Comparison of tomographic and planar imaging for the evaluation of thrombolytic therapy in acute myocardial infarction using pre- and post-treatment myocardial scintigraphy with technetium-99m sestamibi

Comparison of tomographic and planar imaging for the evaluation of thrombolytic therapy in acute myocardial infarction using pre- and post-treatment myocardial scintigraphy with technetium-99m sestamibi Pre- and post-treatment myocardial scintigraphy with technetium-QQm hexakis 2-methoxy-isobutyi-isonitriie (Tc-QQm sestamibi) was performed in patients who underwent thromboiytic therapy for acute myocardiai infarction comparing planar imaging and single-photon emission computed tomography (SPECT). Twenty-one patients were injected with Tc-QQm sestamibi before thromboiytic treatment. SPECT and planar imaging were acquired after completion of the treatment. The scintigraphy was repeated 5 days later in 20 subjects. Planar and SPECT studies were evaluated using an uptake score. Patients were divided according to the status of the infarct-related vessel (patent in 13 patients, group 1, and occluded in seven, group 2) and to the presence of functional recovery in serial echocardiographic controls (present in 10 patients, group A, and absent in 10, group B). The scintigraphic defect extent in the 5-day images correlated with the enzymatic infarct size: SPECT: I = 0.75, p < 0.0002; planar: f = 0.68, p < 0.002. The decrease of the uptake defects correlated with the reduction of the left ventricular wail asynergy (admission versus 1 month echocardiogram): SPECT: r = 0.92, p < 0.000001; planar: r = 0.82, p < 0.00001. The percent decrease of the uptake defects was significantly higher in patients in group 1 and group A compared with group 2 and, respectively, group B-SPECT: group 1: 51.4 * 27.7 versus group 2: 13.1 +- 8.6, p < 0.02; group A: 64.2 + 15.3 versus group B: 11.9 + 8.1, p < 0.0002; planar: group 1: 41 + 30.4 versus group 2: 7.7 + 6.2, p < 0.05; group A: 52.5 f 24.3 versus group B: 6.1 + 6, p < 0.0002. This study confirms the reliability of pre- and post-treatment myocardiai scintigraphy with Tc-QQm sestamibi for evaluating the outcome of thromboiytic treatment in myocardiai infarction. The results seems slightly more accurate using SPECT, but a simple three-view planar study also gives useful data. (AM HEART J 1991;122:13.)

Gianni Bisi, MD, Roberto Sciagrh, MD, Giovanni M Santoro, MD,” Mario Leoncini, MD,a Pier Filippo Fazzini, MD,” and Ugo Meldolesi,

MD.

Florence, Italy

The ideal imaging method for evaluating the results of intravenous thrombolytic treatment in patients with acute myocardial infarction should be able to demonstrate both the jeopardized area present before treatment and the extent of the residual damage after therapy. Myocardial perfusion scintigraphy with thallium-201 performed before and after thromFrom the Nuclear Medicine Unit, Department of Clinical University of Florence; and BDepartment of Cardiology, Received

for publication

Reprint Clinical l-50134

requests: Gianni Pathophysiology, Florence. Italy.

411129350

July

10, 1990;

accepted

Bisi. MD, Nuclear Medicine I’niversity of Florence,

Dec.

Pathophysiology, Careggi Hospital. 12, 1990. Unit, Viale

Department Morgagni

of 85,

bolysis has been employed with interesting results,lW4 but the features of this tracer make its use impractical for the following reasons. (1) Its low emission energy unfavorably affects the image quality, particularly when single-photon emission computed tomography (SPECT) is performed. (2) The long half-life limits the dose that can be administered. (3) The availability of the tracer is reduced in most nuclear medicine laboratories, because it is a cyclotron product. (4) Finally and most importantly, owing to early redistribution, it is necessary to collect the images as soon as possible after the injection, and this might cause a delay in the starting of thrombolytic treatment, which could limit its effective13

14

Bisi et al.

American

July 1991 Heart Journal

ness.5 On the contrary, technetium-99m hexakis 2-methoxy-isobutyl-isonitrile (Tc-99m sestamibi) seems particularly well suited for pre- and posttreatment perfusion imaging.6* 7 The radionuclide has ideal emission energy for gamma camera imaging and the short half-life allows the relatively safe administration of high doses. The lack of significant redistribution of Tc-99m sestamibi makes it possible to inject it before starting the infusion of the thrombolytic agent and to delay the colection of the study even for several hours, without affecting the image quality.8 Furthermore, because of the unlimited availability of the radionuclide and the simple labeling procedure, the tracer can be employed with minimal time limitations. Various reports have already demonstrated the feasibility of pre- and post-treatment Tc-99m sestamibi myocardial scintigraphy and its usefulness in evaluating the results of thrombolytic therapy.‘-14 No attempt has been made, however, to verify in the same patients how far the use of either planar or SPECT imaging influences the reliability of this approach. The aim of this study has therefore been to compare in the same patient population the assessment of the results of thrombolytic treatment obtained by SPECT and planar images.

starting with an initial 10mg bolus,followed by dosesof 50, 20, and 20 mg at eachsuccessivehour, reaching a total dosageof 100mg over 3 hours. Apart from thrombolytic treatment, standard therapy with aspirin (325 mg orally), atenolol (5 to 10 mg intravenously), heparin (25,000 to 30,000U/24 hours intravenously), and nitroglycerin (up to 50 pg/min intravenously) wasgiven; opiates, antiarrhythmic agents, and diuretics were administered according to the condition of the patient. The subjects were subsequently (mean 2.6 + 1.4 hours after tracer injection, range 1 to 4 hours) transported under constant electrocardiographic monitoring and the closesupervision of a cardiological team (including one cardiologist and two experiencednurses)to the Nuclear Medicine Department for the admissionscintigraphy. Five days later patients underwent a secondscintigraphic study after the injection of the same doseof Tc-99m sestamibi for the assessment of the residual myocardial damage.In the meantime, a complete clinical and instrumental evaluation was performed to recognize noninvasively the occurrenceof reperfusion, including follow-up of symptoms, serial electrocardiograms, and blood samples for cardiac enzyme measurement. Twodimensional echocardiography was performed on the patient’s arrival in the hospital, 5 days after admission,and 1 month later. Patients underwent left heart catheterization within 1 week of admission.The study protocol was approved by the Ethics Committee for Human Studies in our institution, and all patients gave their informed consent to participate in the study.

METHODS Patient

Clinical, enzymatic, and electrocardiographic assessment. Blood sampleswere taken every hour for the first 12

The study group included 21 subjects (18 men and 3 women, mean age 59.2 1 10.8 years, range 39 to 80 years), who were admitted to our coronary care unit because of acute myocardial infarction within 4 hours of symptom onset. Clinical, enzymatic, echocardiographic, and quantitative SPECT data of 14 of these population.

patients were already included in a previous report.13The following diagnostic criteria of acute myocardial infarction were fulfilled: chest pain typical for myocardial ischemia lasting more than 30 minutes and unrelieved by sublingual administration of nitrates; ST segmentelevation 20.1 mV in at leasttwo limb leadsor ~0.2 mV in at leasttwo precordial leads.Further criteria for inclusion in the study were: no history of previous myocardial infarction or of other heart disease;no contraindications for thrombolytic therapy; presenceof a satisfactory echocardiographicwindow. Study protocol. As soonasthe arrival of a suspectacute myocardial infarction patient was announced to the coronary care unit by the emergency ambulancecoordination center, the Nuclear Medicine Department wasalerted and the labeling procedure of Tc-99m sestamibi (Cardiolite, E.I. Du Pont de Nemours & Co., Wilmington, Del.) was started. The patients were examined on arrival and, if all the inclusion criteria were fulfilled, 740 MBq of Tc-99m sestamibi were injected. Intravenous thrombolytic treatment was then immediately started. Recombinant tissue plasminogen activator (&PA, Actilyse, Boehringer Ingelheim, Ingelheim am Rhein, Germany) wasadministered

hours, every 3 hours for the following 12 hours, every 6 hours for the following 2 days, and every 12 hours until 96 hours had elapsedsinceadmission.Creatine kinase isoenzyme (CK-MB) activity wasmeasuredusingan immunoenzymatic method (Monotest CK-MB NAC-act, Boehringer Mannheim, Mannheim, Germany). Using the values of the obtained CK-MB curve, the infarct size wasestimated according to the method of Sobel et all5 and was expressed as CK-MB gram-equivalents. Twelve-lead electrocardiograms(ECGs) were performed using a Hewlett Packard 4700A electrocardiograph (Hewlett-Packard Co., Medical Products Group, Andover, Mass.) every 30 minutes during the rt-PA infusion and for the following 2 hours; subsequently the ECGs were performed at the sametime intervals as the blood withdrawals. According to the clinical, ECG, and enzymatic data collected in the first 12 hours of hospitalization, the following findings were consideredindexes of reperfusion; abrupt or rapidly progressivedisappearanceof chest pain; significant reduction of the ST segment elevation with rapid return to the isoelectric line; early peaking of the CK-MB serum levels (within 12 hours of initiation of thrombolysis).‘6-1gHowever, taking into account the poor reliability of thesevariables in predicting reperfusion,20-22 we classifiedas reperfused patients only those patients in whom all three criteria were fulfilled and classifiedas unaffected by the treatment those in whom all three indexes

Volume Number

122 1. Part

Thrombolysis

I

were absent. On the other hand, the data were considered inconclusive if only one or two criteria were fulfilled. Two-dimensional echocardiography. An Aloka SSD710 echocardiograph (Aloka Co., Ltd., Tokyo, Japan), equipped with a mechanical scanning 3 MHz frequency transducer (Aloka ASU-32-3-M) was employed. Images were recorded on a Panasonic NGVlO video cassette recorder (Matsushita Electric Industrial Co., Ltd., Osaka, Japan) to allow an accurate study and the definition of the evolution of each patient’s findings. Parasternal long- and short-axis views and apical four- and two-chamber views were obtained in eachpatient. The subxiphoid window was employed in addition, whenever one of the above-mentioned views wassuboptimal. The left ventricular wall was subdivided into 11 segmentsaccording to a modification of the schemeproposed by Edwards et a1.,23with the apex consideredasa singlesegment,and the wall motion pattern of each segmentwasclassifiedasabnormal if at least 50% of it was either hypokinetic, akinetic, or dyskinetic. The extent of the asynergicterritory wasexpressedasa percent ratio between the number of asynergic segmentsand the total number of segments.The asynergy extents were compared and their changeswere expressedas a percentageof the admission involvement. All evaluations were performed independently by two experienced operators who had no knowledge of the other tests. Interobserver agreement was reached in 620 of 660 segments (94%); the remaining segmentswere reviewed with the help of a third observer and were classifiedby consensus. Coronary angiography. All patients underwent left heart catheterization through either the femoral or the brachial approach approximately 1 week after admission. The infarct-related vesselwas identified according to the electrocardiographic leads showingST segmentelevation, according to the site of wall motion abnormalities in the echocardiogramand by left ventriculography, and according to the location of the uptake defect in myocardial scintigraphy. Vessel patency was considered to be present whenever the TIMI (Thrombolysis In Myocardial Infarction) criteria 2 or 3 were fulfilled (partial perfusion with slowed opacification of the distal vesselor delayed clearance and complete perfusion with normal clearance, respectively).24The angiographic evaluation, and particularly the assessment of infarct-related vesselpatency, were performed by an experienced observerwho had no knowledgeof the results of the other investigations. Myocardial perfusion scintigraphy. Myocardial perfusion scintigraphy was performed using a double-head gammacamera (Rotacamera, SiemensAG, Erlangen, Germany), equipped with ultrahigh resolution collimators, with a 15% window about the 140 keV of technetium-99m emissionphotopeak. The gamma camera was interfaced with a computer (Hewlett-Packard, Model A900) and the acquisition of the SPECT study was performed in the step-and-shot mode, 360-degreerotation arc, 90 projections of 10 secondseach, on 64 X 64 matrices. Even if the acquisition time was contained in order to reduce the patient’s discomfort, the count density in the normally per-

in AMI by 7’~MihI

images

15

fused myocardium wassatifactorily high.’ ’ Subsequently. planar imageswere collected in three standard views (anterior, 45 and 75degree left anterior oblique), with a total of approximately 500,000counts in eachprojection. Planar imageswere acquired in zoom mode (magnification factor 1.5) on 128 x 128 matrices and also in analogic format on x-ray film, using a Micro Dot (SiemensAGI. The SPECT imageswere reconstructed with an iterative algorithm using the conjugated gradient method.?“,‘e In our experience, this reconstruction procedure significantly improves the image resolution, allowing the acquisition at. the depth of the heart of a full-width half-maximum value of the point spreadfunction of 8 mm.zeThe transaxial slices were subsequently rearranged along the vertical and horizontal long axesand the short axis of the heart.27The left, ventricular wall wassubdivided considering t,heshort-axis slicesat three different levels (basal, midventricular, and subapical) and the apical portions of the vertical and horizontal long-axis slices, obtaining a total of 22 segments (6 X 3 in the short-axis imagesplus four pertaining to the apex). In each segment the tracer upt,ake was graded according to the following score:0 = normal. 1 = reduced. and 2 = absentuptake. The jeopardized mgocardiumscore was calculated from the score in the admissionscintigraphy; the residual damage score was computed from the score of the &day SPECT. The difference of the defect scoresbetween the admissionand the s-day imageswas expressedas a percentage of the admissiondefect score. The planar images were subdivided in hive segments each, according to the schemeof liiat et al? The uptake pattern of eachsegmentwasclassifiedaccording to the folowing score:0 = normal, 1 = reduced, and 2 = absent uptake. The comparisonbetweenthe admissronand the 5-day imageswasmadeby expressingthe change;isa percentage of the admissiondefect score. The scoring was performed independently by two experienced observers.Of the 902 examined SPECT segments, a complete agreementin the classification wasachieved in 867 (96”;’ ); of the 615 planar segments,agreementwasarrived at in 584 (95”1). The remaining segments were reviewed with the help of a third ohserver and were finally classifiedby consensus. Statistical analysis. The comparisonsof’ the enzymatic and scintigraphic infarct sizesand of the echocardiographic and scintigraphic percent improvements were performed using both the Pearsoncorrelation coefficient and the linear regression analysis taking into account the probability level of the slope. The comparison between the scintigraphic percent improvement in I he group of successfully versus unsuccessfullytreated patients was made with the Mann-Whitney nonparametric test for unpaired data. The level of significance was fixed in all casesat p < 0.05. RESULTS Evaluation

of thrombolytic treatment results. The features of the patient population are shown in Table I. Of the 21 patients enrolled in the study, one

16

Bisi et al.

Table

American

I. Clinical, electrocardiographic, enzymatic, echocardiographic, and angiographic findings Noninvasive effective

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21

criteria reperfusion

of

Age

Sex

Infarct

Pain

ST

CK-MB

56 37 58 64 60 46 63 64 47 73 39 61 67 58 68 59 49 65 58 72 80

M F M M M M F M M M M M M M M F M M M M M

Ant Ant Ant Inf Ant Inf Inf

Yes Yes Yes Yes Yes Yes Yes

Yes Yes Yes No No No Yes

Yes Yes Yes No Yes No No

Enzymatic infarct size (CK-MB gm equivalents)

9.5

Ant

Yes

No

Yes

Ant Ant Inf Ant Inf Inf Ant Inf Inf Ant Inf Inf

Yes Yes No No

No Yes

No

No No No No No No No No

Yes No Yes No No Yes Yes Yes No No No No

No

No

Ant

No No No Yes No No

No No

No No

21 37.8 28.9 30.6 9.5 14.3 30 13.6 15 33 39 31.3 65 92.7 46.3 34.3 41 25 41.9 -

Echocardiogram percent decrease of asynergy (1 month us admission) 100 50 80 100 66 100 50 33 100 100 0 0 0 0 0 0 0 0 0 0 -

Ant, Anterior; CK-MB, early peaking of CK-MB; inf, inferior; occl, occluded; Pain, early relief of pain; ST, rapid return elevation in ECG. Group 1: patients 1 to 13; group 2: patients 14 to 20; group A: patients 1 to 10; group B: patients 11 to 20.

Table

July 1991 Heart Journal

defect

Patient No.

Adm

B-day

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21

13 22 23 7 19 8 6 14 10 7 14 22 16 17 27 22 19 14 12 24 21

1 8 12 2 8 2 2 9 4 2 12 22 14 13 23 18 17 11 12 23 -

score % decrease 92 64 48 71 58 75 67 36 60 71 14 0 13 23 15 18 11 21 0 4 -

Adm, Admission. Group 1: patients 1 to 13; group 2: patients 10; group B: patients 11 to 20.

Planar

defect

score

Adm

5-day

% decrease

7 14 12 6 11 5 9 12 6 10 8 12 13 15 15 13 13 16 12 14 12

2 8 9 1 5 1 3 9 5 4 8 12 12 13 13 11 12 15 12 14 -

70 43 25 83 54 82 67 25 16 60 0 0 8 14 13 14 8 5 0 0 -

14 to 20: group A: patients

Patent Patent Patent Patent Patent Patent Patent Patent Patent Patent Patent Patent Patent Occl Occl Occl Occl Occl Occl Occl

to isoelectric

line of ST segment

(No. 21) died 3 days after admission because of cardiogenic shock and was thus excluded from any further evaluation, The criteria for reperfusion were fulfilled by three patients, whereas in five other subjects the indicators led one to assume the absence of reflow. The findings of the remaining 12 patients were inconclusive. Regional asynergy was present in all patients at the echocardiographic examination performed on admission. On the 5-day echocardiogram, one of the three patients with signs of reperfusion and two of those with uncertain findings had a significant improvement of the wall motion pattern. The remaining patients all had the same degree of abnormal kinesis. With respect to the status of the infarct-related vessel, all patients with noninvasive data suggesting reperfusion had a patent vessel; of the five without signs of reperfusion, three had an occluded and two had a patent vessel; of the uncertainly classified patients, four had an occluded and eight had a patent

Ii. Scintigraphic findings SPECT

Infarct-related vessel

vessel.

1 to

The results of the one-month echocardiographic control showed a significant reduction of the asynergic area extent compared with the admission and with the 5-day pattern in seven patients, in addition to the three patients who already had normal wall

Volume Number

122 1. Part

1

motion in the 5-day echocardiogram. Of these seven subjects, two belonged to the group classified as effectively treated and five belonged to the group classified as uncertain; all these seven patients had a patent infarct-related vessel. In the remaining 10 subjects no changes of the asynergic area were observed. In conclusion, since the noninvasive criteria of reperfusion were inconclusive in most patients, the study group was divided taking into account both the angiographic findings and the presence of functional recovery in the echocardiogram. According to the angiographic status of the infarct-related vessel, two groups of patients could be identified: a group of 13 patients (No. 1 through 13 in Table I) with a patent infarct-related artery (group l), and one of seven subjects (No. 14 through 20 of Table I) with an occluded vessel (group 2). According to the presence or absence of functional recovery as demonstrated by the echocardiographic controls, a group of 10 patients (No. 1 through 10 of Table I) showed a significant functional recovery (group A), whereas in the remaining LO cases (No. 11 through 20 of Table I) no changes in regional wall motion pattern could be observed (group B). Scintigraphic results. The results of the admission and of the 5-day scintigraphies are summarized in Table II. The admission images in all patients showed a clear-cut uptake defect (Figs. 1 and 2), which was consonant in site with what could be expected according to the ECG and echocardiographic findings. SPECT. In the admission images, the defect score ranged from 6 to 27. In the 5-day images the score ranged from 1 to 23, and a decrease was seen in 18 patients. The defect score of the 5-day scintigraphies showed a correlation with the enzymatic infarct size (r = 0.75, p < 0.0002) (Fig. 3). The percent decrease of the defect score between admission and 5-day images correlated with the percent reduction of the echocardiographic asynergy between admission and 1 month (r = 0.92, p < 0.000001) (Fig. 4). The comparison of the percent decrease of the defect score beween the patients with a patent and those with an occluded infarct-related vessel showed a significant difference (group 1:51.4 +. 27.7 versus group 2: 13.1 it 8.6, p < 0.02) (Fig. 5). The comparison of the percent decrease of the defect score in the patients with functional recovery and in those without it demonstrated a highly significant difference between the two groups (group A: 64.2 + 15.3 versus group B: 11.9 t- 8.1, p < 0.0002) (Fig. 6). Planar imaging. The admission defect score ranged from 5 to 16. The 5-day images demonstrated a score

1. Pre- (top row) and post-treatment (bottom row) imagesof caseNo. 1. On the left is a kklegree left anterior oblique planar image,and on the right is a proximal short,axis SPECT slice. A perfusion defect invo!ving t,heseptum and the anterior wall is present in the pretreatment study (arrows). but is significantly lessevitlent ; 1rhe post -t,reaT ment images. Fig.

2. Pre- (top row) and post-treatment (bottom row) imagesof caseNo. 12. On the left is a 75.degreeleft anterior oblique planar imageand on the right is a midventricular vertical long-axis SPECT slice. A large defect involving the anterior wall and the apex (arrouls~is present in the pretreatment study and appearsalmost 1mchangedin the post-treatment images. Fig.

18

Nisi et al.

American

y =13.8

+ 0.62 x

r = 0.92

SEE = 1 1

July 1991 Heart Journal

l

y = I .44 + 0.28 x r = 0.75 SEE = 4.9

ij6 0l

z

l

0

0 Enzymatic

y = 3.17 + 0.16 x r = 0.68 SEE = 3.5

20 infarct

40 size

60 (CK-MB

80 100 gram-equivalents)

Fig. 3. Comparisonof the enzymatic infarct size with the

scintigraphic estimatesof myocardial damagein the 5-day images,using the SPECT (upper diagram) and the planar (lower diagram) defect scores.

ranging from 1 to 15, with an unchanged

y =7.8 + 0.55 f s m

80

$

60

r = 0.82

x

SEE = 17

pattern in

four patients and some degree of defect decrease in the others. The &day defect score taken as estimate of the residual myocardial damage extent showed a correlation with the enzymatic infarct size (r = 0.68, p < 0.002) (Fig. 3). The percent decrease of the defect score correlated with the reduction of the asynergic area extent score between admission and 1 month (r = 0.82, p < 0.00001) (Fig. 4). The comparison of the percent decrease of the defect score between the patients with a patent and those with an occluded infarct-related vessel showed a significant difference (group 1: 41 + 30.4 versus group 2: 7.7 +- 6.2, p < 0.05) (Fig. 5). The comparison of the percent decrease of the defect score in the patients with functional recovery and in those without it demonstrated a highly significant difference between the two groups (group A: 52.5 f 24.3 versus group B: 6.1 ? 6, p < 0.0002) (Fig. 6). DISCUSSION

The effectiveness of thrombolytic therapy in acute myocardial infarction has been already demonstrated by several trials,2g-3g but the assessment of results in the individual patient is still a major problem. Among the proposed methods, the comparison of pre- and post-treatment myocardial perfusion images is par-

x

0 0

20 Decrease

40

60

80

100

of wall motion abnormalities (Echocardiogram)

Fig. 4. Comparisonof the extent of functional recovery

evaluated usingthe echocardiogramand the decreaseof the scintigraphic perfusion defects betweenthe admissionand the &day study, usingSPECT (upper diagram) and planar images(lower diagram).

titularly attractive. This approach would allow us to identify the extent of the residual damage after intervention, which has an important prognostic value.2g-31p 33-37Furthermore, it would be possible to recognize the amount of myocardium at risk before treatment, which can be very different even in patients with occlusion of the same coronary artery.*O Finally, the salvaged myocardium, which is represented by the difference between the jeopardized territory and the residual damaged area, has been

Volume Number

122 1, Part

Thrombolysis

1

in AMI by T~-Ak/t+l

images

19

0

% O0 0 0

0

tj

cp

n

AA

I

Patent

$$ t Occluded

Infarct-related vessel Fig. 5. Comparisonof the decreaseof the scintigraphic defectsbetweenthe admissionand the s-day study in patients with a patent (group 1) versus those with an occluded infarct-related vessel(group 2). C’ircles represent SPECT data and triangles represent planar imaging data.

demonstrated to be the main determinant of postinfarction ischemia41 Previous animal studies42, 43 have shown that the perfusion defects observed with Tc-99m sestamibi scintigraphy performed after injecting the tracer during temporary occlusion of a coronary artery correlate with the extent of the jeopardized territory. In addition, a significant decrease of the uptake defects was found with a second injection of the tracer after the coronary flow was restored.42s43 On the other hand, images obtained after permanent occlusion corresponded to the histologically estimated infarct size.42 In humans the feasibility of pre- and post-treatment Tc-99m sestamibi myocardial scintigraphy in assessing the results of intravenous thrombolysis has been demonstrated by various authors.g-14 However, its role in the clinical practice is still to be defined. Among the problems to be solved there is the definition of the imaging requirements for obtaining reliable results. Both SPECT and planar images have been employed in different studies in the evaluation of thrombolytic treatment effectiveness with satisfactory results.g-14 The superiority of SPECT over planar imaging in myocardial perfusion studies, however, has been reported,44-46 and seems particularly noteworthy when Tc-99m sestamibi is the employed tracer.28 Furthermore, Verani et a1.42 demonstrated

that the assessment of infarct size with Tc-99m sestamibi in experimental animals was more accurate using quantitative SPECT than quantitative planar imaging, and that the latter method could thus be less effective in estimating blood flow improvement after reperfusion. It therefore seems reasonable to suppose that for the evaluation of thrombolytic treatment the use of SPECT could also be advantageous. On the other hand, the use of planar imaging during the acute phase of myocardial infarction is particularly attractive because it can be performed using a mobile gamma camera at the patient’s bedside, which is simpler and results in less patient discomfort. During the injection of Tc-99m sestamibi, it is also possible to perform high-quality first-pass angiocardiography.4g Therefore a comparison in the same patients of the results achieved with planar and SPECT images appears to be important.ll We evaluated both planar and SPECT images, using a simple scoring scheme, similar to that proposed by others. 28 In our population the defect score in the post-treatment SPECT images was able to provide an acceptable estimate of the infarct size. Using the vessel patency as the end point for classifying the thrombolysis results, the decrease of the SPECT defect score was significantly greater in the group of patients with a patent vessel than in those with an occluded one. A quite broad scatter of values,

20

Bisi et al.

American

ti ot 2

I

Present

I g

July 1991 Heart Journal

*+

Absent

Late functional recovery 6. Comparisonof the decreaseof the scintigraphic defects betweenthe admissionand the 5-day study in patients with functional recovery in the echocardiographic controls (group A) versus those without it (group B). Circles represent SPECT data and the triangles represent planar imaging data. Fig.

however, was found in the first group. This can be explained by the fact that when the angiographic evaluation is performed relatively late, as in our protocol, its value for the assessment of myocardial salvage is reduced. 22 On the contrary, the presence of functional recovery is considered a reliable marker of effective reperfusion,59 47,48 and should probably be regarded as the best end point for assessing the results of thrombolysis. 5o In our study group, the decrease of the SPECT defect score permitted the prediction of the presence of functional recovery, as assessed by serial echocardiographic examinations. Moreover, the defect score decrease was significantly higher in the group of patients with functional recovery compared with the group of those with unchanged wall motion abnormalities, showing a lower dispersion of values in the two groups and no overlap between them. Therefore our data confirm that SPECT allows the clinician to obtain valuable clinical data about the effectiveness of the thrombolytic therapy. The results obtained by the planar scintigrams were only slightly inferior to those obtained by SPECT in terms of estimating infarct size and predicting functional recovery. In the latter instance, the broader scatter of the values can be partly explained by the behavior of one patient (No. 9), who had a small infarct of the middle portion of the interven-

tricular septum and showed a much lower decrease of the planar defect score compared with the SPECT score. It is possible that the superimposition of regions with a normal uptake favored by the small extent of the infarction and by its location in this patient reduced the diagnostic tealiability of the planar images. The dispersion of the defect score decrease values in the patent infarct-related vessel group and in the functional recovery group was higher than when SECT was used; however, the differences between these two groups and the groups of the patients with an occluded artery and without functional recovery, respectively, remained significant. Furthermore, in the latter instance no overlap between the values of the two groups could be demonstrated. According to these data, the use of planar imaging instead of SPECT does not affect significantly the reliability of pre- and post-treatment myocardial scintigraphy with Tc-99m sestamibi. This supports the employment for this evaluation of mobile gamma cameras directly in the coronary care unit or in the emergency room. Consequently, the early assessment of post-treatment perfusion with a second injection of Tc-99m sestamibi immediately after the completion of thrombolytic therapy and the collection of pre-treatment images could be simplified. This approach has been proposed to allow the clinician to make any decision about “rescue” revascularization

Volume Number

122 1, Part

procedures‘@ 51 and would be a logical development of the pre- and post-treatment scintigraphic protocols. If the post-treatment images had to be anticipated, however, other factors than the imaging technique could play a role in conditioning the reliability of early post-treatment images for the evaluation of the results of thrombolytic therapy. The possibility of transient hyperemia after reperfusion should be considered,52 according to what has been demonstrated using thallium-201.53-56 The available data suggest that the improvement of reperfusion after thrombolytic therapy is already recognizable after 18 hours, but it is more marked in the scintigrams performed on the following days.14! 57 Further studies are therefore needed to clarify the problem. In conclusion, this study confirms the reliability of pre- and post-treatment myocardial scintigraphy using Tc-99m sestamibi in the assessment of intravenous thrombolytic therapy irrespective of the imaging method employed. Both by using SPECT and a standard three-view planar study is it possible to obtain clinically useful data in terms of estimates of the residual damage and, above all, in terms of identification of effective reperfusion.

REFERENCES 1.

2.

3.

4.

5.

6. 7. 8.

Thrombolysis in AMI by Tc-MIIU

1

Maddahi J, Ganz W, Ninomiya J, Fishbein M, Mondkar A, Buchbinder N, Marcus H, Geft I, Shah PK, Rozanski A, Swan HJC, Berman DS. Myocardial salvage by intracoronary thrombolysis in evolving acute myocardial infarction: evaluation using intracoronary injection of thallium-201. AM HEART J 1981:102:664-74. Schwarz F, Schuler G, Katus H, Mehmel HC, von Olshausen K, Hoffman M, Herrmann H-J. Kiibler W. Intracoronarv thrombolysis in acute myocardial infarction: correlations among serum enzyme, scintigraphic and hemodynamic findings. Am J Cardiol 1982;50:32-8. Schuler G, Schwarz F, Hoffman M, Mehmel H, Manthey J, MIurer W, Rauch B, Herrmann H-J, Kiibler W. Thrombolysis in acute myocardial infarction using intracoronary streptokinase: assessment by thallium-201 scintigraphy. Circulation 1982;66:658-64. De Coster PM, Melin JA, Detry JMR, Brasseur LA, Beckers C, Co1 J. Coronary artery reperfusion in acute myocardial infarction: assessment by pre- and post-intervention thallium201 myocardial perfusion imaging. Am J Cardiol 1985;55:88995. Schwarz F, Hoffman M, Schuler G, von Olshausen K, Zimmermann R, Kiibler W. Thombolysis in acute myocardial infarction: effect of intravenous followed by intracoronary streptokinase application on estimates of infarct size. Am J Cardiol 1984;53:1505-10. Zaret BL, Wacker FJ. Radionuclide methods for evaluating the results of thrombolytic therapy. Circulation 1987;76(suppl II):8-17. Wackers FJTh. Myocardial perfusion imaging. In: Gottschalk A, Hoffer PB, Potchen EJ, eds. Diagnostic nuclear medicine. Baltimore: ^. -- The -. Williams & Wilkins Co, 1988:291-354. Ukada RD, Glover D, Gaffney T, Williams S. Myocardial ki-

images

21

netics of technetium-99m-hexakis-2-methox~-isobutyl-isonitrile. Circulation 1988;77:491-8. 9. Kayden DS, Mattera JA, Zaret BL, Wackers FJTh. Demonstration of reperfusion after thrombolysis with technetium 99m isonitrile myocardial imaging. J Nucl Med 1988;29:1895‘I.

10. Faraggi M, Assayag P, Messian 0, Brochet El, Haegel A, Valere P. Bok B. Earlv isonitrile SPECT in acute mvocardial infarction: feasibility and results before and after” fibrinolysis. Nucl Med Commun 1989;10:539-49. 11. Wackers FJTh, Gibbons RJ, Verani MS, Kayden DS, Pellikka PA. Behrenbeck T. Mahamarian JJ. Zaret BL. Serial ouantitative planar technetium-99m isoniirile imaging in acuie myocardial infarction: efficacy for noninvasivr assessment of thrombolytic therapy. J Am Co11 Cardiol 1989;14:861-83. 12. GibbonsRJ,VeraniMS,BehrenbeckT,PellikkaPA,O’Connor MK, Mahamarian JJ, Chesebro JH, Wackers FJ. Feasibility of tomographic 99mTc-hexakis-2-methoxy-2-methylpropylisonitrile imaging for the assessment of myocardial area at risk and the effect of treatment in acute mpocardial infarction. Circulation 1989;80:1277-86. 13. Santoro GM, Bisi G, Sciagri R, Leoncini M, Pazzini PF, Meldolesi U. Single photon emission computed tomography with technetium-99m hexakis 2-methoxyisobutyi isonitrile in acute myocardial infarction before and after thrombolytit treatment: assessment of salvaged myocardium and prediction OI late functional recovery. J Am Co11 Cardiol 1990;15:301-14. 14. Pellikka PA, Behrenbeck T, Verani MS, Mahamarian JJ. Wackers FJTh, Gibbons RJ. Serial changcas in myocardiai perfusion usingtomographic technetium-99m-methoxy-z-me thylpropyl-isonitrile imaging following reperfusion therapy ot mvocardial infarction. J Nucl Med 1990:31:1269-75. 15. Sobe1 BE, Roberts R, Larson KB. Estimation of infarct size from serum MB creatine phosphokinase acti1,it.y: applications and limitations. Am J Cardiol 1976;37:474-ir5. 16. Ganz W, Geft I, Shah PK, Lew AS, Rodrl;ruez L, Weiss T, Maddahi J, Berman DS, Charuzi Y, Swan HdC. Intravenous streptokinase in evolving acute myocardial infarction. Am .I Cardiol 1984:53:1209-16. 17. Krucoff MW, Green CE, Satler LF, Miller Ft.,‘,l’allas RS, Kent KM, Del Negro AA, Pearle DL, Fletcher i;
22

Bisi et al.

26. Formiconi AR, Pupi A, Passeri A. Compensation of spatial system response in SPECT with conjugate gradient reconstruction technique. Phys Med Biol 1989;34:69-84. 27. Formiconi AR. Oblique angle sections in emisson computed tomography. J Nucl Me’d All Sci 1984;28:109-14. 28. Kiat H, Maddahi J, Roy LT, Van Train K, Friedman J, Resser K. Berman DS. Comuarison of technetium-99m methoxv isobutyl isonitrile and thallium-201 for evaluation of coronary artery disease by planar and tomographic methods. AM HEART J 1989;117:1-11. 29. Simoons ML, Serruys PW, van den Brand M, Bar F, de Zwaan C, Res J, Verheugt WA, Krauss XH, Remme WJ, Vermeer F, Lubsen J. Improved survival after early thrombolysis in acute myocardial infarction. A randomized trial by the Interuniversity Cardiology Institute in the Netherlands. Lancet 1985; 2:578-82.

The ISAM Study Group. A prospective trial of Intravenous Streptokinase in Acute Myocardial infarction (ISAM): mortality, morbidity and infarct size at 21 days. N Engl J Med 1986;314:1465-71. 31. Guerci AD, Gerstenblith G, Brinker JA, Chandra NC, Gottlieb SO, Bahr RD, Weiss JL, Shapiro EP, Flaherty JT, Bush DE, Chew PH, Gottlieb SH, Halperin HR, Ouyang P, Walford DG, Bell WR, Fatterpaker AK, Llewellyn M, Top01 EJ, Healy B, Siu LC, Weisfeldt ML. A randomized trial of intravenous tissue plasminogen activator for acute myocardial infarction with subsequent randomization to elective coronary angioplasty. N Engl J Med 1987;317:1613-8. 32. Gruppo Italian0 per lo Studio della Streptochinasi nell’Infarto miocardico. Long-term effects of intravenous thrombolysis in acute myocardial infarction: Final report of the GISSI Study. Lancet 1987;2:871-4. 33. White HD, Norris RM, Brown MA, Takayama M, Maslowski A, Bass NM, Ormiston JA, Whitlock T. Effect of intravenous streptokinase on left ventricular function and early survival after acute myocardial infarction. N Engl J Med 1987;317:85030.

5. 34.

35.

36.

37.

38.

39.

40.

Kennedy JW, Martin GV, Davis KB, Maynard C, Stadius M, Sheehan FH, Ritchie JL. The Western Washington Intravenous Streptokinase in Acute Myocardial Infarction randomized trial. Circulation 1988;77:345-52. National Heart Foundation of Australia Coronary Thrombolysis Group. Coronary thrombolysis and myocardial salvage by tissue plasminogen activator given up to 4 hours after onset of myocardial infarction. Lancet 1988;1:203-7. Sheehan FH, Doerr R, Schmidt WG, Bolson EL, Uebis R, von Essen R, Effert S, Dodge HT. Early recovery of left ventricular function after thrombolytic therapy for acute myocardial infarction: an important determinant of survival. J Am Co11 Cardiol 1988;12:289-300. Serruys PW, Simoons ML, Suryapranata H, Vermeer F, Wijns W, van den Brand M, Bar F, Zwaan C, Krauss H, Remme WJ, Res J, Verheugt FWA, van Domburg R, Lubsen J, Hugenholtz PG. Preservation of global and regional left ventricular function after early thrombolysis in acute myocardial infarction. J Am Co11 Cardiol 1986;7:729-42. The AIMS Trial Study Group. Effect of intravenous APSAC on mortality after acute myocardial infarction: preliminary report of a placebo-controlled clinical trial. Lancet 1988;1:5459. ISIS 2 Collaborative Group. Randomized trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS 2. Lancet 1988;2:349-60. Feiring AJ, Johnson MR, Kioschos JM, Kirchner PT, Marcus ML, White CW. The importance of the determination of the myocardial area at risk in the evaluation of the outcome of acute myocardial infarction in patients. Circulation 1987; 75:980-7.

American

July 1991 Heart Journal

41. Weiss AT, Maddahi J, Shah PK, Lew AS, Swan HJC, Ganz W, Berman DS. Exercise-induced ischemia in the streptokinasereperfused myocardium: relationship to extent of salvaged myocardium and degree of residual coronary stenosis. Ahf HEART

J 1989;118:9-16.

42. Verani MS, Jeroudi MO, Mahamarian JJ, Boyce TM, BorgesNeto S, Pate1 B, Bolli R. Quantification of myocardial infarction during coronary occlusion and myocardial salvage after reperfusion using cardiac imaging with technetium-99m hexakis 2methoxyisobutyl isonitrile. J Am Co11Cardiol 1988; 12:1573-81.

43. Li QS, Frank TL, Franceschi D, Wagner HN, Becker LC. Technetium-99m methoxy isobutyl isonitrile (RP30) for quantification of myocardial ischemia and reperfusion in dogs. J Nucl Med 1988;29:1539-48. 44. Ritchie JL, Williams DL, Harp G, Stratton JL, Caldwell JH. Transaxial tomography with thallium-201 for detecting remote myocardial infarction. Am J Cardiol 1982;50:1236-41. 45. Nohara R, Kambara H, Suzuki Y, Tamaki S, Kadota K, Kawai C, Tamaki N, Torizuka K. Stress scintigraphy using singlephoton emission computed tomography in the evaluation of coronary artery disease. Am J Cardiol 1984;53:1250-4. 46. Berman DS, Kiat H, Maddahi J, Shah PK. Radionuclide imaging of myocardial perfusion and viability in assessment of acute myocardial infarction. Am J Cardiol 1989;64:9B-16B. 47. Beller GA. Role of myocardial perfusion imaging in evaluating thrombolytic therapy for acute myocardial infarction. J Am Co11 Cardiol 1987;9:661-8. 48. Reduto LA, Freund GC, Gaeta JM, Smalling RW, Lewis B, Gould KL. Coronary artery reperfusion in acute myocardial infarction: beneficial effects of intracoronary streptokinase on left ventricular salvage and performance. AM HEART J 1981;102:1168-77. 49. Baillet GY, Mena IG, Kuperus JH, Robertson JM, French Wd. Simultaneous technetium-99m MIBI angioaranhv and mvocardial perfusion imaging. J Nucl Med 1989;30:38-44. ” 50. Verani MS, Roberts R. Preservation of cardiac function by coronary thrombolysis during acute myocardial infarction: fact or myth? J Am Co11 Cardiol 1987;10:470-6. 51. Beller GA. Noninvasive assessment of myocardial salvage after coronary reperfusion: a perpetual quest of nuclear cardiology. J Am Co11 Cardiol 1989;14:874-6. 52. Soufer R, Zohgbi S, Vaivoda D, Zaret BL, Wackers FJ. Isonitrile myocardial uptake following prolonged occlusion and reperfusion overestimate flow in the infarct zone [Abstract]. Circulation 1988;78(suppl II):II-386. 53. Melin JA, Becker LC, Bulkley BH. Differences in thallium-201 uptake in reperfused and nonreperfused myocardial infarction. Circ Res 1983;53:414-9. 54. Okada RD, Pohost GM. The use of preintervention and postintervention thallium imaging for assessing the early and late effects of experimental coronary arterial reperfusion in dogs. Circulation 1984;69:1153-9. 55. Granato JE, Watson DD, Flanagan TL, Gascho JA, Beller GA. Myocardial thallium-201 kinetics during coronary occlusion and reperfusion: influence of method of reflow and timing of thallium-201 administration. Circulation 1986;73:150-60. 56. Schafer J, Spielmann RP, Bromel T, Bleifeld W, Mathey DG. Thallium 201/technetium-99m pyrophosphate overlap in patients with acute myocardial infarction after thrombolysis: predition of depressed wall motion despite thallium uptake. AM HEART

J 1986;112:291-5.

57. Gregoire J, Dupras G, Arsenault A, Bilodeau L, Lara Teran J, Gagnon D, Theroux P. Serial Tc-99m methoxy isobutyl isonitrile (MIBI) myocardial SPECT studies to assess reperfusion in patients with acute myocardial infarction [Abstract]. J Nucl Med 1989;3O(suppl):800.