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Myocardial perfusion and angiographic correlations in patients with ST-segment elevation during dobutamine stress perfusion imaging
Myocardial perfusion and angiographic correlations in patients with ST-segment elevation during dobutamine stress perfusion imaging Joseph R. Lee, MD, Zuo-Xiang He, MD, Habib Dakik, MD, and Mario S. Verani, MD, FACC Background. There is scanty information on the angiographic and myocardial perfusion correlates of dobutamine-induced ST-segment elevation. Methods and Results. We studied 39 patients who exhibited ST-segment elevation during dobutamine perfusion tomography and had recent coronary angiography performed (ie, within 3 months of the dobutamine study). Baseline characteristics, extent of coronary artery disease, relationship of Q waves to ST-segment elevation, ischemic burden, and angiographic findings were assessed. Twenty-nine patients (74%) had prior myocardial infarction, and 77% had abnormal Q waves at baseline. Ninety-three percent of patients had abnormal perfusion imaging. Eighty percent of patients had multivessel coronary artery disease. The left ventricular ejection fraction by contrast ventriculography was 35% ± 7% (mean ± SD), the perfusion defect size was 32% ± 15%, and 73% of patients had some degree of myocardial ischemia. A predominance of ischemia (>50% reversibility) occurred in 38% of patients with Q waves and in 70% of those without Q waves. There was also good agreement between the site of ST-segment elevation and the site of ischemia by perfusion imaging (79%) and between the site of ST-segment elevation and the location of the vessel with significant coronary stenosis (95%). Conclusions. Patients with dobutamine-induced ST-segment elevation have a depressed left ventricular ejection fraction, a high frequency of multivessel disease, and markedly abnormal myocardial perfusion tomography. In patients with ST-segment elevation and abnormal Q waves, substantial scarring and superimposed ischemia coexist, whereas in patients without Q waves, ST-segment elevation usually denotes severe ischemia. (J Nucl Cardiol 2001;8:365-70.) Key Words: Dobutamine single photon emission computed tomography • ST-segment elevation • myocardial ischemia • myocardial infarction
Exercise-induced ST-segment elevation has been extensively studied in the past,1-5 with a reported prevalence of approximately 5%. A prevalence of 2.8% was previously reported from our laboratory.6 The occurrence of exercise-induced ST-segment elevation is usually associated with prior myocardial infarction, left ventricular aneurysm, coronary artery spasm, or critical coronary From the Section of Cardiology, Baylor College of Medicine, and The Methodist Hospital, Houston, Tex. Received for publication June 7, 2000; final revision accepted Dec 18, 2000. Reprint requests: Mario S. Verani, MD, FACC, Professor of Medicine, Baylor College of Medicine, Director, Nuclear Cardiology, The Methodist Hospital, 6550 Fannin, SM677, Houston, TX 77030; [email protected]. Copyright © 2001 by the American Society of Nuclear Cardiology. 1071-3581/2001/$35.00 + 0 43/1/114236 doi:10.1067/mnc.2001.114236
artery disease. There is some controversy regarding whether stress-induced ST elevation that occurs in leads with Q waves (denoting previous infarction) is a marker of myocardial ischemia. A highly respected major textbook of cardiology7 states that exercise-induced STsegment elevation that occurs in leads exhibiting Q waves “rarely indicates myocardial ischemia.” However, Fox et al8 reported 32 patients with Q waves and exercise-induced ST-segment elevation, of whom 58% no longer had ST-segment elevation after coronary artery bypass surgery. Similarly, Dunn et al9 showed that the majority of their 25 patients with previous Q-wave myocardial infarction had evidence of scintigraphic ischemia. Others have recently suggested that STsegment elevation that occurs in leads with Q waves may be the result of transient ischemia of viable myocardium, as verified by positron emission tomography and technetium 99m sestamibi perfusion imaging.10,11 365
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Lee et al Patients with dobutamine-induced ST-segment elevation
Table 1. Baseline characteristics (N = 39)
Characteristic
No. of patients (%)
History of MI Recent MI History of PTCA History of CABG Diabetes mellitus Hypertension Hypercholesterolemia History of tobacco use Peripheral vascular disease
29 8 18 16 12 22 12 19 5
(74) (20) (46) (41) (31) (56) (31) (49) (13)
In light of this controversy, and in view of the fact that dobutamine is now commonly used to provoke myocardial ischemia, it is germane to characterize both myocardial perfusion and angiographic findings in patients with dobutamine-induced ST-segment elevation. Accordingly, we performed a retrospective analysis from our large database to assess the myocardial perfusion and coronary angiographic correlates of dobutamine-induced ST-segment elevation. METHODS Patient Population Between 1989 and 1995, 1012 patients underwent dobutamine stress perfusion imaging with single photon emission computed tomography (SPECT) in our laboratory.12 Sixty patients (5.9%) had ST-segment elevation during testing. Of these, 39 had coronary angiography performed within 3 months of the dobutamine stress test and were selected for this study. The 21 remaining patients were excluded because they did not have catheterization within 3 months of the dobutamine test (n = 8), because they had intervening revascularization between catheterization and the scan (n = 9), or because the angiograms could not be retrieved (n = 4). The reasons for performing the test in the study cohort were as follows: chest pain (54%), preoperative evaluation (15%), follow-up after coronary angioplasty (13%), follow-up after myocardial infarction (10%), and dyspnea (7%). The following medications were used by the patients: nitrates (49%), calcium channel blockers (44%), digoxin (21%), angiotensinconverting enzyme inhibitors (18%), diuretics (15%), and βblockers (7%). All of the patients were unable to perform an exercise test and had contraindications to pharmacologic vasodilation with adenosine or dipyridamole, such as a history of asthma, bronchospasm, advanced atrioventricular block without a pacemaker, known allergy to either medication, or recent ingestion of theophylline compounds (<12 hours before testing).
Dobutamine Infusion Protocol Dobutamine was infused at incremental doses of 10, 20, 30, and 40 µg/kg/min at 3-minute intervals. After 1 minute of the maximum tolerated dobutamine dose, thallium 201 (in
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85% of the cohort) or Tc-99m–labeled sestamibi (in 15% of the cohort) was injected, and the dobutamine infusion was continued for 2 more minutes. Patients given Tl-201 were imaged beginning 10 minutes after stress and 4 hours later. Those given Tc-99m sestamibi were imaged 45 to 60 minutes after dobutamine infusion; they were reinjected at rest 4 hours later and then reimaged 1 hour later. Patients who weighed 90 kg or more and women with large breasts (bra cup size D or larger) were preferentially given Tc-99m sestamibi, whereas other patients received Tl-201. Heart rate, blood pressure, and 12-lead electrocardiography (ECG) were monitored continuously and recorded every minute throughout the stress and recovery periods. During dobutamine infusion, ST-segment elevation of 1.0 mm or greater in 2 contiguous leads in excess of any elevation present at baseline was noted and recorded. The presence and site of Q waves and location of leads with ST-segment elevation were also recorded.
Dobutamine Myocardial SPECT Myocardial perfusion SPECT was performed as previously reported from our laboratory.13 Tomograms were interpreted qualitatively and quantitatively by an experienced nuclear cardiologist. The tomographic images were processed with standard computer-generated polar maps to quantify the total left ventricular perfusion defect size and extent of scar and ischemia. The percentage of ischemia within the infarct zone was computer-quantified as follows: the number of pixels exhibiting an increase in tracer concentration in the rest or redistribution images was divided by the total number of abnormal pixels within the infarct area, and the result was multiplied by 100. The vascular territories of the 3 major coronary arteries were assigned as previously reported.13
Angiographic Evaluation Selective coronary angiography was performed with standard techniques and views. Angiograms were read by 2 independent investigators. Coronary stenosis of 70% or greater of the luminal diameter was considered significant. The left ventricular ejection fraction was calculated from the 30° right anterior oblique contrast left ventriculogram, along with a qualitative assessment of segmental wall motion in the anterior, apical, and inferior segments.
Statistical Analysis Unless otherwise noted, continuous variables are presented as mean ± SD. Perfusion and ECG findings were compared by paired t tests. A P value < .05 was considered significant.
RESULTS Patient Cohort Characteristics The mean age of the study group was 63 ± 15 years, and 66% were men. Baseline characteristics are shown in Table 1.
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Table 2. Comparison of dobutamine myocardial perfusion findings in patients with and without ST-segment elevation
Abnormal SPECT Defect size (% LV) Reversible defects
With ST elevation
Without ST elevation
P value
37/39 (93%) 32 ± 15 29/39 (74%)
447/952 (47%) 21 ± 14 314/952 (33%)
<.001 .01 <.001
Baseline ECG and Dobutamine Stress Test Normal sinus rhythm was present in 97% of the study cohort, and 77% had pathologic Q waves on baseline ECG. ST-segment elevation and depression were present at baseline in 26% and 8% of patients, respectively. The maximum tolerated dobutamine dose was 37 ± 12 µg/kg/min, and the infusion time was 12 ± 3 minutes. The amount of ST-segment elevation above baseline was 2.0 ± 0.5 mm, and the mean time to maximum STsegment elevation was 11 ± 3 minutes. Only 2 of the 39 (5%) patients were given atropine for inadequate heart rate response to dobutamine. Myocardial Perfusion SPECT Ninety-three percent of patients had abnormal SPECT results, with 28% having predominantly irreversible defects, 23% balanced reversible and irreversible defects, 20% predominantly reversible defects, and another 20% only irreversible defects. Only 1 patient (2.0%) showed a completely reversible perfusion defect. Comparison of Dobutamine SPECT Results in Patients With and Without ST-segment Elevation Table 2 summarizes the SPECT results in patients with and without ST-segment elevation. Compared with patients without ST-segment elevation, those with STsegment elevation on dobutamine stress were more likely to have abnormal SPECT results (P < .001), larger defect size (P = .01), and a significantly higher percentage of reversible defects (P < .001). Angiographic Results The majority of patients with ST-segment elevation (80%) had multivessel coronary artery disease; only 20% had single-vessel disease. Total left anterior descending artery occlusion occurred in 56% of patients. Of the 15 patients with a bypass to the left anterior descending artery, 40% had left internal thoracic artery grafts, and all grafts were patent. Angiographic collaterals were visual-
ized in 44% of patients. The left ventricular ejection fraction by contrast angiography was 35% ± 7%. Relationship of Q Waves to ST-segment Elevation, Ischemic Burden, and Angiographic Results Table 3 shows the relationship between the site of Q waves and the site of ST elevation, amount of ischemic burden, and angiographic findings. The STsegment elevation occurred in leads with pathologic Q waves in 67% of patients and in leads without Q waves in 33%. Predominant ischemia (defined as >50% of defect reversibility) occurred in 38% of patients with Q waves. In patients without Q waves, a higher percentage (70%) had evidence of substantial ischemia. Patients with Q waves were more likely to have singlevessel disease and a lower ejection fraction. Relationship Between Site of ST-segment Elevation and Site of Ischemia by Perfusion Imaging Table 4 shows the agreement between the site of STsegment elevation on dobutamine stress ECG and the site of ischemia as noted on perfusion imaging. Of the 29 patients with ST-segment elevation who showed some degree of myocardial ischemia, 23 (79%) had STsegment elevation in leads that matched the area of ischemia. Relationship Between Site of ST-segment Elevation and Site of Significant Coronary Stenosis Table 5 shows the agreement between the site of STsegment elevation and the site of significant coronary artery stenosis. There was a 95% agreement between these 2 parameters. Two patients had no significant stenoses noted in their bypass grafts despite having STsegment elevation on dobutamine stress testing. Both had a history of remote myocardial infarction and had akinetic wall motion in the previously infarcted myocardial segment.
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Table 3. Relationship between Q waves, ST-segment elevation, ischemic burden, and angiographic results
ST-segment elevation Substantial ischemia* 1-Vessel disease 2-Vessel disease 3-Vessel disease Ejection fraction
With Q waves
Without Q waves
P value
26/39 (67%) 11/29 (38%) 7/29 (24%) 11/29 (38%) 11/29 (38%) 34%
13/39 (33%) 7/10 (70%) 1/10 (10%) 3/10 (30%) 6/10 (60%) 44%
.02 .01 .04 .3 .1 .03
*Defined as >50% reversibility.
Table 4. Relationship between site of ST-segment elevation and site of ischemia by perfusion imaging
Site of ST elevation Site of ischemia by perfusion imaging Anterior Inferior Lateral Anterior Inferior Lateral
10 2 –
2 9 1
– 1 4
Data for 29 patients with ischemia are shown, with 79% (23/29) agreement.
Table 5. Relationship between site of ST-segment elevation and site of significant coronary stenosis
Site of ST elevation Site of significant coronary stenosis LAD RCA CFx
LAD
RCA
CFx
13 1 –
1 16 –
– – 6
Data for 37 of 39 patients with ST elevation and at least 1 significant coronary stenosis are shown, with 95% (35/37) agreement. LAD, Left anterior descending artery; RCA, right coronary artery; CFx, circumflex coronary artery.
DISCUSSION It is not known whether ST-segment elevation that occurs during dobutamine stress testing has a similar meaning as that which occurs during exercise stress testing. In this study we have described the electrocardiographic, myocardial perfusion, and angiographic correlates of patients with ST-segment elevation during dobutamine stress testing. Dobutamine was administered
in high doses in a deliberate attempt to provoke myocardial ischemia in our patients. The results of dobutamine stress testing in more than 1000 patients have recently been reported from our laboratory.12 Noncardiac side effects were common but were generally well tolerated. Nonsustained ventricular tachycardia occurred in 4.2% of patients but was also well tolerated. ST-segment elevation occurred in 6% of patients and formed the basis of this detailed report. Previous Studies In patients without previous myocardial infarction, exercise-induced ST elevation denotes extensive ischemia and severe coronary artery stenosis.6,14 Ricci et al15 studied patients an average of 10 days after uncomplicated Q-wave myocardial infarction and showed that dobutamine-induced ST elevation was not associated with a higher incidence and extent of myocardial ischemia or viability, as measured by stress echocardiography. The authors, however, did not have correlative angiographic or perfusion data. Elhendy et al16 correlated dobutamineinduced ST-segment elevation that occurred in leads with Q waves to myocardial perfusion findings and found a similar prevalence of ischemia, regardless of ST-segment elevation (53% with ST-segment elevation vs 48% without ST-segment elevation). Correlative angiographic data, however, were incomplete. Lombardo et al17 suggested that ST-segment elevation that occurs in leads with Q waves during low-dose dobutamine infusion in patients with previous myocardial infarction is highly specific for potentially reversible contractile dysfunction, as assessed by echocardiography. However, there were no myocardial perfusion or angiographic data available in that study. Present Study Compared with patients at our institution who did not have ST-segment elevation during dobutamine stress, those
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with ST-segment elevation had a higher percentage of abnormal perfusion scans. To a large extent, this was associated with a high prevalence of prior infarction in these patients. The overall perfusion defect size was significantly larger in patients with ST-segment elevation during dobutamine stress (Table 2), and most had some evidence of myocardial ischemia. Thus, in our patient cohort, ST-segment elevation was a sign of a large perfusion defect with a high likelihood of at least some degree of ischemia. A comparison between patients with and those without pathologic Q waves revealed that ST-segment elevation occurred more commonly in the former, whereas predominant ischemia (>50% reversibility) occurred more often in the latter (Table 3). These findings are consistent with those of previous reports of patients with and without old myocardial infarction.6,8,9,18 In our study substantial dobutamine-induced ischemia occurred in 38% of patients with Q waves. This is similar to the occurrence of exercise-induced ischemia reported by Dunn et al9 and Lahiri et al18 (52% and 36%, respectively). ST-segment elevation in leads without Q waves is usually caused by severe myocardial ischemia, whereas ST elevation in leads with Q waves is believed to be caused by either regional wall motion abnormalities or peri-infarction ischemia. As shown in Table 3, in comparison with patients with pathologic Q waves, those without Q waves had a higher percentage of multivessel disease (90% vs 78%, respectively) and a higher angiographic ejection fraction (44% vs 34%, respectively), signifying more extensive coronary artery disease and more myocardium at risk but less LV dysfunction. The myocardial perfusion and angiographic correlates in patients displaying ST-segment elevation during dobutamine stress testing have not been previously reported. We found good agreement between the site of ST-segment elevation and (1) the site of ischemia by perfusion imaging (Table 4) and (2) the site of significant coronary stenosis (Table 5). In patients with prior myocardial infarction, exercise-induced ST elevation has not been as consistent in localization of the sites of coronary stenosis8,9; however, there is a much better correlation between the site of ST-segment elevation and the site of perfusion abnormality.9,11,18 This inconsistency may be due in part to the fact that fewer ECG leads were used to monitor the stress test in older studies. In one study,16 dobutamine-induced ST elevation was predictive of significant disease in the corresponding coronary artery; however, only 48% of the patients with ST-segment elevation underwent coronary angiography. The authors nonetheless concluded that ST-segment elevation in patients with a history of myocardial infarction was not specific for ischemia, as assessed by perfusion imaging or stress echocardiography.
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CONCLUSION Our results show that patients with dobutamineinduced ST-segment elevation have a depressed ejection fraction, a high likelihood of multivessel disease, and markedly abnormal myocardial perfusion. Compared with patients without ST-segment elevation, these patients have larger perfusion defects and often have ischemia on perfusion imaging. Patients with Q waves and ST-segment elevation have prominent scarring and variable amounts of superimposed ischemia on perfusion imaging, which is substantial in 38% of patients. Conversely, patients without Q waves have a high incidence (70%) of predominant ischemia, and 90% of them have multivessel disease.
References 1. Nosratian FJ, Froelicher VF. ST elevation during exercise testing. Am J Cardiol 1989;63:986-8. 2. Chahine RA, Raizner AE, Ishimori T. The clinical significance of exercise-induced ST-segment elevation. Circulation 1976;54:209-13. 3. Bruce RA, Gey GO, Cooper MN, Fisher LD, Peterson DR. Seattle heart watch: initial clinical, circulatory and electrocardiographic responses to maximal exercise. Am J Cardiol 1974;33:459-69. 4. de Feyter PJ, Majid PA, van Eenige MJ, Wardeh R, Wempe FN, Roos JP. Clinical significance of exercise-induced ST-segment elevation. Correlative angiographic study in patients with ischemic heart disease. Br Heart J 1981;46:84-92. 5. Bruce RA, Fisher LD, Pettinger M, Weiner DA, Chaitman BR. STsegment elevation with exercise: a marker of poor ventricular function and prognosis. Coronary Artery Surgery Study (CASS) confirmation of Seattle Heart Watch results. Circulation 1988;77:897-905. 6. Gallik DM, Mahmarian JJ, Verani MS. Therapeutic significance of exercise-induced ST-segment elevation in patients without previous myocardial infarction. Am J Cardiol 1993;72:1-7. 7. Chaitman BR. Exercise stress testing. In: Braunwald E, editor. Heart disease: a textbook of cardiovascular medicine. Philadelphia: Saunders; 1997. p. 153-76. 8. Fox KM, Jonathan A, Selwyn A. Significance of exercise induced ST segment elevation in patients with previous myocardial infraction. Br Heart J 1983;49:15-9. 9. Dunn RF, Bailey IK, Uren R, Kelly DT. Exercise-induced ST-segment elevation: correlation of thallium-201 myocardial perfusion scanning and coronary arteriography. Circulation 1980;61:989-95. 10. Margonato A, Chierchia SL, Xuereb RG, Xuereb M, Fragasso G, Capelletti A, et al. Specificity and sensitivity of exercise-induced ST segment elevation for detection of residual viability: comparison with fluorodeoxyglucose and positron emission tomography. J Am Coll Cardiol 1995;25:1032-8. 11. Margonato A, Ballarotto C, Bonetti F, Cappelletti A, Sciammarella M, Cianflone D, et al. Assessment of residual tissue viability by exercise testing in recent myocardial infarction: comparison of the electrocardiogram and myocardial perfusion scintigraphy. J Am Coll Cardiol 1992;19:948-52. 12. Dakik HA, Vempathy H, Verani MS. Tolerance, hemodynamic changes, and safety of dobutamine stress perfusion imaging. J Nucl Cardiol 1996;5:410-4. 13. Hays JT, Mahmarian JJ, Cochran AJ, Verani MS. Dobutamine thal-
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lium-201 tomography for evaluating patients with suspected coronary artery disease unable to undergo exercise or pharmacologic stress testing. J Am Coll Cardiol 1993;21:1583-90. 14. Candell Riera J, Castell J, Rius A, Buxeda M, Moragas G, Palet J, et al. ST segment elevation during exercise testing and perfusion scintigraphy in patients without infarction [in Spanish]. Rev Esp Cardiol 1995; 48:600-5. 15. Ricci R, Bigi R, Galati A, Bandini P, Coletta C, Fiorentini C, et al. Dobutamine-induced ST-segment elevation in patients with acute myocardial infarction and the role of myocardial ischemia, viability and ventricular dyssynergy. Am J Cardiol 1997;79:733-7. 16. Elhendy A, Geleijinse ML, Roelandt J, van Domburg RT, Cornel JH,
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TenCate FJ, et al. Evaluation by quantitative 99m-technetium MIBI SPECT and echocardiography of myocardial perfusion and wall motion abnormalities in patients with dobutamine-induced ST-segment elevation. Am J Cardiol 1995;76:441-8. 17. Lombardo A, Loperfido F, Pennestri F, Rossi E, Patrizi R, Cristinziani G, et al. Significance of transient ST-T segment changes during dobutamine testing in Q wave myocardial infarction. J Am Coll Cardiol 1996;27:599-605. 18. Lahiri A, Balasubramanian V, Millar-Craig MW, Crawley J, Raftery EB. Exercise-induced ST-segment elevation: electrocardiographic, angiographic and scintigraphic evaluation. Br Heart J 1980; 43:582-8.
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Exercise-induced ST-segment elevation has been extensively studied in the past,1-5 with a reported prevalence of approximately 5%. A prevalence of 2.8% was previously reported from our laboratory.6 The occurrence of exercise-induced ST-segment elevation is usually associated with prior myocardial infarction, left ventricular aneurysm, coronary artery spasm, or critical coronary From the Section of Cardiology, Baylor College of Medicine, and The Methodist Hospital, Houston, Tex. Received for publication June 7, 2000; final revision accepted Dec 18, 2000. Reprint requests: Mario S. Verani, MD, FACC, Professor of Medicine, Baylor College of Medicine, Director, Nuclear Cardiology, The Methodist Hospital, 6550 Fannin, SM677, Houston, TX 77030; [email protected]. Copyright © 2001 by the American Society of Nuclear Cardiology. 1071-3581/2001/$35.00 + 0 43/1/114236 doi:10.1067/mnc.2001.114236
artery disease. There is some controversy regarding whether stress-induced ST elevation that occurs in leads with Q waves (denoting previous infarction) is a marker of myocardial ischemia. A highly respected major textbook of cardiology7 states that exercise-induced STsegment elevation that occurs in leads exhibiting Q waves “rarely indicates myocardial ischemia.” However, Fox et al8 reported 32 patients with Q waves and exercise-induced ST-segment elevation, of whom 58% no longer had ST-segment elevation after coronary artery bypass surgery. Similarly, Dunn et al9 showed that the majority of their 25 patients with previous Q-wave myocardial infarction had evidence of scintigraphic ischemia. Others have recently suggested that STsegment elevation that occurs in leads with Q waves may be the result of transient ischemia of viable myocardium, as verified by positron emission tomography and technetium 99m sestamibi perfusion imaging.10,11 365
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Lee et al Patients with dobutamine-induced ST-segment elevation
Table 1. Baseline characteristics (N = 39)
Characteristic
No. of patients (%)
History of MI Recent MI History of PTCA History of CABG Diabetes mellitus Hypertension Hypercholesterolemia History of tobacco use Peripheral vascular disease
29 8 18 16 12 22 12 19 5
(74) (20) (46) (41) (31) (56) (31) (49) (13)
In light of this controversy, and in view of the fact that dobutamine is now commonly used to provoke myocardial ischemia, it is germane to characterize both myocardial perfusion and angiographic findings in patients with dobutamine-induced ST-segment elevation. Accordingly, we performed a retrospective analysis from our large database to assess the myocardial perfusion and coronary angiographic correlates of dobutamine-induced ST-segment elevation. METHODS Patient Population Between 1989 and 1995, 1012 patients underwent dobutamine stress perfusion imaging with single photon emission computed tomography (SPECT) in our laboratory.12 Sixty patients (5.9%) had ST-segment elevation during testing. Of these, 39 had coronary angiography performed within 3 months of the dobutamine stress test and were selected for this study. The 21 remaining patients were excluded because they did not have catheterization within 3 months of the dobutamine test (n = 8), because they had intervening revascularization between catheterization and the scan (n = 9), or because the angiograms could not be retrieved (n = 4). The reasons for performing the test in the study cohort were as follows: chest pain (54%), preoperative evaluation (15%), follow-up after coronary angioplasty (13%), follow-up after myocardial infarction (10%), and dyspnea (7%). The following medications were used by the patients: nitrates (49%), calcium channel blockers (44%), digoxin (21%), angiotensinconverting enzyme inhibitors (18%), diuretics (15%), and βblockers (7%). All of the patients were unable to perform an exercise test and had contraindications to pharmacologic vasodilation with adenosine or dipyridamole, such as a history of asthma, bronchospasm, advanced atrioventricular block without a pacemaker, known allergy to either medication, or recent ingestion of theophylline compounds (<12 hours before testing).
Dobutamine Infusion Protocol Dobutamine was infused at incremental doses of 10, 20, 30, and 40 µg/kg/min at 3-minute intervals. After 1 minute of the maximum tolerated dobutamine dose, thallium 201 (in
Journal of Nuclear Cardiology May/June 2001
85% of the cohort) or Tc-99m–labeled sestamibi (in 15% of the cohort) was injected, and the dobutamine infusion was continued for 2 more minutes. Patients given Tl-201 were imaged beginning 10 minutes after stress and 4 hours later. Those given Tc-99m sestamibi were imaged 45 to 60 minutes after dobutamine infusion; they were reinjected at rest 4 hours later and then reimaged 1 hour later. Patients who weighed 90 kg or more and women with large breasts (bra cup size D or larger) were preferentially given Tc-99m sestamibi, whereas other patients received Tl-201. Heart rate, blood pressure, and 12-lead electrocardiography (ECG) were monitored continuously and recorded every minute throughout the stress and recovery periods. During dobutamine infusion, ST-segment elevation of 1.0 mm or greater in 2 contiguous leads in excess of any elevation present at baseline was noted and recorded. The presence and site of Q waves and location of leads with ST-segment elevation were also recorded.
Dobutamine Myocardial SPECT Myocardial perfusion SPECT was performed as previously reported from our laboratory.13 Tomograms were interpreted qualitatively and quantitatively by an experienced nuclear cardiologist. The tomographic images were processed with standard computer-generated polar maps to quantify the total left ventricular perfusion defect size and extent of scar and ischemia. The percentage of ischemia within the infarct zone was computer-quantified as follows: the number of pixels exhibiting an increase in tracer concentration in the rest or redistribution images was divided by the total number of abnormal pixels within the infarct area, and the result was multiplied by 100. The vascular territories of the 3 major coronary arteries were assigned as previously reported.13
Angiographic Evaluation Selective coronary angiography was performed with standard techniques and views. Angiograms were read by 2 independent investigators. Coronary stenosis of 70% or greater of the luminal diameter was considered significant. The left ventricular ejection fraction was calculated from the 30° right anterior oblique contrast left ventriculogram, along with a qualitative assessment of segmental wall motion in the anterior, apical, and inferior segments.
Statistical Analysis Unless otherwise noted, continuous variables are presented as mean ± SD. Perfusion and ECG findings were compared by paired t tests. A P value < .05 was considered significant.
RESULTS Patient Cohort Characteristics The mean age of the study group was 63 ± 15 years, and 66% were men. Baseline characteristics are shown in Table 1.
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Table 2. Comparison of dobutamine myocardial perfusion findings in patients with and without ST-segment elevation
Abnormal SPECT Defect size (% LV) Reversible defects
With ST elevation
Without ST elevation
P value
37/39 (93%) 32 ± 15 29/39 (74%)
447/952 (47%) 21 ± 14 314/952 (33%)
<.001 .01 <.001
Baseline ECG and Dobutamine Stress Test Normal sinus rhythm was present in 97% of the study cohort, and 77% had pathologic Q waves on baseline ECG. ST-segment elevation and depression were present at baseline in 26% and 8% of patients, respectively. The maximum tolerated dobutamine dose was 37 ± 12 µg/kg/min, and the infusion time was 12 ± 3 minutes. The amount of ST-segment elevation above baseline was 2.0 ± 0.5 mm, and the mean time to maximum STsegment elevation was 11 ± 3 minutes. Only 2 of the 39 (5%) patients were given atropine for inadequate heart rate response to dobutamine. Myocardial Perfusion SPECT Ninety-three percent of patients had abnormal SPECT results, with 28% having predominantly irreversible defects, 23% balanced reversible and irreversible defects, 20% predominantly reversible defects, and another 20% only irreversible defects. Only 1 patient (2.0%) showed a completely reversible perfusion defect. Comparison of Dobutamine SPECT Results in Patients With and Without ST-segment Elevation Table 2 summarizes the SPECT results in patients with and without ST-segment elevation. Compared with patients without ST-segment elevation, those with STsegment elevation on dobutamine stress were more likely to have abnormal SPECT results (P < .001), larger defect size (P = .01), and a significantly higher percentage of reversible defects (P < .001). Angiographic Results The majority of patients with ST-segment elevation (80%) had multivessel coronary artery disease; only 20% had single-vessel disease. Total left anterior descending artery occlusion occurred in 56% of patients. Of the 15 patients with a bypass to the left anterior descending artery, 40% had left internal thoracic artery grafts, and all grafts were patent. Angiographic collaterals were visual-
ized in 44% of patients. The left ventricular ejection fraction by contrast angiography was 35% ± 7%. Relationship of Q Waves to ST-segment Elevation, Ischemic Burden, and Angiographic Results Table 3 shows the relationship between the site of Q waves and the site of ST elevation, amount of ischemic burden, and angiographic findings. The STsegment elevation occurred in leads with pathologic Q waves in 67% of patients and in leads without Q waves in 33%. Predominant ischemia (defined as >50% of defect reversibility) occurred in 38% of patients with Q waves. In patients without Q waves, a higher percentage (70%) had evidence of substantial ischemia. Patients with Q waves were more likely to have singlevessel disease and a lower ejection fraction. Relationship Between Site of ST-segment Elevation and Site of Ischemia by Perfusion Imaging Table 4 shows the agreement between the site of STsegment elevation on dobutamine stress ECG and the site of ischemia as noted on perfusion imaging. Of the 29 patients with ST-segment elevation who showed some degree of myocardial ischemia, 23 (79%) had STsegment elevation in leads that matched the area of ischemia. Relationship Between Site of ST-segment Elevation and Site of Significant Coronary Stenosis Table 5 shows the agreement between the site of STsegment elevation and the site of significant coronary artery stenosis. There was a 95% agreement between these 2 parameters. Two patients had no significant stenoses noted in their bypass grafts despite having STsegment elevation on dobutamine stress testing. Both had a history of remote myocardial infarction and had akinetic wall motion in the previously infarcted myocardial segment.
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Table 3. Relationship between Q waves, ST-segment elevation, ischemic burden, and angiographic results
ST-segment elevation Substantial ischemia* 1-Vessel disease 2-Vessel disease 3-Vessel disease Ejection fraction
With Q waves
Without Q waves
P value
26/39 (67%) 11/29 (38%) 7/29 (24%) 11/29 (38%) 11/29 (38%) 34%
13/39 (33%) 7/10 (70%) 1/10 (10%) 3/10 (30%) 6/10 (60%) 44%
.02 .01 .04 .3 .1 .03
*Defined as >50% reversibility.
Table 4. Relationship between site of ST-segment elevation and site of ischemia by perfusion imaging
Site of ST elevation Site of ischemia by perfusion imaging Anterior Inferior Lateral Anterior Inferior Lateral
10 2 –
2 9 1
– 1 4
Data for 29 patients with ischemia are shown, with 79% (23/29) agreement.
Table 5. Relationship between site of ST-segment elevation and site of significant coronary stenosis
Site of ST elevation Site of significant coronary stenosis LAD RCA CFx
LAD
RCA
CFx
13 1 –
1 16 –
– – 6
Data for 37 of 39 patients with ST elevation and at least 1 significant coronary stenosis are shown, with 95% (35/37) agreement. LAD, Left anterior descending artery; RCA, right coronary artery; CFx, circumflex coronary artery.
DISCUSSION It is not known whether ST-segment elevation that occurs during dobutamine stress testing has a similar meaning as that which occurs during exercise stress testing. In this study we have described the electrocardiographic, myocardial perfusion, and angiographic correlates of patients with ST-segment elevation during dobutamine stress testing. Dobutamine was administered
in high doses in a deliberate attempt to provoke myocardial ischemia in our patients. The results of dobutamine stress testing in more than 1000 patients have recently been reported from our laboratory.12 Noncardiac side effects were common but were generally well tolerated. Nonsustained ventricular tachycardia occurred in 4.2% of patients but was also well tolerated. ST-segment elevation occurred in 6% of patients and formed the basis of this detailed report. Previous Studies In patients without previous myocardial infarction, exercise-induced ST elevation denotes extensive ischemia and severe coronary artery stenosis.6,14 Ricci et al15 studied patients an average of 10 days after uncomplicated Q-wave myocardial infarction and showed that dobutamine-induced ST elevation was not associated with a higher incidence and extent of myocardial ischemia or viability, as measured by stress echocardiography. The authors, however, did not have correlative angiographic or perfusion data. Elhendy et al16 correlated dobutamineinduced ST-segment elevation that occurred in leads with Q waves to myocardial perfusion findings and found a similar prevalence of ischemia, regardless of ST-segment elevation (53% with ST-segment elevation vs 48% without ST-segment elevation). Correlative angiographic data, however, were incomplete. Lombardo et al17 suggested that ST-segment elevation that occurs in leads with Q waves during low-dose dobutamine infusion in patients with previous myocardial infarction is highly specific for potentially reversible contractile dysfunction, as assessed by echocardiography. However, there were no myocardial perfusion or angiographic data available in that study. Present Study Compared with patients at our institution who did not have ST-segment elevation during dobutamine stress, those
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with ST-segment elevation had a higher percentage of abnormal perfusion scans. To a large extent, this was associated with a high prevalence of prior infarction in these patients. The overall perfusion defect size was significantly larger in patients with ST-segment elevation during dobutamine stress (Table 2), and most had some evidence of myocardial ischemia. Thus, in our patient cohort, ST-segment elevation was a sign of a large perfusion defect with a high likelihood of at least some degree of ischemia. A comparison between patients with and those without pathologic Q waves revealed that ST-segment elevation occurred more commonly in the former, whereas predominant ischemia (>50% reversibility) occurred more often in the latter (Table 3). These findings are consistent with those of previous reports of patients with and without old myocardial infarction.6,8,9,18 In our study substantial dobutamine-induced ischemia occurred in 38% of patients with Q waves. This is similar to the occurrence of exercise-induced ischemia reported by Dunn et al9 and Lahiri et al18 (52% and 36%, respectively). ST-segment elevation in leads without Q waves is usually caused by severe myocardial ischemia, whereas ST elevation in leads with Q waves is believed to be caused by either regional wall motion abnormalities or peri-infarction ischemia. As shown in Table 3, in comparison with patients with pathologic Q waves, those without Q waves had a higher percentage of multivessel disease (90% vs 78%, respectively) and a higher angiographic ejection fraction (44% vs 34%, respectively), signifying more extensive coronary artery disease and more myocardium at risk but less LV dysfunction. The myocardial perfusion and angiographic correlates in patients displaying ST-segment elevation during dobutamine stress testing have not been previously reported. We found good agreement between the site of ST-segment elevation and (1) the site of ischemia by perfusion imaging (Table 4) and (2) the site of significant coronary stenosis (Table 5). In patients with prior myocardial infarction, exercise-induced ST elevation has not been as consistent in localization of the sites of coronary stenosis8,9; however, there is a much better correlation between the site of ST-segment elevation and the site of perfusion abnormality.9,11,18 This inconsistency may be due in part to the fact that fewer ECG leads were used to monitor the stress test in older studies. In one study,16 dobutamine-induced ST elevation was predictive of significant disease in the corresponding coronary artery; however, only 48% of the patients with ST-segment elevation underwent coronary angiography. The authors nonetheless concluded that ST-segment elevation in patients with a history of myocardial infarction was not specific for ischemia, as assessed by perfusion imaging or stress echocardiography.
Lee et al Patients with dobutamine-induced ST-segment elevation
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CONCLUSION Our results show that patients with dobutamineinduced ST-segment elevation have a depressed ejection fraction, a high likelihood of multivessel disease, and markedly abnormal myocardial perfusion. Compared with patients without ST-segment elevation, these patients have larger perfusion defects and often have ischemia on perfusion imaging. Patients with Q waves and ST-segment elevation have prominent scarring and variable amounts of superimposed ischemia on perfusion imaging, which is substantial in 38% of patients. Conversely, patients without Q waves have a high incidence (70%) of predominant ischemia, and 90% of them have multivessel disease.
References 1. Nosratian FJ, Froelicher VF. ST elevation during exercise testing. Am J Cardiol 1989;63:986-8. 2. Chahine RA, Raizner AE, Ishimori T. The clinical significance of exercise-induced ST-segment elevation. Circulation 1976;54:209-13. 3. Bruce RA, Gey GO, Cooper MN, Fisher LD, Peterson DR. Seattle heart watch: initial clinical, circulatory and electrocardiographic responses to maximal exercise. Am J Cardiol 1974;33:459-69. 4. de Feyter PJ, Majid PA, van Eenige MJ, Wardeh R, Wempe FN, Roos JP. Clinical significance of exercise-induced ST-segment elevation. Correlative angiographic study in patients with ischemic heart disease. Br Heart J 1981;46:84-92. 5. Bruce RA, Fisher LD, Pettinger M, Weiner DA, Chaitman BR. STsegment elevation with exercise: a marker of poor ventricular function and prognosis. Coronary Artery Surgery Study (CASS) confirmation of Seattle Heart Watch results. Circulation 1988;77:897-905. 6. Gallik DM, Mahmarian JJ, Verani MS. Therapeutic significance of exercise-induced ST-segment elevation in patients without previous myocardial infarction. Am J Cardiol 1993;72:1-7. 7. Chaitman BR. Exercise stress testing. In: Braunwald E, editor. Heart disease: a textbook of cardiovascular medicine. Philadelphia: Saunders; 1997. p. 153-76. 8. Fox KM, Jonathan A, Selwyn A. Significance of exercise induced ST segment elevation in patients with previous myocardial infraction. Br Heart J 1983;49:15-9. 9. Dunn RF, Bailey IK, Uren R, Kelly DT. Exercise-induced ST-segment elevation: correlation of thallium-201 myocardial perfusion scanning and coronary arteriography. Circulation 1980;61:989-95. 10. Margonato A, Chierchia SL, Xuereb RG, Xuereb M, Fragasso G, Capelletti A, et al. Specificity and sensitivity of exercise-induced ST segment elevation for detection of residual viability: comparison with fluorodeoxyglucose and positron emission tomography. J Am Coll Cardiol 1995;25:1032-8. 11. Margonato A, Ballarotto C, Bonetti F, Cappelletti A, Sciammarella M, Cianflone D, et al. Assessment of residual tissue viability by exercise testing in recent myocardial infarction: comparison of the electrocardiogram and myocardial perfusion scintigraphy. J Am Coll Cardiol 1992;19:948-52. 12. Dakik HA, Vempathy H, Verani MS. Tolerance, hemodynamic changes, and safety of dobutamine stress perfusion imaging. J Nucl Cardiol 1996;5:410-4. 13. Hays JT, Mahmarian JJ, Cochran AJ, Verani MS. Dobutamine thal-
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lium-201 tomography for evaluating patients with suspected coronary artery disease unable to undergo exercise or pharmacologic stress testing. J Am Coll Cardiol 1993;21:1583-90. 14. Candell Riera J, Castell J, Rius A, Buxeda M, Moragas G, Palet J, et al. ST segment elevation during exercise testing and perfusion scintigraphy in patients without infarction [in Spanish]. Rev Esp Cardiol 1995; 48:600-5. 15. Ricci R, Bigi R, Galati A, Bandini P, Coletta C, Fiorentini C, et al. Dobutamine-induced ST-segment elevation in patients with acute myocardial infarction and the role of myocardial ischemia, viability and ventricular dyssynergy. Am J Cardiol 1997;79:733-7. 16. Elhendy A, Geleijinse ML, Roelandt J, van Domburg RT, Cornel JH,
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TenCate FJ, et al. Evaluation by quantitative 99m-technetium MIBI SPECT and echocardiography of myocardial perfusion and wall motion abnormalities in patients with dobutamine-induced ST-segment elevation. Am J Cardiol 1995;76:441-8. 17. Lombardo A, Loperfido F, Pennestri F, Rossi E, Patrizi R, Cristinziani G, et al. Significance of transient ST-T segment changes during dobutamine testing in Q wave myocardial infarction. J Am Coll Cardiol 1996;27:599-605. 18. Lahiri A, Balasubramanian V, Millar-Craig MW, Crawley J, Raftery EB. Exercise-induced ST-segment elevation: electrocardiographic, angiographic and scintigraphic evaluation. Br Heart J 1980; 43:582-8.
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