Comparison of Early Myocardial Technetium-99m Pyrophosphate Uptake to Early Peaking of Creatine

Kinase and Xreatine Kinase-MB as Indicators of Early Reperfusion in Acute Myocardial Infarction

MAKOTO KONDO, MD, YOUSUKE YUZUKI, MD, HIDENORI ARAI, MD, KEISHI SHIMIZU, MD, MASARU MORIKAWA, MD, and YUKIO SHIMONO, MD

The value of technetium-99m pyrophosphate (Tc- 99m-PYP) scintigraphy as an indicator of reperfu- sion 2.8 to 8 hours after the onset of symptoms of acute myocardial infarction was compared with the value of early peak creatine kinase (CK) and CK- MB release within 18 hours after the onset of symp- toms. In 29 patients who received thrombolytic therapy, recanalization was seen (group 1) and in 7 it was not (group 2). In 23 patients (79%) in group 1 scintigraphic findings were positive and in all 7 in group 2 they were negative. In 15 patients (52%) in group 1 and 1 patient (14 % ) in group 2, CK reached its peak level within 18 hours. In 20 pa- tients (89%) in group 1 and 3 (43 % ) in group 2

the CK-MB level reached a peak within 18 hours. The sensitivity, specificity and predictive accuracy of positive results of early Tc-99m-PYP scintigraphy in predicting the reperfusion were 79%, 100% and 83 % . These values are significantly higher than or similar to those of early peaking of CK and CK-MB release. In contrast to measurements of enzyme re- lease, reperfusion data for Tc-99m-PYP scintigraphy are available immediately after thrombolytic thera- py. Therefore, early Tc-99m-PYP scintigraphy (3 to 8 hours after onset of symptoms) is valuable as a noninvasive technique for early diagnosis of reperfusion.

(Am J Cardiol 1987;.80:782-785)

0 c&ding coronary thrombi are present in 86% of the patients with acute myocardial infarction (AMI) who are studied within 6 hours after the onset of symp- toms,! and intracoronary thrombolysis therapy results in recanalization in 60 to 87% of acutely occluded coronary arteries. 2-4 Recent studies show that recana- lization results in a rapid release of creatine kinase (CKj5p6 and early myocardial technetium-99m pyro- phosphate (Tc-99m-PYP] uptake within 12 hours after the onset of symptoms .7-12 Although recanalization can be achieved by intravenous urokinase or streptokinase infusion in 31 to 79% of the patients with AMI,13-16 noninvasive indicators of early successful recanaliza- tion have been limited to early peak CK and CK-MB activity and occurrence of transient arrhythmias.17

From the Division of Cardiology, Shimada City Hospital, Shi- mada, Shizuoka, Japan. Manuscript received March 30, 1987; revised manuscript received and accepted June 4,1987.

Address for reprints: Makoto Kondo, MD, Division of Cardi- ology, Shimada City Hospital, 1200-5 Noda Shimada, Shizuoka 427, Japan.

We examined whether early Tc-99m-PYP scintig- raphy can be used as an indicator for early successful recanalization in place of the early peaking of CK and CK-MB release. For this purpose, we compared Tc- 99m-PYP scintigrams recorded immediately after in- tracoronary thrombolysis with early peak CK and CK-MB activity [within 16 hours after the onset of symptoms] in patients with AMI.

Methods Study patients: Thirty-six patients with established

AM1 received intracoronary urokinase infusion. All patients met all the entry criteria: (1) admission to the hospital within 6 hours after the onset of acute chest pain that lasted for more than 30 minutes, (21 electro- cardiographic findings of AM1 as shown by ST eleva- tion 2 mm or new pathologic Q waves that persisted after administration of 0.6 mg of sublingual nitroglyc- erin, (31 no history of remote myocardial infarction, and (4 consent given for emergency coronary arteriog- raphy and left ventriculography and intracoronary thrombolysis. The mean (A standard deviation] age of the patients (13 women, 23menj was 63 f 12 years.

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3ctober

All patients underwent catheterization 3.9 & 1.1 hours (range 1.9 to 5.91 after the onset of AMI. At the start of the procedure, heparin, 3,000 IU, was adminis- tered intravenously. Using the percutaneous femoral Seldinger approach, single-plane left ventricular cine- angiography was performed in the 30~ right anterior oblique projection. Selective arteriography of right and left coronary artery was performed in several pro- jections. When a coronary occlusion was clearly visu- alized, continuous intracoronary urokinase infusion was begun. Injections of contrast material were re- peated every 10 minutes. The total dose of urokinase ranged from 720,000 to 1.68 million IU. After infusion of urokinase was stopped, left and right coronary arte- riography was repeated.

Technetium-99m-pyrophosphate scintigraphy: Immediately after coronary thrombolysis, all patients received intravenous injection of Tc-99m-PYP (20 mCi) 2.8 to 8.0 hours after the onset of AM1 (early scintigram). Imaging was performed 2 hours after in- travenous injection. In patients with negative scinti- graphic findings, scintigraphy was repeated 22 to 58 hours after the onset of AM1 (late scintigram). Images were recorded in the anterior, 45O left anterior oblique and left lateral projections. Studies were performed using a Hitachi RC-X-1635 LD scintillation camera equipped with a low-energy, high-resolution, parallel- hole collimator.

All images were interpreted visually by 3 experi- enced physicians without knowledge of the patient’s clinical data. Scintigrams were graded 0 to 4+ as de- scribed by Willerson et al? Scintigraphic findings were considered positive if the grade was 2+ or great- er. Scintigrams were also classified as showing focal or diffuse uptake.

Determination of early peaking of creatine kinase and creatine kinase-MB release: Blood samples were collected on admission, every 4 hours for the first 24 hours, every 6 hours for the next 24 hours, every 8 hours for the next 24 hours and every 24 hours thereaf- ter for 4 more days. CK activity was measured by the technique of Rosalki and CK-MB isoenzyme was quantitatively measured using a radioimmunoassay technique. Peak CK and CK-MB release within 16 hours after the onset of symptoms of AM1 was used as an indicator of reperfusion?J6

Statistical analysis: Analysis of difference was per- formed using the chi-square test or unpaired t test. Results were expressed as the mean f standard devi- ation. A significant difference was considered pres- ent at the p <O&5 level. Standard methodslg were used to calculate sensitivity, specificity and predictive accuracy.

Results Emergency coronary arteriographic and throm-

bolytic findings: The patients were separated into 2 groups. After intracoronary urokinase infusion, pa- tients in group 1 (n = 29) showed early recanalization and those in group 2 (n = 7) did not. There was no differences in sex ratio, age, time to cardiac catheter- ization or location of AM1 in the 2 groups (Table I). In group 1 at initial coronary arteriography, 4 patients

LE f Subject Characteristics ~-----_- _____-

Group 1 (n = 29)

~-__II

Age W 63 f 12 Sex (female/male) 11/16 Time to CA (hr) 3.9 i 1.3 Infarct location

Anteriar 14 Inferior 11 Lateral 4

There were no significant differences. CA = coronary arteriography.

Group 2 (n = 7)

66% 11 2f5

4.4 f 1.3

4 2 1

showed spontaneous good reperfusion and 25 had to- tal occlusion or subtotal occlusion with delayed wash- out of contrast material. All 25 patients showed suc- cessful recanalization with intracoronary infusion of urokinase.

Early technetium-99m-pyrophosphate scinti- graphic data (Fig. 1): The interval between onset of symptoms of AM1 and injection of the tracer was shorter (p <O-05) in group 1 (5.4 f 1.2 hours) than in group 2 (6.4 f 1.0 hours). Twenty-three patients (79%) in group 1 had positive scintigraphic findings immedi- ately after thrombolytic therapy. Thirteen patients showed 2+ activity, 8 of whom showed focal uptake. Nine patients showed 3+ activity and 1 patient 4-t- activity. All 7 patients in group 2 yielded negative re- sults on the early scintigram.

In 11 of the 13 patients in whom scintigraphic re- sults were negative, Tc-99m-PYP scintigraphy was re- peated 22 to 58 hours after the onset of AMI. In only 1 patient in group 1 (5 patients) did the late scintigram show positive findings. In contrast, in group 2 the late scintigram showed positive findings in 5 of the 6 patients.

Early peaking of creatine kinase and creatine ki- nase-MB release (Table II, Fig. 1): Peak CK and CK- MB concentrations were similar in the 2 groups. How- ever, the interval from onset of symptoms of AM1 until peak enzyme level was significantly shorter (p <O.Ol)

FIGURE 1. Results of early technetium-99m pyrophosphate (Tc- 99m-PYP) scintigraphy and early peaking of creatine klnase (CK) and CK-MB to detect the early reperfusion of infarcted vessels.

764 COMPARISON STUDY OF INDICATORS OF REPERFUSION

TABLE II Cardiac Enzyme Kinetics

Group 1 Group 2 P

Time to enzyme peak (hr) CK CK-MB

Peak enzyme concentrations (U/liter) CK CK-MB

15.1 f 5.6 22.0 f 3.6 <O.Ol 13.2 f 5.4 18.0 f 4.1 <O.Ol

1,377 i 759 1,792 f 862 NS 261 f 158 283 f 129 NS

Normal values: CK = <80 U/liter; CK-MB = <4 U/liter. CK-MB = creatine kinase-MB; NS = not significant.

TABLE Ill Comparison of Early Technetium-99m-Pyrophosphate Scintlgraphy and Early Creatine Kinase, Creatine Kinase-MB Peak (Within 16 Hours) as an Indicator of Early Reperfusion

Sensitivity Specificity Predictive Accuracy

Early Tc-99m-PYP scan 79% (23/29)l* 100% (7/7) Early CK peak 52% (15/29Y 86% (677) Early CK-MB peak 69% (20/29) 57% (4/7)

l p <0.05. CK-MB = creatine kinase-MB; ToSSm-PYP = technetium-99m pyrophosphate.

83 % (30/36b* 58% (21/36? 87% (24/36)

in group 1 than in group 2. CK release in 15 of the 29 patients (52%] in group 1 and 1 of the 7 patients (14%) in group 2 reached the peak level within 16 hours. CK- MB release in 20 patients (69%) in group 1 and 3 (43%) in group 2 reached the peak level within 16 hours.

Comparison between early technetium-ggm pyro- phosphate scan and early peak creatine kinase or creatine kinase-MB release (Table III): The sensitiv- ity, specificity and predictive accuracy of positive re- sults of early Tc-99m-PYP scintigraphy in predicting the presence of early reperfusion were 79% (23 of 29), 100% (7 of 7) and 83% (30 of 36). These were larger percentages than those for early peak CK and CK-MB release, although a significant difference was noted only in sensitivity and predictive accuracy of early peak CK release (p <0.05].

Discussion Unlike intracoronary thrombolysis, evidence for

reperfusion after intravenous thrombolysis cannot be based on coronary arteriography. Therefore, assess- ment of reperfusion by a noninvasive technique is necessary.

Superiority of early technetium-Wm-pyrophos- phate scintigraphy as an indicator for early recanali- zation: Several clinical and experimental studies have been reported on early myocardial Tc-99m-PYP up- take immediately after reperfusion.7-12 Wheelan et all2 described the significance of early Tc-99m-PYP scin- tigraphy as an indicator of reperfusion in patients who show early peak CK and CK-MB activity after intrave- nous thrombolysis. However, they did not compare early scintigraphic findings with early peak enzyme levels with regard to their significance as noninvasive indicators of reperfusion. Peaking of CK or CK-MB release within 16 hours after the onset of symptoms of AM1 is believed to be a sensitive indicator of reperfu- sion.12J6 However, it is of limited value in deciding

whether to start anticoagulant therapy immediately af- ter successful reperfusion because at least 1 day is needed for peak CK or CK-MB release after thrombo- lytic therapy. In contrast, Tc-99m-PYP scintigraphic findings can be examined immediately after intrave- nous thrombolysis. Adequate anticoagulant therapy after reperfusion is necessary to prevent the rethrom- bosis at the site of the previous obstructionzO Accord- ingly, we compared early myocardial Tc-99m-PYP up take with the early peak CK and CK-MB release. The sensitivity, specificity and predictive accuracy of ear- ly myocardial Tc-99m-PYP uptake in predicting the early reperfusion were superior or similar to those of early peak CK and CK-MB release within 16 hours after the onset of symptoms of AMI.

Mechanisms of early myocardial technetium- gtim-pyrophosphate uptake: The primary cellular mechanism of Tc-99m-PYP uptake is irreversible cel- lular damage with calcium accumulation, but uptake is related importantly to coronary flow.7-gJ1 Moreover, sudden restoration of large blood flow to the nonper- fused myocardium results in massive calcium over- load to the ischemic cells and causes contraction band necrosis immediately after reflow in human and ani- mal models.8~22~23 Therefore, if flow is limited to the infarct region, one generally must wait 1 to 3 days after the event to detect the infarct with Tc-99m-PYP imag- ing,l* whereas if flow is restored immediately, one may detect infarction during reperfusion.7-12 We suggest that early Tc-99m-PYP uptake directly reflects reper- fusion necrosis.ll Finally, one may also size the extent of infarction accurately with Tc-99m-PYP early in the reperfusion period if injection of the tracer is de- layed for approximately 90 minutes after the onset of reperfusion.24

Limitations: A diffuse pattern of 2+ was regarded as positive for diagnosis of early recanalization in pa- tients with AM1 in this study. Prasquier et a125 reported

that the incidence of diffuse uptake among patients with heart disease is not statistically different from that in the group without evidence of heart disease. They concluded that the 2+ diffusely positive pattern ap- peared nonspecific for diagnosis of AMI. In contrast, Willerson et alz6 showed that this diffuse pattern is common in patients with acute subendocardial infarc- tion and not in patients without electrocardiographic or enzymatic evidence of AMI. In our institution, Tc- 99m-PYP scintigraphy was performed in 133 patients admitted with chest pain of uncertain origin during the past 6 years. The initial images were recorded 1 to 7 days after the onset of symptoms. A 2+ diffuse pattern was recognized in 36 patients. Twenty-nine of the 36 patients (81%] had electrocardiographic and enzymat- ic evidence of AMI. We believe that the 2+ diffuse pattern is a valuable scintigraphic finding for diagno- sis of early recanalization in patients admitted with acute chest pain strongly suspected to be the result of AM1 and who received coronary thrombolysis.

Failure to detect a few reperfused infarcts in this study using planar Tc-99m-PYP imaging may indicate that the infarcts were fairly small, i.e., less than 3 g, or were atypically placed. 27~2~ Smaller and atypically lo- cated infarcts may be detected with enhanced sensi- tivity [as well as sized accurately) by Tc-99m-PYP im- aging if the technique is combined with single-photon emission-computed tomography.2g

Acknowledgment: We are indebted to the nursing and technical personnel at the 2nd Station of Internal Medicine and the Department of Radiology, whose generous help made this study possible, and to Dr. Hisayoshi Fujiwara of the Kyoto University Internal Medicine Department for his advice.

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