Dobutamine echocardiography in predicting improvement in global left ventricular systolic function after coronary bypass or angioplasty in patients with healed myocardial infarcts

Dobutamine Echocardiogra hy in Predicting Improvement in G Pobal Left Ventricular Systolic Function After coronary Bypass or Angioplasty in Patients With Healed Myocardial Infarcts Jaroslav Meluzin, MD, Carlos G. Cigarroa, MD, M. Elizabeth Brickner, MD, Jan Cerny, MD, Lenka Spinarova, MD, Milan Frelich, MD, Frantisek Stetka, MD, Ladislav Groch, MD, and Paul A. Grayburn, MD The aim of this stu was to determine whether lowdose dobutamine ec % ocardiography (DE) could r-edict quantitative improvement in global left ventricu Par (Lv) s stolic function after coronary revascularization. lowcrose DE was performed in 71 consecutive patients with coronary artery disease and LV dysfunction. Successful coronary bypass surgery or angioplasty was performed in 4.4 patients, 37 of whom had a resting echocardiogram 1 to 3 months afterward. Group A consisted of 20 patients with contractile reserve during DE, and group B consisted of 17 patients without contractile reserve. As expected, regional wall motion score index (mean + SD) improved in group A (1.62 f 0.39 to 1.38 f 0.31 , p ~0.01) but not group B (1.56 f 0.42 to 1.57 k 0.41, p = NS). In addition, LV ejection frac-

tion (LVEF) improved after bypass surgery or an ioplasty in group A (38 + 5% to 42 + 5%, p
ibemating myocardium is characterized by abnormal resting left ventricular (LV) function in the setH ting of coronary artery diseasethat is fully or partially

or angioplasty was performed in 47 of these patients within 3 months after DE. Of these, 3 died of postoperative LV failure and 4 were excluded becauseLV aneurysmectomy was performed during bypass surgery. An additional 3 patients were excluded becauseof stroke (n = 1) or myocardial infarction (n = 2) before their followup echocardiography. The remaining 37 patients were divided into 2 groups based on the presence(group A) or absence(group B) of contractile reserveduring DE. The clinical characteristics of these patients are shown in Table I. Prior myocardial infarction was documented in 27 patients. In the remaining 10 patients, LV dysfunction may have been due to clinically undetectedmyocardial infarction, hibernating myocardium,or cardiomyopathy.Patientsin group B were more likely to have had prior myocardial infarction; otherwise, the groups were similar. Bypasssurgery was performed in all 35 patients with 2- or 3-vesselcoronary artery disease.In each of 9 patients with multivesse1disease,a single artery could not be bypassedbecause the distal vessel was too small with inadequaterunoff (n = 5), or becauseof multiple severestenosesthroughout the length of the vessel (n = 4). Angioplasty was successfully performed in the 2 patients with l-vessel disease. Dobutamine echocardiography: Echocardiogramswere performed with the patients in the left lateral decubitus position using an ATL Ultramark 7 (ATL, Bathello, Washington) with a 2.5 MHz transducer or a Vingmed CFM 750 (Vingmed Sound, Salt Lake City, Utah) with a 3.25 MHz transducer. After resting images were ob-

reversible after bypasssurgery.1,2Thus, the ability to preoperatively predict which patients have hibernating myocardium has becomea clinically important goal in terms of assessmentof prognosis and selection of patients who will benefit from bypass surgery.3Recently, contractile reserve during low-dose dobutamine echocardiography (DE) has been used to identify hibernating myocardium and predict LV functional recovery,as manifestedby improved regional wall motion scoreafter bypasssurge#t5 or angioplasty.6 This study was performed to determine whether contractile reserve during low-dose DE could predict quantitative improvement in global LV systolic function after coronary bypass surgery or angioplasty.

METHODS Patient group: Low-dose DE was performed in 71 consecutivepatients with coronary artery diseaseand an LV ejection fraction (EF) ~50%. All patients were in sinus rhythm and none had unstable angina or myocardial infarction within 2 months of DE. Bypass surgery From the First Internal Department, St. Anna Hospital and the Center of Cardiovascular and Transplant Surgery, Brno, Czech Republic, and the Department of Internal Medicine, Division of Cardiology, Universi of Texas, Southwestern and Veterans Affairs Medical Centers, Dalas, ‘y Texas. Manuscript received March 29, 1995; revised manuscript received and accepted August 4, 1995. Address for re rints: Jaroslav Meluzin, MD, First Internal Department, St. Anna Hospita P, Pekarska 53, Bmo, 656 91, Czech Republic.

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TABLE I Clinical Without (group Echocardiography

Characteristics of Patients With (group A) and B) Contractile Reserve During Dobutamine

Age (yr) [mean * SD) Healed myocardial infarction Hypertension Number of coronary arteries narrowed ~-50% in diameter 3 2 1 Bypass surgery Mean number of grafts per patient Complete revosculorization

Group A (n = 20)

Group

B

55 * 8 10 (50)

57 * 8 17 (loo)*

(n = 17)

5 125)

5 (29)

12 (60)

13 (76)

6 (301

4 (24)

2 (10

0 (0)

18 (90) 2.5 17 (85)

17 (100) 2.4 11 (65)

*p
tained, dobutamine was administered intravenously at dosesof 5 and 10 pg/kg/min at 3-minute intervals. Echocardiographic imaging was performed at each dose of dobutamine and recorded on SVHS videotape for subsequentanalysis. The electrocardiogram was monitored continuously during the dobutamine infusion and blood pressure was measured at each stage. Beta-blocking medications were withdrawn 2 days before DE in 29 patients; 8 patients were taking a small doseof metoprolol. Follow-up echocardiography was obtained 1 to 3 months (mean 2.8) after coronary revasculatization in 37 patients. Of these,35 underwent coronary bypasssurgery and 2 underwent coronary angioplasty. Echacardiagraphic analysis: Regional wall motion was assessedusing the 16-segmentmodel recommended by the American Society of Echocardiography.’ Each segment was graded with the following scale: 1 = normal or hyperkinetic; 2 = hypokinetic; 3 = akinetic; and 4 = dyskinetic, by visual evaluation of systolic wall g

s

.-5

.F m a 3 5 K

12-

r-0.91 y= -0.28+ pc0.0001

,o-

thickening. Wall thickening was assessedat a distance of 21 cm from the adjacent segment to minimize the effect of tethering.*TgA regional wall motion scoreindex was derived by summing the scores for each segment and dividing by the total number of segments.Sinceboth normal and hyperkinetic segmentsare given a score of 1, dobutamine-induced hyperkinesia does not improve the regional wall motion score index. Regional wall motion during DE was assessedby consensusof 2 experienced observers who were blinded to the clinical and angiographic data. Regional wall motion during follow-up echocardiographywas assessed by the same observers blinded to the results of DE. A wall motion score index was calculated at baseline and at each stage of DE. Contractile reserve was defined as an improvement of at least 1 grade in at least 2 adjacent segmentsat any doseof dobutamine.A changefrom dyskinetic to akinetic was not considered to be improved wall motion. LV volumes were assessedseparatelyfrom wall motion scoring and in the sameblinded fashion. End-diastolic and end-systolic frames from the apical 4- and 2chamberviews were tracedon a Kontron C200 (Munich, Germany) image processingcomputer.End-diastole was defined as the frame coincident with the onset of the QRS complex and end-systole as the subsequentframe with the smallest cavity area.Volumes and EF were calculated from an average of 3 to 5 consecutive heart cycles using the biplane Simpson’s rule method recommendedby the American Society of Echocardiography.’ Statistical analysis: Data are presentedas mean + SD. Categoric variables were assessedby the chi-square test with Yates’ correction. Differences in continuous variables from before and after revascularization were assessedby paired t test, whereas group differences were assessedby unpaired t test. For patients in group A, linear regression was used to compare the change in wall motion score index during DE and the number of segments with contractile reserve to the change in EF after revascularization. A p value co.05 was considered statistically significant.

1.18x

RESULTS

FIGURE 1. plot comparin f) the number of Tments with contractile reserve during do utamine echocar mgraphy and the improvement in left ventricular ejection fraction (LVEF) after revascularization in 20 patients with contractile reserve during dobutamine echocardiograph (group A). A strong correlation was present (r = 0.91, p 43. &Ol,.

Observer variability: Inter- and intraobservervariability were determined in the first 25 patients before and after bypass surgery. The 2 observers were concordant on wall motion scoring in 742 of 800 segments(93%). Of 121dysfunctioning segments,the 2 observersagreed on the presenceor absenceof contractile reserve in 111 (92%). Intraobserver variability was concordant for wall motion scoring in 769 of 800 segments(96%), and for contractile reserve in 115of 121 segments(95%). Echacardiagraphic and hemadynamic variables: Table II demonstratesthe hemodynamic and echocardiographic data before and after bypasssurgery (n = 35) or angioplasty (n = 2). Variables influencing EF, such as heart rate, systolic blood pressure,and end-diastolic volume, were not significantly different between groups at baseline. As expected, wall motion score index improved after bypass surgery or angioplasty in group A (1.62 f 0.39 to 1.38 + 0.31, p
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EF improved in group A (38 f 5% to 42 f 5%, p
TABLE II Hemodynamic Without

(group

and Echocardiographic B) Contractile Reserve During

Data in Patients With (group A) and Dobutamine Echocardiography

Group A (n = 20)

Variable Heart rate (beats/min) Systolic blood pressure

Group B (n = 17)

Baseline

After Revascularization

69 f 11 124 * 16

72 f 11 125 * 16

69 * 9 130*20

74 * 11 132 * 15

124*27 42 * 5*

147 * 35 38 * 7

148 * 38’ 39 i 8

(mm Hgl End-diastolic volume (ml) 129 * 33 Left ventricular ejection 38 iz 5 fraction (“A) Regional wall motion 1.62 i 0.39 score index

1.38

* 0.31*

1.56

* 0.42

*p qO.01 versus baseline; tp ~0.05 versus 9roup A postrevascularization Values me expressed as mem * SD.

DISCUSSION

Previous studies have shown that contractile reserve during DE predicts recovery of LV function after bypass surgery in patients with hibemating myocardium. This was Iirst shown by Cigarroa et al4 who demonstratedthat contractile reservehad a positive and negative predictive value of 82% and 86%, respectively, in predicting improvement in LV regional wall motion score. La Canna et al5 showed similar findings with positive and negative predictive values of 90% and 77%, respectively. More recently, Afridi et al6 demonstrated that a “biphasic” response manifested by contractile reserve at low-dose DE followed by ischemia at higher dosespredicted improved wall motion score after angioplasty. The present study demonstratesthat contractile reserve predicts quantitative improvement in global LV function after bypass surgery or angioplasty. Moreover, this study shows that the postprocedural improvement in EF dependson the number of myocardial segmentswith contractile reserve,as well as on the magnitude of their functional improvement, as reflected by the wall motion score index. Prognostic importance of left ventricular ejection fraction: In patients with coronary artery disease, LV sys-

tolic function is an important predictor of survival. Poor EF is associatedwith decreasedsurvival in both medically treated patients and those undergoing bypass surgery.‘&13However, in patients with coronary artery diseaseand severeLV dysfunction, bypass surgery prolongs survival compared with medical therapy, an effect that is more pronounced at a lower preoperative EF.13-i6 On the other hand, as EF declines, operative mortality increases.I7 Thus, the ability to identify patients in whom revascularization is likely to result in improved EF is an important clinical goal. This study shows that the number of segmentsexhibiting contractile reserveduring DE predicts improvement in EF after bypass surgery or angioplasty. Larger studies are needed to determine whether contractile reserve is able to predict operative mortality and long-term clinical outcome. Other techniques to assess hibernating

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1.57

* 0.41

value.

tomography has also been shown to predict recovery of LV function after bypasssurgery.20,21 Moreover, patients with hibernating myocardium revealedby positron emission tomography (decreasedmyocardial blood flow with preservedmetabolic activity) who are not revascularized appear to have a higher risk of cardiac death compared with those who are revascularized and those who have nonviable myocardium.22q23 To our knowledge, no studieshave directly compared thallium-201 reinjection, positron emission tomography, and DE in predicting functional recovery of hibernating myocardium. Positron emission tomography assesses myocardial blood flow and myocyte metabolic activity. Thallium reinjection techniques depend on myocardial perfusion and cell membrane integrity. Contractile reserve, on the other hand, requires gross functional integrity of a dyssynergic myocardial segment. Bodenheimer et a124obtained punch biopsies during bypass surgery and showed that myocardial segmentswith contractile reservehad minimal fibrosis, whereasareaslacking contractile reserve had extensive fibrosis but also 3 5 ‘2 m .z -m 2

v) 2 d z sr: m

12IO -

64-

5 -I .c 8

2-

:

0

6

kO.90 y= -0.31 + 16.9x pc0.0001

a-

0 0

I 01

I 0.2 Change

myocardium:

Thallium scintigraphy and positron emission tomography have also been used to identify viable myocardium in patients with coronary artery disease and LV dysfunction3 In such patients, late reinjection of thallium201 may identify areasof regional LV dysfunction that improve after bypass surgery.t8,i9 Positron emission

After Revascularization

Baseline

I 0.3 in WMSI

I 04

I 0.5

I 06

1

07

with Dobutamine

FIGURE 2. Plot comparing the change in regional wall motion score index (W/VW) with dobutamine versus the change in left ventricular ejection fraction (LVEF) after revaxularization in 20 patients v+th contractile reserve during dobutamine chocardiography (group A). A strong correlation was present (r = 0.90, p 4LOOOl).

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contained islands of viable myocytes.Thus, perfusion by thallium scintigraphy is probably more sensitive than contractile reserve by DE in identifying regions containing viable myocytes.25However, contractile reserve by DE may prove to be more specific than perfusion techniques in predicting LV functional recovery.26T27 Study limitations: Although we correlated improvement in EF with the number of segmentswith contractile reserve,we did not take into account the location of thesesegments.Becauseof the heterogeneityof LV segmental wall thickening, the contribution of different segmentsto overall LV function may ~ary.*~Moreover, echocardiographic evaluation of regional wall motion is a subjective method that can be influenced by tethering8~9 andpostoperativeparadoxic septalmotion.29We attempted to minimize thesepotential confounding influencesby specifically assessingsystolic wall thickening rather than wall motion. We did not perform follow-up coronary angiography to verify the extent of revascularization. Instead, we assumedthat revascularization was successfulbasedon the absenceof perioperative complications and postoperative angina. 1. Rahimtoola SH. The hibernating myocardium. Am Hearr J 1989;117:211-221. 2. Braunwald E, Rutherford ID. Reversible ischemic left ventricular dysfunction: evidence for the “hibernating myocardium.” JAm Coil Cardiol 1986;8: 1467-1470. 3. Dilsizian V, Bonow RO. Current diagnostic techniques of assessing myocardial viability in patients with hibernating and stunned myocardium. Circulation 1993; 87:1-20. 4. Cigarroa CG, deFilippi CR, Brickner ME, Alvarez LG. Wait MA, Graybum PA. Dobutamine stress echocardiography identifies hibernating mywardium and predicts recovery of left ventricular function after coronary revascularization. Circrclotion 1993;88:43@436. 5. La Canna G, Altieri 0, Giubbiui R, Gargauo M, Ferrari R, Visioli 0. Echwardiography during infusion of dobutamine for identification of reversible dysfunction in patients with chronic coronary artery disease. .I Am CON Cardiol 1994;23:617-626. 6. Afridi I, Kleiman NS, Raizner AE, Zoghbi WA. Dobutamine echocardiography in myocardial hibernation: optimal dose and accuracy in predicting recovery of ventricular function after coronary angioplasty. Circulation 1995;91:663-670. 7. Schiller NB, Shah PM, Crawford M, DeMaria A, Devereaux R, Feigenbaum H, Gutgesell H, Reicbek N, Sahn D, Schnittger I, Silverman NH, Tajik AJ. Recommendations for quantitation of the left ventricle by two-dimensional echocxdiography. JAm Sot Echo 1989;2:358-367. 8. Force T, Kernper A, Perkins L, Gilfoil M, Cohen C, Parisi AF. Overestimation of infarct size by quantitative two-dimensional echocardiography: the role of tethering and of analytic procedures. Circularion 1986;73:136&1368. 9. Buda Al, Zotz RJ, Gallagher KP. The effect of inotropic stimulation on normal and ischemic myocardium after coronary occlusion. Circulation 1987;76: 163-172. 10. Mock MB, Ringqvist I, Fisher LD, Davis KB, Chaitman BR, Kouchoukos NT, Kaiser GC, Alderman E, Ryan TJ, Russell RO Jr, Mullin S, Fray D, Killip T III, and participants in the Coronary Artery Surgery Study. Survival of medically treated patients in the Coronary Artery Surgery Study (CASS) registry. Circulation 1982;66:562-568.

11. Hammermeister KE, DeRouen TA, Dodge HT. Variables predictive of survival in patients with coronary disease. Circulation 1979;59:421-430. 12. Hochberg MS, Parsonnet V, Gielchinsky I, Hussain SM. Coronary artery bypass grafting in patients with ejection fractions below forty percent. J Thorac Cardiovast Surg 1983;86:519-527. 13. Bounos EP, Mark DB, Pollock BG, Hlatky MA, Harm11 FE Jr, Lee K, Rankin JS, Wechsler AS, Pryor DB, Califf RM. Surgical survival benefits for coronary zutery disease patients with left ventricular dysfunction. Circulation 1988;78(suppl 1):1-151-I-157. 14. Alderman EL, Fisher LD, Litwin P, Kaiser GC, Myers WO, Maynard CH, Levine F, Schloss M. Results of coronary tiery surgery in patients with poor left ventricular function (CASS). Circulation 1983;68:785-795. IS. Faulkner SL, Stoney WS, Alford WC, Thomas CS, Burrus GD, Frist RA, Page HL. Ischemic cardiomyopathy: medical versus surgical treatment. J Thorac Cardiovmc Surg 1977;74:77-82. 16. Pigott JD, Koucboukos NT, Oberman A, Cutter GR. Late results of surgical and medical therapy for patients with coronary artery disease and depressed left ventricular function. J Am CON Cardiol 1985;5: 103&1045. 17. Kennedy JW, Kaiser GC, Fisher LD, Fritz JK, Myers W, Mudd JG, Ryan TJ. Clinical and angiographic predictors of operative mortality from the collaborative study in coronary artery surgery (CASS). Circulation 1981;63:79>801. 18. Dilsizian V, Rocco TP, Freedman NMT, Leon MB, Bonow RO. Enhanced detection of ischemic but viable myocardium by the reinjection of thallium after stress-redistribution imaging. N Engl J Med 1990;323:141-146. 19. Ohtani H, Tamaki N, Yonekura Y, Mohiuddin IH, Hirata K, Ban T, Konisbi J. Value of thallium-201 reinjection after delayed SPEIX imaging for predicting reversible ischemia after coronary artery bypass grafting. Am J Cnrdiol 1990;66: 394-399. 20. Tillisch J, Bmnken R, Marshall R, Schwaiger M, Mandelkem M, Phelps M, Schelbert HR. Reversibility of cardiac wall-motion abnormalities predicted by positron tomography. N Engl J Med 1986;314:88&888. 21. Tamaki N, Yonekura Y, Yamashita K, Saji H, Magata T, Senda M, Konishi Y, Hirata K, Ban T, Konishi J. Positron emission tomography using fluorine-18 deoxyglucose in evaluation of coronary artery bypass grafting. Am J Cardiol 1989; W86Ck865. 22. Eitzman D, Al-Aouar Z, Kanter HI,, vom Dabl J, Kirsh M, Deeb GM, Schwaiger M. Clinical outcome of patients with advanced coronary artery disease after viability studies with positron emission tomography. JAm CON Cardioll992;20:55%565. 23. Lee KS, Marwick TH, Cook SA, Go RT, Fii JS, James KB, Sapp SK, MacIntyre WJ, Thomas JD. Prognosis of patients with left ventricular dysfunction, with and without viable myocardium after myocardial infarction: relative efficacy of medical therapy and revascularization. Circularion 1994,90:2687-2694. 24. Bodenheimer MM, Banka VS, Hermann GA, Trout RG, Pasdar H, Helfant R. Reversible asynergy: histopathologic and electrocardiographic correlations in patients with coronary artery dldase. Circulation 1976;53:792-796. 25. Panza JA, Dilsizian V, Laurienzo JM, Curie1 RV, Katsiyiannis FT. Relation between thallium uptake and contractile response to dobutamine: implications regarding myocardial viability in patients with chronic coronary artery disease and left ventricular dysfunction. Circulation 1995;91:99&998. 26. deFilippi CR, Willett DL, Imni WL, Eichhom EJ, Velasco CE, Graybum PA. Comparison of myocardial contrast echocardiography and dobutamine stress echocardiography in predicting recovery of regional let? ventricular function after coronary mvascularization. Circulation 1995; in press. 27. Amese M, Come1 JH, Salustri A, Maat APWM, Elhendy A, Reijs AEM, Ten Cate FJ, Keane D, Balk AHMM, Roelandt JRTC, Fioretti PM. Prediction of improvement of regional left ventricular function after surgical revascularization: a comparison of low-dose dobutamine echocardiography with 201Tl single-photon emission computed tomography. Circulation 1995;9 1:2748-2752. 28.Pandian NG, Skorton DJ, Collins SM, Falsetti HL, Burke ER, Kerber RE. Heterogeneity of left ventricular segmental wall thickening and excursion in 2dimen. sional echocardiograms of normal human subjects. Am JCardioll983;51:1667-1673. 29. Kerter RE, Litcbfield R. Postoperative abnormalities of interventricular septal motion: two-dimensional and M-mode echocardiographic correlations. Am Hean J 1982;104:263-268,

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