Diagnostic Criteria and Accuracy

The main sign of ischemia during stress echocardiography (SE) is the transient regional wall motion abnormality (RWMA) caused by a flow-limiting coronary artery disease (CAD). RWMA can be provoked by exercise or pharmacologic stressors, either by increased myocardial oxygen demand or decreased subendocardial myocardial oxygen supply with vasodilators determining underperfusion through horizontal and vertical steal phenomena. ^, All main SE modalities (exercise, dobutamine, vasodilators) have comparable diagnostic accuracy for the diagnosis of obstructive CAD, with higher specificity and slightly lower sensitivity compared with methods based on perfusion changes, such as myocardial contrast echocardiography, stress cardiac magnetic resonance imaging (CMRI) with contrast, and myocardial perfusion scintigraphy. Vasodilators have the same ischemic power than exercise and dobutamine, when appropriately high doses (state of art since 20 years) are used (0.84 mg/kg in 6 min), in presence of vulnerable coronary anatomy (flow-limiting epicardial stenosis, complex-type plaques, coronary collateral circulation favoring horizontal steal phenomena).

The higher sensitivity of perfusion changes compared with RWMA is easily understood on the basis of the ischemic cascade ( Fig. 50.1 ), an experimental paradigm established in myocardial ischemia caused by coronary occlusion or stress-induced ischemia with coronary stenosis. Regional perfusion abnormalities are the prerequisite and an earlier event than RWMA. However, in clinical practice, this reassuring one-size-fits-all model of classical ischemic cascade is challenged because of the frequent occurrence of microvascular angina. Patients with microvascular angina typically have exercise-related angina, electrocardiographic (ECG) or perfusion evidence of exercise-related ischemia, and either no stenoses or mild stenoses (<50%) that are deemed functionally nonrelevant. Coronary microvascular dysfunction can be either primary (in cardiac syndrome X) or secondary to left ventricular (LV) hypertrophy (e.g., hypertrophic cardiomyopathy, aortic stenosis, and hypertensive heart disease). In all these conditions, stress-induced RWMAs are the exception rather than the rule and occur in fewer than 10% of patients with perfusion changes, identifying a less favorable outcome.

SE does not imply exposure to ionizing radiation associated with coronary computed tomography angiography and nuclear perfusion imaging. The radiation risks are not negligible and are cumulative: exposure adds to exposure, dose to dose, and risk to risk during the lifetime. This must be taken into account in the risk–benefit assessment, especially in more sensitive groups such as young individuals and women. Contraindications to contrast agents (iodine contrast for computed tomography angiography and gadolinium-based chelates for magnetic resonance), cost considerations, and environmental impact (100-fold lower for SE compared to CMRI) need also to be considered. The increasing demand for SE activity posed by recent guidelines recommendations, cost considerations, growing concern about radiation exposure, and the expansion of indications and applications of SE well beyond CAD can be met by a laboratory performing a minimum of 100 studies per year, with availability of contrast agents for LV opacification, adequate knowledge of mechanisms of action and rate of complications of different physical and pharmacologic stresses, and resuscitation facilities readily available. SE is a part of the core curriculum in cardiology, ultrasound machines are ubiquitously available, and the technique is used by cardiologists living an imaging experience, not by radiologists living a cardiology experience.

The Main Sign Of Ischemia: Regional Wall Motion Abnormalities

The response of LV function to ischemia is monotonous and independent of the stress used. Normal myocardium shows systolic thickening and endocardial movement toward the center of the cavity. The normal hyperkinetic response during stress indicates an increase in normal movement and thickening. The hallmark of transient, stress-induced myocardial ischemia is the RWMA, in its three degrees of increasing severity: hypokinesia (decreased systolic thickening), akinesia (absent or negligible thickening), and dyskinesia (stretching). The severity of RWMA mirrors the severity of the regional subendocardial hypoperfusion. A reduction in subendocardial blood flow of about 20% produces a 20% decrease of wall thickening; a 50% reduction in subendocardial blood flow decreases regional wall thickening by about 40%, and when subendocardial blood flow is reduced by 80%, akinesia occurs. Dyskinesia appears when the flow deficit is extended to the subepicardial layer and ischemia is transmural.

The 17- or 16-segments model of the left ventricle represents the anatomical background for rapid (real-time) semiquantitative assessment of wall motion (from 1 = normal, to 4 = dyskinesis). The difference between rest and stress wall motion score index provides a simple assessment of the induced ischemia, combining the horizontal extent (the number of involved segments) with the vertical depth of ischemia (the severity of abnormality of each segment, from hypo- to dyskinesia). Definition of risk is important because patients at high risk benefit from revascularization with better survival and amelioration of symptoms. High risk is defined as a cardiac mortality rate greater than 3% per year, and low risk as a cardiac mortality rate less than 1% per year. The high risk is defined as stress-induced RWMA (hypokinesia, akinesia, or dyskinesia) is 3 or more segments out of 16. The low risk is defined by absence of RWMA during stress. The degree of RWMA also predicts the placebo-controlled symptomatic benefit after myocardial revascularization. The greater the downstream SE abnormality caused by the stenosis, the greater the reduction in symptoms after percutaneous coronary intervention.

Stress Echocardiography In Four Equations

Four diagnostic equations centered on RWMA describe the main SE response patterns: normal, ischemic, viable, and necrotic ( Table 50.1 ). A normal response shows a normal-hyperkinetic, synchronous wall motion with reduced ventricular volumes at peak stress ( Fig. 50.2 and ). An abnormal response shows a RWMA of territories fed by a stenotic coronary artery ( Fig. 50.3 and ). A viable response is an akinetic segment becoming normokinetic. A necrotic or scar response is an akinetic segment with a fixed response during stress. The biphasic response is a combination of viable and ischemic responses and corresponds to a viable response at low doses (akinesia becoming normokinesia) followed by ischemic response at high doses (normokinesia becoming hypo-, a- or dyskinesia).

TABLE 50.1

Stress Echocardiography in Four Patterns

Rest	Stress	Diagnosis
Normokinesis (score 1)	Normo- or hyperkinesis (score 1)	Normal
Normokinesis (score 1)	Hypo-, a-, or dyskinesia (score ≥2)	Ischemia
Akinesis (score 3)	Hypo- or normokinesis (score 1 or 2)	Viable
A- or dyskinesis (score 3 or 4)	A- or dyskinesis (score 3 or 4)	Necrosis

Figure 50.2, Stress echocardiogram: normal response. A normal wall thickening at rest ( A ) with hyperkinetic wall motion and reduced left ventricular cavity during stress ( B ). End-systolic frames are shown from the apical four-chamber view. A normal dipyridamole stress echocardiogram is shown in accompanying Video 50.2 .

Figure 50.3, Stress echocardiogram: ischemic response. A normal wall thickening at rest ( A ) with akinetic septum and dilated left ventricular cavity during stress ( B ). End-systolic frames are shown from the parasternal long-axis view. (An abnormal dipyridamole stress is shown in accompanying Video 50.3 .)

Video 50.2. A normal dipyridamole stress echocardiogram. Upper panels, Rest. Lower panels, Stress. Right panels, Pulsed Doppler flow velocity of the left anterior descending coronary artery showing a normal increase in flow. (Video courtesy of Josè Pretto, MD, Passo Fundo, Brasil.)

Video 50.3. An abnormal dipyridamole stress echocardiogram. Apical four-chamber view shows a normal wall motion at rest (left) , with akinesia of the apex after a high dose (right) . (Video courtesy of Jorge Lowenstein, MD, Buenos Aires, Argentina.)

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