15 Exercise Echocardiography
Stress echocardiography integrates echocardiographic imaging with exercise electrocardiographic (ECG) testing to aid in real-time evaluation of ischemic, valvular, and cardiopulmonary heart disease. Accuracy for stress echocardiography to detect extent and location of myocardial ischemia is excellent, particularly when baseline ECG abnormalities render standard exercise ECG testing nondiagnostic.1,2 In addition to initial coronary disease diagnosis, stress echocardiography is used to monitor disease progression in patients with known disease and assess clinical response to medical therapy. Stress echocardiography provides valuable information on myocardial viability, risk stratification, and prognostication. Nonischemia applications of stress echocardiography include evaluation and clinical management of cardiopulmonary, congenital, and valvular heart disease. Future advances include three-dimensional (3D) imaging, spectral Doppler interrogation with stress, myocardial strain and strain rate analysis, and integration of coronary flow reserve data using myocardial perfusion images.
The premise of stress echocardiography is provocation of transient myocardial ischemia by one of various cardiac stressors.3–6 Nonexercise cardiac stressors include pharmacologic and pacing protocols (see Chapter 16). Pharmacologic stressors include agents that increase myocardial contractility and oxygen demand (dobutamine) and agents that induce transient regional hypoperfusion via coronary vasodilation (dipyridamole). Exercise stress is generally preferred over pharmacologic stress, as it allow for evaluation of exercise tolerance, symptom provocation, and prognostication.7 Exercise stressors include treadmill and bicycle ergometry protocols. Images are acquired during peak exercise or, because of imaging difficulty due to patient motion, immediately after exercise cessation. Imaging data are then integrated with ECG data, exercise tolerance, and patient symptoms for final interpretation.
Capability for echocardiography to detect myocardial ischemia was shown more than three decades ago in animal models demonstrating concordance between severity and duration of coronary perfusion impairment and visualized regional wall motion abnormalities.8,9 Early corroborating human studies using M-mode imaging demonstrated left anterior descending artery territory ischemia via reduced interventricular septal motion.10 In one of the earliest descriptions of inducible ischemia during bicycle exercise, septal wall motion abnormalities, visualized by M-mode imaging, correlated with occlusion of the left anterior descending artery.11 However, inability to image more than a discrete portion of the heart with M-mode imaging limited its overall utility as a diagnostic tool. Subsequent development of two-dimensional (2D) imaging allowed tomographic cardiac imaging, increasing utility for ischemia assessment.12 Advances in transducer performance and development of harmonic imaging and digital loop grabbers have dramatically improved image quality and simplified interpretation. Stress echocardiography is now widely available.13 Clinical guidelines provide recommendations regarding application of stress echocardiography as a first-line diagnostic tool.5,6
Physiologic Principles of Exercise Echocardiography
During exercise, increases in myocardial oxygen demand results in augmented systolic function with increased myocardial thickening. With a hemodynamically significant coronary stenosis, the relative disparity in oxygen delivery to the distal coronary bed cannot meet increases in myocardial oxygen demand. Transient hypoperfusion results in mechanical dysfunction of affected myocardium. Stress echocardiography is well suited to assess this ischemic response by visualizing global and regional myocardial motion, allowing for localization of coronary lesions, given that coronary artery anatomy and myocardial distribution are relatively similar among patients (see Chapter 13).14
Myocardial ischemia generally progresses in a defined sequence of events, termed the ischemic cascade.15 Ischemia is initiated by regional hypoperfusion of a distal coronary bed. After resultant metabolic changes within affected myocardium, alterations in function occur; initially with abnormalities in myocardial relaxation (diastolic dysfunction), and subsequently with systolic dysfunction of affected segments. Only in the later stages of ischemia are characteristic ECG changes, such as ST segment depression, and frank angina manifest (Fig. 15-1).16,17 Propagation of ischemia generally proceeds from the subendocardium outward to the subepicardial layer in cases of more severe or prolonged ischemia.18 However, because endocardial myocardial oxygen demand is higher, only moderate ischemia is needed to produce visually identifiable contractile dysfunction. With exercise ECG testing, ischemia diagnosis occurs with onset of angina or ECG changes, occurring in the later stages of the ischemic cascade (Fig. 15-2), contributing to acknowledged limitations in diagnostic accuracy for exercise ECG testing. In contrast, stress testing with integrated cardiac imaging identifies ischemia earlier, at onset of regional hypoperfusion (nuclear perfusion stress) or with systolic dysfunction (echocardiography). With stressor cessation and restoration of adequate coronary flow, induced abnormalities typically recover rapidly, but may persist if ischemia is severe. Early studies using echocardiographic imaging during angioplasty balloon inflation demonstrate onset of regional systolic dysfunction as early as 19 seconds after balloon inflation, with subsequent ischemic ECG changes and angina occurring 30 to 40 seconds after inflation. These abnormalities typically resolved within 10 to 20 seconds after balloon deflation.17,19,20 Angioplasty balloon inflation models represent ischemia from a dynamic obstruction; imaging during provoked ischemia with a fixed coronary obstruction has shown a similar temporal progression with mechanical dysfunction preceding ECG changes and angina.21,22
1. Hypokinesis, myocardial thickening with inward motion less than 5 mm or relatively less than the rest of the myocardium
2. Akinesis, absence of thickening or inward motion
3. Dyskinesis, thinned myocardium with paradoxical outward systolic motion, a passive myocardial response to increased intraventricular pressure23
In absence of disease, baseline systolic function is generally normal and myocardial response to exercise is hyperdynamic (Fig. 15-3). In ischemic but noninfarcted myocardium, the stress response is concordant with ischemia severity: hypokinesis in mild cases progressing to akinesis in more severe cases. Chronically infarcted regions with permanent transmural injury appear thinned and akinetic or dyskinetic. Acutely infarcted myocardium appears hypokinetic or akinetic with normal wall thickness as postinfarction remodeling has not yet occurred. If blood flow is rapidly restored to acutely infarcted myocardium, return of function is variable temporally and spatially. Regions of transmural infarct resulting from prolonged ischemia typically remain hypocontractile, but tissue subjected to only a short duration of coronary flow limitation typically regains contractility. Time duration of myocardial recovery after an infarction varies from days to months and is termed stunned myocardium. Prediction of functional recovery stunned segments may be accomplished with low dose dobutamine stress echocardiography or other modalities of viability testing (see Chapter 16).
The effect of ischemic on myocardial wall motion and thickening is proportional to the severity of impaired coronary blood flow.22,24 For intermediate-range lesions (50% to 60% stenosis of the epicardial vessel) or single-vessel disease where only a few myocardial segments are affected, abnormalities during ischemia are typically subtle and transient or may be absent altogether. Assuming use of an adequate stressor, the severity of coronary narrowing where systolic dysfunction is perceptible is approximately 60% stenosis, with progression to akinesis when greater than 80% stenosis is present (Fig. 15-4). Note that visual estimates of stenosis severity based on planar angiographic images may not necessarily correlate with physiologically significant occlusions.24–26 In the absence of significant coronary stenoses, exercise-induced reductions in relative coronary flow reserve may occur in patients with microvascular disease or increased myocardial mass, as occurs in left ventricular hypertrophy. In these cases, although a stressor may produce characteristic ECG changes or anginal symptoms, frank regional wall motion abnormalities may not be evident.27,28
Exercise Stressors Used for Stress Echocardiography
In individuals able to exercise maximally, exercise stress is preferred over nonexercise stressors, as it allows for a contextual understanding of results relative to patient symptoms and functional capacity.29 Metabolic equivalents (METs) are a measure of oxygen (O2) consumption where 1 MET (resting metabolic state) equals 3.5 mL O2 per kg/min. Exercise stressors should be used unless the patient is unable to achieve at least 5 METs or use the exercise equipment. Exercise protocols most widely used are treadmill and bicycle ergometry (upright or supine). In the United States, treadmill protocols are more common, unless the patient has neurologic, vascular, or orthopedic constraints that limit treadmill exercise performance.
Regardless of exercise stress type, an adequate workload is necessary to provide a diagnostic study. The most common hemodynamic target used is achievement of a heart rate goal based on patient age and gender, calculated as 85% of the maximal predicted heart rate: (estimated 220 − patient’s age − For men and 210 – patient age for women). If necessary, workload can be augmented with other measures such as hyperventilation or handgrip exercise.30 During the stress study, patients should subjectively report exertion level, using standardized scales, such as the Borg rating of perceived exertion (Box 15-1).31 It is institution and physician dependent whether exercise is discontinued once hemodynamic targets are achieved, or whether the patient continues to maximum exercise capacity.
With treadmill exercise protocols, baseline echocardiographic images are obtained in a left lateral decubitus position to facilitate acoustic windows (Table 15-1). Exercise then commences according to standardized protocols.31 Most patients who are reasonably active perform the Bruce protocol. However, in patients with mobility restrictions or limited exercise tolerance, the Cornell or Naughton protocols are other options to allow for at least 6 to 12 minutes of continuous exercise. Systolic blood pressure is monitored throughout the study and should increase by at least 20 mm Hg with exercise. The treadmill portion is halted for:
(1) concerning symptoms (severe angina, ataxia, dizziness, pallor,
(2) severe hypertension (systolic blood pressure greater than 220 mm Hg),
(3) hypotensive response (more than 10 mm Hg drop in systolic blood pressure),
(4) concerning ECG changes or arrhythmias, or
(5) hemodynamic targets are achieved.31 Based on total exercise duration, a nomogram based on age, gender, and degree of physical conditioning provides an estimate of functional aerobic impairment.32
TABLE 15-1 Exercise Stress Protocols for Echocardiography
| Treadmill | Upright Bicycle | Supine Bicycle |
Because patient motion limits imaging during active treadmill use, “stress” imaging is performed immediately after exercise cessation without a cool-down period. The duration of ischemia induced abnormalities is variable, dependent on coronary occlusion severity, number of vessels affected, presence of collateral blood flow, and achieved workload.33 Although ischemic abnormalities can persist for some time after exercise cessation, most reverse within minutes. Therefore, expeditious imaging is critical; image acquisition within 60 to 90 seconds after exercise completion is generally adequate. Reasonable patient agility is required to transition to the imaging table, reassume a left lateral decubitus position, and allow imaging within this time window (see Table 15-1). If prolonged delays in patient transfer occur or acoustic windows are suboptimal, transient ischemia may be missed. This is particularly true with intermediate-range occlusions or single-vessel disease where induced abnormalities are often fleeting. Although feasibility of peak stress imaging on the treadmill has been demonstrated, the minimal incremental benefit attributable to time savings while scanning upright coupled with difficulties in obtaining reproducible results limits widespread use.34
For bicycle ergometry, baseline images are obtained in a left lateral decubitus position (see Table 15-1). Patients perform either upright or supine bicycle exercise with a goal of achieving increases in wattage, 2 to 3 minutes per stage. At each stage, pedal resistance increases in a stepwise manner and the patient must maintain a constant cadence (about 60 rpm). Because workload is effort driven, achievement of maximal workload is more patient dependent than in treadmill protocols. After completion of exercise, the patient reassumes a left lateral decubitus position for further imaging. If apical windows are not easily accessible, subcostal views provide an alternative. During upright or supine ergometry, most myocardial segments can be well visualized.35 However, care must be taken to avoid apical foreshortening as can occur with even mild head elevation. For supine bicycle ergometry, integrated imaging stretchers allow patient rotation and positioning such that transition to a separate imaging bed is obviated, resulting in time savings (see Table 15-1). Bicycle protocols allow for a relatively stationary position for simultaneous image acquisition during active exercise.36,37 Imaging concurrent with peak stress, as opposed to immediate posttreadmill imaging, increases sensitivity for detecting transient ischemia.36,38,39
In the United States, treadmill stress is favored over bicycle ergometry because of widespread availability of treadmills in hospital settings and familiarity of walking as a form of exercise. Treadmill ECG testing, as an established diagnostic modality, is well validated, providing a wealth of prognostic information referenced to exercise duration and ECG response to exercise. With treadmill exercise, patients generally achieve higher workloads than with bicycle exercise, increasing likelihood of attaining hemodynamic targets. Supine ergometry stress typically produces a lower heart rate increase and a systolic blood pressure response about 20 mm Hg higher than that of upright exercise because of physiologic differences in preload. Additionally, maximum oxygen uptake tends to be lower with bicycle ergometry (10% to 20%) and should be considered during study interpretation.31 Last, with supine ergometry, where the lower extremities must be supported against gravity, if quadriceps fatigue precedes maximal workload, patients may prematurely discontinue exercise.
In Europe, where bicycling is a more common form of exercise, bicycle protocols are favored. Guided by real-time wall motion evaluation, bicycle protocols allow for ischemia detection at onset, allowing identification of the ischemic threshold, in contrast to treadmill protocols that use ECG changes or symptom onset as a time point to discontinue exercise. Real-time ischemia identification allows for increased detection of subtle or transient ischemia with single-vessel disease or intermediate-severity lesions. Bicycle protocols allows imaging without the “all-or nothing” constraints of a narrow immediate poststress imaging window, as seen in treadmill protocols. The choice of which stressor to employ should be individualized to the ability of the patient to perform exercise, experience level of the personnel administering the study, and availability of equipment. Published reports demonstrate comparable accuracy between different exercise protocols.39–41 As long as an adequate workload is achieved, overall accuracy is likely equivalent regardless of the stressor employed.42
Methodology
Equipment
The standard for laboratories performing exercise echocardiography includes high-quality instruments with a digital frame grabber, harmonic imaging capability, and an offline analysis system. Appropriate equipment (treadmill or bicycle ergometer) should be available, as should imaging beds with lateral cutouts to facilitate apical imaging. A cardiac arrest cart and defibrillator should be easily accessible.5,6
Digital frame grabbers and split-screen displays allow side-by-side comparison of rest and stress images to facilitate identification of regional wall motion abnormalities. Digital frame capture rates ranging from 20- to 100-ms intervals are looped and replayed continuously for analysis.43,44 These intervals allow for variable capture within the cardiac cycle ranging from systole alone to the entire cardiac cycle. Most systems acquire eight frame digital loops per view with about 50 ms for each frame. However, if heart rate exceeds 150 bpm, image quality may be improved by reducing the capture interval to 30 to 40 ms. Digital clips of about 10 to 20 seconds per view are needed for adequate wall motion analysis. Gating of baseline and stress images to the ECG allows comparative analysis of endocardial motion at the same point in the cardiac cycle, optimizing identification of interval changes in regional function. A videotaped backup recording of the study is helpful to ensure that digital loops accurately reflect myocardial motion.45
Procedure
A brief history is taken to document symptoms, atherosclerosis risk factors, and current medications and to review basic laboratory findings. Written informed consent should be obtained before the procedure. An activity-specific questionnaire may aid in predicting peak exercise capacity.46 Patients should refrain from oral intake 3 to 4 hours before the procedure.31 Medications that may affect maximal workload (i.e., atrioventricular nodal blocking agents) should be held for one or two doses, unless the study purpose is to diagnose ischemia while on active therapy or risk of an adverse event off medication is deemed too high. Telemetry leads are placed at standard limb and precordial sites, slightly displacing leads that interfere with acoustic windows. One ECG lead is concurrently displayed on the echocardiography monitor to allow image gating and correlate changes in wall motion with ECG abnormalities. Information on heart rate, rhythm, exercise capacity, and blood pressure is recorded (Box 15-2).29 Common ECG criteria for ischemia are greater than 1 mm horizontal or down-sloping ST depression at least 60 ms after the end of the QRS complex in anatomically contiguous leads.29 Patients should be intermittently asked for presence or severity of symptoms. If severe symptoms occur or ischemia develops, the study should be discontinued. Monitoring should continue until blood pressure, heart rate, and ECG have returned to near-baseline levels and any induced symptoms have resolved. Study results should be conveyed to the referring provider promptly, with immediate discussion when the stress test is strongly positive.
Box 15-2
Exercise ECG Testing Measurement Parameters
Hemodynamic and Symptomatic Parameters
Adapted from Gibbons L, Balady GJ, Bricker JT, et al: ACC/AHA Guideline update for exercise testing: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 40:1431-1440, 2002.
Optimal acoustic windows are located and baseline echocardiographic images obtained. If baseline abnormalities are seen, a brief transthoracic study should be performed to evaluate ventricular dysfunction, significant valvular abnormalities, or pericardial effusion. If baseline image quality is suboptimal (up to 20% of cases), transpulmonary contrast aids endocardial border definition (Fig. 15-5). Transpulmonary contrast is particularly helpful for assessing anterior and lateral wall motion, regions that may be more difficult to see in larger patients or those with underlying pulmonary disease. However, because contrast lasts only 1 to 2 minutes after injection, separate injections are needed for baseline and stress images. For treadmill studies, contrast is injected during peak exercise so it is in place during poststress imaging.
Imaging
Myocardial segments are evaluated in multiple views to avoid misdiagnosis due to an oblique image plane. Prestress optimization of image planes and views is critical to maximize diagnostic accuracy. The four basic views used are concordant with standard transthoracic tomographic planes: the parasternal short- and long-axis views and the apical four- and two-chamber views. Subcostal views are not commonly used but may be substituted in the rare instance when they provide better images, such with intervening lung tissue due to chronic pulmonary disease.35 Once baseline images are obtained, acoustic windows are identified and marked to minimize transducer repositioning on poststress imaging. Because induced ischemia may normalize quickly, sequencing for poststress imaging typically starts with apical windows, moving to parasternal windows. Several digital loops are acquired in each view in rapid sequence to optimize loop selection for comparison. Vigorous cardiac contraction, tachycardia, and exaggerated respiration increases translational and rotational movement of the heart. Patients with excessive cardiac motion should briefly halt respiration at end- or midexpiration to aid in maintaining a relatively constant imaging plane. With normalization of heart rate near to baseline, an additional set of images should be obtained to evaluate for late-onset ischemia.
Doppler
Doppler echocardiography is not routinely performed during stress echocardiography for ischemia evaluation. Rapid heart rate and additional time requirements for imaging do not allow for reliable data acquisition. Doppler-derived indicators of myocardial response to stress include left ventricular (LV) ejection velocity, aortic systolic ejection rates, transmitral filling velocities, and tissue Doppler interrogation of myocardial velocities. Although research-based applications using Doppler interrogation during peak stress suggest some additive value, the additional time demands of Doppler interrogation in its current state, coupled with relatively small incremental gain in information, limit routine use. In patients with valve lesions who have equivocal symptoms or are asymptomatic, tailored Doppler interrogation during exercise echocardiography provides objective data on exercise tolerance, symptom provocation, hemodynamic effects of exercise, and pulmonary pressure response to exercise (see later discussion).47
Room Layout
Room layout is critical to success of the procedure. The narrow time window between exercise cessation and recording of poststress images necessitates spatial optimization to maximize time savings and facilitate image acquisition. A typical floor plan minimizes the number of steps and impediments for patient transfers (Fig. 15-6).48 Adequate space around the imaging bed for the ECG and echocardiography instruments, sonographer, and medical professionals is necessary. Patients should receive clear instructions on maneuvers required after exercise termination to avoid introducing unnecessary delay. Often, it helps to have a “practice” transition from the treadmill to the imaging bed so the patient knows what is expected. Emergency medical equipment, drugs, and supplies should be readily available.
Personnel
Staffing for exercise echocardiography requires at least two people: a sonographer and a medical professional to monitor the patient and evaluate for symptom onset.6 A physician trained in advanced cardiac life support should be in the immediate vicinity of the stress laboratory and available for emergencies.29,49 In many laboratories, physician supervision is a requirement, either physically or more remotely, observing from a monitor. However, several studies document the safety of exercise supervision by properly trained allied health professionals such as physician assistants, exercise physiologists, or registered nurses.50,51 Regardless of the personnel used, considerable skill on the part of the medical supervisor, sonographer, and/or technician is needed to facilitate an adequate study and recognize signs and symptoms of ischemic heart disease.
There is a significant learning curve associated with the technical challenges of image acquisition, study implementation, and interpretation. To optimize imaging, sonographers should have completed training in standard transthoracic imaging with an additional 3 months of training in exercise echocardiography and should possess basic knowledge of coronary anatomy and myocardial distribution. It is recommended that sonographers complete more than 50 stress studies to claim proficiency and perform more than 10 studies per month to maintain appropriate skill level. Physicians responsible for supervision and interpretation should be at least level II trained in echocardiography (Box 15-3). Supervised overreading of at least 100 studies by a level III–trained echocardiographer with independent interpretation of 200 studies is recommended to attain a minimum competence level for independent interpretation, and additional interpretation of more than 15 studies per month is recommended to maintain skills.6,52 Although these volumes are reasonable for routine study interpretation, more specialized applications, such as evaluation of valvular heart disease, warrant more clinical expertise and volume.53 Continuous quality-improvement practices should be employed to ensure consistency and accuracy of interpretations.54
Box 15-3 Recommended Physician Knowledge for Performance and Interpretation of Stress Echocardiography6
• Understand indications and limitations of exercise echocardiography with knowledge of alternative diagnostic procedures
• Knowledge of cardiovascular drugs and effects on stress response
• Understand study endpoints and indications for study termination
• Understand diagnostic accuracy and prognostic value of stress echocardiography in different patient populations
• Identify LV wall segments, recognize wall motion abnormalities, and interpret digitally acquired images
• Understand conditions and circumstances for indeterminate or false test results
• Competence in cardiopulmonary resuscitation
• Apply Doppler data to physiologic changes occurring during stress (hemodynamic studies)
Interpretation
A normal study is one where there is normal resting wall motion with a hyperdynamic response to exercise (see Fig. 15-3). With abnormal studies, location, extent, and severity of interval changes are noted and recorded (Table 15-2). During interpretation, provoked abnormalities concordant with a coronary artery distribution should be noted. More detailed segmental analysis using the 16-segment LV model (see Figure 13-3) and standard wall motion analysis scale (normal, hypokinetic, akinetic, dyskinetic) may be used for reporting.14 Several factors affect myocardial appearance and response to stress:
TABLE 15-2 Interpretation of Myocardial Response to Stress
| Resting Myocardial Appearance | Myocardial Response to Exercise | Interpretation |
|---|---|---|
| Normal | Hyperdynamic | Nonischemic |
| Normal | Hypokinetic or akinetic | Ischemic |
| Normal | Unchanged (lack of hyperdynamic response) | Microvascular ischemia or balanced ischemia |
| Hypokinetic | Akinetic | Infarcted myocardium |
| Akinetic | Dyskinetic | Transmural infarct |
With prolonged ischemia, compensatory hyperdynamic function in regions remote to ischemic zones occurs because of a physiologic response of the ventricle to maintain overall cardiac output.55 If pronounced, this may mask stress induced abnormalities in ischemic segments. Nonischemic segments adjacent to ischemic myocardium may show decreased motion despite the presence of adequate blood flow because of tethering from akinetic regions, leading to overestimation of ischemic burden.56 Stress-induced global hypokinesis, or a lack of hyperdynamic response to exercise, may be seen in patients with disease in all major epicardial coronary arteries, or “balanced” ischemia. However, other markers of coronary artery disease are usually identifiable, such as decreased exercise tolerance, ischemic ECG changes, or angina. Rarely, a lack of hyperdynamic response occurs in absence of major coronary artery obstruction, such as in left ventricular hypertrophy, diabetes, severe arterial hypertension, and hypertrophic cardiomyopathy. Angiographic studies in these subsets suggest a reduction in coronary flow reserve due to microvascular disease, with smaller regions of ischemia failing to manifest in frank mechanical dysfunction. Because heterogeneity in wall motion is absent, diagnostic accuracy to identify ischemia is lowered.57,58 Although current diagnostic testing does not allow for definitive diagnosis of microvascular ischemia, advances in myocardial contrast perfusion imaging may increase understanding of this disease process in the future.
Interpretation of stress echocardiography remains largely qualitative, with visualized wall motion abnormalities the core marker of ischemia. This approach is generally adequate for patient management. Reliability and reproducibility of study interpretation are largely dependent on interpreter experience.59 Adequate physician and sonographer training and conservative interpretation criteria improve diagnostic sensitivity, consistency, reliability and validity.60,61 A logical approach to interpretation is essential. Echocardiographers should be cognizant of the patient’s clinical history. For example, in patients with prior coronary bypass surgery, wall motion analysis may suggest collateralized vessels, not a typical pattern for patients without coronary disease. Similarly, in individuals with prior infarcts, tethering effects on adjacent nonischemic regions should be considered.
Interpreters should be vigilant for induced wall motion changes that do not actually signify ischemia. Such “false-positive” findings include abnormal septal motion with ventricular pacing, an intrinsic conduction abnormality, or postoperative changes. Another false-positive septal abnormality is early relaxation of the anteroseptal region relative to other segments. “Early relaxation” can usually be timed in the cardiac cycle to just before mitral valve opening and is not indicative of ischemia.62 Other commonly misdiagnosed regions include the basal inferior wall. Without prior bypass revascularization, an isolated basal wall motion abnormality should be scrutinized closely, given the unlikelihood of an isolated proximal wall abnormality with hyperdynamic mid and distal segments.59 Falsely negative studies are most commonly due to procedural difficulties, such as inadequate workload, performance below the ischemic threshold, inexperienced interpreters, poor endocardial border definition, and inferior image quality. Myocardial regions more subject to “false negatives” or missed ischemia include the lateral wall, particularly in obese patients, and those where interposed lung tissue hinders imaging.
With residual coronary occlusion and chronic ischemia, stress echocardiography can be used to evaluate for viable myocardium. Viable myocardium is hypokinetic, as minimally adequate blood flow meets basal metabolic needs but is insufficient to support normal function. Distinguishing between viable or infarcted myocardium has been applied to coronary revascularization, based on the premise that revascularization of viable tissue improves systolic function and reduces ischemic burden.4 For stress echocardiography, a “biphasic” response is the hallmark of viable myocardium where mild augmentation in wall motion occurs following a low-level stressor, but with higher stressor doses, segments become frankly ischemic and decrease contractility, again becoming hypokinetic or akinetic. Because of the subtlety in wall motion assessment during viability testing, exercise stressors have not proven reliable, and conventional protocols use pharmacologic stressors (see Chapter 16). The future role of viability testing is not clear. A recent substudy of the Surgical Treatment for Ischemic Heart Failure Trial found that identification of substantial viable myocardium did significantly affect 5-year mortality comparing medical therapy with and without bypass surgery, implying that viability assessment alone should not be the deciding factor in determining treatment strategy.63
More quantitative approaches to exercise echocardiography provide standardized interpretation but are labor intensive to implement. The most commonly used semiquantitative application is the wall motion score index, in which the LV is divided into segments and regional wall motion of each segment is assessed (see Chapter 13, page 239).14 Wall motion is graded between 1 and 4 depending on abnormality severity (0 hyperkinetic, 1 normal motion, 2 hypokinetic, 3 akinetic, and 4 dyskinetic). The summed total is divided by the number of segments evaluated to calculate a global wall motion score index. Alternatively, individual coronary artery distributions can be assigned to obtain a regional wall motion score index. Similar to qualitative interpretation, overscoring of nonischemic segments “tethered” to ischemic myocardium overestimates ischemic burden.
Computer-driven algorithms offer the potential for decreasing time demands for quantitative analysis. The centroid and centerline algorithms gauge wall motion referenced to a “baseline” within the LV. With the centroid method, multiple radii extending from a geometric center of mass to the endocardial and epicardial surfaces of the LV are generated and relative differences in wall motion between rest and stress images are compared. With the centerline method, distance measurements of the endocardium and epicardium perpendicular to the midpoint of the myocardium are compared. However, subjective decision making by the interpreter is still needed in marking endocardial and epicardial borders. (See Chapter 12.) Availability of automated endocardial border recognition algorithms is increasing. However, the need for superior image quality for accurate border delineation is paradoxic, because excellent qualitative interpretation is usually possible without the time demands of quantitative measurement. Moreover, most available analysis packages rely on radial motion analysis and do not reliably account for torsional or translational movement. Although a quantitative tool is an attractive concept to increase ease and reliability of interpretation, with the added labor requirements no currently available tools supplant standard qualitative analysis.64
Diagnostic Accuracy of Exercise Echocardiography
Diagnostic accuracy of cardiac stress testing is generally reported as sensitivity and specificity to detect angiographically identified lesions. However, consideration of stenosis severity that denotes disease presence should be made. Stenosis thresholds create artificial distinctions (disease present versus not present) in a process that actually represents a spectrum. If the “set point” is higher (use of greater than 70% versus greater than 50% coronary artery stenosis used as the definition of disease presence), patients with true ischemia but less severe occlusion would be erroneously labeled “false positive.” Higher set points increase sensitivity by increasing true positive likelihood and reducing false negatives.24,65–70 Additionally, there are acknowledged limitations of 2D angiography in measuring hemodynamic significance of lesions.71,72 However, limited data using quantitative angiography demonstrate excellent correlation with stress echocardiography results.22,25
Diagnostic accuracy is affected by factors that introduce bias.73,74 Early exercise echocardiography studies suffered from reporting bias, where newer modalities are favored over old. For example, if echocardiographic stress test accuracy is compared with standard ECG testing, the exercise ECG portion is the same. Echocardiographic imaging is only additive with impossibility for a “worse” performance. Validation studies for exercise echocardiography tended to be performed at higher-volume centers with increased clinical expertise, drawing from patient groups with prior myocardial infarction or known disease, where higher pretest probability increased test sensitivity. With acceptance of test validity of a modality, posttest referral bias is introduced (Fig. 15-7), where only positive tests are referred for confirmatory testing (in this case, angiography), and negative tests are accepted as correct without verification.75 Last, with accepted use of a modality and more widespread application, pretest disease probability drops with drifts in sensitivity and specificity. This has been documented with nuclear perfusion stress, for which larger-cohort data are available.76
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