Dobutamine echocardiography and resting-redistribution thallium-201 scintigraphy predicts recovery of hibernating myocardium after coronary revascularization

Dobutamine echocardiography and resting-redistribution thallium-201 scintigraphy predicts recovery of hibernating myocardium after coronary revascularization

Charney et al. 21. Young MA, Vatner DE, Knight DR, Graham RM, Homey CJ, Vatner SF. ol-Adrenergic vasoconstriction and receptor subtypes in large coron...

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Charney et al. 21. Young MA, Vatner DE, Knight DR, Graham RM, Homey CJ, Vatner SF. ol-Adrenergic vasoconstriction and receptor subtypes in large coronary arteries of calves. Am J Physiol 1988;255:H1452-9. 22. Chen DG, Dai XZ, Bathe RJ. Postsynaptic adrenoceptor-mediated vasoconstriction in coronary and femoral vascular beds. Am J Physiol 1988;23:H984-92. 23. Woodman OL, Vatner SF. Coronary Vasoconstriction mediated by oland us-adrenoceptors in conscious dogs. Am J Physiol1987;253:388-93. 24. Seitelberger R, Guth BD, Heusch G, Katayama L, Ross J Jr. Intracoronary os-adrenergic receptor blockade attenuates ischemia in conscious dogs during exercise. Circ Res 1988;62:436-42. 25. Taddei S, Salvetti A, Pedrinelli R. Further evidence of the existence of as-mediated adrenergic vssoconstriction in human vessels. Eur J Clin Pharmacol 1988;34:407-10. 26. Heistad DD, Armstrong ML, Marcus ML, Piegors DJ, Mark AL. Augmented responses to vssoconstrictor stimuli in hypercholesterolemic and atherosclerotic monkeys. Circ Res 1984;54:711-8. 27. Young MA, Vatner SF. Enhanced adrenergic constriction of iliac artery with removal of endothelium in conscious dogs. Am J Physiol 1986; 250:H892-7.

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28. Kern MJ, Horowitz JD, Ganz P, Gaspar J, Colucci WS, Lore11 BH, Barry WH, Mudge GH. Attenuation of coronary vascular resistance by selective alphal-adrenergic blockade in patients with coronary artery disease. J Am Co11 Cardiol 1988;5:840-6. 29. Winniford MD, Wheelan KR, Kremers MS, Ugolini V, Van Den Berg E, Niggemann EH, Jansen DE, Hillis LD. Smoking-induced coronary vasoconstriction in patients with atherosclerotic coronary artery disease: evidence for adrenergically mediated alterations in coronary tone. Circulation 1986;73:662-7. 30. Lam JY, Chesebro JH, Steele PM, Badimon L, Fuster V. Is vasospasm related to platelet deposition? relation in a porcine preparation of arterial injury in viva. Circulation 1987;75:243-5. 31. Sigal SLIJ, Sanrembock PJ, LaVeau PJ, Yang TL, Ezekowits MO. A specific serotonin receptor antagonist prevents proximal but not distal spasm following balloon angioplasty. Circulation 19%;1-278-87. 32. Peterson MB, Machaj V, Block PC, Palacios I, Philbin D, Watkins D. Thromboxane release during percutaneous coronary angioplasty. AM HEART J 1986:111:1-6.

Dobutamine echocardiography and resting-redistribution thallium-201 scintigraphy predicts recovery of hibernating myocardium after coronary revascularization The value of dobutamine echocardiography and resting thallium-201 rcintigraphy to predict reversal of regional left ventricular wail motion dysfunction after revascuiarization in patients with chronic coronary artery disease was assessed. improvement in wail motion during dobutamine echocardiography and normal or mildly decreased uptake on thallium-201 scanning are strong predictors of reversible left ventricular dysfunction. Dobutamine echocardiography and resting thallium-201 scanning are simple and safe methods of assessing hibernating myocardium. (AM HEART J 1994;128:864-9.)

Richard Charney, MD,” Matthew E. Schwinger, MD,a Jenny Chun, MD,” Michael V. Cohen, MD,a Michele Nanna, MD,a Mark A. Menegus, MD,a John Wexler, MD, PhD,b Hugo Spindola France, MD: and Mark A. Greenberg,

MD”

Bronx, N. Y.

Revascularization with coronary artery bypass surgery and percutaneous transluminal coronary angioFrom the BDiviaion of Cardiology, Department of Medicine, and the Departments of bNuclear Medicine and Radiology, Mont&ore Medical Center/Albert Einstein College of Medicine. Received for publication Oct. 26, 1993; accepted Feb. 14, 1994 Reprint requests: Richard Charney, MD, Division of Cardiology, Department of Medicine, Montefiore Medical Center, 111 E. 210th St., Bronx, NY 10467. Copyright Q 1994 by Mosby-Year Book, Inc. 0002-8703/94/$3.00 + 0 4/l/68129

plasty has been shown to reverse ischemic regional wall motion dysfunction.1-3 The identification of chronically ischemic hibernating myocardium may be important in the decision-making process regarding revascularization.4 Positron emission tomography has been used to assess hibernating myocardium but is only available in a few centers.5p6 Exercise thallium-201 scanning with 24-hour follow-up and reinjection has also been used to identify dysfunctional but viable myocardium.7, 8

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Previous studies have demonstrated that postischemic systolic dysfunction can be reversed with dopamine, epinephrine, or isoproterenoLgy lo Postextrasystolic potentiation augments systolic function in areas of viable but hypocontractile myocardium.rr We have compared the utility of low-dose dobutamine echocardiography to rest-redistribution thallium-201 scintigraphy to assess their accuracy in predicting postrevascularization left ventricular functional recovery in patients with chronic coronary artery disease. METHODS Study population. Ten men and 7 women with a mean age 63 + 8.2 years and the following characteristics were studied: (1) documented coronary artery disease;(2) regional wall motion abnormalities that correlate with the location of the coronary stenosis,(3) scheduledfor revascularization by coronary artery bypasssurgery or percutaneous transluminal coronary angioplasty and (4) highquality echocardiographic images.Patients with the following characteristics were excluded: (1) myocardial infarction within 14 days, (2) rest angina, (3) episodeof anginawithin previous 24hours, (4) history of tachyarrythmias,(5) history of uncontrolled hypertension, (6) valvular heart disease,and (7) therapy with other inotropic agents such as digoxin or dopamine. Six patients did not have a previous myocardial infarction, six patients had a previous Q-wave infarction and five patients had a previous non-Qwave myocardial infarction. Twelve patients underwent revascularization with coronary artery bypasssurgery, and five patients underwent percutaneoustransluminal coronary angioplasty. This study wasapproved by the hospital institutional review board; informed consentwasobtained from each patient. Dobutamine echocardiography. Before revascularization a two-dimensional echocardiogram was recorded at baseline with a Hewlett-Packard 500 (Andover, Mass.) with a 3.5 mHz transducer. The parasternal long axis, parasternal short axis at the level of the papillary muscle, and apical four- and two-chamber views were recorded on videotape for off-line analysis. The left ventricle was divided into 10 segments;their relation to the coronary arteries is asfollows: anterolateral, apical, and anterior septum: left anterior descending;apical lateral, anterior diaphragmatic, true lateral, posterior lateral, and middiaphragmatic: left circumflex; and posterior diaphragmatic and basalseptum: right coronary. During continuous electrocardiographic monitoring an intravenous infusion of dobutamine at 5 pg/kg/min followed by 10 pg/kg/min was given for 4 minutes. All echocardiographicviews were repeated at the end of each4-minute period during continuous dobutamine infusion. Follow-up echocardiograms were performed in all patients at 7.3 & 3.4 days after revascularization. Regional left ventricular systolic wall motion and thickening scoreswere evaluated for the 10 segmentsby two blind independent observersunaware of the angiographic,clinical, or scintigraphic data. Segmental wall motion was graded as: 3, normal wall motion and

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Table I. Heart rate and mean arterial pressure at baseline, during dobutamine echocardiography, and at follow-up Heart rate beatslmin

Baseline 68.9 Dobutamineinfusion 5 &!&min 69.5 10 &kg/min 69.6 Follow-up 71.4

Mean pressure

arterial (mm Hg)

k 16.9

87.5 + 4.9

+ 14.7 + 16.1 t 9.6

87.3 c 4.9 88.1 + 5.2 84.2 -e 4.6

thickening; 2, mild hypokinesis; 1, severe hypokinesis; 0, akinesis/dyskinesia.Ejection fraction was not calculated becausechangesin global function may mask changesin regional function. Improvement in segmentalwall motion by one grade during dobutamine or after revascularization

compared to baseline was considered significant. The recordings on videotape were digitized off-line and analyzed with a Nova Microsonics Color Vue II version 6.4

(Allendale, N. J.) system. The baseline, low-dose and highdose dobutamine and postrevascularization echocardiograms were randomly assigned to a cineloop quadrant to insure that the reader blindness. Discrepanciesbetween the two observerswere resolvedby consensusafter reevaluation of the images.A unanimousdecisionwasreachedin 151(89%) of 170segments,and in the remaining segments a consensus was reached. Thallium-201 single-photon emission computed tomography. Scintigraphic data were acquired 30 minutes after thallium-201 chloride (3.5 to 4 mCi) injection at rest with a large-field, single crystal camera equipped with a high-resolution, parallel-hole collimator (Elscint, Hackensack, N. J., Apex 409 AG) in 14 patients. The acquisition wasperformed over a l&O-degreeanterior arc (from 45-degree right anterior oblique to 45-degree left posterior oblique) in 3-degreeintervals for 20 secondsper stop. The

same imaging procedure was repeated at 24 hours. Transaxial reconstruction used a back-projection technique with a Butterworth filter. Reconstructed tomographic slicesof 7 mm thickness were reoriented in the standard short, horizontal long, and vertical long axes. These imageswere read by two experienced observers blind to the clinical, echocardiographic, and angiographic

findings of the patient. A qualitative comparison was made of perfusion between early and 24-hour delayed imageson a segmentalbasis.This segmentationcorrespondedto that used for echocardiography. Myocardial segmentswere interpreted as showingnormal perfusion, reduced perfusion (25% to 75% reduction), severelyreducedperfusion (>75 ?A reduction), or absent activity. Decision was reached by consensuswhen there wasdisagreement.A unanimousdecision was made in 135 (96%) 140 segments. Coronary arteriography and revascularization. All patients underwent selective coronary arteriography and biplane left ventriculography before enrolling in the study. The referring physician and operator used clinical indications to determine which arteries would be revascularized. Clinicians were unaware of the results of the dobutamine echocardiogramand resting thallium scans.Coronary re-

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Fig. 1. Diastolic and systolic short-axis midpapillary level frames in patient with posterolateral wall (arrows) akinesis at baseline (1A and IB), which improved during dobutamine infusion (2A and 28) and after revascularization (3A and 3B).

vascularization was performed with coronary artery bypass surgery or percutaneous transluminal coronary angioplasty by means of standard techniques. After the procedures, serial electrocardiograms and cardiac enzymes were performed to identify periprocedural myocardial infarctions. Statistical analysis. Student t tests were performed to determine the changes in heart rate and blood pressure at baseline, during dobutamine infusion, and at follow-up.

Chi-squared analysis was performed to test for dobutamine infusion. Sensitivity and specificity of the tests were determined. RESULTS Angiogtaphic data. Coronary arteriography demonstrated one-, two-, and three-vessel disease in 4,2, and 11 patients, respectively. The mean diame-

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Table II. Results of dobutamine

echocardiography and resting-thallium

Segment

response

Yes No

scans

dobutamine Results

10 pglkglmin

5 pglkglmin Improvement after revascularization

to

No. of segments No. improved

18 5

No. not responsive

5 30

867

No. improved 22 2

ter of stenosis of the arteries revascularized was 87.9 % ? 13.3%. The mean ejection fraction was 45.6% f 8.9%. Hemodynamics. Table I summarizes the hemodynamic data in all patients at baseline, during dobutamine infusion, and at follow-up. There were no significant changes in heart rate or blood pressure. No patient had angina, ST-segment changes, or arrhythmias during the infusion. Dobutamine echocardiogram. Echocardiograms of the 17 patients were divided into 170 segments. Fourteen segments could not be adequately visualized for analysis. Two segments were excluded from the analysis because of intraoperative myocardial infarction. Ninety-six segments were normal at baseline. Fifty-eight segments divided between the 17 patients had abnormal wall motion at baseline and were included in the analysis. During the infusion of 5 pg/kg/min of dobutamine, 23 segments improved, 18 after revascularization. Five of the 35 segments that did not improve with 5 pg/kg/min dobutamine infusion also improved after revascularization. During higher dose dobutamine infusion (10 pg/kg/min), 24 segments demonstrated improved wall motion and 22 of these segments improved after revascularization. Of the 34 segments that did not improve with higher-dose dobutamine, nine demonstrated improvement after revascularization. The difference in response to dobutamine was significant 0, < 0.001). A patient with posterolateral hypokinesis at baseline that improved with dobutamine and after coronary artery bypass surgery is demonstrated (Fig. 1). Resting thallium scan results. Forty-one segments were analyzed in 10 patients. These segments correlated to areas of abnormal wall motion on the baseline echocardiogram. No segments were eliminated for technical reasons. Nineteen of the 21 segments that demonstrated normal or mild decrease in thallium uptake had improved wall motion after revascularization. Only one of the 12 segments with severe decrease or absence of thallium uptake improved after revascularization (Tables II and III).

No. not responsive

of resting-thallium

__

9 25

thallium

with

severe defect or

uptake

absen,ce

of thallium 1

19 2

11

Table Ill. Results of dobutamine

resting thallium

scan

No. of segments

with

normal or mildly decreased

.

echocardiography and

scans Sensitivity

Specificity

Predictive value Positive

Negative

86% 74s; 925;

Dobutamine echocardiotmphy 5 ag/kg/min 10 pg/kg/min Resting thallium

78%

86%

78%

71% 95%

93%

92 56

85%

90%

DlSClJSSlON Dobutamine echocardiiraphy.

One previous study investigated the utility of dobutamine echocardiography in predicting improvement in regional wall motion after revascularization in patients with chronic multivessel coronary artery disease.12 Nine (82 %) of the 11 patients who manifested contractile reserve during dobutamine had improved regional thickening after coronary revascularization. Twelve (86%) of the 14 who had no significant contractile improvement during dobutamine infusion did not improve after revascularization. Three patients had angina at 20 pglkglmin of dobutamine; and one patient had asymptomatic hypotension at 15 pgjkglmin of dobutamine. In addition, one patient had chest pain and new-onset atria1 fibrillation after infusion. The maximal dose of dobutamine in our study was 10 gg/kg/min. We had no adverse effects to the infusion. Marzullo et aLI3 compared the utility of resting planar thallium 201 scintigraphy, technetium-99m sestamibi scintigraphy, and dobutamine echocardiography in detecting myocardial viability in 14 patients with previous myocardial infarctions. Dobutamineechocardiography, thallium-201 scintigraphy, and sestamibi scintigraphy correctly identified 82 % , 86%, and 75% and 92%, 92%, and 84% of postoperative viable and nonviable segments, respectively.

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Sestamibi tended to underestimate viable segments, suggesting that it is primarily a perfusion agent. Mechanism of dobutamine stimulation. The mechanism whereby dobutamine augments the contractility of ischemic myocardium is controversial. McGillem et a1.14 used an open-chest dog model to show that dobutamine caused an increase in regional shortening in the absence of a significant stenosis and during mild stenosis (>20% control reactive hyperemia). In contrast, during severe stenosis (<20% control reactive hyperemia) there was no increase in fractional shortening of the ischemic zone. During total coronary occlusion in 11 open-chest dogs, Buda et al. l5 showed that dobutamine did not increase systolic function in the central ischemic zone but increased function in the border zone, resulting in a significant decrease in the extent of the functional border zone. Schulz et a1.r6 demonstrated that during intracoronary infusion of dobutamine (2.5 + 1 cl.g/kg/min) and a decrease in coronary inflow that produced a decrease in coronary artery pressure to 46 + 5 mm Hg (control 115 + 8 mm Hg) there was asynchronous ventricular contractions with early systolic augmentation of wall thickening. Buda et al. developed a myocardial work index in which the sum of the instantaneous left ventricular pressure-wall product was derived for estimation of regional myocardial work. There was a significant increase in the work index during the addition of dobutamine during hypoperfusion. Recently Schulz et all7 demonstrated that the addition of a dobutamine infusion to left anterior descending artery hypoperfusion increased myocardial work for 5 minutes; after 85 minutes of dobutamine infusion myocardial work was below baseline. The addition of dobutamine to ischemic myocardium further decreased the creatine phosphate content and ATP. Prolonged dobutamine infusion further decreased ATP. Although there was an increase in cardiac work for a short period of time, they demonstrated that there was an increase in the infarct size in animals undergoing 85-minute infusions of dobutamine when compared to blood flow reduction alone. In our patient population mean arterial pressure and heart rate did not increase during dobutamine infusion. Because dobutamine is a stronger PI-receptor agonist than Bs- or a-receptor agonist, there is an increase in cardiac output with a fall in systemic vascular resistance; therefore there is minimal change in mean arterial pressure. It has been demonstrated that heart rate increases slightly with doses of <15 pg/kg/min.18 Thallium-201 scintigraphy

in detection

of viable myo-

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cardium. We used rest-redistribution thallium-201 scintigraphy to predict myocardial viability. Studies have shown that 77 % to 82 % of the regions with reversible segmental thallium defects have improved left ventricular function postoperatively.1g-22 However, 22 % to 67 % with irreversible defects also improved after revascularization. In a small study by Ragosta et a1.23 with quantitative resting thallium201 scintigraphy, 23 % of the segments deemed nonviable by thallium improved with revascularization. Takemoto et a1.24 found that 13% of patients with thallium defects 20 minutes after rest injection had reversibility at 18 to 72 hours. In our study only three patients had significant increase in perfusion on late scanning. Study limitations. The follow-up echocardiogram in our study was performed 7.3 f 3.4 days after revascularization on the day of discharge to insure complete follow-up and limit the loss of myocardial function from graft closure and restenosis after angioplasty. Conversely, it has been demonstrated that there is increased adrenergic activity in the immediate postoperative period. The measurement of electromechanical systole has been correlated with adrenergic tone. This increase in adrenergic tone may mask the presence of left ventricular dysfunction. These alterations return to baseline over the ensuing 3 months, and it has been suggested that the measurement of left ventricular function should be assessed after that period. 25 On the other hand, data support the assessment of left ventricular function in the immediate postoperative period. In 20 patients who underwent coronary artery bypass surgery there was no further improvement in systolic wall motion between the intraoperative transesophageal echocardiogram and the echocardiogram performed 8.4 f 2.3 days after revascularization.26 In 10 patients who underwent percutaneous transluminal coronary angioplasty for chronic coronary disease; immediate improvement was determined by left ventriculogram.2 Rubenson et a1.27also compared regional wall motion by echocardiography 1 and 6 weeks after coronary artery bypass surgery. At both time points, the number of segments that had documented improved wall motion was similar (12 and 13, respectively).27 An additional late follow-up echocardiogram may have some additional wall improvement and therefore decrease the number of falsepositives. We only used two doses of dobutamine up to 10 pg/kg/min; therefore it is unknown whether infusing higher doses of dobutamine would favorably change the sensitivity or specificity of the test. Left ventricular ejection fraction was not calcu-

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lated during echocardiography. Although this would have provided additional quantitative data, we believe the increased contractility of the normal segments in response to dobutamine would make the data misleading and would not provide additional information concerning - regional response. Although we used single-photon emission computed tomographic technology for the thallium-201 scintigraphy, the actual anatomic correlations between isotopit and echocardiographic data are not exact. Clinical implications. Our results indicate that lowdose dobutamine echocardiography and resting thallium-201 scintigraphy are able to identify viable but hypocontractile myocardium in patients with chronic coronary artery disease. Improvement in myocardial thickening during dobutamine infusion predicted recovery of systolic function after revascularization. Detection of hibernating mvocardium may be obtained with these widelyavailable, safe, a&l simple noninvasive methods. Our data suggest that these methods, which have already been found to be useful in patients immediately after infarct may also be useful in determining the risks and benefits of revascularization in patients with chronic coronary artery disease. REFERENCES

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