Stress echocardiography, which was introduced in the early 1980s, has matured to a reliable cost-effective method for diagnosing and risk-stratifying patients with suspected or known coronary artery disease (CAD). The use of stress echocardiography as the non-invasive method of choice for assessment of CAD has increased exponentially worldwide. In the US alone, approximately three million stress echoes were performed last year. The hallmark of myocardial ischemia during stress echocardiography is reduced systolic wall thickening when myocardial O2 demand exceeds myocardial blood supply. This precedes the occurrence of chest pain and ST-T changes. The induction of reduced regional systolic wall thickening is specific to CAD. The advent of harmonic imaging, availability of contrast microbubbles and the advancement of digital imaging and display technologies have made stress echocardiography a reliable and reproducible technique for the assessment of CAD.
The diagnostic accuracy of any test for CAD varies according to the pre-test likelihood of finding it in the population. For example, if the pre-test likelihood of CAD is low then a positive test is likely to be false positive. Conversely, if the pre-test likelihood is high a negative test is likely to be false negative. It is also clear that non-invasive tests will have the greatest clinical value only in the population with an intermediate likelihood of CAD. In a meta-analysis, based on 44 studies where radionuclide perfusion imaging (another widely used investigation for the detection of CAD) was directly compared in patients with high to intermediate likelihood of CAD, stress echocardiography had a sensitivity of 85% (95% CI, 83-87%) with a specificity of 77% (95% CI, 50-74%) while single positron emission computed tomography (SPECT) had a sensitivity of 87% (95% CI 86-88%) with a specificity of 64% (95% CI, 60-68%). In models comparing the discriminatory abilities of stress echocardiography and SPECT against exercise testing with ECG alone, both stress imaging techniques performed significantly better. However, the incremental improvement in performance was greater for stress echocardiography (3:43%; 95% CI, 2.74-4). than for SPECT (1.49%; 95% CI, 0.91-2.08).
Another attribute of an ideal non-invasive test is to identify patients at high risk of having multi-vessel coronary artery disease, because these patients have poor outcome even in the presence of normal LV function. Clinical variables on their own can identify such patients and exercise electrocardiogram (ECG) also improves detection of multivessel disease (MVD). The question of stress echocardiography improves detection of MVD over and above the clinical and exercise data. In a study by Rogers et al., the presence of abnormality in multiple vascular territories during exercise echocardiography identified additional patients with MVD, confirmed in another study using dobutamine echocardiography.
Outcome After Normal Stress Echocardiography
The outcome of normal stress echocardiography has been assessed in several large studies. In a study of 2,829 patients with normal rest and exercise echocardiography, followed up for six years, mortality was less than 1% per annum. The cardiac mortality in 4,479 patients with normal pharmacological stress echocardiography was 0.7% per patient per year in another study. In a smaller study involving 252 patients in a busy UK district general hospital, patients with a normal stress echocardiogram in a group with predominantly intermediate, pre-test likelihood of CAD followed for two to eight years, cardiac mortality was only 0.4% per year and a combined end-point of cardiac mortality and acute myocardial infarction (AMI) was 0.8% per year.
Outcome After an Abnormal Stress Echocardiography
Stress echocardiography can quantify the severity and extent of myocardium in jeopardy, thereby predicting risk. The total amount can be assessed at peak stress by adding the peak stress score and dividing by the number of segments (summed stress score) assessed in a polar map using the American Society of Echocardiography 16-segment left ventricular model. In a study involving 5,375 patients undergoing exercise echocardiography in which the patients were followed up for 10.6 years, the extent of wall motion abnormality calculated as summed stress score, incrementally predicted cardiac mortality.
Similar predictive power of a positive result to a test was demonstrated using dobutamine stress echo-cardiography in a study involving 3,156 patients, followed up for nine years. Ischemia and the extent of abnormal wall motion were shown to be independent predictors of cardiac death. The type of dobutamine response predicted outcome. Patients who showed resting left ventricular (LV) dysfunction with additional ischemia had a worse outcome compared with those with ischemia alone, suggesting greater amounts of myocardium in jeopardy. The prognostic value of pharmacological stress echocardiography relative to coronary angiography was addressed in a subgroup of 4,037 patients who underwent coronary angiography without an intervention. Coronary arteriorgraphy data did not add significant predictive power to the model compared with stress cardiographic variables.
Risk Stratification After Acute Myocardial Infarction
Thombolysis is widely used in the UK in patients, with evolving ST-elevation AMI. Despite its early use, many patients are left with significant residual LV dysfunction due to post-ischemic stunning or myocardial necrosis. Post-ischemic stunning implies good prognosis as patients almost always recover LV 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 echo-cardiography to accurately discriminate between stunned and necrotic myocardium after AMI. The lack of dobutamine-induced contractile response suggests a poor prognosis as demonstrated by at least two recent studies. In one study, dobutamine echocardiography was performed in 214 patients at 12±6 days after AMI. During a follow-up period of 9±7 months, 12 cardiac deaths occurred. Absence of dobutamine response resulted in a greater incidence of hard cardiac events. In another study, comprising 212 patients, performed in a similar group of patients sooner (4±3 days) after AMI but with a longer follow-up, indicated for the first time that the most powerful marker of mortality is the lack of dobutamine response of the infarct-related region - irrespective of whether patients subsequently underwent revascularistion or medical therapy.
Cost-effectiveness of Stress Echocardiography
One of the major arguments against the early performance of a stress imaging test, as opposed to the widely used stress ECG, with known or suspected CAD is the greater cost implications of such a strategy. However, this argument does not take into account differences in downstream costs that may arise from the use of a less accurate initial test. These include the possible inappropriate use of more expensive investigations and a failure to identify patients who go on to potentially costly complications. One major study supported by the American Society of Echocardiography addressed the cost-effectiveness of stress echo compared with stress ECG for patients with known or suspected CAD. Although initial procedural costs were greater, exercise echo was associated with a greater incremental life-expectation (0-2 years) and a lower cost of additional diagnostic procedures when compared with exercise ECG. Exercise echo was more cost-effective (Ôé¼2,615 per life-year saved) than exercise ECG. It was further concluded that patients with symptoms who need non-invasive evaluation are less likely to undergo coronary angiography and, hence, revascularisation if a stress echo is performed in preference to exercise ECG.
In another recent randomised study conducted in the UK, 432 patients presenting to the emergency department with suspected CAD, but with non-diagnostic ECG and negative cardiac enzymes, underwent stress echocardiography or exercise ECG for further risk stratification. Stress echocardiography was superior to exercise ECG in risk-stratifying these patients to low and high-risk groups and resulted in higher rate of early hospital discharge in the stress echo arm. Significantly more patients underwent additional testing based on exercise ECG results compared with stress echocardiography. The study showed that this strategy resulted in potentially significant cost-saving compared with stress ECG.
Future of Stress Echocardiography
Rapid development of myocardial perfusion imaging using ultrasound contrast agents may now allow simultaneous assessment of function and perfusion. This will perhaps allow not only improved assessment of wall motion both at rest and during stress but may also enhance the diagnostic value of stress echocardiography for the detection of CAD.