8 Stress Echocardiography

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From: Contemporary Cardiology: Essential Echocardiography: A Practical Handbook With DVD Edited by: S. D. Solomon © Humana Press, Totowa, NJ

149 Stress Echocardiography

Indications, Protocols, and Interpretation

Edmund A. Bermudez, ^MD , ^MPH and Ming Hui Chen, ^MD , ^MMS

^C

C

ONTENTS

I

NTRODUCTION

I

NDICATIONS

S

TRESS

P

ROTOCOLS

I

NTERPRETATION

P

ITFALLS

S

UGGESTED

R

EADING

8

INTRODUCTION

Stress echocardiography is a common diagnostic procedure used in the evaluation of coronary artery dis- ease. In fact, stress echocardiography is now a widely accepted test utilized for the diagnosis, prognostication, and risk stratification of ischemic heart disease (Fig. 1).

Imaging is most often coupled with treadmill stress, however, it can be easily coupled with pharmacological stress, bicycle exercise, or pacing. In skilled hands, stress echocardiography is safe, versatile, and accurate, providing important information on segmental wall motion and overall ventricular function.

The interpretation of echocardiographic images is based on changes in regional myocardial thickening with stress. In the setting of significant coronary artery disease, regional myocardial thickening will decrease as a result of oxygen supply–demand mismatch. The area supplied by the stenosed coronary artery will, therefore, display a change in contraction, enabling the identification and extent of underlying coronary ischemic disease. In the absence of hemodynamically significant coronary stenoses, an increase in systolic wall thickening should be observed in all coronary terri- tories with a decrease in the size of the left ventricular cavity. Therefore, localization and burden of ischemic heart disease can be routinely assessed.

INDICATIONS

Stress echocardiography is indicated in the diagnosis of coronary artery disease in those with an intermediate likelihood of coronary artery disease and an abnormal electrocardiogram (Fig. 1, Table 1). Those individuals with left bundle branch block, Wolff-Parkinson-White syndrome, left ventricular hypertrophy, digoxin use, or more than 1 mm ST segment depression on electrocar- diogram should undergo imaging with stress as inter- pretation of ST segments are an unreliable marker of ischemia in these settings. If the patient is able to exercise, treadmill stress, or bicycle stress (supine or upright) should be performed. When this is not feasible, dobutamine stress may be used. In the United States, vasodilator stress is an uncommon modality for stress echocardiography.

In peri-operative evaluations for noncardiac surgery, stress echocardiography can aid in risk stratification.

According to the American College of Cardiology/

American Heart Association guidelines, stress echocar-

diography is indicated when there are intermediate pre-

dictors of cardiovascular risk with low functional

capacity or when a high-risk surgical procedure is

planned. When high-risk results are obtained (extensive

inducible wall motion abnormalities) from this testing,

coronary angiography is usually warranted. However,

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when no wall motion abnormalities can be induced with adequate stress, surgery can usually be performed at rel- atively low risk for perioperative events.

Stress echocardiography can be used for prognostic purposes in those with chronic coronary artery disease and in post-myocardial infarction. As in risk stratifica- tion, the extent and severity of ischemia as evidenced by inducible wall motion abnormalities is a main deter- minant of prognosis, as well as overall left ventricular function. Among individuals with known or suspected

coronary disease, a normal stress echocardiogram por- tends a more benign prognosis compared to those with abnormal stress echocardiography results. In addition, the presence of viability with dobutamine echocardiog- raphy (biphasic response) in those with coronary artery disease can identify those in whom revascularization and functional recovery is more likely (see Chapter 5, Fig. 17).

Finally, stress echocardiography can be utilized with

Doppler to evaluate valvular function. In those individuals

Fig. 1. American College of Cardiology/American Heart Association (ACC/AHA) guideline update on stress testing. (Modified from ACC/AHA Exercise Testing Guidelines: http://www.acc.org/clinical/guidelines/exercise/fig1.htm.)

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with small, calculated aortic valve areas, low ejection fractions, and low transaortic gradients, stress echocar- diography can be used to increase cardiac output and further define the severity of aortic stenosis by calcu- lating changes in aortic valve area with stress. In a similar fashion, mitral stenosis can be evaluated and pulmonary systolic pressures calculated after or at peak stress. Therefore, in situations where the severity of stenotic valve lesions is questioned, stress echocar- diography may provide important information to guide management decisions.

STRESS PROTOCOLS Exercise Echocardiography (Fig. 2) Standardized images are acquired before the initiation of exercise and immediately after exercise. Two paraster- nal views (parasternal long axis and parasternal short axis) and two apical views (apical four-chamber and apical two-chamber) are used to assess endocardial wall

motion (Fig. 3; please see companion DVD for corre- sponding video). A common practice is to hold atrioven- tricular nodal blocking agents prior to testing, as the attainment of at least 85% of predicted maximal heart rate is desirable. It is important that the acquisition of images occurs immediately postexercise when using the treadmill machine. If images are acquired late after exer- cise, the heart rate may decrease substantially, giving time for any peak wall motion abnormalities to subside and, therefore, go undetected. The use of a supine bicycle machine may improve the timing of image acquisition, as images can be acquired at almost any time point during exercise and give true peak stress imaging. It is, there- fore, believed that supine bicycle imaging may improve the sensitivity of testing over treadmill exercise.

Pharmacological Stress Echocardiography (Fig. 4) Pharmacological stress echocardiography is utilized when patients are unable to exercise maximally. In the diagnosis of the coronary artery disease, stress to maximal

Fig. 2. Exercise stress echocardiography protocol.

Table 1

Overview of Qualitative Reporting of Left Ventricular Wall Motion Abnormalities During Stress Echocardiography

Wall motion/endocardial Wall motion/endocardial

thickening at baseline thickening at peak stress Interpretation

Normal Hyperdynamic Normal

Normal Hypokinetic-akinetic Ischemic

Hypokinetic Worsening hypokinesis Ischemic

Akinetic (± wall thinning) Akinetic-dyskinetic Infarcted

Hypokinetic/akinetic Augmentation with lower dose Viability with ischemia of dobutamine; deterioration

with high dose (biphasic response)

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Fig. 3. This 45-yr-old man with a history of hypertension and new right bundle branch block exercised for 12 min on a standard Bruce protocol, stopping secondary to fatigue. Heart rate and blood pressure at peak exercise was 179 bpm and 168/78 mmHg, respectively. There was 1-mm ST segment depression in lead III, becoming upsloping in V4–V6. Baseline left ventricular dimen- sions were within normal limits with estimated ejection fraction of 60–65%. No regional wall motion abnormalities were present.

Immediate postexercise imaging showed appropriate decrease in left ventricular chamber size with augmented contractility of all ventricular (A,B). (Please see companion DVD for corresponding video.)

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levels is an important component in the evaluation.

However, in regard to viability testing, dobutamine echocardiography is primarily utilized over exercise stress in the identification, localization, and extent of viable myocardium.

Dobutamine is the most commonly utilized pharma- cological agent that is combined with echocardiography for the assessment of coronary artery disease. This car- diac inotrope provides stress through β1 receptor stimu- lation and increasing myocardial oxygen consumption.

Typically, dobutamine is infused in 3–5 min stages start- ing at low doses (5 μg/kg/min) and increased until the maximal predicted heart rate is achieved or peak infu- sion levels are reached (40 μg/kg/min) ( Figs. 4 and 5).

Additional intravenous injections of atropine may be used to augment the heart rate in some individuals whom higher heart rates are needed. At peak levels, it is not uncommon to observe a drop in systolic blood pressure, owing to the mild vasodilatory effects of dobutamine. In contrast to exercise stress, this drop is not specific for severe coronary ischemia.

Echocardiographic images are obtained in the same views as treadmill testing, i.e., the parasternal long, parasternal short, apical four-, and apical two-chamber views. Images are acquired at rest before infusion, low dose infusion (5 or 10 μg/kg/min), peak infusion, and postinfusion. Images are displayed in quad-screen format (the four views mentioned previously on one

screen) for each stage and routinely digitized for inter- pretation (Fig. 5; please see companion DVD for corre- sponding video). This protocol is often augmented when resting wall motion abnormalities are seen on the echocardiographic images. In this case, images are often acquired at both low dose levels (5 and 10 μg/kg/min) to capture any changes in wall motion with low-dose infusion.

Vasodilator and Pacing Stress

As in nuclear stress testing, vasodilator stress has been used in combination with echocardiography. The agents typically used are dipyridamole or adenosine, both of which cause coronary vasodilation and perfu- sion mismatch with subsequent ischemia when signifi- cant stenoses are present. This approach has not been routinely applied in the United States, however, has been more extensively used in Europe.

Pacing can be used when exercise and pharmacolog-

ical means are not feasible because of contraindica-

tions. Pacing is more favorably achieved via the atrium,

as ventricular pacing may cause differential wall con-

traction and theoretically pacing induced wall motion

abnormalities. Atrial pacing can be accomplished through

esophageal pacing leads. This modality has not gained

wide use, because it appears more invasive than pharma-

cological stress and may cause discomfort in some

patients. Nonetheless, this modality offers an alternative

Fig. 4. Dobutamine stress echocardiography protocol.

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to pharmacological measures, and ensures the ability to achieve maximal heart rates.

INTERPRETATION

The myocardium is divided into 16 segments (see Chapter 5, Fig. 10A) corresponding to different coronary

territories: left anterior descending distribution, right

coronary artery distribution, and left circumflex distri-

bution. In general, the anterior, septal, and apical seg-

ments are supplied by the left anterior descending,

lateral, and basal posterior segments by the left circum-

flex, and the inferior and posterior segments by the right

Fig. 5. (See legend facing page)

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coronary artery (see Chapter 7, Figs. 3–5). However, there can be considerable overlap in perfusion territories and depends on coronary dominance, which should be taken into consideration when interpreting segments that may belong to more than one coronary distribution.

More recently, a 17-segment model has been developed that takes into account the true apex (see Chapter 5, Fig. 10B). This model has neither been routinely used, nor made a significant change in interpretation of stress echocardiographic images to date.

First, each myocardial segment is assessed for sys- tolic thickening at rest and overall ventricular function.

Areas of prior infarction are identified by thinned seg- ments of hypokinesia or akinesia. Thickening is the pri- mary measure of regional function, not myocardial motion itself. Second, the myocardial segments are examined at peak stress or post stress. Normal myocar- dial segments should sufficiently thicken to a greater extent with stress. The stress images are then analyzed in addition to the size of the left ventricular cavity,

Fig. 5. A 64-yr-old female with coronary artery disease and aortic valve disease underwent dobutamine stress echocardiography.

Graded doses of dobutamine were infused in 3 min stages to a peak dose of 40 μg/kg/min. Atropine (0.4 mg × 3) was given to achieve heart rate targets. Maximal heart rate achieved was 118 bpm (74% of predicted heart rate) and blood pressure was 110/82 mmHg.

Patient had no symptoms. Baseline electrocardiogram showed normal sinus rhythm with ST abnormalities suggestive of a digitalis effect. Baseline echocardiogram showed dialated ventricular cavity size with estimated ejection fraction (EF) of 40–45% with akinesis and thinning of the basal-to-midanteroseptal and anterior wall. Images at peak infusion showed no increase in global systolic function (estimated EF 40%). The akinetic anteroseptal and anterior segments became progressively dyskinetic during the infusion—consistent with a transmural infarct/scarring. In addition, the inferior wall, mildly hypokinetic at baseline, becomes akinetic at the high dose of dobutamine. Overall study was consistent with a large anterior and anteroseptal infarct with no significant peri-infarct ischemia.

Sensitivity was limited because target heart rate was not achieved. (Please see companion DVD for corresponding video.)

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which should become smaller with augmentation of ejection fraction. When a myocardial segment thickens less with stress, hypokinesia or akinesia is present and signifies stress-induced ischemia (Fig. 6). Dyskinesia is defined by the presence of outward movement of the myocardium in systole in an area of akinesis (Fig. 5;

please see companion DVD for corresponding video).

If an abnormal area at rest does not change with stress, this result is likely secondary to infarcted or scarred myocardium. The thought is that the greater the supply–demand mismatch, the greater will be the deficit during systolic thickening. Areas surrounding zones of ischemia may display decreased thickening, or so-called tethering. Overall, the territories correspon- ding to areas of decreased thickening define the coro- nary distribution and extent of ischemia (Fig. 7; please see companion DVD for corresponding video).

A qualitative or quantitative approach to interpreta- tion can be used. Qualitatively, each myocardial seg- ment is observed at rest and with stress and an appreciation for single or multivessel ischemia can be

assessed. However, quantitative schemes have been developed in order to gain a more objective, standard- ized interpretation for stress echocardiograms. In this light, each of the 16 myocardial segments is given a score: 1 for normal segments; 2 for hypokinetic seg- ments; 3 for areas of akinesis; 4 for dyskinetic areas;

5 for aneurysmal segments (see Chapter 5, Fig. 1B).

Areas that are unable to be visualized adequately are not scored. An overall index for wall motion is then calculated by summing all of the wall scores and then dividing by the number of segments analyzed.

This can be done for the rest images and also for the stress images.

When dobutamine is used for the assessment of

myocardial viability, the changes in myocardial thicken-

ing are assessed at rest, low dose, and peak images (see

Chapter 5, Fig. 17). Viable myocardium that is more

likely to recover function with revascularization is typical

when a biphasic response is observed: hypokinesis at rest,

improvement with low-dose dobutamine and worsening

with high-dose dobutamine. This is the most specific

Fig. 6. A 72-yr-old female patient underwent dobutamine infusion with atropine to achieve targeted heart rate. Baseline echocardio- graphic images showed borderline left ventricular hypertrophy with preserved systolic function. Minimal septal hypokinesis was noted. With increasing doses of dobutamine, augmentation of all segments accompanied by decrease in left ventricular cavity size up to a heart rate of 110 bpm. However, at heart rates more than 115 bpm, left ventricular dilatation accompanied by hypokinesis of the postero-inferior walls from base to apex was observed. These findings were consistent with ischemia in the right coronary/left circumflex artery territory. The septal wall that appeared mildly hypokinetic at baseline augmented during stress testing, suggesting no ischemia in this territory.

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Fig. 7. A 58-yr-old man with a history of aortic insufficiency stopped 1 min 50 s into a standard Bruce protocol. Baseline echocar- diogram showed hypokinesis of the basal inferior segment. Despite suboptimal test, peak systolic images showed modest increase in overall systolic function with estimated ejection fraction of 65–70%. All left ventricular segments, including the basal inferior segment, showed augmented contractility, with no inducible wall motion abnormalities. This finding indicates viable nonischemic myocardium with non-flow limiting coronary artery stenosis. (Please see companion DVD for corresponding video.)

response for recovery of function following surgical revas- cularization. A uniphasic response is seen when an area of hypokinesis improves continuously with dobutamine infusion and also indicates myocardial viability but this area appears to be less likely to recover full function after revascularization. The definition of ischemia is the same as with exercise modalities, i.e., worsening of wall thick- ening with stress infusion of dobutamine.

The range of left ventricular wall motion character- istics seen during stress echocardiography and their interpretation are summarized in Table 1.

PITFALLS

Stress echocardiography has its advantages and dis- advantages (Table 2). Several caveats should be taken into account during interpretation. False-positive stress echocardiograms can result from a number of issues.

First, a hypertensive response has been associated with a higher likelihood of wall motion abnormalities with stress in the setting of nonobstructive coronary artery disease. A hypertensive response has been defined as a systolic blood pressure over 220 mmHg for men and systolic blood pressure higher than 190 mmHg for women or as an increase in diastolic blood pressure higher than 10 mmHg with exercise or diastolic blood pressure higher than 90 mmHg during exercise. The exact mechanisms for this phenomenon are unclear but may be

a result of abnormal loading conditions that eventually lead to subendocardial ischemia at the microvascular level.

Left bundle branch block may be a cause for false- positive readings (Fig. 8; please see companion DVD for corresponding video). With left bundle branch block, septal motion may be abnormal with systole as a result of the interventricular conduction delay. In this setting, one should again focus on thickening of the myocardium in the septal area and not on the septal motion. False-positive results may be related to increased heart rates in this setting. Therefore, one might speculate that vasodilator stress may be more specific in this setting, as has been the case with adeno- sine nuclear perfusion imaging.

Finally, interpretation of echocardiographic images

can be difficult in certain patients. These patients may

be obese individuals in whom inadequate penetration of

the ultrasound beam results in poor endocardial resolu-

tion. Myocardial diseases, e.g., myocarditis can affect

systolic performance and regional wall motion. Stress

testing in this setting (for evaluation of chest pain)

should be interpreted with caution (Fig. 9). Further,

patients with chronic obstructive lung disease and

hyperinflated lungs may impede the quality of echocar-

diographic images. In situations where endocardial

border definition may be tenuous, the addition of intra-

venous echocontrast agents may help to better delineate

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regional endocardial thickening (Figs. 8 and 10;

please see companion DVD for corresponding video for Fig. 8). This procedure should be routinely employed should any question arise regarding image resolution on rest imaging. Ideally, if one should use

contrast, it should be used for each set of images (rest and stress) so as to compare similar images with one another.

Acquisition of images post-treadmill exercise demands extensive experience in obtaining quality images for

Fig. 8. A 62-yr-old man with baseline left bundle branch block (LBBB) exercised for 3 min, achieving peak heart rate of 115 bpm and peak blood pressure of 110/60 mmHg. Definity^®(perflutren lipid microspheres) contrast agent was administered to improve endocardial border definition. Baseline images revealed moderately impaired left ventricular systolic function with abnormal septal motion (likely related to his LBBB) and hypokinesis of the mid- and distal septum. Postexercise images showed no increased contractility and worsening of septal hypokinesis. Findings are consistent with ischemia in the mid- and distal ante- rior septum—areas supplied by the left anterior descending coronary artery (see Chapter 7, Figs. 3–5; see also companion DVD for corresponding video).

Table 2

Advantages/Disadvantages of Stress Echocardiography Advantages

Sensitivity and specificity comparable to exercise nuclear imaging Utility in diagnosis, prognosis, and risk-stratification

Assessment of multiple parameters: systolic function, valvular function, and ischemia Widely available

Portability

Relatively inexpensive No radiation

No need for iodinated contrast agents Disadvantages

Highly dependent on sonographer and interpreter skills

Difficult acoustic windows can limit imaging. Echocontrast agents may be necessary

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Fig. 9. A 35-yr-old woman with recent onset chest pain and dyspnea exercised for 13 min on the Bruce protocol, stopping owing to fatigue.

At rest (heart rate 60 bpm), basal inferior wall hypokinesis with preserved function of the remaining left ventricular segments were present. Immediate postexercise images obtained between heart rates 136–180 bpm showed abnormal septal motion with augmented contractility of the remaining segments. The differential diagnosis included postmyocarditis or a cardiomyopathy with possible exercise-induced septal ischemia at achieved workload. Clinical correlation and/or further evaluation with another investigative modality was recommended.

Fig. 10. A 47-yr-old male status postheart transplant. Myocardial contrast agent (Definity^®, perflutren lipid micropsheres) was used to improve endocardial definition both at baseline and during image acquisition. Dobutamine was infused up to a peak dose of 20μg/kg/min.

The target heart rate of 160 bpm was achieved. Peak blood pressure was 180/87 mmHg. Echocardiographic parameters were normal at baseline, and dobutamine stress echocardiography images revealed normal recruitment of systolic function with no evidence of ischemia.

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interpretation. Correct image orientation is essential to accurate diagnoses. In turn, accurate interpretation and diagnosis depends chiefly on experience of the sonographer in acquiring images and on the expertise of the physician interpreting them. Therefore, it is essential that the interpreting physician have a complete under- standing of resting transthoracic principles prior to gain- ing experience with stress echocardiography.

In summary, stress echocardiography is a routine diagnostic procedure for the initial assessment of coronary artery disease, the follow up of patients with known coronary artery disease, and for management decisions regarding revascularization in patients with chronic coronary disease. It is a powerful tool in the assessment of regional and overall myocardial func- tion in skilled hands. As its use broadens, new appli- cations are emerging, such as the assessment of