Frequency of Myocardial lndium- 111 Antimyosin Uptake After Uncomplicated Coronary Artery Bypass Grafting Bob van Vlies, MD, Eric A. van Royen, MD, Cees A. Visser, MD, Nice G. Meyne, MD, Monique M. G. van Buul, MD, Ron J. G. Peters, MD, and Arend J. Dunning, MD
The reported incidence of myocardial damage after coronary artery bypass grafting (CABG) is highly related to the methods used. Since indium- 111 monoclonal antimyosin antibody scintigraphy has been shown to be highly specific and sensitive for myocardial necrosis, even in small lesions, uptake of this radiotracer was evaluated after CABG. In 23 consecutive patients without previous myocardial infarction who underwent CABG for stable angina, 80 MBq indium-111 antimyosin was injected on the third postoperative day. Planar images were obtained 48 hours later and analyzed for myocardial uptake of indium- 111 antimyosin. Scintigraphic results were related to creatine kinase MB levels, duration of both aortic cross-clamping and cardiopulmonary bypass, and electrocardiographic changes. In all patients surgical procedure and postoperative course was uncomplicated. Indium111 antimyosin uptake was present in 19 of 23 patients (BZ%). It was diffused in 7 patients and localized in 12. No pathologic Q waves occurred postoperatively. Fourteen patients exhibited STsegment changes. No good relation was found among indium-11 1 antimyosin uptake and creatine kinase MB levels, duration of cross-clamping or bypass, and ST-T changes. It is concluded that some degree of myocardial damage, though silent, is common after CABG. (Am J Cardiol 1990;66:1191-1195)
oronary artery bypassgrafting (CABG) has been shown to be an effective treatment in relieving symptoms caused by myocardial ischemia.’ Improved surgical skills, anesthesiologic techniques and myocardial protection, all aimed at preventing myocardial injury, have enhanced outcome.2 Nevertheless, myocardial damage after CABG is not infrequent.3,4 The amount of damage appeared to be an important determinant for postoperative mortality and morbidity.5,6The incidence of perioperative myocardial infarction has been reported to range from about 5 to >40%. This range is due to differences in diagnostic procedures and diverging reference values. Routinely used tests for diagnosing acute myocardial infarction, enzyme measurements and electrocardiography have-in this respect-proved to be of limited value.4 In a postmortem study, subendocardial contraction band necrosis, a result of reperfusion injury, was demonstrated in regions with well-functioning bypass grafts in >80% of patients.7 Recently Weisel et al8 demonstratedmyocardial membrane damage after cardioplegia due to free oxygen-derived radicals. Indium-1 11 antimyosin scintigraphy has proved to be highly specific for myocardial necrosis,9and localized uptake of this monoclonal antibody has been demonstrated even in small and nontransmural myocardial lesions.‘OTherefore, the present study was undertaken to investigate the uptake of this radiopharmaceutic as a measureof myocardial damage in patients after uncomplicated CABG.
C
METHODS Patient selection
and surgical procedure: The study group consisted of 23 consecutivepatients, 18 men and 5 women, mean age 60.6 years. All patients underwent elective CABG for stable angina (New York Heart Association class III). None of the patients had a history of myocardial infarction, congestiveheart failure or cardiac surgery. Three-vessel disease was documented in 16 patients, 2-vesseldiseasein 5 and l-vessel diseasein ._ 2. Informed consent was given according to the criteria From the Departments of Cardiology, Nuclear Medicine and Thoracic Surgery, Academic Medical Center, Amsterdam, the Netherlands. of the institutional ethics committee, which had apThis study was presentedat the 39th annual meeting of the American proved the study. College of Cardiology, March 1990, New Orleans, Louisiana. ManuDuring surgery all patients were subject to routine script receivedApril 9, 1990;revisedmanuscript receivedand accepted anesthesiologicand monitoring procedures.During carJuly 10,199O. Addressfor reprints: Bob van Vlies, MD, Department of Cardiolo- diopulmonary bypass St. Thomas’ cardioplegic solution gy, Academic Medical Center, Meibergdreef 9, 1105AZ Amsterdam, was used in combination with systemic hypothermia (27” C). An average of 3.9 f 1.5 vesselswas grafted. The Netherlands. THE AMERICAN JOURNAL OF CARDIOLOGY
NOVEMBER 15, 1990
P191
TABLE
for changes of the ST-segment or T wave compared with preoperative registrations.
I Summary of Individual Patient Data
No. Pts.
No. Grafts
Antimyosin Uptake
CKMB W/b
ST Change
ACC (min)
CPB (min)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
1 1 2 2 3 3 3 3 3 4 4 4 4 4 5 5 5 5 5 5 6 6 7
diffuse localized diffuse negative localized localized localized negative localized negative diffuse localized localized diffuse negative localized diffuse localized localized localized diffuse localized diffuse
12 21 13 14 33 35 29 42 36 20 87 27 99 18 80 58 51 29 20 27 25 23 145
+
12 22 26 30 30 51 38 46 54 50 52 54 57 74 48 54 65 56 66 66 87 62 93
33 35 57 76 54 73 75 77 95 83 87 90 102 113 83 87 91 96 105 128 126 126 144
Indium-1
11 antimyosin
administration
and imag-
Mean aortic cross-clamp time was 51 f 19 minutes; bypass time was 88 f 27 minutes.
For the antimyosin studies, a murine monoclonal antibody Fab fragment (Myoscint”, Centocor Europe) was used. Eighty MBq of indium-1 11 was added to a single vial containing 2 ml of antimyosin-Fab-DTPA preparation in citrate buffer. The labeling efficiency was >9590. Indium- 111 antimyosin was injected intravenously on the third day after surgery. All drain systemshad been removed 124 hours earlier without signs of ongoing pericardial leakage. Planar images were obtained after 48 hours in the anterior and 45” left anterior oblique position. A General Electric Maxi 400 large-field-of-view gamma camera was used, fitted with a medium energy collimator. A 20% energy window was set to the 170 and 247 keV photon peak. Analog and digital images for each view were acquired for a lo-minute period, using a 128 X 128 matrix for the latter. All studies were assessedby 2 experienced investigators unaware of clinical and biochemical data. When present, myocardial uptake was defined as localized or diffuse. Statistical analysis: All data are expressedas mean f 1 standard deviation. Student t tests are usedto analyze differences between groups. A p value 70 IU/liter.
In none of the patients did pathologic Q waves appear on the electrocardiogram after surgery. In 14 patients ST-segmentor T-wave changes were present (individual data are listed in Table I). Indium-1 1 i antimyosin sciatigraphy: No side effects were noticed after injection of indium-1 11 antimyosin. Images could be obtained in all 23 patients. In 19 patients (82%) myocardial uptake of indium-1 11 antimyosin was demonstrated (Figure 1); uptake was localized in 12 patients and diffuse in 7. In 4 patients no uptake was found. All but 1 of these 4 patients had a creatine phosphokinaseMB peak value of 570 IU/liter, the postoperativeupper normal limit. Only in 3 of the 19 patients with myocardial uptake did creatine kinase MB value exceedthe level of 70 IU/liter. In the other 16 patients ereatine kinase MB value was above the laboratory normal limit, but 570 IU/liter. There was no good relation between the type of antimyosin uptake (negative, local or diffuse) and creatine kinase MB levels (Figure 2). Electrocardiographic changes involving the ST-segment or T wave occurred in all 3 groups. Again, no differences between patients with local uptake versus patients with diffuse uptake were found (Figure 3). There proved to be no good relation between aorta cross-clamptime (43 f 8, 58 f 28, 51 f 13 minutes) or duration of cardiopulmonary bypass (80 f 3, 93 f 35, 89 f 26 minutes) and degree of iridium-1 11 antimyosin
CK-MB
vs. IN-111 ANTIMYOSIN
UPTAKE
uptake (Figures 4 and 5). Mean values did not differ significantly. Indium- 111 antimyosin uptake was present in the 2 patients with l-vessel diseaseand in 17 of 21 patients with multivessel disease.Localized uptake was consistently situated in grafted areas. ISCUSSION
Since myocardial injury is a major prognostic determinant after cardiac surgery, data on its incidence and extent may be important. However, controversy exists regarding the frequency and clinical implications of postoperative myocardial infarction. The incidence highly dependson the selection of patients and the techniques used to measure myocardial damage. Furthermore, several preoperative factors may predispose to postoperative myocardial infarction, such as recent infarction, depressedleft ventricular function, extent of coronary artery disease and unstable angina.” The changing profile of patients undergoing CABG-that is, increasing emergency procedures, patients with unstable angina, CABG in the elderly, combined procedures-increases the risk.r2 Finally, anesthesia-related problems, inadequate myocardial protection and a long duration of both aorta cross-clamping and cardiopulmonary bypass may also contribute to myocardial injury.13 The assessmentof the presenceand magnitude of myocardial necrosis after CABG is difficult. Mechanisms of onset, clinical presentation and even ultrastructural characteristics of postoperative myocardial damage differ from the classic type of myocardial infarction.14 This
IU/I 160 I
STT
CHANQE
ISZB NO
STT
CHANGE
140 120
.
100
i-i M s
60
.
60
. .
40
1 ! .
20
m .
z :
: i
NO
0
UPTAKE INDIUM-Ill
NO UPTAKE
DIFFUSE
LOCAL
LOCAL
DIFFUSE ANTIMYOSIN
UPTAKE
- r of patients with presence or absence of T-~~~e~t or T wave (STT) changes. ST-T changes occur in all growps. No difference was present when patients with ar local uptake of indium411 antimyosin were com-
THE AMERICAN JOURNAL OF CARDIOLOGY
NOVEMBER 15, 1990
difference may complicate the interpretation of routine diagnostic tests. Furthermore, methodologic differences in various studies, although using the same test, complicate the comparison of results. Routine tests, such as enzyme measurements and electrocardiography, give rise to diverging and unsatisfying results. Postoperative myocardial infarction is diagnosed in about 5% of patients when the appearance of new Q waves is used, whereas the number goes up to 40% when ST-segment changes are taken into account.15The presenceof new Q waves is strongly related to postoperative myocardial infarction, but their absencewill underestimate the incidence of small, especially subendocardial lesions. Creatine kinase MB isoenzymes,the gold standard for the diagnosis of myocardial infarction, are elevated in almost all patients after CABG,16 but their clinical relevance in the absence of other signs of postoperative myocardial infarction remains doubtful. Infarct imaging with technetium-99m pyrophosphate has been reported to be positive in more than 20% of patients after CABG. l7 This technique, however, is known to have a lower sensitivity in the setting of subendocardial necrosis,18which is the most frequent site of perioperative myocardial damage. Also, studies on left ventricular wall motion are conflicting, and improvement19 as well as deterioration of function20,21have been demonstrated.
Becausethe imaging technique usedherein is highly specific for myocardial damage, the following question has to be answered in the light of the present findings: What is a normal test result in this particular population? Some myocardial necrosismay be almost obligatory after CABG, but the favorable outcomein the majority of patients emphasizesthe limitation of its importance. Despite all precautions before and during operation, coronary bypasssurgery seemsto be an insult to the myocardium. Acute changes in hemodynamics, temperature changes and direct contact with surgical instruments will damagemyocardial cells. Additionally, reperfusion of previously ischemic myocardium may be harmful and may lead to necrosis.22%23 Bulkley et al7 reported the postmortem results in patients who died within 30 days after CABG. They found evidencein 48 of 58 patients (83%) for subendocardial contractionband necrosis,which is one of the pathologic features of reperfusion injury,22,24localized in areas with widely patent bypass grafts. They concluded that reperfusion injury was common after CABG. Weisel et al8 demonstrated the generation of free oxygen radicals after cardioplegic arrest leading to membrane damage in myocardial biopsy specimensobtained during surgery. In the present study all patients had an elevatedcreatine kinase MB level when compared to the normal referencevalue in a healthy population. Only 4 patients
CPB TIME Vs. IN-111 ANTIMYOSIN CROSS-CLAMP
TIME vs. ANTIMYOSIN
UPTAKE
UPTAKE MIN 160
120
. 140 100
.
C g
. .
120
.
100
s
9f
.
80
E
C .
E T
. .
60
80
. . :
. .
a..
Ii E
. L
T
A
40
E
.
.
.
.
. .
.
40
. .
20
20
.
0 -
0 NO UPTAKE
DIFFUSE
LOCAL
FIGURE 4. Relation between aorta cross-clamp time (in minutes) and indium-1 11 antimyosin uptake. Mean values, indicated by black lines, do not differ significantly.
1194
60
7
. . . : . .
I . . .
:
THE AMERICAN JOURNAL OF CARDIOLOGY
VOLUME 66
NO UPTAKE
DIFFUSE
LOCAL
FIGURE 5. Relation between cardiopulmonary bypass (CPB) time (in minutes) and indium-1 11 (IN-1 11) antimyosin uptake. Mean values, indicated by black lines, do not differ significantly.
(17%) had a value >70 IU/liter, used as the normal Chaitman BR, Alderman EL, Kaiser CG, Faxon DP, Bourassa MG. Detrimental of perioperative myocardial infarction on late survival after coronary artery upper limit after CABG, a percentage in keeping with effect bypass. J Thorac Cardiovasc Surg 1984;89:972-981. the data of McGregor et a1.25Indium-I 1I antimyosin 7. Bulkley BH, Hutchins GM. Myocardial consequences of coronary artery scintigraphy showed uptake in 82% of our patients and bypass graft surgery. The paradox of necrosis in areas of revascularization. Circu1977;56:906-913. gaveevidencefor myocardial necrosis,which did not af- 8.lation Weisel RD, Mickle DAG, Finkle CD, Tumiati LC, Madonik MM, Ivanov J, fect clinical course. The incidence of perioperative ne- Burton GW, Ingold KU. Myocardial free-radical injury after cardioplegia. Circucrosis in our patients, assessedwith indium-111 anti- lation1989;(suppl 111)80:111-14-111-18. Khaw BA, Yasuda T, Gold HK, Leinbach RC, Johns JA, Kanke M, Barlaimyosin, is in keeping with the postmortem data of Bulk- 9.Kovach M, Strauss HW, Haber E. Acute myocardial infarction imaging with ley et a1.7 However, they studied a highly selected indium-111 labeled monoclonal antimyosin Fab. J Nucl Med 1987;28:1671population. Our data, in contrast, were obtained in pa- 1678. 10. Van Vlies B, Baas J, Visser CA, Van Royen E, Delemarre BJ, Bot H, tients with an uneventful postoperative course in whom Dunning AJ. Predictive value of indium-1 11 antimyosin uptake for improvement the previously mentioned factors, which may predispose of left ventricular wall motion after thrombolysis in acute myocardial infarction. J Cardiol 1989;64:167-171. for postoperative myocardial infarction, were also ab- Am Il. Roberts AJ. Perioperative myocardial infarction in open heart surgery. In: sent. This indicates that some degree of myocardial Utley JR, ed. Perioperative Cardiac Dysfunction. Cardiothoracic Surgery Series. damagemay be a common phenomenon even after un- vol. 3. Baltimore, London, Los Angeles, Sydney: Williams 8r Wilkins, 1985: complicated surgery. Furthermore, indium- 111 anti- 1077121. 12. Naunheim KS, Fiore AC, Wadley JJ, McBride LR, Kanter KR, Pennington myosin uptake was not related to the duration of aorta DG, Barrier HB, Kaiser CG, Willman VL. The changing profile of the patient undergoing coronary artery bypass surgery. J Am Coil Cardiol1988;11:47 l-477. cross-clampingor cardiopulmonary bypass. 13. Baur HR, Peterson TA, Arnar 0, Gannon PG, Gobel FL. Predictors of A gold standard for the diagnosis of postoperative perioperative myocardial infarction in coronary artery operation. Ann Thorac myocardial infarction doesnot exist. Myocardial injury, Surg 1981;31:36-44. 14. Kirklin JW, Barratt-Boyes BG. Cardiac Surgery. New York: John Wiley, however,seemsto be frequent, and related to the surgi- 1986:85-89. cal procedure. When it will becomerelevant for clinical 115. Hultgren HN, Shettigar UR, Pfeifer JF, Angel1 WW. Acute myocardial course,or to what extent it may be acceptedas normal infarction and ischemic injury during surgery for coronary artery disease. Am J 1977;94:146-153. in this particular situation, should be the subject of fur- Heart 16. du Cailar C, Maille JG, Jones W, Solymoss BC, Chabot M, Goulet C, Delva ther study. Comparison of patients who have an un- E, Grondin CM. MB creatine kinase and the evaluation of myocardial injury aortacoronary bypass operation. Ann Thorac Surg 1980;29:8-14. eventful course with patients who have overt periopera- following 17. Burns JB, Gladstone PJ, Tremblay PC, Feindel CM, Salter DR, Lipton IH, tive damage is needed. Quantification of indium-1 11 Ogilvie RR, David TE. Myocardial infarction determined by technetium-99m antimyosin uptake will be necessaryto use it as a dis- pyrophosphate single-photon tomography complicating elective coronary artery grafting for angina pectoris. Am J COrniol 1989;63:1429-1434. criminating technique. Moreover, the relation with bypass 16. Massie BM, Botvinick EH, Werner JA, Chatterjee K, Parmley WW. Myochangesin left ventricular function has to be studied, cardial scintigraphy with technetium-99m stannous pyrophosphate: an insensitive for nontransmural myocardial infarction. Am J Cardiol 1979;43:186-197. sinceonly clinical coursewas considered;however, there test 19. Koolen JJ, Visser CA, van Wezel HB, Mcyne NG, Dunning AJ. Influence of were no signs of hemodynamic deterioration. coronary artery bypass surgery on regional left ventricular wall motion: an intraoperative two-dimensional
transesophageal echocardiographic
study. J Cardio-
rhorac An&h 1987;1:276-283.
REFERENCES 1. CASS Principal Investigators and their associates. Coronary artery surgery study (CASS): A randomized trial of coronary artery bypass surgery. Quality of life in patients randomly assigned to treatment groups. Cimdation 1985;68:95ll
960. 2. Califf RM, Harrel FE, Lee KL, Rankin JS, Hlatky MA, Mark DB, Jones RH, Muhlbaier LH, Newland Oldham H, Pryor DB. The evolution of medical and surgical therapy for coronary artery disease. A 15-year perspective. JAMA l989;261:2077-2086. 3. Roberts AJ. Perioperative myocardial infarction and changes in left ventricular performance related to coronary artery bypass graft surgery. Ann Thorac Surg 1983;35:208-225. 4. Warren SG, Wagner GS, Bethea CF, Roe CR, Newland Oldham H, Kong Y. Diagnostic and prognostic significance of electrocardiographic and CPK isoenzyme changes following coronary bypass surgery: correlation with findings at one year. Am Heart J 1977;93:189-196. 8. Hall RJ, Elayda MA, Gray A, Mathur VS, Garcia E, De Castro CM, Massumi A, Cooley DA. Coronary artery bypass: long-term follow-up of 22,284consecutive patients. Circulntion 1983;(suppl II)68:11-20-E-26. 6. Schaff HV, Gersh BJ, Fisher LD, Fry RL, Mock MB, Ryan TJ, Ells RB,
20. Hammermeister KE, Kennedy JW, Hamilton GW, Stewart DK, Gould KL, Lipscomb N, Murray JA. Aortocoronary saphenous vein bypass. Failure of successful grafting to improve resting left ventricular function in chronic angina. N Engl J Med 1977;290:186-192. 21. Wolf NM, Kreulen TH, Bove AA, McDonough MT, Kessler KM, Strong M, Le Mole 6, Span” JF. Left ventricular function following coronary bypass surgery. Circulation 1978;58:63-70. 22. Braunwald E, Kloner RA. Myocardial reperfusion: a double-edged sword? J Clin Inuest 1985;76:1713-1719. 23. Miyazaki S, Fujiwara H, Onodera T, Kihara Y, Matsuda M, Wu DJ, Nakmura Y, Kumada T, Sasayama S, Kawai C, Hamashima Y. Quantitative analysis of contraction band necrosis after ischemia and reperfusion in the porcine heart. Circulation 1987;75:1074-1082. 24. Matsuda MM, Fujiwara H, Onodera T, Tanaka M, Wu DJ, Fujiwara T, Hamashima Y, Kawai C. Quantitative analysis of infarct size, contraction band necrosis, and coagulation necrosis in human autopsied hearts with acute myocardial infarction after treatment with selective intracoronary thrombolysis. Circulation 1987;76:98 l-989. 25. McGregor CGA, Muir AL, Smith AF, Miller HC, Hannan WJ, Cameron EWJ, Wheatley DJ. Myocardial infarction related to coronary artery bypass graft surgery. Br Heart J 1984;51:399-406.
THE AMERICAN
JOURNAL
OF CARDIOLOGY
NOVEMBER
15. 1990
11%
The reported incidence of myocardial damage after coronary artery bypass grafting (CABG) is highly related to the methods used. Since indium- 111 monoclonal antimyosin antibody scintigraphy has been shown to be highly specific and sensitive for myocardial necrosis, even in small lesions, uptake of this radiotracer was evaluated after CABG. In 23 consecutive patients without previous myocardial infarction who underwent CABG for stable angina, 80 MBq indium-111 antimyosin was injected on the third postoperative day. Planar images were obtained 48 hours later and analyzed for myocardial uptake of indium- 111 antimyosin. Scintigraphic results were related to creatine kinase MB levels, duration of both aortic cross-clamping and cardiopulmonary bypass, and electrocardiographic changes. In all patients surgical procedure and postoperative course was uncomplicated. Indium111 antimyosin uptake was present in 19 of 23 patients (BZ%). It was diffused in 7 patients and localized in 12. No pathologic Q waves occurred postoperatively. Fourteen patients exhibited STsegment changes. No good relation was found among indium-11 1 antimyosin uptake and creatine kinase MB levels, duration of cross-clamping or bypass, and ST-T changes. It is concluded that some degree of myocardial damage, though silent, is common after CABG. (Am J Cardiol 1990;66:1191-1195)
oronary artery bypassgrafting (CABG) has been shown to be an effective treatment in relieving symptoms caused by myocardial ischemia.’ Improved surgical skills, anesthesiologic techniques and myocardial protection, all aimed at preventing myocardial injury, have enhanced outcome.2 Nevertheless, myocardial damage after CABG is not infrequent.3,4 The amount of damage appeared to be an important determinant for postoperative mortality and morbidity.5,6The incidence of perioperative myocardial infarction has been reported to range from about 5 to >40%. This range is due to differences in diagnostic procedures and diverging reference values. Routinely used tests for diagnosing acute myocardial infarction, enzyme measurements and electrocardiography have-in this respect-proved to be of limited value.4 In a postmortem study, subendocardial contraction band necrosis, a result of reperfusion injury, was demonstrated in regions with well-functioning bypass grafts in >80% of patients.7 Recently Weisel et al8 demonstratedmyocardial membrane damage after cardioplegia due to free oxygen-derived radicals. Indium-1 11 antimyosin scintigraphy has proved to be highly specific for myocardial necrosis,9and localized uptake of this monoclonal antibody has been demonstrated even in small and nontransmural myocardial lesions.‘OTherefore, the present study was undertaken to investigate the uptake of this radiopharmaceutic as a measureof myocardial damage in patients after uncomplicated CABG.
C
METHODS Patient selection
and surgical procedure: The study group consisted of 23 consecutivepatients, 18 men and 5 women, mean age 60.6 years. All patients underwent elective CABG for stable angina (New York Heart Association class III). None of the patients had a history of myocardial infarction, congestiveheart failure or cardiac surgery. Three-vessel disease was documented in 16 patients, 2-vesseldiseasein 5 and l-vessel diseasein ._ 2. Informed consent was given according to the criteria From the Departments of Cardiology, Nuclear Medicine and Thoracic Surgery, Academic Medical Center, Amsterdam, the Netherlands. of the institutional ethics committee, which had apThis study was presentedat the 39th annual meeting of the American proved the study. College of Cardiology, March 1990, New Orleans, Louisiana. ManuDuring surgery all patients were subject to routine script receivedApril 9, 1990;revisedmanuscript receivedand accepted anesthesiologicand monitoring procedures.During carJuly 10,199O. Addressfor reprints: Bob van Vlies, MD, Department of Cardiolo- diopulmonary bypass St. Thomas’ cardioplegic solution gy, Academic Medical Center, Meibergdreef 9, 1105AZ Amsterdam, was used in combination with systemic hypothermia (27” C). An average of 3.9 f 1.5 vesselswas grafted. The Netherlands. THE AMERICAN JOURNAL OF CARDIOLOGY
NOVEMBER 15, 1990
P191
TABLE
for changes of the ST-segment or T wave compared with preoperative registrations.
I Summary of Individual Patient Data
No. Pts.
No. Grafts
Antimyosin Uptake
CKMB W/b
ST Change
ACC (min)
CPB (min)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
1 1 2 2 3 3 3 3 3 4 4 4 4 4 5 5 5 5 5 5 6 6 7
diffuse localized diffuse negative localized localized localized negative localized negative diffuse localized localized diffuse negative localized diffuse localized localized localized diffuse localized diffuse
12 21 13 14 33 35 29 42 36 20 87 27 99 18 80 58 51 29 20 27 25 23 145
+
12 22 26 30 30 51 38 46 54 50 52 54 57 74 48 54 65 56 66 66 87 62 93
33 35 57 76 54 73 75 77 95 83 87 90 102 113 83 87 91 96 105 128 126 126 144
Indium-1
11 antimyosin
administration
and imag-
Mean aortic cross-clamp time was 51 f 19 minutes; bypass time was 88 f 27 minutes.
For the antimyosin studies, a murine monoclonal antibody Fab fragment (Myoscint”, Centocor Europe) was used. Eighty MBq of indium-1 11 was added to a single vial containing 2 ml of antimyosin-Fab-DTPA preparation in citrate buffer. The labeling efficiency was >9590. Indium- 111 antimyosin was injected intravenously on the third day after surgery. All drain systemshad been removed 124 hours earlier without signs of ongoing pericardial leakage. Planar images were obtained after 48 hours in the anterior and 45” left anterior oblique position. A General Electric Maxi 400 large-field-of-view gamma camera was used, fitted with a medium energy collimator. A 20% energy window was set to the 170 and 247 keV photon peak. Analog and digital images for each view were acquired for a lo-minute period, using a 128 X 128 matrix for the latter. All studies were assessedby 2 experienced investigators unaware of clinical and biochemical data. When present, myocardial uptake was defined as localized or diffuse. Statistical analysis: All data are expressedas mean f 1 standard deviation. Student t tests are usedto analyze differences between groups. A p value 70 IU/liter.
In none of the patients did pathologic Q waves appear on the electrocardiogram after surgery. In 14 patients ST-segmentor T-wave changes were present (individual data are listed in Table I). Indium-1 1 i antimyosin sciatigraphy: No side effects were noticed after injection of indium-1 11 antimyosin. Images could be obtained in all 23 patients. In 19 patients (82%) myocardial uptake of indium-1 11 antimyosin was demonstrated (Figure 1); uptake was localized in 12 patients and diffuse in 7. In 4 patients no uptake was found. All but 1 of these 4 patients had a creatine phosphokinaseMB peak value of 570 IU/liter, the postoperativeupper normal limit. Only in 3 of the 19 patients with myocardial uptake did creatine kinase MB value exceedthe level of 70 IU/liter. In the other 16 patients ereatine kinase MB value was above the laboratory normal limit, but 570 IU/liter. There was no good relation between the type of antimyosin uptake (negative, local or diffuse) and creatine kinase MB levels (Figure 2). Electrocardiographic changes involving the ST-segment or T wave occurred in all 3 groups. Again, no differences between patients with local uptake versus patients with diffuse uptake were found (Figure 3). There proved to be no good relation between aorta cross-clamptime (43 f 8, 58 f 28, 51 f 13 minutes) or duration of cardiopulmonary bypass (80 f 3, 93 f 35, 89 f 26 minutes) and degree of iridium-1 11 antimyosin
CK-MB
vs. IN-111 ANTIMYOSIN
UPTAKE
uptake (Figures 4 and 5). Mean values did not differ significantly. Indium- 111 antimyosin uptake was present in the 2 patients with l-vessel diseaseand in 17 of 21 patients with multivessel disease.Localized uptake was consistently situated in grafted areas. ISCUSSION
Since myocardial injury is a major prognostic determinant after cardiac surgery, data on its incidence and extent may be important. However, controversy exists regarding the frequency and clinical implications of postoperative myocardial infarction. The incidence highly dependson the selection of patients and the techniques used to measure myocardial damage. Furthermore, several preoperative factors may predispose to postoperative myocardial infarction, such as recent infarction, depressedleft ventricular function, extent of coronary artery disease and unstable angina.” The changing profile of patients undergoing CABG-that is, increasing emergency procedures, patients with unstable angina, CABG in the elderly, combined procedures-increases the risk.r2 Finally, anesthesia-related problems, inadequate myocardial protection and a long duration of both aorta cross-clamping and cardiopulmonary bypass may also contribute to myocardial injury.13 The assessmentof the presenceand magnitude of myocardial necrosis after CABG is difficult. Mechanisms of onset, clinical presentation and even ultrastructural characteristics of postoperative myocardial damage differ from the classic type of myocardial infarction.14 This
IU/I 160 I
STT
CHANQE
ISZB NO
STT
CHANGE
140 120
.
100
i-i M s
60
.
60
. .
40
1 ! .
20
m .
z :
: i
NO
0
UPTAKE INDIUM-Ill
NO UPTAKE
DIFFUSE
LOCAL
LOCAL
DIFFUSE ANTIMYOSIN
UPTAKE
- r of patients with presence or absence of T-~~~e~t or T wave (STT) changes. ST-T changes occur in all growps. No difference was present when patients with ar local uptake of indium411 antimyosin were com-
THE AMERICAN JOURNAL OF CARDIOLOGY
NOVEMBER 15, 1990
difference may complicate the interpretation of routine diagnostic tests. Furthermore, methodologic differences in various studies, although using the same test, complicate the comparison of results. Routine tests, such as enzyme measurements and electrocardiography, give rise to diverging and unsatisfying results. Postoperative myocardial infarction is diagnosed in about 5% of patients when the appearance of new Q waves is used, whereas the number goes up to 40% when ST-segment changes are taken into account.15The presenceof new Q waves is strongly related to postoperative myocardial infarction, but their absencewill underestimate the incidence of small, especially subendocardial lesions. Creatine kinase MB isoenzymes,the gold standard for the diagnosis of myocardial infarction, are elevated in almost all patients after CABG,16 but their clinical relevance in the absence of other signs of postoperative myocardial infarction remains doubtful. Infarct imaging with technetium-99m pyrophosphate has been reported to be positive in more than 20% of patients after CABG. l7 This technique, however, is known to have a lower sensitivity in the setting of subendocardial necrosis,18which is the most frequent site of perioperative myocardial damage. Also, studies on left ventricular wall motion are conflicting, and improvement19 as well as deterioration of function20,21have been demonstrated.
Becausethe imaging technique usedherein is highly specific for myocardial damage, the following question has to be answered in the light of the present findings: What is a normal test result in this particular population? Some myocardial necrosismay be almost obligatory after CABG, but the favorable outcomein the majority of patients emphasizesthe limitation of its importance. Despite all precautions before and during operation, coronary bypasssurgery seemsto be an insult to the myocardium. Acute changes in hemodynamics, temperature changes and direct contact with surgical instruments will damagemyocardial cells. Additionally, reperfusion of previously ischemic myocardium may be harmful and may lead to necrosis.22%23 Bulkley et al7 reported the postmortem results in patients who died within 30 days after CABG. They found evidencein 48 of 58 patients (83%) for subendocardial contractionband necrosis,which is one of the pathologic features of reperfusion injury,22,24localized in areas with widely patent bypass grafts. They concluded that reperfusion injury was common after CABG. Weisel et al8 demonstrated the generation of free oxygen radicals after cardioplegic arrest leading to membrane damage in myocardial biopsy specimensobtained during surgery. In the present study all patients had an elevatedcreatine kinase MB level when compared to the normal referencevalue in a healthy population. Only 4 patients
CPB TIME Vs. IN-111 ANTIMYOSIN CROSS-CLAMP
TIME vs. ANTIMYOSIN
UPTAKE
UPTAKE MIN 160
120
. 140 100
.
C g
. .
120
.
100
s
9f
.
80
E
C .
E T
. .
60
80
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FIGURE 4. Relation between aorta cross-clamp time (in minutes) and indium-1 11 antimyosin uptake. Mean values, indicated by black lines, do not differ significantly.
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THE AMERICAN JOURNAL OF CARDIOLOGY
VOLUME 66
NO UPTAKE
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FIGURE 5. Relation between cardiopulmonary bypass (CPB) time (in minutes) and indium-1 11 (IN-1 11) antimyosin uptake. Mean values, indicated by black lines, do not differ significantly.
(17%) had a value >70 IU/liter, used as the normal Chaitman BR, Alderman EL, Kaiser CG, Faxon DP, Bourassa MG. Detrimental of perioperative myocardial infarction on late survival after coronary artery upper limit after CABG, a percentage in keeping with effect bypass. J Thorac Cardiovasc Surg 1984;89:972-981. the data of McGregor et a1.25Indium-I 1I antimyosin 7. Bulkley BH, Hutchins GM. Myocardial consequences of coronary artery scintigraphy showed uptake in 82% of our patients and bypass graft surgery. The paradox of necrosis in areas of revascularization. Circu1977;56:906-913. gaveevidencefor myocardial necrosis,which did not af- 8.lation Weisel RD, Mickle DAG, Finkle CD, Tumiati LC, Madonik MM, Ivanov J, fect clinical course. The incidence of perioperative ne- Burton GW, Ingold KU. Myocardial free-radical injury after cardioplegia. Circucrosis in our patients, assessedwith indium-111 anti- lation1989;(suppl 111)80:111-14-111-18. Khaw BA, Yasuda T, Gold HK, Leinbach RC, Johns JA, Kanke M, Barlaimyosin, is in keeping with the postmortem data of Bulk- 9.Kovach M, Strauss HW, Haber E. Acute myocardial infarction imaging with ley et a1.7 However, they studied a highly selected indium-111 labeled monoclonal antimyosin Fab. J Nucl Med 1987;28:1671population. Our data, in contrast, were obtained in pa- 1678. 10. Van Vlies B, Baas J, Visser CA, Van Royen E, Delemarre BJ, Bot H, tients with an uneventful postoperative course in whom Dunning AJ. Predictive value of indium-1 11 antimyosin uptake for improvement the previously mentioned factors, which may predispose of left ventricular wall motion after thrombolysis in acute myocardial infarction. J Cardiol 1989;64:167-171. for postoperative myocardial infarction, were also ab- Am Il. Roberts AJ. Perioperative myocardial infarction in open heart surgery. In: sent. This indicates that some degree of myocardial Utley JR, ed. Perioperative Cardiac Dysfunction. Cardiothoracic Surgery Series. damagemay be a common phenomenon even after un- vol. 3. Baltimore, London, Los Angeles, Sydney: Williams 8r Wilkins, 1985: complicated surgery. Furthermore, indium- 111 anti- 1077121. 12. Naunheim KS, Fiore AC, Wadley JJ, McBride LR, Kanter KR, Pennington myosin uptake was not related to the duration of aorta DG, Barrier HB, Kaiser CG, Willman VL. The changing profile of the patient undergoing coronary artery bypass surgery. J Am Coil Cardiol1988;11:47 l-477. cross-clampingor cardiopulmonary bypass. 13. Baur HR, Peterson TA, Arnar 0, Gannon PG, Gobel FL. Predictors of A gold standard for the diagnosis of postoperative perioperative myocardial infarction in coronary artery operation. Ann Thorac myocardial infarction doesnot exist. Myocardial injury, Surg 1981;31:36-44. 14. Kirklin JW, Barratt-Boyes BG. Cardiac Surgery. New York: John Wiley, however,seemsto be frequent, and related to the surgi- 1986:85-89. cal procedure. When it will becomerelevant for clinical 115. Hultgren HN, Shettigar UR, Pfeifer JF, Angel1 WW. Acute myocardial course,or to what extent it may be acceptedas normal infarction and ischemic injury during surgery for coronary artery disease. Am J 1977;94:146-153. in this particular situation, should be the subject of fur- Heart 16. du Cailar C, Maille JG, Jones W, Solymoss BC, Chabot M, Goulet C, Delva ther study. Comparison of patients who have an un- E, Grondin CM. MB creatine kinase and the evaluation of myocardial injury aortacoronary bypass operation. Ann Thorac Surg 1980;29:8-14. eventful course with patients who have overt periopera- following 17. Burns JB, Gladstone PJ, Tremblay PC, Feindel CM, Salter DR, Lipton IH, tive damage is needed. Quantification of indium-1 11 Ogilvie RR, David TE. Myocardial infarction determined by technetium-99m antimyosin uptake will be necessaryto use it as a dis- pyrophosphate single-photon tomography complicating elective coronary artery grafting for angina pectoris. Am J COrniol 1989;63:1429-1434. criminating technique. Moreover, the relation with bypass 16. Massie BM, Botvinick EH, Werner JA, Chatterjee K, Parmley WW. Myochangesin left ventricular function has to be studied, cardial scintigraphy with technetium-99m stannous pyrophosphate: an insensitive for nontransmural myocardial infarction. Am J Cardiol 1979;43:186-197. sinceonly clinical coursewas considered;however, there test 19. Koolen JJ, Visser CA, van Wezel HB, Mcyne NG, Dunning AJ. Influence of were no signs of hemodynamic deterioration. coronary artery bypass surgery on regional left ventricular wall motion: an intraoperative two-dimensional
transesophageal echocardiographic
study. J Cardio-
rhorac An&h 1987;1:276-283.
REFERENCES 1. CASS Principal Investigators and their associates. Coronary artery surgery study (CASS): A randomized trial of coronary artery bypass surgery. Quality of life in patients randomly assigned to treatment groups. Cimdation 1985;68:95ll
960. 2. Califf RM, Harrel FE, Lee KL, Rankin JS, Hlatky MA, Mark DB, Jones RH, Muhlbaier LH, Newland Oldham H, Pryor DB. The evolution of medical and surgical therapy for coronary artery disease. A 15-year perspective. JAMA l989;261:2077-2086. 3. Roberts AJ. Perioperative myocardial infarction and changes in left ventricular performance related to coronary artery bypass graft surgery. Ann Thorac Surg 1983;35:208-225. 4. Warren SG, Wagner GS, Bethea CF, Roe CR, Newland Oldham H, Kong Y. Diagnostic and prognostic significance of electrocardiographic and CPK isoenzyme changes following coronary bypass surgery: correlation with findings at one year. Am Heart J 1977;93:189-196. 8. Hall RJ, Elayda MA, Gray A, Mathur VS, Garcia E, De Castro CM, Massumi A, Cooley DA. Coronary artery bypass: long-term follow-up of 22,284consecutive patients. Circulntion 1983;(suppl II)68:11-20-E-26. 6. Schaff HV, Gersh BJ, Fisher LD, Fry RL, Mock MB, Ryan TJ, Ells RB,
20. Hammermeister KE, Kennedy JW, Hamilton GW, Stewart DK, Gould KL, Lipscomb N, Murray JA. Aortocoronary saphenous vein bypass. Failure of successful grafting to improve resting left ventricular function in chronic angina. N Engl J Med 1977;290:186-192. 21. Wolf NM, Kreulen TH, Bove AA, McDonough MT, Kessler KM, Strong M, Le Mole 6, Span” JF. Left ventricular function following coronary bypass surgery. Circulation 1978;58:63-70. 22. Braunwald E, Kloner RA. Myocardial reperfusion: a double-edged sword? J Clin Inuest 1985;76:1713-1719. 23. Miyazaki S, Fujiwara H, Onodera T, Kihara Y, Matsuda M, Wu DJ, Nakmura Y, Kumada T, Sasayama S, Kawai C, Hamashima Y. Quantitative analysis of contraction band necrosis after ischemia and reperfusion in the porcine heart. Circulation 1987;75:1074-1082. 24. Matsuda MM, Fujiwara H, Onodera T, Tanaka M, Wu DJ, Fujiwara T, Hamashima Y, Kawai C. Quantitative analysis of infarct size, contraction band necrosis, and coagulation necrosis in human autopsied hearts with acute myocardial infarction after treatment with selective intracoronary thrombolysis. Circulation 1987;76:98 l-989. 25. McGregor CGA, Muir AL, Smith AF, Miller HC, Hannan WJ, Cameron EWJ, Wheatley DJ. Myocardial infarction related to coronary artery bypass graft surgery. Br Heart J 1984;51:399-406.
THE AMERICAN
JOURNAL
OF CARDIOLOGY
NOVEMBER
15. 1990
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