© 2003 by European Society of Cardiology
Copyright © 2003, The European Society of Cardiology
Accuracy of peak treadmill exercise echocardiography to detect multivessel coronary artery disease: comparison with post-exercise echocardiography
Unit of Echocardiography and Department of Cardiology, Juan Canalejo Hospital, A. Coruna, Spain
* Address correspondence to: Jesus C. Peteiro, P/Ronda 5-4° izda, 15011-A Coruña, Spain. Fax: 34-81-178-001. jpeteiro{at}mundo-r.com
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Abstract |
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Aims: Although peak exercise echocardiography has been reported for both bicycle and treadmill exercise and has shown higher sensitivity than post-exercise imaging, little is known about its utility for identifying multivessel involvement. We sought to compare feasibility and accuracy of peak treadmill exercise echocardiography vs post-exercise echocardiography for identification of multivessel coronary artery disease and to assess its incremental value when combined with clinical and exercise test variables.
Methods and Results: The study group included 335 patients (228 men; mean (±SD) age 60 ± 11 years). Two hundred and seventy-nine patients were included on the basis of having had an exercise echocardiography and a coronary angiography within 4 months of the exercise test. To avoid bias to coronary angiography, a subgroup of 56 consecutive non-diabetic patients referred for exercise echocardiography with pretest probability of coronary artery disease <10% and had atypical chest pain or were asymptomatics were also included and considered as having no coronary artery disease. Multivessel coronary artery disease (
50% diameter stenosis in <1 vessel) was confirmed in 170 patients, whereas 165 patients were considered to have one-vessel coronary artery disease or no coronary lesions. Positive exercise echocardiography was defined as ischaemia or necrosis in at least two coronary territories. Post-exercise images were acquired within 125 s after exercise (49±15). Mean heart rate (bpm) was 139±19 at peak vs 117±22 at post-exercise imaging (P<0.001). Interpretable peak and post-exercise images were obtained for all patients. Sensitivity for predicting multivessel disease was higher with peak than with post-exercise imaging (79 vs 55%, P<0.001), with lower specificity (79 vs 88%, P<0.05). Predictive positive value was similar (80 vs 83%). Negative predictive value was again higher with peak imaging (78 vs 66%, P<0.01). Total accuracy was not different (79 vs 72%). A stepwise logistic regression analysis identified peak exercise echocardiography positivity for multivessel coronary artery disease as the strongest independent predictor of multivessel disease (odds ratio (OR): 7.36); also significant were male gender (OR: 4.22), diabetes mellitus (OR: 4.28), previous myocardial infarction (OR: 3.12) and increment of product heart rate x blood pressure (OR: 1.00).
Conclusions: Peak treadmill exercise echocardiography is technically feasible and has higher sensitivity and negative predictive value for predicting multivessel disease than post-treadmill exercise echocardiography. This method adds independent and incremental values to clinical and exercise variables for the diagnosis of multivessel coronary artery disease. Therefore, in the clinical setting, peak exercise echocardiography should be performed to diagnose multivessel coronary artery disease.
Keywords: treadmill exercise echocardiography; peak exercise echocardiography; post-exercise echocardiography; multivessel coronary artery disease
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Introduction |
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Exercise echocardiography is an increasingly used test for evaluating patients with known or suspected coronary artery disease. As opposed to dobutamine stress echocardiography, images are acquired during the immediate post-exercise period, especially when treadmill is used rather than bicycle. One disadvantage of this approach is that heart rate and blood pressure may rapidly decrease with ischaemia relief, especially if patients are taking beta-blockers. This problem has been traditionally considered as a limitation of exercise echocardiography as compared with nuclear techniques or dobutamine stress echocardiography[1].
We have previously demonstrated the possibility of acquiring images during peak treadmill exercise[2]. As left ventricular global and regional functions are worse at peak exercise than immediately after exercise in coronary artery disease patients, we hypothesized that acquiring images at peak exercise may detect multivessel disease more accurately. Thus, the aims of this study were to compare the value of exercise echocardiography obtaining images at peak stress vs exercise echocardiography obtaining images immediately after exercise for the detection of multivessel coronary artery disease and to assess the incremental value of exercise echocardiography when combined with clinical and exercise variables.
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Patients
The study group included 335 patients (228 men, 107 women; mean (±SD) age 60 ± 11 years). Two hundred and seventy-nine patients were retrospectively included on the basis of having had an exercise echocardiography between December 1998 and December 2000 and a coronary angiography within 4 months of the exercise test. To avoid bias to coronary angiography, a subgroup of 56 consecutive non-diabetic patients referred for exercise echocardiography with pretest probability of coronary artery disease <10% who had atypical chest pain or were asymptomatics were also included. These latter patients were considered as having no coronary artery disease. Both peak and post-exercise two-dimensional images were obtained for all patients. The decision to perform exercise echocardiography included chest pain (55%), coronary lesion functional significance (8%), myocardial infarction (22%), revascularization procedures (6%) and other reasons (9%). Previous myocardial infarction was reported in 30%, and revascularization procedures in 17% (angioplasty in 10% and bypass surgery in 7%). At the time of the exercise echocardiography, beta-blockers were being taken by 10%, as our policy is to withdraw them previous to exercise testing, nitrates by 42%, calcium channel blocking agents by 23% and ACE inhibitors by 31%. There were no exclusion criteria. Four patients were found to have aortic valve disease (mild or moderate aortic stenosis in two and moderate aortic insufficiency in two). Left ventricular dysfunction defined by an ejection fraction of <45% was present in 55 patients (16%), left bundle branch block in 41 (12%) and atrial fibrillation in nine (3%). Written informed consent was obtained. The decision to perform angiography was based on the clinical situation, patient cardiologist's responsibility and exercise echocardiography result.
Exercise echocardiography
Heart rate, blood pressure and a 12-lead ECG were obtained at baseline and at 3-min stages. Patients were encouraged to perform a treadmill exercise test (Bruce protocol 306, modified Bruce 15 and Naugthon 14) until exhaustion or until they reached an endpoint. Endpoints included ST-segment depression <2 mm, significant arrhythmia, severe hypertension (systolic blood pressure <240 mmHg or diastolic blood pressure <110 mmHg) or severe hypotensive response (decrease <20 mmHg from baseline).
Two-dimensional echocardiography using either fundamental (Vingmed CFM 750, Vingmed Sound, Horten, Norway) or harmonic imaging (HP-5500, Agilent Technologies, MA, USA) was performed by an expert physician echocardiographer in the parasternal long- and short-axis and apical two- and four-chamber views, at baseline, peak exercise and immediately after exercise. Peak exercise echocardiography was performed when signs of exhaustion were present or an endpoint was reached. The patient was asked to walk quickly rather than run, to decrease body and respiratory movements. The transducer was firmly positioned on the cardiac apex to obtain the four-chamber apical view. The physician applied slight pressure to the patient's back with the left hand, maintaining the patient between the transducer and the left hand, to avoid movement. The transducer was then rotated while an attempt was made to avoid displacement to obtain the two-chamber apical view. Finally, the transducer was positioned in the parasternal region to obtain short- and long-axis parasternal views. Post-exercise images were obtained in the same order with the patient lying on the left lateral decubitus position. Mean acquisition time for the post-exercise images was 49 ± 15s (range 21–125 s). Image acquisition was performed on-line and stored on an optical disk.
Image analysis
Echocardiographic two-dimensional analysis was performed on a digital quad screen display system. The left ventricle was divided into 16 segments[3]. Each of the 16 segments was assigned to one of the three coronary artery territories[4]. The development of new regional dysfunction (hypokinesia, akinesia or dyskinesia) or worsening from hypokinesia to akinesia or dyskinesia was considered an ischaemic response. The persistence of regional baseline dysfunction affecting at least one segment in one coronary artery territory, or worsening from akinesia to dyskinesia, was considered as infarction without ischaemia, except for left bundle branch block patients. In these patients, isolated septal hypokinesia was not considered necrosis. A positive exercise echocardiography for coronary artery disease was defined when there was ischaemia or necrosis in at least one coronary territory[4–6], while a positive exercise echocardiography for multivessel coronary artery disease was considered when there was ischaemia or necrosis in at least two coronary artery territories. An RWM score index (at rest, peak and post-exercise) was calculated, with normal wall motion scoring 1, hypokinetic 2, akinetic 3 and dyskinetic 4.
All exercise echocardiography were analysed by an expert physician echocardiographist (>3500 exercise echocardiography), blind to clinical history, ECG and coronary angiography. Rest and post-exercise echocardiography and rest compared with peak exercise echocardiography were analysed for every patient from optical disk-stored images on separate days.
Each peak and post-exercise image was qualified from 0 to 6 points according to the number of clearly visualized endocardial segment borders and systolic excursion by view. In case a view was not obtained, a value of 0 was given. Interpretable view was defined as a view with 4 clearly visualized endocardial segment borders and systolic excursion. Patients were considered to have interpretable peak and post-exercise echocardiography studied when there was at least two standard interpretable views available for visualization of all or part of each coronary territory. Left ventricular ejection fraction was measured from optical disk-stored images by biplane Simpson's rule[4].
Coronary angiography
Coronary angiography was performed up to 4 months before (8%) or after (92%) the exercise echocardiographic study, showing 223 patients (80%) with significant coronary lesions (50% luminal diameter narrowing in a coronary artery, major branch, or bypass graft), and 56 (20%) without. One-vessel disease was found in 53 (19%) and multivessel disease in 170 (61%).
Patient classification
Of the 335 patients, 170 had multivessel disease as demonstrated in coronary angiography, whereas 165 were considered to have no multivessel disease. The latter patients included the 109 patients who had no coronary artery lesions (56 patients) or one-vessel coronary artery disease (53 patients: 22 with left anterior descending artery stenosis, which was proximal in 12) in coronary angiography and the 56 patients not submitted to coronary angiography who had a pretest probability of coronary artery disease <10%.
Statistical analysis
Values are reported as mean ± 1 SD. Student's t-test for paired or unpaired data was used for comparison when appropriate. Qualitative data were compared with the 
2-test. A P value <0.05 was considered significant. To assess the incremental value of echocardiographic variables in relation to clinical and exercise variables, stepwise logistic regression was used in a hierarchic manner. First, we obtained a model based on clinical variables. Then, the significant clinical variables were forced into the model, and the exercise variables were allowed into the model. Finally, the significant clinical and exercise variables were forced in, and the echocardiographic variables were allowed in.
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Results |
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Feasibility of peak and post-exercise echocardiography (Table 1)
Apical views were easily obtained at peak and post-exercise, whereas parasternal views were more easily acquired at post-exercise. Failure to obtain both apical views occurred in the same two patients at peak and at post-exercise, whereas failure to obtain both parasternal views was more frequent at peak exercise.
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The image quality of apical views was similar for peak and post-exercise (Table 2), whereas parasternal views were better scored at post-exercise than at peak exercise. Interpretable peak and post-exercise echocardiography, as defined previously, were obtained for all patients.
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Patients characteristics
There were significant clinical, exercise and echocardiographic differences between patients with and without multivessel coronary artery disease. Patients with multivessel coronary artery disease were older (63 ± 9 years vs 57 ± 11 years, P<0.001). More patients in this group were males (83 vs 52%, P<0.001) and had diabetes mellitus (16 vs 9%, P<0.001), and the frequency of previous myocardial infarction was higher (56 vs 19%, P<0.001). Patients with multivessel disease achieved lower METs (9.0±3.3 vs 9.8±2.7, P<0.05) and rate-pressure product (24 202±5398 vs 27 712±5832, P<0.001). Angina and ST depression during exercise were more common in patients with multivessel disease (37 vs 18%, P<0.001 and 36 vs 16%, P<0.001, respectively). RWM score index and left ventricular ejection fraction were worse at rest (1.3±0.03 vs 1.1±0.3, P<0.001 and 52±11 vs 57±10, P<0.001, respectively) and at peak exercise (1.7±0.3 vs 1.2±0.3, P<0.001 and 47±14 vs 60±14, P<0.001, respectively) in patients with multivessel disease.
Stepwise logistic regression analysis
The stepwise logistic regression analysis model identified five variables as independent predictors of the presence of multivessel disease: male gender, diabetes mellitus, presence of previous myocardial infarction, increment of rate-pressure product and detection of multivessel disease at peak exercise (Table 3). The strongest predictor was peak exercise echocardiography positivity for multivessel disease.
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Accuracy of peak vs post-exercise echocardiography for multivessel coronary artery disease
The maximum heart rate was 144 ± 20 bpm, not unlike the mean heart rate at the time peak images were acquired (139 ± 19 bpm). The mean heart rate after exercise was 117 ± 22 bpm (P<0.001 vs peak exercise echocardiography), ranging from a maximum of 125 ± 23 bpm at the time the first image was acquired (four-chamber apical view) to a minimum of 108 ± 23 at the time the last image was acquired (parasternal short axis).
An RWM abnormality was present at rest in 115 patients (34%). Overall, 204 of 223 patients with any coronary lesion had a positive finding by peak exercise echocardiography and 178 by post-exercise echocardiography, resulting in a sensitivity of 91 vs 80% for the detection of coronary artery disease. However, our goal was to compare the ability of peak and post-exercise echocardiography to detect multivessel coronary artery disease. Fig. 1 shows the percentage of patients with and without multivessel coronary artery disease having normal result, ischaemia in one or more than one territory, necrosis in one or more than one territory and ischaemia at a distance in peak vs post-exercise echocardiography. Ischaemia in more than one territory and ischaemia at a distance were more frequent at peak exercise echocardiography in patients with multivessel coronary artery disease. Sensitivity, specificity, predictive value, and accuracy of peak and post-exercise echocardiography for the detection of multivessel coronary artery disease in the global of patients as in patients with and without necrosis on rest echocardiography are shown in Fig. 2. The difference in sensitivity was even higher in patients with normal wall motion at rest. No differences in sensitivity, specificity and accuracy were found between the 238 patients (71%) who exercised maximally and the 97 patients (29%) who did not achieve 85% of the age-predicted maximal heart rate.
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Figs. 3 and 4
show an example of a patient with a history of inferior myocardial infarction who had akinesia of the posterior wall at rest and severe hypokinesia of the anterior wall at peak exercise, which had resolved by the time imaging was done after exercise.
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Discussion |
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Several studies have demonstrated high sensitivity, specificity and accuracy of treadmill exercise echocardiography for coronary artery disease[5–10]. However, most of them have been carried out with post-treadmill imaging and no one has attempted to compare exercise and post-exercise imaging. It is known that the accuracy of post-exercise echocardiography depends on rapid image acquisition to avoid heart rate and blood pressure recovery, the main determinants of oxygen uptake. Hence, the lack of achievement of an 85% age-predicted maximum heart rate has been demonstrated to be an important cause of limited sensitivity[9]. We have previously demonstrated the feasibility and superiority of peak treadmill exercise echocardiography[2]. In this study, we extended those results by assessing the ability of this technique to identify multivessel coronary artery disease to patients who would potentially benefit from revascularization procedures. We also studied the incremental value of the echocardiographic variables for the detection of more extensive coronary artery disease.
Peak vs post-exercise imaging in previous studies
Some investigators have compared exercise and after-exercise bicycle echocardiography, although no one has specifically compared both modalities for the detection of multivessel coronary artery disease. Presti et al.[11] reported greater sensitivity for imaging at peak exercise (100%) than after exercise (70%). Ryan et al. studied 309 patients with peak and post-exercise imaging by upright bicycle and coronary angiography[12]. For these patients, only apical images were obtained at peak echocardiography. The sensitivity of post-exercise imaging was 83% compared with 91% for peak exercise imaging. Applegate et al.[13] compared peak exercise echocardiography during bicycle with post-treadmill echocardiography, observing a similar detection frequency of wall motion abnormalities. However, it is known that 5–11% higher levels of oxygen consumption are achieved during treadmill as opposed to bicycle[14].
A recent study by Badruddin et al.[15] demonstrated the superiority of peak imaging with supine bicycle as compared with post-treadmill imaging in 79 patients. Ischaemia was more frequently detected with bicycle (75 vs 61%). Sensitivity for the detection of coronary artery disease based on rest and peak imaging was also higher with bicycle (82 vs 75%), although these differences did not reach statistical significance. Although the achieved product heart rate x blood pressure was similar in the two modalities, the examination time was significantly longer with bicycle (12±3 vs 7±1, P<0.001). Other recognized limitations of bicycle are that the patient may stop the test when minimal symptoms begin and that only a subset of patients are accustomed to cycling, as opposed to walking.
In our previous study[2], sensitivity of peak treadmill imaging was 94%, significantly higher than post-treadmill imaging (73%, P<0.001) and similar to the reported sensitivity with peak imaging during supine bicycling.
Present study
Although treadmill is widely used, it has been assumed that imaging during treadmill exercise is not feasible. We demonstrate that interpretable images can be acquired, especially apical views, and, what is more important from a clinical point of view, a significant percentage of patients can be diagnosed as having multivessel disease. In fact, multivessel coronary artery disease would have been misdiagnosed in 24% of our patients if imaging had been limited to post-exercise. Although parasternal views were more easily obtained after exercise and the image quality of these views was better at this time, no differences were found with respect to apical views. Therefore, the superiority of peak imaging is likely due to adequate image quality of apical views. Our results also demonstrate that exercise echocardiography add independent and incremental values to clinical and exercise variables alone.
Limitations
The first limitation of many studies investigating the value of non-invasive tests to assess coronary artery disease is the altered referral pattern, because in most cases, patients are submitted to coronary angiography by the clinician aware of the exercise echocardiography results. Therefore, specificity reigns lower and sensitivity higher[16,17]. To avoid this limitation, we also studied a subgroup of patients with very low probability of having coronary artery disease and considered that these patients did not have any coronary artery disease. However, ideally, these patients should have undergone coronary angiography. As opposed to previous studies[7,18,19], we did not exclude patients with valvular heart disease, poor imaging quality, prolonged imaging acquisition time, submaximal exercise or left ventricular dysfunction. Therefore, patients are likely to be representative of the practice in an exercise echocardiography laboratory.
Imaging at peak was performed with the patients in a position different than after exercise. This does not preclude the possibility of positional factors playing a role in exercise-induced RWM abnormalities, affecting specificity. However, a study done with radionuclide ventriculography demonstrated that segmental wall motion was similar with upright and supine exercise[20].
The sensitivity for predicting multivessel coronary artery disease with post-treadmill imaging in this study is low as compared with a previous one[5]. Several explanations account for this lack of sensitivity. Firstly, imaging analysis was blind with regard to clinical history, clinical signs and ECG response to exercise. Secondly, there were no exclusion criteria. A significant percentage (38%) of patients considered to have multivessel disease did not achieve 85% age-predicted maximum heart rate.
Imaging during peak exercise may require a greater degree of expertise than post-exercise imaging and may limit the application of the technique. However, an advantage of this approach is the relative lack of hurry when imaging is performed at peak, as opposed to the limited time window for imaging acquisition after exercise.
Previous studies have demonstrated that the persistency time of RWM abnormalities after exercise is related to more severe coronary artery disease[21]. Post-ischaemic recovery of left ventricular function is also related to the duration of ischaemic burden[22]. Because echocardiographic monitoring was not performed in this study, we cannot preclude the fact that patients with persistent RWM abnormalities did not have more ischaemic time during exercise.
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