Echocardiography is the most widely used non-invasive imaging method in cardiology worldwide. Several reasons justify its success, the most important being its ability to answer easily and repeatedly the pertinent clinical questions posed every day by clinicians about their patients. In addition, it has accommodated itself to the continuous technological and scientific developments of the last five decades. The early diagnosis of coronary artery disease (CAD) is extremely important, since it can be used to identify a subgroup of patients at higher risk of developing cardiovascular events, including sudden death. In addition, knowing that a patient has CAD may be extremely useful in different ways, including for risk stratification after an acute coronary syndrome, planning a therapeutic strategy, including the ideal method of revascularisation and, most importantly, guiding and monitoring the intervention.
The role of stress echocardiography in its different modalities has been well established over the years, demonstrating a high sensitivity and specificity in the diagnosis of previously unknown CAD, as well as in assessing patients with chronic CAD and after revascularisation procedures.1–3 During stress echocardiography, the presence of regional ischaemia is shown as the development of new wall-motion abnormalities not present at rest. Different stressors can be used, including exercise or pharmacological, such as dobutamine, dypiridamol or adenosine. The accuracy of stress echocardiography is dependent on the ability to visualise clearly the endocardial contours. It is known that in about 20% of patients endocardial definition is not good, limiting the ability to detect wall-motion abnormalities, defined as the development of impaired systolic thickening.4 Several technological developments over the last few years have helped in diminishing this limitation. These include the introduction of second harmonic imaging and the use of contrast agents to obtain left-ventricular opacification, thereby improving endocardial visualisation (see Figure 1).5
The presence of wall-motion abnormalities induced by myocardial ischaemia is secondary to the imbalance of myocardial blood flow and increased oxygen demand that occurs during stress. However, several studies have also demonstrated that stress echocardiography has a good sensitivity and specificity for multiple-vessel disease, but is more limited in the presence of single-vessel disease. This is particularly relevant in patients taking beta blockers, who have great difficulty in reaching adequate heart rates.3 Other methods have been introduced more recently to improve the accuracy of stress echocardiography in the diagnosis of CAD. These include the use of contrast agents in what is called myocardial contrast echocardiography (MCE) or myocardial perfusion imaging (MPI).
The use of MCE has been advocated by some to overcome the limitation of using myocardial thickening only to diagnose induced ischaemia (see Figure 2). MCE has the ability to assess microcirculatory flow. At baseline, approximately 8% of left-ventricular mass is made up of blood present in the microcirculation – myocardial blood volume (MBV) – 90% of which is blood in the capillaries. When contrast microbubbles are administered at a constant infusion rate and a steady state is achieved (approximately one to two minutes), the acoustic intensity measured from the myocardium after background subtraction (to eliminate native backscatter from myocardial tissue) provides a measure of MBV fraction.
Because 90% of MBV fraction comprises capillary blood, a single MCE image provides an assessment of capillary density in the different myocardial regions. Resting MBF and myocardial systolic wall thickening remain normal despite up to 85% of luminal narrowing. However, beyond 85% luminal stenosis, in the absence of collateral blood flow due to exhaustion of auto-regulation at this level of stenosis, resting myocardial blood flow (MBF) is reduced, resulting in acute myocardial necrosis. For the detection of coronary stenosis less than 85%, hyperaemic MBF or coronary flow reserve (CFR) (hyperaemic MBF/resting MBF) needs to be measured. During maximal hyperaemia achieved by vasodilator, dobutamine or exercise stress, MBF increases by approximately five times the resting value – i.e. CFR of five in the normal myocardium, whereas in the myocardium subtended by >50% stenosis CFR is much lower. MCE, by virtue of its ability to measure both resting and hyperaemic MBF, can measure CFR.6 MCE has also been shown to detect coronary stenosis by visual assessment of signal intensity and microbubble velocity. During hyperaemia, in the absence of significant tachycardia, myocardium subtended by normal coronary artery shows no change in microbubble signal intensity. However, in the presence of coronary stenosis hyperaemia results in a decrease in MBV proportional to the severity of stenosis and a resultant perfusion defect on MCE.
Besides its use as a diagnostic tool for myocardial ischaemia, stress echocardiography has also been used for risk stratification and assessment of prognostic outcome. Tsutsui et al.7 assessed myocardial perfusion and wall motion during dobutamine stress echocardiography (DSE) in predicting the outcome of patients with known or suspected CAD during a median follow-up of 20 months. MPI showed a significant incremental value over clinical factors, resting ejection fraction and wall-motion responses in predicting events. The three-year event-free survival was 95% for patients with normal wall motion and perfusion, 82% for normal wall motion and abnormal perfusion and 68% for abnormal wall motion and abnormal perfusion. Thus, the combination of perfusion and wall motion offers the best prognostic data in this group of patients.
The assessment of myocardial viability in order to differentiate viable from necrotic, non-viable myocardium is crucial in patients after an acute myocardial infarction (AMI) or in chronic CAD. The main purpose of this distinction is to identify those patients who will benefit most from revascularisation procedures, such as percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft (CABG). Low-dose DSE (LDSE) has been used to assess myocardial viability and contractile reserve. MCE has also been used in this setting based on the persistence of capillary integrity in the viable myocardial segments. It has been suggested that presence of preserved microvasculature (capillary integrity) is a more sensitive marker of recovery of function than contractile reserve on DSE, despite a lower specificity.8,9 In addition, it has been shown that the amount of residual myocardial viability assessed by MCE is a strong predictor of hard cardiac events in patients following AMI and thrombolysis.10
Senior et al.11 showed an incremental value of MCE in patients undergoing LDSE for the assessment of myocardial viability following AMI. They demonstrated that the presence of contrast enhancement even in segments that lacked contractile response during DSE resulted in improvement in regional function compared with those with no contrast enhancement. Therefore, the simultaneous evaluation of contractile reserve and perfusion during LDSE may improve the detection of viable myocardium.
The use of Doppler myocardial imaging (DMI), including tissue velocity imaging (TVI) and strain-rate imaging (SRI), is feasible during DSE. TVI may be used in patients with normal resting function.12,13 In patients with wall-motion abnormalities at baseline, however, SRI provides quantitative and objective parameters of clinical significance that are at least equivalent when assessed by an experienced observer. Voight et al. showed that SRI is superior to TVI in identifying regional ischaemia.14 Thus, SRI may be used as an additional tool to objectify DSE reading in difficult circumstances and to shorten the learning curves of novices.
In brief, the use of stress echocardiography in the diagnosis of patients with suspected or known CAD, as well as in prognostic assessment of these patients, has been pivotal, and recent years have seen several refinements in the technique, including the addition of other technologies, such as contrast and myocardial velocity and deformation parameters. In the future it will continue to be a powerful tool in this regard.