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Predicting the severity of coronary lesions by the continuous recording method of exercise two-dimensional echocardiography
Predicting the Severity of Coronary Lesions by the Continuous Recording Method of Exercise Two-dimensional Echocardiography Takeshi Mitsuhashi, MD, Akira Shiina, MD, Toshio Kuroda, MD, Masanori Yamasawa, MD, Toshihiro Fujita, MD, Osamu Suzuki, MD, Yoshitane Seino, MD, Masanori Nishinaga, MD, and Kazuyuki Shimada, MD, Minamikawachi-Machi, Kawachi-Gun, Tochigi-Ken,Japan
We estimated the severity of coronary artery disease by the continuous-recording method of exercise two-dimensional echocardiography (Ex.2DE) in 56 patients with angiographically significant coronary artery stenosis (>50% diameter narrowing) who had undergone both Ex.2DE and coronary angiography. Patients were divided into two groups on the basis o f findings of coronary angiography: group 1 had 50% to 89% stenosis (n = 24) and group 2 had 90% or greater stenosis (n = 32). The sensitivity and specificity of Ex.2DE for the detection of ischemic segments were 82% and 88%, Wall motion abnormalities are detectable in evolving myocardial ischemia before the onset o f chest pain or electrocardiographic changes. Twodimensional echocardiography is useful for evaluating wall motion in real time. The usefulness o f exercise echocardiography for noninvasive diagnosis of coronary artery disease is well established. ~-12 In most studies, exercise echocardiography has been performed just after clectrocardiographically monitored treadmill exercise or supine bicycle ergometry.1319 H e c h t et al. 15a6 and Ryan et al.lr reported that the peak exercise image was superior to the postexercise image obtained with echocardiography. M t h o u g h there are some problems associated with performing cchocardiography during exercise, therc is no suitable alternative m e t h o d of monitoring wall motion in evolving ischemia. We assessed the wall motion profile during supine bicycle exercise by the continuous-recording method o f exercise two-dimensional echocardiography (Ex.2DE) and determined a correlation between echocardiographic findings and coronary artery stenosis.
From the Department of Cardiology,Iichi Medical School. Reprint requests: Toshio Kuroda, MD, Department of Cardiology, Jichi Medical School, Minamikawachi-Machi, Kawachi-Gun, Tochigi-Ken 329-04, Japan. Copyright 9 1995 by the American Societyof Echocardiography. 0894-7317/95 $5.00 + 0 27/1/64063
respectively, in the overall patient population. The sensitivity was 67% in group 1 and 94% in group 2. Hyperkinesis occurred at the beginning of exercise in 21 (88 %) of 24 patients in group I and in 15 (47%) of 32 patients in group 2 (p < 0.05). Our findings demonstrated that patients who did not show hyperkinesis at the beginning of exercise had more severe coronary artery disease. Careful observation of serial wall motion during exercise by the continuous-recording method may provide important information about myocardial ischemia. (J AlvlSoc ECHOCARDIOGR1995;8:703-9.)
METHODS Patients
We selected 56 patients with angiograpbically significant coronary artery stenosis (>50% diameter narrowing) who had undergone coronary angiography (CAG) within 1 month of Ex.2DE. Patients with evidence of myocardial infarction or a history of myocardial infarction were excluded. Patients were divided into two groups on the basis of findings of CAG: 24 patients had 50% to 89% coronary stenosis (group 1 ) and 32 patients had 90% or greater stenosis (group 2) (Table 1). The control group consisted of 16 patients with angiographically normal coronary arteries (group N). All patients had undergone CAG because of chest pain or some other cardiac condition. Exercise Two-Dimensional Echocardiography
Supine bicycle crgometry was begun at a workload of 50 W and was increased by 25 W every 3 minutes until the patient's symptom-limiting end point was reached or the development of asynergy was detected. Exercise was continued until 85% of the age-predicted maximal heart rate was achieved, unless signs of ischemia or fatigue were observed. A 12-lead electrocardiogram was recorded simultaneously. Two-dimensional echocardiography was recorded at rest, during supine bicycle exercise, and after exercise with a Toshiba SSH-65A and 165A (Toshiba, Tokyo, Japan) with 3.75 MHz or 2.5 MHz transducers. Digitized images were displayed in a four-quadrant format on a Freeland Cineview system (Prism Imaging, Inc., Broomfield, Colo.). Parasternal long-axis, short-axis, apical long-axis, two-chamber, and four-chamber views were recorded at 703
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IS P
observer reviewed the recorded study and a consensus was reached. Interobserver and intraobserver agreement on wall motion analysis at rest was 93% and 95%, respectively, and 84% and 86%, respectively, during and after exercise.
AL I or
P " ~ l m W ~ I L or PL
AL
~ IL or I
Coronary Angiography
PL or P
IL
A
I
LAD territory RCA territory LCX territory. LAD or RCA territory
F i g u r e 1 Schematic representation of regional wall segments and distribution of coronary perfusion. (A, Anterior; AL, anterolateral; IL, infcrolateral; I, inferior; IS, inferior septum; AS, anterior septum; PL, posterolateral; P, posterior; PS, posterior septum; LAD, left anterior descending artery; RCA, right coronary artery; LCX, left circumflex artery.)
Left-sided heart catheterization was performed within 1 month o f post-Ex.2DE. Coronary arteriography was performed in multiple projections to visualize all parts o f coronary vessels by either Sones' or Judkins' technique. The severity of stenosis was assessed by quantitative CAG and cinevideodensitometric analysis with a Cardio 500 (Kontron Instruments, Inc., Tokyo, Japan). Significant coronary stenosis was defined as greater than 50% narrowing of the luminal diameter o f a major epicardial coronary artery or a major branch. The coronary artery jeopardy score was calculated according to the method o f Califfet al.2~ The coronary artery was divided into six segments: the left anterior descending artery, the major anterolateral (diagonal) branch, the first major septal perforator, the left circumflex artery, the major circumflex marginal branch, and the posterior descending artery. In patients with a left dominant system, the right coronary artery was assigned a score of 0. Each segment with a 50% or greater reduction in luminal diameter was assigned a score of 2 points. Each vessel distal to a 50% or greater stenosis was also assigned a score of 2 points. Thus the maximal number o f possible points was 12.
Statistical Analysis All results are expressed as the mean + 1 SD. Sensitivity and specificity were determined according to standard methods. Differences between categoric variables were analyzed by )C analysis. Continuous variables were comparcd by paired and unpaired Student t tests. Any p value < 0.05 was considered as indicating a statistical significance.
RESULTS rest. Patients were maintained in a slight left lateral position for as long as they exercised, with a cushion placed between the right side o f the patient's back and the table to obtain as accurate a recording as possible during exercise. If necessary, we asked patients to exhale for a few seconds. For wall motion analysis, we subdivided the left ventricular wall into 16 segments (Figure 1), according to the recommendations of the American Society o f Echocardiography. 2~Wall motion in each segment was assessed semiquantitatively as follows: 0=hyperkinetic, i =normal, 2 = hypokinetic, 3 = akinetic, or 4 = dysldnetic. Mild hypokinesis was defined as a grade of 1.5 and severe hypokinesis as a grade of 2.5. The anterior, anterior septal, anterolateral, and apex areas were considered to be perfused by the left anterior descending artery. The inferior, posterior, inferior septal, and posterior septal areas were perfused by the right coronary artery. The inferolateral and posterior lateral wall were perfused by the left circumflex artery. An ischemic response was defined as the worsening of wall motion in any segment during exercise by at least one grade. Two expert echocardiographers analyzed the wall nmtion separately. When a discrepancy occurred, a third
Patient Characteristics T h e r e were n o significant differences in age or gcnd e r b e t w e e n g r o u p 1 and g r o u p 2 (Table 1). T h e n u m b c r o f w o m e n was slightly h i g h e r in g r o u p N than in the o t h c r groups. C o r o n a r y a r t e r i o g r a p h i c variablcs were similar in g r o u p s 1 a n d 2, except for the absence o f left m a i n t r u n k disease in g r o u p 1. M a x i m a l exercise (285% o f the a g e - p r e d i c t e d maximal h e a r t rate) was achieved by l l patients. Exercise was d i s c o n t i n u e d in t w o patients in g r o u p 2 because o f the o c c u r r e n c e o f m a r k e d asynergy. I n t h e r e m a i n i n g 59 patients, exercise was submaximal because o f m a r k e d ST s e g m e n t d e p r e s s i o n (_>0.2 m V ) ( n = 16), chest pain ( n = 13), or leg fatigue a n d dyspnea (n = 30). T h e r e wcrc n o significant differences a m o n g g r o u p s in systolic b l o o d pressure o r t h e d e g r e e o f S T s e g m e n t d e p r e s s i o n , b u t the m a x i m a l h e a r t rate a n d maximal pressure-rate p r o d u c t were significantly h i g h e r in g r o u p N c o m p a r e d w i t h
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Table 1 Patient characteristics
Age range (yr) Mea n age (yr) Male/female (n) Coronary artery disease (n/%) SVD MVD LAD RCA LCX LMT Total occlusion Jeopardy score Exercise characteristics Maximal SBP ( m m Hg) Maximal H R (beats/min) Maximal PRP Exercise duration (see) Workload (W) Maximal ST segment depression (mV)
Group 1 (n = 24)
Group 2 (n = 32)
Group N (n = 16)
41--66 57 20/4
29-66 52 27/5
48-66 55 7/9
10/42 14/58 17/71 13/54 10/42 0 0 5.3 +_2.9
12/38 20/63 24/75 15/47 14/44 5/16 10/31 6.7 + 2.9
161 125 20179 390 97 -0.11
+ + + + + +
15 16 3170 171 31 0.14
157 110 17400 293 76 -0.14
+ 21 _+ 19 + 4155 + i24J" +- 22* + 0.10
162 146 23758 424 100 -0.07
_+ 16 + 11" + 3275* + 105 +- 26 + 0.08
Values are means + SD. SVD, Single-vessel disease; MVD, multivessel disease; LAD, left anterior descending artery; RCA, right coronary artery; LCX, left circumflex artery; LMT, left main trunk; SBP,systolic blood pressure; HR, heart rate; PRP,pressure-rate product, SBP x HR. *p < 0.01 versus other groups. 1-P < 0.01 versus group N, and p < 0.05 versus group 1.
groups 1 and 2 (p < 0.01). In group 2, exercise duration was significantly shorter (p < 0.01 versus group N and p < 0.05 versus group 1) and achieved workload was significantly lower (p < 0.01) compared with the other groups (Table 1). Detection o f Coronary Artery Disease by Ex.2DE Worsening of wall motion was seen in 46 (82%) of 56 patients. All patients with triple-vessel disease and left main trunk disease showed asynergy on Ex.2DE. Of the 10 paticnts with false-ncgativc results, eight had single-vessel disease and two had doublc-vesscl disease (mean coronary jeopardy score of false-negative rcsults: 3.6). Exercise 2~ myocardial scintigraphy had bccn performed in eight of" these patients; six showcd no abnormal pcrfusion images. One patient with a false-negative result had a positive excrcisc electrocardiographic result, but he had a normal thallium pcrfusion image. The sensitivity of Ex.2DE for the dctection of ischemic segments in groups 1 and 2 was 67% and 94%, respectivcly. A total of 93 coronary artery lesions with more than 50% diametcr stenosis were idcntificd. Wall motion abnormalities during exercise were detected in 35 (85%) of 41 lesions in the left antcrior descending artery, 21 (75%) of 28 lesions in thc right coronary artery, and 13 (58 %) of 24 lesions in the left circumflex artcry lesions. No abnormal wall motion was detected in 14 (88 %)
of the 16 control subjects. Two patients who showed asynergy had slight left ventricular hypertrophy. Wall Motion Profile during Exercise and Coronary Artery Disease Wc classified serial wall motion changes associated with the most pronounced asyncrgy rccordcd during excrcise into three pattcrns (Table 2). Hyperkincsis at the beginning of exercise occurred in 21 (88%) of 24 patients in group 1 and 15 (47%) of 32 patients in group 2 (p < 0.05). Severe coronary artery stenosis was present in 17 (85%) of 20 patients who did not have hyperkinesis compared with 15 (42%) of 36 patients who did have hyperldnesis (p < 0.01). The coronary jeopardy score was significantly higher in patients without hypcrkinesis ( 7 . 3 + 2 . 9 versus 5.4 + 2.6; p < 0.05). Hypcrkincsis was not detected in three patients in group 1 (two patients with double-vessel disease and one patient with triplevessel disease). Their coronary jeopardy scorcs were 6, 8, and 10, respectively. An ST segment depression of 0.1 mV or greater was detected in significantly more of the patients without hypcrkinesis than in the patients with hyperkinesis in group 2 (Table 3). The maximal heart rate was considcrably higher in thc subgroup without hyperkinesis than in the subgroup with hyperkinesis (117 + 22 bcats/min versus 103 + 10 beats/min; p < 0.05), but there were no significant differences in other exercise parameters. There were no significant
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Table 2 Relation of changes in serial wall motion during exercise to coronary artery stenosis
N o asynergy (normal-->hyperkinesis) Normal ~ hyperkinesis ---) hypokinesis Normal -~ hypokinesis Total
differences in the distribution of coronary artery lesions or the jeopardy score between patients in group 2 with and without hyperkinesis (Table 3). Exercise Characteristics in the Overall Patient P o p u l a t i o n
There were no significant differences in the maximal heart rate, maximal blood pressure, and maximal pressure-rate products between patients with and without hyperkinesis in the overall patient population (Table 4). The worldoad was significantly lower and the exercise duration was significantly shorter in patients without hyperkinesis. The prevalence of chest pain was similar in both groups, but the degree of ST segment depression was significantly higher in the group without hyperkinesis. There were no signs ofischemia, such as ST segment depression and chest pain, observed in 20 of 36 patients with hyperkinesis compared with five of 20 patients without hyperkinesis. The coronary jeopardy score was significantly higher in the group without hyperkinesis than in the group with hyperkinesis (7.3 + 2.6 versus 5.4 _+2.9; p < 0,05). Hyperkincsis was recognized during the first stage of our protocol. Systolic blood pressure 2 minutes after the beginning of exercise was significantly higher in the group with hypcrkincsis than in the group without hyperkinesis (157 _+ 15 mm Hg versus 147 + 18 mm Hg; p < 0.05).
DISCUSSION
In this study, Ex.2DE had a sensitivity of 82% and a specificity of 88% for detection of coronary artery disease, which is similar to the results of previous studies obtained with exercise stress echocardiography. 3'4'9'~s Most previous studies that used exercise echocardiography analyzed wall motion just a few minutes after the cessation of exercise rather than serial wall motion changes. Although treadmill exercise echocardiography is useful for noninvasive evaluation of coronary artery disease, Ryan et al. 17 reported that the wall motion abnormalities were observed only at peak exercise in some patients. The
Group N
Group 1
Group 2
14 2 0 16
8 13 3 24
2 13 17 32
continuous-recording method has the advantage of analyzing left ventricular function in real time. In this study, patients who did not show hyperkinesis immediately after the beginning of exercise were shown to have more severe coronary artery disease, suggesting that analysis of serial wall motion changes during exercise provides important information, even though respiration or excessive motion of the whole heart and chest wall can complicate imaging during exercise. In this series, although there were some inadequate records during exercise, especially in the parasternal approach, we excluded no patients from our study because of poor imaging. If it was too difficult to obtain an image adequate enough to analyze from the parasternal approach, we attached more importance on analysis of the apical images. Exercise tolerance was poorer in patients without hyperkinesis: the exercise workload was lower and exercise duration was shorter in patients without hyperkinesis than in patients with hyperkinesis. The degree of ST segment depression was increased more in the group without hyperkinesis. The severity of coronary artery disease may have been responsible for the absence of hyperkinesis. Hyperkinesis may depend on the balance between the ischemic myocardial response and afterload. However, in this study, systolic blood pressure 2 minutes after the beginning of exercise was higher in the group with hyperkinesis, and the coronary jeopardy score was higher in the group without hyperkinesis, suggesting that hyperkinesis depended more on the severity of coronary artery stenosis and the extent of the area at risk than on the change in afterload. Because there were only 12 patients with collateral circulation (total 12; hyperkinesis n = 5; nonhyperkinesis n = 7), we were unable to assess the role of collateral circulation. Left circumflex and right coronary lesions tended to be misdiagnosed as being normal in our study (false-negative results). Ryan et al?7 previously found that the false-negative rate associated with exercise echocardiography for the left circumflex artery was higher. Anatomic variability or the extent of myocardium perfused by the left circumflex artery
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Table 3
M i t s u h a s h i et al.
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Clinical characteristics of patients in group 2 with and without hyperidnesis Hyperkinesis + (n = aS)
Coronary artery disease (n) SVD MVD LAD RCA LCX LMT Jeopardy score Total occlusion (n) % Diameter stenosis Culprit lesion (n) LAD RCA LCX Exercise test >_0.1 mV ST segment depression (n/%) Chest pain (~/%) Maximal H R (beats/min) Maximal SBP (mm Hg) Maximal PRP Workload (W) Exerise duration (see) Maximal ST segment depression (mV)
-
5 12 13 8 10 1 6.I _+2.9
(n = 17)
7 8 11 7 4 3 7.2 + 2.7
6
4
97 _+ 3
94 -+ 4
11 3 3
14 1 0
7/47 7/47
14/82" 3/18 117 _+22* 155 _+ 119 18290 + 4662 69 + 24 265 + I32 -0.17 + 0.10
103 156 16392 83 324 -0.10
+ 10 _+24 + 3368 +- 18 _+ 111 + 0.10
Values are means -+SD. Abbreviations are given in Table 1. *p < 0.05 versus group without hyperkinesis.
Table 4
Exercise characteristics in all patients with coronary artery disease with and without hyperkinesis Hyperkinesis + (n = 36)
Maximal SBP ( m m Hg) Maximal H R (beats/min) Maximal PRP Exercise duration (see)* Workload (W)t ST segment depression (mV):~ End point (n/%) Chest pain Fatigue Asynergy _>0.i mV ST segment depression
161 116 18785 375 94 -0.10
+ 19 _+ 18 + 3962 + i52 + 27 + 0.12
9/25 20/56 0 7/19
-
(n = 20)
153 118 18242 262 69 -0.18
+ 18 + 21 + 4382 + 127 + 23 _+0.12
4/20 3/15 2/10 9/45
Values are means _+SD, Abbreviations are given in Table 1. *p < 0.01 between two groups. ~'p < 0.001 between two groups. :~p < 0.05 between two groups.
may be responsible for this result. Asynergy in the posterior and lateral walls tends to be difficult to judge because o f p o o r lateral resolution and attenuation o f cchodensity. These factors may be more pronounced during exercise.
Limitations
There arc some thcorctic and tcchnical difficulties associated with Ex.2DE. The greatest disadvantage is that two dimensional echocardiograms are inadequate for some patients. Sensitivity tended to bc
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lower in patients with right c o r o n a r y artery a n d left circumflex artery lesions in w h o m respiration a n d excessive chest wall m o t i o n interfere with recordings. A l t h o u g h n o patients were excluded from this study because o f p o o r - q u a l i t y recordings, detailed evaluat i o n was difficult in seven patients; three o f t h e m were u n d e r e s t i m a t e d . S o m e studies have suggested that exercise echocardiography is m o r e sensitive in patients with multivessel disease? -5 Use o f the d e v e l o p m e n t o f asynergy as o n e o f the e n d points in this study may have resulted in an u n d e r d i a g n o s i s o f the n u m b e r o f diseased vessels. Marked asynergy was the exercise e n d p o i n t in two patients in w h o m single-vessel disease was diagnosed, a l t h o u g h double-vessel disease was in fact the case. I f these patients had c o n t i n u e d exercising u n t i l o n e o f the other e n d p o i n t s was reached, a correct diagnosis could have b e e n made. Semiquantitative assessment o f wall m o t i o n lacks objectivity. Q u a n t i t a t i v e wall m o t i o n analysis with computer-assisted systems m a y bc possible. I n o u r o p i n i o n , quantitative analysis o f t w o - d i m e n s i o n a l echocardiography is limited because definition o f endocardial borders with an a u t o m a t i c system is difficult a n d sometimes inaccurate. However, wall m o t i o n at rest a n d d u r i n g exercise can be assessed accurately by a well-trained echocardiographer. I n this study, i n t e r o b s e r v e r a n d i n t r a o b s e r v e r a g r e e m e n t o n wall m o t i o n analysis at rest was 93% a n d 95%, respectively, a n d 84% a n d 86%, respectively, d u r i n g a n d after exercise. Conclusion I n this study, E x . 2 D E was useful for the evaluation o f the severity o f c o r o n a r y artery disease. Patients w h o did n o t show hyperkincsis at the b e g i n n i n g o f exercise were s h o w n to have m o r e severe c o r o n a r y artery disease. Careful o b s e r v a t i o n o f serial wall m o t i o n d u r i n g exercise by the c o n t i n u o u s - r e c o r d i n g m e t h o d m a y provide i m p o r t a n t i n f o r m a t i o n a b o u t myocardial ischemia.
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We are grateful to Ms. Sachiko Tanaka and Ms. Keiko Shiraku for their secretarial assistance.
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REFERENCES
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1. Wann LS, Faris IV, Childress RH, WeymanAF, Feigenbaum H. Exercise cross-sectional echocardiography in ischemic heart disease. Circulation 1979;60:1300-8. 2. Robertson WS, Feigenbaum H, Armstrong WF, Dillon JC, O'Donnel J, McHenry PW. Exercise echocardiography: a
18.
clinicallypractical addition in the evaluation of coronary artery disease. J Ban Coil Cardiol 1983;2:1085-91. Armstrong WF, O'Donnel J, Ryan T, Feigenbaum H. Effect of prior myocardial infarction and extent and location of coronary artery disease on accuracy of exercise echocardiog raphy. J Am Coil Cardiol 1987;10:531-8. Marwick TH, Nemec JJ, Pashkow FJ, Stewart WJ, Salcedo EE. Accuracy and limitations of exercise echocardiography in a routine clinical setting. J Am Coil Cardiol 1992;19:7481. Limacher MC, Quinones MA, Poliner LR, Nelson JG, Winters WL, Waggoner AD. Detection of coronary artery disease with exercise two-dimensional echocardiography: description of a clinically applicable method and comparison with radionuclide ventriculography. Circulation 1983; 67:1211-8. Armstrong WF, O'Donnel J, McHenry PL, Morris SN, Feigenbaum H. Complementary value of two-dimensional exercise echocardiography to routine treadmill testing. Ann Intern Med 1986;105:829-35. Maurer G, Nanda NC. Two dimensional echocardiographic evaluation of exercise-induced left and fight ventricular asynergy: correlation with thallium scanning. Am J Cardiol 1981;48:720-7. Heng MK, Simard M, Lake R, Udhoji VH. Exercise twodimensional echocardiography for diagnosis of coronary artery disease. Am J Cardiol 1984;54:502-7. Ryan T, Vasey CG, Presti CF, O'Donnel JA, Feigenbaum H, Armstrong WF. Exercise echocardiography: detection of coronary artery disease in patients with normal left ventricular wall motion at rest. J Am Coll Cardiol 1988;11:993-9. Sheikh KH, Bengtson JR, Helmy S, et al. Relation of quantitative coronary lesion measurements to the development of exercise-inducedischemiaassessed by exercise echocardiography. J Am Coil Cardiol 1990;15:1043-51. SawadaSG, Ryan T, Fineberg NS, et al. Exercise echocardiographic detection of coronary artery disease in women. J Am Coll Cardiol 1989;14:1440-7. Armstrong WF. Stress echocardiography for detection of coronary artery disease. Circulation 1991;84(suppl):43-9. Dohan A, Ryan T, Sawada SG, et al. Detection of coronary artery disease using bicycle stress echocardiography [Abstract]. Circulation 1990;82(suppl):191. Pozzoli MMA, Fioretti PM, SalustriA, Reijs AEM, Roelandt JRTC. Exercise echocardiography and technetium-99m MIBI single-photon emission computed tomography in evaluation of coronary artery disease. Ban J Cardiol 1991; 67:350-5. Hecht HS, DeBord L, Shaw R, et al. Digital supine bicycle stress echocardiography: a new technique for evaluatingcoronary artery disease. J Am Coll Cardiol 1993;21:950-6. Hecht HS, DeBord L, Sotomayor N, Shaw R, Dunlap R, Ryan C. Supine bicyclestress echocardiography: peak exercise imaging is superior to postexercise imaging. J AM Soc ECHOCARDIOGR 1993;6:265-71. Ryan T, Segar DS, Sawada SG, et al. Detection of coronary artery disease with upright bicycleexercise echocardiography. J AM Soc ECHOCAV,DIOCR1993;6:186-97. Hecbt HS, DeBord L, Shaw R, et al. Supine bicycle stress echocardiography versus tomographic thallium-201 exercise imaging for the detection of coronary artery disease. J AMSoc ECHOCmd~IOGR1993;6:177-85.
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19. Hecht HS, DeBord L, Sotomayor N, Show R, Ryan C. Truly silent ischemia and the relationship of chest pain and ST segment changes to the amount of ischemic myocardium: evaluation by supine bicycle stress echocardiography. J Am Coil Cardiol 1994;23:369-76. 20. American Society of Echocardiography Committee on Stan-
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dards. Recommendations for quantification of the left ventricle by two-dimensional echocardiography. J" AM Soc ECHOCaP,DIOC• 1989;2:358-67. 21. CaliffRM, Phillips HR, Hindman MC, et al. Prognostic value of a coronary artery jeopardy score. J Am Coil Cardiol 1985;5:1053-63.
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Mosby
We estimated the severity of coronary artery disease by the continuous-recording method of exercise two-dimensional echocardiography (Ex.2DE) in 56 patients with angiographically significant coronary artery stenosis (>50% diameter narrowing) who had undergone both Ex.2DE and coronary angiography. Patients were divided into two groups on the basis o f findings of coronary angiography: group 1 had 50% to 89% stenosis (n = 24) and group 2 had 90% or greater stenosis (n = 32). The sensitivity and specificity of Ex.2DE for the detection of ischemic segments were 82% and 88%, Wall motion abnormalities are detectable in evolving myocardial ischemia before the onset o f chest pain or electrocardiographic changes. Twodimensional echocardiography is useful for evaluating wall motion in real time. The usefulness o f exercise echocardiography for noninvasive diagnosis of coronary artery disease is well established. ~-12 In most studies, exercise echocardiography has been performed just after clectrocardiographically monitored treadmill exercise or supine bicycle ergometry.1319 H e c h t et al. 15a6 and Ryan et al.lr reported that the peak exercise image was superior to the postexercise image obtained with echocardiography. M t h o u g h there are some problems associated with performing cchocardiography during exercise, therc is no suitable alternative m e t h o d of monitoring wall motion in evolving ischemia. We assessed the wall motion profile during supine bicycle exercise by the continuous-recording method o f exercise two-dimensional echocardiography (Ex.2DE) and determined a correlation between echocardiographic findings and coronary artery stenosis.
From the Department of Cardiology,Iichi Medical School. Reprint requests: Toshio Kuroda, MD, Department of Cardiology, Jichi Medical School, Minamikawachi-Machi, Kawachi-Gun, Tochigi-Ken 329-04, Japan. Copyright 9 1995 by the American Societyof Echocardiography. 0894-7317/95 $5.00 + 0 27/1/64063
respectively, in the overall patient population. The sensitivity was 67% in group 1 and 94% in group 2. Hyperkinesis occurred at the beginning of exercise in 21 (88 %) of 24 patients in group I and in 15 (47%) of 32 patients in group 2 (p < 0.05). Our findings demonstrated that patients who did not show hyperkinesis at the beginning of exercise had more severe coronary artery disease. Careful observation of serial wall motion during exercise by the continuous-recording method may provide important information about myocardial ischemia. (J AlvlSoc ECHOCARDIOGR1995;8:703-9.)
METHODS Patients
We selected 56 patients with angiograpbically significant coronary artery stenosis (>50% diameter narrowing) who had undergone coronary angiography (CAG) within 1 month of Ex.2DE. Patients with evidence of myocardial infarction or a history of myocardial infarction were excluded. Patients were divided into two groups on the basis of findings of CAG: 24 patients had 50% to 89% coronary stenosis (group 1 ) and 32 patients had 90% or greater stenosis (group 2) (Table 1). The control group consisted of 16 patients with angiographically normal coronary arteries (group N). All patients had undergone CAG because of chest pain or some other cardiac condition. Exercise Two-Dimensional Echocardiography
Supine bicycle crgometry was begun at a workload of 50 W and was increased by 25 W every 3 minutes until the patient's symptom-limiting end point was reached or the development of asynergy was detected. Exercise was continued until 85% of the age-predicted maximal heart rate was achieved, unless signs of ischemia or fatigue were observed. A 12-lead electrocardiogram was recorded simultaneously. Two-dimensional echocardiography was recorded at rest, during supine bicycle exercise, and after exercise with a Toshiba SSH-65A and 165A (Toshiba, Tokyo, Japan) with 3.75 MHz or 2.5 MHz transducers. Digitized images were displayed in a four-quadrant format on a Freeland Cineview system (Prism Imaging, Inc., Broomfield, Colo.). Parasternal long-axis, short-axis, apical long-axis, two-chamber, and four-chamber views were recorded at 703
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IS P
observer reviewed the recorded study and a consensus was reached. Interobserver and intraobserver agreement on wall motion analysis at rest was 93% and 95%, respectively, and 84% and 86%, respectively, during and after exercise.
AL I or
P " ~ l m W ~ I L or PL
AL
~ IL or I
Coronary Angiography
PL or P
IL
A
I
LAD territory RCA territory LCX territory. LAD or RCA territory
F i g u r e 1 Schematic representation of regional wall segments and distribution of coronary perfusion. (A, Anterior; AL, anterolateral; IL, infcrolateral; I, inferior; IS, inferior septum; AS, anterior septum; PL, posterolateral; P, posterior; PS, posterior septum; LAD, left anterior descending artery; RCA, right coronary artery; LCX, left circumflex artery.)
Left-sided heart catheterization was performed within 1 month o f post-Ex.2DE. Coronary arteriography was performed in multiple projections to visualize all parts o f coronary vessels by either Sones' or Judkins' technique. The severity of stenosis was assessed by quantitative CAG and cinevideodensitometric analysis with a Cardio 500 (Kontron Instruments, Inc., Tokyo, Japan). Significant coronary stenosis was defined as greater than 50% narrowing of the luminal diameter o f a major epicardial coronary artery or a major branch. The coronary artery jeopardy score was calculated according to the method o f Califfet al.2~ The coronary artery was divided into six segments: the left anterior descending artery, the major anterolateral (diagonal) branch, the first major septal perforator, the left circumflex artery, the major circumflex marginal branch, and the posterior descending artery. In patients with a left dominant system, the right coronary artery was assigned a score of 0. Each segment with a 50% or greater reduction in luminal diameter was assigned a score of 2 points. Each vessel distal to a 50% or greater stenosis was also assigned a score of 2 points. Thus the maximal number o f possible points was 12.
Statistical Analysis All results are expressed as the mean + 1 SD. Sensitivity and specificity were determined according to standard methods. Differences between categoric variables were analyzed by )C analysis. Continuous variables were comparcd by paired and unpaired Student t tests. Any p value < 0.05 was considered as indicating a statistical significance.
RESULTS rest. Patients were maintained in a slight left lateral position for as long as they exercised, with a cushion placed between the right side o f the patient's back and the table to obtain as accurate a recording as possible during exercise. If necessary, we asked patients to exhale for a few seconds. For wall motion analysis, we subdivided the left ventricular wall into 16 segments (Figure 1), according to the recommendations of the American Society o f Echocardiography. 2~Wall motion in each segment was assessed semiquantitatively as follows: 0=hyperkinetic, i =normal, 2 = hypokinetic, 3 = akinetic, or 4 = dysldnetic. Mild hypokinesis was defined as a grade of 1.5 and severe hypokinesis as a grade of 2.5. The anterior, anterior septal, anterolateral, and apex areas were considered to be perfused by the left anterior descending artery. The inferior, posterior, inferior septal, and posterior septal areas were perfused by the right coronary artery. The inferolateral and posterior lateral wall were perfused by the left circumflex artery. An ischemic response was defined as the worsening of wall motion in any segment during exercise by at least one grade. Two expert echocardiographers analyzed the wall nmtion separately. When a discrepancy occurred, a third
Patient Characteristics T h e r e were n o significant differences in age or gcnd e r b e t w e e n g r o u p 1 and g r o u p 2 (Table 1). T h e n u m b c r o f w o m e n was slightly h i g h e r in g r o u p N than in the o t h c r groups. C o r o n a r y a r t e r i o g r a p h i c variablcs were similar in g r o u p s 1 a n d 2, except for the absence o f left m a i n t r u n k disease in g r o u p 1. M a x i m a l exercise (285% o f the a g e - p r e d i c t e d maximal h e a r t rate) was achieved by l l patients. Exercise was d i s c o n t i n u e d in t w o patients in g r o u p 2 because o f the o c c u r r e n c e o f m a r k e d asynergy. I n t h e r e m a i n i n g 59 patients, exercise was submaximal because o f m a r k e d ST s e g m e n t d e p r e s s i o n (_>0.2 m V ) ( n = 16), chest pain ( n = 13), or leg fatigue a n d dyspnea (n = 30). T h e r e wcrc n o significant differences a m o n g g r o u p s in systolic b l o o d pressure o r t h e d e g r e e o f S T s e g m e n t d e p r e s s i o n , b u t the m a x i m a l h e a r t rate a n d maximal pressure-rate p r o d u c t were significantly h i g h e r in g r o u p N c o m p a r e d w i t h
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Table 1 Patient characteristics
Age range (yr) Mea n age (yr) Male/female (n) Coronary artery disease (n/%) SVD MVD LAD RCA LCX LMT Total occlusion Jeopardy score Exercise characteristics Maximal SBP ( m m Hg) Maximal H R (beats/min) Maximal PRP Exercise duration (see) Workload (W) Maximal ST segment depression (mV)
Group 1 (n = 24)
Group 2 (n = 32)
Group N (n = 16)
41--66 57 20/4
29-66 52 27/5
48-66 55 7/9
10/42 14/58 17/71 13/54 10/42 0 0 5.3 +_2.9
12/38 20/63 24/75 15/47 14/44 5/16 10/31 6.7 + 2.9
161 125 20179 390 97 -0.11
+ + + + + +
15 16 3170 171 31 0.14
157 110 17400 293 76 -0.14
+ 21 _+ 19 + 4155 + i24J" +- 22* + 0.10
162 146 23758 424 100 -0.07
_+ 16 + 11" + 3275* + 105 +- 26 + 0.08
Values are means + SD. SVD, Single-vessel disease; MVD, multivessel disease; LAD, left anterior descending artery; RCA, right coronary artery; LCX, left circumflex artery; LMT, left main trunk; SBP,systolic blood pressure; HR, heart rate; PRP,pressure-rate product, SBP x HR. *p < 0.01 versus other groups. 1-P < 0.01 versus group N, and p < 0.05 versus group 1.
groups 1 and 2 (p < 0.01). In group 2, exercise duration was significantly shorter (p < 0.01 versus group N and p < 0.05 versus group 1) and achieved workload was significantly lower (p < 0.01) compared with the other groups (Table 1). Detection o f Coronary Artery Disease by Ex.2DE Worsening of wall motion was seen in 46 (82%) of 56 patients. All patients with triple-vessel disease and left main trunk disease showed asynergy on Ex.2DE. Of the 10 paticnts with false-ncgativc results, eight had single-vessel disease and two had doublc-vesscl disease (mean coronary jeopardy score of false-negative rcsults: 3.6). Exercise 2~ myocardial scintigraphy had bccn performed in eight of" these patients; six showcd no abnormal pcrfusion images. One patient with a false-negative result had a positive excrcisc electrocardiographic result, but he had a normal thallium pcrfusion image. The sensitivity of Ex.2DE for the dctection of ischemic segments in groups 1 and 2 was 67% and 94%, respectivcly. A total of 93 coronary artery lesions with more than 50% diametcr stenosis were idcntificd. Wall motion abnormalities during exercise were detected in 35 (85%) of 41 lesions in the left antcrior descending artery, 21 (75%) of 28 lesions in thc right coronary artery, and 13 (58 %) of 24 lesions in the left circumflex artcry lesions. No abnormal wall motion was detected in 14 (88 %)
of the 16 control subjects. Two patients who showed asynergy had slight left ventricular hypertrophy. Wall Motion Profile during Exercise and Coronary Artery Disease Wc classified serial wall motion changes associated with the most pronounced asyncrgy rccordcd during excrcise into three pattcrns (Table 2). Hyperkincsis at the beginning of exercise occurred in 21 (88%) of 24 patients in group 1 and 15 (47%) of 32 patients in group 2 (p < 0.05). Severe coronary artery stenosis was present in 17 (85%) of 20 patients who did not have hyperkinesis compared with 15 (42%) of 36 patients who did have hyperldnesis (p < 0.01). The coronary jeopardy score was significantly higher in patients without hypcrkinesis ( 7 . 3 + 2 . 9 versus 5.4 + 2.6; p < 0.05). Hypcrkincsis was not detected in three patients in group 1 (two patients with double-vessel disease and one patient with triplevessel disease). Their coronary jeopardy scorcs were 6, 8, and 10, respectively. An ST segment depression of 0.1 mV or greater was detected in significantly more of the patients without hypcrkinesis than in the patients with hyperkinesis in group 2 (Table 3). The maximal heart rate was considcrably higher in thc subgroup without hyperkinesis than in the subgroup with hyperkinesis (117 + 22 bcats/min versus 103 + 10 beats/min; p < 0.05), but there were no significant differences in other exercise parameters. There were no significant
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Table 2 Relation of changes in serial wall motion during exercise to coronary artery stenosis
N o asynergy (normal-->hyperkinesis) Normal ~ hyperkinesis ---) hypokinesis Normal -~ hypokinesis Total
differences in the distribution of coronary artery lesions or the jeopardy score between patients in group 2 with and without hyperkinesis (Table 3). Exercise Characteristics in the Overall Patient P o p u l a t i o n
There were no significant differences in the maximal heart rate, maximal blood pressure, and maximal pressure-rate products between patients with and without hyperkinesis in the overall patient population (Table 4). The worldoad was significantly lower and the exercise duration was significantly shorter in patients without hyperkinesis. The prevalence of chest pain was similar in both groups, but the degree of ST segment depression was significantly higher in the group without hyperkinesis. There were no signs ofischemia, such as ST segment depression and chest pain, observed in 20 of 36 patients with hyperkinesis compared with five of 20 patients without hyperkinesis. The coronary jeopardy score was significantly higher in the group without hyperkinesis than in the group with hyperkinesis (7.3 + 2.6 versus 5.4 _+2.9; p < 0,05). Hyperkincsis was recognized during the first stage of our protocol. Systolic blood pressure 2 minutes after the beginning of exercise was significantly higher in the group with hypcrkincsis than in the group without hyperkinesis (157 _+ 15 mm Hg versus 147 + 18 mm Hg; p < 0.05).
DISCUSSION
In this study, Ex.2DE had a sensitivity of 82% and a specificity of 88% for detection of coronary artery disease, which is similar to the results of previous studies obtained with exercise stress echocardiography. 3'4'9'~s Most previous studies that used exercise echocardiography analyzed wall motion just a few minutes after the cessation of exercise rather than serial wall motion changes. Although treadmill exercise echocardiography is useful for noninvasive evaluation of coronary artery disease, Ryan et al. 17 reported that the wall motion abnormalities were observed only at peak exercise in some patients. The
Group N
Group 1
Group 2
14 2 0 16
8 13 3 24
2 13 17 32
continuous-recording method has the advantage of analyzing left ventricular function in real time. In this study, patients who did not show hyperkinesis immediately after the beginning of exercise were shown to have more severe coronary artery disease, suggesting that analysis of serial wall motion changes during exercise provides important information, even though respiration or excessive motion of the whole heart and chest wall can complicate imaging during exercise. In this series, although there were some inadequate records during exercise, especially in the parasternal approach, we excluded no patients from our study because of poor imaging. If it was too difficult to obtain an image adequate enough to analyze from the parasternal approach, we attached more importance on analysis of the apical images. Exercise tolerance was poorer in patients without hyperkinesis: the exercise workload was lower and exercise duration was shorter in patients without hyperkinesis than in patients with hyperkinesis. The degree of ST segment depression was increased more in the group without hyperkinesis. The severity of coronary artery disease may have been responsible for the absence of hyperkinesis. Hyperkinesis may depend on the balance between the ischemic myocardial response and afterload. However, in this study, systolic blood pressure 2 minutes after the beginning of exercise was higher in the group with hyperkinesis, and the coronary jeopardy score was higher in the group without hyperkinesis, suggesting that hyperkinesis depended more on the severity of coronary artery stenosis and the extent of the area at risk than on the change in afterload. Because there were only 12 patients with collateral circulation (total 12; hyperkinesis n = 5; nonhyperkinesis n = 7), we were unable to assess the role of collateral circulation. Left circumflex and right coronary lesions tended to be misdiagnosed as being normal in our study (false-negative results). Ryan et al?7 previously found that the false-negative rate associated with exercise echocardiography for the left circumflex artery was higher. Anatomic variability or the extent of myocardium perfused by the left circumflex artery
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Table 3
M i t s u h a s h i et al.
707
Clinical characteristics of patients in group 2 with and without hyperidnesis Hyperkinesis + (n = aS)
Coronary artery disease (n) SVD MVD LAD RCA LCX LMT Jeopardy score Total occlusion (n) % Diameter stenosis Culprit lesion (n) LAD RCA LCX Exercise test >_0.1 mV ST segment depression (n/%) Chest pain (~/%) Maximal H R (beats/min) Maximal SBP (mm Hg) Maximal PRP Workload (W) Exerise duration (see) Maximal ST segment depression (mV)
-
5 12 13 8 10 1 6.I _+2.9
(n = 17)
7 8 11 7 4 3 7.2 + 2.7
6
4
97 _+ 3
94 -+ 4
11 3 3
14 1 0
7/47 7/47
14/82" 3/18 117 _+22* 155 _+ 119 18290 + 4662 69 + 24 265 + I32 -0.17 + 0.10
103 156 16392 83 324 -0.10
+ 10 _+24 + 3368 +- 18 _+ 111 + 0.10
Values are means -+SD. Abbreviations are given in Table 1. *p < 0.05 versus group without hyperkinesis.
Table 4
Exercise characteristics in all patients with coronary artery disease with and without hyperkinesis Hyperkinesis + (n = 36)
Maximal SBP ( m m Hg) Maximal H R (beats/min) Maximal PRP Exercise duration (see)* Workload (W)t ST segment depression (mV):~ End point (n/%) Chest pain Fatigue Asynergy _>0.i mV ST segment depression
161 116 18785 375 94 -0.10
+ 19 _+ 18 + 3962 + i52 + 27 + 0.12
9/25 20/56 0 7/19
-
(n = 20)
153 118 18242 262 69 -0.18
+ 18 + 21 + 4382 + 127 + 23 _+0.12
4/20 3/15 2/10 9/45
Values are means _+SD, Abbreviations are given in Table 1. *p < 0.01 between two groups. ~'p < 0.001 between two groups. :~p < 0.05 between two groups.
may be responsible for this result. Asynergy in the posterior and lateral walls tends to be difficult to judge because o f p o o r lateral resolution and attenuation o f cchodensity. These factors may be more pronounced during exercise.
Limitations
There arc some thcorctic and tcchnical difficulties associated with Ex.2DE. The greatest disadvantage is that two dimensional echocardiograms are inadequate for some patients. Sensitivity tended to bc
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lower in patients with right c o r o n a r y artery a n d left circumflex artery lesions in w h o m respiration a n d excessive chest wall m o t i o n interfere with recordings. A l t h o u g h n o patients were excluded from this study because o f p o o r - q u a l i t y recordings, detailed evaluat i o n was difficult in seven patients; three o f t h e m were u n d e r e s t i m a t e d . S o m e studies have suggested that exercise echocardiography is m o r e sensitive in patients with multivessel disease? -5 Use o f the d e v e l o p m e n t o f asynergy as o n e o f the e n d points in this study may have resulted in an u n d e r d i a g n o s i s o f the n u m b e r o f diseased vessels. Marked asynergy was the exercise e n d p o i n t in two patients in w h o m single-vessel disease was diagnosed, a l t h o u g h double-vessel disease was in fact the case. I f these patients had c o n t i n u e d exercising u n t i l o n e o f the other e n d p o i n t s was reached, a correct diagnosis could have b e e n made. Semiquantitative assessment o f wall m o t i o n lacks objectivity. Q u a n t i t a t i v e wall m o t i o n analysis with computer-assisted systems m a y bc possible. I n o u r o p i n i o n , quantitative analysis o f t w o - d i m e n s i o n a l echocardiography is limited because definition o f endocardial borders with an a u t o m a t i c system is difficult a n d sometimes inaccurate. However, wall m o t i o n at rest a n d d u r i n g exercise can be assessed accurately by a well-trained echocardiographer. I n this study, i n t e r o b s e r v e r a n d i n t r a o b s e r v e r a g r e e m e n t o n wall m o t i o n analysis at rest was 93% a n d 95%, respectively, a n d 84% a n d 86%, respectively, d u r i n g a n d after exercise. Conclusion I n this study, E x . 2 D E was useful for the evaluation o f the severity o f c o r o n a r y artery disease. Patients w h o did n o t show hyperkincsis at the b e g i n n i n g o f exercise were s h o w n to have m o r e severe c o r o n a r y artery disease. Careful o b s e r v a t i o n o f serial wall m o t i o n d u r i n g exercise by the c o n t i n u o u s - r e c o r d i n g m e t h o d m a y provide i m p o r t a n t i n f o r m a t i o n a b o u t myocardial ischemia.
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We are grateful to Ms. Sachiko Tanaka and Ms. Keiko Shiraku for their secretarial assistance.
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REFERENCES
17.
1. Wann LS, Faris IV, Childress RH, WeymanAF, Feigenbaum H. Exercise cross-sectional echocardiography in ischemic heart disease. Circulation 1979;60:1300-8. 2. Robertson WS, Feigenbaum H, Armstrong WF, Dillon JC, O'Donnel J, McHenry PW. Exercise echocardiography: a
18.
clinicallypractical addition in the evaluation of coronary artery disease. J Ban Coil Cardiol 1983;2:1085-91. Armstrong WF, O'Donnel J, Ryan T, Feigenbaum H. Effect of prior myocardial infarction and extent and location of coronary artery disease on accuracy of exercise echocardiog raphy. J Am Coil Cardiol 1987;10:531-8. Marwick TH, Nemec JJ, Pashkow FJ, Stewart WJ, Salcedo EE. Accuracy and limitations of exercise echocardiography in a routine clinical setting. J Am Coil Cardiol 1992;19:7481. Limacher MC, Quinones MA, Poliner LR, Nelson JG, Winters WL, Waggoner AD. Detection of coronary artery disease with exercise two-dimensional echocardiography: description of a clinically applicable method and comparison with radionuclide ventriculography. Circulation 1983; 67:1211-8. Armstrong WF, O'Donnel J, McHenry PL, Morris SN, Feigenbaum H. Complementary value of two-dimensional exercise echocardiography to routine treadmill testing. Ann Intern Med 1986;105:829-35. Maurer G, Nanda NC. Two dimensional echocardiographic evaluation of exercise-induced left and fight ventricular asynergy: correlation with thallium scanning. Am J Cardiol 1981;48:720-7. Heng MK, Simard M, Lake R, Udhoji VH. Exercise twodimensional echocardiography for diagnosis of coronary artery disease. Am J Cardiol 1984;54:502-7. Ryan T, Vasey CG, Presti CF, O'Donnel JA, Feigenbaum H, Armstrong WF. Exercise echocardiography: detection of coronary artery disease in patients with normal left ventricular wall motion at rest. J Am Coll Cardiol 1988;11:993-9. Sheikh KH, Bengtson JR, Helmy S, et al. Relation of quantitative coronary lesion measurements to the development of exercise-inducedischemiaassessed by exercise echocardiography. J Am Coil Cardiol 1990;15:1043-51. SawadaSG, Ryan T, Fineberg NS, et al. Exercise echocardiographic detection of coronary artery disease in women. J Am Coll Cardiol 1989;14:1440-7. Armstrong WF. Stress echocardiography for detection of coronary artery disease. Circulation 1991;84(suppl):43-9. Dohan A, Ryan T, Sawada SG, et al. Detection of coronary artery disease using bicycle stress echocardiography [Abstract]. Circulation 1990;82(suppl):191. Pozzoli MMA, Fioretti PM, SalustriA, Reijs AEM, Roelandt JRTC. Exercise echocardiography and technetium-99m MIBI single-photon emission computed tomography in evaluation of coronary artery disease. Ban J Cardiol 1991; 67:350-5. Hecht HS, DeBord L, Shaw R, et al. Digital supine bicycle stress echocardiography: a new technique for evaluatingcoronary artery disease. J Am Coll Cardiol 1993;21:950-6. Hecht HS, DeBord L, Sotomayor N, Shaw R, Dunlap R, Ryan C. Supine bicyclestress echocardiography: peak exercise imaging is superior to postexercise imaging. J AM Soc ECHOCARDIOGR 1993;6:265-71. Ryan T, Segar DS, Sawada SG, et al. Detection of coronary artery disease with upright bicycleexercise echocardiography. J AM Soc ECHOCAV,DIOCR1993;6:186-97. Hecbt HS, DeBord L, Shaw R, et al. Supine bicycle stress echocardiography versus tomographic thallium-201 exercise imaging for the detection of coronary artery disease. J AMSoc ECHOCmd~IOGR1993;6:177-85.
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19. Hecht HS, DeBord L, Sotomayor N, Show R, Ryan C. Truly silent ischemia and the relationship of chest pain and ST segment changes to the amount of ischemic myocardium: evaluation by supine bicycle stress echocardiography. J Am Coil Cardiol 1994;23:369-76. 20. American Society of Echocardiography Committee on Stan-
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dards. Recommendations for quantification of the left ventricle by two-dimensional echocardiography. J" AM Soc ECHOCaP,DIOC• 1989;2:358-67. 21. CaliffRM, Phillips HR, Hindman MC, et al. Prognostic value of a coronary artery jeopardy score. J Am Coil Cardiol 1985;5:1053-63.
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