The predictive value of myocardial scintigraphy with ggmtechnetium pyrophosphate in diagnosingacute myocardial infarction P. F. Harilund-Carlsen, J. Badskjaer, J. Boetius Hertz, 0. Helmer Sarrensen, 1. Christiansen and A. Uhrenholdt Dept. of Clinical Physiology and Medical Department, Cardiological section, Hvidovre hospital, COPENHAGEN, DENMARK

Abstract Myocardial scintigraphy with 99mtechnetiumpyrophosphate was performed in two selected groups of patients, consisting of 20 who had acute myocardial infarction (AMI) clinically and 18 who had no AM1 clinically. The purpose was to estimate the value of this method in the detection or disproof of AM1 compared with usual procedures (ECG and serum enzyme determination - GO-transaminase and ai-fraction of LDH). Each of the 20 patients with clinical AM1 had positive scintigrams. There were no falsenegative findings. Out of 18 without AMI, 15 had negative scintigrams; in the other 3, scintigraphic findings were false-positive. The prevalence of AM1 among patients admitted to the cardiological department was 0.39. In this population of patients, the calculated predictive value of a positive scintigram was 0.80, whereas the predictive value of a negative was 1.0. In patients admitted to the coronary care unit, the prevalence of AM1 was 0.51; the corresponding predictive values of a pcsitive scintigram was 0.86 and of a negative 1.0. The identity between scintigraphic and electrocardiographic infarct localization was good. Infarct size estimated by scintigraphy was not significantly correlated to the maximum elevation of serum enzyme concentr2tion. In patients suspected of having AMI, it is

highly probable that a negative scintigram obtained from day 2 to day 6 after the onset of symptoms will rule out the presence of acute myocardial infarction.

Introduction The diagnosis of acute myocardial infarction (AMI) based on the occurrence of chest pain, sequential electrocardiographic changes, and elevation of serum enzyme activity cannot always be made with certainty. In recent years, the search for safer methods for detecting or excluding the presence of AM1 has led to the use of isotope scintigraphic technique for visualizing the infarcted area of the myocardium (2, 3, 9). The purpose of this study was to determine the predictive value of a positive and a negative myocardial scintigram.

Material and methods 20 patients with and 20 patients without

clinical AM1 were investigated. The diagnosis was based on the simultaneous presence of two of the following three phenomena: typical history of disease, characteristic ECGchanges, and temporary elevation of serum enzyme activity (serum aspartateaminotransferase [ASAT] and ai-fraction of serumlactatedehydrogenase [LDHI. Fourteen patients in the group with AM1 had transmural infarction, 2 had non-penetrating (nontransmural) infarction, 3 had subendocardial infarction, and one had left bundle branch

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block, which made judgement of the ECG impossible. T w o were excluded from the control group of patients without clinical AMI. One because she had streptoc(iccus endocarditis. The other because he had earlier had myocardial infarction. Informed consent was obtained from each patient on entering the study. The investigation was made with a gamma camera with high resolution collimator collection 500,000 counts one hour after the intravenous injection of 15 mCi 99mTc-pyrophosphate (Tc-PYP). Pictures were obtained in the anterior (Al’), the left anterior oblique (LAO), and the left lateral (LL) projecticns. The scintigrams were evaiuated jointly by two investigators withcut previous knowledge of the clinical diagnosis. T h e degree of intensity of myocartiial uptake was graded according to an arbitrary scale described by l’arkery et al. (8): 0 (no activity), 1+ (questionable activity), 2 (definite activity), 3 and 4 (increasing degrees of activity within the infarct zone). Zero and 1+ were considered negative; 2 + , 3 + and 4 + in only one projection were considered positive. Infarct localizations were estimated as anteroseptal, antero-apical, antero-lateral, and inferior, or combinations of these.

Figure 1A-C shows a normal (negative) scintigram of a patient without clinical evidence of AMI. Figure 2A-C demonstrates typical scintigrams in three projections from a patient with AMI. Note typical doughnut o r horseshoe appearance of increased myocardial uptake surrounding central area with sparse activity. Figure 3A-C demonstrates an inferior infarction characterized by a disclike activity in the diaphragmatic wall. Being viewed from the side in all three projections, the infarct size cannot be estimated, and a central decrease in activity cannot be observed. In the patients with AMI, scintigraphy was performed within day 1 to day 6 of observation (mean 3.0 days). Each of the 20 patients had a positive scintigram (Table I). Fifteen of

Fig. 1. Negative (normal) myocardial scintigrams o f a patient without acute myocardial infarction shown in the three standard views A ) antcrior, B ) 41i0 left anterior oblique, C ) left lateral.

Note activity in the sternum in the middle o f A ) and to the left in B), and activity in the vertebral column behind ribs i n the middle of B ) and to the right in C).

+

56

+

+

Infarct size was estimated as follows: small (smaller than the width of 2 ribs with interjacent intercostal space), medium (coricspcnding to the width of 2 ribs), large (larger than the width of 2 ribs). Electrocardiographic infarct localization was defined as follows: antero-septa1 ( V I - ~ ) , antero-apical (v3-6), antero-lateral (V4-43, AVL, I), inferior (11, 111 and AVF).

Results

Fig. 2. Positive ( 4 + ) scintigrams o f a patient with extensive acute anterior wall infarction

shown in A ) anterior, B ) 4 1 O left anterior obliqwe, C ) left lateral views.

Fig. 3. Positive scintigrams a f a patient with acute infero-lateral infarction shown in A ) an-

terior, B ) views.

the 18 without clinical AM1 had a negativc scintigram; scintigraphic findings were positive in the remaining three. Nosographically. this metnt that the probability of a positive

Table I. Scintigraphic compared with clinical diagnosis.

20 20

scintigram in patients with AM1 was -

45O

left anterior oblique, C ) left lateral

1

SCINTIGRAPHY

I

I

+

~ 1 . 0 ,wtereas the probability of a negative 15

scintigram in those without AM1 was 18

=0.83.

The diagnostic probabilities were calculated with Bayes’ theorem (14). The prevalence of AM1 among patients admitted to the cardiological department in Hvidovre hospital was 0.39. The corresponding predictive value of a positive scintigrarn was 0.80, and that of a negative scintigram was 1.0.

I

- I

3

15

In patients admitted to the coionary care unit in Hvidovre hospital, the prevalence of AM1 was 0.51. The corresponding figure for the predictive value of a positive scintigram was 0.86 and for a negative, 1.0.

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Table 11. Sci tigraphic compared with electrocardiogi .phic infarct localization.

Our material did not contain either electrocardiographic or scintigraphic posterior infarctions.

SCINTIGRAPHY Anterior

inferior

Anterior ECG Inferior I +:) 1 patient h d left bundle branch block. Scintigraphic infarct size was not significantly correlated to the maximum elevation of serum enzyme activity in patients with AMI. In the group of patients with clinical AMI, 7 had inferior infarction on both scintigram and electrocardiogram; 13 showed an anterior infarction on the scintigram and 12 of them had corresponding electrocardiographic localization. T h e other patient had left bundle branch block that did not permit determination of infact localization, but autopsy one week later revealed recent infarction in the anterior wall of the left ventricle. Table 111 gives a comparison of scintigraphic and electrocardiographic subdivisions of anterior wall infarctions.

Discussion Since 1974, 99mTc-labelled radiopharmaceuticals which sequester in acutely infarcted myocardium have been used clinically for positive scintigraphic visualization of AMI. Among several compounds, the bone-seeking technetium phosphates have gained the greatest popularity. In animals, they concentrate in infarcted myocardial tissue with an infarct!normal myocardium ratio of about 10 (2). I t was recently shown (4) that TcPYP is superior to both 99mTc-tetracycline and 99mTc-glucoheptonate in detecting acute myocardial infarction. The mechanism of uptake in infarcted, and possibly severely ischaemic, myocardial tissue is not known with certainty. A certain perfusion is necessary for the tracers to reach their target (7, 9), and they are likely to localize primarily in the border zone of the infarcted area. Necrotic myocardial cells accumulate calcium ions. These are probably bound in hydroxyapatite-like structures that have been observed in infarcted and perhaps also in ischaemic myocardial cells (3, 8, 9, 10). We found a positive scintigram in each

Table 111. Anterior infarct localization. Thirty-four scintigraphic localizations compared with 32 electrocardiographic localizations. SCINTYGRAPHY Anteroseptal Anteroseptal Anteroapical Rnterolateral Undetected 58

Anteroapical

Antero-

Undetected

of the 20 patients with clinical AMI. This described on the scintigrams. In these cases, corresponds to the findings of other investi- scintigraphy overestimated the extent of gators, who have no false negative scinti- infarction, indicating that Tc-PYP might grams with Tc-PYP where myocardial scinti- not only mark necrotic myocardial tissue, graphy was carried out from 18 hours to 6 but possibly also severely ischaemic myodays after the onset of symptoms. The false- cardial cells, as has been shown experipositive scintigrams that we found might be mentally in animals (7). due to insufficient selection of the control In one patient with electrocardiographical group. O n the other hand, some patients with inferior and antero-lateral infarct, the scintiheart aneurism (1, 6 ) and unstable angina graphic localization was inferior and antero(13) have been reported to demonstrate po- septal. Here, too, the explanation might be sitive scintigrams in the absence of clinical labelling of ischaemic cells, because shortly evidence of AMI. False-positive scintigrams afterwards the patient developed anterohave also been described in patients after septal infarction that was later verified at left radical mastectomy, in a patient with autopsy. carcinoma of the left lung treated with XThe method is not specific, but applied to rays (11), and in an instance of secondary patients admitted to a coronary care unit hyperparathyreoidism with complicating with suspicion of AMI, the predictive value uraemic pericarditis (5). of a positive scintigram was reasonably high In patients with AMI, positive scintigrams (0.86). Naturally, this information has with T-PYP and other bone-seeking tech- limited value, because the scintigraphic menetium labelled phosphates will become ne- thod was compared with other investigations gative within one or two weeks after the (ECG and serum enzyme activity) whose onset of symptoms, unless left ventricular diagnostic value is not definitely known. aneurism or akinesis develops. The use of However, in patients with AMI, the scintiTc-PYP after this period makes the demon- grams almost always seem to be positive on stration of repeated infarcts possible. With the second or third day after the onset of 99mTc-tetracycline and 20lthallium, scinti- symptoms. Combined with a predictive grams will be positive in patients with old value of a negative scintigram of 1.0, this infarctions. implies that a negative scintigram obtained In our investigation, it was possible to on the third day of observation can exclude distinguish between anterior and inferior in- with considerable certainty the presence of farctions (Table 11). It was also possible to AM1 (defined according to current criteria). estimate the localization and extension of In conclusion, we find that the method has anterior infarctions with satisfactory accu- its most important diagnostic values where racy (Table 111). T w o antero-septa1 localiza- the electrocardiogram might fail to disclose tions were overlooked on the scintigrams; an acute myocardial infarction: in patients undoubtedly, accumulation of activity in the with bundle branch block, old myocardial sternum made interpretation difficult. In two infarction, o r subendocardial infarction (12). patients, scintigrams did not reveal an antero- O u r investigation showed that a negative lateral localization which was registered myocardial scintigram will rule out the preelectrocardiographically. One of these pa- sence of AM1 with a high degree of protients had a subendocardial infarction with bability. Time will show whether the mea rather faint and diffuse accumulation of thod will gain additional importance in the activity, whereas the other had an inferior early detection of postinfarction aneurisms, infarction both electrocardiagraphically and in estimating the infarct size, particularly scintigraphically, but ECG also showed during infarct-limiting treatment, and hopechanges in lead VS. Conversely, 4 antero- fully become a useful tool for a better underlateral and 2 antero-apical infarct localiza- standing of the pathophysiology of acute tions that were not seen on the ECG were myocardial infarction. 59

References 1. Ahmad, M., Dubiel, J. P., Verdcn, T. A., Jr. & Martin, R. H.: Technetium 99m stmnous pyrophosphate myocardial imaging in patients with and without left ventricular aneurysm. Circulation 53: 883, 1976. 2. Bonte, F. J., Parkey, R. W., Graham, K. D. & Moore, J. G.: Distributions of several agents useful in imaging myocardial infarcts. J. Nucl. Med. 16: 132, 1975. 3. D’Agostino, A. N. & Chiga, M.: Mitochondrial mineralization in human myocardium. Am. J. Clin. Pathol. 53: 820, 1970. 4. Holman, B. L., Tanaka, T. T. & Lesch, M.: Evaluation of radiopharmaceuticals for the detection of acute myocardial infarction in man. Radiology 121: 427, 1976. 5. Janowitz, W. R. & Serafini, A. N.: Intense myocardial uptage of 99mTcdiphosphonate in a uremic patient with secondary hyperparathyroidism and pericarditis: pase report. J. Nucl. Med. 17: 896, 1976. 6. Kelly, R. J., Cowan, R. J., Maynard, C. D., Headly, R. N. & Kahl, F. R.: Localization of 99mTc-Sn-Pyrophosphate in left ventricular aneurysms. J. Nucl. Med. 18: 342, 1977. 7. Marcus, M. L., Tomanek, R. J., Ehrhardt, J. C., Kerber, R. E., Brown, D. D. & Abboud, F. M.: Relationship between myocardial perfusion, myocardial necrosis, and technetium-99m pyrophosphate uptake in dogs subjected to sudden coronary occlusion. Circulation 54: 647, 1976.

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8. Parkey, R. W., Bonte, F. J. Mcyer, S. L., Atkins, J. M., Currey, G. L., Stokely, E. M. & Willerson, J. T.: A new method for radionuclide imaging of acute myocardial infarction in humans. Circulation 50: 540, 1974. 9. Poe, N. D.: Present status of positive scintigraphic imaging of myocardial infarction. Scand. J. Clin. Lab. Invest. 36: 401, 1976. 10. Shen, A. C. & Jennings, R. B.: Myocardial calcium and magnesium in acute ischemic injury. Am. J Pathol. 67: 417, 1972. 11. Soin, J. S., Burdine, J. A. & Beal, W.:

Myocardial localization of 99mTc-pyrcphosphate without evidence of acute myocardial infarction. J. Nucl. Med. 16: 944, 1975. 12. Willerson, J. T., Parkey, R. W., Bonte, F. J., Meyer, S . L. & Stokely, E. M.: Acute subendocardial myocardial infarction in patients. Its detection by technetium 99-m stannous pyrophosphate myocardial scintigrams. Circulation 51: 436, 1975. 13. Willerson, J. T., Parkey, R. W., Bonte, F. J., Meyer, S . L., Atkins, J. M. & Stokely, E. M.: Technetium stannous pyrophosphate myocardial scintigrams in patients with chest pain of varying etiology. Circulation 51: 1046, 1975. 14. Wulff, H. R.: Rationel klinik. Munksgaards Forlag, Kebenhavn 1973.

The predictive value of myocardial scintigraphy with 99mtechnetium pyrophosphate in diagnosing acute myocardial infarction.

The predictive value of myocardial scintigraphy with ggmtechnetium pyrophosphate in diagnosingacute myocardial infarction P. F. Harilund-Carlsen, J. B...
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