Stress Echocardiography Expert Consensus Statement--Executive Summary: European Association of Echocardiography (EAE) (a registered branch of the ESC)
Year: 2008
Type: article
Abstract: Stress echocardiography is the combination of echocardiography with a physical, pharmacological, or electrical stress. The diagnostic endpoint for the detection of myocardial ischaemia is the induction of a transient worsening in regional function during stress. Stress echocardiography provides similar diagnostic and prognostic accuracy to radionuclide stress perfusion imaging, but at a substantially lower cost, without environmental impact, and with no biohazards for the patient and the physician. Among different stresses of comparable diagnostic and prognostic accuracy, semisupine exercise is the most used, dobutamine the best test for viability, and dipyridamole the safest and simplest pharmacological stress and the most suitable for combined wall motion coronary flow reserve assessment. The additional clinical benefit of myocardial perfusion contrast echocardiography and myocardial velocity imaging has been inconsistent to date, whereas the possibility of performing coronary flow reserve evaluation of the left anterior descending coronary artery by transthoracic Doppler echocardiography adds another potentially important dimension to stress echocardiography. New emerging fields of application taking advantage of the versatility of the technique are Doppler stress echo in valvular heart disease and in dilated cardiomyopathy. In spite of its dependence on the operator's training, stress echocardiography is today the best (most cost-effective and risk-effective) possible imaging choice to achieve the still elusive target of sustainable cardiac imaging in the field of non-invasive diagnosis of coronary artery disease. In 1935, Tennant and Wiggers 1 demonstrated that coronary occlusion immediately resulted in instantaneous abnormality of wall motion. A large body of evidence 2–5 recognized for the first time that transient dys-synergy was an early, sensitive, specific marker of transient ischaemia, clearly more accurate than ECG changes and pain. In European clinical practice, 6–10 stress echo has been embedded in the legal and cultural framework of existing European laws and medical imaging referral guidelines. The radiation used for medical examinations and tests is the greatest man-made source of radiation exposure. 11 Small individual risks of each test performed with ionizing radiation multiplied by a billion examinations become significant population risks. For this reason, in Europe, both the law 11 and the referral guidelines for medical imaging 12 recommend a justified, optimized, and responsible use of testing with ionizing radiation. European Commission referral guidelines were released in 2001 in application of the Euratom Directive, and explicitly state that a non-ionizing technique must be used whenever it will give information grossly comparable with an ionizing investigation. For instance, ‘because MRI does not use ionizing radiation, MRI should be preferred when both CT and MRI would provide similar information and when both are available’. 12 In this perspective of the medical, as well as socio-economic and biological impact of medical imaging, it is imperative to increase all efforts to improve appropriateness 13 and minimize the radiation burden of stress imaging for the population and the individual patient. 14 The imperative of sustainability of medical imaging is likely to become increasingly important in the near future, also from a US perspective. 15 , 16 In the quest for sustainability, stress echocardiography has unsurpassed assets of low cost, absence of environmental impact, and lack of biological effects for both the patient 17 and the operator compared with equally accurate, but less sustainable, competing techniques. 18 Stress echocardiography is the combination of 2D echocardiography with a physical, pharmacological, or electrical stress. 19 The diagnostic endpoint for the detection of myocardial ischaemia is the induction of a transient change in regional function during stress. The stress echo sign of ischaemia is a stress-induced worsening of function in a region contracting normally at baseline. The stress echo sign of myocardial viability is a stress-induced improvement of function during low levels of stress in a region that is abnormal at rest. A transient regional imbalance between oxygen demand and supply usually results in myocardial ischaemia, the signs and symptoms of which can be used as a diagnostic tool. Myocardial ischaemia results in a typical ‘cascade’ of events in which the various markers are hierarchically ranked in a well-defined time sequence. 20 Flow heterogeneity, especially between the subendocardial and subepicardial perfusion, is the forerunner of ischaemia, followed by metabolic changes, alteration in regional mechanical function, and only at a later stage by electrocardiographic changes, global left ventricular (LV) dysfunction, and pain. The pathophysiological concept of the ischaemic cascade is translated clinically into a gradient of sensitivity of different available clinical markers of ischaemia, with chest pain being the least and regional malperfusion the most sensitive. This is the conceptual basis of the undisputed advantages of imaging techniques, such as perfusion imaging or stress echocardiography over electrocardiogram (ECG) for the non-invasive detection of coronary artery disease. 21 The reduction of coronary reserve is the common pathophysiological mechanism. Regardless of the stress used and the morphological substrate, ischaemia tends to propagate centrifugally with respect to the ventricular cavity: 21 , 22 it involves primarily the subendocardial layer, whereas the subepicardial layer is affected only at a later stage if the ischaemia persists. In fact, extravascular pressure is higher in the subendocardial than in the subepicardial layer; this provokes a higher metabolic demand (wall tension being among the main determinants of myocardial oxygen consumption) and an increased resistance to flow. In the absence of coronary artery disease, coronary flow reserve (CFR) can be reduced in microvascular disease (e.g. in syndrome X) or LV hypertrophy (e.g. arterial hypertension). In this condition, angina with ST-segment depression can occur with regional perfusion changes, typically in the absence of any regional wall motion abnormalities during stress. Wall motion abnormalities are more specific than CFR and/or perfusion changes for the diagnosis of coronary artery disease. 23–28 Key point: wall motion and perfusion (or CFR) changes are highly accurate, and more accurate than ECG changes, for detection and location of underlying coronary artery disease. However, wall motion is more specific and requires ischaemia; perfusion changes are more sensitive and may occur in the absence of true ischaemia. The three most common stressors are exercise, dobutamine, and dipyridamole ( Figures 1 and 2 ). Exercise is the prototype of demand-driven ischaemic stress and the most widely used. However, out of five patients, one cannot exercise, one exercises submaximally, and one has an uninterpretable ECG. Thus, the use of an exercise-independent approach allows the diagnostic domain of a stress test laboratory to be expanded. 29 , 30 Pharmacological stressors minimize factors such as hyperventilation, tachycardia, hypercontraction of normal walls, and excessive chest wall movement, which render the ultrasonic examination difficult during exercise. All these factors degrade image quality and—in stress echo—worse image quality dramatically leads to higher interobserver variability and lower diagnostic accuracy. Dipyridamole (or adenosine) and dobutamine act on different receptor populations: dobutamine stimulates adrenoreceptors whereas dipyridamole (which accumulates endogenous adenosine) stimulates adenosine receptors. 31 They induce ischaemia through different haemodynamic mechanisms: dobutamine primarily increases myocardial oxygen demand 32 and dipyridamole (or adenosine) mainly decreases subendocardial flow supply 33 ( Table 1 ). In the presence of coronary atherosclerosis, appropriate arteriolar dilation can paradoxically exert detrimental effects on regional myocardial layers or regions already well perfused in resting conditions at the expense of regions or layers with a precarious flow balance in resting conditions. In ‘vertical steal’, the anatomical requisite is the presence of an epicardial coronary artery stenosis and the subepicardium ‘steals’ blood from the subendocardial layers. The mechanism underlying vertical steal is a fall in perfusion pressure across the stenosis. In the presence of a coronary stenosis, the administration of a coronary vasodilator causes a drop in post-stenotic pressure and, therefore, a critical drop in subendocardial perfusion pressure, which in turn provokes a decrease in absolute subendocardial flow, even with subepicardial overperfusion. Regional thickening is closely related to subendocardial rather than transmural flow, and this explains the regional asynergy with ischaemia, despite regionally increased transmural flow. Since endocardial oxygen demands are greater than epicardial demands, the resistance vessels of the endocardium are more dilated than those of the subepicardium, ultimately resulting in selective subendocardial hypoperfusion. ‘Horizontal steal’ requires the presence of collateral circulation between two vascular beds, with the victim of the steal being the myocardium fed by the more stenotic vessel. The arteriolar vasodilatory reserve must be preserved, at least partially, in the donor vessel and abolished in the vessel receiving collateral flow. After vasodilation, the flow in the collateral circulation is reduced in comparison with resting conditions. Despite the different pathophysiological mechanism, ischaemia induction when appropriately high doses with state-of-the-art protocols are used, dipyridamole and dobutamine tests show a similar diagnostic accuracy. 34–37 State-of-the art protocol for dobutamine stress echocardiography. State-of-the art protocol for dipyridamole stress echocardiography. Pharmacological stresses Pharmacological stresses Key point: exercise, dobutamine, and vasodilators (at appropriately high doses) are equally potent ischaemic stressors for inducing wall abnormalities in the presence of a critical epicardial coronary artery stenosis. Dobutamine and exercise mainly act through increased myocardial oxygen demand, and dipyridamole and adenosine through reduced subendocardial flow supply subsequent to inappropriate arteriolar vasodilation and steal phenomena. All stress echocardiographic diagnoses can be easily summarized into equations centred on regional wall function describing the fundamental response patterns as normal, ischaemic, viable, and necrotic myocardium. In the normal response, a segment is normokinetic at rest and normal or hyperkinetic during stress. In the ischaemic response, a segment worsens its function during stress from normokinesis to hypokinesis, akinesis, or dyskinesis (usually at least two adjacent segments are required for test positivity) ( Table 2 ). In the necrotic response, a segment with resting dysfunction remains fixed during stress. In the viability response, a segment with resting dysfunction may show either a sustained improvement during stress, indicating a non-jeopardized myocardium (stunned), or improve during early stress with subsequent deterioration at peak (biphasic response). This response would indicate a jeopardized region (hibernating myocardium) often improving after revascularization. 19 , 38 A resting akinesis which becomes dyskinesis during stress usually reflects a purely passive, mechanical consequence of increased intraventricular pressure developed by normally contracting walls, and should not be considered a true active ischaemia. 39 Stress echocardiography in four equations Stress echocardiography in four equations As with most imaging techniques, patient-dependent factors can limit image quality in stress echocardiography, which can adversely affect accuracy. Obesity and lung disease, for example, may lead to poor acoustic windows in ∼10% of patients. Harmonic imaging and ultrasound contrast agents for LV opacification are now recommended to enhance endocardial border detection. Given that the interpretation of contractile function is subjective, improved image quality can reduce inter-reader variability. Key point: all stress echo responses follow four basic patterns: normal (rest = stress = normal function); ischaemia (rest = normal; stress = abnormal); necrotic (rest = stress = abnormal); and viability (rest = abnormal; stress = normal or biphasic). Clear endocardial definition is crucial for optimal interpretation and it is recommended that harmonic imaging, when available, be routinely used for optimal endocardial border detection. Contrast-enhanced endocardial border detection could be used when suboptimal imaging is present. Exercise, 23 , 40–50 high-dose dobutamine, 51–55 and high-dose (accelerated or with atropine) dipyridamole 29 , 35 , 36 , 46 , 52 , 56 , 57 have not only similar accuracies, but also similar sensitivities. 35 , 36 , 58 ( Tables 3 and 4 ). Familiarity with all forms of stress is an index of the quality of the echo lab. In this way, indications in the individual patient can be optimized, thereby avoiding the relative and absolute contraindications of each test. For instance, a patient with severe hypertension and/or a history of significant atrial or ventricular arrhythmias can more reasonably undergo the dipyridamole stress test which, unlike dobutamine, has no arrhythmogenic or hypertensive effect. In contrast, a patient with severe conduction disturbances or advanced asthmatic disease should undergo the dobutamine stress test, since adenosine has a negative chronotropic and dromotropic effect, as well as a documented bronchoconstrictor activity. Patients either taking xanthine medication or under the effect of caffeine contained in drinks (tea, coffee, and cola) should undergo the dobutamine test. Both dipyridamole and dobutamine have overall tolerance and feasibility. The choice of one test over the other depends on patient characteristics, local drug cost, and the physician's preference. It is important for all stress echocardiography laboratories to become familiar with all stresses in order to achieve a flexible and versatile diagnostic approach that enables the best stress to be tailored to individual patient needs. Antianginal medical therapy (in particular, β-blocking agents) significantly affects the diagnostic accuracy of all forms of stress; therefore, it is recommended, whenever possible, to withhold medical therapy at the time of testing to avoid a false-negative result. Dipyridamole-stress vs dobutamine-stress echocardiography for detection of coronary artery disease Dipyridamole-stress vs dobutamine-stress echocardiography for detection of coronary artery disease Dipyridamole (DIP) stress vs exercise (EXE) stress echocardiography for detection of coronary artery disease Dipyridamole (DIP) stress vs exercise (EXE) stress echocardiography for detection of coronary artery disease Key point: physical or pharmacological (inotropic or vasodilator) stress echocardiography have comparable diagnostic accuracies. The choice of one test over the other will depend on relative contraindications. Large volume laboratories should be fully acquainted with all the three main forms of stress in order to apply the test in all patients. In the presence of a submaximal first-line stress for limiting side effects, the second choice should be applied, since submaximal (physical or pharmacological) stresses have suboptimal diagnostic value. The presence (or absence) of inducible wall motion abnormalities separates patients with different prognoses. Information has been obtained from data banks of thousands of patients—also with multicentre design—for exercise, 59–75 dobutamine, 76–80 and dipyridamole. 81–85 A normal stress echocardiogram yields an of on a of patients, the as for a normal stress myocardial perfusion in patients with coronary artery disease, a normal stress echocardiogram and coronary can be The and the negative response can be with with clinical dysfunction, and therapy at the time of resting echo LV and stress echo and The prognostic stress echo with relative are in Tables and Stress echo of a test coronary flow left anterior descending left coronary wall motion Stress echo of a test coronary flow left anterior descending left coronary wall motion Stress echo of a negative test coronary flow Stress echo of a negative test coronary flow Key point: physical or pharmacological (inotropic or vasodilator) stress echocardiography have a comparable prognostic of The most evidence is available with dobutamine, and exercise A normal and stress echocardiogram an for of the as for a normal stress myocardial perfusion Thus, in patients with coronary artery disease, a normal stress echocardiogram an and coronary can be the is available with dobutamine stress echocardiography, , , the preferred for myocardial However, it is also possible to the presence of myocardial viability exercise, or In the of ischaemia, of myocardial contractile function may be to myocardial or myocardial usually to myocardial dysfunction, and of myocardial of but often to as or viable, has as an important in the of heart to coronary artery disease. have that patients with ischaemic LV dysfunction and a significant of myocardium least five segments or a wall motion index have lower greater in regional and global LV function, heart and improved after than patients with large of myocardium. Key point: dobutamine stress echocardiography is by the most widely used for myocardium. This is highly recommended in patients with LV dysfunction may benefit from coronary revascularization. dobutamine is or not well other stresses exercise, and can be used to a regional reserve in myocardium. but side effects the of pharmacological stress in of patients with dobutamine and in patients with dipyridamole stress. The most and during stress echo and are in Tables The data pharmacological stress tests should be performed with an present. test a not all stress tests the of and dobutamine stress testing may be more than other forms of pharmacological stress, such as those by dipyridamole or from multicentre of and the of on data and data stress with exercise is than pharmacological , in multicentre and multicentre for dobutamine stress echocardiography a and effects were myocardial myocardial ventricular ventricular in multicentre and multicentre for dobutamine stress echocardiography a and effects were myocardial myocardial ventricular ventricular in multicentre and multicentre for dipyridamole stress echocardiography myocardial ventricular in multicentre and multicentre for dipyridamole stress echocardiography myocardial ventricular of pharmacological stress echocardiography ventricular ventricular of pharmacological stress echocardiography ventricular ventricular Key point: exercise is than pharmacological stress. 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Source: European Heart Journal
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2179377441