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Improved detection of inferobasal ischemia during dobutamine echocardiography with doppler tissue imaging
ORIGINAL ARTICLES
Improved Detection of Inferobasal Ischemia During Dobutamine Echocardiography With Doppler Tissue Imaging Marina Leitman, MD, Stanislav Sidenko, Ruth Wolf, Edgar Sucher, MD, Simha Rosenblatt, MD, Eli Peleg, MD, Ricardo Krakover, MD, and Zvi Vered, MD, FACC, Tel Aviv, Israel
Objectives: The purpose of this study was quantitative evaluation of the inferobasal segment during dobutamine stress echocardiography using Doppler tissue imaging (DTI). Background: Overdiagnosis of myocardial ischemia during dobutamine echocardiography is a common problem. DTI may permit more accurate quantitative diagnosis of ischemia. Methods: A total of 50 patients with normal contraction of the inferobasal segment at rest were referred for dobutamine stress echocardiography. All underwent coronary angiography. Systolic and diastolic myocardial velocities were measured from apical
2-chamber view at rest and at the peak of dobutamine infusion. Results: Stenosis of the right coronary artery > 70% was detected in 11 patients. Conventional stress echocardiography was falsely positive in 10.3% and falsely negative in 27.3%. When DTI was combined with conventional stress echocardiography, sensitivity and specificity was 81.8% and 97.4%, respectively. Conclusion: DTI may enhance the diagnosis of inferior ischemia during dobutamine echocardiography and can be added to conventional imaging in the treatment of these patients. (J Am Soc Echocardiogr 2003;16:403-8.)
Wall-motion analysis of the inferobasal segment of
METHODS
the left ventricle is a common problem during dobutamine echocardiography and may be a cause for unnecessary coronary angiography. Even resting imaging of the inferobasal segment often demonstrates abnormal motion as a result of close proximity of the mitral valve and atrioventricular grove. During dobutamine infusion this impairment may become more prominent and can be incorrectly interpreted as ischemia. Overdiagnosis of ischemia has usually occurred in patients with intermediategrade coronary stenosis.1 We investigated changes of the inferobasal segment during dobutamine stress echocardiography (DSE) with Doppler tissue imaging (DTI). Normal and ischemic segments have their characteristic systolic and diastolic parameters2-6 at rest and during stress.7-13 We evaluated the additive value of DTI over conventional wall-motion analysis and correlated the results with coronary angiography.
From the Cardiology Department, Assaf Harofeh Medical Center, Zerifin, Sackler Faculty of Medicine, Tel Aviv University. Reprint requests: Marina Leitman, MD, Cardiology Department, Assaf Harofeh Medical Center, Zerifin 70300, Israel. (E-mail: [email protected]). Copyright 2003 by the American Society of Echocardiography. 0894-7317/2003/$30.00 ⫹ 0 doi:10.1016/S0894-7317(03)00015-4
In all, 50 consecutive patients with normal resting contraction of the inferobasal segment, referred for DSE, were included. All patients had undergone coronary angiography before dobutamine echocardiography or coronary angiography was planned as a result of conventional indications unrelated to this study. Dobutamine was infused intravenously in incremental doses (5-10-20-30-40-50 g/kg/min) every 3 minutes with the addition of atropine (0.25-2 mg intravenously) if necessary. The end points of the test were the achievement of target heart rate or the development of ischemia. “Target heart rate” was defined as 85% of the age-predicted maximal value. DTI studies of the inferobasal segment were obtained from apical 2-chamber view. DTI early systolic velocity (S1), late systolic velocity (S2), early diastolic velocity (E), and late diastolic velocity (A) were obtained at rest and at peak dose of dobutamine. All the conventional and DTI studies were performed with high-resolution second harmonic imaging mode using a system V (Vingmed, General Electric, Horten, Norway). Coronary angiography was analysed independently by an interventional cardiology team. DTI results were analyzed by 2 experienced observers independently. The extra time needed for these measurements was no more than several minutes. Statistical Methods All statistical analysis were undertaken using standard Student t test and chi-square test. Significance was determined as P ⬍ .05. Data are presented as mean ⫾ SD.
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Table 1 Patients characteristics (N ⫽ 50) Age (y) EF (%) Female Males Hypertension CAD LVH RCA patient RCA stenosis ⬎70%
62 55.4 15 35 34 43 28 39 11
(42-77) (33-65) 30% 70% 68% 86% 56% 78% 22%
EF, Ejection fraction; CAD, coronary artery disease; LVH, left ventricular hypertrophy; RCA, right coronary artery.
Patients Characteristics Patient characteristics are shown in Table 1. Mean age was 62 years (range: 42-77). Mean ejection fraction was 55.4% (range: 33%-65%). There were 15 females (30%) and 35 males (70%). Hypertension was present in 34 patients (68%) and 43 patients (86%) had a history of coronary artery disease (CAD). Left ventricular hypertrophy was present in 28 patients (56%). Coronary angiography detected 3-vessel CAD in 7 patients, 2-vessel CAD in 11 patients, and 1-vessel CAD in 9 patients. In 11 patients, 70% or more right coronary artery (RCA) stenoses were present.
RESULTS Patients were divided into 2 groups: group A had stenosis of the RCA ⱖ 70%; and group B had either patent or less significant stenosis. There was no significant difference in patient age between groups (group A: 62 years [range: 51-77]; group B: 61.8 years [range: 42-77]). Mean ejection fraction in group A was 56.5 ⫾ 6.5% and in group it was B 55.2 ⫾ 8.5% (difference not significant). The total dose of dobutamine used in each group was similar. Baseline and stress characteristics of 39 patients with patent RCA are presented in Table 2. Systolic velocity obtained from 2-chamber view usually had 2 peaks: S2 was higher than S1 (5.4 ⫾ 1.45 cm/s vs 4.3 ⫾ 0.84 cm/s, P ⬍ .05). During stress, S1 became higher than S2 (11.2 ⫾ 2.8 cm/s vs 9.4 ⫾ 2.7 cm/s, P ⬍ .05). Time to peak systolic myocardial velocity shortened significantly at stress (0.03 ⫾ 0.02 seconds vs 0.13 ⫾ 0.14 seconds, P ⫽ .001). In regard to diastolic parameters, myocardial E/A ratio at stress was lower than at rest (0.4 ⫾ 0.2 vs 0.6 ⫾ 0.4, P ⬍ .0003) and this occurred as a result of higher A at stress than at rest (12.0 ⫾ 2.6 cm/s vs 8.3 ⫾ 2.24 cm/s, P ⬍ .000001). E at rest was 5.3 ⫾ 2.6 cm/s, and did not change significantly during stress. Comparison of patient groups A and B is presented in Table 3. During stress, peak myocardial S1 was higher in group B than in group A (11.5 ⫾ 2.8 cm/s vs 8.2 ⫾ 4.0 cm/s, P ⫽ .004). Maximal peak systolic myocardial velocity was also higher in group
B than in group A (12.3 ⫾ 2.1 cm/s vs 10.4 ⫾ 1.8 cm/s, P ⫽ .01). Absolute increase of peak myocardial systolic velocity ([Sms-Smr]/Smr [%]) during stress was higher in group B than in group A (6.6 ⫾ 1.6 cm/s vs 3.6 ⫾ 1.4 cm/s). Relative increment in systolic myocardial velocity was also higher in group B than in group A (126 ⫾ 49% vs 54 ⫾ 22.7%, P ⫽ .000001). Echocardiographic inferobasal ischemia was detected by conventional stress echocardiography in 72.7% of group A (8 patients) and in 10.3% of group B (4 patients) (P ⬍ .00001). Conventional stress echocardiography was falsely negative in 3 patients with 70% or more RCA stenosis (27.3%). In these patients DTI was diagnostic in one patient, borderline (79% increase of peak systolic myocardial velocity) in another, and negative in the third. Falsepositive results with conventional echocardiography were present in 10.3%. In 2 patients with normal RCA, conventional stress echocardiography was falsely positive and DTI produced normal findings. In 2 other cases with 50% RCA stenosis, conventional stress echocardiography was positive for ischemia and DTI was borderline (73% increase in peak systolic myocardial velocity) in one patient and normal in another. In one patient DTI was falsely positive but this occurred during a submaximal stress test (67% from maximal predicted heart rate). For detection of 70% or more RCA stenosis when the cutoff of myocardial systolic velocity increment during the stress test was 70%, sensitivity was 81.8% and specificity was 89.7%; when the cutoff was 80%, sensitivity was 90.9% and specificity was 79.5%; and when this point was 90%, sensitivity was 90.9% and specificity was 71.8%. When DTI was combined with conventional stress echocardiography and cutoff increment of peak systolic myocardial velocity was 70%, sensitivity and specificity for detection of at least 70% RCA stenosis was 81.8% and 97.4%, respectively. Figure 1 demonstrates quantitative assessment of myocardial velocities in the inferobasal segment during dobutamine echocardiography in a patient with normal RCA. Myocardial velocity increased by 103%. Figure 2 demonstrates myocardial velocities during dobutamine echocardiography in a patient with inferior ischemia and 80% stenosis of RCA. Increment of myocardial velocity was 33.3%.
DISCUSSION Accurate analysis of the inferobasal segment is a common problem during stress echocardiography. Among 342 cases, 39 met the criteria for falsely positive DSE test results (wall-motion abnormalities and ⬍50% coronary artery stenosis).1 Regional wallmotion abnormalities occurred predominantly in women (72%), were more common in posterior
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Table 2 Normal Doppler tissue imaging characteristics of the inferobasal segment at rest and stress S1 rest, cm/s S2 rest, cm/s S1 stress, cm/s S2 stress, cm/s T to S rest, s T to S stress, s E rest, cm/s E stress, cm/s A rest, cm/s A stress, cm/s E/A myocardial rest E/A myocardial stress
Average
Range
SD
4.3 5.4 11.2 9.4 0.13 0.03 5.3 4.8 8.3 12 0.6 0.4
0.2-10.0 2.1-8.0 1.7-15.0 5.0-14.5 0.01-0.90 0.01-0.06 1.5-12 0.7-13 2.5-13 5.0-15.0
0.84 1.45 2.8 2.7 0.14 0.02 2.6 0.8 2.24 2.6 0.4 0.2
P value
S2 rest⬎ S1 rest
⬍.05
s1 stress⬎ S2 stress T to S rest ⬎ T to S stress
⬍.05 .001
NS ⬍.000001
A stress⬎ A rest E/A rest ⬎ E/A stress
.0003
T to S, Time from the onset of systole to peak myocardial systolic velocity; S1, early peak systolic velocity; S2, late peak systolic velocity; E, early diastolic velocity; A, late diastolic velocity; NS, not significant.
Table 3 Doppler tissue imaging characteristics of inferobasal segment during stress No. of patients Ejection fraction, % S1m stress, cm/s Max S stress, cm/s Sms-Smr, cm/s % (Sms-Smr) Inferobasal ischemia*
Group A
SD
11 56.5 8.2 (0-13.0) 10.4 (7.8-13.0) 3.6 (0.02-6.7) 54 (29-106) 8 (72.7%)
6.5 4 1.8 1.4 22.7
Group B
39 55.2 11.5 (1.7-15) 12.3 (5.7-15) 6.6 (3.2-10.0) 126 (50-217) 4 (10.3%)
SD
8.5 2.8 2.1 1.6 49
P value
.004 .01 .00001 .000001 .00001
Group A, patients with ⬎ 70% right coronary artery (RCA) stenosis; Group B, patients with patent RCA; S1m stress, early peak systolic myocardial velocity at stress; Max S stress, maximal systolic myocardial velocity at stress; Sms-Smr, absolute increase of myocardial systolic velocity; % (Sms-Smr), relative increase in systolic myocardial velocity. *By conventional stress echocardiography. All the represented measurements were obtained from 2 chamber view.
circulation (62%), were often limited to the basal segments (65%), and were unlikely to be associated with coronary stenosis. Approximately one third of false-positive results occurred in patients with intermediate-grade coronary stenosis (28% of 43 wallmotion segments) and could reflect true inducible ischemia, poor endocardial visualization, and abnormal motion as a result of tethering to the fibrous skeleton of the heart.1 In our study false-positive results occurred in 4 patients (10.3%). Pulsed wave DTI permits accurate assessment of myocardial velocities during each phase of the cardiac cycle. Myocardial velocity profiles obtained from different segments of 20 healthy patients showed significant lateral and septal basal-apical myocardial velocity reductions in systolic shortening, and early and late diastolic lengthening; and a basal-apical increase in the early/late diastolic lengthening ratio.2 Systolic wave (Sw) velocity has 2 components: early and late, representing isovolumic contraction and the systolic ejection phase.3 In one report early Sw was greater than late Sw.4 In our study, at rest S2 was higher than S1, but during stress this ratio reversed. Diastolic wave of myocardial DTI has 2 components: early and late velocity. One study showed that
in each myocardial segment, the ratio of early to late diastolic wave velocity correlated with the same ratio in the mitral inflow in 131 healthy children aged 7.5 ⫾ 5.5 years.5 In our study, the ratio of myocardial E and A lengthening correlated with mitral inflow pattern and annular diastolic velocity. During stress, myocardial E/A ratio decreased as a result of the impact of increased A and unchanged E. But there was no difference between patients with stenosed and patent RCA. In one study, the peak descent Sw velocity and the time from electrocardiographic Q wave to the peak of the Sw were measured at 6 mitral annular sites in 45 patients with previous myocardial infarction. The mean Sw at the sites corresponding to the infarct regions was significantly lower and the mean time from electrocardiographic Q wave to the peak of the Sw was significantly longer in the myocardial infarction groups than in the control group.6 In our study there was no significant difference in the length of the time from Q wave to the peak systolic velocity between patients who were ischemic and nonishemic. Another study of 31 healthy patients showed resting velocity in basal segments was significantly greater than in mid or apical segments (5.6 ⫾ 1.3
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Figure 1 Myocardial velocities of inferobasal segment obtained from apical 2-chamber view of patient with normal right coronary artery. At rest (A) peak systolic velocity is 6.8 cm/s and during dobutamine infusion (B) it is 13.8 cm/s. Increment of systolic velocity during stress is 103%. A, Late diastolic velocity; E, early diastolic velocity; S1, early systolic velocity; S2, late systolic velocity.
Figure 2 Myocardial velocities obtained from patient with 80% stenosis of right coronary artery. Peak late systolic myocardial velocity (S2) at rest (A) is 6 cm/s and during dobutamine infusion (B) 8 cm/s. Increment in myocardial velocity is 33.3%. A, Late diastolic velocity; E, early diastolic velocity; S1, early systolic velocity.
cm/s vs 2.2 ⫾ 1.7 cm/s, P ⬍ .001). This gradient remained with exercise (10.6 ⫾ 3.2 vs 7.8 ⫾ 3.0 cm/s and 4.5 ⫾ 3.4 cm/s, P ⬍ .001). The velocity increment during stress was similar in basal and mid segments.7 The normal range in tethered segments (septum, anteroseptal, and inferior) was ⬎7 cm/s in the basal segments and ⬎5 cm/s in the midsegments. In the free wall (anterior, lateral, and poste-
rior) the cutoff was ⬎6 cm/s in the base and ⬎4 cm/s in the midventricle.8 In general, ischemic segments during dobutamine echocardiography had less peak S1 than nonischemic segments and if the culprit artery was the left anterior descending, signs of midsystolic paradoxical septal motion appeared: midsystolic outward motion instead of inward and opposite during early
Journal of the American Society of Echocardiography Volume 16 Number 5
diastole (postsystolic contraction pattern). This reversed outward wall motion during midsystole (negative direction) and marked positive E had been suggested as a marker of myocardial ischemia.9 In 104 patients with known or suspected CAD who underwent DSE, normal and hypokinetic/akinetic segments showed significant differences in mean peak systolic velocity (7.9 ⫾ 3.8 cm/s and 5.9 ⫾ 3.3 cm/s, respectively, P ⬍ .001) and time to peak velocity (84 ⫾ 40 milliseconds and 95 ⫾ 48 ⫾ milliseconds, respectively, P ⫽ .005). A stenosed coronary artery was associated with significant differences from normally perfused segments (peak systolic velocity, 8.1 ⫾ 3.4 cm/s; time to peak velocity, 78 ⫾ 50 milliseconds compared with 92 ⫾ 45 milliseconds; P ⬍ .001). Ischemic myocardium has less peak systolic velocity and longer time to peak velocity.10 Excluding apical segments, a peak endocardial velocity of ⬍5.5 cm/s at peak stress had an average sensitivity of 96%, specificity of 81%, and predictive accuracy of 86% for identifying abnormal segments at peak stress during DSE.11 In 116 patients referred for exercise single photon emission computed tomography for the assessment of CAD, segments with a stress defect had a marked reduction in peak exercise velocity and less increment in velocity than normal segments.7 A total of 65 patients with inferior ischemia determined by single photon emission computed tomography and 34 healthy patients underwent a standard DSE with pulsed wave DTI and subsequent coronary angiography. The peak stress mean E/A ratio was lower in patients with CAD when compared with patients without CAD (0.78 ⫾ 0.2 vs 1.29 ⫾ 0.11, P ⬍ .0001). Also, the peak stress E/A ratio of healthy patients was significantly higher than for patients who had CAD (1.19 ⫾ 0.3 vs 0.78 ⫾ 0.2, P ⬍ .0001). The peak stress E/A ratio was higher than 1 in all patients with a false-positive perfusion defect. Systolic S velocity increase during DSE was significantly lower in patients with CAD (54% ⫾ 17 vs 99% ⫾ 24, P ⫽ .01). The analysis of S velocity increase yielded 81% sensitivity and 76% specificity for prediction of CAD when a 70% increase was accepted as a cut-off value.12 Yamada et al13 reported a ⬍90% increase in systolic myocardial velocity from baseline to peak dobutamine dose, with 83% sensitivity and 87% specificity in the myocardial segments with ischemia. In our study there was no significant difference in clinical characteristics between the groups. Peak S2 (systolic ejection) was higher than peak S1 (isovolumic contraction). During stress, S1 component increased and became higher than the late component. Time to systolic peak velocity during stress was shorter than during rest and is explained by achievement of target heart rate. The expected increment of systolic velocity during dobutamine
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echocardiography was significant and the best predictor of ischemia. For the diagnosis of RCA stenosis of 70% or more, increment of 70% in systolic velocity during dobutamine echocardiography was predictive for ischemia with a sensitivity of 81.8% and specificity of 89.7%. An 80% increment of systolic velocity was a break point for ischemia with sensitivity of 90.9% and specificity of 79.5%, and if the increment in systolic velocity was at least 90%, specificity decreased to 71.8% but sensitivity was not changed. An increment of 70% to 80% in systolic velocity seems an acceptable value for the diagnosis of no ischemia during dobutamine echocardiography with satisfactory sensitivity and specificity. In our study conventional stress echocardiography was falsely negative in 3 patients with 70% or more RCA stenosis (normal wall motion and wall thickening in the inferobasal region). DTI was diagnostic in one of these patients, borderline in another, and negative in the third. We believe that this may reflect a somewhat better sensitivity for DTI for the diagnosis of inferobasal ischemia. This method may serve as an adjunct to traditional wall motion and wall thickening, and there is no need for DTI when inferobasal segment shows normal contraction. Limitations of our study include a rather small cohort, different timing between dobutamine echocardiography and coronary angiography, and a wide range of measurements. Other factors that may affect systolic velocity include aging, left ventricular hypertrophy, the significance of cardiac fibrosis, pretreatment with -blockers and other medications, and neurohormonal status (catecholamine level and thyroid hormones). Alternative techniques that have been suggested to better detect ischemia include ultrasonic tissue characterization,14 which has been limited to the parasternal views only, and, more recently, ultrasonic contrast agents injected intravenously that may offer data on myocardial blood flow and perfusion, and may be combined with conventional stress echocardiography.15 Conclusion Quantitative evaluation of the inferobasal segment during dobutamine echocardiography with DTI may be useful for diagnosis of ischemia and may enhance the diagnosis when used in conjunction with conventional imaging.
REFERENCES 1. Bach DS, Muller DW, Gros BJ, Armstrong WF. False positive dobutamine stress echocardiograms: characterization of clinical, echocardiographic and angiographic findings. J Am Coll Cardiol 1994;24:928-33. 2. Palmes PP, Masuyama T, Yamamoto K, Kondo H, Sakata Y, Takiuchi S, et al. Myocardial longitudinal motion by tissue
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velocity imaging in the evaluation of patients with myocardial infarction. J Am Soc Echocardiogr 2000;13:818-26. Waggoner AD, Bierig SM. Tissue Doppler imaging: a useful echoardiographic method for the cardiac sonographer to assess systolic and diastolic ventricular function. J Am Soc Echocardiogr 2001;14:1143-52. Oki T, Tabata T, Mishiro Y, Yamada H, Abe M, Onose Y, et al. Pulsed tissue Doppler imaging of left ventricular systolic and diastolic wall motion velocities to evaluate differences between long and short axes in healthy subjects. J Am Soc Echocardiogr 1999;12:308-13. Mori K, Hayabuchi Y, Kuroda Y, Nii M, Manabe T. Left ventricular wall motion velocities in healthy children measured by pulsed wave Doppler tissue echocardiography: normal values and relation to age and heart rate. J Am Soc Echocardiogr 2000;13:1002-11. Fukuda K, Oki T, Tabata T, Iuchi A, Ito S. Regional left ventricular wall motion abnormalities in myocardial infarction and mitral annular descent velocities studied with pulsed tissue Doppler imaging. J Am Soc Echocardiogr 1998;11:841-9. Pasquet A, Armstrong G, Rimmerman C, Marwick TH. Correlation of myocardial Doppler velocity response to exercise with independent evidence of myocardial ischemia by dualisotope single-photon emission computer tomography. Am J Cardiol 2000;85:536-42. Cain P, Baglin T, Case C, Spicer D, Short L, Marwick TH. Application of tissue Doppler to interpretation of dobutamine echocardiography and comparison with quantitative coronary angiography. Am J Cardiol 2001;87:525-31.
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9. Edvardsen T, Aakhus S, Endresen K, Bjomerheim R, Smiseth OA, Ihlen H. Acute regional myocardial ischemia identified by 2-dimensional multiregion tissue Doppler imaging technique. J Am Soc Echocardiogr 2000;13:986-94. 10. Tsutsui H, Uematsu M, Yamagishi M, Haruta S, Shimakura T, Miyatake K. Usefulness of the subendocardial myocardial velocity gradient in low-dose dobutamine stress echocardiography. Heart Vessels 2000;15:11-7. 11. Katz WE, Gulati VK, Mahler CM, Gorcsan J 3rd. Quantitative evaluation of the segmental left ventricular response to dobutamine stress by tissue Doppler echocardiography. Am J Cardiol 1997;79:1036-42. 12. Altinmakas S, Dagdeviren B, Turkmen M, Gursurer M, Say B, Tezel T, et al. Usefulness of pulse-wave Doppler tissue sampling and dobutamine stress echocardiography for identification of false positive inferior wall defects in SPECT. Jpn Heart J 2000;41:141-52. 13. Yamada E, Garcia M, Thomas JD, Marwick TH. Myocardial Doppler velocity imaging: a quantitative technique for interpretation of dobutamine echocardiography. Am J Cardiol 1998;82:806-9. 14. Milunski MR, Mohr GA, Perez JE, Vered Z, Wear KA, Gessler CJ, et al. Ultrasonic tissue characterization with integrated backscatter: acute myocardial ischemia, reperfusion, and stunned myocardium in patients. Circulation 1989;80:491503. 15. Lafitte S, Matsugata H, Peters B, Togni M, Strachan M, Kwan OL, et al. Comparative value of dobutamine and adenosine stress in the detection of coronary stenosis with myocardial contrast echocardiography. Circulation 2001;103:2724-30.
Improved Detection of Inferobasal Ischemia During Dobutamine Echocardiography With Doppler Tissue Imaging Marina Leitman, MD, Stanislav Sidenko, Ruth Wolf, Edgar Sucher, MD, Simha Rosenblatt, MD, Eli Peleg, MD, Ricardo Krakover, MD, and Zvi Vered, MD, FACC, Tel Aviv, Israel
Objectives: The purpose of this study was quantitative evaluation of the inferobasal segment during dobutamine stress echocardiography using Doppler tissue imaging (DTI). Background: Overdiagnosis of myocardial ischemia during dobutamine echocardiography is a common problem. DTI may permit more accurate quantitative diagnosis of ischemia. Methods: A total of 50 patients with normal contraction of the inferobasal segment at rest were referred for dobutamine stress echocardiography. All underwent coronary angiography. Systolic and diastolic myocardial velocities were measured from apical
2-chamber view at rest and at the peak of dobutamine infusion. Results: Stenosis of the right coronary artery > 70% was detected in 11 patients. Conventional stress echocardiography was falsely positive in 10.3% and falsely negative in 27.3%. When DTI was combined with conventional stress echocardiography, sensitivity and specificity was 81.8% and 97.4%, respectively. Conclusion: DTI may enhance the diagnosis of inferior ischemia during dobutamine echocardiography and can be added to conventional imaging in the treatment of these patients. (J Am Soc Echocardiogr 2003;16:403-8.)
Wall-motion analysis of the inferobasal segment of
METHODS
the left ventricle is a common problem during dobutamine echocardiography and may be a cause for unnecessary coronary angiography. Even resting imaging of the inferobasal segment often demonstrates abnormal motion as a result of close proximity of the mitral valve and atrioventricular grove. During dobutamine infusion this impairment may become more prominent and can be incorrectly interpreted as ischemia. Overdiagnosis of ischemia has usually occurred in patients with intermediategrade coronary stenosis.1 We investigated changes of the inferobasal segment during dobutamine stress echocardiography (DSE) with Doppler tissue imaging (DTI). Normal and ischemic segments have their characteristic systolic and diastolic parameters2-6 at rest and during stress.7-13 We evaluated the additive value of DTI over conventional wall-motion analysis and correlated the results with coronary angiography.
From the Cardiology Department, Assaf Harofeh Medical Center, Zerifin, Sackler Faculty of Medicine, Tel Aviv University. Reprint requests: Marina Leitman, MD, Cardiology Department, Assaf Harofeh Medical Center, Zerifin 70300, Israel. (E-mail: [email protected]). Copyright 2003 by the American Society of Echocardiography. 0894-7317/2003/$30.00 ⫹ 0 doi:10.1016/S0894-7317(03)00015-4
In all, 50 consecutive patients with normal resting contraction of the inferobasal segment, referred for DSE, were included. All patients had undergone coronary angiography before dobutamine echocardiography or coronary angiography was planned as a result of conventional indications unrelated to this study. Dobutamine was infused intravenously in incremental doses (5-10-20-30-40-50 g/kg/min) every 3 minutes with the addition of atropine (0.25-2 mg intravenously) if necessary. The end points of the test were the achievement of target heart rate or the development of ischemia. “Target heart rate” was defined as 85% of the age-predicted maximal value. DTI studies of the inferobasal segment were obtained from apical 2-chamber view. DTI early systolic velocity (S1), late systolic velocity (S2), early diastolic velocity (E), and late diastolic velocity (A) were obtained at rest and at peak dose of dobutamine. All the conventional and DTI studies were performed with high-resolution second harmonic imaging mode using a system V (Vingmed, General Electric, Horten, Norway). Coronary angiography was analysed independently by an interventional cardiology team. DTI results were analyzed by 2 experienced observers independently. The extra time needed for these measurements was no more than several minutes. Statistical Methods All statistical analysis were undertaken using standard Student t test and chi-square test. Significance was determined as P ⬍ .05. Data are presented as mean ⫾ SD.
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Table 1 Patients characteristics (N ⫽ 50) Age (y) EF (%) Female Males Hypertension CAD LVH RCA patient RCA stenosis ⬎70%
62 55.4 15 35 34 43 28 39 11
(42-77) (33-65) 30% 70% 68% 86% 56% 78% 22%
EF, Ejection fraction; CAD, coronary artery disease; LVH, left ventricular hypertrophy; RCA, right coronary artery.
Patients Characteristics Patient characteristics are shown in Table 1. Mean age was 62 years (range: 42-77). Mean ejection fraction was 55.4% (range: 33%-65%). There were 15 females (30%) and 35 males (70%). Hypertension was present in 34 patients (68%) and 43 patients (86%) had a history of coronary artery disease (CAD). Left ventricular hypertrophy was present in 28 patients (56%). Coronary angiography detected 3-vessel CAD in 7 patients, 2-vessel CAD in 11 patients, and 1-vessel CAD in 9 patients. In 11 patients, 70% or more right coronary artery (RCA) stenoses were present.
RESULTS Patients were divided into 2 groups: group A had stenosis of the RCA ⱖ 70%; and group B had either patent or less significant stenosis. There was no significant difference in patient age between groups (group A: 62 years [range: 51-77]; group B: 61.8 years [range: 42-77]). Mean ejection fraction in group A was 56.5 ⫾ 6.5% and in group it was B 55.2 ⫾ 8.5% (difference not significant). The total dose of dobutamine used in each group was similar. Baseline and stress characteristics of 39 patients with patent RCA are presented in Table 2. Systolic velocity obtained from 2-chamber view usually had 2 peaks: S2 was higher than S1 (5.4 ⫾ 1.45 cm/s vs 4.3 ⫾ 0.84 cm/s, P ⬍ .05). During stress, S1 became higher than S2 (11.2 ⫾ 2.8 cm/s vs 9.4 ⫾ 2.7 cm/s, P ⬍ .05). Time to peak systolic myocardial velocity shortened significantly at stress (0.03 ⫾ 0.02 seconds vs 0.13 ⫾ 0.14 seconds, P ⫽ .001). In regard to diastolic parameters, myocardial E/A ratio at stress was lower than at rest (0.4 ⫾ 0.2 vs 0.6 ⫾ 0.4, P ⬍ .0003) and this occurred as a result of higher A at stress than at rest (12.0 ⫾ 2.6 cm/s vs 8.3 ⫾ 2.24 cm/s, P ⬍ .000001). E at rest was 5.3 ⫾ 2.6 cm/s, and did not change significantly during stress. Comparison of patient groups A and B is presented in Table 3. During stress, peak myocardial S1 was higher in group B than in group A (11.5 ⫾ 2.8 cm/s vs 8.2 ⫾ 4.0 cm/s, P ⫽ .004). Maximal peak systolic myocardial velocity was also higher in group
B than in group A (12.3 ⫾ 2.1 cm/s vs 10.4 ⫾ 1.8 cm/s, P ⫽ .01). Absolute increase of peak myocardial systolic velocity ([Sms-Smr]/Smr [%]) during stress was higher in group B than in group A (6.6 ⫾ 1.6 cm/s vs 3.6 ⫾ 1.4 cm/s). Relative increment in systolic myocardial velocity was also higher in group B than in group A (126 ⫾ 49% vs 54 ⫾ 22.7%, P ⫽ .000001). Echocardiographic inferobasal ischemia was detected by conventional stress echocardiography in 72.7% of group A (8 patients) and in 10.3% of group B (4 patients) (P ⬍ .00001). Conventional stress echocardiography was falsely negative in 3 patients with 70% or more RCA stenosis (27.3%). In these patients DTI was diagnostic in one patient, borderline (79% increase of peak systolic myocardial velocity) in another, and negative in the third. Falsepositive results with conventional echocardiography were present in 10.3%. In 2 patients with normal RCA, conventional stress echocardiography was falsely positive and DTI produced normal findings. In 2 other cases with 50% RCA stenosis, conventional stress echocardiography was positive for ischemia and DTI was borderline (73% increase in peak systolic myocardial velocity) in one patient and normal in another. In one patient DTI was falsely positive but this occurred during a submaximal stress test (67% from maximal predicted heart rate). For detection of 70% or more RCA stenosis when the cutoff of myocardial systolic velocity increment during the stress test was 70%, sensitivity was 81.8% and specificity was 89.7%; when the cutoff was 80%, sensitivity was 90.9% and specificity was 79.5%; and when this point was 90%, sensitivity was 90.9% and specificity was 71.8%. When DTI was combined with conventional stress echocardiography and cutoff increment of peak systolic myocardial velocity was 70%, sensitivity and specificity for detection of at least 70% RCA stenosis was 81.8% and 97.4%, respectively. Figure 1 demonstrates quantitative assessment of myocardial velocities in the inferobasal segment during dobutamine echocardiography in a patient with normal RCA. Myocardial velocity increased by 103%. Figure 2 demonstrates myocardial velocities during dobutamine echocardiography in a patient with inferior ischemia and 80% stenosis of RCA. Increment of myocardial velocity was 33.3%.
DISCUSSION Accurate analysis of the inferobasal segment is a common problem during stress echocardiography. Among 342 cases, 39 met the criteria for falsely positive DSE test results (wall-motion abnormalities and ⬍50% coronary artery stenosis).1 Regional wallmotion abnormalities occurred predominantly in women (72%), were more common in posterior
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Table 2 Normal Doppler tissue imaging characteristics of the inferobasal segment at rest and stress S1 rest, cm/s S2 rest, cm/s S1 stress, cm/s S2 stress, cm/s T to S rest, s T to S stress, s E rest, cm/s E stress, cm/s A rest, cm/s A stress, cm/s E/A myocardial rest E/A myocardial stress
Average
Range
SD
4.3 5.4 11.2 9.4 0.13 0.03 5.3 4.8 8.3 12 0.6 0.4
0.2-10.0 2.1-8.0 1.7-15.0 5.0-14.5 0.01-0.90 0.01-0.06 1.5-12 0.7-13 2.5-13 5.0-15.0
0.84 1.45 2.8 2.7 0.14 0.02 2.6 0.8 2.24 2.6 0.4 0.2
P value
S2 rest⬎ S1 rest
⬍.05
s1 stress⬎ S2 stress T to S rest ⬎ T to S stress
⬍.05 .001
NS ⬍.000001
A stress⬎ A rest E/A rest ⬎ E/A stress
.0003
T to S, Time from the onset of systole to peak myocardial systolic velocity; S1, early peak systolic velocity; S2, late peak systolic velocity; E, early diastolic velocity; A, late diastolic velocity; NS, not significant.
Table 3 Doppler tissue imaging characteristics of inferobasal segment during stress No. of patients Ejection fraction, % S1m stress, cm/s Max S stress, cm/s Sms-Smr, cm/s % (Sms-Smr) Inferobasal ischemia*
Group A
SD
11 56.5 8.2 (0-13.0) 10.4 (7.8-13.0) 3.6 (0.02-6.7) 54 (29-106) 8 (72.7%)
6.5 4 1.8 1.4 22.7
Group B
39 55.2 11.5 (1.7-15) 12.3 (5.7-15) 6.6 (3.2-10.0) 126 (50-217) 4 (10.3%)
SD
8.5 2.8 2.1 1.6 49
P value
.004 .01 .00001 .000001 .00001
Group A, patients with ⬎ 70% right coronary artery (RCA) stenosis; Group B, patients with patent RCA; S1m stress, early peak systolic myocardial velocity at stress; Max S stress, maximal systolic myocardial velocity at stress; Sms-Smr, absolute increase of myocardial systolic velocity; % (Sms-Smr), relative increase in systolic myocardial velocity. *By conventional stress echocardiography. All the represented measurements were obtained from 2 chamber view.
circulation (62%), were often limited to the basal segments (65%), and were unlikely to be associated with coronary stenosis. Approximately one third of false-positive results occurred in patients with intermediate-grade coronary stenosis (28% of 43 wallmotion segments) and could reflect true inducible ischemia, poor endocardial visualization, and abnormal motion as a result of tethering to the fibrous skeleton of the heart.1 In our study false-positive results occurred in 4 patients (10.3%). Pulsed wave DTI permits accurate assessment of myocardial velocities during each phase of the cardiac cycle. Myocardial velocity profiles obtained from different segments of 20 healthy patients showed significant lateral and septal basal-apical myocardial velocity reductions in systolic shortening, and early and late diastolic lengthening; and a basal-apical increase in the early/late diastolic lengthening ratio.2 Systolic wave (Sw) velocity has 2 components: early and late, representing isovolumic contraction and the systolic ejection phase.3 In one report early Sw was greater than late Sw.4 In our study, at rest S2 was higher than S1, but during stress this ratio reversed. Diastolic wave of myocardial DTI has 2 components: early and late velocity. One study showed that
in each myocardial segment, the ratio of early to late diastolic wave velocity correlated with the same ratio in the mitral inflow in 131 healthy children aged 7.5 ⫾ 5.5 years.5 In our study, the ratio of myocardial E and A lengthening correlated with mitral inflow pattern and annular diastolic velocity. During stress, myocardial E/A ratio decreased as a result of the impact of increased A and unchanged E. But there was no difference between patients with stenosed and patent RCA. In one study, the peak descent Sw velocity and the time from electrocardiographic Q wave to the peak of the Sw were measured at 6 mitral annular sites in 45 patients with previous myocardial infarction. The mean Sw at the sites corresponding to the infarct regions was significantly lower and the mean time from electrocardiographic Q wave to the peak of the Sw was significantly longer in the myocardial infarction groups than in the control group.6 In our study there was no significant difference in the length of the time from Q wave to the peak systolic velocity between patients who were ischemic and nonishemic. Another study of 31 healthy patients showed resting velocity in basal segments was significantly greater than in mid or apical segments (5.6 ⫾ 1.3
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Figure 1 Myocardial velocities of inferobasal segment obtained from apical 2-chamber view of patient with normal right coronary artery. At rest (A) peak systolic velocity is 6.8 cm/s and during dobutamine infusion (B) it is 13.8 cm/s. Increment of systolic velocity during stress is 103%. A, Late diastolic velocity; E, early diastolic velocity; S1, early systolic velocity; S2, late systolic velocity.
Figure 2 Myocardial velocities obtained from patient with 80% stenosis of right coronary artery. Peak late systolic myocardial velocity (S2) at rest (A) is 6 cm/s and during dobutamine infusion (B) 8 cm/s. Increment in myocardial velocity is 33.3%. A, Late diastolic velocity; E, early diastolic velocity; S1, early systolic velocity.
cm/s vs 2.2 ⫾ 1.7 cm/s, P ⬍ .001). This gradient remained with exercise (10.6 ⫾ 3.2 vs 7.8 ⫾ 3.0 cm/s and 4.5 ⫾ 3.4 cm/s, P ⬍ .001). The velocity increment during stress was similar in basal and mid segments.7 The normal range in tethered segments (septum, anteroseptal, and inferior) was ⬎7 cm/s in the basal segments and ⬎5 cm/s in the midsegments. In the free wall (anterior, lateral, and poste-
rior) the cutoff was ⬎6 cm/s in the base and ⬎4 cm/s in the midventricle.8 In general, ischemic segments during dobutamine echocardiography had less peak S1 than nonischemic segments and if the culprit artery was the left anterior descending, signs of midsystolic paradoxical septal motion appeared: midsystolic outward motion instead of inward and opposite during early
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diastole (postsystolic contraction pattern). This reversed outward wall motion during midsystole (negative direction) and marked positive E had been suggested as a marker of myocardial ischemia.9 In 104 patients with known or suspected CAD who underwent DSE, normal and hypokinetic/akinetic segments showed significant differences in mean peak systolic velocity (7.9 ⫾ 3.8 cm/s and 5.9 ⫾ 3.3 cm/s, respectively, P ⬍ .001) and time to peak velocity (84 ⫾ 40 milliseconds and 95 ⫾ 48 ⫾ milliseconds, respectively, P ⫽ .005). A stenosed coronary artery was associated with significant differences from normally perfused segments (peak systolic velocity, 8.1 ⫾ 3.4 cm/s; time to peak velocity, 78 ⫾ 50 milliseconds compared with 92 ⫾ 45 milliseconds; P ⬍ .001). Ischemic myocardium has less peak systolic velocity and longer time to peak velocity.10 Excluding apical segments, a peak endocardial velocity of ⬍5.5 cm/s at peak stress had an average sensitivity of 96%, specificity of 81%, and predictive accuracy of 86% for identifying abnormal segments at peak stress during DSE.11 In 116 patients referred for exercise single photon emission computed tomography for the assessment of CAD, segments with a stress defect had a marked reduction in peak exercise velocity and less increment in velocity than normal segments.7 A total of 65 patients with inferior ischemia determined by single photon emission computed tomography and 34 healthy patients underwent a standard DSE with pulsed wave DTI and subsequent coronary angiography. The peak stress mean E/A ratio was lower in patients with CAD when compared with patients without CAD (0.78 ⫾ 0.2 vs 1.29 ⫾ 0.11, P ⬍ .0001). Also, the peak stress E/A ratio of healthy patients was significantly higher than for patients who had CAD (1.19 ⫾ 0.3 vs 0.78 ⫾ 0.2, P ⬍ .0001). The peak stress E/A ratio was higher than 1 in all patients with a false-positive perfusion defect. Systolic S velocity increase during DSE was significantly lower in patients with CAD (54% ⫾ 17 vs 99% ⫾ 24, P ⫽ .01). The analysis of S velocity increase yielded 81% sensitivity and 76% specificity for prediction of CAD when a 70% increase was accepted as a cut-off value.12 Yamada et al13 reported a ⬍90% increase in systolic myocardial velocity from baseline to peak dobutamine dose, with 83% sensitivity and 87% specificity in the myocardial segments with ischemia. In our study there was no significant difference in clinical characteristics between the groups. Peak S2 (systolic ejection) was higher than peak S1 (isovolumic contraction). During stress, S1 component increased and became higher than the late component. Time to systolic peak velocity during stress was shorter than during rest and is explained by achievement of target heart rate. The expected increment of systolic velocity during dobutamine
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echocardiography was significant and the best predictor of ischemia. For the diagnosis of RCA stenosis of 70% or more, increment of 70% in systolic velocity during dobutamine echocardiography was predictive for ischemia with a sensitivity of 81.8% and specificity of 89.7%. An 80% increment of systolic velocity was a break point for ischemia with sensitivity of 90.9% and specificity of 79.5%, and if the increment in systolic velocity was at least 90%, specificity decreased to 71.8% but sensitivity was not changed. An increment of 70% to 80% in systolic velocity seems an acceptable value for the diagnosis of no ischemia during dobutamine echocardiography with satisfactory sensitivity and specificity. In our study conventional stress echocardiography was falsely negative in 3 patients with 70% or more RCA stenosis (normal wall motion and wall thickening in the inferobasal region). DTI was diagnostic in one of these patients, borderline in another, and negative in the third. We believe that this may reflect a somewhat better sensitivity for DTI for the diagnosis of inferobasal ischemia. This method may serve as an adjunct to traditional wall motion and wall thickening, and there is no need for DTI when inferobasal segment shows normal contraction. Limitations of our study include a rather small cohort, different timing between dobutamine echocardiography and coronary angiography, and a wide range of measurements. Other factors that may affect systolic velocity include aging, left ventricular hypertrophy, the significance of cardiac fibrosis, pretreatment with -blockers and other medications, and neurohormonal status (catecholamine level and thyroid hormones). Alternative techniques that have been suggested to better detect ischemia include ultrasonic tissue characterization,14 which has been limited to the parasternal views only, and, more recently, ultrasonic contrast agents injected intravenously that may offer data on myocardial blood flow and perfusion, and may be combined with conventional stress echocardiography.15 Conclusion Quantitative evaluation of the inferobasal segment during dobutamine echocardiography with DTI may be useful for diagnosis of ischemia and may enhance the diagnosis when used in conjunction with conventional imaging.
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