindications to exercise stress
on the indication and the method of stress but when echocardiography.
reporting, it is important to indicate the heart rate and
1. Acute myocardial infarction (within 2 days)
stage at which ischaemia first occurs. The addition of
2. Unstable angina not previously stabilised by medical
intermediate stages improves sensitivity and assessment of therapy
functional significance of CAD (25). It is essential to record 3. Uncontrolled cardiac arrhythmias causing symptoms or
haemodynamic compromise
the same views when recording multiple stages and it is
4. Symptomatic severe aortic stenosis
this specific skill which is particularly demanding during 5. Uncontrolled heart failure
SE. Images should be obtained in recovery to demonstrate 6. Acute myocarditis or pericarditis
7. Hypertension >200/110 mmHg at baseline
normalisation of any regional changes in myocardial
disease
Table 3 End points for stress echocardiography.
(a) Absolute Drop in SBP† >10 mmHg from baseline with symptoms

Sustained VT*
ST elevation >1 mm with symptoms (other than aVR or V1)
Central nervous system symptoms (ataxia, pre-syncope)
Left ventricular thrombus
(b) Relative Predicted maximum heart rate >1 and maximal effort
New wall motion abnormality
Progressive LV dilatation
New onset or progressive global LV dysfunction
Drop in SBP >10 mmHg from baseline without other evidence of ischaemia
ST depression >2 mm or axis shift
Stress-induced arrhythmia: AF, SVT, NSVT**
Severe hypertension >230 mmHg
HR falling >20% starting rate
†SBP, systolic blood pressure; *VT, ventricular tachycardia; **AF, atrial fibrillation; SVT, supraventricular tachycardia; NSVT, non-sustained ventricular
tachycardia (47).
cardiovascular events in those who do not achieve their Dobutamine stress echocardiography
target but have normal images is higher than those who
do achieve their target and have normal images (29). Dobutamine is a sympathomimetic agent that increases
Similarly, failure to achieve a reasonable absolute level of myocardial oxygen demand by increasing heart rate
exercise (defined as <7 metabolic equivalents (METs) for (chronotropic effect) and the force of contraction (inotropic
men and <5 METs for women) is a predictor of subsequent effect) through action on β1 adrenoceptors. In addition, it
cardiac events even if SE is normal (30). has weaker action on β2 adrenoceptors resulting in a degree
of vasodilatation. Use in SE requires infusion of supra-
(a) Semi-supine bike – the recommended protocol to use
pharmacologic doses (up to 40 µg/kg/min), frequently with
is the World Health Organisation 25 Watt programme
the addition of atropine (which improves sensitivity of the
with load increased in increments of 25 Watts every
test) (33) and requires a degree of caution and expertise.
2 or 3 min, with the patient maintaining a cadence
Every test carries a definite risk of complications, although
of approximately 60 revolutions per minute (25). It
the administration of these agents in the era of LVO has
is standard practice to acquire images at rest and at
been shown to be safe, with a risk of myocardial infarction
peak stress, but the acquisition of additional images
and life-threatening arrhythmia below 1% (34). Moreover,
at 25W and 50W during semi-supine bicycle improves
there is evidence that dobutamine-atropine (DA) SE can
diagnostic performance (25). The major consideration
is to ensure that the patient achieves their maximum
workload, since this is an important discriminator of Table 4 Contraindications to dobutamine-atropine SE.
outcome irrespective of protocol (31). Protocols should
Absolute
therefore be tailored to the physical capability of the
1. Previous hypersensitivity/allergy to dobutamine or
patient and supplemented with hand-grip exercise or atropine
atropine to optimise heart rate response (32). 2. Recent myocardial infarction (within 3 days)
3. Ongoing unstable angina
(b) Treadmill – the recommended protocol to use is the
4. Acute heart failure
standard Bruce exercise treadmill protocol, with the 5. Left ventricular thrombus
modified Bruce for the less physically able patient or 6. Recent significant ventricular arrhythmia (within 3 days)
7. Recurrent persistent supraventricular arrhythmias
an accelerated Bruce (first stage skipped) for a super
8. High-grade AV block (second or third degree)
fit patient. Images are taken at baseline and within 9. Active endocarditis or myocarditis
90 s of termination of exercise, although as discussed 10. Severe arterial hypertension – systolic >200 mmHg,
diastolic >110 mmHg
above, there is some evidence of improved sensitivity
Relative contraindications/cautions
by imaging during exercise. The main issue is to avoid 1. Paroxysmal supraventricular arrhythmia
missing abnormalities when patient recovery is rapid 2. Moderate aortic stenosis
or by inappropriate delay to imaging. 3. Resting left ventricular outflow tract obstruction
>30 mmHg
End points for exercise SE are listed in Table 3. 4. Aortic aneurysm >4 cm
disease
Table 5 Common drugs in SE: dosage and supplementary information.
Drug Dose
Atropine 300 µg aliquots; up to 1.2 mg in total

Side effects: dry mouth, constipation, mydriasis
Contraindications: angle closure glaucoma, prostate hypertrophy (difficulty in micturition)
Dobutamine 5–40 µg/kg/min; dilution as an infusion via syringe driver
Side effects: nausea, tremor, palpitations, chest pain, hyper/hypotension, arrhythmia, myocardial
infarction
Contraindications: see Table 4
Adenosine 140 µg/kg/min; often diluted as an infusion 1 mg/mL
Side effects: flushing, chest pain, shortness of breath, metallic taste, bradyarrhythmia
Contraindications: sinus node disease, high-grade AV block (second or third degree); reversible
airways disease. Note: effect antagonised by methylxanthines, e.g. coffee.
Dipyridamole 0.56 mg/kg over 4 min; followed after 2 min by 0.28 mg/kg over 2 min (low dose enough for perfusion
assessment; high dose may also invoke RWMA)
Side effects: chest pain, flushing, arrhythmia, hypersensitivity reactions, bronchospasm, hypotension
Contraindications: prior hypersensitivity, unstable angina
Regadenoson 400 µg in 5 mL pre-loaded syringe IV bolus over 5–10 s
Side effects: chest pain, nausea, dizziness, headache, conduction abnormalities.
Contraindications: sinus node disease, high-grade AV block (second or third degree); prior
hypersensitivity. Note: effect antagonised by methylxanthines, e.g. coffee.
Aminophylline 240 mg IV; routinely infused at end of dipyridamole infusion
Side effects:
Contraindications
Metoprolol 1 mg aliquots
Up to 5 mg if required
Side effects:
Contraindications: asthma or severe airways disease of any kind. Caution with pre-existing
high-grade AV block or known tachybrady syndrome
Anaphylaxis
Adrenaline 0.5 mg–1 mg (1:1000 strength) intramuscular injection
Chlorpheniramine 10 mg
Hydrocortisone 100 mg
Salbutamol Nebuliser 5 mg – may be given repeatedly
This Table lists common and major risks, but is not exhaustive, and any operator must have a full working knowledge of the side effects and contraindications
of these drugs. Local hospital administration requirements must be met.
be supervised by doctors, nurses and physiologists when At higher doses, however, the β2 agonism can result in
adequately trained with equivalent risk and safety (35). peripheral vasodilation resulting in a fall in blood pressure,
Contraindications to SE with DA are listed in Table 4 and particularly in the diastolic component. Occasionally,
risk factors of common pharmacological agents, doses and there can be a paradoxical slowing of heart rate during
contraindications used in SE are given in Table 5. high-dose dobutamine. This is typically mediated
Dobutamine is infused continuously through an via the Bezold-Jarisch reflex that results in increased
intravenous cannula according to a weight-adjusted dose parasympathetic activity and inhibition of sympathetic
(Fig. 1). The aim of DA SE is to achieve the maximum activity. This results in a ‘vagal’ response and can lead to a
target heart rate which is calculated (220 – age), although precipitous fall in blood pressure. This can be avoided by
sensitivity of the test does not appear to fall providing monitoring carefully for any paradoxical slowing of heart
imaging is performed above 85% of the maximum heart rate and if this occurs to administer atropine and/or to ask
rate. Atropine is often required in 300 µg aliquots up to the patient to undertake hand-grip exercises by repeatedly
1.2 mg to augment the heart rate response, improves squeezing a ball or similar object.
sensitivity compared to the use of dobutamine alone,
and can be helpful in reducing the likelihood of adverse
hypotensive and vagal reactions (Fig. 1). Myocardial perfusion stress echocardiography
The latter adverse effects of dobutamine are due to
mixed action at β1 and β2 adrenoceptors. At low doses, Myocardial perfusion stress echocardiography (MPSE)
the inotropic and chronotropic effects of dobutamine improves detection of ischaemia, since perfusion
lead to a slight augmentation of blood pressure. abnormalities occur before the occurrence of loss of wall
disease
Figure 1
Dobutamine infusion schedule.
thickening (36). The addition of perfusion imaging to during DA SE (refer to Table 5 for common side effects).
regional wall motion analysis improves the sensitivity Quantitative analysis of perfusion and myocardial blood
for detection of ischaemia and improves prediction flow may be performed using steady-state infusion
of risk (37). The incremental value of MPSE has been and flash replenishment, and there is some evidence of
demonstrated on exercise (38), with DA, and following additional accuracy compared to qualitative perfusion
vasodilator stress without significant addition to the risk of analysis, although data are limited (41). Moreover, visual
the test (34). MPSE may also have particular advantages in assessment is easier and faster.
improving sensitivity in the context of resting wall motion MPSE is performed at rest and during stress
abnormalities, such as left bundle branch block (39). immediately after standard images for wall motion
Multiple studies have been performed using vasodilator analysis have been acquired. Standard protocols are below
stress, which has the advantages of being quick to perform, (Figs 2, 3 and 4). The key to obtaining high-quality MPSE
providing good image quality at lower heart rate, while images is to ensure optimal machine settings and to
avoiding the issue of translational motion of the heart with familiarise yourself with the adjustable settings:
rapid breathing and producing equivalent accuracy to other
stress agents. Vasodilator stress agents induce abnormalities (a) Setup. A contrast-specific preset should be selected
in wall thickening by enhancing flow inhomogeneity due specifically for perfusion, which will involve very
to underlying stenosis, and do not increase heart rate and low mechanical index imaging <0.2 (preferably <0.1
blood pressure significantly. The most common agents (SonoVue) or <0.15 (Optison/Luminity)). The depth
used are adenosine and dipyrimadole, although studies should be adjusted so that the left ventricle fills in
have also confirmed equivalent accuracy of MPSE with screen. Overall gain should be between 60 and 65%.
regadenoson (40) and perfusion can also be done The transitional and lateral gain compensation controls
Figure 2
Myocardial perfusion stress echocardiography
protocol during exercise stress.
disease
Figure 3
Myocardial contrast echocardiography during
dobutamine stress echocardiography.
should be in mid-positions, and the focus should be at Wait 2–3 beats then press flash. The loop length should
the mitral valve level but can be moved to the near be 15 beats so images should be optimised until the
field when apical perfusion is being evaluated. The end of the acquisition.
default loop length should be set to 15 beats. Images (d)
Check Images. It is important ensure adequate
can be obtained in real-time (40 frames per RR interval) microbubble destruction in all segments of the
and using triggered imaging (1 frame per RR interval). myocardium (the myocardium will appear almost black)
(b) Flash Parameters. The flash setting involves delivering a with minimal amount of microbubble destruction in
brief (5–10 flash frames) high mechanical index (MI > 0.8) the LV cavity. If there is incomplete bubble destruction
impulse to clear contrast within the myocardium, (Fig. 6), consider the following steps:
following which replenishment is analysed on the end-
systolic images. The flash power button will increase •• Increase flash frames for example from 8 to 15 to 20
the flash power. The flash frames button can be used to if still incomplete destruction;
adjust the number of flash frames per beat. •• Increase flash power for example from 0.8 to 1.0;
(c) Myocardial Contrast. Although small bolus injections •• Reduce overall gain while maintaining opacification
with saline flush given slowly can create periods when of the myocardium;
steady-state kinetics are achieved to examine flash- •• Reducing infusion rate for example 0.8 mL/min to
replenishment, most MPSE is performed with contrast 0.7 mL/min if above fails.
infusion via a pump or IV giving set 0.7–1 mL/min. It If there is too much bubble destruction in LV cavity,
is important to ensure homogenous opacification of consider the following:
the left ventricular cavity and myocardium (Fig. 5).
Once the endocardial/epicardial borders are well •• Reduce flash frames, for example from 8 to 6;
visualised, press acquire to start recording of images. •• Reduce flash power, for example from 0.8 to 0.6.
Figure 4
Vasodilator stress echocardiography. Note: low
dose enough for perfusion assessment; high dose
may also invoke RWMA, so that infusion dose may
be modified accordingly.
disease
bubble replenishment following bubble clearance is

expected within 5 s or five beats if the heart rate is
60 bpm. At peak stress, bubble replenishment is expected
within 1–2 s. If the heart rate is 120 bpm replenishment is
expected within 2–3 beats. Video 1 shows an example of a
perfusion defect identified during MPSE.
Video 1
Real-time myocardial contrast echocardiography. After
two beats a perfusion defect remains in the mid–to-apical
infero-septum and lateral wall. This eventually resolves
after a further 10–12 beats. View Video 1 at http://
movie-usa.glencoesoftware.com/video/10.1530/ERP-18-
Figure 5
0068/video-1.
Initial settings optimised for myocardial contrast echocardiography.
Once image quality and microbubble destruction are

Coronary flow reserve
considered satisfactory, the above steps can be repeated
using triggered imaging. If the wall motion is normal at Coronary blood flow can increase approximately four-
rest, perfusion will always be normal. Thus, to save time, to-six-fold in the healthy individual to meet increasing
only the apical four-chamber view need be obtained to myocardial oxygen demands. This effect is mediated by
optimise image at rest. The settings after optimisation must vasodilation of the arteriolar bed, which reduces vascular
be held constant during acquisition of stress imaging. The resistance, thereby increasing coronary flow. Coronary
only parameters which can be changed during stress are flow reserve (CFR) represents the capacity of the coronary
the number of flash frames and flash MI for optimisation circulation to dilate following an increase in myocardial
of bubble clearance. metabolic demands and can be expressed by the difference
When reviewing images following MPSE, freeze the between hyperaemic flow and resting flow. It has long been
cine loop on the frame exactly after the flash and ensure known that there is an inverse curvilinear relationship
that there has been adequate bubble destruction (i.e. between the narrowing of the lumen of coronary artery
myocardium should be black). Review both real-time and and hyperemic capacity, up to a complete annulment or
triggered image, and when starting, it may be helpful to absence of CFR for stenosis >90% significance (42). Although
analyse each cine-loop frame by frame. At rest, complete in clinical practice, there are a number of factors that
affect the curvilinear nature of the link between CFR and
stenosis severity, for example arterial spasm, left ventricular
hypertrophy and pharmacotherapy, Doppler-derived CFR
can be measured reproducibly and in agreement with values
from positron emission tomography, which is considered
gold standard (43). Doppler-derived CFR adds incremental
diagnostic and prognostic value to wall motion analysis
(44) and perfusion (45) in the assessment of patients with
known or suspected CAD and can be used whether or not
anti-ischaemic medication is continued at the time of the
test (46).
Doppler-derived CFR is possible not only for the
left anterior descending (LAD) artery but also in the
right and left circumflex arteries (47). In experienced
hands, CFR by echocardiography is achievable within
the LAD artery in >90% cases, and in nearly all with the
Figure 6
use of intravenous contrast agents. In difficult cases, the
Incomplete microbubble destruction basal/mid-infero-septum (arrow). intravenous injection of small boluses of transpulmonary
disease
contrast helps to improve both the colour Doppler signal As discussed earlier in indications for SE, dyspnoea
for location of the arterial segment and/or to obtain clear on exertion is a common symptom that may often
Pulse Doppler signals in the artery in question, particularly reflect ischaemia but the differential diagnosis may be
in the overweight and obese (48). Measurement of wide. Exercise SE can unmask diastolic dysfunction
CFR is technically challenging, particularly since the and can provide an explanation for breathlessness by
measurement of absolute blood velocity is dependent estimating changes in filling pressure in the form of E/e’
on the incident angle between the Doppler beam and and maximal tricuspid regurgitant velocity (57). This can
blood flow and reliability requires a consistent position better be performed using a semi-supine bicycle ergometer
throughout assessment. As a result of this and other to enable estimation throughout low-dose exercise, with
technical reasons, including the use of velocity ratio as abnormality defined by increased transmitral E-wave
a surrogate for CFR, it is recommended that Doppler velocity, reduced A wave velocity, unchanged e’ and
measurement of CFR is performed using vasodilator stress, increased E/e’ (usually >14).
ideally used as a first step in a multiparametric study that
includes assessment of regional wall thickening/motion
and/or perfusion (49). A cut-off value of two for detecting 3D acquisitions in SE
significant epicardial coronary stenosis or ischaemia has
been demonstrated in a number of studies of CFR (46). The use of 3D echocardiography during SE reduces the time
taken for image acquisition (58), improve foreshortened
imaging planes (58) and increase reproducibility between
Myocardial strain, diastolic function and SE imaging planes acquired at different stages of stress (59).
New and relatively fast 3D ultrasound imaging devices
The term strain is used to describe the shortening and are entering the market offering superior image quality,
thickening of myocardium during the cardiac cycle in higher frame (3D volume) rates and ever-expanding
the longitudinal, circumferential and radial planes as capabilities that increase the potential for routine use.
a reflection of contractility. Strain is a dimensionless
change in length of tissue between two points, whereas
strain rate is the change of strain over time. Strain Modes of 3D SE
can be measured by tissue Doppler imaging, which
3D systems offer several different imaging modes:
was the method used for initial validation (50, 51),
but this has largely been replaced by speckle tracking (a) Real-Time 3D (RT3D) Multislice Imaging. Detection of
echocardiography, which avoids some of the issues haemodynamically-significant CAD with RT3D relies on
relating to angle dependency. Characteristic changes in the detection of changes in wall motion and thickening
diagnosis of ischaemia include reduction in peak strain, between rest and peak stress in the same way as 2D SE.
systolic lengthening and post-systolic shortening (52). The availability of multislice and multiplane RT3D
The advantage of adding strain imaging to standard permits simultaneous viewing of standard parasternal
regional thickening and wall motion is that this replaces long, parasternal short and apical volumetric data, such
qualitative assessment with quantitative assessment and that specificity and accuracy may be better than 2D SE
reduces inter-observer variability (53). Strain imaging (60). In fact, any chosen imaging plane of the LV can
can be performed during pharmacological stress or theoretically be visualised allowing a more detailed
during bicycle exercise, although the stable positioning wall motion analysis than is currently available from
of the patient during DA make this an ideal format in standard 2D imaging planes. This improves detection
which to combine strain imaging with wall thickening of wall motion abnormalities in the apical segments
and motion (54). There are data to indicate incremental and allows off-axis images to be interrogated, while
value of reduction in peak strain, systolic lengthening preserving overall accuracy (60). Moreover, since the
and post-systolic shortening in addition to wall motion whole LV is imaged simultaneously, image acquisition
analysis (55). More documentation of added clinical becomes greatly simplified and faster (61).
value is needed, however, before strain imaging can (b) Real-Time 3D Full Volume Data Acquisition (RT3DFV):
be recommended for routine use in the evaluation of With RT3DFV, full volume 3D datasets are acquired
patients with chest pain, particularly in linking the with the transducer positioned over the apex with
adoption of strain in SE to improved outcomes (56). the volume size adjusted to incorporate the entire left
disease
Table 6 Interpretation of images according to wall motion in individual segments.
Rest Stress Diagnosis
Normal Hyperdynamic Normal

Normal Hypokinetic/akinesia/dyskinesia Ischaemia
Hypokinetic Hypokinetic Partial thickness infarction
Hypokinetic/akinetic Normal Viability
Hypokinetic/akinetic Normal at low dose followed by hypokinesia/akinesia at high Viability and ischaemia –
dose ‘biphasic response’
Akinetic Akinetic/dyskinetic Scar
LV size and function LV dilatation/fall in EF with regional WMA Extensive ischaemia
ventricle. Initial studies involving dobutamine stress producing whole volume short axis slices for analysis.
echocardiography show shorter image acquisition These derived 2D images can be ‘shuffled’ and displayed
times for 3D imaging than 2D imaging (62). There is side by side for visual analysis in any format required. The
no need to acquire parasternal images. As yet, data key, however, to improving workflow for 3D SE will be the
predominantly show equivalent overall accuracy automation of the cropping and reconstruction process,
compared to 2D SE with RT3DFV datasets (63). and the quantification of LV wall motion and thickening.
3D volume data acquisition Reporting

The patient should be asked to stop breathing at A comprehensive report should include:
end-expiration during the full volume acquisition to
minimise issues with ‘fault lines’ between sub-volumes 1. The indications for the study;
after reconstruction. Care should be given to ensure 2. Details of stress technique used to include heart rate
good-quality ECG gating and currently obtaining good- and blood pressure at rest and peak, workload achieved,
quality RT3DFV studies is difficult in patients with dose of pharmacological agents, with the addition of
arrhythmias, particularly atrial fibrillation. With exercise other relevant changes such as a fall in blood pressure
SE, RT3DFV is more challenging and stitching artefacts during the test;
due to hyperventilation and cardiac translation are more 3. Use of contrast, including dose and type;
likely to occur, so much of the data acquired in existing 4. Symptoms occurring during the test e.g. whether the
publications relate to pharmacological stress. patient had their typical symptoms during stress;
In an otherwise suboptimal harmonic 3D SE study, 5. Assessment of the 12-lead ECG findings if used;
LVO contrast has been shown to improve endocardial 6. Image quality: good/moderate/poor;
border delineation to a similar level to that achieved 7. LV size and function at rest and peak;
by contrast-enhanced 2D (64). A limitation to the use 8. Wall motion assessment/scoring at each stage. Most
of LVO in 3D SE is that this does cause a reduction in modern echo systems have a template for reporting
temporal resolution (65). This has significance during based on a 16-segment model. The 17-segment model
peak exercise, when the heart rate is high and the number which includes the LV apex is less commonly used in
of 3D volumes per cardiac cycle is at levels that may be SE since the apex is stationary in the true long axis
too low for diagnostic use. and therefore wall motion is less applicable. Reporting
is based on the development of delay in onset of
contraction (tardokinesis), reduction in systolic
Workflow and display
thickening (hypokinesis), absent wall thickening in
Present workflow issues for 3D stress analysis include systole (akinesis) and paradoxical wall motion in
cropping the 3D datasets to create a multiplane systole (dyskinesis). The interpretation of wall motion
reconstruction equivalent to standard 2D image planes. abnormalities is given in Table 6. Examples of regional
However, this takes time and despite initially acquiring a abnormalities are given in Videos 2, 3, 4, 5, 6, 7, 8, 9,
3D image, the time taken to create the necessary anatomical 10, 11, 12, 13, 14 and 15;
views may have an impact on the clinical workflow of SE. 9. Qualitative perfusion at rest and peak stress;
There are commercially available 3D stress software packages 10. Interpretation and diagnosis including a conclusion
for processing 3D stress images that improve workflow, regarding risk stratification.
disease
Video 2 Video 10
Quad screen for normal SE (peak stress images). View Invasive coronary angiogram confirming flow-limiting
Video 2 at http://movie-usa.glencoesoftware.com/ stenosis in the circumflex artery. View Video 10 at http://
video/10.1530/ERP-18-0068/video-2. movie-usa.glencoesoftware.com/video/10.1530/ERP-18-
0068/video-10.
Video 3
Quad screen for normal SE (resting images). View Video 3 Video 11
at http://movie-usa.glencoesoftware.com/video/10.1530/ Stress echocardiogram (apical four-chamber)
ERP-18-0068/video-3. demonstrating ischaemia in the right coronary artery.
View Video 11 at http://movie-usa.glencoesoftware.com/
Video 4 video/10.1530/ERP-18-0068/video-11.
Apical four-chamber images from stress echocardiogram
with left ventricular opacification contrast demonstrating Video 12
ischaemia in the left anterior descending artery. View Stress echocardiogram (apical two-chamber)
Video 4 at http://movie-usa.glencoesoftware.com/ demonstrating ischaemia in the right coronary artery.
video/10.1530/ERP-18-0068/video-4. View Video 12 at http://movie-usa.glencoesoftware.com/
video/10.1530/ERP-18-0068/video-12.
Video 5
Apical two-chamber images from stress echocardiogram Video 13
with left ventricular opacification contrast demonstrating Stress echocardiogram (apical three-chamber)
ischaemia in the left anterior descending artery. View demonstrating ischaemia in the right coronary artery.
Video 5 at http://movie-usa.glencoesoftware.com/ View Video 13 at http://movie-usa.glencoesoftware.com/
video/10.1530/ERP-18-0068/video-5. video/10.1530/ERP-18-0068/video-13.
Video 6 Video 14
Invasive coronary angiogram confirming flow-limiting Invasive coronary angiogram confirming flow-limiting
stenosis in the left anterior descending artery. View Video stenosis in the circumflex artery. View Video 14 at http://
6 at http://movie-usa.glencoesoftware.com/ movie-usa.glencoesoftware.com/video/10.1530/ERP-18-
video/10.1530/ERP-18-0068/video-6. 0068/video-14.
Video 7 Video 15
Stress echocardiogram (apical four-chamber) Rest and stress images in the apical two chamber view
demonstrating ischaemia in the circumflex artery. View demonstrating thinning and loss of systolic thickening in
Video 7 at http://movie-usa.glencoesoftware.com/ the inferior wall consistent with completed myocardial
video/10.1530/ERP-18-0068/video-7. infarction. View Video 15 at http://movie-usa.
glencoesoftware.com/video/10.1530/ERP-18-0068/
Video 8 video-15.
Stress echocardiogram (apical two-chamber)
demonstrating ischaemia in the circumflex artery. View
Video 8 at http://movie-usa.glencoesoftware.com/
Audit
video/10.1530/ERP-18-0068/video-8.
Departments should regularly audit and review the
Video 9 indications, safety and outcomes of SE. This is important
Stress echocardiogram (apical three-chamber) to demonstrate a high-quality service with accurate
demonstrating ischaemia in the circumflex artery. View and reproducible results. The findings of any further
Video 9 at http://movie-usa.glencoesoftware.com/ investigations for example coronary angiography or
video/10.1530/ERP-18-0068/video-9. clinical events such as hospital admissions with an
disease
acute coronary syndrome should be fed back to the 3 Thaden JJ, Tsang MY, Ayoub C, Padang R, Nkomo VT, Tucker SF,
Cassidy CS, Bremer M, Kane GC & Pellikka PA. Association between
echo department to cross check SE data. Joint reporting
echocardiography laboratory accreditation and the quality of
and review of studies on a regular basis contributes to imaging and reporting for valvular heart disease. Circulation:
achieving high standards. Audits should be considered in Cardiovascular Imaging 2017 10 e006140. (https://doi.org/10.1161/
CIRCIMAGING.117.006140)
a cycle and may include:
4 Nesto RW & Kowalchuk GJ. The ischemic cascade: temporal
sequence of hemodynamic, electrocardiographic and symptomatic
•• Audit of outcomes following SE, e.g. using Hospital
expressions of ischemia. American Journal of Cardiology 1987 59
Episode Statistics (death, myocardial infarction, 23C–30C. (https://doi.org/10.1016/0002-9149(87)90192-5)
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a systematic review and meta-analysis of prospective studies.
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6 Bouzas-Mosquera A, Peteiro J, Alvarez-Garcia N, Broullon FJ,
sub-maximal exercise). One such audit every year to be
Mosquera VX, Garcia-Bueno L, Ferro L & Castro-Beiras A. Prediction
considered reasonable; of mortality and major cardiac events by exercise echocardiography
•• Double-reading or review of 10% of studies, e.g. on a in patients with normal exercise electrocardiographic testing. Journal
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7 Panoulas VF, Keramida K, Boletti O, Papafaklis MI, Flessas D,
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Conclusion echocardiography in patients with stable coronary artery disease.
EuroIntervention 2018 13 1959–1966. (https://doi.org/10.4244/EIJ-D-
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8 Neumann F-J, Sousa-Uva M, Ahlsson A, Alfonso F, Banning AP,
a commonly requested investigation. Adherence to
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together with robust quality assurance process is vital to 2019 2018 87–165. (https://doi.org/10.1093/eurheartj/ehy394)
9 National Institute for Health and Care Excellence. Chest pain of recent
ensure patient safety and best results from SE.
onset: assessment and diagnosis. London, UK: NICE, 2010. (available
at: https://www.nice.org.uk/guidance/cg95)
10 Douglas PS, Hoffmann U, Patel MR, Mark DB, Al-Khalidi HR,
Cavanaugh B, Cole J, Dolor RJ, Fordyce CB, Huang M, et al.
Declaration of interest Outcomes of anatomical versus functional testing for coronary
P Nihoyannopoulos and V Sharma are Co-Editors-in-Chief, R P Steeds and artery disease. New England Journal of Medicine 2015 372 1291–1300.
M J Monaghan are Strategic Editors, R Senior is an Associate Editor, and (https://doi.org/10.1056/NEJMoa1415516)
R Wheeler is an editorial board member of Echo Research and Practice. 11 Knuuti J, Ballo H, Juarez-Orozco LE, Saraste A, Kolh P, Rutjes AWS,
They were not involved in the review or editorial process for this paper, on Jüni P, Windecker S, Bax JJ & Wijns W. The performance of non-
which they are listed as an author. The other authors do not have actual or invasive tests to rule-in and rule-out significant coronary artery
perceived conflicts of interest with the contents of this manuscript. stenosis in patients with stable angina: a meta-analysis focused
on post-test disease probability. European Heart Journal 2018 39
3322–3330. (https://doi.org/10.1093/eurheartj/ehy267)
12 Shah BN, Balaji G, Alhajiri A, Ramzy IS, Ahmadvazir S & Senior R.
Incremental diagnostic and prognostic value of contemporary
Funding
stress echocardiography in a chest pain unit: mortality and
This work did not receive any specific grant from any funding agency in the
morbidity outcomes from a real-world setting. Circulation:
public, commercial, or not-for-profit sector.
Cardiovascular Imaging 2013 6 202–209. (https://doi.org/10.1161/
CIRCIMAGING.112.980797)
13 Cook DG & Shaper AG. Breathlessness, angina pectoris and coronary
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Received in final form 18 December 2019

Accepted 28 March 2019
Accepted Manuscript published online 28 March 2019

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R P Steeds et

al. Stress echo in coronary 6:2 G17–G33

GUIDELINES AND RECOMMENDATIONS

Stress echocardiography in coronary artery

Richard P Steeds1,*, Richard Wheeler2,*, Sanjeev Bhattacharyya3, Joseph Reiken4, Petros Nihoyannopoulos5,*,

4Department of Cardiology, Kings College Hospital, London, UK

5Department of Cardiology, National Heart Lung Institute, Hammersmith Hospital, London, UK

6Department of Cardiology, Royal Brompton Hospital, London, UK

7Department of Cardiology, Royal Liverpool and Broadgreen University Hospital, Liverpool, UK

Correspondence should be addressed to R P Steeds: rick.steeds@uhb.nhs.uk

†(V Sharma is the Guidelines Chair)

1. Significant valve disease. If this is a new diagnosis, then

There are two main techniques to achieve exercise stress

Table 3 End points for stress echocardiography.

(a) Absolute Drop in SBP† >10 mmHg from baseline with symptoms

Table 5 Common drugs in SE: dosage and supplementary information.

Atropine 300 µg aliquots; up to 1.2 mg in total

bubble replenishment following bubble clearance is

Once image quality and microbubble destruction are

Table 6 Interpretation of images according to wall motion in individual segments.

Rest Stress Diagnosis

Normal Hyperdynamic Normal

3D volume data acquisition Reporting

of Echocardiography 2015 28 1393–1400. (https://doi.org/10.1016/j. 52 Skulstad H, Edvardsen T, Urheim S, Rabben SI, Stugaard M,

Received in final form 18 December 2019

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Richard P Steeds1,, Richard Wheeler2,, Sanjeev Bhattacharyya3, Joseph Reiken4, Petros Nihoyannopoulos5,*,