Non-Invasive Cardiology Adv. Cardiol., vol. 22, pp. 23-28 (Karger, Basel 1978)
Noninvasive Diagnosis of Acute Myocordial Infarction with 99Tcm-Pyrophosphate Scintigraphy DANIEL
s. BERMAN and DEAN T. MASON
Cardiovascular Medicine, University of California, School of Medicine, Davis, Calif.
A variety of radionuclidic techniques are now available for the noninvasive assessment of acute myocardial infarction. These techniques can be divided into two major groupings: (1) cold spot myocardial imaging in which the infarction is detected as an area of decreased radioactivity and (2) hot spot myocardial imaging in which the abnormal area is visualized as an area of increased radioactivity. The hot spot imaging agents can be utilized not only for detection of presence, location, and size, but also are very useful in determining whether an infarction is acute or old. The major advance in the development of hot spot imaging agents followed the discovery that the bone seeking radiopharmaceutical 99Tcm-pyrophosphate (99Tc m_PYP) accumulates in acutely infarcted myocardium [1]. This agent has become the radionuclide of choice in the detection of acute myocardial infarction. 99Tc m_PYP offers a combination of the radioisotope with ideal physical characteristics (99Tc m) with a phosphate complex that has advantageous biological characteristics for imaging myocardial infarction. The agent is rapidly cleared from the blood, so that imaging can be performed as early as 1 h after injection. In addition, there is avid accumulation of the radiopharmaceutical in the region of acute infarction, with high activity ratios between infarction and surrounding tissue. Finally, although the radiopharmaceutical accumulates in bone, there is no liver accumulation. Thus it is not difficult to detect inferior wall infarction. The bone accumulation has not been a major detriment to determining the presence of infarction even when the infarctions are small. The reason for this is that multiple views are routinely obtained which allow separation of the regions of acute infarction from the overlying ribs.
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Introduction
BERMAN/MASON
24
Materials and Methods In the Coronary Care Unit, 15 mCi of 99Tc m _PYP is injected intravenously [2]. 2 h after injection imaging is performed in the adjacent Nuclear Cardiology Laboratory. We have chosen the 2-hour interval to minimize the problem of separating normal blood background from abnormal myocardial uptake. Recent developments in nuclear instrumentation now allow for the performance of this study in the Coronary Care Unit itself using a portable scintillation camera. Imaging is performed with the scintillation camera equipped with a high resolution collimator. 500,000 count images are obtained in the anterior, left anterior oblique (LAO), left lateral, and right anterior oblique positions, using both Polaroid and Microdot films. The scintigraphic data are also collected on computer disc for blood pool [3] and rib subtractions [2]. The degree of radionuclidic uptake in the cardiac region is assessed as follows: 4 + indicates greater activity than bone, 3 + is activity equal to bone, 2 + is less than bone but moderate, 1 + is slight, and 0 is no detectable activity. In addition, the uptake pattern is judged to be focal or diffuse. The scintigraphic study is considered negative if there is o to 1 + myocardial activity. A positive study is one in which there is 3 + to 4 + myocardial activity in either focal or diffuse patterns, or 2 + focal activity. The interpretation of the 2 + diffuse pattern represents the principal difference in our criteria from those of previous workers; we classify this type of scan as equivocal rather than positive [2].
Results
Abnormal Study In the presence of acute transmural infarction a focal increase in radioactivity is seen in the infarcted region [2). In acute anterior myocardial infarction (fig. 1, bottom panel), a large area of increa~ed activity is observed on the anterior view, and the LAO and left lateral views confirm the anterior location of the radioactivity. In inferior myocardial infarction, an area of
Downloaded by: University of Cambridge 131.111.164.128 - 3/19/2019 1:08:56 AM
Normal Study In a typical normal study, the ribs and sternum are well visualized, but the heart is not seen (fig. 1, top panel). Frequently, however, diffuse activity may be observed throughout the region of the heart, representing radioactivity remaining in the blood pool not yet having been cleared by either bone or kidneys. If there is no evidence of selective localization within the myocardium, the study is probably normal and considered not to represent acute infarction. When the blood pool is seen prominently, additional delayed imaging 3-4 h after injection may show further decrease in blood pool activity, and thereby increase observer certainty about the absence of infarction.
99TcID-Pyrophosphate Scintigraphy
25
Fig. 1. Normal (top panel) and acute anterior myocardial infarction (M!) (bottom panel) 99Tcm-pyrophosphate scintigrams. ANT = Anterior; LAO = left anterior oblique; LLAT = left lateral views. From BERMAN et at. [2].
Equivocal Studies We have found it useful to define a third category of scintigraphic interpretation comprising patients who have apparent blood pool radioactivity [2]. This group constitutes an equivocal study intermediate between
Downloaded by: University of Cambridge 131.111.164.128 - 3/19/2019 1:08:56 AM
increased activity is seen at the inferior border of the heart on all views. Posterolateral myocardial infarction is detected as a region of increased activity along the lateral border of the heart seen best on the anterior view, with the LAO and lateral views confirming the posterolateral location of the radioactivity. Occasionally a transmural myocardial infarction will present as a diffuse increase in radioactivity throughout the left ventricle; however, this pattern is unusual. There is excellent correlation between electrocardiographic and scintigraphic determination of the location of acute transmural infarctions. Nontransmural myocardial infarction is more difficult to detect with the 99Tc ffi _PYP technique. If a definite abnormality is present, it may either be a focal area of increased activity, or diffuse increase in radioactivity throughout the left ventricular myocardium. However, subendocardial infarctions may simply present as an increase in apparent blood pool activity and thereby go undetected.
BERMAN/ MASON
26
those with distinctly abnormal scintigrams and those with definitely negative scintigrams. The rationale for this separation is that only a small percentage of patients with the equivocal pattern have acute infarction. Thus in a recent study of 235 patients with acute chest pain syndromes at our institution, 50 patients exhibited the pattern of apparent blood pool activity [2]. 9 of these 50 patients had acute nontransmural myocardial infarction documented by standard electrocardiographic and myocardial enzymatic criteria. Of the remainder, 5 had acute transmural infarction, 35 had no laboratory evidence of acute myocardial infarction, and in 1, the clinical diagnosis of infarction was equivoca l. Recently there have been a number of reports of false-positive infarct scintigrams using 99Tc ffi _PYP. However, a large proportion of these images exhibited the pattern which we classify as equivocal. We find that by separating this equivocal group from those with distinctly positive scans, the specificity of 99Tc m _PYP imaging for acute myocardial infarction is greatly increased, with only slight loss in sensitivity. This decrease in sensitivity noted in our series was principally confined to the nontransmural infarction group.
Specificity of PYP Scintigraphy for Acute M y ocardial Infarction When our strict criteria for a positive study were employed, the specificity of the technique for acute infarction was also quite high [2]. Thus of 126 patients with no evidence of acute myocardial infarction by clinical or laboratory criteria, only 4 demonstrated definitely positive 99Tc m _PYP ' patients had focal uptake in regions scintigrams. 2 of these 4 false-positive' of left ventricular dyskinesis secondary to remote myocardial infarction. The findings in these 2 patients are consistent with those of others who previously have reported focal uptake of 99Tc m _PYP in chronic coronary patients with ventricular aneurysms. Both the high sensitivity and high specificity in this study are a d irect result of the use of our classification which employs an equivocal category for the 2 + diffuse scintigram.
Downloaded by: University of Cambridge 131.111.164.128 - 3/19/2019 1:08:56 AM
Sensitivity of PYP SCintigraphy in Detecting Presence of Acute Infarction Our results demonstrate that with the new modified classification the 99Tc m _PYP imaging technique is a highly sensitive method for detection of acute myocardial infarction [2]. Of 81 patients with acute transmural myocardial infarction none had a negative scintigram, and of 18 patients with acute nontransmural infarction only 2 demonstrated false-negative studies. Thus only 2 % of the patients with acute infarction, transmural or nontransmural, had negative PYP scintigraphy.
99Tcm-Pyrophosphate Scintigraphy
27
False-Positive Studies
A large number of reported false-positive studies in the literature would not be considered positive if strict criteria for positive studies were utilized [2]. Nevertheless, despite strict criteria for positive study, certain conditions other than acute myocardial infarction may result in increased uptake of 99Tc m _PYP within the myocardium. Thus we noted this finding in only 4 of 126 patients with no clinical evidence of infarction. The clinical conditions which have occasionally been associated with false-positive studies are as follows: (1) unstable angina pectoris; (2) valvular calcification (multiple scintigraphic views and chest X-ray easily distinguish this pattern from that of acute infarction); (3) left ventricular aneurysm; (4) old myocardial infarction (rarely intense) without definite clinical evidence of acute myocardial infarction; and (5)postelectric cardioversion. Therefore, when strict criteria for positive study are utilized, the frequency of a false-positive study is quite low.
The principal clinical usefulness of the infarct scintigram at the present time is the detection of the presence of acute myocardial infarction in patients in whom the diagnosis of infarction is obscure. This group includes patients with left bundle branch block, previous myocardial infarction with new infarction in an adjacent region, intraoperative myocardial infarction, infarction in patients who have received intramuscular injections, true posterior myocardial infarction, and nontransmural myocardial infarction. The study is also useful in assessing chest pain of uncertain etiology. In the presence of an entirely normal study, acute myocardial infarction, either transmural or nontransmural, less than 7 days old, is extremely unlikely [2]. In addition, certain noncardiac conditions which are responsible for chest pain may be diagnosed. In this regard, multiple rib fractures and arthritis can be detected. Even when the diagnosis of acute infarction is not obscure, the study often has clinical utility. It is a highly accurate method of detecting the location of acute myocardial infarction [2]. In addition, the study may be helpful in determining infarct size, although this particular aspect of infarct scintigraphy requires further study. Finally, the study can be utilized to assess the course of infarction. This is particularly useful in patients with recurrent chest pain during hospitalization in whom it is important to exclude the possibility of extension of the infarction.
Downloaded by: University of Cambridge 131.111.164.128 - 3/19/2019 1:08:56 AM
Discussion
BERMAN/ MASON
28
References
2
3
PARKEY, R. W.; BONTE, F. J.; MEYER, S. L.; ATKINS, J. M.; CURRY, G. L.; STOKELY, E. M., and WILLERSON, J. T. : A new method for radionuclide imaging of acute myocardial infarction in humans. Circulation 50 : 540-546 (1974). BERMAN, D. S.; AMSTERDAM, E. A.; HINES, H . H . ; SALEL, A. F . ; BAILEY, G. 1.; DENARDO, G. L., and MASON, D. T.: A new approach to the interpretation of Tc-99m-pyrophosphate scintigraphy in the detection of acute myocardial infarction. Clinical assessment of diagnostic accuracy. Am. J. Cardiol. 39: 341-346 (1977). BERMAN, D. S. ; AMSTERDAM, E. A. ; HINES, H. H . ; DENARDO, G. L.; SALEL, A. F .; IKEDA, R.; JANSHOLT, A., and MASON, D . T.: The problem of diffuse cardiac uptake of Tc-99m-pyrophosphate in the diagnosis of acute myocardial infarction. Enhanced scintigraphic accuracy by computerized selective blood pool subtraction. Am. J. Cardiol. (in press).
DEAN T. MASON, MD, Professor and Chief, Cardiovascular Medicine, University of California, School of Medicine, Davis, CA 95616 (USA)
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5
Noninvasive Diagnosis of Acute Myocordial Infarction with 99Tcm-Pyrophosphate Scintigraphy DANIEL
s. BERMAN and DEAN T. MASON
Cardiovascular Medicine, University of California, School of Medicine, Davis, Calif.
A variety of radionuclidic techniques are now available for the noninvasive assessment of acute myocardial infarction. These techniques can be divided into two major groupings: (1) cold spot myocardial imaging in which the infarction is detected as an area of decreased radioactivity and (2) hot spot myocardial imaging in which the abnormal area is visualized as an area of increased radioactivity. The hot spot imaging agents can be utilized not only for detection of presence, location, and size, but also are very useful in determining whether an infarction is acute or old. The major advance in the development of hot spot imaging agents followed the discovery that the bone seeking radiopharmaceutical 99Tcm-pyrophosphate (99Tc m_PYP) accumulates in acutely infarcted myocardium [1]. This agent has become the radionuclide of choice in the detection of acute myocardial infarction. 99Tc m_PYP offers a combination of the radioisotope with ideal physical characteristics (99Tc m) with a phosphate complex that has advantageous biological characteristics for imaging myocardial infarction. The agent is rapidly cleared from the blood, so that imaging can be performed as early as 1 h after injection. In addition, there is avid accumulation of the radiopharmaceutical in the region of acute infarction, with high activity ratios between infarction and surrounding tissue. Finally, although the radiopharmaceutical accumulates in bone, there is no liver accumulation. Thus it is not difficult to detect inferior wall infarction. The bone accumulation has not been a major detriment to determining the presence of infarction even when the infarctions are small. The reason for this is that multiple views are routinely obtained which allow separation of the regions of acute infarction from the overlying ribs.
Downloaded by: University of Cambridge 131.111.164.128 - 3/19/2019 1:08:56 AM
Introduction
BERMAN/MASON
24
Materials and Methods In the Coronary Care Unit, 15 mCi of 99Tc m _PYP is injected intravenously [2]. 2 h after injection imaging is performed in the adjacent Nuclear Cardiology Laboratory. We have chosen the 2-hour interval to minimize the problem of separating normal blood background from abnormal myocardial uptake. Recent developments in nuclear instrumentation now allow for the performance of this study in the Coronary Care Unit itself using a portable scintillation camera. Imaging is performed with the scintillation camera equipped with a high resolution collimator. 500,000 count images are obtained in the anterior, left anterior oblique (LAO), left lateral, and right anterior oblique positions, using both Polaroid and Microdot films. The scintigraphic data are also collected on computer disc for blood pool [3] and rib subtractions [2]. The degree of radionuclidic uptake in the cardiac region is assessed as follows: 4 + indicates greater activity than bone, 3 + is activity equal to bone, 2 + is less than bone but moderate, 1 + is slight, and 0 is no detectable activity. In addition, the uptake pattern is judged to be focal or diffuse. The scintigraphic study is considered negative if there is o to 1 + myocardial activity. A positive study is one in which there is 3 + to 4 + myocardial activity in either focal or diffuse patterns, or 2 + focal activity. The interpretation of the 2 + diffuse pattern represents the principal difference in our criteria from those of previous workers; we classify this type of scan as equivocal rather than positive [2].
Results
Abnormal Study In the presence of acute transmural infarction a focal increase in radioactivity is seen in the infarcted region [2). In acute anterior myocardial infarction (fig. 1, bottom panel), a large area of increa~ed activity is observed on the anterior view, and the LAO and left lateral views confirm the anterior location of the radioactivity. In inferior myocardial infarction, an area of
Downloaded by: University of Cambridge 131.111.164.128 - 3/19/2019 1:08:56 AM
Normal Study In a typical normal study, the ribs and sternum are well visualized, but the heart is not seen (fig. 1, top panel). Frequently, however, diffuse activity may be observed throughout the region of the heart, representing radioactivity remaining in the blood pool not yet having been cleared by either bone or kidneys. If there is no evidence of selective localization within the myocardium, the study is probably normal and considered not to represent acute infarction. When the blood pool is seen prominently, additional delayed imaging 3-4 h after injection may show further decrease in blood pool activity, and thereby increase observer certainty about the absence of infarction.
99TcID-Pyrophosphate Scintigraphy
25
Fig. 1. Normal (top panel) and acute anterior myocardial infarction (M!) (bottom panel) 99Tcm-pyrophosphate scintigrams. ANT = Anterior; LAO = left anterior oblique; LLAT = left lateral views. From BERMAN et at. [2].
Equivocal Studies We have found it useful to define a third category of scintigraphic interpretation comprising patients who have apparent blood pool radioactivity [2]. This group constitutes an equivocal study intermediate between
Downloaded by: University of Cambridge 131.111.164.128 - 3/19/2019 1:08:56 AM
increased activity is seen at the inferior border of the heart on all views. Posterolateral myocardial infarction is detected as a region of increased activity along the lateral border of the heart seen best on the anterior view, with the LAO and lateral views confirming the posterolateral location of the radioactivity. Occasionally a transmural myocardial infarction will present as a diffuse increase in radioactivity throughout the left ventricle; however, this pattern is unusual. There is excellent correlation between electrocardiographic and scintigraphic determination of the location of acute transmural infarctions. Nontransmural myocardial infarction is more difficult to detect with the 99Tc ffi _PYP technique. If a definite abnormality is present, it may either be a focal area of increased activity, or diffuse increase in radioactivity throughout the left ventricular myocardium. However, subendocardial infarctions may simply present as an increase in apparent blood pool activity and thereby go undetected.
BERMAN/ MASON
26
those with distinctly abnormal scintigrams and those with definitely negative scintigrams. The rationale for this separation is that only a small percentage of patients with the equivocal pattern have acute infarction. Thus in a recent study of 235 patients with acute chest pain syndromes at our institution, 50 patients exhibited the pattern of apparent blood pool activity [2]. 9 of these 50 patients had acute nontransmural myocardial infarction documented by standard electrocardiographic and myocardial enzymatic criteria. Of the remainder, 5 had acute transmural infarction, 35 had no laboratory evidence of acute myocardial infarction, and in 1, the clinical diagnosis of infarction was equivoca l. Recently there have been a number of reports of false-positive infarct scintigrams using 99Tc ffi _PYP. However, a large proportion of these images exhibited the pattern which we classify as equivocal. We find that by separating this equivocal group from those with distinctly positive scans, the specificity of 99Tc m _PYP imaging for acute myocardial infarction is greatly increased, with only slight loss in sensitivity. This decrease in sensitivity noted in our series was principally confined to the nontransmural infarction group.
Specificity of PYP Scintigraphy for Acute M y ocardial Infarction When our strict criteria for a positive study were employed, the specificity of the technique for acute infarction was also quite high [2]. Thus of 126 patients with no evidence of acute myocardial infarction by clinical or laboratory criteria, only 4 demonstrated definitely positive 99Tc m _PYP ' patients had focal uptake in regions scintigrams. 2 of these 4 false-positive' of left ventricular dyskinesis secondary to remote myocardial infarction. The findings in these 2 patients are consistent with those of others who previously have reported focal uptake of 99Tc m _PYP in chronic coronary patients with ventricular aneurysms. Both the high sensitivity and high specificity in this study are a d irect result of the use of our classification which employs an equivocal category for the 2 + diffuse scintigram.
Downloaded by: University of Cambridge 131.111.164.128 - 3/19/2019 1:08:56 AM
Sensitivity of PYP SCintigraphy in Detecting Presence of Acute Infarction Our results demonstrate that with the new modified classification the 99Tc m _PYP imaging technique is a highly sensitive method for detection of acute myocardial infarction [2]. Of 81 patients with acute transmural myocardial infarction none had a negative scintigram, and of 18 patients with acute nontransmural infarction only 2 demonstrated false-negative studies. Thus only 2 % of the patients with acute infarction, transmural or nontransmural, had negative PYP scintigraphy.
99Tcm-Pyrophosphate Scintigraphy
27
False-Positive Studies
A large number of reported false-positive studies in the literature would not be considered positive if strict criteria for positive studies were utilized [2]. Nevertheless, despite strict criteria for positive study, certain conditions other than acute myocardial infarction may result in increased uptake of 99Tc m _PYP within the myocardium. Thus we noted this finding in only 4 of 126 patients with no clinical evidence of infarction. The clinical conditions which have occasionally been associated with false-positive studies are as follows: (1) unstable angina pectoris; (2) valvular calcification (multiple scintigraphic views and chest X-ray easily distinguish this pattern from that of acute infarction); (3) left ventricular aneurysm; (4) old myocardial infarction (rarely intense) without definite clinical evidence of acute myocardial infarction; and (5)postelectric cardioversion. Therefore, when strict criteria for positive study are utilized, the frequency of a false-positive study is quite low.
The principal clinical usefulness of the infarct scintigram at the present time is the detection of the presence of acute myocardial infarction in patients in whom the diagnosis of infarction is obscure. This group includes patients with left bundle branch block, previous myocardial infarction with new infarction in an adjacent region, intraoperative myocardial infarction, infarction in patients who have received intramuscular injections, true posterior myocardial infarction, and nontransmural myocardial infarction. The study is also useful in assessing chest pain of uncertain etiology. In the presence of an entirely normal study, acute myocardial infarction, either transmural or nontransmural, less than 7 days old, is extremely unlikely [2]. In addition, certain noncardiac conditions which are responsible for chest pain may be diagnosed. In this regard, multiple rib fractures and arthritis can be detected. Even when the diagnosis of acute infarction is not obscure, the study often has clinical utility. It is a highly accurate method of detecting the location of acute myocardial infarction [2]. In addition, the study may be helpful in determining infarct size, although this particular aspect of infarct scintigraphy requires further study. Finally, the study can be utilized to assess the course of infarction. This is particularly useful in patients with recurrent chest pain during hospitalization in whom it is important to exclude the possibility of extension of the infarction.
Downloaded by: University of Cambridge 131.111.164.128 - 3/19/2019 1:08:56 AM
Discussion
BERMAN/ MASON
28
References
2
3
PARKEY, R. W.; BONTE, F. J.; MEYER, S. L.; ATKINS, J. M.; CURRY, G. L.; STOKELY, E. M., and WILLERSON, J. T. : A new method for radionuclide imaging of acute myocardial infarction in humans. Circulation 50 : 540-546 (1974). BERMAN, D. S.; AMSTERDAM, E. A.; HINES, H . H . ; SALEL, A. F . ; BAILEY, G. 1.; DENARDO, G. L., and MASON, D. T.: A new approach to the interpretation of Tc-99m-pyrophosphate scintigraphy in the detection of acute myocardial infarction. Clinical assessment of diagnostic accuracy. Am. J. Cardiol. 39: 341-346 (1977). BERMAN, D. S. ; AMSTERDAM, E. A. ; HINES, H. H . ; DENARDO, G. L.; SALEL, A. F .; IKEDA, R.; JANSHOLT, A., and MASON, D . T.: The problem of diffuse cardiac uptake of Tc-99m-pyrophosphate in the diagnosis of acute myocardial infarction. Enhanced scintigraphic accuracy by computerized selective blood pool subtraction. Am. J. Cardiol. (in press).
DEAN T. MASON, MD, Professor and Chief, Cardiovascular Medicine, University of California, School of Medicine, Davis, CA 95616 (USA)
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5
