Effect of left ventricular global systolic function, mitral regurgitation, and left ventricular inflow pattern on exercise echocardiography results

Diagnosis of coronary artery disease (CAD) by exercise echocardiography is usually based on rest or exercise-induced regional wall-motion abnormalities. Mitral regurgitation (MR), left ventricular (LV) global systolic function, and LV inflow measurements can be assessed during exercise echocardiography; however, their diagnostic value has not been analyzed consistently. Treadmill exercise echocardiography and coronary angiography were performed in 120 patients (94 male, 26 female; mean age 61 +/- 10 years [+/- 1 SD]) to evaluate known or suspected CAD. Positive exercise echocardiography was defined either as a rest- or exercise-induced regional wall-motion abnormalities. An abnormal response of LV ejection fraction (EF), LV volumes, MR (as assessed by color Doppler), and LV inflow pattern was defined as a fall in LVEF, a LV end-diastolic volume increase, a LV end-systolic volume increase, a new or increased MR, or a change from an impaired relaxation pattern (E < A) to a "pseudonormalized" pattern (E > A) from rest to exercise, respectively. CAD (> or = 50% luminal narrowing in at least one vessel) was found in 89 (74%) patients. EE-based regional wall-motion abnormality analysis was positive in 95 (79%) patients and negative in 25 (21%) patients. Feasible images for regional wall-motion abnormalities, LVEF and volumes, LV inflow, and MR measurements were acquired in 90% of patients. Regional wall-motion abnormality analysis and LVEF decrease provided the greatest sensitivities for CAD (94% and 75%, respectively), while the highest specificity was given by a new or increased MR (90%), the development of a pseudonormalized pattern (88%), and the appearance of angina (87%). A positive electrocardiogram (ECG) finding in patients with interpretable ECGs provided good sensitivity and specificity (67% and 85%, respectively). In conclusion, a complete rest and exercise Doppler echocardiography approach is feasible in most patients. Regional wall-motion abnormalities are the most accurate exercise echocardiography variable for diagnosing CAD, whereas exercise ECG remains a good test in patients with interpretable ECGs. Exercise echocardiography, exercise ECG, newly developed or increased MR, and change to a pseudonormalized LV inflow pattern are highly specific.     

Exercise echocardiography after coronary artery bypass grafting.

Exercise echocardiography was used to assess the adequacy of regional myocardial perfusion in 125 patients who had undergone coronary artery bypass grafting. There were 108 men and 17 women (mean age 65 years) evaluated from 6 weeks to 16 years (mean 7 years) after surgery. Resting parasternal long- and short-axis and apical 4- and 2-chamber echocardiograms were recorded, digitized and stored. Maximal, symptom-limited upright treadmill exercise was then performed with continuous electrocardiographic monitoring. Repeat echocardiographic imaging and digitization were repeated within 1 minute of exercise termination. Resting and postexercise digitized echocardiograms were compared. A normal regional wall motion response to exercise consisted of improved segmental contraction and was used to predict uncompromised regional vascular supply. Unimproved or worsened segmental contraction after exercise was abnormal and was used as a predictor of regional vascular insufficiency. All patients underwent cardiac catheterization within 1 month after exercise testing. Regional coronary insufficiency was considered to exist when a segment's major vascular conduit exhibited greater than or equal to 50% luminal diameter reduction. Compared with the simultaneously acquired stress electrocardiogram, exercise echocardiography had superior sensitivity (98 vs 41%), specificity (92 vs 67%), positive predictive value (99 vs 91%), and negative predictive value (86 vs 12%) (p less than 0.001, 0.1, 0.01 and less than 0.001, respectively). In addition, exercise echocardiography correlated closely with the extent and regional distribution of compromised vascular supply. Exercise echocardiography is a highly sensitive, specific and accurate screening test for abnormal global and regional myocardial vascular supply in patients who have undergone coronary artery bypass grafting.     

二维超声室壁运动异常与冠脉病变范围的关联性

目的 :分析心肌梗死患者二维超声室壁运动异常节段分布与冠状动脉损伤间的关系。方法 :回顾性分析 92例心梗患者二维超声室壁运动异常节段分布情况 ,并与冠状动脉病变范围进行比较。结果 :1冠状动脉梗塞后左前降支 （L AD）受累最为多见 （45 % ） ;2 L AD单支病变与前壁、前间隔及心尖部室壁运动异常有关 （P<0 .0 5 ）。 L AD与左回旋支病变 ,主要为前间隔和下壁运动异常 ;而单纯的下壁室壁运动异常多为左旋支与右冠状动脉病变引起。 3支病变造成心肌运动普遍减低 ,且以侧壁及前侧壁的室壁运动异常则更为显著 （P<0 .0 5 ）。结论 :二维超声心动图室壁运动异常与冠脉病变范围有较好的关联性。     

Exercise echocardiography follow-up in percutaneous transluminal coronary angioplasty

Exercise echocardiography has emerged as an excellent tool in the diagnosis of coronary artery disease and has proven to correlate very closely with the distribution and extent of coronary stenoses. In this report we describe our experience with the use of this noninvasive technique in evaluating patients at various stages before, shortly after, and later after percutaneous transluminal coronary angioplasty (PTCA). Coronary restenosis following PTCA occurs at rates between 25% and 40% and currently available screening tests including clinical history, routine exercise electrocardiography, and thallium scintigraphy have proven disappointing correlating with the presence or absence of restenosis. We have found that exercise echocardiography is useful not only in identifying patients who have coronary disease and in predicting the extent and distribution of this disease, but also in demonstrating even very early after angioplasty left ventricular functional improvement both at rest and with exercise. Once patients are discharged from the hospital and followed serially over 5 years, we have found that this tool is extremely valuable in predicting not only coronary restenosis at the site(s) of angioplasty but is also highly predictive of the development of new coronary stenoses. The capabilities of exercise echocardiography to predict restenosis and new disease far exceed the reliability of exercise electrocardiography or the presence or absence of symptoms as indicators of these problems. We have found exercise echocardiography to be an unexcelled screening test in the management of angioplasty patients.     

Dipyridamole echocardiography

Intravenous dipyridamole is a potent coronary vasodilator that has been extensively investigated over the past several years in the noninvasive assessment of patients with suspected coronary artery disease when exercise cannot be performed or is suboptimal. As an alternative to exercise studies, dipyridamole has been used in combination with different cardiac imaging techniques such as echocardiography, thallium scintigraphy, and radionuclide ventriculography. Extensive experience has been obtained with dipyridamole thallium-201 imaging for coronary artery disease screening, risk stratification, and prognosis after an acute coronary event. However, experience with the use of dipyridamole in combination with two-dimensional echocardiography has been limited. Dipyridamole increases coronary blood flow in nondiseased coronary vessels relative to coronary vessels with significant luminal narrowings. These provide the basis for detecting regional differences in flow by using different cardiac imaging techniques. Two-dimensional echocardiography would show regional wall-motion abnormalities in response to those regional differences in coronary blood flow. In this article, the most commonly used protocols, safety, and practicability of dipyridamole echocardiography are reviewed. As an alternative to exercise, dipyridamole echocardiography shares all the indications of a standard exercise test. Clinical applications of dipyridamole echocardiography include coronary artery disease screening, suspected coronary artery spasm, postmyocardial infarction risk stratification, evaluation of percutaneous transluminal coronary angioplasty results, and prognosis following an acute coronary event. Compared to conventional (ECG) exercise testing, dipyridamole echocardiography appears to be equally sensitive but more specific. Compared to atrial pacing, dipyridamole provokes ischemia at a lower rate pressure product and results in a greater ST segment depression suggesting that dipyridamole induces more profound myocardial ischemia than atrial pacing. Dipyridamole thallium and exercise thallium have shown to be equally sensitive and specific in the assessment of coronary artery disease. High dose dipyridamole echocardiography appeared to be equally sensitive and more specific. Experimental studies have demonstrated that dobutamine appears to be a more powerful pharmacological agent in inducing wall-motion abnormalities. Dipyridamole echocardiography as compared to stress echocardiography offers the advantage of obtaining better quality postintervention images. With regard to sensitivity and for coronary artery disease diagnosis, both techniques appear to render similar results. Although further studies are needed, the available data indicates that cardiac ultrasound imaging prior to and following the intravenous administration of dipyridamole may be an attractive alternative to thallium perfusion imaging in the clinical setting, particularly when radionuclide capabilities are not present.     

Exercise echocardiography

Exercise echocardiography is a versatile, noninvasive diagnostic test that involves the recording and interpretation of 2-dimensional echocardiograms prior to, during, and after exercise. By analyzing and comparing wall motion at each stage, a prediction about the presence or absence of coronary artery disease can be made. The development of a wall motion abnormality is both sensitive and specific for the presence of a significant coronary stenosis. Changes in regional systolic function during exercise enable the clinician to distinguish between infarction and ischemia. Thus, the test yields information on the presence, extent, severity, and location of coronary artery disease. Echocardiography can be adapted to almost any form of stress, although treadmill or bicycle exercise are most commonly employed. An advantage of bicycle stress echocardiography is the opportunity to image during exercise, rather than relying on postexercise recording. This contributes to enhanced sensitivity, although false-positive results may increase due to the difficulties of analyzing wall motion during strenuous exercise. Exercise echocardiography increases the diagnostic accuracy of stress testing in a manner similar to radionuclide perfusion imaging. It is particularly useful in the setting of an ambiguous stress electrocardiography (ECG) or when a false-negative or false-positive result is suspected. It has been successfully applied to patients following revascularization and yields useful prognostic data in a variety of clinical situations. Exercise echocardiography is being increasingly utilized as a safe and accurate test in patients with known or suspected coronary artery disease.     

Exercise echocardiographic detection of coronary artery disease in women

The utility of exercise echocardiography for the diagnosis of coronary artery disease has been demonstrated in populations consisting largely of men with a high prevalence of disease. To determine the diagnostic value of exercise echocardiography in women, 57 women who presented with chest pain were studied with coronary cineangiography and echocardiography combined with either treadmill (n = 38) or bicycle exercise (n = 19). Significant coronary artery disease (greater than or equal to 50% reduction in luminal diameter) was present in 28 (49%) of 57 patients, including 16 (84%) of 19 who had typical angina, and 12 (32%) of 38 who had atypical chest pain. The overall sensitivity and specificity of echocardiography were both 86%. Exercise echocardiography correctly determined the presence or absence of coronary artery disease in 32 (84%) of 38 patients who had atypical chest pain and in 17 (89%) of 19 who had typical angina (p = NS). The exercise electrocardiogram (ECG) was nondiagnostic in 17 patients (30%) who had rest ST segment depression or ST depression with exercise that could also be induced by hyperventilation or changes in position. The correct diagnosis was made by echocardiography in 14 (82%) of 17 patients with a nondiagnostic exercise ECG. In conclusion, exercise echocardiography has a clinically useful level of sensitivity and specificity for the detection of coronary artery disease in women. The technique provides diagnostic information in women presenting with atypical chest pain and in those who have a nondiagnostic exercise ECG.     

The role of stress echocardiography in children

Exercise and pharmacological stress echocardiography are well-accepted techniques of evaluating coronary artery disease in adults. In children, however, experience with stress echocardiography is limited and continues to evolve. The objective of this focused review was to describe the experience with exercise and dobutamine stress echocardiography in the pediatric population, with an emphasis on technique, current indications, and future directions. Experience is reported in children with prior Kawasaki disease or heart transplant recipients, as well as patients with congenital coronary abnormalities. In addition, stress echocardiography has been used in patients who have undergone coronary artery bypass graft surgery to evaluate short- and long-term graft patterning. Stress echocardiography appears to be a feasible, safe, and useful modality for the noninvasive assessment of flow-limiting stenosis in the pediatric population and can be used serially in the routine follow-up and risk stratification in children at risk for coronary events.     

Bicycle Stress Echocardiography

Bicycle stress echocardiography involves the recording and interpretation of two-dimensional echocardiographic information before, during, and after bicycle exercise. The exercise test can be performed in the supine or upright posture. While there are important physiological differences between these two positions, they appear to provide similar diagnostic information on the presence or absence of coronary artery disease. A major advantage of bicycle stress echocardiography compared to treadmill exercise is the ability to image at peak exercise, rather than relying solely on pre- and postexercise imaging. This contributes to the greater sensitivity of the test for the detection of ischemia. The recent application of digital processing techniques may also improve sensitivity by permitting side-by-side comparison of rest and stress images. In summary, bicycle stress echocardiography is a useful tool in the management of patients with known or suspected coronary artery disease. It is a versatile and accurate technique, which competes favorably with other imaging modalities and provides information on regional and global left ventricular function.     

Bicycle stress echocardiography

Bicycle stress echocardiography involves the recording and interpretation of two-dimensional echocardiographic information before, during, and after bicycle exercise. The exercise test can be performed in the supine or upright posture. While there are important physiological differences between these two positions, they appear to provide similar diagnostic information on the presence or absence of coronary artery disease. A major advantage of bicycle stress echocardiography compared to treadmill exercise is the ability to image at peak exercise, rather than relying solely on pre- and postexercise imaging. This contributes to the greater sensitivity of the test for the detection of ischemia. The recent application of digital processing techniques may also improve sensitivity by permitting side-by-side comparison of rest and stress images. In summary, bicycle stress echocardiography is a useful tool in the management of patients with known or suspected coronary artery disease. It is a versatile and accurate technique, which competes favorably with other imaging modalities and provides information on regional and global left ventricular function.     

Usefulness of exercise echocardiography in ischemic heart disease: comparison with exercise cardiac scintigraphy

Exercise echocardiography and exercise thallium-201 (201Tl) single photon emission computed tomography (SPECT) were performed in 152 patients with suspected coronary artery disease, including 61 patients with old myocardial infarction. All patients underwent coronary arteriography, and coronary artery disease was defined as > or = 75% diameter stenosis. Digital two-dimensional echocardiography was performed before and after the treadmill exercise test, and wall motion abnormality was evaluated using quad-screen. Sensitivity and specificity for the diagnosis of coronary artery disease were similar for the 2 exercise tests (77% and 80% for echocardiography and 75%, and 83% for SPECT, respectively). Diagnoses for one-vessel disease, 2-vessel disease and 3-vessel disease were similar for echocardiography (79%, 72% and 77%, respectively) and SPECT (74%, 75% and 77%, respectively). Sensitivity for the diagnosis of ischemia at the area remote from infarct area was low for both exercise echocardiography and exercise SPECT (45% and 48%, respectively). Exercise echocardiography has comparable diagnostic value to SPECT for the detection of coronary artery disease. However, both exercise tests have limitations for the diagnosis of ischemia at the area remote from infarct area.     

Dobutamine stress echocardiography: its role in the diagnosis of coronary artery disease.

We have assessed the usefulness of dobutamine infusion for the diagnosis of coronary artery disease by using two-dimensional echocardiography and 12-lead electrocardiogram. Dobutamine was infused at incremental doses (up to a maximum of 40 micrograms kg-1 min-1) in 52 patients with chest pain; all the patients underwent coronary angiography; significant coronary artery disease was quantitatively defined as greater than or equal to 50% diameter stenosis. Thirty-six patients were on betablockers. The test was considered positive when new regional wall motion abnormalities appeared during dobutamine infusion. No significant side effects occurred in any patient during the test. Transient wall motion abnormalities were detected in 20 of 37 patients with coronary artery disease (sensitivity = 54%); ischaemic ST segment changes were present on ECG in nine patients (sensitivity = 24%). Dobutamine stress echocardiography was negative in 12 of 15 patients with coronary artery diameter stenosis less than 50% (specificity = 80%). Exercise electrocardiography (ECG) was performed in 35 of these 52 patients. Maximum heart rate and systolic blood pressure were significantly higher during exercise than during dobutamine stress test (127 +/- 23 vs 99 +/- 24 beats min-1, P less than 0.0001; 179 +/- 25 vs 152 +/- 30 mmHg, P less than 0.0001). The exercise ECG test was positive in 12 of the 26 patients with significant coronary artery disease (sensitivity = 46%), and dobutamine stress echocardiography in 16 (sensitivity = 62%). Dobutamine stress echocardiography test is a safe and feasible diagnostic test for the noninvasive diagnosis of coronary artery disease and can be performed in patients unable to exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Short term reproducibility of exercise testing in patients with ST segment elevation and different responses to the dipyridamole test.

The short term reproducibility of exercise testing in 25 patients who had exercise induced ST segment elevation without baseline regional asynergy or a previous myocardial infarction, who had different responses to the dipyridamole test, was assessed. The patients performed a dipyridamole echocardiography test and a second exercise stress test. All underwent coronary arteriography. Seventeen patients had transient regional asynergy after dipyridamole (group 1) and either ST segment elevation (14 patients) or depression (three patients); a second group of eight had no asynergy and no electrocardiographic changes (group 2). The repeated exercise stress test was positive in 16 of the 17 patients of group 1 (11 with ST elevation and five with ST depression) and in two patients of group 2 (both had ST depression and one had coronary artery disease). The dipyridamole echocardiography test was positive in 17 of the 19 patients with coronary artery disease and was negative in all six patients without coronary artery disease. The repeated exercise stress test was positive in 17 of the 19 patients with coronary artery disease and in one patient without. The dipyridamole echocardiography test and a repeated exercise stress test, but not a single exercise stress test, identified coronary artery disease causing exercise induced ST segment elevation.     

Exercise echocardiography as a screening test for coronary artery disease and correlation with coronary arteriography

We evaluated exercise echocardiography as a screening test for coronary artery disease in 228 patients, all of whom underwent subsequent coronary angiography. After an echocardiogram at rest was obtained, each patient performed maximal, symptom-limited, upright treadmill exercise, immediately after which repeat imaging was performed. The exercise echocardiogram was abnormal if any segment failed to become hypercontractile with exercise, and these regional wall motion abnormalities were used to predict the extent and distribution of coronary disease. At subsequent angiography, coronary stenosis was defined as significant if luminal diameter was reduced greater than or equal to 50%. Compared with electrocardiography, exercise echocardiography was more sensitive (97 vs 51%) and specific (64 vs 62%), and had higher positive (90 vs 82%) and negative (87 vs 28%) predictive accuracies. Exercise echocardiography was also highly predictive of the extent (no, 1-, 2- or 3-vessel disease) and distribution (which vessel) of coronary stenoses. It is concluded that exercise echocardiography is an excellent screening test for the presence, extent and distribution of coronary artery disease.     

Short term reproducibility of exercise testing in patients with ST segment elevation and different responses to the dipyridamole test

The short term reproducibility of exercise testing in 25 patients who had exercise induced ST segment elevation without baseline regional asynergy or a previous myocardial infarction, who had different responses to the dipyridamole test, was assessed. The patients performed a dipyridamole echocardiography test and a second exercise stress test. All underwent coronary arteriography. Seventeen patients had transient regional asynergy after dipyridamole (group 1) and either ST segment elevation (14 patients) or depression (three patients); a second group of eight had no asynergy and no electrocardiographic changes (group 2). The repeated exercise stress test was positive in 16 of the 17 patients of group 1 (11 with ST elevation and five with ST depression) and in two patients of group 2 (both had ST depression and one had coronary artery disease). The dipyridamole echocardiography test was positive in 17 of the 19 patients with coronary artery disease and was negative in all six patients without coronary artery disease. The repeated exercise stress test was positive in 17 of the 19 patients with coronary artery disease and in one patient without. The dipyridamole echocardiography test and a repeated exercise stress test, but not a single exercise stress test, identified coronary artery disease causing exercise induced ST segment elevation.     

Effect of the degree of effort on exercise echocardiography for the detection of restenosis after coronary artery angioplasty.

To determine whether the accuracy of exercise echocardiography is affected by the degree of effort during exercise, we examined 101 patients who had 6 months earlier undergone successful coronary artery angioplasty, with resting and immediate postexercise echocardiography and same-day coronary angiography. A positive exercise echocardiographic response was defined as the development of a new or worsening wall motion abnormality postexercise, compared with resting wall motion. Significant coronary disease (greater than 50% diameter stenosis) was present in 48 patients, 38 of whom had single-vessel disease and 10 of whom had two-vessel disease. Exercise echocardiography correctly identified 32 patients with significant disease (sensitivity 67%) and 44 patients without significant disease (specificity 83%). The effect of the degree of exercise effort on the sensitivity and specificity of the test was evaluated by three criteria; (1) the percentage of maximum predicted heart rate (MHR), (2) the duration of exercise (DUR), and (3) the double product (DP). To determine the influence of the degree of effort upon sensitivity and specificity, the effort criteria were compared between patients with true positive (TP) tests to those with false negative tests (FN), and in patients with true negative (TN) tests compared with those with false positive (FP) tests. No significant differences were detected in MHR, DUR, or DP between TP versus FN patients or between TN versus FP patients. These results indicate that for symptom-limited exercise echocardiography in postangioplasty patients, neither sensitivity nor specificity is significantly affected by the degree of effort during exercise.     

Echocardiographic detection of coronary artery disease: Detection of effects of ischemia on regional myocardial wall motion and visualization of left main coronary artery disease

M mode and cross-sectional echocardiographic studies at rest have been used to detect regional left ventricular wall motion abnormalities as a sign of hemodynamically significant coronary artery disease. These techniques have proved to be fairly specific but not highly sensitive. Detection of new regional wall motion abnormalities with cross-sectional echocardiography during exercise appeared practical in 80 percent of patients in preliminary studies; the finding of such abnormalities is highly specific for the presence of coronary artery disease and, with this approach, the sensitivity of echocardiography is improved. Thus, patients with anatomically severe coronary artery disease on angiography may not manifest an echocardiographic abnormality in regional wall motion even during exercise. The direct noninvasive detection of the left main coronary artery in up to 90 percent of patients studied with cross-sectional echocardiography using the short axis or apical approach, or both, has been well defined. A high sensitivity and specificity of detecting anatomically severe left main coronary artery disease using the criteria of both luminal impingement and the presence of high intensity echoes have been confirmed. Further advances in imaging techniques may allow for better definition of the coronary arterial treë.     

The noninvasive diagnosis of coronary artery disease in patients with left bundle-branch block

The prognosis in patients with left bundle-branch block (LBBB) is related primarily to the presence or absence of underlying cardiac disease. Because coronary artery disease (CAD) is the most common underlying disease found in these patients, it would be desirable, in the presence of LBBB, to have a noninvasive method of differentiating between patients with and without CAD. We reviewed our experience in patients with LBBB who had undergone coronary arteriography with regard to electrocardiographic (ECG) stress testing, exercise radionuclide ventriculography (RNV), and exercise thallium scintigraphy; we also reviewed their clinical histories. A clinical history of typical angina pectoris was specific for CAD, a false-positive history being present in only one of 12 patients without CAD. The frequency of a positive ECG ST response to exercise was equal in patients with and without CAD. False-positive ejection fraction and wall-motion responses to exercise were frequent by RNV. A modification of the usual RNV criteria for positivity improved specificity but resulted in poor sensitivity for CAD. False-positive thallium study results also were. frequent in these patients. The perfusion defects usually involved the ventricular septum; the inferior and posterior walls were involved only in patients with CAD. We conclude that the usual noninvasive diagnostic tests for CAD are of limited value in patients with LBBB.     

Exercise echocardiography versus 201Tl single-photon emission computed tomography in evaluation of coronary artery disease. Analysis of 292 patients.

BACKGROUND. Exercise echocardiography (digital cine-loop technique) and 201Tl single-photon emission computed tomography (SPECT) were performed simultaneously in 292 patients being evaluated for coronary artery disease. METHODS AND RESULTS. Pretreadmill and posttreadmill echocardiographic images of diagnostic quality were obtained in 289 patients, and the left ventricle was divided into anterior, inferior, and lateral regions. Any wall motion or perfusion abnormality observed within each region was classified as totally reversible, fixed, or partially reversible. Exercise echocardiography and SPECT were normal in 137 patients and abnormal in 118 (88% agreement). Equal numbers of regional abnormalities were detected by one test when missed by the other. The two tests had an 82% agreement in detecting the same type of finding within the regions analyzed. SPECT detected more reversible abnormalities than echocardiography, whereas echocardiography detected more fixed abnormalities than SPECT. Regions with a fixed abnormality by echocardiography frequently showed partial reversibility of a perfusion defect by SPECT. Nearly one third of regions with fixed perfusion defects by SPECT demonstrated normal resting function or reversible abnormalities by echocardiography. Sensitivity for coronary artery disease by angiography (greater than or equal to 50% diameter stenosis) in 112 patients was similar for the two tests, ranging from 58% and 61% (echocardiography and SPECT, respectively) for one-vessel disease to 94% for three-vessel disease. The specificities for echocardiography and SPECT were 88% and 81%, respectively. CONCLUSIONS. Exercise echocardiography had a diagnostic accuracy comparable to that of SPECT for the detection of regional abnormalities produced by significant coronary artery disease. A greater number of abnormal regions were detected with the combined use of both tests.