EDITORIAL COMMENT
Echocardiographic Monitoring Throughout ExerciseBetter Than the Post-Treadmill Approach?*
Luc A. Piérard, MD, PhD, FACC*
University Hospital Sart Tilman, Liège, Belgium.
* Reprint requests and correspondence: Dr. Luc A. Piérard, Division of Cardiology, University Hospital Sart Tilman, 4000 Liège, Belgium. (Email: lpierard{at}chu.ulg.ac.be).
Echocardiographic imaging coupled with cardiovascular stress testing had been proposed in 1979 but was really applied as a clinical tool in the late 1980s and early 1990s. It is now increasingly used for the diagnosis of coronary artery disease; the functional assessment of intermediate stenoses, risk stratification, and prognosis; identification of myocardial viability; and, more recently, in valvular heart disease (1–3). A series of successive improvements led to a progressively widespread acceptance: digital echocardiographic techniques, allowing capture and synchronized display of the same view at different stages, introduction of dipyridamole and dobutamine as pharmacologic stressors (4,5), improved endocardial border detection by harmonic imaging, and ultrasound contrast agents that opacify the left ventricle. New developments are still in a process of validation: myocardial contrast echocardiography during stress for the simultaneous assessment of regional perfusion and function, more objective analysis of regional function through the measurement of myocardial deformation by tissue Doppler imaging or speckle tracking, and real time 3-dimensional echocardiography. In daily practice, the interpretation of stress echocardiography is still based on the visual, qualitative, and, thus, subjective analysis of regional direction and amplitude of endocardial motion, regional wall thickening and thinning, and regional asynchrony in cross-sectional views usually displayed in a quad-screen format.
Exercise is the most physiologic stressor and, thus, is preferable in patients who are capable of exercising. However, 20% of patients cannot exercise and 20% can only perform a submaximal exercise test. In the U.S., most laboratories use the post-treadmill approach with imaging at rest and as soon as possible during the recovery period. In Europe, many laboratories use pharmacologic stressors even in patients who are able to exercise, but a number of centers have implemented their stress echocardiography laboratory with a dedicated bed or table allowing bicycle exercise in a semi-supine position and real-time continuous imaging throughout exercise. Intuitively, the incorporation of 1 or more intermediate stages of exercise could improve the accuracy of the method and help the evaluation of the ischemic threshold. However, this hypothesis has not yet been tested appropriately.
In this issue of the Journal, Park et al. (6) highlight the usefulness of recording and interpretation of intermediate stages of exercise that improve the diagnostic accuracy for both experienced and less experienced observers. Furthermore, they found that the ischemic threshold provides a physiologic assessment of the severity of coronary stenosis and that changes in left ventricular end-systolic volume during exercise can also be useful. The study included 104 individuals: 91 patients who underwent both exercise echocardiography and quantitative coronary angiography and 13 normal subjects without cardiovascular risk factors. Exercise echocardiography was performed using a dedicated bed; images were obtained at rest, at 25 W, 50 W, and at peak exercise, but not in the recovery phase. For the analysis, the images of the 2 intermediate stages could be masked allowing the comparison between interpretation of only rest and peak exercise images and the addition of the 2 intermediate stages. The majority (84%) of ischemic responses were described as a biphasic response: increased contractility at the intermediate stages compared to rest, followed by worsening function with a higher stress level or at peak exercise. The incorporation of the intermediate stages increased the sensitivity by 20%. When only rest and peak exercise were available, ischemia was missed in 8% of patients and was misclassified by coronary distribution in 12%. Several aspects of the study may be of importance. The antianginal medications were not withdrawn. Therefore, only 37% of patients reached the target heart rate during exercise. Contrast injection was used in 86% of the population for improving endocardial detection. Coronary arteries were normal or had no significant stenosis in 41% of the patients, allowing adequate assessment of specificity.
Accurate performance of exercise echocardiography relies on 2 steps: appropriate recording of images and correct interpretation of serial changes in wall motion and thickening. What are the skills required for recording appropriate images? Harmonic imaging is used in nearly all patients. Complete cardiac cycles should be captured. Retrospective capture is preferable during exercise: it is more practical to select the previous than the next cardiac cycle. The need for left ventricular opacification by a contrast agent should be considered from the quality of resting images to avoid a systematic placement of an intravenous catheter. It is essential to record exactly the same views at the different stages; real-time 3-dimensional echocardiography could be the solution in the future.
An adequate selection of the stages and their timing is desirable. One stage should be saved for the recovery period: the sensitivity of the test is increased if the development of ischemia during recovery is considered as a criterion of positivity. It is still questionable whether the recording of intermediate stages should be selected according to a specific charge of exercise, a specific heart rate, or when the echocardiographer detects a change in contraction. A learning curve is necessary for correct interpretation of exercise echocardiograms. An important drawback is the qualitative assessment. Moderate reproducibility has been observed with dobutamine echocardiography even by experts (7), and the level of agreement has not yet been tested for exercise echocardiography. Recent ultrasonic modalities such as tissue Doppler imaging and speckle tracking can provide measurements of myocardial deformation using strain rate. Such measurements may be more sensitive and accurate, especially in patients with intermediate coronary lesions (8).
Numerous factors affect the sensitivity of exercise echocardiography: the severity of stenoses; their location, length, and morphology; the presence or absence of collateral circulation; the presence or absence of antianginal medications; the maximum heart rate reached; and a too-much-delayed capture of images after exercise. Thus, the expertise of the reader is crucial to provide a high diagnostic accuracy.
Park et al. (6) demonstrate the importance of a continuous monitoring and selective recording throughout exercise. In most abnormal tests, the comparison between peak exercise and low charge was easier and more accurate than the comparison between peak stress and baseline. The incorporation of intermediate stages may be more crucial for enhancing accuracy when some factors could reduce sensitivity such as a largely submaximal heart rate at peak exercise and interpretation by an unexperienced observer. However, if obvious stress-induced dyssynergy is considered as an end point, continuous monitoring of images could potentially reduce the detection of multivessel disease if 1 of the stenoses is more severe than the others. Indeed, alteration in thickening appears earlier in the ischemic cascade that ST-segment changes and angina that are the classical end points of a treadmill exercise test.
The term "biphasic response" used by Park et al. (6) for the description of ischemic responses can be somewhat misleading. Clinical and experimental studies have used incremental doses of dobutamine to identify akinetic but viable myocardium perfused by a flow-limiting coronary stenosis. In this setting, a biphasic response implies that a ventricular region is dyssynergic at baseline, recovers contraction at low levels of stress, and deteriorates subsequently because of absent or limited coronary flow reserve. Contractile reserve of viable, akinetic myocardium can also be recruited and observed during low-level exercise as well as a biphasic response by continuous echocardiographic examination during semi-supine exercise (9,10). If contraction is normal at rest, hyperkinesia can develop during the first charges of exercise, followed by a reduction in wall motion at later stages. Is this kind of biphasic response sufficiently accurate as a marker of exercise-induced ischemia? A biphasic response has been frequently observed with dobutamine stress in healthy subjects: myocardial thickening and wall motion increased during the low stages and frequently stopped to increase or even decreased at peak exercise. A biphasic response for both radial and longitudinal deformation has been observed in normal subjects not only during dobutamine stress but also during upright and supine exercise (11). The biphasic strain response appears to reflect the changes in stroke volume induced by the heart rate increase and is common to all forms of stress. A biphasic response in stroke volume has indeed been observed in normal hearts during exercise (12). However, the eyeballing interpretation of exercise echocardiography by experts subtly integrates changes in regional morphology, motion, thickening, thinning, synchrony, and/or early or delayed relaxation.
The evaluation of not only the presence but the severity of coronary stenoses is clinically relevant. The onset of electrocardiographic abnormalities or chest pain is known to be unrelated to the ischemic threshold that can be assessed during exercise echocardiography by determining the level of myocardial oxygen demand at which ischemia develops. The online identification of ischemic threshold has been shown to be reliable and reproducible (13). The heart rate–blood pressure product at the ischemic threshold is correlated with the severity of coronary stenosis: r = –0.61 in the study by Park et al. (6) and r = –0.72 in the study by Garot et al. (13). Coronary physiology based on fractional flow reserve might probably provide a better correlation.
There are other reasons why continuous monitoring of echocardiographic parameters is preferable to the recording of images limited to the early recovery period. Several hemodynamic and prognostic informations are obtainable during exercise in patients with coronary artery disease. The ratio of early diastolic transmitral velocity to early diastolic tissue velocity (E/E') during exercise can identify patients with elevated left ventricular diastolic pressure (14). Systolic pulmonary pressure during exercise can be estimated in the presence of an even trivial tricuspid regurgitation. The increase in pulmonary arterial systolic pressure during exercise is unrelated to the level of pulmonary pressure at rest (15). Dynamic ischemic mitral regurgitation can be identified and has prognostic implications (16,17).
In summary, continuous echocardiographic monitoring throughout an exercise test and appropriate recording improve the diagnostic accuracy of coronary artery disease. The possible assessment of the ischemic threshold in addition to the site, extent, and severity of induced ischemia might be a useful tool for stratifying the need for coronary revascularization in symptomatic patients. Supine bicycle echocardiography, by offering the possibility of obtaining numerous informations during exercise, appears to be more useful than the post-treadmill approach.
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Footnotes
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* Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology. 
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