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Selective intracoronary injection of sestamibi to detect myocardial viability: prediction of perfusion and contractile recovery after percutaneous transluminal coronary angioplasty
Selective intracoronary injection of sestamibi to detect myocardial viability: Prediction of perfusion and contractile recovery after percutaneous transluminal coronary angioplasty Carlo Trani, MD,a Alessandro Giordano, MD,b Antonella Lombardo, MD,a Alessandro Lupi, MD,a Francesca Reale, MD,b Roberto Patrizi, MD,a Giampiero Patrizi, MD,a Mario A. Mazzari, MD,a Giovanni Schiavoni, MD,a and Attilio Maseri, MD, FACCa Background. The main limitation of myocardial single photon emission computed tomography (SPECT) in detecting hibernating myocardium is the poor delivery of radiotracers in hypoperfused areas supplied by severely stenotic coronary arteries. Increasing local availability of radiotracers by intracoronary injection might represent an attractive solution. The hypothesis that the intracoronary administration of sestamibi could improve myocardial SPECT accuracy in detecting hibernating myocardium was addressed in this pilot study. Methods and Results. Seven patients with prior myocardial infarction and severe stenosis of the infarct-related artery underwent myocardial SPECT after intracoronary injection of technetium 99m sestamibi immediately before percutaneous transluminal coronary angioplasty (PTCA). Wall motion and perfusion were evaluated, before and 1 month after PTCA, by 2-dimensional echocardiography and rest-redistribution thallium 201 SPECT. A “low-flow area” was identified on the pre-PTCA Tl-201 SPECT image as the area with less than 50% of maximum radiotracer uptake. Changes in wall motion and perfusion in the low-flow area were compared with results of intracoronary sestamibi imaging. On a pixel-by-pixel analysis, intracoronary sestamibi predicted perfusion recovery within the low-flow area with a 91% sensitivity, a 78% specificity, and an 82% overall accuracy. Only in the 5 patients with an extent of sestamibi uptake greater than one third of the low-flow area was an improved regional and global left ventricular wall motion observed after PTCA (wall motion score index decreased from 1.95 ⴞ 0.28 to 1.60 ⴞ 0.34, P ⴝ .007; left ventricular ejection fraction increased from 42% ⴞ 7% to 49% ⴞ 7%, P ⴝ .001; asynergic segments in the low-flow area decreased from 3.6 ⴞ 0.9 to 1.8 ⴞ 1.5, P ⴝ .021). Conclusions. In patients with prior myocardial infarction and severe stenosis of the infarct-related artery, sestamibi uptake after intracoronary administration identified viable myocardium that was undetected after rest-redistribution thallium SPECT but capable of clinically significant contractile improvement after revascularization. (J Nucl Cardiol 2003;10: 473-81.) Key Words: Percutaneous transluminal coronary angioplasty • single photon emission computed tomography • myocardial viability • revascularization
The main limitation of scintigraphy in the prediction of the functional outcome of asynergic myocardium after From the Institute of Cardiologya and Institute of Nuclear Medicine,b Universita` Cattolica del Sacro Cuore, Rome, Italy. Received for publication May 22, 2002; final revision accepted Feb 12, 2003. Reprint requests: Alessandro Giordano, MD, Istituto di Medicina Nucleare, Universita` Cattolica del Sacro Cuore, Largo A. Gemelli, 8, 00168, Roma, Italy; [email protected]. Copyright © 2003 by the American Society of Nuclear Cardiology. 1071-3581/2003/$30.00 ⫹ 0 doi:10.1016/S1071-3581(03)00522-1
revascularization is the intrinsic characteristics of the perfusion tracers used in viability assessment.1-7 Radiotracer uptake depends on regional blood flow, and if its local availability is extremely reduced, as could occur in severely hypoperfused areas, it would not reliably represent the amount of viable myocardium. This might impair the accuracy of scintigraphic techniques in predicting the functional recovery of hibernated myocardium,8 a state of dysfunction of myocardial contractility resulting from chronic hypoperfusion.9 To overcome this limitation, it seems reasonable to increase the local delivery of radiotracers in the low-flow 473
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Table 1. Principal clinical data of study population
Patient No.
Age (y)
IRA
Time from AMI (d)
LVEF (%)
AMI site
IRA stenosis (%)
1 2 3 4 5 6 7
56 63 67 42 47 59 47
Cx LAD LAD LAD LAD LAD LAD
45 35 40 40 30 90 160
52 35 40 40 50 48 33
Inferior Anterior Anterior Anterior Anterior Anterior Anterior
90 95 95 95 95 95 90
Cx, Circumflex coronary artery; LAD, left anterior descending coronary artery.
areas by injecting tracers selectively into the coronary artery perfusing the area of interest. To address this hypothesis, we injected technetium 99m sestamibi into the infarct-related coronary artery (IRA) of patients with previous acute myocardial infarction (AMI) and single-vessel disease undergoing percutaneous transluminal coronary angioplasty (PTCA); we evaluated whether intracoronary sestamibi imaging could detect viability within asynergic areas with severe thallium 201 defects. METHODS Study Population We studied 7 consecutive patients scheduled for PTCA with (1) 1- to 2-month-old AMI (6 anterior and 1 inferior), (2) severe asynergy (akinesis or dyskinesis) of the infarct area, (3) single-vessel disease with severe residual stenosis (ⱖ90%) of the IRA, and (4) postinfarction angina. Patients with symptoms of severe left ventricular dysfunction in the week preceding the PTCA were excluded. The clinical and angiographic characteristics of the patients are summarized in Table 1.
Study Protocol Each patient underwent baseline 2-dimensional echocardiography and rest-redistribution Tl-201 single photon emission computed tomography (SPECT). Immediately before angioplasty, sestamibi was injected selectively into the IRA. After successful PTCA and within 3 hours of radiotracer injection, scintigraphic imaging was performed. Both echocardiography and thallium scintigraphy were repeated 1 month after PTCA. The protocol was approved by the local Ethical Committee, and each patient gave written informed consent.
Images were recorded from parasternal long-axis and short-axis views as well as from apical 4- and 2-chamber views. Pre- and post-revascularization studies were read side by side by 2 observers. Analysis of regional wall motion, performed blindly to all other imaging results, was qualitatively assessed by use of a left ventricular 16-segment model, with a conventional 4-point scoring system,10 and the wall motion score index (WMSI) was calculated according to Smart et al.11 Recovery of individual segmental dysfunction after revascularization was defined as development of systolic wall thickening in an akinetic/dyskinetic segment. In each patient improvement of left ventricular function after revascularization was established when all of the following findings were observed: (1) decrease in WMSI, (2) improvement in left ventricular ejection fraction (LVEF), and (3) contractile improvement of 1 point or more in at least 1 asynergic segment of the low-flow area (see below).
Tl-201 Imaging All patients underwent the study while undergoing therapy (oral nitrates included). After an overnight fast, 74 MBq Tl-201 was injected intravenously at rest. SPECT was carried out 30 minutes and 4 hours later with a wide-field-of-view gamma camera (Elscint Apex 409; Elscint, Haifa, Israel) equipped with a low-energy medium-resolution (general-purpose) collimator. The camera was rotated over a 180° arc in a circular orbit around the patient’s thorax at 6° increments for 45 seconds each. The acquisition matrix was 64 ⫻ 64, with a zoom factor of 1.2⫻. After filtered backprojection with a Butterworth filter (cutoff frequency, 0.35 cycles/pixel; order, 5), a series of short-axis slices was generated, and after data compression to 15 slices, bull’s-eye polar plots were obtained as previously reported.12
Echocardiographic Data Analysis
Intracoronary Sestamibi Administration and SPECT Imaging
Echocardiographic studies were performed with a Toshiba 270 System (Toshiba Medical Systems Europe, Zoetermeer, Netherlands) equipped with a 2.75-MHz transducer and were recorded on a 3/4-inch videorecorder for subsequent analysis.
Before PTCA, through an 8F guiding catheter positioned in the left coronary ostium, a coaxial dilatation catheter was advanced over the wire and positioned in the proximal portion of the vessel. The guidewire was removed and 74 MBq Tc-99m
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Figure 1. Images for comparing intracoronary sestamibi (IC MIBI) and Tl-201 SPECT. Upper row, Tl-201 bull’s-eye maps before PTCA (left) and after PTCA (right); the orange ROI superimposed on the maps represents the low-flow area. Lower row, Intracoronary sestamibi bull’s-eye map (left) and silhouette of the low-flow area (right). As shown, the perfusion recovery within the low-flow area is accurately predicted by intracoronary sestamibi.
sestamibi diluted in 0.5 mL of saline solution was selectively injected through the lumen of the catheter. The catheter lumen was slowly flushed with another 10 mL of saline solution; PTCA of the stenosis was then carried out. After PTCA, the sestamibi scan was begun within 3 hours, in the Department of Nuclear Medicine (Rome, Italy), with the same protocol used for thallium scintigraphy but with a high-resolution low-energy collimator. So that thallium and sestamibi studies could be compared, the reconstruction and processing were carried out by use of the same geometrical parameters for the recognition of left ventricular edges and for angles of reorientation of the slices. This was automatically obtained by use of commercial software for stress/redistribution studies and assigning the delayed thallium study to “stress” and the intracoronary sestamibi study to “redistribution.” As for Tl-201 SPECT, a bull’seye plot was obtained.
superimposed on both intracoronary sestamibi and post-PTCA Tl-201 delayed bull’s-eye maps (Figure 1). On the intracoronary sestamibi bull’s-eye map, the presence in the low-flow area ROI of pixels with sestamibi uptake was assumed to represent amounts of viable myocardium that were undetected by pre-PTCA thallium imaging. Pixels with sestamibi uptake were those whose count was above 20% of maximum. We chose this arbitrary criterion to exclude the interference of noise counts generated by filtered backprojection in areas without significant tracer uptake. On the post-PTCA Tl-201 delayed bull’s-eye map, the presence in the low-flow area ROI of pixels with a thallium uptake higher than 50% of maximum was considered to represent post-PTCA perfusion recovery. The criteria reported in Table 2 were used on a pixel-bypixel basis to calculate the sensitivity and specificity of intracoronary sestamibi in detecting perfusion recovery in the low-flow area.
Scintigraphic Data Analysis For each patient, on the pre-PTCA Tl-201 delayed bull’seye map, an automatic region of interest (ROI) bordering pixels with lower than 50% of the maximum count (low-flow area) was obtained. This area was considered an index of the extent of the nonviable myocardium, in agreement with the criteria of Dilsizian et al13 (Figure 1). The low-flow area ROI was then
Statistical Analysis The sensitivity, specificity, and accuracy of intracoronary sestamibi in detecting perfusion recovery on a pixel-by-pixel analysis were calculated. WMSI values, LVEF values, and the number of asynergic segments per patient, before and after PTCA, were compared by paired t test or Wilcoxon signed rank
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Table 2. Criteria for calculation of sensitivity and specificity of intracoronary sestamibi in predicting perfusion recovery
True positive True negative False positive False negative
Intracoronary sestamibi
Tl-201 post-PTCA*
Present Absent Present Absent
Present Absent Absent Present
*Tracer uptake greater than 50% in the low-flow area.
test, as appropriate. Data are expressed as mean ⫾1 SD. P ⬍ .05 was considered to be statistically significant.
RESULTS All patients underwent successful PTCA (residual stenosis ⬍20%) and were asymptomatic at the time of repeated Tl-201 SPECT and echocardiography. Prediction of Viability in Terms of Perfusion Recovery by Intracoronary Sestamibi The sensitivity, specificity, and overall accuracy for the prediction of perfusion recovery were 91%, 78%, and 82%, respectively. In other words, out of 2071 pixels within low-flow areas that improved Tl-201 uptake after PTCA, 1888 (91%) had shown sestamibi uptake after intracoronary administration, thus having been correctly predicted as viable. Conversely, out of 4358 pixels within low-flow areas that did not improve Tl-201 uptake after PTCA, 3389 (78%) had not shown sestamibi uptake after intracoronary administration, thus having been correctly predicted as nonviable. In Figures 2 and 3 representative short-axis slices and polar maps of the scintigraphic studies of patients 2 and 6 are shown, respectively. Prediction of Viability in Terms of Contractile Recovery by Intracoronary Sestamibi Of the 7 patients who underwent revascularization, 2 showed no contractile recovery after PTCA; in the remaining 5 patients, angioplasty improved the contractile function, as demonstrated by the observed reduction in WMSI (from 1.95 ⫾ 0.28 to 1.60 ⫾ 0.34, P ⫽ .007), increase in LVEF (from 42% ⫾ 7% to 49% ⫾ 7%, P ⫽ .001), and reduction in the number of asynergic segments in the low-flow area (from 3.6 ⫾ 0.9 to 1.8 ⫾ 1.5, P ⫽ .021). (Table 3). The first 5 patients showing an area of sestamibi
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uptake greater than one third of the low-flow area demonstrated congruent changes in all three echocardiographic parameters after PTCA—namely, reduction in WMSI, improvement in LVEF, and contractile improvement of one or more a-dyssynergic segment. Conversely, in the 2 patients showing an area of sestamibi uptake smaller than one third of the low-flow area, none of the three parameters improved after PTCA. DISCUSSION In this study the intracoronary injection of sestamibi provided an accurate prediction of both perfusion and contractile recovery after PTCA in selected patients with previous AMI and residual severe stenosis of the IRA. Quantitative rest-redistribution Tl-201 SPECT represents a well-established clinical tool for viability detection. Sestamibi has also been proposed for viability studies, on the basis of the experimental demonstration that its retention requires cellular integrity,3-6 even if it has been suggested that myocardial viability could be underestimated by this tracer.14-17 Indeed, the availability of any perfusion tracer in hypoperfused areas supplied by severely stenotic coronary arteries can be so extremely reduced that the uptake would not reliably represent the amount of viable myocardium. Several approaches have been proposed to improve radiotracer uptake, such as 24-hour delayed redistribution,18 Tl-201 reinjection,19,20 Tl-201 rest-redistribution,20,21 ribose infusion,22 and nitrate administration before or during Tc-99m–labeled perfusion tracer administration.23-25 The direct intracoronary injection could represent an attractive solution to maximize the local availability of the radiotracers. The feasibility of myocardial imaging after intracoronary injection of radiotracers has been previously demonstrated,26-31 and we have already reported on the possibility of detecting hibernating myocardium by intracoronary administration of sestamibi.32,33 The choice of sestamibi for the intracoronary procedures was dictated by practical reasons, as the injection had to be performed in the Catheterization Laboratory (Rome, Italy) before PTCA whereas imaging had to be carried out later, in the Department of Nuclear Medicine. The usually negligible redistribution of sestamibi, setting the perfusion state at the time of the injection despite subsequent changes in coronary blood flow,34-37 allowed us to delay the imaging after PTCA.37,38 Our findings confirm that sestamibi uptake reflects myocardial viability and predicts recovery of myocardial dysfunction. In this study sestamibi uptake in the lowflow area predicted post-PTCA perfusion recovery with a good sensitivity (91%). Moreover, all patients with a large extent of sestamibi uptake in the low-flow areas showed contractile recovery, confirming that a sizeable
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Trani et al Selective intracoronary injection of sestamibi to detect myocardial viability
Figure 2. A, Short-axis slices from the apex (left) to the base (right) of the left ventricle of patient 2. Upper row, Tl-201 before PTCA showing a severe perfusion defect that involves the middle and distal anteroseptal wall and the apex; middle row, intracoronary sestamibi before PTCA showing tracer uptake in the anteroseptal wall; lower row, Tl-201 1 month after PTCA showing normalization of perfusion in the anteroseptal wall, as correctly predicted by intracoronary sestamibi before PTCA. B, Polar maps corresponding to the scintigraphic studies of A (the lower level of the color scale was set to 20% of maximum). IC MIBI, Intracoronary sestamibi.
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Figure 3. A, Short-axis slices from the apex (left) to the base (right) of the left ventricle of patient 6. Upper row, Tl-201 before PTCA showing a severe perfusion defect of the apex extended to the distal anteroseptal wall and distal inferior wall; middle row, intracoronary sestamibi before PTCA showing absence of uptake in the regions with Tl-201 defect; lower row, Tl-201 1 month after PTCA showing unchanged perfusion pattern as compared with the pre-PTCA one, as correctly predicted by intracoronary sestamibi before PTCA. B, Polar maps corresponding to the scintigraphic studies of A (the lower level of the color scale was set to 20% of maximum). IC MIBI, Intracoronary sestamibi.
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Table 3. Intracoronary sestamibi to predict contractile recovery
Patient Intracoronary No. sestamibi* 1 2 3 4 5 6 7
47% 72% 45% 47% 62% 0% 28%
WMSI prePTCA
WMSI postPTCA
LVEF prePTCA
LVEF postPTCA
No. of adyssynergic segments pre-PTCA
1.75 1.78 1.88 1.89 2.44 1.89 1.67
1.25 1.44 1.44 1.78 2.11 1.89 1.89
51% 32% 40% 40% 47% 50% 33%
56% 39% 50% 46% 54% 50% 28%
3 3 4 3 5 4 2
No. of adyssynergic segments Contractile post-PTCA recovery 0 2 1 2 4 4 2
Yes Yes Yes Yes Yes No No
*Extension of sestamibi uptake expressed in percent of the low-flow area.
amount of viable myocardium is required for left ventricular function improvement after revascularization.39 These observations are particularly remarkable, because the low-flow area consisted of myocardium judged to be irreversibly injured on Tl-201 scintigraphy before PTCA.40 On the other hand, the suboptimal specificity of intracoronary sestamibi (78%) in predicting perfusion recovery must be interpreted according to its clinical relevance. In fact, perfusion recovery and improvement of left ventricular function do not necessarily correlate. As a matter of fact, the two patients in our series judged to have viable myocardium by intracoronary sestamibi criteria but without perfusion recovery did have improved contractile function after revascularization. Thus, in patients with previous AMI and severe stenosis of the IRA, the increased local delivery of sestamibi in the asynergic myocardium obtained by selective intracoronary administration improves the scintigraphic detection of hibernated myocardium. We deliberately did not take into consideration the amount and distribution of Tl-201 uptake both within and outside the low-flow area borders in the pre-PTCA study because our aim was to try to clarify the significance of the eventual uptake of intracoronary sestamibi in the infarct area. Conversely, the significance of the amount and distribution of Tl-201 uptake in terms of viable myocardium has been addressed by several studies whose sample size was remarkably superior to ours.39 Of note is that in all of our patients, intracoronary sestamibi distribution was in the IRA vascular territory; this finding excludes the possible spillover of the tracer into other vascular regions through collaterals. Limitations It is possible that the partial volume effect might have influenced our results. Indeed, normal myocardium,
hibernating myocardium, and infarcted myocardium have different wall thickness and wall motion measurements; thus comparisons of counts recorded in different pathophysiological conditions (pre- and post-PTCA) should always be considered with caution. This is a pilot study; indeed, the small number of patients studied does not allow us to draw definitive conclusions, even if an apparently clear-cut discrimination has been obtained between the 5 patients with improved left ventricular function and the 2 without it. Caution is required in applying these results to all patients with coronary artery disease and the need for myocardial viability assessment. Indeed, as the goal of our study was to investigate whether severe flow-limiting stenoses impair the accuracy of myocardial scintigraphy and whether the intracoronary injection can overcome this limitation, stringent selection criteria were required.
Conclusions After selective intracoronary administration, sestamibi uptake in the dyssynergic area is capable of correctly identifying viable myocardium undetected by Tl201 rest-redistribution myocardial scintigraphy. Our findings confirm that poor delivery of perfusion tracers in low-flow areas affects the accuracy of myocardial scintigraphy in detecting viable dyssynergic myocardium. From a practical point of view, the application of our method is limited because in the vast majority of cases PTCA immediately follows diagnostic coronary angiography. However, in selected patients in whom revascularization carries a non-negligible risk, it is common practice to defer the revascularization until the demonstration of viability has been obtained in order to improve the risk-benefit ratio. Thus in these patients the intracoronary sestamibi procedure could have a practical
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clinical application, provided that our results are confirmed in larger series. Acknowledgment The authors have indicated they have no financial conflicts of interest.
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using technetium-99m isonitrile imaging. Am Heart J 1991;122: 7-12. Haronian HL, Remetz MS, Sinusas AJ, et al. Myocardial risk area defined by technetium-99m sestamibi imaging during percutaneous transluminal coronary angioplasty: comparison with coronary angiography. J Am Coll Cardiol 1993;22:1033-43. Haronian HL, Sinusas AJ, Remetz MS, et al. Effects of altered left ventricular geometry on quantitative technetium 99m sestamibi defect size in humans: perfusion imaging during coronary angioplasty. J Nucl Cardiol 1994;1:150-8. Ragosta M, Beller GA, Watson DD, Kaul S, Gimple W. Quantitative planar rest-redistribution imaging in detection of myocardial viability and prediction of improvement in left ventricular function after coronary bypass surgery in patients with severely depressed left ventricular function. Circulation 1993;86:1630-41. Dilsizian V, Perrone Filardi P, Arrighi JA, et al. Concordance and discordance between stress-redistribution-reinjection and rest-redistribution thallium imaging for assessing viable myocardium. Circulation 1993;88:941-51.
The main limitation of scintigraphy in the prediction of the functional outcome of asynergic myocardium after From the Institute of Cardiologya and Institute of Nuclear Medicine,b Universita` Cattolica del Sacro Cuore, Rome, Italy. Received for publication May 22, 2002; final revision accepted Feb 12, 2003. Reprint requests: Alessandro Giordano, MD, Istituto di Medicina Nucleare, Universita` Cattolica del Sacro Cuore, Largo A. Gemelli, 8, 00168, Roma, Italy; [email protected]. Copyright © 2003 by the American Society of Nuclear Cardiology. 1071-3581/2003/$30.00 ⫹ 0 doi:10.1016/S1071-3581(03)00522-1
revascularization is the intrinsic characteristics of the perfusion tracers used in viability assessment.1-7 Radiotracer uptake depends on regional blood flow, and if its local availability is extremely reduced, as could occur in severely hypoperfused areas, it would not reliably represent the amount of viable myocardium. This might impair the accuracy of scintigraphic techniques in predicting the functional recovery of hibernated myocardium,8 a state of dysfunction of myocardial contractility resulting from chronic hypoperfusion.9 To overcome this limitation, it seems reasonable to increase the local delivery of radiotracers in the low-flow 473
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Table 1. Principal clinical data of study population
Patient No.
Age (y)
IRA
Time from AMI (d)
LVEF (%)
AMI site
IRA stenosis (%)
1 2 3 4 5 6 7
56 63 67 42 47 59 47
Cx LAD LAD LAD LAD LAD LAD
45 35 40 40 30 90 160
52 35 40 40 50 48 33
Inferior Anterior Anterior Anterior Anterior Anterior Anterior
90 95 95 95 95 95 90
Cx, Circumflex coronary artery; LAD, left anterior descending coronary artery.
areas by injecting tracers selectively into the coronary artery perfusing the area of interest. To address this hypothesis, we injected technetium 99m sestamibi into the infarct-related coronary artery (IRA) of patients with previous acute myocardial infarction (AMI) and single-vessel disease undergoing percutaneous transluminal coronary angioplasty (PTCA); we evaluated whether intracoronary sestamibi imaging could detect viability within asynergic areas with severe thallium 201 defects. METHODS Study Population We studied 7 consecutive patients scheduled for PTCA with (1) 1- to 2-month-old AMI (6 anterior and 1 inferior), (2) severe asynergy (akinesis or dyskinesis) of the infarct area, (3) single-vessel disease with severe residual stenosis (ⱖ90%) of the IRA, and (4) postinfarction angina. Patients with symptoms of severe left ventricular dysfunction in the week preceding the PTCA were excluded. The clinical and angiographic characteristics of the patients are summarized in Table 1.
Study Protocol Each patient underwent baseline 2-dimensional echocardiography and rest-redistribution Tl-201 single photon emission computed tomography (SPECT). Immediately before angioplasty, sestamibi was injected selectively into the IRA. After successful PTCA and within 3 hours of radiotracer injection, scintigraphic imaging was performed. Both echocardiography and thallium scintigraphy were repeated 1 month after PTCA. The protocol was approved by the local Ethical Committee, and each patient gave written informed consent.
Images were recorded from parasternal long-axis and short-axis views as well as from apical 4- and 2-chamber views. Pre- and post-revascularization studies were read side by side by 2 observers. Analysis of regional wall motion, performed blindly to all other imaging results, was qualitatively assessed by use of a left ventricular 16-segment model, with a conventional 4-point scoring system,10 and the wall motion score index (WMSI) was calculated according to Smart et al.11 Recovery of individual segmental dysfunction after revascularization was defined as development of systolic wall thickening in an akinetic/dyskinetic segment. In each patient improvement of left ventricular function after revascularization was established when all of the following findings were observed: (1) decrease in WMSI, (2) improvement in left ventricular ejection fraction (LVEF), and (3) contractile improvement of 1 point or more in at least 1 asynergic segment of the low-flow area (see below).
Tl-201 Imaging All patients underwent the study while undergoing therapy (oral nitrates included). After an overnight fast, 74 MBq Tl-201 was injected intravenously at rest. SPECT was carried out 30 minutes and 4 hours later with a wide-field-of-view gamma camera (Elscint Apex 409; Elscint, Haifa, Israel) equipped with a low-energy medium-resolution (general-purpose) collimator. The camera was rotated over a 180° arc in a circular orbit around the patient’s thorax at 6° increments for 45 seconds each. The acquisition matrix was 64 ⫻ 64, with a zoom factor of 1.2⫻. After filtered backprojection with a Butterworth filter (cutoff frequency, 0.35 cycles/pixel; order, 5), a series of short-axis slices was generated, and after data compression to 15 slices, bull’s-eye polar plots were obtained as previously reported.12
Echocardiographic Data Analysis
Intracoronary Sestamibi Administration and SPECT Imaging
Echocardiographic studies were performed with a Toshiba 270 System (Toshiba Medical Systems Europe, Zoetermeer, Netherlands) equipped with a 2.75-MHz transducer and were recorded on a 3/4-inch videorecorder for subsequent analysis.
Before PTCA, through an 8F guiding catheter positioned in the left coronary ostium, a coaxial dilatation catheter was advanced over the wire and positioned in the proximal portion of the vessel. The guidewire was removed and 74 MBq Tc-99m
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Figure 1. Images for comparing intracoronary sestamibi (IC MIBI) and Tl-201 SPECT. Upper row, Tl-201 bull’s-eye maps before PTCA (left) and after PTCA (right); the orange ROI superimposed on the maps represents the low-flow area. Lower row, Intracoronary sestamibi bull’s-eye map (left) and silhouette of the low-flow area (right). As shown, the perfusion recovery within the low-flow area is accurately predicted by intracoronary sestamibi.
sestamibi diluted in 0.5 mL of saline solution was selectively injected through the lumen of the catheter. The catheter lumen was slowly flushed with another 10 mL of saline solution; PTCA of the stenosis was then carried out. After PTCA, the sestamibi scan was begun within 3 hours, in the Department of Nuclear Medicine (Rome, Italy), with the same protocol used for thallium scintigraphy but with a high-resolution low-energy collimator. So that thallium and sestamibi studies could be compared, the reconstruction and processing were carried out by use of the same geometrical parameters for the recognition of left ventricular edges and for angles of reorientation of the slices. This was automatically obtained by use of commercial software for stress/redistribution studies and assigning the delayed thallium study to “stress” and the intracoronary sestamibi study to “redistribution.” As for Tl-201 SPECT, a bull’seye plot was obtained.
superimposed on both intracoronary sestamibi and post-PTCA Tl-201 delayed bull’s-eye maps (Figure 1). On the intracoronary sestamibi bull’s-eye map, the presence in the low-flow area ROI of pixels with sestamibi uptake was assumed to represent amounts of viable myocardium that were undetected by pre-PTCA thallium imaging. Pixels with sestamibi uptake were those whose count was above 20% of maximum. We chose this arbitrary criterion to exclude the interference of noise counts generated by filtered backprojection in areas without significant tracer uptake. On the post-PTCA Tl-201 delayed bull’s-eye map, the presence in the low-flow area ROI of pixels with a thallium uptake higher than 50% of maximum was considered to represent post-PTCA perfusion recovery. The criteria reported in Table 2 were used on a pixel-bypixel basis to calculate the sensitivity and specificity of intracoronary sestamibi in detecting perfusion recovery in the low-flow area.
Scintigraphic Data Analysis For each patient, on the pre-PTCA Tl-201 delayed bull’seye map, an automatic region of interest (ROI) bordering pixels with lower than 50% of the maximum count (low-flow area) was obtained. This area was considered an index of the extent of the nonviable myocardium, in agreement with the criteria of Dilsizian et al13 (Figure 1). The low-flow area ROI was then
Statistical Analysis The sensitivity, specificity, and accuracy of intracoronary sestamibi in detecting perfusion recovery on a pixel-by-pixel analysis were calculated. WMSI values, LVEF values, and the number of asynergic segments per patient, before and after PTCA, were compared by paired t test or Wilcoxon signed rank
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Table 2. Criteria for calculation of sensitivity and specificity of intracoronary sestamibi in predicting perfusion recovery
True positive True negative False positive False negative
Intracoronary sestamibi
Tl-201 post-PTCA*
Present Absent Present Absent
Present Absent Absent Present
*Tracer uptake greater than 50% in the low-flow area.
test, as appropriate. Data are expressed as mean ⫾1 SD. P ⬍ .05 was considered to be statistically significant.
RESULTS All patients underwent successful PTCA (residual stenosis ⬍20%) and were asymptomatic at the time of repeated Tl-201 SPECT and echocardiography. Prediction of Viability in Terms of Perfusion Recovery by Intracoronary Sestamibi The sensitivity, specificity, and overall accuracy for the prediction of perfusion recovery were 91%, 78%, and 82%, respectively. In other words, out of 2071 pixels within low-flow areas that improved Tl-201 uptake after PTCA, 1888 (91%) had shown sestamibi uptake after intracoronary administration, thus having been correctly predicted as viable. Conversely, out of 4358 pixels within low-flow areas that did not improve Tl-201 uptake after PTCA, 3389 (78%) had not shown sestamibi uptake after intracoronary administration, thus having been correctly predicted as nonviable. In Figures 2 and 3 representative short-axis slices and polar maps of the scintigraphic studies of patients 2 and 6 are shown, respectively. Prediction of Viability in Terms of Contractile Recovery by Intracoronary Sestamibi Of the 7 patients who underwent revascularization, 2 showed no contractile recovery after PTCA; in the remaining 5 patients, angioplasty improved the contractile function, as demonstrated by the observed reduction in WMSI (from 1.95 ⫾ 0.28 to 1.60 ⫾ 0.34, P ⫽ .007), increase in LVEF (from 42% ⫾ 7% to 49% ⫾ 7%, P ⫽ .001), and reduction in the number of asynergic segments in the low-flow area (from 3.6 ⫾ 0.9 to 1.8 ⫾ 1.5, P ⫽ .021). (Table 3). The first 5 patients showing an area of sestamibi
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uptake greater than one third of the low-flow area demonstrated congruent changes in all three echocardiographic parameters after PTCA—namely, reduction in WMSI, improvement in LVEF, and contractile improvement of one or more a-dyssynergic segment. Conversely, in the 2 patients showing an area of sestamibi uptake smaller than one third of the low-flow area, none of the three parameters improved after PTCA. DISCUSSION In this study the intracoronary injection of sestamibi provided an accurate prediction of both perfusion and contractile recovery after PTCA in selected patients with previous AMI and residual severe stenosis of the IRA. Quantitative rest-redistribution Tl-201 SPECT represents a well-established clinical tool for viability detection. Sestamibi has also been proposed for viability studies, on the basis of the experimental demonstration that its retention requires cellular integrity,3-6 even if it has been suggested that myocardial viability could be underestimated by this tracer.14-17 Indeed, the availability of any perfusion tracer in hypoperfused areas supplied by severely stenotic coronary arteries can be so extremely reduced that the uptake would not reliably represent the amount of viable myocardium. Several approaches have been proposed to improve radiotracer uptake, such as 24-hour delayed redistribution,18 Tl-201 reinjection,19,20 Tl-201 rest-redistribution,20,21 ribose infusion,22 and nitrate administration before or during Tc-99m–labeled perfusion tracer administration.23-25 The direct intracoronary injection could represent an attractive solution to maximize the local availability of the radiotracers. The feasibility of myocardial imaging after intracoronary injection of radiotracers has been previously demonstrated,26-31 and we have already reported on the possibility of detecting hibernating myocardium by intracoronary administration of sestamibi.32,33 The choice of sestamibi for the intracoronary procedures was dictated by practical reasons, as the injection had to be performed in the Catheterization Laboratory (Rome, Italy) before PTCA whereas imaging had to be carried out later, in the Department of Nuclear Medicine. The usually negligible redistribution of sestamibi, setting the perfusion state at the time of the injection despite subsequent changes in coronary blood flow,34-37 allowed us to delay the imaging after PTCA.37,38 Our findings confirm that sestamibi uptake reflects myocardial viability and predicts recovery of myocardial dysfunction. In this study sestamibi uptake in the lowflow area predicted post-PTCA perfusion recovery with a good sensitivity (91%). Moreover, all patients with a large extent of sestamibi uptake in the low-flow areas showed contractile recovery, confirming that a sizeable
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Trani et al Selective intracoronary injection of sestamibi to detect myocardial viability
Figure 2. A, Short-axis slices from the apex (left) to the base (right) of the left ventricle of patient 2. Upper row, Tl-201 before PTCA showing a severe perfusion defect that involves the middle and distal anteroseptal wall and the apex; middle row, intracoronary sestamibi before PTCA showing tracer uptake in the anteroseptal wall; lower row, Tl-201 1 month after PTCA showing normalization of perfusion in the anteroseptal wall, as correctly predicted by intracoronary sestamibi before PTCA. B, Polar maps corresponding to the scintigraphic studies of A (the lower level of the color scale was set to 20% of maximum). IC MIBI, Intracoronary sestamibi.
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Figure 3. A, Short-axis slices from the apex (left) to the base (right) of the left ventricle of patient 6. Upper row, Tl-201 before PTCA showing a severe perfusion defect of the apex extended to the distal anteroseptal wall and distal inferior wall; middle row, intracoronary sestamibi before PTCA showing absence of uptake in the regions with Tl-201 defect; lower row, Tl-201 1 month after PTCA showing unchanged perfusion pattern as compared with the pre-PTCA one, as correctly predicted by intracoronary sestamibi before PTCA. B, Polar maps corresponding to the scintigraphic studies of A (the lower level of the color scale was set to 20% of maximum). IC MIBI, Intracoronary sestamibi.
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Table 3. Intracoronary sestamibi to predict contractile recovery
Patient Intracoronary No. sestamibi* 1 2 3 4 5 6 7
47% 72% 45% 47% 62% 0% 28%
WMSI prePTCA
WMSI postPTCA
LVEF prePTCA
LVEF postPTCA
No. of adyssynergic segments pre-PTCA
1.75 1.78 1.88 1.89 2.44 1.89 1.67
1.25 1.44 1.44 1.78 2.11 1.89 1.89
51% 32% 40% 40% 47% 50% 33%
56% 39% 50% 46% 54% 50% 28%
3 3 4 3 5 4 2
No. of adyssynergic segments Contractile post-PTCA recovery 0 2 1 2 4 4 2
Yes Yes Yes Yes Yes No No
*Extension of sestamibi uptake expressed in percent of the low-flow area.
amount of viable myocardium is required for left ventricular function improvement after revascularization.39 These observations are particularly remarkable, because the low-flow area consisted of myocardium judged to be irreversibly injured on Tl-201 scintigraphy before PTCA.40 On the other hand, the suboptimal specificity of intracoronary sestamibi (78%) in predicting perfusion recovery must be interpreted according to its clinical relevance. In fact, perfusion recovery and improvement of left ventricular function do not necessarily correlate. As a matter of fact, the two patients in our series judged to have viable myocardium by intracoronary sestamibi criteria but without perfusion recovery did have improved contractile function after revascularization. Thus, in patients with previous AMI and severe stenosis of the IRA, the increased local delivery of sestamibi in the asynergic myocardium obtained by selective intracoronary administration improves the scintigraphic detection of hibernated myocardium. We deliberately did not take into consideration the amount and distribution of Tl-201 uptake both within and outside the low-flow area borders in the pre-PTCA study because our aim was to try to clarify the significance of the eventual uptake of intracoronary sestamibi in the infarct area. Conversely, the significance of the amount and distribution of Tl-201 uptake in terms of viable myocardium has been addressed by several studies whose sample size was remarkably superior to ours.39 Of note is that in all of our patients, intracoronary sestamibi distribution was in the IRA vascular territory; this finding excludes the possible spillover of the tracer into other vascular regions through collaterals. Limitations It is possible that the partial volume effect might have influenced our results. Indeed, normal myocardium,
hibernating myocardium, and infarcted myocardium have different wall thickness and wall motion measurements; thus comparisons of counts recorded in different pathophysiological conditions (pre- and post-PTCA) should always be considered with caution. This is a pilot study; indeed, the small number of patients studied does not allow us to draw definitive conclusions, even if an apparently clear-cut discrimination has been obtained between the 5 patients with improved left ventricular function and the 2 without it. Caution is required in applying these results to all patients with coronary artery disease and the need for myocardial viability assessment. Indeed, as the goal of our study was to investigate whether severe flow-limiting stenoses impair the accuracy of myocardial scintigraphy and whether the intracoronary injection can overcome this limitation, stringent selection criteria were required.
Conclusions After selective intracoronary administration, sestamibi uptake in the dyssynergic area is capable of correctly identifying viable myocardium undetected by Tl201 rest-redistribution myocardial scintigraphy. Our findings confirm that poor delivery of perfusion tracers in low-flow areas affects the accuracy of myocardial scintigraphy in detecting viable dyssynergic myocardium. From a practical point of view, the application of our method is limited because in the vast majority of cases PTCA immediately follows diagnostic coronary angiography. However, in selected patients in whom revascularization carries a non-negligible risk, it is common practice to defer the revascularization until the demonstration of viability has been obtained in order to improve the risk-benefit ratio. Thus in these patients the intracoronary sestamibi procedure could have a practical
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clinical application, provided that our results are confirmed in larger series. Acknowledgment The authors have indicated they have no financial conflicts of interest.
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