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Myocardial scintigraphy with technetium-99m pyrophosphate during the early phase of acute infarction
Myocardial Scintigraphy With Technetium-99m Pyrophosphate During the Early Phase of Acute Infarction
B. LEONARD HOLMAN, MD, FACC” MICHAEL LESCH, MD, FACCt JOSEPH S. ALPERT, MD, FACC Boston, Massachusetts
From the DepaWnents of Badiokqy and Medicine, Harvard Medical School and Peter Bent Brigham Hospital, Boston, Massachusetts. This study was supported in part by Grants GM 18674 and HL 17739 and Contract NO1 HV 53000 from the U.S. Public Health Service, Bethesda, Maryland, and by Grant 75 796 from the American Heart Association, Dallas, Texas. Manuscript received February 28, 1977: revised manuscript received July 1, 1977, accepted July 6, 1977. Address for reprints: B. Leonard Holman, MD, Department of Radiology, Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115. Established Investigator. American Heart Association. T Present address: Department of Medicine, Northwestern Universlty School of Medicine, Chicago, Illinois. l
To determine the sensitivity of myocardiai scintigraphy with technetium-99m pyrophosphate during the early phase of acute myocardial infarction, 31 patients admitted to the coronary care unit with prolonged ischemlc pain underwent imaging within 4 to 6 hours and again at 24 hours after the onset of symptoms. In 11 of 15 patients with documented acute myocardial infarction, increased focal myocardial uptake was demonstrated on early myocardial scintigraphy. Focal uptake was observed in only 2 of 16 patients with unstable angina pectoris. Three of four patients with normal early scintigrams had massive transmural myocardial infarction. Normal early scintigrams in these three patients may have reflected poor perfusion because the images were abnormal at 24 hours. In four patients the extent of technetium-99m pyrophosphate uptake increased more than 20 percent at 24 hours without other evidence of infarct extension. In the other seven patients, there was no significant change in the area of the abnormal radioactive uptake between early and delayed scintiscans. This study suggests that technetium-99m pyrophosphate scintigraphy can detect acute myocardial infarctlon as early as 4 hours after the onset of symptoms although the sensitivity rate (73 percent) is less than that at 24 hours.
Scintigraphic techniques using infarct-avid radiotracers provide a direct method for determining the extent of acute myocardial infarction.1-3 Previous investigators4 have suggested that 12 hours is the earliest time after the onset of symptoms for accurate detection of infarction. With the advent of therapeutic maneuvers aimed at limiting the extent of myocardial necrosis,5 it has become increasingly important to measure infarct size accurately during the early phase of acute infarction. We have, therefore, determined the accuracy of myocardial scintigraphy with technetium-99m pyrophosphate for detecting acute infarction and predicting its size in the first hours after onset of symptoms. Methods Myocardial scintigraphy using technetium-99m pyrophosphate was performed in 31 patients admitted to the coronary care unit with suspected acute myocardial infarction. Patients were selected for study only if they had a clearly defined onset of precordial chest pain occurring no more than 8 hours before imaging, an uncomplicated course during the first 24 hours after admission and no previously documented myocardial infarction. Patients: Acute myocardial infarction was diagnosed if the following three criteria were met: (1) a history of typical chest pain lasting 1 hour or more, (2)
the presence of a characteristic pattern of elevation in the creatine kinase (CK) serum activity above normal levels with subsequent resolution, and (3) appearance of Q waves (transmural infarction) or evolution of ST-T wave changes (nontransmural infarction) characteristic of infarction in the electrocardiogram.
January 1978
The Amorlcan Journal of CARDIOLOGY
Vo\ume 41
39
EARLY INFARCT SCINTIGRAPHY-HOLMAN
ET AL.
TABLE I Summary of Findings in 15 Cases of Acute Myocardial Infarction Case no.
Early Scintigraphy 6-6 Hr 4-5 Hr
+ :
z +
f
.
2: 9
:7 :x :t
. .
.. .. ... . . ... . ...
: : : + .. -
Peak CK+ (M/liter)
l
CK+ -
+4.6 -1.6 -6.3
.. ..
:
Change in ggmTcPY P Uptake (%)
1060 190 2766 1950 624 246 726 3250 574 524 532 1104 4540 354 5000
-
/ ,::y +
+21.0 +3.3 i i-45.6 +33.8 / +I.8 ( +33.6
: + :
-t
... . ... ...
:
Location of Infarction Nontransmural Transmural
..
Anterior
Anterior Posterolateral Inferior
. ApiG Inferior
’ .
Lateral’ ’ Anterolateral
Anterdseptal Inferior . Inferior Posterior Anterolateral Anterolaterals Anterolaterall
. .
.. ...
+ Percent change in area of uptake between early and delayed scintigraphy. + Serum creatine kinase at time of early scintigraphy. t Normal value: 50 to 180 Wliter. 5 Patient died within 24 hours of infarction. 7 Patient died within 3 days of infarction. + = abnormal; - = normal; ggR*TcPYP = technetium-99m pyrophosphate.
Unstable angina pectoris was defined as prolonged chest pain, ischemic in character and of recent onset (less than 1 month), that had increased in frequency, severity or duration in the month before admission. Patients with this diagnosis had no electrocardiographic evidence of acute myocardial infarction and a peak serum CK value in the 3 days after admission that was less than the upper limit of normal. Fifteen of the 31 patients had an acute myocardial infarction that was transmural in 11 and nontransmural in 4, as judged from electrocardiographic changes. The remaining 16 patients had unstable angina pectoris. Scintigraphy was performed in all patients within 4 to 8 hours after the onset of chest pain. Myocardial scintigraphy: The procedure was performed as soon as possible after the patients’ admission to the coronary care unit and was repeated 24 hours later. Imaging was performed 90 minutes after the administration of 10 mCi (5 mg) of technetium-99m pyrophosphate using an Anger scintillation camera with a low energy all purpose collimator and a pulse height analyzer window peaked symmetrically over the 140 kev photopeak of technetium-99m. Imaging was performed in the anterior, left anterior oblique and left lateral projections, collecting 400,000 counts in each view. The scintigraphic images were obtained on Polaroid@ film (type 52) and were interpreted independently by two observers without prior knowledge of the clinical diagnosis. The extent of technetium-99m pyrophosphate uptake was measured from the anterior projection with use of planimetry in the patients with documented acute myocardial infarction. (The borders of the focal myocardial uptake were obscured by overlying osseous activity in the left anterior oblique and left lateral views. These projections were therefore not used to measure infarct size.) The percent change in the area of the myocardial uptake between 4 and 24 hours was then determined. The reproducibility of the planimetric measurement was assessed in four control patients with acute infarction. Repeat scintigraphy was performed in the anterior position after the camera detector was repositioned. The area of technetium-
40
January 1978
The An&can
Journal of CARDIOLOGY
99m pyrophosphate uptake in each of the two anterior views was measured with planimetry.
Results Myocardial infarction:In 11 of the 15 patients with acute infarction (Patients 1 to 11, Table I), increased focal myocardial activity was demonstrated on early myocardial scintigraphy. In all cases, myocardial uptake was less intense in early scintigrams (4 to 8 hours) than in the 24 hour study. In 5 of the 11 (Cases 1 to 5), serum CK activity was within normal limits at the time scintigraphy was performed (Fig. 1). In one case (Patient 12), diffuse myocardial uptake was evident on early scintigraphy performed 90 minutes after injection. Results of repeat scintigraphy 3 hours after injection were normal, suggesting that the initial diffuse uptake was caused by blood pool activity. In the other three patients (Cases 13 to 15) with normal myocardial scintigrams, imaging was performed 4 hours (one patient) and 8 hours (two patients) after the onset of pain. In one patient (Case 13), serum CK was within normal limits at the time of imaging. All three patients had a massive transmural myocardial infarction. Two of these patients (Cases 14 and 15) died of pump failure within 1 week of infarction, and the third patient’s course was complicated by cardiogenic shock. Subsequent scintigrams were abnormal in the two patients surviving 24 hours after infarction. Unstable angina pectoris: Of the 16 patients with unstable angina pectoris, 12 had normal early scintigrams. Of the remaining four patients, two had focal and two had diffuse myocardial uptake (Table II). With use of focal myocardial uptake as the criterion for the diagnosis of acute myocardial infarction, the sensitivity
Volume 41
EARLY INFARCT SCINTIGRAPHY-HOLMAN ET AL.
TABLE II Summary of Scintigraphic Results in Early Myocardial Scintigraphy Normal Diffuse uptake Focal uptake Total patients
FIGURE 1. Case 1 (Table I). Scintigraphy performed with technetium99m pyrophosphate in the anterior and left anterior oblique (LAO) projections 4 hours (upper panel) and 24 hours (lower panel) after the onset of symptoms in a patient with acute anteroseptal myocardial infarction. The serum CK level was normal at 4 hours.
rate of early scintigraphy was 73 percent and the specificity rate 88 percent. Reproducibility: In the four control patients with documented myocardial infarction who underwent imaging twice in the anterior position, the percent change in area between the first and second measurements was 5.3 f 1.2 percent (mean f standard error of the mean). The change in area of the abnormal radioactive uptake between early and delayed scintiscans in 7 of the 11 patients with early focal myocardial uptake was not significantly different from the results obtained in testing the reproducibility of the method (Table I). The area of technetium-99m pyrophosphate uptake increased in eight patients between early and delayed scintigraphy. In four of these eight patients, the increase was greater than 20 percent. The area decreased slightly in the remaining three patients. Discussion Acute myocardial infarction can be detected with technetium-99m pyrophosphate within 4 hours of the onset of chest pain and before elevation of serum creatine kinase activity. The detection rate is somewhat lower with early compared with delayed (24 hours to 7 days) scintigraphy. 4~sHowever, three of the four patients with normal early scintigraphy in this study had massive transmural infarcts and did not present diagnostic problems on admission. The specificity rate of
31 Cases
Diagnosis (no. of patients) Acute Myocardial Unstable Angrna Infarction Pectoris ;: (27%) 11 (73%) 15
12 (75%) 2 (12.5%) 2 (12.5%) 16
early scintigraphy was high, with normal or diffuse patterns observed in 88 percent of patients with unstable angina pectoris. Of course, we cannot rule out the possibility that focal uptake of technetium-99m in two patients with unstable angina pectoris actually represented an area of myocardial necrosis. The failure of massive infarcts to concentrate pyrophosphate early is analogous to the normal scintigrams obtained in a canine model of infarction 7 hours after permanent coronary occlusion; in animals subjected to temporary occlusion, early scintigraphy was abnormal.7 Because pyrophosphate uptake is flow-limited, large infarcts receive insufficient tracer to be detected with early scintigraphy. That delayed scintigraphy is abnormal in these patients suggests that the initial marked reduction in flow is followed by rapid establishment of collateral flow. Estimating changes in extent of infarction: The substantial increase in size of the technetium-99m pyrophosphate uptake in four patients may indicate some extension of the infarct during the first 24 hours; this could not be confirmed by other criteria. Thus, the extent of technetium-99m pyrophosphate uptake appears time-dependent in at least some patients with acute infarction without other evidence of reinfarction. For myocardial scintigraphy to be useful in estimating changes in the size of infarction, the time interval between infarction and scintigraphy will have to be known and serial scintigraphy will probably be necessary. In any case, the extent of infarction can probably be determined as early as 4 hours after the onset of symptoms (assuming that there is good correlation between infarct size and tracer uptake)7-12 although prediction of ultimate size cannot be made in many patients. Currently no other technique is available that accurately measures the size of acute infarction during the early period, 4 to 8 hours, after the onset of symptoms. Creatine kinase clearance curves require 10 to 12 hours before accurate sizing is possible.13 Use of myocardial perfusion scintigraphy with potassium analogs and measurements of wall motion abnormalities with radionuclide techniques cannot distinguish between alterations in function due to the acute process, ischemia or old infarction.14 S-T segment mapping provides a qualitative index of the size of infarction and can signal directional changes in the size of the evolving infarct, but it cannot quantitate the degree of necrosis.15 Implications: Although infarct scintigraphy may
January 1979
The American Journal of CARDIOLOGY Volume 41
41
EARLY INFARCT SOINTIGRAPHY-H~LMAN ET AL.
estimate infarct size in most cases within 8 hours of symptoms, technetium-99m pyrophosphate uptake may not reflect the degree of necrosis within the borders of the infarct. The uptake of the radiotracer in any given tissue section is related not to the degree or amount of infarction but only to the presence of necrosis.7v8 As a result, the border zone of the infarct may concentrate pyrophosphate in small nests of necrotic tissue interspersed between zones of reversibly ischemic tissue
which can be salvaged by early treatment. Conversely, at the time of early scintigraphy, the tracer may be concentrating in ischemic tissue destined for ultimate necrosis but potentially salvageable with appropriate interventions.16 Thus, the use of early scintigraphy to provide a quantitative measure of the efficacy of drug therapy will require a clearer understanding of the mechanism of technetium-99m pyrophosphate localization.
References 1. Holman EL, Dewanjee MK, ldolne J, et al: Detection and localization of experimental myocardial infarction with QQmTc-tetracycline. J Nucl f&d 14595-599, 1973 2. Hdman BL, Lesch M, Zwelman FG, et al: Detection and sizing of acute myocardial infarcts with QQ~c(Sn)tetracycline. N Engl J f&d 291:159-163, 1974 3. Parkey RW, Bonte FJ, Meyer SL, el al: A new method for radionuclide imaging of acute myocardial infarction in humans. Circulation 50540-546, 1974 4. WilIerson JT, Parkey RW, Bonie FJ, et al: Technetium stannous pyrophosphate myocardial scintigrams in patients with chest pain of varying etiology. Circulation 51:1046-1052, 1975 5. Maroko PR, Braunwald E: Modification of myocardial infarction size after coronary occlusion. Ann Intern Med 79:720-733. 1973 6. Holman BL, Tanaka ll, Lesch M: Evaluation of radiopharmaceuticals for the detection of acute myocardial infarction in man. Radiology 1211427-430, 1976 7. Bruno FP, Cobb FR, Rlvas F, el al: Evaluation of QQmtechnetium stannous pyrophosphate as an imaging agent in acute myocardial infarction. Circulation 54:71-76, 1976 6. Marcus ML, Tomanek RJ, Ehrhardt JC, et al: Relationships between myocardial perfusion, myocardial necrosis, and technetium-99m pyrophosphate uptake in dogs subjected to sudden coronary occlusion. Circulation 54:647-653, 1976 9. Holman BL, Ehrle M, Lesch M: Correlation of acute myocardial
42
January 1978
10.
11.
12.
13.
14.
15.
16.
The Amerkan Journal of CARDlOLOGY VolumO41
infarct scintigraphy with postmortem studies. Am J Cardiol 37: 311-313, 1976 Buje LM, Parkey RW, Dees JH, el al: Morphologic correlates of technetium-99m stannous pyrophosphate imaging of acute myocardial infarcts in dogs. Circulation 52:596-607, 1975 Stokely EM, Buja LM, Lewis SE, et al: Measurement of acute myocardial infarcts in dogs with QQmTc-stannous pyrophosphate scintigrams. J Nucl Med 17:1-5, 1976 Henning H, Bchelbert H, O’Rourke RA, et al: Dual myocardial imaging with Tc-99m-pyrophosphate and thallium 201 for diagnosing and sizing acute myocardial infarction (abstr). J Nucl Med 17:524, 1976 Shell WE, Lavelle JF, Covell JW, et al: Early estimation of myocardiil damage in conscious dogs and patients with evolving acute myocardial infarction. J Clin Invest 52:2579-2590, 1973 Holman BL: Radionuclide methods in the evaluation of myocardial ischemia and infarction. Circulation 53:Suppl l:l-112-l-119, 1976 Maroko PR, Llbby P, Covell JW, el al: Precordial S-T segment elevation mapping: an atraumatic method for assessing alterations in the extent of myocardial ischemic injury. The effects of pharmacologic and hemodynamic interventions. Am J Cardiol 29: 223-230, 1972 Zwelman FG, Holman BL, O’Keefe A, et al: Selective uptake of QQTc-complexes and 67Ga in acutely infarcted myocardium. J Nucl Med 16:975-979, 1975
B. LEONARD HOLMAN, MD, FACC” MICHAEL LESCH, MD, FACCt JOSEPH S. ALPERT, MD, FACC Boston, Massachusetts
From the DepaWnents of Badiokqy and Medicine, Harvard Medical School and Peter Bent Brigham Hospital, Boston, Massachusetts. This study was supported in part by Grants GM 18674 and HL 17739 and Contract NO1 HV 53000 from the U.S. Public Health Service, Bethesda, Maryland, and by Grant 75 796 from the American Heart Association, Dallas, Texas. Manuscript received February 28, 1977: revised manuscript received July 1, 1977, accepted July 6, 1977. Address for reprints: B. Leonard Holman, MD, Department of Radiology, Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115. Established Investigator. American Heart Association. T Present address: Department of Medicine, Northwestern Universlty School of Medicine, Chicago, Illinois. l
To determine the sensitivity of myocardiai scintigraphy with technetium-99m pyrophosphate during the early phase of acute myocardial infarction, 31 patients admitted to the coronary care unit with prolonged ischemlc pain underwent imaging within 4 to 6 hours and again at 24 hours after the onset of symptoms. In 11 of 15 patients with documented acute myocardial infarction, increased focal myocardial uptake was demonstrated on early myocardial scintigraphy. Focal uptake was observed in only 2 of 16 patients with unstable angina pectoris. Three of four patients with normal early scintigrams had massive transmural myocardial infarction. Normal early scintigrams in these three patients may have reflected poor perfusion because the images were abnormal at 24 hours. In four patients the extent of technetium-99m pyrophosphate uptake increased more than 20 percent at 24 hours without other evidence of infarct extension. In the other seven patients, there was no significant change in the area of the abnormal radioactive uptake between early and delayed scintiscans. This study suggests that technetium-99m pyrophosphate scintigraphy can detect acute myocardial infarctlon as early as 4 hours after the onset of symptoms although the sensitivity rate (73 percent) is less than that at 24 hours.
Scintigraphic techniques using infarct-avid radiotracers provide a direct method for determining the extent of acute myocardial infarction.1-3 Previous investigators4 have suggested that 12 hours is the earliest time after the onset of symptoms for accurate detection of infarction. With the advent of therapeutic maneuvers aimed at limiting the extent of myocardial necrosis,5 it has become increasingly important to measure infarct size accurately during the early phase of acute infarction. We have, therefore, determined the accuracy of myocardial scintigraphy with technetium-99m pyrophosphate for detecting acute infarction and predicting its size in the first hours after onset of symptoms. Methods Myocardial scintigraphy using technetium-99m pyrophosphate was performed in 31 patients admitted to the coronary care unit with suspected acute myocardial infarction. Patients were selected for study only if they had a clearly defined onset of precordial chest pain occurring no more than 8 hours before imaging, an uncomplicated course during the first 24 hours after admission and no previously documented myocardial infarction. Patients: Acute myocardial infarction was diagnosed if the following three criteria were met: (1) a history of typical chest pain lasting 1 hour or more, (2)
the presence of a characteristic pattern of elevation in the creatine kinase (CK) serum activity above normal levels with subsequent resolution, and (3) appearance of Q waves (transmural infarction) or evolution of ST-T wave changes (nontransmural infarction) characteristic of infarction in the electrocardiogram.
January 1978
The Amorlcan Journal of CARDIOLOGY
Vo\ume 41
39
EARLY INFARCT SCINTIGRAPHY-HOLMAN
ET AL.
TABLE I Summary of Findings in 15 Cases of Acute Myocardial Infarction Case no.
Early Scintigraphy 6-6 Hr 4-5 Hr
+ :
z +
f
.
2: 9
:7 :x :t
. .
.. .. ... . . ... . ...
: : : + .. -
Peak CK+ (M/liter)
l
CK+ -
+4.6 -1.6 -6.3
.. ..
:
Change in ggmTcPY P Uptake (%)
1060 190 2766 1950 624 246 726 3250 574 524 532 1104 4540 354 5000
-
/ ,::y +
+21.0 +3.3 i i-45.6 +33.8 / +I.8 ( +33.6
: + :
-t
... . ... ...
:
Location of Infarction Nontransmural Transmural
..
Anterior
Anterior Posterolateral Inferior
. ApiG Inferior
’ .
Lateral’ ’ Anterolateral
Anterdseptal Inferior . Inferior Posterior Anterolateral Anterolaterals Anterolaterall
. .
.. ...
+ Percent change in area of uptake between early and delayed scintigraphy. + Serum creatine kinase at time of early scintigraphy. t Normal value: 50 to 180 Wliter. 5 Patient died within 24 hours of infarction. 7 Patient died within 3 days of infarction. + = abnormal; - = normal; ggR*TcPYP = technetium-99m pyrophosphate.
Unstable angina pectoris was defined as prolonged chest pain, ischemic in character and of recent onset (less than 1 month), that had increased in frequency, severity or duration in the month before admission. Patients with this diagnosis had no electrocardiographic evidence of acute myocardial infarction and a peak serum CK value in the 3 days after admission that was less than the upper limit of normal. Fifteen of the 31 patients had an acute myocardial infarction that was transmural in 11 and nontransmural in 4, as judged from electrocardiographic changes. The remaining 16 patients had unstable angina pectoris. Scintigraphy was performed in all patients within 4 to 8 hours after the onset of chest pain. Myocardial scintigraphy: The procedure was performed as soon as possible after the patients’ admission to the coronary care unit and was repeated 24 hours later. Imaging was performed 90 minutes after the administration of 10 mCi (5 mg) of technetium-99m pyrophosphate using an Anger scintillation camera with a low energy all purpose collimator and a pulse height analyzer window peaked symmetrically over the 140 kev photopeak of technetium-99m. Imaging was performed in the anterior, left anterior oblique and left lateral projections, collecting 400,000 counts in each view. The scintigraphic images were obtained on Polaroid@ film (type 52) and were interpreted independently by two observers without prior knowledge of the clinical diagnosis. The extent of technetium-99m pyrophosphate uptake was measured from the anterior projection with use of planimetry in the patients with documented acute myocardial infarction. (The borders of the focal myocardial uptake were obscured by overlying osseous activity in the left anterior oblique and left lateral views. These projections were therefore not used to measure infarct size.) The percent change in the area of the myocardial uptake between 4 and 24 hours was then determined. The reproducibility of the planimetric measurement was assessed in four control patients with acute infarction. Repeat scintigraphy was performed in the anterior position after the camera detector was repositioned. The area of technetium-
40
January 1978
The An&can
Journal of CARDIOLOGY
99m pyrophosphate uptake in each of the two anterior views was measured with planimetry.
Results Myocardial infarction:In 11 of the 15 patients with acute infarction (Patients 1 to 11, Table I), increased focal myocardial activity was demonstrated on early myocardial scintigraphy. In all cases, myocardial uptake was less intense in early scintigrams (4 to 8 hours) than in the 24 hour study. In 5 of the 11 (Cases 1 to 5), serum CK activity was within normal limits at the time scintigraphy was performed (Fig. 1). In one case (Patient 12), diffuse myocardial uptake was evident on early scintigraphy performed 90 minutes after injection. Results of repeat scintigraphy 3 hours after injection were normal, suggesting that the initial diffuse uptake was caused by blood pool activity. In the other three patients (Cases 13 to 15) with normal myocardial scintigrams, imaging was performed 4 hours (one patient) and 8 hours (two patients) after the onset of pain. In one patient (Case 13), serum CK was within normal limits at the time of imaging. All three patients had a massive transmural myocardial infarction. Two of these patients (Cases 14 and 15) died of pump failure within 1 week of infarction, and the third patient’s course was complicated by cardiogenic shock. Subsequent scintigrams were abnormal in the two patients surviving 24 hours after infarction. Unstable angina pectoris: Of the 16 patients with unstable angina pectoris, 12 had normal early scintigrams. Of the remaining four patients, two had focal and two had diffuse myocardial uptake (Table II). With use of focal myocardial uptake as the criterion for the diagnosis of acute myocardial infarction, the sensitivity
Volume 41
EARLY INFARCT SCINTIGRAPHY-HOLMAN ET AL.
TABLE II Summary of Scintigraphic Results in Early Myocardial Scintigraphy Normal Diffuse uptake Focal uptake Total patients
FIGURE 1. Case 1 (Table I). Scintigraphy performed with technetium99m pyrophosphate in the anterior and left anterior oblique (LAO) projections 4 hours (upper panel) and 24 hours (lower panel) after the onset of symptoms in a patient with acute anteroseptal myocardial infarction. The serum CK level was normal at 4 hours.
rate of early scintigraphy was 73 percent and the specificity rate 88 percent. Reproducibility: In the four control patients with documented myocardial infarction who underwent imaging twice in the anterior position, the percent change in area between the first and second measurements was 5.3 f 1.2 percent (mean f standard error of the mean). The change in area of the abnormal radioactive uptake between early and delayed scintiscans in 7 of the 11 patients with early focal myocardial uptake was not significantly different from the results obtained in testing the reproducibility of the method (Table I). The area of technetium-99m pyrophosphate uptake increased in eight patients between early and delayed scintigraphy. In four of these eight patients, the increase was greater than 20 percent. The area decreased slightly in the remaining three patients. Discussion Acute myocardial infarction can be detected with technetium-99m pyrophosphate within 4 hours of the onset of chest pain and before elevation of serum creatine kinase activity. The detection rate is somewhat lower with early compared with delayed (24 hours to 7 days) scintigraphy. 4~sHowever, three of the four patients with normal early scintigraphy in this study had massive transmural infarcts and did not present diagnostic problems on admission. The specificity rate of
31 Cases
Diagnosis (no. of patients) Acute Myocardial Unstable Angrna Infarction Pectoris ;: (27%) 11 (73%) 15
12 (75%) 2 (12.5%) 2 (12.5%) 16
early scintigraphy was high, with normal or diffuse patterns observed in 88 percent of patients with unstable angina pectoris. Of course, we cannot rule out the possibility that focal uptake of technetium-99m in two patients with unstable angina pectoris actually represented an area of myocardial necrosis. The failure of massive infarcts to concentrate pyrophosphate early is analogous to the normal scintigrams obtained in a canine model of infarction 7 hours after permanent coronary occlusion; in animals subjected to temporary occlusion, early scintigraphy was abnormal.7 Because pyrophosphate uptake is flow-limited, large infarcts receive insufficient tracer to be detected with early scintigraphy. That delayed scintigraphy is abnormal in these patients suggests that the initial marked reduction in flow is followed by rapid establishment of collateral flow. Estimating changes in extent of infarction: The substantial increase in size of the technetium-99m pyrophosphate uptake in four patients may indicate some extension of the infarct during the first 24 hours; this could not be confirmed by other criteria. Thus, the extent of technetium-99m pyrophosphate uptake appears time-dependent in at least some patients with acute infarction without other evidence of reinfarction. For myocardial scintigraphy to be useful in estimating changes in the size of infarction, the time interval between infarction and scintigraphy will have to be known and serial scintigraphy will probably be necessary. In any case, the extent of infarction can probably be determined as early as 4 hours after the onset of symptoms (assuming that there is good correlation between infarct size and tracer uptake)7-12 although prediction of ultimate size cannot be made in many patients. Currently no other technique is available that accurately measures the size of acute infarction during the early period, 4 to 8 hours, after the onset of symptoms. Creatine kinase clearance curves require 10 to 12 hours before accurate sizing is possible.13 Use of myocardial perfusion scintigraphy with potassium analogs and measurements of wall motion abnormalities with radionuclide techniques cannot distinguish between alterations in function due to the acute process, ischemia or old infarction.14 S-T segment mapping provides a qualitative index of the size of infarction and can signal directional changes in the size of the evolving infarct, but it cannot quantitate the degree of necrosis.15 Implications: Although infarct scintigraphy may
January 1979
The American Journal of CARDIOLOGY Volume 41
41
EARLY INFARCT SOINTIGRAPHY-H~LMAN ET AL.
estimate infarct size in most cases within 8 hours of symptoms, technetium-99m pyrophosphate uptake may not reflect the degree of necrosis within the borders of the infarct. The uptake of the radiotracer in any given tissue section is related not to the degree or amount of infarction but only to the presence of necrosis.7v8 As a result, the border zone of the infarct may concentrate pyrophosphate in small nests of necrotic tissue interspersed between zones of reversibly ischemic tissue
which can be salvaged by early treatment. Conversely, at the time of early scintigraphy, the tracer may be concentrating in ischemic tissue destined for ultimate necrosis but potentially salvageable with appropriate interventions.16 Thus, the use of early scintigraphy to provide a quantitative measure of the efficacy of drug therapy will require a clearer understanding of the mechanism of technetium-99m pyrophosphate localization.
References 1. Holman EL, Dewanjee MK, ldolne J, et al: Detection and localization of experimental myocardial infarction with QQmTc-tetracycline. J Nucl f&d 14595-599, 1973 2. Hdman BL, Lesch M, Zwelman FG, et al: Detection and sizing of acute myocardial infarcts with QQ~c(Sn)tetracycline. N Engl J f&d 291:159-163, 1974 3. Parkey RW, Bonte FJ, Meyer SL, el al: A new method for radionuclide imaging of acute myocardial infarction in humans. Circulation 50540-546, 1974 4. WilIerson JT, Parkey RW, Bonie FJ, et al: Technetium stannous pyrophosphate myocardial scintigrams in patients with chest pain of varying etiology. Circulation 51:1046-1052, 1975 5. Maroko PR, Braunwald E: Modification of myocardial infarction size after coronary occlusion. Ann Intern Med 79:720-733. 1973 6. Holman BL, Tanaka ll, Lesch M: Evaluation of radiopharmaceuticals for the detection of acute myocardial infarction in man. Radiology 1211427-430, 1976 7. Bruno FP, Cobb FR, Rlvas F, el al: Evaluation of QQmtechnetium stannous pyrophosphate as an imaging agent in acute myocardial infarction. Circulation 54:71-76, 1976 6. Marcus ML, Tomanek RJ, Ehrhardt JC, et al: Relationships between myocardial perfusion, myocardial necrosis, and technetium-99m pyrophosphate uptake in dogs subjected to sudden coronary occlusion. Circulation 54:647-653, 1976 9. Holman BL, Ehrle M, Lesch M: Correlation of acute myocardial
42
January 1978
10.
11.
12.
13.
14.
15.
16.
The Amerkan Journal of CARDlOLOGY VolumO41
infarct scintigraphy with postmortem studies. Am J Cardiol 37: 311-313, 1976 Buje LM, Parkey RW, Dees JH, el al: Morphologic correlates of technetium-99m stannous pyrophosphate imaging of acute myocardial infarcts in dogs. Circulation 52:596-607, 1975 Stokely EM, Buja LM, Lewis SE, et al: Measurement of acute myocardial infarcts in dogs with QQmTc-stannous pyrophosphate scintigrams. J Nucl Med 17:1-5, 1976 Henning H, Bchelbert H, O’Rourke RA, et al: Dual myocardial imaging with Tc-99m-pyrophosphate and thallium 201 for diagnosing and sizing acute myocardial infarction (abstr). J Nucl Med 17:524, 1976 Shell WE, Lavelle JF, Covell JW, et al: Early estimation of myocardiil damage in conscious dogs and patients with evolving acute myocardial infarction. J Clin Invest 52:2579-2590, 1973 Holman BL: Radionuclide methods in the evaluation of myocardial ischemia and infarction. Circulation 53:Suppl l:l-112-l-119, 1976 Maroko PR, Llbby P, Covell JW, el al: Precordial S-T segment elevation mapping: an atraumatic method for assessing alterations in the extent of myocardial ischemic injury. The effects of pharmacologic and hemodynamic interventions. Am J Cardiol 29: 223-230, 1972 Zwelman FG, Holman BL, O’Keefe A, et al: Selective uptake of QQTc-complexes and 67Ga in acutely infarcted myocardium. J Nucl Med 16:975-979, 1975