In the UK there is still an emphasis on coronary anatomy as currently assessed using coronary angiography; however, high-grade coronary lesion may not cause myocardial ischaemia, for example in the presence of extensive collateral vessels. Dynamic imaging to show the physiological effect of any coronary stenosis is therefore an important part of the investigation of patients with stable symptoms; however, dynamic imaging is still grossly underused in the UK. In the US, approximately three million stress echoes were performed last year (2004). In the UK, workforce documents suggest that 3.8 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 (ECG).
Defining Stress ECG
The hallmark of myocardial ischaemia during stress ECG is the occurrence of reduced systolic wall thickening. This precedes chest pain and electrocardiographic changes which makes stress ECG more sensitive than exercise ECG treadmill testing. Rest and stress images are interpreted for global and regional left ventricular size, shape and function (see Figure 1) and stress echocardiography can identify the site of coronary stenoses (see Figure 2). The total amount of myocardium in jeopardy predicts risk, and prolonged persistence of systolic wall thickening abnormality may also identify severe coronary artery disease (CAD).4 Stress echocardiography can also predict the presence of myocardial hibernation.
Evidence that Stress Echocardiography is Effective
Diagnosis of CAD
The sensitivities for the detection of CAD are 85%, 80% and 78% for exercise, dobutamine and dipyridamole stress, respectively, and the corresponding specificities are 77%, 86% and 91%.5,6 Stress ECG can also identify multivessel disease,8,9 which is important since such patients have poor outcome even in the presence of normal left ventricle (LV) function.
A normal stress ECG gives an annual risk of 0.4% to 0.9% based on a total of 9,000 patients,10-13 the same as for a normal stress myocardial perfusion scan.20,21 This also holds true for patients with diabetes;15 thus, in patients with suspected CAD, a normal stress ECG confers an excellent prognosis and coronary angiography can safely be avoided. By contrast, an abnormal stress ECG is associated with a far higher risk of events, which is directly related to the extent of the wall motion abnormality (see Figure 3) in patients with15 and without diabetes.10
In clinical practice, the important question is whether a test provides incremental and independent information over and above clinical data. Information derived from exercise ECG10 is incremental and independent of clinical data, Duke score and resting LV function. In a study of 3,156 patients followed for nine years,14 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 LV dysfunction and additional ischaemia had the worse outcome compared with ischaemia alone. In another study involving 7,333 patients12 undergoing pharmacological stress ECG, the outcome of 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, coronary arteriography data did not add significant predictive power to the model (see Figure 4).
Detection of Hibernating Myocardium
Hibernation implies myocardium that fails to contract normally but which may recover after revascularisation. It occurs in the presence either of 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. Revascularisation is effective in heart failure (HF) only in patients with hibernating myocardium.34 The sensitivity and specificity of low-dose dobutamine ECG for predicting recovery of regional function following revascularisation are 84% and 81%, respectively, comparable with more expensive techniques (see Table 1).22,39 Furthermore, revascularising myocardium designated as hibernating on dobutamine ECG improves survival.23-26 Randomised trials are under way to address the relative benefit of revascularisation versus medical therapy in patients with hibernating myocardium.27
Despite thrombolysis, many patients are left with significant residual LV dysfunction, either due to post-ischaemic stunning or myocardial necrosis. Post-ischaemic stunning implies a good prognosis as patients almost always recover LV function in the absence of residual flow limiting infarct-related artery stenosis. ECG during low doses of dobutamine demonstrates increased contractility in these dysfunctional segments. Several studies have confirmed the ability of dobutamine ECG to accurately discriminate between stunned and necrotic myocardium after acute myocardial infarction (AMI)16,17 with similar sensitivity to but higher specificity than radionuclide perfusion imaging.18 Myocardial necrosis or a lack of dobutamine-induced contractile response is a more accurate marker of a poor prognosis19 than angiography or clinical variables (see Figure 4) with or without subsequent revascularisation.20 Stress ECG can also stratify risk by demonstrating distant wall motion abnormalities implying multivessel disease.19 Indeed, after revascularisation, the extent of non-viable myocardium in one study19 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 disease were independent predictors of cardiac events.
Cost-effectiveness of Stress ECG
Stress imaging is more expensive than treadmill exercise testing, but ultimately leads to cost savings because of its greater accuracy. Marwick et al28 studied 7,656 patients undergoing exercise testing, of which half underwent stress ECG. Compared with exercise ECG, stress ECG identified more patients as low risk and fewer as intermediate and high risk (see Table 2). Survival was greater in low and intermediate risk and lower in high risk patients and was better classified by stress ECG than exercise ECG. Although initial procedural costs were greater, exercise ECG was associated with a greater incremental life-expectation (0 to two years) and a lower cost of additional diagnostic procedures compared with exercise ECG. Exercise ECG was more cost-effective (Ôé¼2,615/life year saved) than exercise ECG. 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 ECG is performed in preference to exercise ECG. Similar results were obtained in a study of patients presenting with chest pain to an accident and emergency (A&E) department in the UK29 and in patients with asymptomatic diabetes mellitus.30
Comparing Stress ECG with other Imaging Techniques
Radionuclide single-photon-emission tomography (SPECT) has a slightly higher sensitivity than stress ECG and a lower specificity. In a meta-analysis7 based on 44 studies when the two techniques were directly compared in patients without prior AMI and without past history of known ischaemic heart disease (i.e., in patients with high-intermediate likelihood of CAD), stress ECG had a sensitivity of 85% (95% confidence interval (CI), 83% to 87%) with a specificity of 77% (95% CI, 74% to 50%), while SPECT had a sensitivity of 87% (95% CI, 86% to 88%) with a specificity of 64% (95% CI, 60% to 68. In a study by Nagle et al., magnetic resonance imaging (MRI) was found to be superior to ECG for the diagnosis of CAD, but only in patients with suboptimal ECG imaging.31 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.1-3,32,33
ECG machines are universally available and relatively inexpensive, while MRI and SPECT are expensive. ECG does not involve ionising radiation and has the important advantage of being portable so that it can be taken to patients in emergency or coronary care units (CCUs). All techniques require training. In the case of stress ECG, 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. National workforce planning suggests the need for 11-15 ECG consultants per million, compared with 2.9 per million for nuclear medicine and one per million for developing specialities including MRI and cardiac computed tomography (CT). The development of stress ECG, as for all cardiac imaging, is seriously limited by a dearth of adequately trained cardiologists.
The Future of Stress ECG
Rapid development of myocardial perfusion imaging using ultrasound contrast agents now allows simultaneous assessment of both function and perfusion.34-36 This may allow not only improved assessment of wall motion both at rest and during stress but may also enhance the diagnostic value of stress ECG for the detection of CAD.37 Myocardial perfusion can be quantified, which would further enhance the diagnostic ability of stress ECG.38,39
With refinements in tissue Doppler imaging, assessment of myocardial velocity allows qualitative and reproducible assessment of myocardial wall motion. In a recent multicentre study, assessment of myocardial velocity provided parameters for quantitative evaluation of wall motion for the diagnosis of CAD;2 thus, in future, usage of ultrasound contrast agents and tissue Doppler imaging is likely to form an integral part of stress ECG.
Clinical evidence involving more than 30,000 patients in multiple controlled trials has established stress ECG as a powerful, cost-effective non-invasive tool not only for diagnosis of CAD but also for risk stratifying patients with known or suspected CAD. Dobutamine stress ECG is also accurate for the detection of hibernating or viable myocardium after MI or in patients with HF. It allows early discharge from A&E departments or from the ward after MI. It also reduces the need for coronary angiography.