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Establishing an approach for patients with recent coronary occlusion: Identification of viable myocardium
Establishing an approach for patients with recent coronary occlusion: Identification of viable myocardium IL S. B. Beanlands, MD, M. Labinaz, MD, T. D. Ruddy, MD, J. E Marquis, MD, W. Williams, MD, M. LeMay, MD, L. A. L a r a m e e , MD, E. O'Brien, MD, S. A. Kearns, RN, M. A u n g , MRT(N), H. J o h a n s e n , PhD, a n d L. A. J. H i g g i n s o n , MD
Background. Revascularization of occluded coronary arteries after myocardial infarction (MI) may restore flow to viable myocardium and improve ventricular function. The aim of this pilot study was to determine the potential utility of thallium-201 viability imaging for the prediction of recovery of regional ventricular function in patients undergoing revascularization of total or subtotal occlusion of infarct-related arteries (TIMI 0-2 flow) during the convalescent period after MI. Methods. Twenty-three patients were identified < 6 weeks after MI and underwent TI-201 viability imaging (rest imaging, n = 16; stress/reinjection imaging, n = 7) and radionuclide angiography. Patients were revascularized with percutaneous transluminal coronary artery in 10, stent in 10, and bypass in 3. Follow-up radionuclide angiography at 3 months was used to assess recovery of regional wall motion. Results. Among 41 abnormal wall motion segments in the infarct territories, the sensitivity, specificity, and accuracy for TI-201 imaging in the prediction of recovery of regional function were 89% (25128), 54% (7/13), and 78% (32/41), respectively. When 8 segments supplied by vessels with restenosis to >70% were excluded, specificity improved to 70%. Wall motion scores improved in those with adequate revascularization (1.6 ± 1.4 vs 2.7 _+ 1.6; P < .001) but not in those with restenosis or occlusion (1.8 _+1.0 vs 2.0 _+1.6; P = NS). Conclusions. In patients with an occluded artery after MI, TI-201 viability imaging can detect recoverable myocardium with reasonable accuracy and may help select which patients will most benefit from revascularization. (J Nucl Cardiol 1999;6:298-305.) Key words: TI-201 • revascularization • angioplasty • stent ° post-myocardial infarction
Thrombolytic therapy has had significant impact on the reduction of death from acute myocardial infarction (MI).1,2 Patients who achieve normal resting flow (TIMI 3) after thrombolysis have a better prognosis in comparison to those with inadequate reperfusion caused by complete or subtotal occlusions (TIMI grade 0 to 2). 3 Incomplete reperfusion is common, occurring in 42% to 49% of cases after different thrombolytic regimens. 3 The role of revascularization in these patients during the convalescent phase after thrombolytic therapy has not been From the Divisionof Cardiology,Universityof Ottawa HeartInstitute, Ottawa, Ontario,Canada. Supportedby the Medical ResearchCouncil of Canada, the Heart and StrokeFoundationof Canada. Presented in part at the annual meeting of the American Heart Associationin 1996. Submitted for publication March 6, 1998; revision acceptedJuly 28, 1998. Reprint requests: Rob Beanlands, MD, University of Ottawa Heart Institute, 1053 Carling Ave, Room H1-149, Ottawa, Ontario, K1Y 4E9; rbeanlan@ heartinst.on.ca. Copyright© 1999 by the AmericanSocietyof NuclearCardiology. 1071-3581/99/$8.00+ 0 43/1/93460 298
well studied. In previous work evaluating post-MI management, patients with subtotal or total occlusions have often been excluded from undergoing revascularization.4, 5 A recent study, however, has reported that establishing vessel patency in symptom-free patients with occluded vessels after MI is associated with improvement in left ventricular function. 6 Improvement in ventricular function may depend on the presence of viable myocardium in the infarct territory. It is now well established that recovery of regional ventricular function after revascularization in patients with chronic ischemic heart disease can be predicted by viability imaging. 7-12 Fluorodeoxyglucose metabolic imaging has been considered to represent the optimal means for defining such viable myocardium.7-10,13 Thallium-201 viability imaging, however, offers reasonable accuracy and is more widely available.9,11,12,14-20 The utility of viability imaging in a setting of total or subtotal coronary artery occlusion after MI is not known. The principle aim of this pilot study was to determine the potential utility of T1-201 viability imaging for the prediction of recovery of regional ventricular function in
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Table 1. A n g i o g r a p h i c d a t a
Patient
Age
Gender
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 Mean SD
46 57 67 52 51 51 64 57 67 57 69 64 71 67 66 58 61 46 61 71 55 55 34 58.6 9.2
M M M F M M M M M F M M M M F F M M M M M M M
Post-Mlcatheterization (days) 8 9 23 5 13 2 8 1 7 1 12 28 6 10 10 2 4 10 1 14 10 10 16 9.1 6.8
IRA
TIM1 flow (0-3)
Method of revascularization
RCA RCA RCA RCA RCA CCX LAD RCA RCA RCA LAD LAD CO( CCX RCA RCA LAD LAD CCX LAD RCA RCA LAD
1 0 0 0 0 1 0 0 0 0 1 1 0 0 1 0 0 2 0 2 0 0 0
STENT PTCA* STENT STENT STENT STENT STENT STENT STENT STENT STENT PTCA PTCA PTCA PTCA PTCA PTCA PTCA PTCA PTCA CABG CABG CABG
IRA MLD (mm) Immed post 3 mos 2.6 1.5 2.6 2.4 2.3 1.6 1.2 1.8 2. l 2.0 2.7 2.7 0.0 0.0 1.3 1.2 1.0 1.9 t .9 1.0 . . . 1.7 0.8
. . .
3.0 0.0 2.1 2.6 1.6 1.1 1.6 2.4 1.9 5" 2.0 1.2 0.0 0.0 1.0 0.0 0.9 1.6 0.8 . . . 1.3 0.9
Percent stenosis Immed post 3 mos 21 40 41 29 18 11 52 42 32 17 0 27 100 100 64 50 60 46 4t 60 . . . 43 26
19 100 5l 24 30 39 41 33 46 t 20 66 100 100 75 100 72 43 73 -
57 29
IRA, Infarct related artery; REVASC, revascularization;MLD, minimum lumen diameter; IA/iMEDPOST, immediately after PTCAor stent; RCA, right coronary artery; CCX, circumorbital coronary artery; LAD, left anterior descending coronary artery. ~Stent insertion failed, switched to PTCA. tSymptomatic occlusion occurred at 7 weeks/had repeat stent insertion; asymptomatic at 3 months.
patients undergoing revascularization of total or subtotally occluded infarct-related arteries during the convalescent period after MI.
METHODS
tions; previous Q-wave MI; or were unable to give informed consent. T1-201 viability imaging and radionuclide angiography (RNA) were performed before revascularization, and the RNA was repeated at 3 months follow-up. The protocol was reviewed and approved by the Research Ethics Committee for the University of Ottawa Heart Institute in the Ottawa Civic Hospital. Informed consent was a prerequisite for inclusion in the study.
Patient Population Twenty-three consecutive patients meeting inclusion criteria and having complete nuclear imaging data were prospectively recruited for this study between May 1994 and March 1996. Patients were included if they were identified within 6 weeks of their first transmural (Q-wave) MI and had total occlusion or subtotal occlusion (also termed "functional" occlusion21) of the infarct related artery (TIMI grade 0 to 2 flow). Patients were excluded if they had TIMI grade 3 flow on angiography; required acute intervention for post-MI complica-
Coronary Angiography All baseline angiograms were reviewed by 2 experienced angiographers blinded to clinical and imaging data except the site of MI on electrocardiogram (ECG). The infarct-related artery was defined. Vascular territory supplied by the infarctrelated artery was also determined. Quantitative coronary angiographic measurements were obtained from a segment proximal to the lesion and at the site of the lesion itself to deter-
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mine the minimum luminal diameter and the percent diameter stenosis as previously described by our laboratory. 22 When a 100% occlusion was identified visually, quantitative coronary angiography was not applied, and the minimal luminal diameter was assumed to be 0 mm. The 3-month follow-up angiograms were evaluated in the same manner and read by the experienced observers blinded to other clinical, imaging, and baseline angiographic data. The 3-month time-point was selected to coincide with the expected time for recovery of ventricular function assessed by RNA used in previous studies evaluating myocardial viability. 7,8,23 Restenosis was defined as >50% diameter stenosis on the follow-up angiogram at the site of angioplasty or stent. Moderate to severe restenosis was defined as >70% stenosis on follow-up. Stent Insertion. For patients undergoing stent insertion, this was done by use of bare stent delivery under high pressure. Stents used were J & J Palmaz-Shatz stents hand mounted on the dilation catheter.
Thallium Viability Imaging Before revascularization, patients underwent T1-201 viability imaging. Among the 23 patients with complete nuclear imaging data, 16 had viability assessed by rest/redistribution T1-201 single photon emission computed tomography (SPECT) imaging. After an overnight fast, patients received 90 to 110 MBq of T1-201 intravenously. Patients were then positioned under the SPECT camera (Siemens ZLC), which was rotated through 180 degrees at 6-degree increments starting angle -45 degrees right anterior oblique (RAO); by use of 25 seconds/view, 64 views, 64 x 64 matrix. The T1-201 images were reconstructed by applying a Butterworth filter, with a cut-off frequency of 0.5 nyquist and filter order of 5.0 with a Siemens Vax Maxdelta computer. Images were then reoriented in the vertical long-axis, short-axis, and horizontal long-axis views. The same imaging procedure was repeated 3 hours later for the redistribution study, and the images were compared. In 7 patients stress T1-201 perfnsion imaging had been arranged for clinical purposes. In these circumstances a stress/redistribution/reinjectionT1-201 imaging approach was used for assessment of viability. 12 In these patients an additional 35 MBq of T1-201 was administered intravenously at rest after the redistribution images. Postreinjection images were acquired 30 minutes later. The logistics of the study did not permit an additional rest redistribution scan in the patients who had the stress imaging protocol. The aim of this study was not to evaluate a particular method for T1-201 imaging but rather to define viability before revascularization of totally or subtotally occluded vessels. The two approaches have been used by others and provide similar results.1624,25 Therefore it was considered reasonable to include patients studied by either method. Viability imaging Analysis. The reoriented T1-201 images were viewed by 2 experienced observers blinded to other clinical and imaging data except the knowledge of the infarct-related artery and its vascular territory. The left ventricle was divided into 9 sectors that included a basal and mid ventricular segment of the anterior, septum, lateral, and inferior walls, as well as a sector at the apex. Each sector was scored by
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use of the following grading scale: 0, absent uptake (comparable to background activity); 1, severe defect; 2, moderate defect; 3, minor defect; 4, normal. For each myocardial sector it was determined whether activity was _>50% of peak myocardial T1-201 activity in that left ventricle. This was defined for the sectors in the vascular territory supplied by the infarct related artery. All of the pixels in a particular sector had to be _>50% for the entire sector to be considered _>50% of peak myocardial TI-201 activity. Definition of Viability. Viable myocardium on T1-201 imaging was defined as partial or complete reversibility (improvement by _>1perfusion score to a score of_>2) or by having _>50% of peak myocardial T1-201 activity in the sector on the redistribution or reinjection image. 11,13,16,26,27 RNA. RNA was performed at baseline and 3 months after revascularization. Red blood cells were labeled with technetium 99m-O~ with a modified ex-vivo technique. ECG gated left ventricular blood pool images were acquired in 3 projections, anterior, left anterior oblique (LAO), and lateral (Siemens Technicare 420). RNA Analysis. The ejection fraction was calculated from the LAO projection. Regional wall motion was evaluated on the gated images in the 3 projections. Two experienced observers evaluated the images blinded to other clinical and imaging data including whether the study was baseline or follow-up. Nine left ventricular wall segments corresponding to the perfusion sectors were evaluated from the 3 projections. As described previously the anterior wall was graded from the anterior view, the septum and the lateral walls from the left anterior oblique view and the inferior wall from the lateral view. 8 The apex was scored by averaging all projections where the apex was analyzable. Regional wall motion was scored visually on the following scale: -1, dyskinesis; 0, akinesis; 1, severe hypokinesis; 2, moderate hypokinesis; 3, mild hypokinesis; and 4, normal. Wall Motion Recovery. Wall motion recovery was used as a standard of comparison for the T1-201 viability imaging. Wall motion recovery was defined as an improvement by _>1 wall motion score. All walls were scored; however, analysis was confined to walls corresponding to the infarct-related artery. Statistical Analysis. All values are expressed as mean _+ standard deviation. The sensitivity and specificity of T1-201 viability imaging for predicting recovery of regional ventricular function in the infarct related artery zone was determined for segments with abnormal baseline wall motion. Baseline and follow-up wall motion scores were compared by use of Student's t-testing.
RESULTS
Patient Characteristics Twenty-three patients (19 men, 4 women) with a mean age of 59 + 9 years were enrolled in this study. The patients were identified 9.1 _+ 6.8 days after Q-wave MI. The infarct-related artery was the left anterior descending
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Figure 1. Vertical long-axis (upper) and short-axis (lower), rest (left) and redistribution (right) T1-201 images. A, Images show a severe fixed inferior wall defect indicating scar. These regions did not recover with revascularization. B, There is mild to moderate intensity defect (>50% of maximum T1-201 uptake) in the inferior to interolateral wall. Wall motion abnormalities in these regions improved with revascularization.
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100
• PatentVessel ~(>70%)
8O 6O %
4O 20 0
Sensitivity Specificity Accuracy
Figure 2. Sensitivity, specificity, and accuracy for T1-201 viability imaging (solid bars); after excluding patients with moderate to severe restenosis (>70%) (open bars). (LAD) in 7, the right coronary artery (RCA) in 12 and the left circumflex artery in 4. Eighteen patients had symptoms: 16 had angina and 2 had dyspnea (mean functional class was 2.3 _+ 1.5). Revascularization was attempted in all 23 patients an average of 21 + 14 days after infarction. Ten patients underwent percutaneous transluminal coronary angioplasty (PTCA), whereas 10 others also had stent insertion. Three patients underwent coronary artery bypass grafting (Table 1). One of these patients required urgent surgery because an attempt to cross the LAD occlusion was complicated by a left main dissection.
Viability Imaging and Wall Motion Recovery The angiographic data are summarized in Table 1. Among the 23 patients with complete baseline and 3month follow-up nuclear imaging data for viability imaging analysis, four had a confirmed total occlusion by coronary angiography at 3 months. These patients were excluded from the primary analysis of the viability imaging because of unsuccessful revascularization. Of the remaining 19, follow-up coronary angiography was not available in 2 of the 3 patients who underwent bypass grafting. One patient who underwent PTCA had renal insufficiency and thus did not have a follow-up angiogram. For the purpose of the T1-201 viability imaging analysis, the vessels to the infarct territories in these patients were assumed to b e patent. One other patient had development of chest pain at 7 weeks and was found to have an occluded stent that was reopened with repeat PTCA and stent insertion. The patient was symptom free at the 3-month follow-up time point, so the infarct-related artery was considered to be patent for the purposes of the viability analysis. Thus 19 patients were considered to have patent vessels at 3 months. Among these patients 171 segments were defined. There were 4 l segments in the vascular territories of infarct-related arteries with abnormal wall motion. Among these, there were 28 segments that
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improved in wall motion with revascularization and 13 that did not. Among segments that improved in wall motion, 25/28 (89%) were defined as viable on T1-201 imaging. Seven of 13 (54%) segments with no improvement in wall motion were defined as scar by T1-201 imaging. Examples of patients with viable myocardium or scar in the infarct zone are shown in Figure 1. The positive predictive value of T1-201 viability imaging for defining improvement in wall motion in abnormal infarct-related artery segments was 81% (25/31) and negative predictive value of 70% (7/10), with an overall accuracy of 78% (32/41). To investigate whether the low specificity was related in part to inadequate revascularization because of restenosis, the accuracies were reevaluated after excluding 8 abnormal baseline wall motion segments supplied by vessels with moderate to severe restenosis (more than 70% diameter stenosis). After excluding these 8 segments, the sensitivity and specificity of T1-201 viability imaging for detection of wall motion recovery were 87% (20/23) and 70% (7/10) (Figure 2). Six additional abnormal segments supplied by the vessels that were occluded at 3 months were also evaluated. Four of these were viable by T1-201 imaging at baseline. Among these 6 segments, 5 (83%) had a reduction in wall motion by >1 wall motion score at 3 months follow-up (3 were viable and 2 were scar at baseline). Thus a reduction in regional ventricular function occurred in most segments where revascularization could not be achieved. To further evaluate this, the wall motion recovery was compared among abnormal segments between those with incomplete revascularization (occlusion or restenosis; n = 14 segments) and those with presumed patent vessels (n = 33 segments). For incomplete revascularization wall motion score did not change between baseline and 3 months follow-up (1.8 _+ 1.0 vs 2.0 +_.1.6, P = NS); whereas in those with patent vessels, wall motion improved (1.6 _+ 1.4 vs 2.7 _+ 1.6, P < .001). The change in wall motion score was significantly greater for those with adequate revascularization compared with those where it was incomplete (1.2 _+ 1.2 vs 0.2 _+ 1.4, P = .02). Considering those regions with adequate revascularization, the change in wall motion score improved in those with viable myocardium (n = 23) and not with scar (n = 10) (change in wall motion for viable: 1.5 _+ 1.0 vs scar: 0.4 _+ 1.3, P = .01).
Ventricular Function and Symptom Change Revascularization in general did not lead to a significant change in overall ventricular function (53% _+8% to 54% _+ 7%, range 36% to 65%, P = NS). Some of this
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lack of improvement may have been related to hypercontractile noninfarcted myocardium at baseline in some patients with smaller infarcts. To further evaluate this, patients with EF < 55% (n -- 12) were considered separately. There was a significant improvement in overall ventricular function after revascularization in this group from 48% _+ 5% to 52% _+ 7% (P < .05). Among all 23 patients revascularization, overall, led to an improvement in angina (or dyspnea when this was the only symptom) from Canadian Cardiovascular Society class 2.3 +_ 1.5 to 1.0 _+ 1.4 (P < .01).
DISCUSSION Previous studies evaluating myocardial viability in the convalescent phase after unsuccessful thrombolysis have been limited. This study demonstrates that, after revascularization of a recently occluded infarctrelated artery, regional wall motion is more likely to improve if there is viable myocardium defined by T1201 imaging.
Myocardial Viability The detection of myocardial viability is useful in predicting recovery of myocardial function after revascularization in patients with chronic stable coronary artery disease.7-9,11,12A6 Modifications of T1-201 imaging with either stress-delayed imaging with reinjection protocol or rest-delayed T1-201 imaging protocol have been useful in this regard. 9,11A2,14-18,2° The sensitivity (89%) and specificity (54%) of T1-201 viability imaging in this study are in the range reported previously in other clinical settings. 11-20,26-28 In contrast to this study, previous investigations have not specifically evaluated T1-201 viability imaging in regions with an occluded vessel. Previous studies have principally evaluated patients without recent MI, 12-15,17-19,26-28 and the revascularization method was often bypass. 11,13-15,17,19,26 In this study the sensitivity of T1-201 imaging to detect viable recoverable myocardium after MI was good. As in previous studies, however, the specificity was suboptimal. One factor accounting for this observation may relate to the mixture of perfused viable tissue with necrotic tissue in a given segment of myocardium. Some dysfunctional segments may contain subendocardial necrosis leading to mild perfusion defects. Such segments may not improve function in spite of adequate revascularization, even though much of the segment is viable.~ 1,27 Also relevant to the suboptimal specificity is the adequacy of revascularization. Follow-up angiographic data has been limited in previous studies evaluating viability
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imaging.26, 28 In one study, only 14 of the 38 patients had angiography, and all had patent vessels. 26 In another, 9/19 segments without improvement in function had a restenosis of >50% and were excluded from follow-up analysis. 28 However, in the study by Ragosta et al,11 investigators used follow-up perfusion imaging to determine which patients were adequately revascularized. This study evaluated multiple segments among 21 patients with chronic disease and severe ventricular dysfunction undergoing coronary artery bypass grafting. Rest/redistribution TI-201 imaging had a positive predictive value of 57% and negative predictive value of 77% for prediction of regional wall motion recovery. The calculated sensitivity and specificity from their data were 80% and 53%, respectively. When patients without adequate revascularization were excluded, the false-positive rate decreased (the reported positive predictive value improved to 73%). When patients with development of a >70% restenosis were excluded from analysis in this study, the specificity improved. Both the study by Ragosta et a111 and this study indicate that an important factor in the accuracy of T1-201 viability imaging is achieving adequate revascularization. Recovery may not occur in viable segments unless vessel patency free of significant restenosis is achieved. T1-201 viability imaging provides a means to predict whether successful revascularization could lead to recovery of regional ventricular function in these patients after infarction. These data suggest that viability assessment should be considered in conjunction with clinical and angiographic parameters before attempting revascularization of an occluded coronary artery:
Mechanisms for Improvement in Regional Ventricular Function This study indicates that the presence of viable myocardium is an important factor in the potential for an infarct zone to recover after restoration of flow. Moreover, restoration of flow may also help to prevent infarct expansion. A rim of viable myocardium may be necessary to structurally buttress the expanding infarct zone. 29 It is of interest that 5 of 6 abnormal wall motion segments without adequate revascularization had further deterioration in ventricular function. This reduction in function may be explained in part by some infarct expansion resulting from failure to achieve sufficient scaffolding.29 The other key factor for wall motion recovery is achieving and maintaining patency without significant restenosis. This is necessary to deliver nutrient flow to the dysfunctional but viable myocardium to allow it to recover.
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Incomplete Reperfusion and Post-Ml Revascularizatlon Studies In the GUSTO trial, complete reperfusion with TIMI grade 3 flow was achieved at 5 to 7 days in 51% to 58% of cases. 3 Complete reperfusion was associated with better ventricular function and lower mortality rates than incomplete reperfusion. The latter patients represent a high-risk group that has not been well studied in the past. The TIMI-IIB study showed that after thrombolysis there was no advantage to early PTCA (18 to 48 hours) over a "wait and watch" approach with noninvasive risk stratification, 4 but patients with occluded vessels were excluded from this analysis and did not undergo PTCA. Ellis et al showed similar findings for late (4 to 14 days after MI) elective PTCA in low-risk patients, but only 4 of 42 PTCA-treated patients had a totally occluded infarct-related artery. 3° Our group previously showed that establishing vessel patency in patients with total coronary artery occlusion at <6 weeks after MI 6 leads to a significant improvement in ventricular function. Other investigators have also shown that successful recanalization can lead to improved ventricular function31 and may improve survival rates, 32 but these studies principally involved patients with chronic coronary artery occlusion more remote from previous infarction than the patients in this study.
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regional ventricular function used in other studies evaluating myocardial viability.7,8, 23 This pilot study used a cutoff of > 50% of maximum myocardial uptake to define viable myocardium.11,13,16,26,27 Although this cut-off is useful, others have reported that the degree of T1-201 uptake also relates to the likelihood of recovery.27 The extent to which this is relevant for this patient population may be better addressed in larger clinical trials. However, the data from this study do indicate that viability imaging should be considered along with clinical and angiographic information before proceeding with revascularization of occluded arteries after MI.
CONCLUSION In spite of the presence of an occluded coronary artery, viable myocardium was often present after myocardial infarction. T1-201 viability imaging detected recoverable myocardium with reasonable accuracy. The low specificity observed in this pilot study related in part to a lack of improvement in wall motion in segments with significant restenosis. Evaluation for the presence of viable myocardium may help select which patients will most benefit from revascularization of occluded arteries after MI We express our gratitude to Darlene Morris-Maheral for her excellent help in preparing the manuscript.
Technical Factors and Limitations Coronary angiography was used as a means for followup and determination of adequate revascularization. Only patients in whom there was definite occlusion at the time of follow-up were excluded from the primary analysis. Four patients did not have follow-up angiography at 3 months: two had bypass grafting as a method of revascularization; one had kidney failure that precluded followup coronary angiography; the fourth patient had symptomatic occlusion at 7 weeks that was reopened, and the patient remained symptom free at 3 months. In these 4 patients the vessels were assumed to be patent and without restenosis at 3 months follow-up. If any of these patients did not have adequate revascularization, then the overall accuracy of T1-201 viability imaging may be slightly better than reported in this study. The population size was comparable to most previous studies evaluating recovery of function predicted by T1-201 viability imaging in patients with chronic disease. 11-15,18,20,26-28 With one exception 19 these studies have had follow-up on 10 to 38 patients. The primary aim of the study was to assess the role of T1-201 imaging. Thus a 3-month follow-up was used to coincide with the expected time course of recovery of
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8. vom Dahl J, Eitzman DT, A1-Aouar ZR, Kanter HL, Hicks RJ, Deeb GM, et al. Relation of regional function, peffusion, and metabolism in patients with advanced coronary artery disease undergoing surgical revascularization. Circulation 1994;90:2356-65. 9. Maddahi J, Schelbert H, Bmnken R, Di Carli M. Role of T1-201 and PET imaging in evaluation of myocardial viability and management of patients with coronary artery disease and left ventricular dysfunction. J Nucl Med 1994;35:707-15. 10. Schelbert H, Bonow R, Geltman E, Maddahi J, Schwaiger M. Position statement: clinical use of cardiac positron emission tomography--position paper of the Cardiovascular Council of the Society of Nuclear Medicine. J Nucl Med 1993;34:1385-8. 11. Ragosta M, Beller GA, Watson DD, Kaul S, Gimple LW. Quantitative planar rest-redistribution 201 TI 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;87:1630-1. 12. Dilsizian V, Rocco TP, Freedman NMT, Leon MB, Bonow RO. Enhanced detection of ischemic but viable myocardium by the reinjection of thallium after stress-redistribution imaging. N Engl J Med 1990; 323:141-6. 13. Bax JJ, Cornel JH, Visser FC, Fioretti PM, Van Lingen A, Reijs AEM, et al. Prediction of recovery of myocardium dysfunction after revascularization comparison of fluorine-18 fhiorodeoxyglucose/T1-201 SPECT, T1-201 stress-reinjection SPECT and dobutamine echocardiography. JACC 1996;25:558-64. 14. Mori T, Minamiji K, Kurongane H, Ogawa K, Yoshida Y. Rest-injected thallium-201 imaging for assessing viability of severe asynergic regions. J Nucl Med 1991 ;23:1718-24. 15. Iskandrian AS, Hakld A, Kane SA, et al. Rest and redistribtion thallium-201 myocardial scintigraphy to predict improvement in left ventricular function after coronary artery bypass grafting. Am J Cardiol 1983;51:1312-6. 16. Bonow RO. Identification of viable myocardium. Circulation 1996; 94:2674-80. 17. Udelson JE, Coleman PS, Metherall J, Pandian NG, Gomez AR, Gfiffith JL, et al. Predicting recovery of severe regional ventricular dysfunction: comparison of resting scintigraphy with 201-T1 and 99m-Tcsestamibi. Circulation 1994;89:2552-61. 18. Charney R, Schwinger ME, Chun J, Cohen MV, Nanna M, Menegus MA, et al. Dobutamine echocardiography and resting-redistribution thallium-201 scintigraphy predicts recovery of hibernating myocardium after coronary revascularization. Am Heart J 1994;128:864-9. 19. Vanoverschelde JJ, D'Hondt A, Marwick T, Gerber BL, DeKock M, Dion R, et al. Head-to-head comparison of exercise-redistribution-reinjection thallium single-photon emission computed tomography and low dose dobutamine echocardiography for prediction of reversibility of chronic left ventricular ischemic dysfunction. JACC 1996;28:432-42. 20. Phtani H, Tarnaki N, Yonekura Y, Mohiuddin IH, Hirata K, Ban T, et al. Value of thallium-201 reinjection after delayed SPECT imaging for
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predicting reversible ischemia after coronary artery bypass grafting. Am J Cardiol 1990;66:394-9. Simes PA, Golf S, Myreng Y, Molstad E Emanuetsson H, Albertsson P, et al. Stenting in chronic coronary occlusion (SICCO): a randomized controlled trial of adding stent implantation after successful angioplasty. JACC 1996;28:1444-51. Morton BC, Gill JB, Roberts RS, Larocque BG, Jozwiak LA, Cairns JA. Does it matter how coronary projections are combined to assess restenosis following PTCA? Int J Card Imaging 1995;11:145-9. Carrel T, Jenni R, Haubold-Reuter S, yon Schulthess G, Pasic M, Turina M. Improvement of severely reduced left ventficular function after surgical revascularization in patients with preoperative myocardial infarction. Eur J Cardiothorac Surg t992;6:479-84. Dilsizian V, Perrone-Filardi R Arrighi JA, Bacharach SL, Quyyumi AA, Freedman NMT, et al. Concordance and discordance between stressredistribution-reinjection and rest-redistribution thallium imaging for assessing viable myocardium: comparison with metabolic activity by positron emission tomography. Circulation 1993;88:941-52. Skopicki HA, Weissman NJ, Rose GA, Murkerjee A, Coulter SA, Fischman A, et al. Thallium imaging, dobutamine echocardiography and positron emission tomography for the assessment of myocardial viability. JACC 1996;27(Suppl A):162A. Arnese M, Cornel JH, Salustri A, Maat APWM, Elhendy A, Reijs AEM, et al. Prediction of improvement of regional left ventricular function after surgical revascularization: a comparison of low-dose dobutamine echocardiography with 201-T1 single photon emission computed tomography. Circulation 1995;91:2748-52. Perrone-Filardi P, Pace L, Prastaro M, Squame F, Betocchi S, Soricelli A, et al. Assessment of myocardial viability in patients with chronic coronary artery disease: rest-4-Hour-24-hour 201 T1 tomography versus dobutamine echocardiography. Circulation 1996;94:2712-9. Haque T, Fumkawa T, Takahashi M, Kinoshita M. Identification of hibernating myocardium by dobutamine stress echocardiography: comparison with thallium-201 reinjection imaging. Am Heart J 1995;130:553-63. Califf RM, Topoi EJ, Gersh BJ. From myocardial salvage to patient salvage in acute myocardial infarction: the role of repeffusion therapy. JACC 1989;14:1382-8. Ellis SG, Mooney MR, George BS, Ribeiro da Silva EE, Talley DJ, Flanagan WH, et al. Randomized trial of late elective angioplasty versus conservative management for patients with residual stenoses after thrombolytic treatment of myocardial infarction. Circulation 1992;86:1400-6. Melchior JP, Doriot PA, Chatelain P, Meier B, Urban P, Finci L, et al. Improvement of left ventricular contraction and relaxation synchronism after recanalization of chronic total coronary occlusion by angioplasty. JACC 1987;9:763-8. Ivanhoe RJ, Weintraub WS, Douglas JS, et al. Percutaneous transhiminal coronary angioplasty of chronic total occlusions: primary success, restenosis, and long-term clinical follow up. Circulation 1992;85:10615.
Background. Revascularization of occluded coronary arteries after myocardial infarction (MI) may restore flow to viable myocardium and improve ventricular function. The aim of this pilot study was to determine the potential utility of thallium-201 viability imaging for the prediction of recovery of regional ventricular function in patients undergoing revascularization of total or subtotal occlusion of infarct-related arteries (TIMI 0-2 flow) during the convalescent period after MI. Methods. Twenty-three patients were identified < 6 weeks after MI and underwent TI-201 viability imaging (rest imaging, n = 16; stress/reinjection imaging, n = 7) and radionuclide angiography. Patients were revascularized with percutaneous transluminal coronary artery in 10, stent in 10, and bypass in 3. Follow-up radionuclide angiography at 3 months was used to assess recovery of regional wall motion. Results. Among 41 abnormal wall motion segments in the infarct territories, the sensitivity, specificity, and accuracy for TI-201 imaging in the prediction of recovery of regional function were 89% (25128), 54% (7/13), and 78% (32/41), respectively. When 8 segments supplied by vessels with restenosis to >70% were excluded, specificity improved to 70%. Wall motion scores improved in those with adequate revascularization (1.6 ± 1.4 vs 2.7 _+ 1.6; P < .001) but not in those with restenosis or occlusion (1.8 _+1.0 vs 2.0 _+1.6; P = NS). Conclusions. In patients with an occluded artery after MI, TI-201 viability imaging can detect recoverable myocardium with reasonable accuracy and may help select which patients will most benefit from revascularization. (J Nucl Cardiol 1999;6:298-305.) Key words: TI-201 • revascularization • angioplasty • stent ° post-myocardial infarction
Thrombolytic therapy has had significant impact on the reduction of death from acute myocardial infarction (MI).1,2 Patients who achieve normal resting flow (TIMI 3) after thrombolysis have a better prognosis in comparison to those with inadequate reperfusion caused by complete or subtotal occlusions (TIMI grade 0 to 2). 3 Incomplete reperfusion is common, occurring in 42% to 49% of cases after different thrombolytic regimens. 3 The role of revascularization in these patients during the convalescent phase after thrombolytic therapy has not been From the Divisionof Cardiology,Universityof Ottawa HeartInstitute, Ottawa, Ontario,Canada. Supportedby the Medical ResearchCouncil of Canada, the Heart and StrokeFoundationof Canada. Presented in part at the annual meeting of the American Heart Associationin 1996. Submitted for publication March 6, 1998; revision acceptedJuly 28, 1998. Reprint requests: Rob Beanlands, MD, University of Ottawa Heart Institute, 1053 Carling Ave, Room H1-149, Ottawa, Ontario, K1Y 4E9; rbeanlan@ heartinst.on.ca. Copyright© 1999 by the AmericanSocietyof NuclearCardiology. 1071-3581/99/$8.00+ 0 43/1/93460 298
well studied. In previous work evaluating post-MI management, patients with subtotal or total occlusions have often been excluded from undergoing revascularization.4, 5 A recent study, however, has reported that establishing vessel patency in symptom-free patients with occluded vessels after MI is associated with improvement in left ventricular function. 6 Improvement in ventricular function may depend on the presence of viable myocardium in the infarct territory. It is now well established that recovery of regional ventricular function after revascularization in patients with chronic ischemic heart disease can be predicted by viability imaging. 7-12 Fluorodeoxyglucose metabolic imaging has been considered to represent the optimal means for defining such viable myocardium.7-10,13 Thallium-201 viability imaging, however, offers reasonable accuracy and is more widely available.9,11,12,14-20 The utility of viability imaging in a setting of total or subtotal coronary artery occlusion after MI is not known. The principle aim of this pilot study was to determine the potential utility of T1-201 viability imaging for the prediction of recovery of regional ventricular function in
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Table 1. A n g i o g r a p h i c d a t a
Patient
Age
Gender
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 Mean SD
46 57 67 52 51 51 64 57 67 57 69 64 71 67 66 58 61 46 61 71 55 55 34 58.6 9.2
M M M F M M M M M F M M M M F F M M M M M M M
Post-Mlcatheterization (days) 8 9 23 5 13 2 8 1 7 1 12 28 6 10 10 2 4 10 1 14 10 10 16 9.1 6.8
IRA
TIM1 flow (0-3)
Method of revascularization
RCA RCA RCA RCA RCA CCX LAD RCA RCA RCA LAD LAD CO( CCX RCA RCA LAD LAD CCX LAD RCA RCA LAD
1 0 0 0 0 1 0 0 0 0 1 1 0 0 1 0 0 2 0 2 0 0 0
STENT PTCA* STENT STENT STENT STENT STENT STENT STENT STENT STENT PTCA PTCA PTCA PTCA PTCA PTCA PTCA PTCA PTCA CABG CABG CABG
IRA MLD (mm) Immed post 3 mos 2.6 1.5 2.6 2.4 2.3 1.6 1.2 1.8 2. l 2.0 2.7 2.7 0.0 0.0 1.3 1.2 1.0 1.9 t .9 1.0 . . . 1.7 0.8
. . .
3.0 0.0 2.1 2.6 1.6 1.1 1.6 2.4 1.9 5" 2.0 1.2 0.0 0.0 1.0 0.0 0.9 1.6 0.8 . . . 1.3 0.9
Percent stenosis Immed post 3 mos 21 40 41 29 18 11 52 42 32 17 0 27 100 100 64 50 60 46 4t 60 . . . 43 26
19 100 5l 24 30 39 41 33 46 t 20 66 100 100 75 100 72 43 73 -
57 29
IRA, Infarct related artery; REVASC, revascularization;MLD, minimum lumen diameter; IA/iMEDPOST, immediately after PTCAor stent; RCA, right coronary artery; CCX, circumorbital coronary artery; LAD, left anterior descending coronary artery. ~Stent insertion failed, switched to PTCA. tSymptomatic occlusion occurred at 7 weeks/had repeat stent insertion; asymptomatic at 3 months.
patients undergoing revascularization of total or subtotally occluded infarct-related arteries during the convalescent period after MI.
METHODS
tions; previous Q-wave MI; or were unable to give informed consent. T1-201 viability imaging and radionuclide angiography (RNA) were performed before revascularization, and the RNA was repeated at 3 months follow-up. The protocol was reviewed and approved by the Research Ethics Committee for the University of Ottawa Heart Institute in the Ottawa Civic Hospital. Informed consent was a prerequisite for inclusion in the study.
Patient Population Twenty-three consecutive patients meeting inclusion criteria and having complete nuclear imaging data were prospectively recruited for this study between May 1994 and March 1996. Patients were included if they were identified within 6 weeks of their first transmural (Q-wave) MI and had total occlusion or subtotal occlusion (also termed "functional" occlusion21) of the infarct related artery (TIMI grade 0 to 2 flow). Patients were excluded if they had TIMI grade 3 flow on angiography; required acute intervention for post-MI complica-
Coronary Angiography All baseline angiograms were reviewed by 2 experienced angiographers blinded to clinical and imaging data except the site of MI on electrocardiogram (ECG). The infarct-related artery was defined. Vascular territory supplied by the infarctrelated artery was also determined. Quantitative coronary angiographic measurements were obtained from a segment proximal to the lesion and at the site of the lesion itself to deter-
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mine the minimum luminal diameter and the percent diameter stenosis as previously described by our laboratory. 22 When a 100% occlusion was identified visually, quantitative coronary angiography was not applied, and the minimal luminal diameter was assumed to be 0 mm. The 3-month follow-up angiograms were evaluated in the same manner and read by the experienced observers blinded to other clinical, imaging, and baseline angiographic data. The 3-month time-point was selected to coincide with the expected time for recovery of ventricular function assessed by RNA used in previous studies evaluating myocardial viability. 7,8,23 Restenosis was defined as >50% diameter stenosis on the follow-up angiogram at the site of angioplasty or stent. Moderate to severe restenosis was defined as >70% stenosis on follow-up. Stent Insertion. For patients undergoing stent insertion, this was done by use of bare stent delivery under high pressure. Stents used were J & J Palmaz-Shatz stents hand mounted on the dilation catheter.
Thallium Viability Imaging Before revascularization, patients underwent T1-201 viability imaging. Among the 23 patients with complete nuclear imaging data, 16 had viability assessed by rest/redistribution T1-201 single photon emission computed tomography (SPECT) imaging. After an overnight fast, patients received 90 to 110 MBq of T1-201 intravenously. Patients were then positioned under the SPECT camera (Siemens ZLC), which was rotated through 180 degrees at 6-degree increments starting angle -45 degrees right anterior oblique (RAO); by use of 25 seconds/view, 64 views, 64 x 64 matrix. The T1-201 images were reconstructed by applying a Butterworth filter, with a cut-off frequency of 0.5 nyquist and filter order of 5.0 with a Siemens Vax Maxdelta computer. Images were then reoriented in the vertical long-axis, short-axis, and horizontal long-axis views. The same imaging procedure was repeated 3 hours later for the redistribution study, and the images were compared. In 7 patients stress T1-201 perfnsion imaging had been arranged for clinical purposes. In these circumstances a stress/redistribution/reinjectionT1-201 imaging approach was used for assessment of viability. 12 In these patients an additional 35 MBq of T1-201 was administered intravenously at rest after the redistribution images. Postreinjection images were acquired 30 minutes later. The logistics of the study did not permit an additional rest redistribution scan in the patients who had the stress imaging protocol. The aim of this study was not to evaluate a particular method for T1-201 imaging but rather to define viability before revascularization of totally or subtotally occluded vessels. The two approaches have been used by others and provide similar results.1624,25 Therefore it was considered reasonable to include patients studied by either method. Viability imaging Analysis. The reoriented T1-201 images were viewed by 2 experienced observers blinded to other clinical and imaging data except the knowledge of the infarct-related artery and its vascular territory. The left ventricle was divided into 9 sectors that included a basal and mid ventricular segment of the anterior, septum, lateral, and inferior walls, as well as a sector at the apex. Each sector was scored by
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use of the following grading scale: 0, absent uptake (comparable to background activity); 1, severe defect; 2, moderate defect; 3, minor defect; 4, normal. For each myocardial sector it was determined whether activity was _>50% of peak myocardial T1-201 activity in that left ventricle. This was defined for the sectors in the vascular territory supplied by the infarct related artery. All of the pixels in a particular sector had to be _>50% for the entire sector to be considered _>50% of peak myocardial TI-201 activity. Definition of Viability. Viable myocardium on T1-201 imaging was defined as partial or complete reversibility (improvement by _>1perfusion score to a score of_>2) or by having _>50% of peak myocardial T1-201 activity in the sector on the redistribution or reinjection image. 11,13,16,26,27 RNA. RNA was performed at baseline and 3 months after revascularization. Red blood cells were labeled with technetium 99m-O~ with a modified ex-vivo technique. ECG gated left ventricular blood pool images were acquired in 3 projections, anterior, left anterior oblique (LAO), and lateral (Siemens Technicare 420). RNA Analysis. The ejection fraction was calculated from the LAO projection. Regional wall motion was evaluated on the gated images in the 3 projections. Two experienced observers evaluated the images blinded to other clinical and imaging data including whether the study was baseline or follow-up. Nine left ventricular wall segments corresponding to the perfusion sectors were evaluated from the 3 projections. As described previously the anterior wall was graded from the anterior view, the septum and the lateral walls from the left anterior oblique view and the inferior wall from the lateral view. 8 The apex was scored by averaging all projections where the apex was analyzable. Regional wall motion was scored visually on the following scale: -1, dyskinesis; 0, akinesis; 1, severe hypokinesis; 2, moderate hypokinesis; 3, mild hypokinesis; and 4, normal. Wall Motion Recovery. Wall motion recovery was used as a standard of comparison for the T1-201 viability imaging. Wall motion recovery was defined as an improvement by _>1 wall motion score. All walls were scored; however, analysis was confined to walls corresponding to the infarct-related artery. Statistical Analysis. All values are expressed as mean _+ standard deviation. The sensitivity and specificity of T1-201 viability imaging for predicting recovery of regional ventricular function in the infarct related artery zone was determined for segments with abnormal baseline wall motion. Baseline and follow-up wall motion scores were compared by use of Student's t-testing.
RESULTS
Patient Characteristics Twenty-three patients (19 men, 4 women) with a mean age of 59 + 9 years were enrolled in this study. The patients were identified 9.1 _+ 6.8 days after Q-wave MI. The infarct-related artery was the left anterior descending
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Figure 1. Vertical long-axis (upper) and short-axis (lower), rest (left) and redistribution (right) T1-201 images. A, Images show a severe fixed inferior wall defect indicating scar. These regions did not recover with revascularization. B, There is mild to moderate intensity defect (>50% of maximum T1-201 uptake) in the inferior to interolateral wall. Wall motion abnormalities in these regions improved with revascularization.
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100
• PatentVessel ~(>70%)
8O 6O %
4O 20 0
Sensitivity Specificity Accuracy
Figure 2. Sensitivity, specificity, and accuracy for T1-201 viability imaging (solid bars); after excluding patients with moderate to severe restenosis (>70%) (open bars). (LAD) in 7, the right coronary artery (RCA) in 12 and the left circumflex artery in 4. Eighteen patients had symptoms: 16 had angina and 2 had dyspnea (mean functional class was 2.3 _+ 1.5). Revascularization was attempted in all 23 patients an average of 21 + 14 days after infarction. Ten patients underwent percutaneous transluminal coronary angioplasty (PTCA), whereas 10 others also had stent insertion. Three patients underwent coronary artery bypass grafting (Table 1). One of these patients required urgent surgery because an attempt to cross the LAD occlusion was complicated by a left main dissection.
Viability Imaging and Wall Motion Recovery The angiographic data are summarized in Table 1. Among the 23 patients with complete baseline and 3month follow-up nuclear imaging data for viability imaging analysis, four had a confirmed total occlusion by coronary angiography at 3 months. These patients were excluded from the primary analysis of the viability imaging because of unsuccessful revascularization. Of the remaining 19, follow-up coronary angiography was not available in 2 of the 3 patients who underwent bypass grafting. One patient who underwent PTCA had renal insufficiency and thus did not have a follow-up angiogram. For the purpose of the T1-201 viability imaging analysis, the vessels to the infarct territories in these patients were assumed to b e patent. One other patient had development of chest pain at 7 weeks and was found to have an occluded stent that was reopened with repeat PTCA and stent insertion. The patient was symptom free at the 3-month follow-up time point, so the infarct-related artery was considered to be patent for the purposes of the viability analysis. Thus 19 patients were considered to have patent vessels at 3 months. Among these patients 171 segments were defined. There were 4 l segments in the vascular territories of infarct-related arteries with abnormal wall motion. Among these, there were 28 segments that
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improved in wall motion with revascularization and 13 that did not. Among segments that improved in wall motion, 25/28 (89%) were defined as viable on T1-201 imaging. Seven of 13 (54%) segments with no improvement in wall motion were defined as scar by T1-201 imaging. Examples of patients with viable myocardium or scar in the infarct zone are shown in Figure 1. The positive predictive value of T1-201 viability imaging for defining improvement in wall motion in abnormal infarct-related artery segments was 81% (25/31) and negative predictive value of 70% (7/10), with an overall accuracy of 78% (32/41). To investigate whether the low specificity was related in part to inadequate revascularization because of restenosis, the accuracies were reevaluated after excluding 8 abnormal baseline wall motion segments supplied by vessels with moderate to severe restenosis (more than 70% diameter stenosis). After excluding these 8 segments, the sensitivity and specificity of T1-201 viability imaging for detection of wall motion recovery were 87% (20/23) and 70% (7/10) (Figure 2). Six additional abnormal segments supplied by the vessels that were occluded at 3 months were also evaluated. Four of these were viable by T1-201 imaging at baseline. Among these 6 segments, 5 (83%) had a reduction in wall motion by >1 wall motion score at 3 months follow-up (3 were viable and 2 were scar at baseline). Thus a reduction in regional ventricular function occurred in most segments where revascularization could not be achieved. To further evaluate this, the wall motion recovery was compared among abnormal segments between those with incomplete revascularization (occlusion or restenosis; n = 14 segments) and those with presumed patent vessels (n = 33 segments). For incomplete revascularization wall motion score did not change between baseline and 3 months follow-up (1.8 _+ 1.0 vs 2.0 +_.1.6, P = NS); whereas in those with patent vessels, wall motion improved (1.6 _+ 1.4 vs 2.7 _+ 1.6, P < .001). The change in wall motion score was significantly greater for those with adequate revascularization compared with those where it was incomplete (1.2 _+ 1.2 vs 0.2 _+ 1.4, P = .02). Considering those regions with adequate revascularization, the change in wall motion score improved in those with viable myocardium (n = 23) and not with scar (n = 10) (change in wall motion for viable: 1.5 _+ 1.0 vs scar: 0.4 _+ 1.3, P = .01).
Ventricular Function and Symptom Change Revascularization in general did not lead to a significant change in overall ventricular function (53% _+8% to 54% _+ 7%, range 36% to 65%, P = NS). Some of this
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lack of improvement may have been related to hypercontractile noninfarcted myocardium at baseline in some patients with smaller infarcts. To further evaluate this, patients with EF < 55% (n -- 12) were considered separately. There was a significant improvement in overall ventricular function after revascularization in this group from 48% _+ 5% to 52% _+ 7% (P < .05). Among all 23 patients revascularization, overall, led to an improvement in angina (or dyspnea when this was the only symptom) from Canadian Cardiovascular Society class 2.3 +_ 1.5 to 1.0 _+ 1.4 (P < .01).
DISCUSSION Previous studies evaluating myocardial viability in the convalescent phase after unsuccessful thrombolysis have been limited. This study demonstrates that, after revascularization of a recently occluded infarctrelated artery, regional wall motion is more likely to improve if there is viable myocardium defined by T1201 imaging.
Myocardial Viability The detection of myocardial viability is useful in predicting recovery of myocardial function after revascularization in patients with chronic stable coronary artery disease.7-9,11,12A6 Modifications of T1-201 imaging with either stress-delayed imaging with reinjection protocol or rest-delayed T1-201 imaging protocol have been useful in this regard. 9,11A2,14-18,2° The sensitivity (89%) and specificity (54%) of T1-201 viability imaging in this study are in the range reported previously in other clinical settings. 11-20,26-28 In contrast to this study, previous investigations have not specifically evaluated T1-201 viability imaging in regions with an occluded vessel. Previous studies have principally evaluated patients without recent MI, 12-15,17-19,26-28 and the revascularization method was often bypass. 11,13-15,17,19,26 In this study the sensitivity of T1-201 imaging to detect viable recoverable myocardium after MI was good. As in previous studies, however, the specificity was suboptimal. One factor accounting for this observation may relate to the mixture of perfused viable tissue with necrotic tissue in a given segment of myocardium. Some dysfunctional segments may contain subendocardial necrosis leading to mild perfusion defects. Such segments may not improve function in spite of adequate revascularization, even though much of the segment is viable.~ 1,27 Also relevant to the suboptimal specificity is the adequacy of revascularization. Follow-up angiographic data has been limited in previous studies evaluating viability
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imaging.26, 28 In one study, only 14 of the 38 patients had angiography, and all had patent vessels. 26 In another, 9/19 segments without improvement in function had a restenosis of >50% and were excluded from follow-up analysis. 28 However, in the study by Ragosta et al,11 investigators used follow-up perfusion imaging to determine which patients were adequately revascularized. This study evaluated multiple segments among 21 patients with chronic disease and severe ventricular dysfunction undergoing coronary artery bypass grafting. Rest/redistribution TI-201 imaging had a positive predictive value of 57% and negative predictive value of 77% for prediction of regional wall motion recovery. The calculated sensitivity and specificity from their data were 80% and 53%, respectively. When patients without adequate revascularization were excluded, the false-positive rate decreased (the reported positive predictive value improved to 73%). When patients with development of a >70% restenosis were excluded from analysis in this study, the specificity improved. Both the study by Ragosta et a111 and this study indicate that an important factor in the accuracy of T1-201 viability imaging is achieving adequate revascularization. Recovery may not occur in viable segments unless vessel patency free of significant restenosis is achieved. T1-201 viability imaging provides a means to predict whether successful revascularization could lead to recovery of regional ventricular function in these patients after infarction. These data suggest that viability assessment should be considered in conjunction with clinical and angiographic parameters before attempting revascularization of an occluded coronary artery:
Mechanisms for Improvement in Regional Ventricular Function This study indicates that the presence of viable myocardium is an important factor in the potential for an infarct zone to recover after restoration of flow. Moreover, restoration of flow may also help to prevent infarct expansion. A rim of viable myocardium may be necessary to structurally buttress the expanding infarct zone. 29 It is of interest that 5 of 6 abnormal wall motion segments without adequate revascularization had further deterioration in ventricular function. This reduction in function may be explained in part by some infarct expansion resulting from failure to achieve sufficient scaffolding.29 The other key factor for wall motion recovery is achieving and maintaining patency without significant restenosis. This is necessary to deliver nutrient flow to the dysfunctional but viable myocardium to allow it to recover.
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Incomplete Reperfusion and Post-Ml Revascularizatlon Studies In the GUSTO trial, complete reperfusion with TIMI grade 3 flow was achieved at 5 to 7 days in 51% to 58% of cases. 3 Complete reperfusion was associated with better ventricular function and lower mortality rates than incomplete reperfusion. The latter patients represent a high-risk group that has not been well studied in the past. The TIMI-IIB study showed that after thrombolysis there was no advantage to early PTCA (18 to 48 hours) over a "wait and watch" approach with noninvasive risk stratification, 4 but patients with occluded vessels were excluded from this analysis and did not undergo PTCA. Ellis et al showed similar findings for late (4 to 14 days after MI) elective PTCA in low-risk patients, but only 4 of 42 PTCA-treated patients had a totally occluded infarct-related artery. 3° Our group previously showed that establishing vessel patency in patients with total coronary artery occlusion at <6 weeks after MI 6 leads to a significant improvement in ventricular function. Other investigators have also shown that successful recanalization can lead to improved ventricular function31 and may improve survival rates, 32 but these studies principally involved patients with chronic coronary artery occlusion more remote from previous infarction than the patients in this study.
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regional ventricular function used in other studies evaluating myocardial viability.7,8, 23 This pilot study used a cutoff of > 50% of maximum myocardial uptake to define viable myocardium.11,13,16,26,27 Although this cut-off is useful, others have reported that the degree of T1-201 uptake also relates to the likelihood of recovery.27 The extent to which this is relevant for this patient population may be better addressed in larger clinical trials. However, the data from this study do indicate that viability imaging should be considered along with clinical and angiographic information before proceeding with revascularization of occluded arteries after MI.
CONCLUSION In spite of the presence of an occluded coronary artery, viable myocardium was often present after myocardial infarction. T1-201 viability imaging detected recoverable myocardium with reasonable accuracy. The low specificity observed in this pilot study related in part to a lack of improvement in wall motion in segments with significant restenosis. Evaluation for the presence of viable myocardium may help select which patients will most benefit from revascularization of occluded arteries after MI We express our gratitude to Darlene Morris-Maheral for her excellent help in preparing the manuscript.
Technical Factors and Limitations Coronary angiography was used as a means for followup and determination of adequate revascularization. Only patients in whom there was definite occlusion at the time of follow-up were excluded from the primary analysis. Four patients did not have follow-up angiography at 3 months: two had bypass grafting as a method of revascularization; one had kidney failure that precluded followup coronary angiography; the fourth patient had symptomatic occlusion at 7 weeks that was reopened, and the patient remained symptom free at 3 months. In these 4 patients the vessels were assumed to be patent and without restenosis at 3 months follow-up. If any of these patients did not have adequate revascularization, then the overall accuracy of T1-201 viability imaging may be slightly better than reported in this study. The population size was comparable to most previous studies evaluating recovery of function predicted by T1-201 viability imaging in patients with chronic disease. 11-15,18,20,26-28 With one exception 19 these studies have had follow-up on 10 to 38 patients. The primary aim of the study was to assess the role of T1-201 imaging. Thus a 3-month follow-up was used to coincide with the expected time course of recovery of
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