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Low-dose dobutamine testing using contrast left ventriculography in the same session as coronary angiography predicts the improvement of left ventricular function after coronary angioplasty in postinfarction patients
Low-Dose Dobutamine Testing Using Contrast Left Ventriculography in the Same Session as Coronary Angiography Predicts the Improvement of Left Ventricular Function After Coronary Angioplasty in Postinfarction Patients Juan Sanchis, MD, FESC, Vicente Bodı´, MD, Luis Insa, MD, Ricardo Go´mez-Aldaravı´, MD, Alberto Berenguer, MD, Marı´a P. Lo´pez-Lereu, MD, Francisco J. Chorro, MD, FESC, and Vicente Lo´pez-Merino, MD The role of percutaneous transluminal coronary angioplasty (PTCA) in the subacute or chronic phases of myocardial infarction remains controversial. This study investigates the usefulness of dobutamine contrast left ventriculography in a single session with coronary angiography for predicting the improvement of ventricular function after PTCA. The study group consisted of 30 patients in whom a contrast left ventricular angiogram and PTCA were performed after a first myocardial infarction. The centerline method was used to calculate dysfunction extent at baseline and its variation during dobutamine infusion at 7.5 mg/kg/min; contractile reserve was defined as a significant (>15%) reduction of dysfunction extent. A second ventricular angiogram was performed 6 months later in all patients. Abnormal wall motion extent decreased at 6 months after PTCA (84 6 21% vs 70 6 29%, p 5 0.0001). Wall motion improvement after PTCA correlated with the response to dobutamine (r 5 0.54, p 5 0.002). Ten patients showed a significant reduction (>15%) of dysfunction extent at 6 months; dobutamine testing had a 80% sensitivity, 84% specificity, 67% positive predictive value, and 89% negative predictive value in detecting regional function im-
provement. In the subgroup of 21 patients without restenosis, both the correlation between dysfunction improvement after PTCA and response to dobutamine (r 5 0.72, p 5 0.0001) and the accuracy of dobutamine testing (sensitivity 88%, specificity 92%, positive predictive value 88%, and negative predictive value 92%) increased. The ejection fraction significantly increased (>5%) after PTCA in 6 patients; dobutamine testing had a 67% sensitivity, 74% specificity, 44% positive predictive value, and 88% negative predictive value in predicting the increase in the ejection fraction. In the subgroup without restenosis the improvement of the ejection fraction correlated with the response to dobutamine (r 5 0.63, p 5 0.007), and the sensitivity of dobutamine testing was 80%, specificity 83%, positive predictive value 67%, and negative predictive value 91%. In conclusion, dobutamine contrast left ventriculography testing in the same session as coronary angiography predicts regional function and ejection fraction improvement after PTCA in postinfarction patients, particularly when restenosis does not develop. Q1999 by Excerpta Medica, Inc. (Am J Cardiol 1999;83:15–20)
mong the several tests introduced to assess myocardial viability, low-dose dobutamine testing is A probably the most widespread because echocardiog-
ing contrast left ventriculography could also be applied as a viability test. In this sense, the catheterization laboratory would be a unique scenario for simultaneously evaluating myocardial viability and infarction artery status, to guide the decision for using percutaneous transluminal coronary angioplasty (PTCA) in a single session. In the present study, dobutamine contrast left ventriculography, diagnostic coronary angiography, and PTCA were performed in postinfarction patients in the same session. The aim was to investigate the role of dobutamine contrast left ventriculography in predicting the improvement of ventricular function after PTCA.
1
raphy is a widely available and relatively inexpensive imaging modality. Low-dose dobutamine echocardiography examines the contractile reserve in the infarcted dysfunctional area,2 the improvement of contractility during dobutamine infusion indicates contractile reserve, which in turn suggests viability. A number of studies show that low-dose dobutamine echocardiography allows the identification of viable stunned3–7 and hibernating8 –24 myocardium. Based on the same principles, low-dose dobutamine testing usFrom the Service of Cardiology, University Clinic Hospital, Valencia; and Cardiology Unit, Marina Baixa Hospital, Vila-Joiosa, Spain. Manuscript received May 11, 1998; revised manuscript received and accepted July 24, 1998. Address for reprints: Juan Sanchis, MD, FESC, Servicio de Cardiologı´a, Hospital Clı´nico Universitario, Blasco Iba´n˜ez 17, Valencia 46010, Spain. ©1999 by Excerpta Medica, Inc. All rights reserved.
METHODS
Patient population: The study group included patients subjected to cardiac catheterization in the subacute or chronic phase of a first myocardial infarction who fulfilled the following criteria: (1) significant abnormal wall motion extent ($15% of the myocar0002-9149/99/$–see front matter PII S0002-9149(98)00775-9
15
the right or circumflex coronary arteries (51 to 80 chords) in patients with inferior infarctions.25 Abnormal wall motion extent was defined as the number of chords displaying hypokinetic motion (,1 SD) expressed as a percentage of the total coronary territory analyzed (Figure 1). All measurements were performed by a single observer. Coronary angiography: Quantitative coronary analysis in the infarcted artery was performed using the automatic edge method. PTCA was performed by standard techniques in the same session as the diagnostic angiogram in all patients. Stents were implanted in 13 patients (46%). Dobutamine infusion: Dobutamine testing was performed before PTCA. Dobutamine infusion was started at 5 and 7.5 mg/kg/min, each dose for 4 minutes. Left ventriculography was repeated at the end of the 7.5 mg/kg/min stage. No significant changes in hemoFIGURE 1. Quantification of abnormal wall motion extent at baseline (left) and during dobutamine infusion (right) in a patient with anterior infarction. At basedynamic data were observed during doline, contractility of all chords from the myocardial territory of the left anterior debutamine infusion. The variation of scending artery (10 to 66 chords) are <1 SD from normal reference; thus, abnorabnormal wall motion extent was calmal wall motion extent in the left anterior descending artery territory is 100%. culated as the difference between abDuring dobutamine infusion, dysfunction extent was reduced to 53%. normal wall motion extent at baseline minus abnormal wall motion extent during 7.5 mg/kg/min dobutamine infudial territory of the infarcted artery) in the left ven- sion (Figure 1). Beta-blocker treatment was discontintricular angiogram, (2) severe residual stenosis ued 2 days before in all patients. ($70%) or occlusion in the infarcted artery, (3) ameIntraobserver variability: Intraobserver variability nability to PTCA in the infarcted artery, and (4) suc- was calculated by making duplicate measurements of cessful PTCA (residual stenosis ,35% with grade 3 regional ventricular function and the global ejection Thrombolysis In Myocardial Infarction [TIMI] flow fraction in 20 randomly selected ventriculograms. The and no major complications). Thirty patients were intraobserver average differences between 2 measureincluded. Mean age was 57 6 12 years. The infarction ments of abnormal wall motion extent was 6 6 4% was anterior in 25 patients (81%). A second catheter- and 3 6 1% of the ejection fraction. Thus, a signifiization 6 months later after PTCA (168 6 22 days) cant change in regional function during dobutamine was performed in all patients to evaluate the evolution infusion or at 6 months after PTCA was considered if of ventricular function and restenosis. the abnormal wall motion extent varied $15% comLeft ventriculography: Forty milliliters of contrast pared with the baseline value, and a significant change were injected at an injection speed of 12 ml/s, in the in the ejection fraction at 6 months was defined if it 30° right anterior oblique projection. The software of varied .5% (95% confidence level for detecting a an x-ray digital imaging system (Integris HM 3000, significant change). Analysis of left ventricular funcPhilips, The Netherlands) was used for global and tion was blinded. regional left ventriculogram analysis. Global ejection Statistical analysis: Values are expressed as mean 6 fraction was calculated by the area-length method. SD. Continuous variables were compared by the Centerline chord motion analysis was used to quanti- paired or unpaired t test. Categorical variables were tatively assess regional left ventricular function.25 In compared by the chi-square test. Relation between this technique, endocardial motion is measured along continuous variables was evaluated by linear regres100 chords constructed perpendicular to a centerline. sion analysis. The motion of each chord is normalized by the enddiastolic circumference to yield a fractional shorten- RESULTS ing. This value is then converted into units of SD from Evolution of regional function after PTCA: Mean abthe normal mean motion of each chord as derived normal wall motion extent in the first ventricular anfrom a normal reference population. Wall motion was giogram before angioplasty was 84 6 21%. It deanalyzed in the distribution territory of the left anterior creased 6 months later following PTCA (70 6 29%, descending artery (10 to 66 chords) in patients with p 5 0.0001). Ten patients had a significant reduction anterior infarctions, and in the distribution territory of ($15%) of abnormal wall motion extent at 6 months. 16
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FIGURE 2. Individual data of regional ventricular function in patients with and without improvement after PTCA (in the subgroups with and without restenosis) at baseline (B), with dobutamine (D), and after PTCA (P).
TABLE I Sensitivity (SE), Specificity (SP), Positive Predictive Value (PPV), and Negative Predictive Value (NPV) of Dobutamine Testing for Detecting a Significant Reduction of Abnormal Wall Motion Extent After PTCA, in the Global Group of Patients and in the Subgroup Without Restenosis
Global group No restenosis
SE
SP
PPV
NPV
80% 88%
84% 92%
67% 88%
89% 92%
Patients with and without improvement after PTCA did not differ in age (58 6 11 vs 56 6 12 years), anterior location of infarction (8% to 80% vs 18% to 90%), presence of angina (2% to 20% vs 11% to 55%), or in the baseline extent of dysfunction (75 6 25% vs 87 6 18%, NS). Figure 2 shows individual data of regional ventricular function in patients with and without improvement after PTCA (in the subgroups with and without restenosis) at baseline, with dobutamine, and after PTCA. ROLE OF DOBUTAMINE TESTING: Abnormal wall motion extent decreased during dobutamine infusion (83 6 21% vs 66 6 33%, p 5 0.0001). The reduction of dysfunction extent after PTCA correlated with the response to dobutamine (r 5 0.54, p 5 0.002, B 5 0.41 [0.16 to 0.66]). Twelve patients showed significant wall motion improvement ($15%) with dobutamine; in 8 of them (67%) contractility improved after PTCA (p 5 0.006). On the other hand, in 16 of 18 nonresponders (89%) to dobutamine, contractility likewise did not significantly change after PTCA. Dobutamine testing had a 80% sensitivity, 84% specificity, 67% positive predictive value, and 89% negative predictive value in predicting regional function response after PTCA (Table I).
ROLE OF RESTENOSIS: Nine patients had restenosis at 6 months (stenosis $50% in the previously dilated lesion). Abnormal wall motion extent decreased after PTCA in the subgroup without restenosis (79 6 24 vs 63 6 31, p 5 0.0001), but this decrease did not reach statistical significance in the subgroup with restenosis (93 6 7 vs 85 6 13, NS). In the subgroup of 12 patients with a positive response to dobutamine, regional function increased in 7 of 8 patients without restenosis but in only 1 of the 4 patients with restenosis (p 5 0.1). SUBGROUP WITHOUT RESTENOSIS: The improvement of regional wall motion after PTCA showed a stronger correlation to the improvement with dobutamine (r 5 0.72, p 5 0.0001, B 5 0.62 [0.33 to 0.90]) (Figure 3). Abnormal wall motion extent diminished more in patients with contractile reserve (30 6 12%, n 5 8) than in patients without contractile reserve (7 6 14%, n 5 13, p 5 0.002). Seven of the 8 patients with a positive response to dobutamine showed a significant improvement after PTCA (p 5 0.001) (Figure 3); on the other hand, 12 of the 13 nonresponders (92%) to dobutamine likewise did not exhibit wall motion improvement after PTCA. Low-dose dobutamine testing showed a 88% sensitivity, 92% specificity, 88% positive predictive value, and 92% negative predictive value in predicting the evolution of regional wall motion after PTCA (Table I). Evolution of the ejection fraction after PTCA: For analysis of the evolution of the ejection fraction, 5 patients with baseline normal and/or high ejection fractions (.60%) were excluded, because an improvement in global ejection fraction after revascularization was not to be expected in these patients despite regional function improvement. The mean left ventricular ejection fraction was 48 6 7% before PTCA and 50 6 11% (NS) after PTCA. The improvement of the ejection fraction borderline correlated with the response to dobutamine (r 5 0.36, p 5 0.08). The ejection fraction improved significantly (.5%) after PTCA in 6 patients. ROLE OF DOBUTAMINE TESTING: Among the 9 responders to dobutamine, the ejection fraction increased in 4 (45%) and did not change in 5 (55%), whereas in the 16 nonresponders to dobutamine, the ejection fraction increased after PTCA in 2 (12%) and did not vary significantly in 14 (88%) (p 5 0.1). Dobutamine testing showed a 67% sensitivity, 74% specificity, 44% positive predictive value, and 88% negative predictive value in predicting the variation of the ejection fraction after PTCA (Table II). SUBGROUP WITHOUT RESTENOSIS: As in the case of regional function, the accuracy of dobutamine testing increased in the subgroup of 17 patients without restenosis. The improvement of the ejection fraction after PTCA correlated to the reduction of abnormal wall motion extent during dobutamine infusion (r 5 0.63, p 5 0.007, B 5 0.19 [0.06 to 0.32]) (Figure 4). The ejection fraction increased more in patients with contractile reserve (8 6 5%, n 5 6) than in patients without contractile reserve (0.1 6 5%, n 5 11, p 5 0.02). In 4 of the 6 responders to dobutamine, but in
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FIGURE 3. Regression line between the reduction of abnormal wall motion extent (AWE) during dobutamine infusion (x-axis) and the reduction of abnormal wall motion extent 6 months after PTCA (y-axis) in the subgroup of patients without restenosis. There was a significant correlation (r 5 0.72, p 5 0.0001). The cut-off lines corresponding to a significant dysfunction extent reduction (15%) are traced with dotted lines. Seven of the 8 patients with a positive response to dobutamine showed significant improvement after PTCA (p 5 0.001); on the other hand, 12 of the 13 nonresponders (92%) to dobutamine likewise exhibited no wall motion improvement after PTCA. In some cases improvement after PTCA is greater than improvement with dobutamine; conceivably, the presence of a severe coronary stenosis could limit the response to dobutamine.
TABLE II Sensitivity (SE), Specificity (SP), Positive Predictive Value (PPV), and Negative Predictive Value (NPV) of Dobutamine Testing for Detecting a Significant Increase in Ejection Fraction After PTCA, in the Global Group of Patients and in the Subgroup Without Restenosis
Global group No restenosis
SE
SP
PPV
NPV
67% 80%
74% 83%
44% 67%
88% 91%
only 1 of the 11 nonresponders (p 5 0.05), the ejection fraction increased significantly after PTCA. Dobutamine testing had a 80% sensitivity, 83% specificity, 67% positive predictive value, and 91% negative predictive value (Table II).
DISCUSSION The results of this study indicate that the assessment of contractile reserve in the infarction area via low-dose dobutamine contrast left ventriculography is an accurate test for predicting the improvement of regional function and global ejection fraction after PTCA, particularly when restenosis does not develop during follow-up.
allows the interventional cardiologist to analyze myocardial viability in the same session as coronary angiography, and consequently, it can be a helpful test for deciding to use subsequent PTCA. Additional advantages are the optimal definition of the endocardial border and the quantification of regional ventricular function. Its main limitation is that, because of the risk of volume overload in performing multiple angiograms, a single dose of dobutamine can be checked; in echocardiographic studies, however, different protocols with single or multiple dobutamine doses have been used. The balance between contractile and coronary reserves determines the response to dobutamine. Wall motion may improve at low dobutamine doses but worsen by ischemia at high doses, this being the so-called “biphasic response.”20,22 Contractility worsening usually appears at .20 mg/kg/min, and rarely at low doses,20,22 such those used in the present study.
Prediction of regional function improvement after PTCA: Despite the potential limitation
of the ischemic response masking contractile reserve, analysis of pooled data from studies that have evaluated low-dose dobutamine echocardiography indicate that this technique adequately detects recovery of contractile function after revascularization, with a mean sensitivity of 84% and a mean specificity of 81%.26 These values are concordant with our results of 80% sensitivity and 84% specificity when analyzing the global group of patients. However, in the subgroup of patients without restenosis, sensitivity increased to 88% and specificity to 92%. Most of the echocardiographic studies do not perform angiographic control at follow-up; therefore, vessel or graft stenosis or occlusion can underestimate the specificity of the technique. Our results suggest that the accuracy of lowdose dobutamine testing can be higher than previously reported in the subset of successfully revascularized patients. Prediction of ejection fraction improvement after PTCA: Meluzin et al,27 obtained a strong linear corre-
that contractile reserve elicited by low-dose dobutamine testing using echocardiography is a useful tool in predicting spontaneous recovery of postinfarction stunned myocardium,3–7 and improvement after revascularization of hibernating myocardium.8 –24 The present study assesses myocardial viability by dobutamine contrast left ventriculography. This technique
lation (r 5 0.90) between the increment in regional wall motion score index during dobutamine infusion and the improvement in the ejection fraction after bypass surgery or PTCA. Vanoverschelde et al23 showed that dobutamine echocardiography had a sensitivity of 84% and specificity of 77% in predicting ejection fraction improvement after revascularization. We have found a weak correlation (r 5 0.36) between the response to dobutamine and the increase in ejection fraction after PTCA in the global group, although the correlation improved (r 5 0.63) in the subgroup of patients without restenosis. Sensitivity and specificity for detecting the ejection fraction recovery after
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Dobutamine contrast left ventricular angiogram as viability test: A number of studies have demonstrated
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2. Bolli R, Zhu WX, Myers ML, Hartley CJ, Roberts R.
Beta-adrenergic stimulation reverses postischaemic myocardial dysfunction without producing subsequent functional deterioration. Am J Cardiol 1985;56:946 – 948. 3. Pierard LA, De Landsheere ChM, Berthe Ch, Rigo P, Kulbertus HE. Identification of viable myocardium by echocardiography during dobutamine infusion in patients with myocardial infarction after thrombolytic therapy: comparison with positron emission tomography. J Am Coll Cardiol 1990;15:1021–1031. 4. Smart SC, Sawada S, Ryan Th, Segar D, Atherton L, Berkovitz K, Bourdillon PDV, Feigenbaum H. Lowdose dobutamine echocardiography detects reversible dysfunction after thrombolytic therapy of acute myocardial infarction. Circulation 1993;88:405– 415. 5. Salustri A, Elhendy A, Garyfallydis P, Ciavatti M, Cornel JH, Folkert JtC, Boersma E, Gemelli A, Roelandt JRTC, Fioretti PM. Prediction of improvement of ventricular function after first acute myocardial infarction using low-dose dobutamine stress echocardiography. Am J Cardiol 1994;74:853– 856. 6. Watada H, Ito H, Oh H, Masuyama T, Aburaya M, Hori M, Iwakura M, Higashino Y, Fujii K, Minamino T. Dobutamine stress echocardiography predicts reversFIGURE 4. Regression line between the reduction of abnormal wall motion extent ible dysfunction and quantifies the extent of irreversibly (AWE) during dobutamine infusion (x-axis) and the increase in ejection fraction (EF) 6 damaged myocardium after reperfusion of anterior months after PTCA (y-axis) in the subgroup of patients without restenosis. There was myocardial infarction. J Am Coll Cardiol 1994;24:624 – a significant correlation (r 5 0.63, p 5 0.007). The cut-off lines corresponding to a 630. significant dysfunction extent reduction (15%) and to a significant ejection fraction 7. Sanchis J, Mun˜oz J, Chorro FJ, Insa L, Egea S, Bodı´ increment (5%) are traced with dotted lines. The ejection fraction significantly inV, Lla´cer A, Lo´pez Merino V. Low-dose dobutamine creased after PTCA in 4 of the 6 responders to dobutamine, but in only 1 of the 11 echocardiography identifies stunned myocardium after nonresponders (p 5 0.05). thrombolytic treatment for acute myocardial infarction. Int J Cardiol 1996;53:5–13. 8. Barilla F, Gheorghiade M, Alam M, Khaja F, Goldstein S. Low-dose dobutamine in patients with acute PTCA were lower than previously reported in echo- myocardial infarction identifies viable but not contractile myocardium and prethe magnitude of improvement in wall motion abnormalities in response to cardiographic studies (67% and 74% for the global dicts coronary revascularization. Am Heart J 1991;122:1522–1531. group, and 80% and 75% for the restenosis subgroup). 9. Cigarroa CG, deFilippi Ch, Brickner E, Alvarez LG, Wait MA, Graybun PA. Although the negative predictive value was very high Dobutamine stress echocardiography identifies hibernating myocardium and prerecovery of left ventricular function after coronary revascularization. Cir(88% for the global group and 91% for restenosis dicts culation 1993;88:430 – 436. subgroup), the positive predictive value was low (44% 10. Marzullo P, Parodi O, Reisenhofer B, Sambucetti G, Picano E, Distante A, A, L’Abbate A. Value of rest thallium-201/technetium-99m sestamibi for the whole group and 67% for the restenosis sub- Gimelli scans and dobutamine echocardiography for detecting myocardial viability. Am J group). A significant recovery of the ejection fraction Cardiol 1993;71:166 –172. after PTCA requires wall motion improvement great 11. La Canna G, Alfieri O, Giubbini R, Gargano M, Ferrari R, Visioli O. during the infusion of dobutamine for identification of reversenough to have a repercussion upon global ventricular Echocardiography ible dysfunction in patients with chronic coronary artery disease. J Am Coll function. In this sense, although dobutamine contrast Cardiol 1994;23:617– 626. left ventriculography testing adequately detects re- 12. Perrone-Filardi P, Pace L, Prastaro M, Piscione F, Betocchi S, Squame F, Vezzuto P, Soricelli A, Indolfi C, Salvatore M, Chiariello M. Dobutamine gional function recovery after PTCA, its accuracy echocardiography predicts improvement of hypoperfused dysfunctional myocarseems lower in predicting ejection fraction improve- dium after revascularization in patients with coronary artery disease. Circulation 1995;91:2556 –2565. ment. 13. Voci P, Bilotta F, Caretta Q, Mercanti C, Marino B. Low-dose dobutamine Clinical implications: Severe residual stenosis in the echocardiography predicts the early response of dysfunctioning myocardial seginfarct-related artery supplying a dysfunctional in- ments to coronary artery bypass grafting. Am Heart J 195;129:521–526. 14. Arnesse M, Cornel JH, Salustri A, Maat APWM, Elhendy A, Reijs AEM, farcted area is not unusual in the catheterization lab- Cate FJT, Keane D, Balk AHMM, Roelandt JRTC, Fioretti PM. Prediction of oratory. Although routine PTCA might be justified improvement of regional left ventricular function after surgical revascularization. comparison of low-dose dobutamine echocardiography with 201Tl singlewith the aim of promoting regional function recovery Aphoton emission computed tomography. Circulation 1995;91:2748 –2752. or preventing ventricular remodeling, in the absence 15. deFilippi Ch, Willet D, Irani WN, Eichhorn EJ, Velasco CE, Grayburn PA. of documented recurrent ischemia the benefit of Comparison of myocardial contrast echocardiography and low-dose dobutamine echocardiography in predicting recovery of left ventricular function after PTCA is controversial. Dobutamine contrast left ven- stress coronary revascularization in chronic ischaemic heart disease. Circulation 1995; triculography can be a time-saving tool for guiding the 92:2863–2868. 16. Haque T, Furukawa T, Takahashi M, Kinoshita M. Identification of hiberdecision to use immediate subsequent PTCA. nating myocardium by dobutamine stress echocardiography: comparison with Study limitations: The method used for ventricular thalium-201 reinjection imaging. Am Heart J 1995;130:553–563. function analysis in the present study quantifies the 17. Chan RKM, Lee KJ, Calafiore P, Berlangieri SU, McKay WJ, Tonkin AM. of dobutamine echocardiography and positron emission tomography whole extent of dysfunction (total number of chords Comparison in patients with chronic ischaemic left ventricular dysfunction. J Am Coll Cardiol showing abnormal motion in the infarction artery ter- 1996;27:1601–1607. Picano E, Ostojic M, Varga A, Sicari R, Djordjevic-Dikic A, Nedeljkovic I, ritory). This index does not allow the differentiation of 18. Torres M. Combined low dose dipyridamole-dobutamine stress echocardiography hypokinetic and akinetic segments. to identify myocardial viability. J Am Coll Cardiol 1996;27:1422–1428. 19. Le Feuvre CI, Baubion N, Aubry N, Metzger JP, Vernejoul P, Vacheron A. Assessment of reversible dyssynergic segments after acute myocardial infarction: dobutamine echocardiography v thalium-201 single photon emission computed 1. Dilsizian V, Bonow RO. Current diagnostic techniques of assessing myocartomography. Am Heart J 1996;131:668 – 675. dial viability in patients with hibernating and stunned myocardium. Circulation 20. Afridi I, Kleiman NS, Raizner AE, Zoghbi WA. Dobutamine echocardiog1993;87:1–20. raphy in myocardial hibernation. Optimal dose and accuracy in predicting recov-
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ery of ventricular function after coronary angioplasty. Circulation 1995;91:663– 670. 21. Afridi I, Main ML, Grayburn PA. Accuracy of dobutamine echocardiography for detection of myocardial viability in patients with an occluded anterior descending artery. J Am Coll Cardiol 1996;28:455– 459. 22. Qureshi U, Nagueh SF, Afridi I, Vaduganathan P, Blaustein A, Verani MS, Winters WL, Zoghbi WA. Dobutamine echocardiography and quantitative restdistribution 201Tl tomography in myocardial hibernation. Relation of contractile reserve to 201Tl uptake and comparative prediction of recovery of function. Circulation 1997;95:626 – 635. 23. Vanoverschelde JLJ, D’Hont AM, Marwick T, Gerber BL, De Kock M, Dion R, Wijns W, Melin JA. Head-to-head comparison of exercise-redistributionreinjection thallium single-photon emission computed tomography and low dose dobutamine echocardiography for prediction of reversibility of chronic left ventricular ischemic dysfunction. J Am Coll Cardiol 1996;28:432– 442. 24. Bax JJ, Wijns W, Cornel JH, Visser FC, Boersma E, Fioretti PM. Prediction
of recovery of myocardial dysfunction following revascularization: comparison of F18-fluordeoxyglucose/thallium 201 single photon emission computed tomography and dobutamine echocardiography. J Am Coll Cardiol 1996;28:558 –564. 25. Sheehan FH, Bolson EL, Dodge HT, Mathey DG, Schofer J, Woo HW. Advantages and applications of the centerline method for characterising regional ventricular function. Circulation 1986;74:293–305. 26. Bax JJ, Wijns W, Cornel JH, Visser FC, Boersma E, Fioretti PM. Accuracy of currently techniques for prediction of functional recovery after revascularization in patients with left ventricular dysfunction due to chronic coronary artery disease: comparison of pooled data. J Am Coll Cardiol 1997;30:1451–1460. 27. Meluzin J, Cigarroa CG, Brickner ME, Cerny J, Spinarova L, Frelich M, Stetka F, Groch L, Grayburn PA. Dobutamine echocardiography in predicting improvement in global left ventricular systolic function after coronary bypass or angioplasty in patients with healed myocardial infarcts. Am J Cardiol 1995;76:877– 880.
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provement. In the subgroup of 21 patients without restenosis, both the correlation between dysfunction improvement after PTCA and response to dobutamine (r 5 0.72, p 5 0.0001) and the accuracy of dobutamine testing (sensitivity 88%, specificity 92%, positive predictive value 88%, and negative predictive value 92%) increased. The ejection fraction significantly increased (>5%) after PTCA in 6 patients; dobutamine testing had a 67% sensitivity, 74% specificity, 44% positive predictive value, and 88% negative predictive value in predicting the increase in the ejection fraction. In the subgroup without restenosis the improvement of the ejection fraction correlated with the response to dobutamine (r 5 0.63, p 5 0.007), and the sensitivity of dobutamine testing was 80%, specificity 83%, positive predictive value 67%, and negative predictive value 91%. In conclusion, dobutamine contrast left ventriculography testing in the same session as coronary angiography predicts regional function and ejection fraction improvement after PTCA in postinfarction patients, particularly when restenosis does not develop. Q1999 by Excerpta Medica, Inc. (Am J Cardiol 1999;83:15–20)
mong the several tests introduced to assess myocardial viability, low-dose dobutamine testing is A probably the most widespread because echocardiog-
ing contrast left ventriculography could also be applied as a viability test. In this sense, the catheterization laboratory would be a unique scenario for simultaneously evaluating myocardial viability and infarction artery status, to guide the decision for using percutaneous transluminal coronary angioplasty (PTCA) in a single session. In the present study, dobutamine contrast left ventriculography, diagnostic coronary angiography, and PTCA were performed in postinfarction patients in the same session. The aim was to investigate the role of dobutamine contrast left ventriculography in predicting the improvement of ventricular function after PTCA.
1
raphy is a widely available and relatively inexpensive imaging modality. Low-dose dobutamine echocardiography examines the contractile reserve in the infarcted dysfunctional area,2 the improvement of contractility during dobutamine infusion indicates contractile reserve, which in turn suggests viability. A number of studies show that low-dose dobutamine echocardiography allows the identification of viable stunned3–7 and hibernating8 –24 myocardium. Based on the same principles, low-dose dobutamine testing usFrom the Service of Cardiology, University Clinic Hospital, Valencia; and Cardiology Unit, Marina Baixa Hospital, Vila-Joiosa, Spain. Manuscript received May 11, 1998; revised manuscript received and accepted July 24, 1998. Address for reprints: Juan Sanchis, MD, FESC, Servicio de Cardiologı´a, Hospital Clı´nico Universitario, Blasco Iba´n˜ez 17, Valencia 46010, Spain. ©1999 by Excerpta Medica, Inc. All rights reserved.
METHODS
Patient population: The study group included patients subjected to cardiac catheterization in the subacute or chronic phase of a first myocardial infarction who fulfilled the following criteria: (1) significant abnormal wall motion extent ($15% of the myocar0002-9149/99/$–see front matter PII S0002-9149(98)00775-9
15
the right or circumflex coronary arteries (51 to 80 chords) in patients with inferior infarctions.25 Abnormal wall motion extent was defined as the number of chords displaying hypokinetic motion (,1 SD) expressed as a percentage of the total coronary territory analyzed (Figure 1). All measurements were performed by a single observer. Coronary angiography: Quantitative coronary analysis in the infarcted artery was performed using the automatic edge method. PTCA was performed by standard techniques in the same session as the diagnostic angiogram in all patients. Stents were implanted in 13 patients (46%). Dobutamine infusion: Dobutamine testing was performed before PTCA. Dobutamine infusion was started at 5 and 7.5 mg/kg/min, each dose for 4 minutes. Left ventriculography was repeated at the end of the 7.5 mg/kg/min stage. No significant changes in hemoFIGURE 1. Quantification of abnormal wall motion extent at baseline (left) and during dobutamine infusion (right) in a patient with anterior infarction. At basedynamic data were observed during doline, contractility of all chords from the myocardial territory of the left anterior debutamine infusion. The variation of scending artery (10 to 66 chords) are <1 SD from normal reference; thus, abnorabnormal wall motion extent was calmal wall motion extent in the left anterior descending artery territory is 100%. culated as the difference between abDuring dobutamine infusion, dysfunction extent was reduced to 53%. normal wall motion extent at baseline minus abnormal wall motion extent during 7.5 mg/kg/min dobutamine infudial territory of the infarcted artery) in the left ven- sion (Figure 1). Beta-blocker treatment was discontintricular angiogram, (2) severe residual stenosis ued 2 days before in all patients. ($70%) or occlusion in the infarcted artery, (3) ameIntraobserver variability: Intraobserver variability nability to PTCA in the infarcted artery, and (4) suc- was calculated by making duplicate measurements of cessful PTCA (residual stenosis ,35% with grade 3 regional ventricular function and the global ejection Thrombolysis In Myocardial Infarction [TIMI] flow fraction in 20 randomly selected ventriculograms. The and no major complications). Thirty patients were intraobserver average differences between 2 measureincluded. Mean age was 57 6 12 years. The infarction ments of abnormal wall motion extent was 6 6 4% was anterior in 25 patients (81%). A second catheter- and 3 6 1% of the ejection fraction. Thus, a signifiization 6 months later after PTCA (168 6 22 days) cant change in regional function during dobutamine was performed in all patients to evaluate the evolution infusion or at 6 months after PTCA was considered if of ventricular function and restenosis. the abnormal wall motion extent varied $15% comLeft ventriculography: Forty milliliters of contrast pared with the baseline value, and a significant change were injected at an injection speed of 12 ml/s, in the in the ejection fraction at 6 months was defined if it 30° right anterior oblique projection. The software of varied .5% (95% confidence level for detecting a an x-ray digital imaging system (Integris HM 3000, significant change). Analysis of left ventricular funcPhilips, The Netherlands) was used for global and tion was blinded. regional left ventriculogram analysis. Global ejection Statistical analysis: Values are expressed as mean 6 fraction was calculated by the area-length method. SD. Continuous variables were compared by the Centerline chord motion analysis was used to quanti- paired or unpaired t test. Categorical variables were tatively assess regional left ventricular function.25 In compared by the chi-square test. Relation between this technique, endocardial motion is measured along continuous variables was evaluated by linear regres100 chords constructed perpendicular to a centerline. sion analysis. The motion of each chord is normalized by the enddiastolic circumference to yield a fractional shorten- RESULTS ing. This value is then converted into units of SD from Evolution of regional function after PTCA: Mean abthe normal mean motion of each chord as derived normal wall motion extent in the first ventricular anfrom a normal reference population. Wall motion was giogram before angioplasty was 84 6 21%. It deanalyzed in the distribution territory of the left anterior creased 6 months later following PTCA (70 6 29%, descending artery (10 to 66 chords) in patients with p 5 0.0001). Ten patients had a significant reduction anterior infarctions, and in the distribution territory of ($15%) of abnormal wall motion extent at 6 months. 16
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FIGURE 2. Individual data of regional ventricular function in patients with and without improvement after PTCA (in the subgroups with and without restenosis) at baseline (B), with dobutamine (D), and after PTCA (P).
TABLE I Sensitivity (SE), Specificity (SP), Positive Predictive Value (PPV), and Negative Predictive Value (NPV) of Dobutamine Testing for Detecting a Significant Reduction of Abnormal Wall Motion Extent After PTCA, in the Global Group of Patients and in the Subgroup Without Restenosis
Global group No restenosis
SE
SP
PPV
NPV
80% 88%
84% 92%
67% 88%
89% 92%
Patients with and without improvement after PTCA did not differ in age (58 6 11 vs 56 6 12 years), anterior location of infarction (8% to 80% vs 18% to 90%), presence of angina (2% to 20% vs 11% to 55%), or in the baseline extent of dysfunction (75 6 25% vs 87 6 18%, NS). Figure 2 shows individual data of regional ventricular function in patients with and without improvement after PTCA (in the subgroups with and without restenosis) at baseline, with dobutamine, and after PTCA. ROLE OF DOBUTAMINE TESTING: Abnormal wall motion extent decreased during dobutamine infusion (83 6 21% vs 66 6 33%, p 5 0.0001). The reduction of dysfunction extent after PTCA correlated with the response to dobutamine (r 5 0.54, p 5 0.002, B 5 0.41 [0.16 to 0.66]). Twelve patients showed significant wall motion improvement ($15%) with dobutamine; in 8 of them (67%) contractility improved after PTCA (p 5 0.006). On the other hand, in 16 of 18 nonresponders (89%) to dobutamine, contractility likewise did not significantly change after PTCA. Dobutamine testing had a 80% sensitivity, 84% specificity, 67% positive predictive value, and 89% negative predictive value in predicting regional function response after PTCA (Table I).
ROLE OF RESTENOSIS: Nine patients had restenosis at 6 months (stenosis $50% in the previously dilated lesion). Abnormal wall motion extent decreased after PTCA in the subgroup without restenosis (79 6 24 vs 63 6 31, p 5 0.0001), but this decrease did not reach statistical significance in the subgroup with restenosis (93 6 7 vs 85 6 13, NS). In the subgroup of 12 patients with a positive response to dobutamine, regional function increased in 7 of 8 patients without restenosis but in only 1 of the 4 patients with restenosis (p 5 0.1). SUBGROUP WITHOUT RESTENOSIS: The improvement of regional wall motion after PTCA showed a stronger correlation to the improvement with dobutamine (r 5 0.72, p 5 0.0001, B 5 0.62 [0.33 to 0.90]) (Figure 3). Abnormal wall motion extent diminished more in patients with contractile reserve (30 6 12%, n 5 8) than in patients without contractile reserve (7 6 14%, n 5 13, p 5 0.002). Seven of the 8 patients with a positive response to dobutamine showed a significant improvement after PTCA (p 5 0.001) (Figure 3); on the other hand, 12 of the 13 nonresponders (92%) to dobutamine likewise did not exhibit wall motion improvement after PTCA. Low-dose dobutamine testing showed a 88% sensitivity, 92% specificity, 88% positive predictive value, and 92% negative predictive value in predicting the evolution of regional wall motion after PTCA (Table I). Evolution of the ejection fraction after PTCA: For analysis of the evolution of the ejection fraction, 5 patients with baseline normal and/or high ejection fractions (.60%) were excluded, because an improvement in global ejection fraction after revascularization was not to be expected in these patients despite regional function improvement. The mean left ventricular ejection fraction was 48 6 7% before PTCA and 50 6 11% (NS) after PTCA. The improvement of the ejection fraction borderline correlated with the response to dobutamine (r 5 0.36, p 5 0.08). The ejection fraction improved significantly (.5%) after PTCA in 6 patients. ROLE OF DOBUTAMINE TESTING: Among the 9 responders to dobutamine, the ejection fraction increased in 4 (45%) and did not change in 5 (55%), whereas in the 16 nonresponders to dobutamine, the ejection fraction increased after PTCA in 2 (12%) and did not vary significantly in 14 (88%) (p 5 0.1). Dobutamine testing showed a 67% sensitivity, 74% specificity, 44% positive predictive value, and 88% negative predictive value in predicting the variation of the ejection fraction after PTCA (Table II). SUBGROUP WITHOUT RESTENOSIS: As in the case of regional function, the accuracy of dobutamine testing increased in the subgroup of 17 patients without restenosis. The improvement of the ejection fraction after PTCA correlated to the reduction of abnormal wall motion extent during dobutamine infusion (r 5 0.63, p 5 0.007, B 5 0.19 [0.06 to 0.32]) (Figure 4). The ejection fraction increased more in patients with contractile reserve (8 6 5%, n 5 6) than in patients without contractile reserve (0.1 6 5%, n 5 11, p 5 0.02). In 4 of the 6 responders to dobutamine, but in
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FIGURE 3. Regression line between the reduction of abnormal wall motion extent (AWE) during dobutamine infusion (x-axis) and the reduction of abnormal wall motion extent 6 months after PTCA (y-axis) in the subgroup of patients without restenosis. There was a significant correlation (r 5 0.72, p 5 0.0001). The cut-off lines corresponding to a significant dysfunction extent reduction (15%) are traced with dotted lines. Seven of the 8 patients with a positive response to dobutamine showed significant improvement after PTCA (p 5 0.001); on the other hand, 12 of the 13 nonresponders (92%) to dobutamine likewise exhibited no wall motion improvement after PTCA. In some cases improvement after PTCA is greater than improvement with dobutamine; conceivably, the presence of a severe coronary stenosis could limit the response to dobutamine.
TABLE II Sensitivity (SE), Specificity (SP), Positive Predictive Value (PPV), and Negative Predictive Value (NPV) of Dobutamine Testing for Detecting a Significant Increase in Ejection Fraction After PTCA, in the Global Group of Patients and in the Subgroup Without Restenosis
Global group No restenosis
SE
SP
PPV
NPV
67% 80%
74% 83%
44% 67%
88% 91%
only 1 of the 11 nonresponders (p 5 0.05), the ejection fraction increased significantly after PTCA. Dobutamine testing had a 80% sensitivity, 83% specificity, 67% positive predictive value, and 91% negative predictive value (Table II).
DISCUSSION The results of this study indicate that the assessment of contractile reserve in the infarction area via low-dose dobutamine contrast left ventriculography is an accurate test for predicting the improvement of regional function and global ejection fraction after PTCA, particularly when restenosis does not develop during follow-up.
allows the interventional cardiologist to analyze myocardial viability in the same session as coronary angiography, and consequently, it can be a helpful test for deciding to use subsequent PTCA. Additional advantages are the optimal definition of the endocardial border and the quantification of regional ventricular function. Its main limitation is that, because of the risk of volume overload in performing multiple angiograms, a single dose of dobutamine can be checked; in echocardiographic studies, however, different protocols with single or multiple dobutamine doses have been used. The balance between contractile and coronary reserves determines the response to dobutamine. Wall motion may improve at low dobutamine doses but worsen by ischemia at high doses, this being the so-called “biphasic response.”20,22 Contractility worsening usually appears at .20 mg/kg/min, and rarely at low doses,20,22 such those used in the present study.
Prediction of regional function improvement after PTCA: Despite the potential limitation
of the ischemic response masking contractile reserve, analysis of pooled data from studies that have evaluated low-dose dobutamine echocardiography indicate that this technique adequately detects recovery of contractile function after revascularization, with a mean sensitivity of 84% and a mean specificity of 81%.26 These values are concordant with our results of 80% sensitivity and 84% specificity when analyzing the global group of patients. However, in the subgroup of patients without restenosis, sensitivity increased to 88% and specificity to 92%. Most of the echocardiographic studies do not perform angiographic control at follow-up; therefore, vessel or graft stenosis or occlusion can underestimate the specificity of the technique. Our results suggest that the accuracy of lowdose dobutamine testing can be higher than previously reported in the subset of successfully revascularized patients. Prediction of ejection fraction improvement after PTCA: Meluzin et al,27 obtained a strong linear corre-
that contractile reserve elicited by low-dose dobutamine testing using echocardiography is a useful tool in predicting spontaneous recovery of postinfarction stunned myocardium,3–7 and improvement after revascularization of hibernating myocardium.8 –24 The present study assesses myocardial viability by dobutamine contrast left ventriculography. This technique
lation (r 5 0.90) between the increment in regional wall motion score index during dobutamine infusion and the improvement in the ejection fraction after bypass surgery or PTCA. Vanoverschelde et al23 showed that dobutamine echocardiography had a sensitivity of 84% and specificity of 77% in predicting ejection fraction improvement after revascularization. We have found a weak correlation (r 5 0.36) between the response to dobutamine and the increase in ejection fraction after PTCA in the global group, although the correlation improved (r 5 0.63) in the subgroup of patients without restenosis. Sensitivity and specificity for detecting the ejection fraction recovery after
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Dobutamine contrast left ventricular angiogram as viability test: A number of studies have demonstrated
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2. Bolli R, Zhu WX, Myers ML, Hartley CJ, Roberts R.
Beta-adrenergic stimulation reverses postischaemic myocardial dysfunction without producing subsequent functional deterioration. Am J Cardiol 1985;56:946 – 948. 3. Pierard LA, De Landsheere ChM, Berthe Ch, Rigo P, Kulbertus HE. Identification of viable myocardium by echocardiography during dobutamine infusion in patients with myocardial infarction after thrombolytic therapy: comparison with positron emission tomography. J Am Coll Cardiol 1990;15:1021–1031. 4. Smart SC, Sawada S, Ryan Th, Segar D, Atherton L, Berkovitz K, Bourdillon PDV, Feigenbaum H. Lowdose dobutamine echocardiography detects reversible dysfunction after thrombolytic therapy of acute myocardial infarction. Circulation 1993;88:405– 415. 5. Salustri A, Elhendy A, Garyfallydis P, Ciavatti M, Cornel JH, Folkert JtC, Boersma E, Gemelli A, Roelandt JRTC, Fioretti PM. Prediction of improvement of ventricular function after first acute myocardial infarction using low-dose dobutamine stress echocardiography. Am J Cardiol 1994;74:853– 856. 6. Watada H, Ito H, Oh H, Masuyama T, Aburaya M, Hori M, Iwakura M, Higashino Y, Fujii K, Minamino T. Dobutamine stress echocardiography predicts reversFIGURE 4. Regression line between the reduction of abnormal wall motion extent ible dysfunction and quantifies the extent of irreversibly (AWE) during dobutamine infusion (x-axis) and the increase in ejection fraction (EF) 6 damaged myocardium after reperfusion of anterior months after PTCA (y-axis) in the subgroup of patients without restenosis. There was myocardial infarction. J Am Coll Cardiol 1994;24:624 – a significant correlation (r 5 0.63, p 5 0.007). The cut-off lines corresponding to a 630. significant dysfunction extent reduction (15%) and to a significant ejection fraction 7. Sanchis J, Mun˜oz J, Chorro FJ, Insa L, Egea S, Bodı´ increment (5%) are traced with dotted lines. The ejection fraction significantly inV, Lla´cer A, Lo´pez Merino V. Low-dose dobutamine creased after PTCA in 4 of the 6 responders to dobutamine, but in only 1 of the 11 echocardiography identifies stunned myocardium after nonresponders (p 5 0.05). thrombolytic treatment for acute myocardial infarction. Int J Cardiol 1996;53:5–13. 8. Barilla F, Gheorghiade M, Alam M, Khaja F, Goldstein S. Low-dose dobutamine in patients with acute PTCA were lower than previously reported in echo- myocardial infarction identifies viable but not contractile myocardium and prethe magnitude of improvement in wall motion abnormalities in response to cardiographic studies (67% and 74% for the global dicts coronary revascularization. Am Heart J 1991;122:1522–1531. group, and 80% and 75% for the restenosis subgroup). 9. Cigarroa CG, deFilippi Ch, Brickner E, Alvarez LG, Wait MA, Graybun PA. Although the negative predictive value was very high Dobutamine stress echocardiography identifies hibernating myocardium and prerecovery of left ventricular function after coronary revascularization. Cir(88% for the global group and 91% for restenosis dicts culation 1993;88:430 – 436. subgroup), the positive predictive value was low (44% 10. Marzullo P, Parodi O, Reisenhofer B, Sambucetti G, Picano E, Distante A, A, L’Abbate A. Value of rest thallium-201/technetium-99m sestamibi for the whole group and 67% for the restenosis sub- Gimelli scans and dobutamine echocardiography for detecting myocardial viability. Am J group). A significant recovery of the ejection fraction Cardiol 1993;71:166 –172. after PTCA requires wall motion improvement great 11. La Canna G, Alfieri O, Giubbini R, Gargano M, Ferrari R, Visioli O. during the infusion of dobutamine for identification of reversenough to have a repercussion upon global ventricular Echocardiography ible dysfunction in patients with chronic coronary artery disease. J Am Coll function. In this sense, although dobutamine contrast Cardiol 1994;23:617– 626. left ventriculography testing adequately detects re- 12. Perrone-Filardi P, Pace L, Prastaro M, Piscione F, Betocchi S, Squame F, Vezzuto P, Soricelli A, Indolfi C, Salvatore M, Chiariello M. Dobutamine gional function recovery after PTCA, its accuracy echocardiography predicts improvement of hypoperfused dysfunctional myocarseems lower in predicting ejection fraction improve- dium after revascularization in patients with coronary artery disease. Circulation 1995;91:2556 –2565. ment. 13. Voci P, Bilotta F, Caretta Q, Mercanti C, Marino B. Low-dose dobutamine Clinical implications: Severe residual stenosis in the echocardiography predicts the early response of dysfunctioning myocardial seginfarct-related artery supplying a dysfunctional in- ments to coronary artery bypass grafting. Am Heart J 195;129:521–526. 14. Arnesse M, Cornel JH, Salustri A, Maat APWM, Elhendy A, Reijs AEM, farcted area is not unusual in the catheterization lab- Cate FJT, Keane D, Balk AHMM, Roelandt JRTC, Fioretti PM. Prediction of oratory. Although routine PTCA might be justified improvement of regional left ventricular function after surgical revascularization. comparison of low-dose dobutamine echocardiography with 201Tl singlewith the aim of promoting regional function recovery Aphoton emission computed tomography. Circulation 1995;91:2748 –2752. or preventing ventricular remodeling, in the absence 15. deFilippi Ch, Willet D, Irani WN, Eichhorn EJ, Velasco CE, Grayburn PA. of documented recurrent ischemia the benefit of Comparison of myocardial contrast echocardiography and low-dose dobutamine echocardiography in predicting recovery of left ventricular function after PTCA is controversial. Dobutamine contrast left ven- stress coronary revascularization in chronic ischaemic heart disease. Circulation 1995; triculography can be a time-saving tool for guiding the 92:2863–2868. 16. Haque T, Furukawa T, Takahashi M, Kinoshita M. Identification of hiberdecision to use immediate subsequent PTCA. nating myocardium by dobutamine stress echocardiography: comparison with Study limitations: The method used for ventricular thalium-201 reinjection imaging. Am Heart J 1995;130:553–563. function analysis in the present study quantifies the 17. Chan RKM, Lee KJ, Calafiore P, Berlangieri SU, McKay WJ, Tonkin AM. of dobutamine echocardiography and positron emission tomography whole extent of dysfunction (total number of chords Comparison in patients with chronic ischaemic left ventricular dysfunction. J Am Coll Cardiol showing abnormal motion in the infarction artery ter- 1996;27:1601–1607. Picano E, Ostojic M, Varga A, Sicari R, Djordjevic-Dikic A, Nedeljkovic I, ritory). This index does not allow the differentiation of 18. Torres M. Combined low dose dipyridamole-dobutamine stress echocardiography hypokinetic and akinetic segments. to identify myocardial viability. J Am Coll Cardiol 1996;27:1422–1428. 19. Le Feuvre CI, Baubion N, Aubry N, Metzger JP, Vernejoul P, Vacheron A. Assessment of reversible dyssynergic segments after acute myocardial infarction: dobutamine echocardiography v thalium-201 single photon emission computed 1. Dilsizian V, Bonow RO. Current diagnostic techniques of assessing myocartomography. 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