Stress Echocardiography

The Cleveland Clinic Cardiology Board Review, 2ed.

L. Leonardo Rodriguez and Thomas H. Marwick

Stress echocardiography (SE) is one of the main diagnostic modalities used in the evaluation of patients with known or suspected coronary artery disease (CAD). Stress echo permits an integral evaluation of global and regional ventricular function, valvular integrity, and, most important, myocardial response to stress. The Class I indications for SE in chronic ischemic heart disease are diagnosis of ischemia in symptomatic individuals and the assessment of myocardial viability (hibernating myocardium) for planned revascularization (dobutamine echo). In addition, the referral base to the test is being augmented by situations when the effects of increasing cardiac reserve are sought in patients with valvular heart disease, diastolic dysfunction, pulmonary hypertension, and hypertrophic cardiomyopathy.

The accuracy of SE is superior to stress electrocardiography (ECG) and comparable to that of nuclear stress testing. In general, SE is less sensitive for single vessel CAD but more specific than perfusion imaging.

Numerous studies have validated the prognostic significance of SE, with a negative test carrying a very low risk (<1%) of major cardiac events over the subsequent 4 to 5 years. SE can also distinguish viable from scarred myocardium. The ability to predict which patients with left ventricular (LV) dysfunction will benefit from modern revascularization techniques is an important piece of information that may facilitate the discussion of benefit and risk for intervention that may carry significant risk. Although the accuracy and prognostic implications of dobutamine stress echocardiography (DSE) in the detection of viability are comparable to the more contemporary modalities of positron emission tomography (PET) imaging and magnetic resonance imaging (MRI), the role of dobutamine-induced augmentation in predicting functional recovery has been challenged by the recent results of the STICH trial. Within the realm of valvular heart disease, SE has an increasing role in predicting the functional significance of a variety of valvular lesions. Compared to other noninvasive modalities, SE is safe, widely available, relatively inexpensive, and avoids radiation exposure. However, its interpretation remains subjective and requires a considerable learning curve with substantial interobserver variability. Much effort has been devoted toward quantitation—for example using strain—but this remains challenging.

SE detects ischemia earlier in the ischemic cascade than ECG and before symptoms appear by identifying new regional wall motion abnormalities (RWMA) (Fig. 11.1). SE adds to exercise ECG particularly when the baseline ECG limits ST-segment assessment such as in left bundle branch block (LBBB), intraventricular conduction delay, paced rhythms, left ventricular hypertrophy (LVH), and digitalis effect.

FIGURE 11.1 Ischemic cascade. (From Daly RP. Stress Echocardiography. In: Griffin BP, Topol EJ, eds. Manual of Cardiovascular Medicine, 3rd ed. Philadelphia: Lippincott Williams & Wilkins, 2009:633, with permission from Wolters Kluwer Health.)

FORMS OF STRESS

Exercise Echocardiography

The most physiologic form of stress testing remains exercise. In addition to the echocardiographic data, exercise provides important physiologic information for prognosis and risk stratification. Exercise echo can be done using a treadmill or bicycle. The advantage of bicycle exercise is that imaging can be performed during stress. For treadmill exercise, patients must be taken off the treadmill and the echo images acquired within 1 minute of peak exercise. However, bicycle exercise is more effort dependent and therefore less reliable in reaching a target heart rate. Exercise is also preferred for noncoronary indications such as valvular heart disease or hypertrophic cardiomyopathy.

Pharmacologic Stress Echocardiography

Approximately 30% of patients are unable to exercise for reasons such as peripheral vascular disease, obstructive lung disease, or musculoskeletal problems. For these patients, pharmacologic SE can be performed. There are three options for pharmacologic SE: (a) sympathomimetic agents such as dobutamine, (b) vasodilator agents such as adenosine, and (c) atrial pacing.

Of the sympathomimetic agents, dobutamine has the largest clinical experience. It produces stress through an increase in myocardial oxygen demand via its positive inotropic and chronotropic effects. At low doses, it has positive inotropic effects mediated through cardiac α and β₁ receptors. At high doses it possesses chronotropic effects through the β₂ receptor. Dobutamine can be combined with atropine to achieve a target heart rate of 85% of age-predicted maximum heart rate. Contraindications to atropine use include angle-closure glaucoma and severe benign prostatic hypertrophy. In patients who are morbidly obese without other viable noninvasive options for risk stratification, dobutamine has been combined with transesophageal echo to avoid the potential morbidity of cardiac catheterization. When assessing viability, dobutamine is preferred for assessment of contractile reserve at low doses.

Vasodilators, such as adenosine or dipyridamole, induce ischemia via a coronary steal effect that preferentially shunts blood away from myocardial segments supplied by stenotic coronary arteries. Adenosine has a short half-life, and both have fewer side effects than dobutamine. However, the intensity of ischemia is also less, so the echo findings are also less pronounced, resulting in a lower sensitivity of approximately 50% to 60% and a decreased ability to detect small amounts of ischemia in patients with single-vessel disease. Atropine is required in all subjects in order to gather equivalent data. Vasodilator stress is commonly used in Europe and when myocardial perfusion data are sought with myocardial contrast echocardiography.

Atrial pacing, either by transvenous or transesophageal routes, has been used to achieve stress. The small increases in rate/pressure product and general poor tolerability of pacing have prevented this method from having general acceptance.

IMAGING TECHNIQUE

The typical treadmill protocol involves acquiring a series of resting images: parasternal long-axis, parasternal short-axis (including apical), and apical four-, three-, and two-chamber views. These images are stored digitally and then compared side by side with similar views acquired immediately poststress. During bike stress echo testing, images are recorded at rest and after each increment of load.

The dobutamine echo protocol starts with resting images in the same parasternal and apical views already mentioned. The infusion is started at 10 µg/kg/min, and this dose is increased every 3 minutes to 20, 30, and 40 µg/kg/min. Atropine is administered if the patient does not achieve >85% of predicted maximal heart rate (PMHR) and handgrip can also be added.

Harmonic imaging is now used routinely for better endocardial definition. LV opacification has an important role for patients with suboptimal images to improve visualization of endocardial thickening, as this is the most specific marker for ischemia.

INTERPRETATION OF STRESS ECHO

At rest, akinesis (excursion <2 to 3 mm) and dyskinetic segments are often believed to be consistent with a transmural infarct—certainly, this is more likely if the wall is also thinned (<6 mm). Hypokinetic segments demonstrate a partial infarct or viable myocardium.

Responses to stress echo and their interpretations are summarized in Table 11.1. Results are reported graphically in bull’s-eye form (Fig. 11.2), with segments assumed to correspond to a particular coronary distribution (Fig. 11.3). The traditional 16-segment ASE model has been supplanted by a 17-segment AHA model that includes the apical cap, although it needs to be acknowledged that the apex is often not visualized at 2-D echocardiography. Each wall segment is graded subjectively as normal, mildly hypokinetic, severely hypokinetic, akinetic, or dyskinetic in both the rest and stress images. A normal response to stress echo involves a global increase in contractility and hyperdynamic wall motion, and a gradual increase in heart rate. This is manifested by increased wall thickness, increased endocardial excursion, and a reduction in cavity size with stress.

TABLE

11.1 Stress Echocardiography Responses and Interpretation

From Daly RP. Stress Echocardiography. In: Griffin BP, Topol EJ, eds. Manual of Cardiovascular Medicine, 3rd ed. Philadelphia: Lippincott Williams & Wilkins, 2009:637, with permission from Wolters Kluwer Health.

FIGURE 11.2 Typical bull’s-eye representation used for reporting the 17 myocardial segments model. (From Daly RP. Stress Echocardiography. In: Griffin BP, Topol EJ, eds. Manual of Cardiovascular Medicine, 3rd ed. Philadelphia: Lippincott Williams & Wilkins, 2009: 639, with permission from Wolters Kluwer Health.)

FIGURE 11.3 Relationships among the 17 myocardial segments in the American Heart Association (AHA) classification system and their coronary artery supplies. The four standard views are used to delineate the associations between coronary artery distribution and the segments. (From Daly RP. Stress Echocardiography. In: Griffin BP, Topol EJ, eds. Manual of Cardiovascular Medicine, 3rd ed. Philadelphia: Lippincott Williams & Wilkins, 2009: 638, with permission from Wolters Kluwer Health.)

A decrease in overall ejection fraction (EF) with LV dilation poststress is an abnormal response that usually represents global ischemia. There are, however, other causes of global hypokinesis, such as a hypertensive response and severe valvular regurgitant lesions.

The use of modern display systems for dobutamine stress echo enables comparison of gradation of function at multiple stress levels—typically at rest, low-dose, prepeak, peak, and recovery. The recovery image is a valuable addition as the normal response to dobutamine involved not just an increase in endocardial thickening but also a marked reduction in cavity size, which may reduce wall stress. Because of this, wall motion abnormalities (WMA) may become apparent or more apparent as the LV fills after stress—the same effect can be derived with the use of beta-blockade. Systolic cavity obliteration is not uncommon—although prognostically reassuring, it decreases the sensitivity of the test. Another finding with little clinical significance during dobutamine stress is the development of systolic anterior motion of the mitral valve with a dynamic LVOT gradient.

Reproducibility of SE within centers is generally very good, yet concordance may be <80% between different centers, especially for technically difficult studies or mild CAD. Importantly, the prognostic implications of stress echo hold up across these differences.

USES FOR STRESS ECHOCARDIOGRAPHY

Traditionally, SE has been used for the diagnostic and prognostic assessment of CAD, but other uses include the assessment of myocardial viability with DSE, determining functional significance of valvular heart lesions, and provocation of subclinical disease—including inducible LVOT gradients, diastolic dysfunction, and inducible pulmonary hypertension.

Diagnosis of CAD

The diagnosis of CAD is made when RWMA are present. Ischemia is diagnosed when new or worsening areas of WMA develop with stress. The accuracy of stress echo for the detection of CAD is greater than that of ECG exercise stress testing alone and equivalent to that obtained with myocardial perfusion. The sensitivity ranges from 75% to 87%, and the specificity ranges from 74% to 80%, depending on disease prevalence. As with all noninvasive modalities, SE is less sensitive for single-vessel disease than for multivessel disease. Table 11.2 lists causes of false-positive and falsenegative SE.

TABLE

11.2 Causes of False-Positive and False-Negative Stress Echocardiographic Test Results

DBP, diastolic blood pressure; LBBB, left bundle branch block; LV left ventricular; SBP, systolic blood pressure; WMAs, wall motion abnormalities.

From Daly RP. Stress Echocardiography. In: Griffin BP, Topol EJ, eds. Manual of Cardiovascular Medicine, 3rd ed. Philadelphia:

Lippincott Williams & Wilkins, 2009:641, with permission from Wolters Kluwer Health.

Compared to exercise ECG, SE is more sensitive and specific, as would be predicted based on the ischemic cascade in which RWMA occur prior to ECG changes (see Fig. 11.1). Compared to nuclear stress testing, SE is less sensitive, because perfusion precedes the development of WMA, but is more specific.

DSE has a sensitivity of 68% to 76% and a specificity of 80% to 85%, which is comparable to that of exercise echocardiography. Vasodilator SE demonstrates a significant decrease in sensitivity of 50% to 75%, but with slightly increased specificity of 80% to 100%.

Prognostic Role

Stress echo provides information about the two most important determinants of cardiovascular prognosis, LV function and the severity and extent of ischemia.

Exercise echo offers incremental prognostic information particularly in patients with intermediate risk probability. The total number of abnormal segments both at rest and exercise-induced is important in predicting mortality. In patients with known or suspected disease, a negative test pertains to a low risk of subsequent events (<1% per year), whereas a positive study has a 10% to 30% 1-year event rate of MI, PCI, CABG, or death.

Marwick et al.¹ demonstrated that exercise echo is an independent predictor of death and provides incremental evidence to the traditional Duke treadmill score. It is particularly useful in further stratifying yearly mortality in those with intermediate Duke treadmill scores. Patients with an intermediate Duke treadmill score but normal SE had a 5-year mortality of 1.7%. For those with single-vessel ischemia, the mortality was 3.6%, and for those with multivessel disease, it was 6.7%.

For DSE, ECG changes and hypotension are relatively insensitive markers of ischemia, but RWMA with stress are analogous to ischemia development with exercise. A risk score based on clinical and echocardiographic data may be used to quantify the risk of events in patients undergoing DSE given a lack of exercise data:

Using cutoff values of 1.2 and 2.6, patients are classified into groups with 5-year event-free survivals of >95%, 75% to 95%, and >75%. This prognostic information may help facilitate rational decision making about medical management based on the likelihood of an adverse outcome, rather than a binary approach of whether the test is positive or negative.

Scar pertains to an intermediate prognosis between ischemia (high risk) and a normal study (low risk). In post-MI patients, the extent of LV dysfunction is more important than the extent of ischemic/viable myocardium, suggesting that with modern revascularization techniques, the long-term risk is more related to the inability to recover LV function.

For patients undergoing major noncardiac surgery, a positive DSE is associated with a risk of 7% to 25% for hard events (i.e., death and MI). The negative predictive value of DSE for this patient group is 93% to 100%. A meta-analysis concluded that nuclear stress testing and SE had comparable levels of accuracy for preoperative risk assessment, but that SE was significantly cheaper. Appropriate selection on the basis of pretest and operative risk is important as the use of stress echo in perioperative risk assessment is the most frequent source of inappropriate testing. Although questions remain as to whether preoperative revascularization can alter event rates, more exact knowledge of risk is certainly of value in the risk/benefit discussion in selected patients.

Role of DSE to Assess Viability

In patients with CAD and LV dysfunction, it is important to assess for myocardial viability. This is a Class I indication for the use of dobutamine echocardiography. For viability evaluation, the response to low-dose imaging is critical—continuous imaging is optimal (the period of augmentation can be brief), and an additional set of images is acquired at 5 μg/kg/min. The diagnosis of viability using this technique is based on the presence of contractile reserve, defined as an increase in wall thickening at low-dose dobutamine (5 or 10 μg/kg/min, which should be extended to 20 μg/kg/min in patients on long-acting beta-blockers). Abnormal myocardial segments can respond to dobutamine in a variety of ways (see Table 11.1). A biphasic response (characterized by improvement at low dose and then worsening at peak) is a specific marker of regional recovery after revascularization, and if seen in >4 segments, has an 80% sensitivity and 80% specificity of recovery of global function (e.g., an EF increment >5%) after revascularization. A uniphasic response (improvement at low dose and continued improvement at peak) is a less specific marker of likely recovery. If the segment does not improve at all with low dose or peak dose it is considered irreversibly damaged, or a scar. The accuracy of DSE to predict recovery after revascularization is similar to that of PET, with less sensitivity but greater specificity. DSE is substantially more specific than thallium redistribution imaging for predicting viability. The accuracy of DSE compared to MRI is also similar.

Stress Echo in Valvular Heart Disease

SE helps determine the hemodynamic and functional significance of valvular lesions including aortic stenosis, mitral regurgitation, mitral stenosis, and hypertrophic cardiomyopathy.

DSE is useful in assessing the presence of contractile reserve in patients with aortic stenosis and severe LV dysfunction. Lack of LV function improvement with dobutamine suggests a poor prognosis even after aortic valve replacement. An increase in valve gradients with dobutamine infusion with no change in aortic valve area suggests that the aortic stenosis is the main contributor to low output, and that valve replacement may alter the patient’s longterm prognosis. In some patients this technique may help to differentiate pseudostenosis from true aortic stenosis when severe LV dysfunction is present.

SE helps predict latent LV dysfunction in asymptomatic/minimally symptomatic patients with severe MR and normal LV function at baseline. Patients with increased LV size with stress present an increased risk of LV dysfunction postvalve repair. In patients with symptomatic moderate mitral stenosis or in those who are asymptomatic with apparent severe mitral stenosis, stress echo can evaluate the patient’s functional response to exercise. SE can determine functional capacity as well as pulmonary arterial pressures at peak stress, which can assist with surgical timing. SE can help explain exertional symptoms in a patient with hypertrophic cardiomyopathy with mild or no resting gradients. Furthermore, important prognostic and hemodynamic information, such as hypotension with peak stress, can be gained from SE in this patient population.

CONCLUSIONS

The current era has brought a number of new technologies for the diagnosis of CAD. Nonetheless, SE is a remarkably versatile test, and its simplicity, ease of access, and inexpensiveness are likely to make it even more attractive in the coming era of bundled care.

REFERENCE

1. Marwick TH, Case C, Sawada S, et al. Prediction of mortality by exercise echocardiography: a strategy for combination with Duke treadmill score. Circulation. 2001;103:2566–2571.