Echocardiography in Pediatric and Adult Congenital Heart Disease, 2nd Ed.

34. Stress Echocardiography

Robert A. Bruce, the father of exercise cardiology, once quipped, “You would never buy a used car without taking it out for a drive and seeing how the engine performed while it was running, and the same is true for evaluating the function of the heart.” This eloquent statement succinctly explains both the past motivation of early cardiologists to develop exercise protocols and the current need to modernize our evaluation of pediatric cardiovascular disease.

With the creation of, first, the Master’s Two-Step test and, second, the Bruce standardized treadmill test, cardiologists were provided for the first time with a standardized means to examine their patients outside of the resting condition. The ensuing introduction of the Bruce exercise protocol into the patient evaluation of congenital heart disease allowed cardiologists not only to predict the success of cardiac surgery but also to detect occult cardiovascular problems in otherwise asymptomatic individuals. The continued use of not only exercise but also other forms of stress in evaluating cardiac patients represents an extension of the resting physical examination. As Bruce stated in 1956, “an exercise test represents physical examination of the patient in relation to a reproducible amount of work.”

Despite the advances in and documented usefulness of stress testing, most cardiovascular assessment today unfortunately continues to be performed almost exclusively while the patient is comfortably resting (sometimes even sleeping) in a clinic or echocardiographic examination room. These appraisals, while yielding valuable information about resting conditions, afford little clue as to the behavior of the cardiovascular system when the patient becomes active, which is the typical state during most of the patient’s waking moments. Applying stress assessment in the clinical setting provides the means to observe the patient under conditions that closely mimic these more typically active states.

Further, in the relatively few cases when they are used, stress assessments have traditionally relied on electrocardiographic responses only. Interestingly, when he conceived of the exercise evaluation, Bruce focused attention on and found predictive ability with the hemodynamic responses, not the electrocardiographic changes, occurring with exercise. For instance, he not only discovered that the mechanism of exercise-induced hypotension is a consequence of fixed stroke volume but also that these hemodynamic changes were predictive of adverse long-term outcome. These conclusions acquired both during and after the exercise test were founded on physical examination alone. Since then, echocardiography has revolutionized cardiovascular diagnostics. The coupling of echocardiography with exercise or other forms of stress is a natural progression of exercise science because it provides the window for more direct, accurate, and robust observations of the important and predictive hemodynamic responses discovered by Bruce more than 50 years ago.

EVOLUTION OF STRESS ECHOCARDIOGRAPHY SCIENCE

Stress echocardiography is the culmination of the parallel evolutions of exercise science and cardiac ultrasound imaging driven, primarily, by coronary artery disease as a major public health problem. Exercise science had its beginnings in 1918 when the first objective measure of cardiac dysfunction during stress was made by Bousfield, who observed ST-segment depression occurring with angina. Systematic electrocardiographic exercise testing began 10 years later in patients with angina. In 1935, Master became the first to standardize the exercise test by developing an exercise protocol using a 9-inch two-step. However, this test was too strenuous for most patients and did not allow continuous data acquisition, prompting Bruce to develop first, the one-stage treadmill exercise test in 1949 and then, the multistage test (the Bruce protocol) in 1963.

The origins of stress imaging began in 1935, when Tennant and Wiggers noted by direct observation that interruption of coronary blood flow resulted in abnormal myocardial wall motion. However, it was not until 1970 that this phenomenon was visualized by ultrasound when Kraunz and Kennedy detected abnormal wall motion in patients with coronary artery disease immediately following exercise. The introduction of dobutamine stress echocardiography in 1986 improved image resolution because hyperpnea and patient motion associated with exercise were eliminated. In addition, dobutamine stress echocardiography provided a means to evaluate nonambulatory patients.

Pediatric stress echocardiography use began in 1980 when Alpert et al. performed simultaneous high-fidelity catheter pressure measurements and M-mode echocardiography during supine cycle ergometry in children with left-sided congenital heart disease to assess functional reserve. Exercise echocardiography was used throughout the 1980s in children for detection of subclinical left ventricular dysfunction in aortic insufficiency, insulin-dependent diabetes mellitus, and coarctation of the aorta. Pharmacologic stress echocardiography in children began in 1992, first using dipyridamole in patients after repair of anomalous left coronary artery from the pulmonary artery and, later, using dobutamine in children with a variety of cardiac pathology. However, even with these validated uses, stress echocardiography is underutilized in most pediatric echocardiography laboratories today.

THEORY BEHIND STRESS ECHOCARDIOGRAPHY

Stress echocardiography is a specific diagnostic modality categorized within a broader scheme of stress imaging protocols. However, all stress imaging protocols, including stress echocardiography, are unified by the concept that all use both a stressor (designed to stimulate patient hemodynamics) and a sensor (to evaluate the cardiovascular effects elicited by the specific stressor).

Stress echocardiography is applied for two basic diagnostic issues: (a) suspected impairment in myocardial perfusion or (b) hemodynamic behavior during stress of noncoronary cardiac pathology. In evaluating the first pathologic type (impaired myocardial perfusion) the theory underlying the utility of stress echocardiography simply relates to supply and demand. Myocardial oxygen demand is increased by applying the stressor. If the coronary arteries are normal, perfusion and myocardial oxygen supply also increase to meet the increased demands. However, if the coronary arteries are diseased, perfusion may not increase, creating a demand/supply mismatch, resulting in myocardial ischemia. The sensor is used to detect the resulting abnormality caused by this mismatch. For example, in the case of electrocardiography, demand/supply mismatch is manifest by ST-segment elevation. In the case of echocardiography, ischemia is manifest by a new or worsened myocardial wall motion abnormality. The manifestation of these abnormalities, and, therefore, the sensitivity of the sensors, is dependent on the degree of induced ischemic load (Fig. 34.1). Some sensors (e.g., positron emission tomography) are highly sensitive, and abnormalities (e.g., metabolic derangements) become evident with a brief and light ischemic load. Other sensors (e.g., ECG) are less sensitive, and the abnormalities sensed by them (e.g., ST-segment changes) become evident only with a long and heavy ischemic burden. The ischemia-induced wall motion abnormalities detected by echocardiography require an intermediate level of ischemic burden to become manifest and, therefore, echocardiography has an intermediate sensitivity.

In evaluating the second pathologic type (hemodynamic behavior of noncoronary heart disease) the theory underlying the utility of stress echocardiography is founded on the premise that stress data are more reflective of a patient’s typical diurnal activity state than are traditional data acquired in the resting state. In fact, data acquired during the resting state may be so dissimilar from data acquired during activity that the resting data may lead clinicians to a false sense of security regarding patient health. This premise has been similarly invoked for other cardiovascular tests that currently extend the patient evaluation beyond the office examination room such as ambulatory blood pressure and Holter monitoring. When using these two modalities, the clinician realizes that because symptomatology may not be present in the office milieu, additional data acquired during an active state are needed to capture symptoms and explore etiologies. Likewise, stress echocardiography, as a simulation of the patient’s active state, is used by clinicians to elicit and understand symptoms.

FIGURE 34.1. The ischemic cascade portrays the physiologic derangements (and the diagnostic sensors required to detect these derangements) occurring with a progressive ischemic burden. A low ischemic burden produces metabolic abnormalities that are detected by only highly sensitive sensors (e.g., positron emission tomography). A larger ischemic burden results in progressively deleterious derangements including diastolic dysfunction, wall motion abnormalities, myocardial stunning, and eventually myocardial necrosis. Angina develops with only a marked ischemic burden, making it a relatively insensitive indicator of coronary perfusion abnormalities. Wall motion abnormalities develop with an intermediate ischemic burden so that stress echocardiography has an intermediate sensitivity. (Reprinted with kind permission of Springer Science and Business Media.)

INDICATIONS

The indications for stress echocardiography must be discussed in the context of Bayes theorem which demonstrates that the clinical utility of a test, even with good sensitivity and specificity of the test, is related to the prevalence of disease in the population undergoing testing. For example, if a population has low prevalence of the disease, a positive test will have little predictive valve given the large number of false-positive results.

Bayes Theorem

Bayes theorem is a result in probability theory that demonstrates that the accuracy of a test with imperfect sensitivity and specificity is related to the prevalence of that disease in the population undergoing testing (Fig. 34.2). Specifically, the positive and negative predictive values of a test are dependent on the prevalence of the disease, so that low disease prevalence is associated with a high false-positive rate but a low false-negative rate. For example, in the evaluation of chest pain in an elderly, hypertensive adult patient, the positive predictive value of stress echocardiography would be appropriate and useful because the prevalence of coronary artery disease is high in elderly, hypertensive adults. The same would be true for a patient who has coronary artery strictures and thrombus due to Kawasaki disease. A positive test result would be highly likely to reflect advanced coronary artery disease. However, performing stress echocardiography in a healthy, thin adolescent complaining of chest pain would be of little help in detecting coronary artery disease because its prevalence is so low in healthy, thin adolescents. In this instance, Bayes theorem would predict that the test would have a high false-positive rate, so that a physician receiving a positive test result would still be left wondering if the patient truly has coronary artery pathology or, worse, establishing a false diagnosis of coronary artery disease. On the other hand, because Bayes theorem also predicts a low false-negative rate in this setting, the test is not totally without value. If the test were negative, a physician could conclude with very high certainty that the patient does not have coronary artery disease because Bayes theorem predicts a low false-negative rate in this setting. Proper application and interpretation of stress echocardiography are, therefore, essential in the pediatric population (Table 34.1).

FIGURE 34.2. In general, diagnostic tests are evaluated by their sensitivity (the proportion of patients with disease who have a positive test) and specificity (the proportion of patients without the disease who have a negative test). However, Bayes theorem demonstrates that even with good sensitivity and specificity, a test may have limited clinical usefulness. Positive predictive value (the probability that a person with a positive result actually has the disease) and negative predictive value (the probability that person with a negative result does not have the disease) are better measures of overall clinical usefulness of a test, because they incorporate information on both the test (i.e., sensitivity and specificity) and the population being tested (i.e., prevalence). With high prevalence of disease in the population being tested (90% in Example A here), of 1000 patients, 900 will have the disease and 100 will not. A test with 90% sensitivity and 80% specificity will correctly identify 810 of the 900 patients with disease (90% of 900) and 80 of the 100 patients without disease (80% of 100). Bayes theorem demonstrates that the test has excellent positive predictive value; the likelihood of disease in a patient with a positive test is very high. On the other hand, a negative test would not rule out the disease; the patient would still have more than a 50% chance of having the disease. With low prevalence of disease (3% in Example B here), the test with the same sensitivity and specificity has poor positive predictive value. In other words, it is likely that a patient with a positive test does not have the disease. The test, therefore, would not be useful as a screening test because it would not be able to identify diseased individuals. On the other hand, a patient with a negative test result would be virtually ensured of not having the disease.

Coronary Artery Disease

Like most pathology, coronary artery disease consists of an anatomic substrate with physiologic consequences. It is important to assess both aspects of coronary pathology because even an impressive coronary artery narrowing may have minor or no physiologic consequences as a result of the development of collateral circulation. Intervention in such a case may be unwarranted because it will not improve physiology any more than has already occurred with the natural development of these collateral vessels. Before the advent of stress echocardiography, clinicians were only able to assess the anatomic severity of coronary artery disease. Diagnostic modalities such as coronary arteriography yield detailed images of coronary anatomy but reveal little information regarding actual myocardial perfusion. The application of stress echocardiography provides assessment of physiologic severity of coronary artery disease because it evaluates the degree of compromise in myocardial perfusion for any given anatomic abnormality. A main indication for performing stress echocardiography, therefore, is determining the physiologic significance of anatomically abnormal coronary arteries.

The child with adult coronary heart disease Much emphasis has appropriately been placed on providing care for the adult with congenital heart disease. Because congenital heart surgery survival rates have markedly improved, this heretofore relatively small population is growing.

A parallel situation is occurring in the pediatric population. It is known that the atherosclerotic process begins in childhood. For most children, vascular involvement has been minor, so that treatment has been preventive. However, in some disease states, such as familial hypercholesterolemia, diabetes mellitus, chronic kidney disease, Kawasaki disease, and rheumatologic diseases, the childhood atherosclerotic process is hastened, leading to coronary events in childhood. An even more disturbing problem is that society is in the midst of a childhood obesity epidemic, which is accelerating this process even in children without other disease. Not only has childhood obesity resulted in more adults with cardiovascular disease, but it has also caused adverse cardiovascular risk factor changes during childhood. The presence of coronary artery disease and risk factors in children has resulted in a burgeoning of a heretofore uncommon pediatric population—the child with adult coronary artery disease, which similarly finds itself in the pediatric-adult netherworld previously reserved only for adult patients with congenital heart disease. Recent reports demonstrate that myocardial infarction may occur in adolescents. In children with coronary risk factors such as insulin-dependent diabetes mellitus, left ventricular wall motion is compromised at an age as young as 10 years. The etiology of this remains unclear but may be related to damaged endothelial function. Stress echocardiography will be an important diagnostic tool in evaluating this population.

Post cardiac transplant coronary artery disease Coronary artery pathology in children is most prevalent in the post cardiac transplant population. Transplant graft vasculopathy remains a major cause of late transplant mortality because it can result in chronic graft failure and arrhythmogenic sudden death. The disease is insidious and rapidly progressive. Because the coronary arteries are affected in a diffuse manner, the sensitivity of coronary angiography, which relies on having normal coronary segments adjacent to diseased segments for diagnosis of arterial disease, is imperfect, and more accurate surveillance methods have been required. Intracoronary ultrasound is likely the most sensitive method but it is invasive and may also produce false-negative results. Dobutamine stress echocardiography has proved to be the most sensitive noninvasive test in detecting its presence and has been recommended by the American Heart Association as a means to follow these patients.

Kawasaki disease Myocardial perfusion may be impaired in patients who have had Kawasaki disease because of thrombosed aneurysms and/or strictures at aneurysm sites. In addition, there is evidence that patients without any echocardiographic coronary artery involvement have abnormal endothelial function, putting them at risk for early atherosclerotic heart disease. Stress echocardiography using both exercise and dobutamine has proved effective in following these patients for myocardial perfusion abnormalities. In addition, dobutamine stress echocardiography has been useful in the risk stratification of patients with coronary artery aneurysms and stenoses. Specifically, using dobutamine stress echocardiography, it has been shown that patients in the lowest four American Heart Association risk levels are unlikely to have coronary perfusion abnormalities. Patients in the highest risk level (Category 5) may or may not have perfusion abnormalities, depending on the presence/absence of collateral circulation. Kawasaki disease is another example of how coronary artery physiology may be different in children versus adults. Children and adolescents may have very impressive coronary artery obstruction but have normal stress tests because of the development of collateral vessels. In most of these instances, bypass grafting would not be indicated. Stress echocardiography is an important tool in differentiating those patients who need revascularization from those who may safely undergo observation alone.

Arterial switch operation for transposition of the great vessels The arterial switch operation involves reimplanting the coronary arteries from the native aorta to the main pulmonary artery stump (the neoaorta). Following the arterial switch operation, coronary artery lesions are common and progressive, necessitating routine serial evaluation of perfusion with stress testing and sometimes resulting in the need for revascularization. In addition, stress echocardiography has been able to detect perfusion abnormalities in the absence of symptoms or arteriographic stenoses. The significance of such findings has yet to be determined; a constant finding in these patients is right coronary artery dominance with a hypoplastic distal left anterior descending coronary artery, which may result in the perfusion abnormality. Interestingly, these abnormalities are usually not present after the Ross operation, a procedure that also involves coronary reimplantation.

Coronary ostial stenosis Ischemia can occur in patients with supravalvar aortic stenosis, particularly those with Williams syndrome, because of coronary ostial stenosis, fusion of an aortic valve leaflet to the supravalvar ridge, or diffuse left main coronary artery narrowing. Coronary ostial stenosis may also be seen with an anomalous origin of the left coronary artery from the right sinus of Valsalva or in patients with transposition of the great vessels. This pathology may be very difficult to diagnose angiographically because the catheter is usually engaged in the coronary artery downstream from the narrowing. Stress echocardiography may therefore be particularly helpful in these individuals.

Other congenital heart disease Dobutamine and dipyridamole stress echocardiography has been useful in delineating the need for surgical management of anomalous origin of the left coronary artery from the pulmonary artery and in documentation of ischemia in coronary artery fistula. Other anomalies of the coronary artery origins such as the left main coronary artery from the right sinus of Valsalva or the circumflex coronary artery from the right main coronary artery have a higher incidence of atherosclerosis. Obstruction of left heart structures (valvar aortic stenosis, coarctation of the aorta, hypertrophic cardiomyopathy) is also associated with premature atherosclerosis. Finally, infants with pulmonary atresia and intact ventricular septum may have right ventricular-dependent coronary circulation and focal areas of coronary narrowing or frank coronary arterial interruption or aortocoronary atresia. Stress echocardiography could help to risk stratify these patients.

Ventricular Contractile Reserve

A second indication for stress echocardiography is in the evaluation of ventricular reserve. The contractile response to exogenous catecholamines has prognostic value. Patients with compromised ventricular function have elevated circulating catecholamines, decreased myocardial beta-receptor density, and downregulation of myocardial receptors and, therefore, have minimal response to exogenous catecholamines. Patients with better ventricular performance will have better beta-receptor responsiveness and better response to catecholamine administration. The magnitude of augmentation of cardiac performance during cardiovascular stress is the contractile reserve.

Measurement of left ventricular contractile reserve by stress echocardiography has been helpful in the detection and management of subclinical compromise of ventricular function in pediatric patients at risk for cardiomyopathy. For instance, stress echocardiography has shown that right and left ventricular reserve is depressed in children following repair of tetralogy of Fallot. In children after coarctation of the aorta repair, the resting left ventricular function is enhanced relative to control patients but contractile reserve is preserved (Fig. 34.3). Other investigators have shown that stress echo can detect subclinical left ventricular dysfunction in childhood cancer survivors who have received cardiotoxic chemotherapeutic agents. Some investigators have combined echocardiography with catheter-derived intracardiac pressure measurements during exercise to provide sophisticated contractility data helpful in differentiating mechanisms of ventricular reserve in congenital left-sided lesions. In patients after Fontan operation as the result of single-ventricle physiology, exercise echocardiography demonstrates normal increases in stroke and cardiac index during exercise until late submaximal levels, at which point these indices decrease. In patients who have undergone atrial switch operations for transposition of the great vessels, it has been shown with dobutamine stress magnetic resonance imaging that right ventricular contractile reserve correlates and is a key determinant of exercise capacity. In patients with atrial switch and with decreased right ventricular reserve by dobutamine stress echocardiography, brain natriuretic peptide is elevated, suggesting that either test may be able to predict future cardiovascular compromise.

FIGURE 34.3. Despite elevated left ventricular function at rest, contractile reserve in postoperative coarctation of the aorta patients (filled circles) is maintained relative to that in control children (open circles) as assessed by measurement of left ventricular shortening fraction (SF) during exercise. Data are expressed as mean +/– standard deviation. IPE, 3-PE, and 5-PE indicate immediately, 3, and 5 minutes after exercise, respectively; Max V02, maximal oxygen consumption; 50, 75, and 100, 50%, 75%, and 100% of maximal oxygen consumption, respectively. (From Kimball, Thomas R. Persistent hyperdynamic cardiovascular state at rest and during exercise in children. Am J Cardiol 1994;24:1.)

Many of the other studies documenting the utility of contractile reserve have been performed in adult patients only. For example, the technique has also proved valuable in evaluating contractile reserve in adult patients with obstructive sleep apnea and diabetes mellitus. In addition, left ventricular contractile reserve assessed by dobutamine stress echocardiography predicts 5-year mortality in patients with dilated cardiomyopathy. Evaluation of contractile reserve has also proved valuable in the evaluation of aortic and mitral insufficiency. In adult patients with aortic and mitral insufficiency, contractile reserve by exercise echocardiography is a better predictor of myocardial function after medical or surgical therapy than resting ejection fraction. These results in adult patients are encouraging and, as with most other echocardiographic indices, have found their utility first in the adult population. Similar studies need to be performed in children, as pediatric cardiologists are currently perplexed as to timing and efficacy of interventions in these patients. Stress echocardiography would be a robust tool to help resolve these dilemmas.

Pressure Dynamics

The final indication for stress echocardiography is to evaluate pressure dynamics during a simulated active state. As discussed previously, traditional evaluation of hemodynamics is performed during the resting state and, therefore, affords little information regarding how these parameters change during a child’s normally active life. Such data might prove helpful in conditions such as hypertrophic cardiomyopathy, valve stenosis, and pulmonary hypertension. In patients with rheumatic mitral stenosis, a mean mitral valve gradient of greater than 18 mm Hg at peak dobutamine is predictive of future clinical events (hospitalization, acute pulmonary edema, or supraventricular tachyarrhythmias). In asymptomatic patients with aortic stenosis, the degree of increase in aortic valve gradient during exercise provides incremental predictive value over resting echocardiographic and exercise electrocardiographic indices. In children after the Ross procedure, stress echocardiography has demonstrated that the aortic autograft hemodynamics during exercise are no different than those of normal aortic valves but that transpulmonary gradients are significantly different during exercise compared with normal control patients.

Exercise echocardiography has been used in children after repair of coarctation of the aorta to show that, despite a normal resting gradient, significant hypertension and arch gradients can develop during exercise. In keeping with the theme espoused by early exercise pioneers, these authors emphasize that “clinical assessment and definition of an ‘acceptable’ surgical repair of aortic coarctation should be viewed in the context of the patient’s functional exercise response as well as resting studies.”

In patients with hypertrophic cardiomyopathy, application of stress echocardiography has facilitated our understanding of the disease pathology. Traditionally, nonobstructive hypertrophic cardiomyopathy has been regarded as the predominant form of the disease, but the application of stress demonstrates that even these patients develop marked left ventricular outflow tract gradients. Others have used dobutamine stress echocardiography to assess the effectiveness of surgical myectomy in relieving the left ventricular outflow gradient. Clinicians now suggest that such patients may also be candidates for septal reduction therapy and advocate that stress echocardiography should be a routine component of the evaluation of hypertrophic cardiomyopathy patients without resting gradients.

Stress echocardiography has also been used to assess changes in pulmonary artery pressure. For instance, the technique has been helpful in understanding the elevation of pulmonary artery pressure during exercise in a subgroup of symptomatic patients with mitral stenosis with a relatively large mitral valve area. Exercise echocardiography demonstrates that this is because of poor left atrial compliance. Others have used exercise echocardiography to understand the mechanism of pulmonary hypertension in a variety of chronic lung diseases.

PREPARATION

Training

Administration of almost all stressors requires performing the echocardiogram in unique and sometimes challenging settings. For example, the hyperpnea and tachypnea caused by exercise are significant impediments to diagnostic images. Administration of a pharmacologic agent for the distinct purpose of eliciting myocardial ischemia is by definition a potentially dangerous act. Therefore, training in performance and interpretation of stress echoes is essential. General guidelines for the knowledge and training required to perform and interpret stress echocardiography have been established, but the clinical practice of stress echocardiography in pediatric laboratories varies considerably. Whereas administration of stress tests and evaluation of regional wall motion are staples of adult cardiology training, these topics are not broached in pediatric cardiology training. Pediatric cardiologists with an interest in performing stress echocardiography should obtain training from experienced adult cardiologists before beginning such an endeavor. Further, they should establish an ongoing relationship with adult cardiologists for the purpose of consultation in difficult cases or interpretation of questionable images. Pediatric nurses and cardiac sonographers could also benefit from obtaining training from their adult counterparts.

Stressors

Exercise is just one of many different stressors and may consist of either dynamic exercise (upright or supine cycle and treadmill) or isometric exercise (handgrip). Other stressors include pharmacologic agents (dobutamine, adenosine, dipyridamole, and isoproterenol), electrophysiologic pacing, mental (e.g., time-pressured computer-based tasks), and cold pressor (Table 34.2).

The specific stressor that is to be used is a clinical decision tailored to the patient’s age, exercise ability, cardiac pathology, and type of information desired. Each stressor has its unique advantages and disadvantages. For example, exercise has the advantage of most closely mimicking an athlete’s activity outside the office but carries the disadvantages of (a) negatively affecting the image quality of most sensors because of body motion and heavy breathing and (b) inability to use in younger patients (generally, younger than 7 years). Intravenous dobutamine administration is a stressor that has no age limitations, but the hemodynamic changes with dobutamine may be different than those occurring with physical exercise. In general, with exercise a maximal “stress dose” is administered, immediately after which the sensor (e.g., echocardiography) is used, whereas with pharmacologic stressors, submaximal “stress doses” are given while echocardiography is used continuously. This is advantageous for the patient as the test can be terminated at lesser (i.e., submaximal) stress doses if pathology or a serious adverse reaction is elicited.

Exercise Echocardiography

Exercise testing is a mainstay of pediatric cardiovascular evaluation, yet it is almost always obtained with electrocardiography as the sole diagnostic modality. With the simple addition of echocardiography, which adds no further annoyance to the patient, the test becomes much more robust. Dynamic exercise is the physiologic reference standard. In performing a treadmill test, the patient is exercised until exhaustion at which point he or she is immediately and quickly moved to a supine, left lateral decubitus position on an examination table. Echocardiographic data must be obtained within 60 to 90 seconds of test termination to ensure that the stress effects are still operative. Cycle ergometry can be performed in upright or semirecumbent postures and affords the opportunity of not only obtaining an immediate postexercise test as is done with the treadmill test but also acquiring echocardiographic data during the test itself. While the patient is exercising in an upright position, the sonographer places his or her “nonimaging” hand on the back of the patient to stabilize the chest, reduce patient thorax movement, and enhance imaging. With the patient in a semirecumbent position, the examination table serves this purpose. Using these techniques, it is possible to obtain submaximal and, more important, peak exercise data. These modalities are therefore useful in detecting the hemodynamic differences that sometimes occur between peak exercise and immediate postexercise. In addition, the inclusion of images during the intermediate stages of exercise improves the sensitivity of detecting ischemia.

Sometimes the clinical question does not focus on issues of dynamic exercise. For example, the issue of interest may be the hemodynamic changes occurring in an adolescent wishing to participate in an isometric activity such as high school weight training or wrestling. In these instances, an isometric exercise echocardiogram would be appropriate. Investigators have used isometric exercise (e.g., 3 minutes of handgrip pressure at 33% of patient-specific maximum) echocardiography to demonstrate that children with aortic insufficiency and normal resting function have accentuated systolic blood pressure response and decreased left ventricular systolic performance compared with control subjects.

Pharmacologic Echocardiography

Dobutamine, disopyramide, adenosine, and isoproterenol are the agents used for pharmacologic echocardiography. Dobutamine stimulates beta1-adrenergic receptors, causing increased contractility, heart rate, and myocardial oxygen demand, with little effect on beta2- or alpha-receptors. It is administered intravenously beginning with a dose of 5 to 10 μg/kg per minute and is progressively increased every 4 minutes by 10 μg/kg per minute up to a maximal dose of 50 μg/kg per minute as necessary. Echocardiographic images are obtained at each stage. Atropine (0.01 mg/kg up to 0.25-mg aliquots given every 1 to 2 minutes to a maximum dose of 1 mg) should be given to augment heart rate as needed. In children, maximal dobutamine dose and atropine are usually needed to achieve a target heart rate. Esmolol (10 mg/mL dilution—not the 250 mg/mL dilution used for drips) at a dose of 0.5 mg/kg should be available to rapidly reverse dobutamine in the event of ischemia or adverse events.

Isoproterenol stimulates beta1- and beta2-receptors, increasing heart rate and contractility and also causing systemic arterial vasodilation. It is administered intravenously at doses ranging from 0.05 to 2 μg/kg per minute. With each of these medications, the test termination points are achievement of target heart rate (85% of age-related maximal heart rate [220 – age in years]) or the presence of ischemia (either greater than 2-mm ST-segment depression or a new or worsened regional wall motion abnormality) or a serious adverse event.

Adenosine and dipyridamole are lesser-used agents. Adenosine causes dilatation of normal coronary artery segments, resulting in a steal from diseased segments. Dipyridamole inhibits adenosine reuptake, resulting in the same action. Adenosine is infused at a maximum dose of 140 μg/kg per minute with simultaneous imaging over 4 minutes. Dipyridamole is administered in two stages with continuous imaging. The first stage consists of a dose of 0.56 mg/kg over 4 minutes. The second stage is performed if there are no adverse effects and consists of a dose of 0.28 mg/kg over 2 minutes. Atropine can be used to augment heart rate. Aminophylline should be available for an adverse dipyridamole reaction.

Although similar, the cardiac effects of the pharmacologic agents are not identical to those of exercise. Cnota et al. compared the hemodynamic effects of peak dobutamine to peak exercise. Dobutamine infusion resulted in lower cardiac output, heart rates, and systolic blood pressure. At peak dobutamine (versus exercise), there was smaller left ventricular end-diastolic dimension, higher fractional shortening, and higher contractility as measured by velocity of circumferential fiber shortening. In patients with an atrial switch for transposition of the great vessels, differences between exercise and dobutamine stress have also been observed. For example, in these patients there is little if any right ventricular contractile reserve during exercise; but with dobutamine administration, there is a normal contractile reserve response.

Other Stressors

Other stressing methods are either rarely used or used only for unique situations. Mental stress can be delivered by a variety of means but the easiest are time-pressured computer-based tasks such as arithmetic or word problems. Electrophysiologic pacing can also be used as a stressing method. Cold pressor is a cardiovascular challenge resulting from immersion of one hand in ice water for 2 or more minutes, which increases systemic blood pressure and ventricular afterload.

Sensors

Echocardiography is only one of many potential sensors that can be used to assess the effects of the stressors described above. Although echocardiography is a valuable and robust sensing tool, it is important to remember that one of the other sensors may be more applicable (or combined with echocardiography) in a certain situation. These sensors include electrocardiography, magnetic resonance imaging, nuclear imaging, computed tomography imaging, and positron emission tomography.

Personnel

It is essential to have not only a qualified, trained physician but also an experienced sonographer administer the test as described earlier. In the case of pharmacologic stress, a nurse is needed for intravenous line placement, administration of medications, and monitoring of the patient.

Equipment

The ultrasound system should have the capability of storing motion clips digitally and a display that allows side-by-side comparison of clips from different stress stages. A system equipped with four-dimensional imaging capabilities makes acquisition and interpretation of wall motion particularly easy.

Monitoring equipment should include continuous electrocardiographic monitoring with a system that allows for easy detection of ST-segment changes—ideally, with the capability of comparing current ST segments to resting ST segments. An oxygen saturation probe and intermittent blood pressure monitors are also needed. Resuscitation equipment should be readily available.

Transpulmonary Contrast Agents

Transpulmonary contrast agents are protein microspheres consisting of an albumin, synthetic polymer, or phospholipid shell filled with inert gases (perfluoropropane, nitrogen, decafluorobutane, sulfur hexafluoride) that pass through the pulmonary capillary bed to opacify the left ventricle. The use of transpulmonary contrast agents for left ventricular opacification during stress echocardiography has been helpful in adult patients to decrease the number of non-interpretable wall segments, thereby increasing the diagnostic yield. In these situations, particularly difficult-to-image wall segments, such as the left ventricular apex, can be imaged much more clearly with the addition of a transpulmonary contrast agent. These agents have been shown to be safe and efficacious in children.

In general, stress images in children are of sufficient quality that contrast agents are not necessary. However, in certain patients, the images may be limited so that contrast can be helpful. The agents have also proved helpful and are recommended to confirm or exclude the apical variant of hypertrophic cardiomyopathy, ventricular noncompaction, and apical thrombus.

Commercially marketed contrast agents to date have had a somewhat checkered history. Questions of sterility, potential paradoxical emboli across intracardiac shunts, allergic reactions, possible cardiopulmonary adverse reactions and even death have tempered initial enthusiasm. Contrast agents should not be administered in patients with worsening or clinically unstable heart failure, acute myocardial infarction or acute coronary syndrome, serious ventricular arrhythmias, or respiratory failure. They should also not be administered to patients with right to left, bidirectional, or transient right to left cardiac shunts. Until these issues become resolved, transpulmonary contrast agents should be limited in use to those patients in whom standard imaging modalities are not diagnostic and, even in those cases, should be administered with caution.

CONTRAINDICATIONS AND POTENTIAL COMPLICATIONS

In adults with aortic valve stenosis, dobutamine stress echocardiography can precipitate atrial and ventricular tachyarrhythmias. Even so, this high risk population can undergo the test safely. There are no absolute documented contraindications to performing stress echocardiography in children. Nevertheless, careful thought should be given before administering the test to patients in very high risk populations such as patients with hypertrophic cardiomyopathy, significant aortic valve stenosis, and/or dysrhythmias.

It is known that individuals with structurally normal hearts, particularly if they have refrained from drinking or eating for any considerable time, may develop left ventricular outflow tract gradients during dobutamine stress echocardiography, which, in rare circumstances, could result in diminished cardiac output with syncope or angina. This has not been reported in children.

The most frequent potential complication in the pediatric population with dobutamine stress echocardiography is emesis. This occurs in approximately 10% to 20% of children undergoing the test. When it occurs, it does so most commonly at the peak dobutamine dose and usually after concomitant administration of atropine. In most studies, the peak heart rate images can be obtained and the dobutamine discontinued with prompt (within seconds) improvement in patient symptoms.

OUTPUTS AND INTERPRETATION

Ischemia manifests itself on the echocardiogram as a new or worsened regional wall motion abnormality. Traditionally, four echocardiographic views (parasternal long- and short-axis, apical two- and four-chamber) are acquired. From these four views, 17 different wall segments can be evaluated. A wall motion abnormality in a given segment corresponds to a perfusion abnormality of the coronary artery supplying the given segment (Fig. 34.4).

FIGURE 34.4. The 17 myocardial segments imaged during a stress echocardiogram. The parasternal long- and short-axis and the apical two- and four-chamber views are obtained. From these four views, 17 segments are obtained. Each myocardial segment is perfused by one of the three coronary arteries. A regional wall motion abnormality in a specific myocardial segment corresponds to a perfusion abnormality in the coronary artery serving that wall segment. In general, the septum, anterior wall, and apex are supplied by the left anterior descending coronary artery. The right coronary artery perfuses portions of the basal and mid septum and posterior wall, and the circumflex coronary artery supplies the posterior, lateral, and inferior wall. (From American Heart Association Writing Group; Standardized Myocardial Segmentation and Nomenclature for Tomographic Imaging of the Heart; American Heart Association.)

Identifying a wall motion abnormality may be difficult, particularly for a pediatric cardiologist. It is emphasized that pediatric cardiologists should receive training from adult cardiologists that are expert in stress echocardiography and maintain these relationships so that consultation advice remains readily available. In evaluating the left ventricle for wall motion abnormalities, it is helpful to first survey global left ventricular function. It would be unusual for a regional wall motion abnormality to be present in the face of normal global function. Abnormal regional wall motion is defined as both poorer endocardial excursion and lesser wall thickening. Each segment must be examined methodically for these two features.

Some ultrasound systems are equipped with quantitative or semiquantitative modalities that may assist in detecting regional wall motion abnormalities. These include regional assessment of strain and strain rate using Doppler tissue technology. With these modalities, a sample volume is placed directly on a wall segment of interest and the strain and strain rate are determined for that specific segment. Similar quantitative wall motion can be performed using standard two-dimensional imaging, using speckle tracking, which measures the velocity of the natural “speckles” or echo-densities in the myocardium.

For evaluations other than coronary perfusion, the output data will be specific to the question being asked. For example, this might include Doppler interrogation of antegrade valve flow to determine valve behavior during stress, Doppler interrogation of tricuspid insufficiency to estimate right ventricular/pulmonary artery pressure during stress, or assessment of ventricular function for an evaluation of contractile reserve. Evaluation often includes a combination of these assessments.

Prognostic Significance

The validity of using stress-elicited valve gradients, intracardiac pressure determinations, and ventricular function values for prognostic purposes has been questioned because the natural history of such stress results is unknown. For example, it is unclear whether a mean Doppler aortic valve stenosis gradient of 100 mm Hg elicited during maximal exercise carries the same serious implications of a similar gradient obtained at rest. Admittedly, it probably does not; but, on the other hand, such data should not be dismissed, particularly in light of the fact that the maximal exercise mean semilunar gradient in patients without valvar disease never exceeds 10 to 20 mm Hg.

An interesting study investigating exercise hemodynamics and subsequent cardiac changes in children with hypertension sheds some light. In this study, Mahoney et al. investigated, in hypertensive children, determinants of not only systolic blood pressure but also left ventricular mass, a known cardiovascular risk factor. These investigators found that follow-up (mean duration of 3.4 years) systolic blood pressure was predicted by initial resting blood pressure and initial maximal exercise blood pressure. More important, subsequent left ventricular mass was predicted by initial maximal exercise blood pressure alone, having no relation to initial resting blood pressure. These data support previous reports in adults that show left ventricular mass has only a modest relationship to resting blood pressure but strong relationships to mean 24-hour systolic blood pressure, blood pressure at work, and home blood pressures on a workday. The authors emphasize that exercise measures, not resting measures, are more valuable because they are predictive of future adverse cardiac changes.

RESEARCH

Stress echocardiography has been used to elucidate the mechanisms during exercise for maintenance of cardiac output, on the one hand, and exhaustion on the other. While exercising, children exhibit an initial rise in stroke volume that reaches a plateau at mild-moderate intensities. The initial rise in stroke volume is caused by (a) increased preload from skeletal muscle contraction, thereby mobilizing blood that is “pumped” into the heart and (b) decreased systemic vascular resistance caused by peripheral vasodilatation in the skeletal muscle. The plateau of stroke volume during moderate intensity relates to increased heart rate and shortening of diastole and systole. Although both systolic ejection and diastolic filling periods progressively decrease with exercise, the latter decreases more, so that at higher levels of exercise, the relative durations of diastole and systole are reversed compared with at rest. Decreased filling leads to decreased left ventricular volume, decreased preload, and decreased stroke volume. Rowland et al. performed exercise echocardiography in children with cardiomyopathic states (because of anthracycline toxicity primarily) to demonstrate that to sustain stroke volume at peak exercise (when diastolic filling and ejection times are short), there must be an increase in contractility.

Stress echocardiography in children has also been used to examine the adaptations occurring from training. During exercise, trained children increase cardiac output by increasing stroke volume (even at higher intensities), but in untrained children, higher cardiac output is achieved only by increasing heart rate.

CONCLUSION

The stress echocardiography work that has been highlighted in this chapter has revealed many insights into stress physiology. However, one of the most important is that despite a significant prevalence and diversity of anatomic coronary artery pathology, actual physiologic derangement in the form of ischemia is remarkably uncommon in the pediatric population. Perhaps this is related to a lesser disease severity in children than in the adult population. However, this appears unlikely because there are children who have anatomically severe coronary disease without symptoms or perfusion abnormalities. More likely, this phenomenon is caused by an increased adaptive ability for development of collateral vessels and/or for ischemic tolerance of the myocardium. It is hoped that cardiologists will learn from pediatric stress echocardiography that, in some instances, diagnosis of coronary artery anatomic pathology does not necessarily translate into a need for intervention and that the heart of a child has a robust adaptive ability to treat itself.

Stress echocardiography has provided clinicians and researchers with a window to examine and investigate children outside of the traditional setting of a quiet, resting state. The pediatric responses to stress as evaluated by echocardiography enable clinicians, on the one hand, to diagnose disease earlier in the disease process or, on the other hand, to reassure themselves and their patients that untoward events are unlikely. These modalities have also enabled researchers to establish the mechanisms for cardiac output increase and exhaustion in both trained and untrained children. Stress echocardiography is a powerful, robust tool that extends resting evaluations, thereby improving diagnostic capability and enhancing medical care to children.

SUGGESTED READING

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Questions

1.A family has just moved to your city and is being seen by you for the first time. She is a 12-year-old girl who had Kawasaki Disease at two months of age and reports a six-month history of exertional chest pain. Past history reveals that she is restricted from intense activity because of a past history of moderate-sized coronary artery aneurysms during her acute Kawasaki illness as an infant. There had been some resolution but she was left with residual small aneurysms in the proximal right, left main, and left anterior descending coronary arteries. She has been maintained on one baby aspirin per day. The pain is described as occurring over the mid-sternum, stabbing in quality, without radiation. It occurs when she runs during soccer games. She may also have some associated palpitations. Three months ago, she was seen by her prior cardiologist. At that time, her resting EKG was normal. Her resting echocardiogram showed small aneurysms without change from the previous study a year ago. The right and left ventricular function and size were normal. There were no regional wall motion abnormalities. The valve function was normal. There was no pericardial effusion. What was the best course of action at that time (three months ago) by the pediatric cardiologist?

A.Pulmonary function test with exercise

B.Observation

C.Exercise test

D.Exercise echocardiogram

E.Dobutamine stress echocardiogram

2.Continuing with the same patient described above, the records show that the previous pediatric cardiologist had obtained an exercise test. The peak heart rate was 148 bpm, her rating of perceived exertion was between 14-15 on the Borg scale of 20, and her peak respiratory exchange ratio was 0.9. She had no ST or T-wave changes on her electrocardiogram at peak exercise. Her physical exam reveals a fit, healthy girl. Her lungs are clear. Her heart sounds are normal and there is no click, gallop rhythm, or murmur. She has no hepatosplenomegaly or peripheral edema. Her pulses are strong throughout. Her electrocardiogram and echocardiogram remain normal. What is your next best course of action?

A.Cardiac magnetic resonance imaging

B.Exercise echocardiogram

C.Cardiac catheterization

D.Exercise sestamibi test

3.Continuing with the same patient, an exercise echocardiogram is obtained. At rest, there are no regional wall motion abnormalities and the electrocardiogram is normal. During exercise there is mild ST segment depression in the left precordial leads. Her heart rate reaches 194 bpm and her rating of perceived exertion reaches 20 on the Borg scale. She also complains of chest pain. Immediately after exercise, echocardiography shows hypokinesis and poor wall-thickening of the basal and mid anterior septum. Other wall segments demonstrate normal motion and thickening. These findings are consistent with:

A.decreased perfusion through the left anterior descending coronary artery.

B.right ventricular volume overload.

C.decreased perfusion through the right coronary artery.

D.pulmonary hypertension.

4.Continuing with the same patient, what is your next best course of action after obtaining the results of the exercise echocardiogram above?

A.Referral to cardiovascular surgeon

B.Exercise sestamibi test

C.Positron emission tomography

D.Cardiac catheterization

5.A four-year-old boy with Williams syndrome makes an unscheduled visit to you. The chief complaint is chest pain for the past two months. The pain is poorly described and does not seem related to any particular activity but is regular in frequency, occurring at least three times each week. His last echocardiogram four months ago demonstrated sinotubular narrowing of his aorta with a 70 mm Hg peak, 38 mm Hg mean gradient. There was left ventricular hypertrophy and normal left ventricular function. His physical examination is remarkable for Williams syndrome features, a blood pressure gradient of 25 mm Hg between the right arm (134/56) versus left arm (109/59), an active precordium, a III/VI systolic ejection murmur at the upper right sternal border, no diastolic murmur, normal heart sounds, and normal pulses throughout. He has no peripheral edema or hepatosplenomegaly. The electrocardiogram shows left ventricular hypertrophy. The echocardiogram shows continued narrowing of the sinotubular junction with a 63 mm Hg peak, 31 mm Hg mean gradient. What is your next best course of action?

A.Dobutamine stress echocardiogram

B.Exercise echocardiogram

C.Cardiac catheterization

D.Referral to cardiovascular surgeon

6.A 16-year-old boy comes to your office as a new visit for chest pain. He successfully made the varsity football team at his high school and started weight conditioning three weeks ago. He is starting in his first ever varsity game tomorrow night. Family history reveals a maternal grandfather with a myocardial infarction at 55 years of age. A paternal grandfather is 73 years old and has hypertension. The patient’s chest pain occurs with no specific activity. It is localized to the mid-sternum and left precordium and is described as stabbing in nature. It radiates to the left shoulder. It is not associated with meals, position, palpitations, or dizziness. Pertinent findings on his physical examination are a blood pressure of 143/74, healthy and fit appearing, quiet precordium without tenderness, normal heart sounds without click, gallop, or murmur, positive bowel sounds with no abdominal tenderness and no hepatosplenomegaly, normal pulses throughout, and clear lungs. The electrocardiogram is normal. What is your next best course of action?

A.Exercise echocardiogram

B.Dobutamine stress echocardiogram

C.Reassurance, observation

D.Resting echocardiogram

7.A 13-year-old girl with pulmonary atresia and intact ventricular septum visits you for exertional chest pain. As a newborn, her evaluation showed membranous pulmonary atresia with mild to moderate hypoplasia of the tricuspid valve and right ventricle. She did not have right ventricular dependent coronary circulation, so she underwent catheterization during which the right ventricular outflow tract membrane was perforated and dilated. Since then, she has had good growth of the right side of the heart but has some residual pulmonary stenosis and regurgitation. Her last echocardiogram three months ago demonstrated a small right ventricular outflow tract with a 39 mm Hg peak gradient, free pulmonary insufficiency, slightly small but tripartite right ventricle, slightly small but normally functioning tricuspid valve, a moderate sized patent foramen ovale with bidirectional shunting and normal right and left ventricular systolic function. The estimated right ventricular pressure obtained from a tricuspid insufficiency jet is 50 mm Hg (just under 50% systemic). Her chest pain occurs while running as part of practices for her volleyball team. The pain is over the left chest. There are associated palpitations and dizziness. The pain resolves with termination of exercise. Her physical examination is remarkable for a normal blood pressure, oxygen saturation of 91%, active precordium, normal S1 and single S2 with a 3/6 systolic ejection murmur, and a 3/4 diastolic murmur. There is no hepatosplenomegaly or peripheral edema or clubbing. The lungs are clear. An electrocardiogram shows biventricular hypertrophy and right atrial enlargement. What is your next best course of action?

A.Event recorder

B.Holter monitor

C.Exercise echocardiogram

D.Observation

8.Continuing with the same patient, the patient is scheduled for an exercise echocardiogram. During the preparation for the exercise test, a resting echocardiogram is performed. The wall segments in the apical four- and two-chamber views, particularly the apex itself, are difficult to visualize. You worry that the images may be even more problematic immediately following exercise. What is your next best course of action?

A.Start a peripheral intravenous line and prepare to administer a transpulmonary contrast agent for left ventricular opacification.

B.Instruct patient in breath-holding and position techniques that may improve image quality immediately post exercise.

C.Abort the test.

D.Start an peripheral intravenous line and perform an exercise sestamibi.

9.A 14-year-old patient with congenital mitral and aortic stenosis has undergone mitral valve replacement at five years of age and, at eight years of age, a larger prosthetic mitral valve (21 mm St. Jude) as well as a prosthetic aortic valve (19 mm inverted St. Jude mitral prosthesis) . He now has exercise intolerance. His echocardiogram demonstrates a mean prosthetic aortic valve gradient of 35 mm Hg (peak gradient of 59 mm Hg) and a prosthetic mitral valve mean gradient of 11 mm Hg. There is left ventricular hypertrophy with normal left ventricular function. Right ventricular pressure and left atrial size cannot be obtained. What is your next best course of action?

A.Exercise test

B.Dobutamine stress echocardiogram

C.Cardiac catheterization

D.Exercise echocardiogram

10.Continuing with the same patient, an exercise test is performed with Doppler interrogation of the prosthetic valves at each stage. The blood pressure is 120/76 at rest and increases to 149/87 at peak exercise. The exercise capacity is moderately depressed. The following Doppler data are recorded:

What do these results suggest that the decreased exercise capacity is due to?

A.Decreased fitness

B.Decreased cardiac output due primarily to mitral stenosis

C.Decreased cardiac output due primarily to aortic stenosis

D.Decreased cardiac output due to aortic insufficiency

Answers

1.Answer: D. The patient has exertional chest pain, which in the context of prior coronary artery disease must be assumed to be cardiac in origin (i.e., angina) until proven otherwise. Although exercise-induced bronchospasm is a cause of exertional chest pain, there is no family history of such, and the past medical history steers the differential diagnosis to a cardiac etiology. Observation would be incorrect – this patient requires a work-up for exertional chest pain. An exercise test is appropriate, but the yield by combining it with echocardiography is increased because of the greater sensitivity of echocardiography over electrocardiography alone. Dobutamine stress echocardiography is not necessary in this patient because she is capable of performing an adequate exercise test.

2.Answer: B. The data indicate that the previous exercise test was submaximal. In a fit and healthy girl, she should be able to perform a maximal test given sufficient prompting. A cardiac MRI and catheterization would give important anatomic information but will yield no information about the pathophysiology during exercise. At this point of the work-up, the physiologic significance of her chest pain needs investigation. An exercise sestamibi test could be valuable in this regard, but an exercise echocardiogram would spare the patient the radiation exposure.

3.Answer: A. The basal and mid-anterior septal segments lie in the distribution of the left anterior descending coronary artery. Decreased wall motion and thickening indicate decreased perfusion. Depending on your experience, it would be prudent to validate your interpretation with an adult cardiologist. Right ventricular volume overload and pressure overload (e.g., due to pulmonary hypertension) could cause alterations in septal motion but there is no basis for right ventricular problems in this patient. Decreased perfusion through the right coronary artery is manifested as wall motion abnormalities in the inferior and posterior wall.

4.Answer: D. The patient has a physiologically significant coronary artery lesion as a basis for her chest pain and the anatomic substrate needs to be delineated. Cardiac catheterization would be the most accurate method to do this. Although coronary bypass surgery may be indicated, it would be premature to refer the patient before the anatomy is defined. Exercise sestamibi and positron emission tomography would not be necessary, since the exercise echocardiogram has already detected a perfusion abnormality.

5.Answer: A. This patient with Williams syndrome and sinotubular narrowing of the aorta is at risk of having coronary ostial stenosis. His symptoms of chest pain may be related to a coronary perfusion issue. The patient is too young to perform an adequate exercise test. A dobutamine stress echocardiogram provides a means of stressing this patient in a controlled, staged manner with continuous electrocardiography and echocardiography, allowing termination whenever an abnormality becomes evident. A cardiac catheterization will provide information about the aorta but often may not be able to demonstrate the coronary stenosis that occurs at the ostia in these patients. The patient may warrant cardiac surgery but it is premature to refer the patient until further work-up is performed.

6.Answer: C. The patient has noncardiac chest pain possibly related to muscle or rib/cartilage tenderness. In this instance, stress echocardiography is not indicated as the prevalence of disease in this type of patient is very low. Bayes theorem demonstrates in the instance of low disease prevalence that the positive predictive valve of a test (stress echocardiography in this instance) is low.

7.Answer: C. The patient had exertional chest pain, which should be worked up further with a stress test. Exercise is a particularly appropriate stressor in this instance. The addition of echocardiography to the exercise test will make the test more sensitive and increase yield. Investigating the palpitations with an event recorder or Holter monitor may be helpful, but since these symptoms occur with exercise, an attempt to elicit them with an exercise test is preferred.

8.Answer: B. Often these simple measures such as having the patient lie in a left lateral decubitus position with a drop-out bed and having the patient practice holding an exhaled breath improve the image quality after exercise. Administration of a transpulmonary contrast agent is contraindicated in this patient with a right-to-left atrial level shunt. An exercise sestamibi would allow assessment of myocardial perfusion but exposes the patient to radiation when an echocardiogram may be able to demonstrate the physiology. In addition, the echocardiogram will not only allow assessment of regional wall motion but also allow assessment of pulmonary stenosis and right ventricular pressure during exercise.

9.Answer: D. An exercise test is indicated to quantify and validate the symptom of exercise intolerance. The addition of echocardiography will allow determination of physiology and behavior of the valve gradients during exercise. A dobutamine stress echocardiogram will not allow quantification of exercise capacity. A cardiac catheterization may be indicated after the exercise echocardiogram has been performed.

10.Answer: B. There is a markedly blunted blood pressure response. The Doppler echocardiography data demonstrate that although both gradients increase, the mitral valve increase is much more marked. The mitral valve is unable to accommodate the increased flow during exercise and left ventricular preload cannot increase appropriately; therefore blood pressure and cardiac output during exercise are blunted.