Stress Echocardiography -- Current Status

Roxy Senior; John Chambers

Abstract
Stress echocardiography has a high diagnostic accuracy for the detection of coronary disease. It is as effective as myocardial perfusion imaging for the stratification of risk in patients with coronary disease and can detect myocardial hibernation after myocardial infarction or in heart failure.
Introduction
In the UK there is still an emphasis on coronary anatomy as currently assessed using coronary angiography, although a high-grade coronary lesion, for example, may cause no myocardial ischaemia in the presence of extensive collateral vessels. Functional imaging to show the physiological effect of any coronary stenosis is therefore an important part of the investigation of patients with stable symptoms although it is still grossly underused in the UK. Current workforce documents[1] suggest that six stress studies per 1,000 population each year should be performed, yet the number of centres offering a full service remains limited. This review discusses the evidence for the effectiveness of stress echocardiography.
What is Stress Echocardiography?
The hallmark of myocardial ischaemia during stress echocardiography is the occurrence of reduced systolic wall thickening. This precedes chest pain and ST-T wave changes, which makes stress echocardiography more sensitive than exercise treadmill electrocardiogram (ECG) testing. Rest and stress images are interpreted for global and regional left ventricular size, shape and function (Figure 1). Stress echocardiography can identify the site of coronary stenoses. The total amount of myocardium in jeopardy predicts risk and prolonged persistence of a systolic wall thickening abnormality may also identify severe coronary artery disease.[2] Stress echocardiography can also predict the presence of myocardial hibernation.

Evidence that Stress Echocardiography is Effective
Diagnosis of Coronary Artery Disease
The sensitivities for the detection of coronary artery disease are 85%, 80% and 78% for exercise, dobutamine and dipyridamole stress echocardiography, respectively, with corresponding specificities of 77%, 86% and 91%, respectively.[3,4] Stress echo-cardiography can also identify multi-vessel disease,[5,6] which is important since such patients have a poor outcome, even in the presence of normal left ventricular function.
Risk Stratification
A normal stress echocardiograph gives an annual risk of 0.4-0.9% based on a total of 9,000 patients,[7-10] the same as for a normal stress myocardial perfusion scan.[11] This also holds true for patients with diabetes but the warranty period is less.[12] Thus, in patients with suspected coronary artery disease, a normal stress echocardiogram confers an excellent prognosis and coronary angiography can safely be avoided. By contrast, an abnormal stress echocardiogram is associated with a far higher risk of events, which is directly related to the extent of the wall motion abnormality in patients with[12] and without diabetes.[7]
In clinical practice, it is important whether a test provides incremental and independent information over and above clinical data. Information derived from exercise echocardiography[7] is incremental and independent of clinical data, Duke score and resting left ventricular function. In a study of 3,156 patients followed for nine years,[13] ischaemia and the extent of abnormal wall motion were independent predictors of cardiac death. Furthermore, the type of dobutamine response predicted outcome. Patients with resting left ventricular dysfunction and additional ischaemia had a worse outcome than those with ischaemia alone. In another study involving 7,333 patients[9] undergoing pharmacological stress echocardiography, an abnormal scan provided independent and incremental value over and above clinical data. In a subgroup of 4,037 patients who underwent coronary angiography without an intervention, the results of the coronary arteriogram did not add significant predictive power to the model.
Detection of Hibernating Myocardium
Hibernation implies myocardium which fails to contract normally but which may recover after revascularisation. It occurs in the presence of either repetitive stunning or a chronically sustained low level of blood flow, which is enough to repair 'wear and tear' but not enough to provide energy for contraction. It has been shown in non-randomised studies that revascularisation is effective in heart failure only in patients with hibernating myocardium.[14] The sensitivity and specificity of low-dose dobutamine echocardiography for predicting recovery of regional function following revascularisation is 84% and 81%, respectively, comparable to more expensive techniques ,Furthermore, revascularising myocardium designated as hibernating on dobutamine echocardiography improves survival.[16-19] Randomised trials are under way to address the relative benefit of revascularisation versus medical therapy in patients with hibernating myocardium.[20]
Myocardial Infarction
Despite thrombolysis, many patients are left with significant residual left ventricular dysfunction, either due to post-ischaemic stunning or myocardial necrosis. Post-ischaemic stunning implies a good prognosis as patients almost always recover left ventricular function in the absence of residual flow-limiting infarct-related artery stenosis. Echocardiography during low doses of dobutamine demonstrates increased contractility in these dysfunctional segments.
Several studies have confirmed the ability of dobutamine echocardiography to discriminate between stunned and necrotic myocardium after acute myocardial infarction[21,22] with similar sensitivity but higher specificity compared to radionuclide perfusion imaging.[11] Myocardial necrosis or a lack of dobutamine-induced contractile response is a more accurate marker of a poor prognosis[23] than angiography or clinical variables, with or without subsequent revascularisation.[24] Stress echocardiography can also stratify risk by demonstrating distant wall motion abnormalities implying multi-vessel disease.[23] Indeed, after revascularisation, the extent of non-viable myocardium[23,24] was the only predictor of cardiac events, while in the medically treated patients, both the extent of non-viable myocardium and stress echocardiographic indicators of non-viable myocardium and remote ischaemia were independent predictors of cardiac events.
Cost-effectiveness of Stress Echocardiography
Stress imaging has superior diagnostic and prognostic accuracy to exercise electrocardiography, leading to fewer normal coronary angiograms and fewer coronary events. Thus, despite its higher initial cost, stress echocardiography is likely to be more cost-effective than exercise electrocardiography.
Marwick et al.[25] studied 7,656 patients undergoing exercise testing of whom half underwent stress echocardiography. Compared to exercise electrocardiography, stress echocardiography identified more patients as low risk and fewer as intermediate and high risk Survival was greater in low- and intermediate-risk and less in high-risk patients and was better classified by stress echocardiography than exercise electrocardiography. Although initial procedural costs were greater, exercise echocardiography was associated with a greater incremental life-expectation (0-2 years) and a lower cost of additional diagnostic procedures when compared with exercise electrocardiography. Exercise echocardiography was therefore more cost-effective (€ 2,615/life year saved) than exercise electrocardiography. The authors further concluded that patients with symptoms who need non-invasive evaluation are less likely to undergo coronary angiography and hence revascularisation if a stress echocardiogram is performed in preference to exercise electrocardiography.
Similar results were obtained in a study of patients presenting with chest pain to an emergency department in the UK[26] and in patients with asymptomatic diabetes mellitus.[27]
Comparison With Other Imaging Techniques?
Radionuclide single-photon-emission tomography (SPECT) has a slightly higher sensitivity than stress echocardiography and a lower specificity. In a meta-analysis[28] based on 44 studies in patients without prior acute myocardial infarction or otherwise known ischaemic heart disease, stress echocardiography had a sensitivity of 85% (95% CI, 83-87%) with a specificity of 77% (95% CI, 74-80%), while SPECT had a sensitivity of 87% (95% CI, 86-88%) with a specificity of 64% (95% CI, 60-68%). In a study by Nagel et al.,[29] cardiac magnetic resonance was found to be superior to echocardiography for the diagnosis of coronary artery disease but only in patients with suboptimal echocardiography imaging. Limitations in image quality, undoubtedly a problem in the past, have been largely solved by harmonic imaging, tissue Doppler techniques and contrast microbubbles together with advances in digital imaging and display.[30-4]
Echocardiography machines are universally available and relatively inexpensive while magnetic resonance and SPECT are expensive. Echocardiography does not involve ionising radiation and has the important advantage of being portable so that it can be taken to patients in emergency departments or coronary care units. All techniques require training. In the case of stress echocardiography, a training set of 100 studies is usually recommended since there are significant problems in artefact and interpretation. For example, interpreting isolated basal inferior and septal wall abnormalities often leads to increased false-positive scans. The development of stress echocardiography, as for all cardiac imaging, is seriously limited by a dearth of adequately trained cardiologists. National workforce planning suggest the need for 11-15 echocardiography consultants per million population but it remains rare for a hospital to employ a specialist in echocardiography. The Future of Stress Echocardiography
Myocardial perfusion imaging using ultrasound contrast agents now allows simultaneous assessment of both function and perfusion,[35-37] with an improvement in diagnostic accuracy for the detection of coronary disease.[38] Accuracy is highest when myocardial perfusion is quantified[39,40] and measurement of myocardial velocities using Doppler tissue imaging allows an objective and reproducible assessment of myocardial wall motion.[31] Three-dimensional imaging is also expected to improve the detection of abnormalities of phase or thickening.
Conclusions
Clinical evidence involving more than 30,000 patients in multiple controlled trials has established stress echocardiography as an accurate, cost-effective non-invasive tool not only for the diagnosis of coronary artery disease but also for risk stratifying patients with known or suspected coronary disease and for detecting myocardial hibernation after myocardial infarction or in heart failure. It allows early discharge from accident and emergency departments or from the ward after myocardial infarction.