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Six-month angiographic follow-up after intravascular ultrasound-guided stenting of infarct-related artery: Comparison with non–infarct-related artery
Six-month angiographic follow-up after intravascular ultrasound-guided stenting of infarct-related artery: Comparison with non–infarct-related artery Myeong-Ki Hong, MD, PhD, Seong-Wook Park, MD, PhD, Cheol Whan Lee, MD, PhD, Kyoung-Suk Rhee, MD, Jong-Min Song, MD, PhD, Duk-Hyun Kang, MD, PhD, Jae-Kwan Song, MD, PhD, Jae-Joong Kim, MD, PhD, and Seung-Jung Park, MD, PhD Seoul, Korea
Background Compared with balloon angioplasty, stenting has been established as an effective treatment modality to reduce restenosis in patients with acute myocardial infarction. However, the immediate results that predict favorable longterm outcomes in the acute infarct stenting are unknown. Therefore, we evaluated long-term outcomes of stenting for infarctrelated artery (IRA) lesions by using intravascular ultrasound (IVUS) compared with that of stenting for non-IRA lesions.
Methods IVUS-guided coronary stenting was successfully performed in 510 native coronary lesions (105 IRA vs 405 non-IRA). A 6-month follow-up angiogram was performed in 419 (82.2%) lesions: 87 (82.9%) IRA lesions and 332 (82.0%) non-IRA lesions. Coronary stenting on the IRA lesions was successfully performed within 7 to 10 days after onset of infarction in 42 patients and within 12 hours in 45 patients. Results were evaluated by clinical, angiographic, and IVUS methods.
Results There were no significant differences in clinical and angiographic variables between the two groups. IVUS variables including reference vessel area and minimal stent area were also similar between the two groups. There was no significant difference in angiographic restenosis rate between the two groups in cases of minimal stent area ≥7 mm2: 12.8% (6 of 47) in IRA versus 19.1% (33 of 173) in non-IRA lesions (P = .315). However, the angiographic restenosis rate in cases of minimal stent area <7 mm2 was 50% (20 of 40) in IRA lesions versus 31.5% (50 of 159) in non-IRA lesions (P = .028).
Conclusions Angiographic restenosis is significantly higher in stenting for IRA lesions compared with that for non-IRA lesions in cases of minimal stent area <7 mm2. (Am Heart J 2001;141:832-6.) Compared with thrombolysis, primary balloon angioplasty results in reduced rates of mortality, reinfarction, and stroke in patients with acute myocardial infarction.1 However, the significant residual narrowing after balloon angioplasty in many patients results in angiographic restenosis in 30% to 50% of infarct-related arteries (IRAs) within 6 months.2 After the demonstration of superior results of stents in reducing restenosis in patients undergoing elective intervention,3,4 the feasibility, safety, and efficacy of primary stenting in acute myocardial infarction have been evaluated in a number of observational and registry studies.2 Several studies have shown that stenting can also reduce restenosis compared with balloon angioplasty in patients with From the Department of Internal Medicine, College of Medicine, University of Ulsan, Cardiac Center, Asan Medical Center. Supported by a grant from the Korean Society of Circulation. Submitted August 15, 2000; accepted January 12, 2001. Reprint requests: Seung-Jung Park, MD, PhD, Department of Internal Medicine, College of Medicine, University of Ulsan, Cardiac Center, Asan Medical Center, 3881 Pungnap-dong, Songpa-gu, Seoul, 138-736, Korea. E-mail: [email protected] Copyright © 2001 by Mosby, Inc. 0002-8703/2001/$35.00 + 0 4/1/114200 doi:10.1067/mhj.2001.114200
acute myocardial infarction.5-8 However, it is unknown which immediate results predict favorable long-term outcomes in stenting of IRA lesions in patients with acute myocardial infarction. Therefore, the objective of the current study was to evaluate, with the use of intravascular ultrasound (IVUS), the long-term outcomes of stenting for IRA lesions compared with those of stenting for non-IRA lesions.
Methods Study population IVUS-guided coronary stenting with 1 or 2 overlapped coronary stents was successfully performed in 466 consecutive patients with 510 native coronary lesions. Angiographic follow-up was requested at 6 months. A 6-month follow-up angiogram was performed in 385 (82.6%) patients with 419 (82.2%) lesions. The lesions were divided into 2 groups: (1) 332 non-IRA lesions with stenting in 298 patients with stable or unstable angina and (2) 87 IRA lesions with stenting in 87 patients with acute myocardial infarction. All patients had objective evidence of myocardial ischemia and ≥70% angiographic diameter stenosis by visual estimate. Exclusion criteria included left main coronary artery disease, saphenous vein graft disease, non-IRA lesion stenting in 87 patients with acute
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myocardial infarction (n = 6), and failure to obtain angiographic follow-up (81 patients, 85 lesions). The comparisons between the two groups were performed retrospectively with the use of clinical, angiographic, and IVUS methods. All patients gave their written informed consent to participate in the study. This study was approved by our institutional review board on clinical study.
Stent implantation procedure Details of the stenting technique have been described previously.3,4,9 The following stents were used in this study: the tantalum Cordis stent (Medtronic Interventional Vascular, Kerkrade, The Netherlands), CrossFlex stent (Cordis, Warren, NJ), GFX stent, Crown stent (Cordis), DivYsio stent (Biocompatible, Surrey, UK), Palmaz-Schatz stent (Cordis), Multilink stent (Guidant/Advanced Cardiovascular Systems, Santa Clara, Calif), NIR stent, and Wiktor stent (Medtronics). Among these stents, the CrossFlex stent, GFX stent (Arterial Vascular Engineering, Santa Rosa, Calif), and NIR stent (Sci Med Live Systems, Maple Grove, Minn) were most commonly used in this study (86% of all stenting procedures). IVUS images were obtained after angiographic optimization. Stenting was optimized to achieve predetermined IVUS end points of stent expansion: minimum stent lumen cross-sectional area (CSA) ≥80% of average of proximal and distal reference lumen CSA, full stent–vessel wall apposition, and full lesion coverage. Operators were not blinded to the IVUS findings. Coronary stenting on the IRA lesions was successfully performed within 7 to 10 days after symptom onset in 42 patients and within 12 hours in 45 patients. Acute myocardial infarction was defined as chest pain of ≥30 minutes accompanied with ≥1 mm of ST elevation in >2 contiguous leads on electrocardiography and elevation of cardiac enzymes (creatine kinase-MB) >3-fold. The IRA was determined from the entry electrocardiogram, ventriculographic contraction abnormalities, and coronary angiographic findings. For example, when there was ST elevation in precordial leads on the electrocardiogram, wall motion abnormalities of the left ventricular septum, and severe narrowing with thrombus in the left anterior descending artery, the left anterior descending artery was the IRA. All patients received aspirin (200 mg per day, indefinitely) and ticlopidine (250 mg twice per day for 1 month) as an antithrombotic regimen. Platelet glycoprotein IIb/IIIa receptor inhibitor was not used in this study.
Quantitative coronary angiographic analysis Coronary angiography was performed after intracoronary administration of 0.2 mg nitroglycerin. Coronary angiographic results were analyzed by 2 independent angiographers. By using the guiding catheter for magnification calibration and an on-line quantitative coronary angiographic (QCA) system (ANCOR V2.0, Siemens, Solna, Sweden), percent diameter stenosis, minimal luminal diameter (MLD), and reference vessel diameter were measured before and after intervention and at follow-up from diastolic frames in a single, matched view showing the smallest luminal diameter. Angiographic restenosis was defined as a diameter stenosis of ≥50% at follow-up. Angiographic restenosis rate was compared between IRA lesions and non-IRA lesions according to IVUS stent lumen CSA. On the basis of our previously published data, the cutoff value of stent lumen CSA of 7 mm2 was used.9
Hong et al 833
IVUS imaging protocol Postintervention IVUS imaging was obtained after intracoronary administration of 0.2 mg nitroglycerin. The ultrasound catheter was advanced approximately 10 mm beyond the target lesion, and an imaging run was performed from beyond the target lesion to the aorto-ostial junction. The IVUS system (Boston Scientific/Cardiovascular Imaging System, Inc, San Jose, Calif) was withdrawn automatically at 0.5 mm/s to perform the imaging sequence. The stent length was measured with this automatic pullback device in cases in which we used 2 overlapped coronary stents. Ultrasound studies were recorded on half-inch high-resolution s-VHS tape for off-line analysis.
Quantitative IVUS measurements Validation of plaque composition and CSA measurements of external elastic membrane (EEM), lumen, and plaque + media by IVUS have been reported previously.10,11 Area measurements were performed with a commercially available program for computerized planimetry. The EEM CSA that represents total arterial CSA was measured by tracing the leading edge of the adventitia. Plaque + media CSA (which represents atherosclerotic plaque) was calculated as EEM CSA minus lumen CSA. For the target lesion, both proximal and distal reference segments were assessed by measuring minimum diameter and CSA after intervention. After intervention, the lesion site was image-sliced with the smallest-lumen CSA. Reference segments were defined as the most normal-looking cross sections within 10 mm proximal and distal to the lesions.
Statistical analysis Categoric data are presented as frequencies. Continuous data are presented as mean ± 1 SD. Comparison was performed with a nonpaired t test and chi-square or Fisher exact test. Stepwise logistic regression analysis was performed to determine the predictors of angiographic restenosis. A value of P < .05 denoted statistical significance.
Results The baseline clinical and angiographic characteristics are shown in Tables I and II. There were no significant differences of clinical and angiographic variables between the two groups. The overall angiographic restenosis rate was 26.0% (109 of 419) [IRA lesion, 30.0% (26 of 87) vs non-IRA lesion, 25.0% (83 of 332); P = .431]. Postintervention IVUS findings are shown in Table III. IVUS variables including reference vessel area and minimal stent area were also similar between the two groups. The angiographic and IVUS variables were compared between lesions with and those without restenosis at the 6-month follow-up angiogram. All univariate predictors of angiographic restenosis at a level of P < .2 were entered into the multivariate model. The univariate predictors included mean stent length, reference vessel diameter by QCA, postintervention MLD by QCA, postintervention EEM and lumen CSA of the proximal and distal reference segment, and postintervention IVUS stent lumen CSA. By multivariate logistic regression
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834 Hong et al
Table I. Baseline clinical characteristics (%)
No. of patients Age (y) Men Systemic hypertension Diabetes mellitus Hypercholesterolemia (≥240 mg/dL) Cigarette smoking Clinical presentation Stable angina Unstable angina Acute myocardial infarction No. of narrowed coronary arteries 1 2 3
Table III. Postintervention IVUS findings
IRA
Non-IRA
P value
87 56 ± 8 65 (74.7) 27 (31.0) 14 (16.1) 8 (9.2)
298 57 ± 7 222 (74.5) 102 (34.2) 40 (13.4) 28 (9.4)
.325 .544 .337 .318 .573
36 (41.4)
131 (44.0)
.382
87 (29.1) 211 (70.9)
Proximal reference segment EEM CSA (mm2) Lumen CSA (mm2) Lumen MLD (mm) Lesion segment Lumen CSA (mm2) Lumen MLD (mm) Distal reference segment EEM CSA (mm2) Lumen CSA (mm2) Lumen MLD (mm)
IRA
Non-IRA
P value
16.6 ± 3.6 9.6 ± 3.0 3.2 ± 0.5
16.2 ± 3.8 9.4 ± 2.9 3.2 ± 0.5
.369 .580 .737
7.5 ± 2.1 2.8 ± 0.4
7.4 ± 2.1 2.8 ± 0.4
.611 .827
14.2 ± 4.3 8.5 ± 3.0 3.0 ± 0.5
13.8 ± 4.0 8.3 ± 2.7 3.0 ± 0.5
.314 .538 .904
87 (100.0) .900 57 (65.5) 21 (24.1) 9 (10.3)
188 (63.1) 79 (26.5) 31 (10.4)
Table IV. Angiographic and IVUS findings between IRA and non-IRA lesions in cases of poststent CSA <7 mm2 IRA
Table II. Baseline angiographic characteristics and procedural results (%) IRA
Non-IRA
No. of lesions 87 332 Coronary artery dilated Left anterior descending 51 (58.6) 185 (55.7) Left circumflex 9 (10.3) 45 (13.6) Right 27 (31.0) 102 (30.7) Mean stent length (mm) 19.8 ± 7.2 20.1 ± 6.6 Reference vessel diameter (mm) 3.4 ± 0.5 3.3 ± 0.5 MLD (mm) Before intervention 0.6 ± 0.5 0.8 ± 0.5 After intervention 3.3 ± 0.5 3.3 ± 0.5 Follow-up 2.0 ± 0.9 2.0 ± 0.8 Balloon-to-artery ratio 1.13 ± 0.15 1.13 ± 0.12 Pressure (atm) 13.2 ± 3.2 13.1 ± 3.2 Angiographic restenosis rate 26 (30.0) 83 (25.0)
P value
.720
.487 .578 .263 .958 .942 .885 .764 .431
analysis, the only independent predictor of angiographic restenosis was IVUS stent lumen CSA (odds ratio, 1.42; 95% confidence interval [CI], 1.20 to 1.66, P = .001). The angiographic restenosis rate in cases of IVUS stent lumen CSA <7 mm2 and ≥7 mm2 was 35.2% (70 of 199) and 17.7% (39 of 220), respectively (odds ratio, 0.40; 95% CI, 0.25 to 0.62; P = .001). In a subgroup analysis of non-IRA lesions and IRA lesions, the independent predictor of angiographic restenosis was also IVUS stent lumen CSA (odds ratio, 1.36; 95% CI, 1.14 to 1.64; P = .001 for non-IRA lesions, and odds ratio, 1.60; 95% CI, 1.15 to 2.24; P = .005 for IRA lesions). Tables IV and V show the angiographic and IVUS findings between IRA lesions and non-IRA lesions in cases of IVUS stent lumen CSA <7 mm2 and ≥7 mm2, respectively. There were no significant differences in the angiographic and IVUS variables between IRA lesions and non-IRA lesions in both subgroups. There
No. of coronary narrowings 40 Mean stent length (mm) 20.9 ± 8.6 Reference vessel diameter (mm) 3.1 ± 0.4 MLD (mm) Before intervention 0.6 ± 0.6 After intervention 2.9 ± 0.4 Follow-up 1.6 ± 0.9 Balloon-to-artery ratio 1.15 ± 0.19 Pressure (atm) 12.3 ± 2.3 Angiographic restenosis rate 20 (50.0%) IVUS findings Proximal reference segment EEM CSA (mm2) 14.4 ± 3.0 Lumen CSA (mm2) 7.5 ± 2.0 Lumen MLD (mm) 2.8 ± 0.4 Lesion segment Lumen CSA (mm2) 5.7 ± 0.9 Lumen MLD (mm) 2.4 ± 0.2 Distal reference segment EEM CSA (mm2) 11.5 ± 3.3 Lumen CSA (mm2) 6.6 ± 1.8 Lumen MLD (mm) 2.6 ± 0.4
Non-IRA P value 159 21.3 ± 7.1 3.1 ± 0.3
.884 .781
0.8 ± 0.5 3.0 ± 0.3 1.7 ± 0.7 1.13 ± 0.19 12.3 ± 3.5 50 (31.5%)
.192 .347 .596 .405 .968 .028
14.1 ± 3.0 7.5 ± 1.8 2.9 ± 0.4
.393 .812 .393
5.7 ± 0.9 2.5 ± 0.2
.884 .301
11.3 ± 2.9 6.7 ± 1.6 2.7 ± 0.4
.573 .465 .381
was no significant difference of angiographic restenosis rate between the two groups in cases of IVUS stent lumen CSA ≥7 mm2: 12.8% (6 of 47) in IRA lesions versus 19.1% (33 of 173) in non-IRA lesions (P = .315). However, the angiographic restenosis rate in cases of IVUS stent lumen CSA <7 mm2 was 50% (20 of 40) in IRA lesions versus 31.5% (50 of 159) in non-IRA lesions (P = .028) (Figure 1).
Discussion Previous studies have documented improved longterm outcomes with reduced restenosis after stenting than after balloon angioplasty in patients with acute myocardial infarction.5-8 The angiographic restenosis rate of stenting for IRA lesions ranges from 13% to
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Hong et al 835
Table V. Angiographic and IVUS findings between IRA and non-IRA lesions in cases of poststent CSA ≥7 mm2 IRA No. of coronary narrowings Mean stent length (mm) Reference vessel diameter (mm) MLD (mm) Before intervention After intervention Follow-up Balloon-to-artery ratio Pressure (atm) Angiographic restenosis rate IVUS findings Proximal reference segment EEM CSA (mm2) Lumen CSA (mm2) Lumen MLD (mm) Lesion segment Lumen CSA (mm2) Lumen MLD (mm) Distal reference segment EEM CSA (mm2) Lumen CSA (mm2) Lumen MLD (mm)
47 19.3 ± 5.6 3.6 ± 0.5
Non-IRA
P value
173 19.6 ± 6.1 3.6 ± 0.4
.414 .994
0.6 ± 0.6 0.8 ± 0.5 3.5 ± 0.4 3.5 ± 0.4 2.3 ± 0.7 2.2 ± 0.8 1.11 ± 0.12 1.12 ± 0.12 13.1 ± 3.6 13.6 ± 3.5 6 (12.8%) 33 (19.1%)
.213 .952 .808 .635 .444 .315
18.2 ± 3.1 11.3 ± 2.6 3.5 ± 0.4
17.8 ± 3.5 11.1 ± 2.7 3.5 ± 0.5
.376 .532 .882
9.0 ± 1.4 3.1 ± 0.3
9.0 ± 1.7 3.1 ± 0.3
.553 .428
16.3 ± 3.6 10.2 ± 2.7 3.3 ± 0.5
15.7 ± 3.7 9.8 ± 2.8 3.2 ± 0.4
.276 .268 .557
27.5%.5-8 Several studies have shown that the most important factor determining the angiographic restenosis is IVUS stent lumen CSA in elective stenting for nonIRA lesions.12-15 Our previously published data showed that the angiographic restenosis rates according to stent lumen CSA were as follows: 54.8% in stent lumen CSA <5.0 mm2, 27.4% between 5.0 and 7.0 mm2, 10.5% between 7.0 and 9.0 mm2, and 11.4% in stent lumen CSA ≥9.0 mm2 (P = .001).9 Therefore, the cutoff value of 7 mm2 was used in this study. The findings in the previous studies9,12-15 might be applied to stenting for IRA lesions. Other studies that did not use IVUS showed that several factors, including number of stents, reference vessel size, and poststent MLD, were the independent factors that can predict late angiographic restenosis or adverse cardiac events in stenting for IRA lesions in patients with acute myocardial infarction.8,16 However, there are few published data about the use of IVUS for stenting of IRA lesions. The current study showed that IVUS stent lumen CSA was the only independent predictor of angiographic restenosis in stenting for IRA lesions in patients with acute myocardial infarction as well as that for non-IRA lesions in patients with angina pectoris. Stenting of small coronary arteries is not a generally accepted practice in non-IRA lesions. Despite successful stenting, a higher restenosis rate might be expected if the small vessel size limits the achievement of sufficiently large MLD. These findings might be similar to those of stenting for IRA lesions. Previous studies without the use of IVUS showed a higher restenosis rate for
Figure 1
Angiographic restenosis rate for stenting of IRA and non-IRA lesions according to poststent lumen area <7 mm2 vs ≥7 mm2, respectively.
patients with IRA lesions of small vessel size (<3.0 mm or 3.1 mm).8,16 In the current study, despite successful stenting, the angiographic restenosis rate was high (50%) in stenting for IRA lesions in cases of poststent lumen CSA <7 mm2 (ie, small vessels). Moreover, compared with non-IRA lesions in the same conditions, the angiographic restenosis rate was significantly higher in stenting for IRA lesions (50% vs 31.5%, P = .028). The vulnerable plaque of IRA lesions might be related to triggering the process of more intimal hyperplasia proliferation within the stent.17,18 Several studies have assessed the efficacy of elective stent placement for non-IRA lesions in small coronary arteries and have provided conflicting results.19-22 Therefore, it is still controversial whether stents should be used only to treat suboptimal results or should be recommended as a primary therapy for small-vessel disease. One randomized study comparing optimal balloon angioplasty with provisional stenting versus elective stenting showed that the 6-month angiographic restenosis rate was similar between the two groups (31.9% in angioplasty group vs 35.7% in stent group, P = not significant).23 Therefore, the authors suggested that optimal balloon angioplasty with provisional stenting might be a reasonable approach for treatment of non-IRA lesions in small coronary arteries.23 The question of whether stenting of IRA lesions of small vessels (ie, small lumen area despite successful intervention) will have equivalent, worse, or improved outcome compared with balloon angioplasty is not yet
836 Hong et al
answered. Therefore, elective stenting should be considered carefully before being used for IRA lesions in which poststent lumen CSA might be expected to be <7 mm2. And, as recommended in the previous randomized study in non-IRA lesions,23 optimal balloon angioplasty with provisional stenting might be an option for optimal treatment in IRA lesions. Glycoprotein IIb/IIIa receptor inhibitor may not only maintain patency of the recanalized vessels but also may prevent embolization of platelet aggregates into the distal microcirculation.24 Glycoprotein IIb/IIIa receptor inhibitor was not used in this study. The role of glycoprotein IIb/IIIa receptor inhibitor in reducing late restenosis should also be further investigated in stenting of IRA lesions with poststent lumen CSA <7 mm2. The optimal treatment modalities for such a condition should be further evaluated. This study has several limitations. First, this was a retrospective study. Second, the impact of preintervention IVUS was not evaluated. Third, the results of this study could not be applied to patients with non–IVUSguided stenting because IVUS guidance might be related to a potential for selection bias. Fourth, the number of patients with acute myocardial infarction was small relative to that needed to suggest clinical implications. The groups of stenting for an IRA are in part heterogeneous: primary stenting within 12 hours of symptom onset in 45 of 87 patients and delayed stenting on the IRA within 7 to 10 days after onset in 42 of 87 patients. Finally, various kinds of stents were used in this study. We thank Jae-Yoon Ko, CVT, and other staff of the cardiac catheterization laboratory for their important contributions.
References 1. Weaver WD, Simes RJ, Ellis SG, et al. Comparison of primary coronary angioplasty and intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review. JAMA 1997;278: 2093-8. 2. Stone GW. Primary stenting in acute myocardial infarction: the promise and the proof. Circulation 1998;97:2482-5. 3. Serruys PW, Jaegere PD, Kiemeneij F, et al. A comparison of balloon expandable stent implantation with balloon angioplasty in patients with coronary artery disease. N Engl J Med 1994;331: 489-95. 4. Fischman DL, Leon MB, Baim DS, et al. A randomized comparison of coronary-stent placement and balloon angioplasty in the treatment of coronary artery disease. N Engl J Med 1994;331:496-501. 5. Hong MK, Park SW, Kim JJ, et al. Comparison of six-month results of coronary stenting versus balloon angioplasty alone in patients with acute myocardial infarction. Am J Cardiol 1997; 79:1524-7. 6. Suryapranata H, van’t Hof AWJ, Hoorntje JCA, et al. Randomized comparison of coronary stenting with balloon angioplasty in selected patients with acute myocardial infarction. Circulation 1998;97:2502-5.
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7. Antoniucci D, Santoro GM, Bolognese L, et al. A clinical trial comparing primary stenting of the infarct-related artery with optimal primary angioplasty for acute myocardial infarction: results from the Florence randomized elective stenting in acute coronary occlusions (FRESCO) trial. J Am Coll Cardiol 1998;31:1234-9. 8. Stone GW, Brodie BG, Griffin JJ, et al. Clinical and angiographic follow-up after primary stenting in acute myocardial infarction: the primary angioplasty in myocardial infarction (PAMI) stent pilot trial. Circulation 1999;99:1548-54. 9. Hong MK, Park SW, Mintz GS, et al. Intravascular ultrasonic predictors of angiographic restenosis after long coronary stenting. Am J Cardiol 2000;85:441-5. 10. Tobis JM, Mallery J, Mahon D, et al. Intravascular ultrasound imaging of human coronary arteries in vivo: analysis of tissue characteristics with comparison to in vivo histologic specimens. Circulation 1991;83:913-26. 11. Nishimura RA, Edwards WD, Warnes CA, et al. Intravascular ultrasound imaging: in vitro validation and pathologic correlation. J Am Coll Cardiol 1990;16:145-54. 12. Hoffmann R, Mintz GS, Mehran R, et al. Intravascular ultrasound predictors of angiographic restenosis in lesions treated with PalmazSchatz stents. J Am Coll Cardiol 1998;31:43-9. 13. Kasaoka S, Tobis JM, Akiyama T, et al. Angiographic and intravascular ultrasound predictors of in-stent restenosis. J Am Coll Cardiol 1998;32:1630-5. 14. Moussa I, Moses J, Di Mario C, et al. Dose the specific intravascular ultrasound criterion used to optimize stent expansion have an impact on the probability of stent restenosis? Am J Cardiol 1999; 83:1012-7. 15. Fitzgerald PJ, Oshima A, Hayase M, et al. Final results of the can routine ultrasound influence stent expansion (CRUISE) study. Circulation 2000;102:523-30. 16. Antoniucci D, Valenti R, Santoro GM, et al. Primary coronary infarct artery stenting in acute myocardial infarction. Am J Cardiol 1999; 84:505-10. 17. Pasterkamp G, Falk E, Woutman H, et al. Techniques characterizing the coronary atherosclerotic plaque: influence on clinical decision making? J Am Coll Cardiol 2000;36:13-21. 18. Falk E. Stable versus unstable atherosclerosis: clinical aspects. Am Heart J 1999;138:S421-5. 19. Akiyama T, Moussa I, Reimers B, et al. Angiographic and clinical outcome following coronary stenting of small vessel: a comparison with coronary stenting of large vessels. J Am Coll Cardiol 1998; 32:1610-8. 20. Savage MP, Fischman DL, Rake R, et al. Efficacy of coronary stenting versus balloon angioplasty in small coronary arteries. J Am Coll Cardiol 1998;31:307-11. 21. Elezi S, Kastrati A, Neumann FJ, et al. Vessel size and long-term outcome after coronary stent placement. Circulation 1998;98:1875-80. 22. Foley DP, Melkert R, Serruys PW. Influence of coronary vessel size on renarrowing process and late angiographic outcome after successful balloon angioplasty. Circulation 1994;90:123951. 23. Park SW, Lee CW, Hong MK, et al. Randomized comparison of coronary stenting with optimal balloon angioplasty for treatment of lesions in small coronary arteries. Eur Heart J 2000;21:1785-9. 24. Neumann FJ, Blasini R, Schmitt C, et al. Effect of glycoprotein IIb/IIIa receptor blockade on recovery of coronary flow and left ventricular function after the placement of coronary-artery stents in acute myocardial infarction. Circulation 1998;98: 2695-701.
Background Compared with balloon angioplasty, stenting has been established as an effective treatment modality to reduce restenosis in patients with acute myocardial infarction. However, the immediate results that predict favorable longterm outcomes in the acute infarct stenting are unknown. Therefore, we evaluated long-term outcomes of stenting for infarctrelated artery (IRA) lesions by using intravascular ultrasound (IVUS) compared with that of stenting for non-IRA lesions.
Methods IVUS-guided coronary stenting was successfully performed in 510 native coronary lesions (105 IRA vs 405 non-IRA). A 6-month follow-up angiogram was performed in 419 (82.2%) lesions: 87 (82.9%) IRA lesions and 332 (82.0%) non-IRA lesions. Coronary stenting on the IRA lesions was successfully performed within 7 to 10 days after onset of infarction in 42 patients and within 12 hours in 45 patients. Results were evaluated by clinical, angiographic, and IVUS methods.
Results There were no significant differences in clinical and angiographic variables between the two groups. IVUS variables including reference vessel area and minimal stent area were also similar between the two groups. There was no significant difference in angiographic restenosis rate between the two groups in cases of minimal stent area ≥7 mm2: 12.8% (6 of 47) in IRA versus 19.1% (33 of 173) in non-IRA lesions (P = .315). However, the angiographic restenosis rate in cases of minimal stent area <7 mm2 was 50% (20 of 40) in IRA lesions versus 31.5% (50 of 159) in non-IRA lesions (P = .028).
Conclusions Angiographic restenosis is significantly higher in stenting for IRA lesions compared with that for non-IRA lesions in cases of minimal stent area <7 mm2. (Am Heart J 2001;141:832-6.) Compared with thrombolysis, primary balloon angioplasty results in reduced rates of mortality, reinfarction, and stroke in patients with acute myocardial infarction.1 However, the significant residual narrowing after balloon angioplasty in many patients results in angiographic restenosis in 30% to 50% of infarct-related arteries (IRAs) within 6 months.2 After the demonstration of superior results of stents in reducing restenosis in patients undergoing elective intervention,3,4 the feasibility, safety, and efficacy of primary stenting in acute myocardial infarction have been evaluated in a number of observational and registry studies.2 Several studies have shown that stenting can also reduce restenosis compared with balloon angioplasty in patients with From the Department of Internal Medicine, College of Medicine, University of Ulsan, Cardiac Center, Asan Medical Center. Supported by a grant from the Korean Society of Circulation. Submitted August 15, 2000; accepted January 12, 2001. Reprint requests: Seung-Jung Park, MD, PhD, Department of Internal Medicine, College of Medicine, University of Ulsan, Cardiac Center, Asan Medical Center, 3881 Pungnap-dong, Songpa-gu, Seoul, 138-736, Korea. E-mail: [email protected] Copyright © 2001 by Mosby, Inc. 0002-8703/2001/$35.00 + 0 4/1/114200 doi:10.1067/mhj.2001.114200
acute myocardial infarction.5-8 However, it is unknown which immediate results predict favorable long-term outcomes in stenting of IRA lesions in patients with acute myocardial infarction. Therefore, the objective of the current study was to evaluate, with the use of intravascular ultrasound (IVUS), the long-term outcomes of stenting for IRA lesions compared with those of stenting for non-IRA lesions.
Methods Study population IVUS-guided coronary stenting with 1 or 2 overlapped coronary stents was successfully performed in 466 consecutive patients with 510 native coronary lesions. Angiographic follow-up was requested at 6 months. A 6-month follow-up angiogram was performed in 385 (82.6%) patients with 419 (82.2%) lesions. The lesions were divided into 2 groups: (1) 332 non-IRA lesions with stenting in 298 patients with stable or unstable angina and (2) 87 IRA lesions with stenting in 87 patients with acute myocardial infarction. All patients had objective evidence of myocardial ischemia and ≥70% angiographic diameter stenosis by visual estimate. Exclusion criteria included left main coronary artery disease, saphenous vein graft disease, non-IRA lesion stenting in 87 patients with acute
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myocardial infarction (n = 6), and failure to obtain angiographic follow-up (81 patients, 85 lesions). The comparisons between the two groups were performed retrospectively with the use of clinical, angiographic, and IVUS methods. All patients gave their written informed consent to participate in the study. This study was approved by our institutional review board on clinical study.
Stent implantation procedure Details of the stenting technique have been described previously.3,4,9 The following stents were used in this study: the tantalum Cordis stent (Medtronic Interventional Vascular, Kerkrade, The Netherlands), CrossFlex stent (Cordis, Warren, NJ), GFX stent, Crown stent (Cordis), DivYsio stent (Biocompatible, Surrey, UK), Palmaz-Schatz stent (Cordis), Multilink stent (Guidant/Advanced Cardiovascular Systems, Santa Clara, Calif), NIR stent, and Wiktor stent (Medtronics). Among these stents, the CrossFlex stent, GFX stent (Arterial Vascular Engineering, Santa Rosa, Calif), and NIR stent (Sci Med Live Systems, Maple Grove, Minn) were most commonly used in this study (86% of all stenting procedures). IVUS images were obtained after angiographic optimization. Stenting was optimized to achieve predetermined IVUS end points of stent expansion: minimum stent lumen cross-sectional area (CSA) ≥80% of average of proximal and distal reference lumen CSA, full stent–vessel wall apposition, and full lesion coverage. Operators were not blinded to the IVUS findings. Coronary stenting on the IRA lesions was successfully performed within 7 to 10 days after symptom onset in 42 patients and within 12 hours in 45 patients. Acute myocardial infarction was defined as chest pain of ≥30 minutes accompanied with ≥1 mm of ST elevation in >2 contiguous leads on electrocardiography and elevation of cardiac enzymes (creatine kinase-MB) >3-fold. The IRA was determined from the entry electrocardiogram, ventriculographic contraction abnormalities, and coronary angiographic findings. For example, when there was ST elevation in precordial leads on the electrocardiogram, wall motion abnormalities of the left ventricular septum, and severe narrowing with thrombus in the left anterior descending artery, the left anterior descending artery was the IRA. All patients received aspirin (200 mg per day, indefinitely) and ticlopidine (250 mg twice per day for 1 month) as an antithrombotic regimen. Platelet glycoprotein IIb/IIIa receptor inhibitor was not used in this study.
Quantitative coronary angiographic analysis Coronary angiography was performed after intracoronary administration of 0.2 mg nitroglycerin. Coronary angiographic results were analyzed by 2 independent angiographers. By using the guiding catheter for magnification calibration and an on-line quantitative coronary angiographic (QCA) system (ANCOR V2.0, Siemens, Solna, Sweden), percent diameter stenosis, minimal luminal diameter (MLD), and reference vessel diameter were measured before and after intervention and at follow-up from diastolic frames in a single, matched view showing the smallest luminal diameter. Angiographic restenosis was defined as a diameter stenosis of ≥50% at follow-up. Angiographic restenosis rate was compared between IRA lesions and non-IRA lesions according to IVUS stent lumen CSA. On the basis of our previously published data, the cutoff value of stent lumen CSA of 7 mm2 was used.9
Hong et al 833
IVUS imaging protocol Postintervention IVUS imaging was obtained after intracoronary administration of 0.2 mg nitroglycerin. The ultrasound catheter was advanced approximately 10 mm beyond the target lesion, and an imaging run was performed from beyond the target lesion to the aorto-ostial junction. The IVUS system (Boston Scientific/Cardiovascular Imaging System, Inc, San Jose, Calif) was withdrawn automatically at 0.5 mm/s to perform the imaging sequence. The stent length was measured with this automatic pullback device in cases in which we used 2 overlapped coronary stents. Ultrasound studies were recorded on half-inch high-resolution s-VHS tape for off-line analysis.
Quantitative IVUS measurements Validation of plaque composition and CSA measurements of external elastic membrane (EEM), lumen, and plaque + media by IVUS have been reported previously.10,11 Area measurements were performed with a commercially available program for computerized planimetry. The EEM CSA that represents total arterial CSA was measured by tracing the leading edge of the adventitia. Plaque + media CSA (which represents atherosclerotic plaque) was calculated as EEM CSA minus lumen CSA. For the target lesion, both proximal and distal reference segments were assessed by measuring minimum diameter and CSA after intervention. After intervention, the lesion site was image-sliced with the smallest-lumen CSA. Reference segments were defined as the most normal-looking cross sections within 10 mm proximal and distal to the lesions.
Statistical analysis Categoric data are presented as frequencies. Continuous data are presented as mean ± 1 SD. Comparison was performed with a nonpaired t test and chi-square or Fisher exact test. Stepwise logistic regression analysis was performed to determine the predictors of angiographic restenosis. A value of P < .05 denoted statistical significance.
Results The baseline clinical and angiographic characteristics are shown in Tables I and II. There were no significant differences of clinical and angiographic variables between the two groups. The overall angiographic restenosis rate was 26.0% (109 of 419) [IRA lesion, 30.0% (26 of 87) vs non-IRA lesion, 25.0% (83 of 332); P = .431]. Postintervention IVUS findings are shown in Table III. IVUS variables including reference vessel area and minimal stent area were also similar between the two groups. The angiographic and IVUS variables were compared between lesions with and those without restenosis at the 6-month follow-up angiogram. All univariate predictors of angiographic restenosis at a level of P < .2 were entered into the multivariate model. The univariate predictors included mean stent length, reference vessel diameter by QCA, postintervention MLD by QCA, postintervention EEM and lumen CSA of the proximal and distal reference segment, and postintervention IVUS stent lumen CSA. By multivariate logistic regression
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834 Hong et al
Table I. Baseline clinical characteristics (%)
No. of patients Age (y) Men Systemic hypertension Diabetes mellitus Hypercholesterolemia (≥240 mg/dL) Cigarette smoking Clinical presentation Stable angina Unstable angina Acute myocardial infarction No. of narrowed coronary arteries 1 2 3
Table III. Postintervention IVUS findings
IRA
Non-IRA
P value
87 56 ± 8 65 (74.7) 27 (31.0) 14 (16.1) 8 (9.2)
298 57 ± 7 222 (74.5) 102 (34.2) 40 (13.4) 28 (9.4)
.325 .544 .337 .318 .573
36 (41.4)
131 (44.0)
.382
87 (29.1) 211 (70.9)
Proximal reference segment EEM CSA (mm2) Lumen CSA (mm2) Lumen MLD (mm) Lesion segment Lumen CSA (mm2) Lumen MLD (mm) Distal reference segment EEM CSA (mm2) Lumen CSA (mm2) Lumen MLD (mm)
IRA
Non-IRA
P value
16.6 ± 3.6 9.6 ± 3.0 3.2 ± 0.5
16.2 ± 3.8 9.4 ± 2.9 3.2 ± 0.5
.369 .580 .737
7.5 ± 2.1 2.8 ± 0.4
7.4 ± 2.1 2.8 ± 0.4
.611 .827
14.2 ± 4.3 8.5 ± 3.0 3.0 ± 0.5
13.8 ± 4.0 8.3 ± 2.7 3.0 ± 0.5
.314 .538 .904
87 (100.0) .900 57 (65.5) 21 (24.1) 9 (10.3)
188 (63.1) 79 (26.5) 31 (10.4)
Table IV. Angiographic and IVUS findings between IRA and non-IRA lesions in cases of poststent CSA <7 mm2 IRA
Table II. Baseline angiographic characteristics and procedural results (%) IRA
Non-IRA
No. of lesions 87 332 Coronary artery dilated Left anterior descending 51 (58.6) 185 (55.7) Left circumflex 9 (10.3) 45 (13.6) Right 27 (31.0) 102 (30.7) Mean stent length (mm) 19.8 ± 7.2 20.1 ± 6.6 Reference vessel diameter (mm) 3.4 ± 0.5 3.3 ± 0.5 MLD (mm) Before intervention 0.6 ± 0.5 0.8 ± 0.5 After intervention 3.3 ± 0.5 3.3 ± 0.5 Follow-up 2.0 ± 0.9 2.0 ± 0.8 Balloon-to-artery ratio 1.13 ± 0.15 1.13 ± 0.12 Pressure (atm) 13.2 ± 3.2 13.1 ± 3.2 Angiographic restenosis rate 26 (30.0) 83 (25.0)
P value
.720
.487 .578 .263 .958 .942 .885 .764 .431
analysis, the only independent predictor of angiographic restenosis was IVUS stent lumen CSA (odds ratio, 1.42; 95% confidence interval [CI], 1.20 to 1.66, P = .001). The angiographic restenosis rate in cases of IVUS stent lumen CSA <7 mm2 and ≥7 mm2 was 35.2% (70 of 199) and 17.7% (39 of 220), respectively (odds ratio, 0.40; 95% CI, 0.25 to 0.62; P = .001). In a subgroup analysis of non-IRA lesions and IRA lesions, the independent predictor of angiographic restenosis was also IVUS stent lumen CSA (odds ratio, 1.36; 95% CI, 1.14 to 1.64; P = .001 for non-IRA lesions, and odds ratio, 1.60; 95% CI, 1.15 to 2.24; P = .005 for IRA lesions). Tables IV and V show the angiographic and IVUS findings between IRA lesions and non-IRA lesions in cases of IVUS stent lumen CSA <7 mm2 and ≥7 mm2, respectively. There were no significant differences in the angiographic and IVUS variables between IRA lesions and non-IRA lesions in both subgroups. There
No. of coronary narrowings 40 Mean stent length (mm) 20.9 ± 8.6 Reference vessel diameter (mm) 3.1 ± 0.4 MLD (mm) Before intervention 0.6 ± 0.6 After intervention 2.9 ± 0.4 Follow-up 1.6 ± 0.9 Balloon-to-artery ratio 1.15 ± 0.19 Pressure (atm) 12.3 ± 2.3 Angiographic restenosis rate 20 (50.0%) IVUS findings Proximal reference segment EEM CSA (mm2) 14.4 ± 3.0 Lumen CSA (mm2) 7.5 ± 2.0 Lumen MLD (mm) 2.8 ± 0.4 Lesion segment Lumen CSA (mm2) 5.7 ± 0.9 Lumen MLD (mm) 2.4 ± 0.2 Distal reference segment EEM CSA (mm2) 11.5 ± 3.3 Lumen CSA (mm2) 6.6 ± 1.8 Lumen MLD (mm) 2.6 ± 0.4
Non-IRA P value 159 21.3 ± 7.1 3.1 ± 0.3
.884 .781
0.8 ± 0.5 3.0 ± 0.3 1.7 ± 0.7 1.13 ± 0.19 12.3 ± 3.5 50 (31.5%)
.192 .347 .596 .405 .968 .028
14.1 ± 3.0 7.5 ± 1.8 2.9 ± 0.4
.393 .812 .393
5.7 ± 0.9 2.5 ± 0.2
.884 .301
11.3 ± 2.9 6.7 ± 1.6 2.7 ± 0.4
.573 .465 .381
was no significant difference of angiographic restenosis rate between the two groups in cases of IVUS stent lumen CSA ≥7 mm2: 12.8% (6 of 47) in IRA lesions versus 19.1% (33 of 173) in non-IRA lesions (P = .315). However, the angiographic restenosis rate in cases of IVUS stent lumen CSA <7 mm2 was 50% (20 of 40) in IRA lesions versus 31.5% (50 of 159) in non-IRA lesions (P = .028) (Figure 1).
Discussion Previous studies have documented improved longterm outcomes with reduced restenosis after stenting than after balloon angioplasty in patients with acute myocardial infarction.5-8 The angiographic restenosis rate of stenting for IRA lesions ranges from 13% to
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Hong et al 835
Table V. Angiographic and IVUS findings between IRA and non-IRA lesions in cases of poststent CSA ≥7 mm2 IRA No. of coronary narrowings Mean stent length (mm) Reference vessel diameter (mm) MLD (mm) Before intervention After intervention Follow-up Balloon-to-artery ratio Pressure (atm) Angiographic restenosis rate IVUS findings Proximal reference segment EEM CSA (mm2) Lumen CSA (mm2) Lumen MLD (mm) Lesion segment Lumen CSA (mm2) Lumen MLD (mm) Distal reference segment EEM CSA (mm2) Lumen CSA (mm2) Lumen MLD (mm)
47 19.3 ± 5.6 3.6 ± 0.5
Non-IRA
P value
173 19.6 ± 6.1 3.6 ± 0.4
.414 .994
0.6 ± 0.6 0.8 ± 0.5 3.5 ± 0.4 3.5 ± 0.4 2.3 ± 0.7 2.2 ± 0.8 1.11 ± 0.12 1.12 ± 0.12 13.1 ± 3.6 13.6 ± 3.5 6 (12.8%) 33 (19.1%)
.213 .952 .808 .635 .444 .315
18.2 ± 3.1 11.3 ± 2.6 3.5 ± 0.4
17.8 ± 3.5 11.1 ± 2.7 3.5 ± 0.5
.376 .532 .882
9.0 ± 1.4 3.1 ± 0.3
9.0 ± 1.7 3.1 ± 0.3
.553 .428
16.3 ± 3.6 10.2 ± 2.7 3.3 ± 0.5
15.7 ± 3.7 9.8 ± 2.8 3.2 ± 0.4
.276 .268 .557
27.5%.5-8 Several studies have shown that the most important factor determining the angiographic restenosis is IVUS stent lumen CSA in elective stenting for nonIRA lesions.12-15 Our previously published data showed that the angiographic restenosis rates according to stent lumen CSA were as follows: 54.8% in stent lumen CSA <5.0 mm2, 27.4% between 5.0 and 7.0 mm2, 10.5% between 7.0 and 9.0 mm2, and 11.4% in stent lumen CSA ≥9.0 mm2 (P = .001).9 Therefore, the cutoff value of 7 mm2 was used in this study. The findings in the previous studies9,12-15 might be applied to stenting for IRA lesions. Other studies that did not use IVUS showed that several factors, including number of stents, reference vessel size, and poststent MLD, were the independent factors that can predict late angiographic restenosis or adverse cardiac events in stenting for IRA lesions in patients with acute myocardial infarction.8,16 However, there are few published data about the use of IVUS for stenting of IRA lesions. The current study showed that IVUS stent lumen CSA was the only independent predictor of angiographic restenosis in stenting for IRA lesions in patients with acute myocardial infarction as well as that for non-IRA lesions in patients with angina pectoris. Stenting of small coronary arteries is not a generally accepted practice in non-IRA lesions. Despite successful stenting, a higher restenosis rate might be expected if the small vessel size limits the achievement of sufficiently large MLD. These findings might be similar to those of stenting for IRA lesions. Previous studies without the use of IVUS showed a higher restenosis rate for
Figure 1
Angiographic restenosis rate for stenting of IRA and non-IRA lesions according to poststent lumen area <7 mm2 vs ≥7 mm2, respectively.
patients with IRA lesions of small vessel size (<3.0 mm or 3.1 mm).8,16 In the current study, despite successful stenting, the angiographic restenosis rate was high (50%) in stenting for IRA lesions in cases of poststent lumen CSA <7 mm2 (ie, small vessels). Moreover, compared with non-IRA lesions in the same conditions, the angiographic restenosis rate was significantly higher in stenting for IRA lesions (50% vs 31.5%, P = .028). The vulnerable plaque of IRA lesions might be related to triggering the process of more intimal hyperplasia proliferation within the stent.17,18 Several studies have assessed the efficacy of elective stent placement for non-IRA lesions in small coronary arteries and have provided conflicting results.19-22 Therefore, it is still controversial whether stents should be used only to treat suboptimal results or should be recommended as a primary therapy for small-vessel disease. One randomized study comparing optimal balloon angioplasty with provisional stenting versus elective stenting showed that the 6-month angiographic restenosis rate was similar between the two groups (31.9% in angioplasty group vs 35.7% in stent group, P = not significant).23 Therefore, the authors suggested that optimal balloon angioplasty with provisional stenting might be a reasonable approach for treatment of non-IRA lesions in small coronary arteries.23 The question of whether stenting of IRA lesions of small vessels (ie, small lumen area despite successful intervention) will have equivalent, worse, or improved outcome compared with balloon angioplasty is not yet
836 Hong et al
answered. Therefore, elective stenting should be considered carefully before being used for IRA lesions in which poststent lumen CSA might be expected to be <7 mm2. And, as recommended in the previous randomized study in non-IRA lesions,23 optimal balloon angioplasty with provisional stenting might be an option for optimal treatment in IRA lesions. Glycoprotein IIb/IIIa receptor inhibitor may not only maintain patency of the recanalized vessels but also may prevent embolization of platelet aggregates into the distal microcirculation.24 Glycoprotein IIb/IIIa receptor inhibitor was not used in this study. The role of glycoprotein IIb/IIIa receptor inhibitor in reducing late restenosis should also be further investigated in stenting of IRA lesions with poststent lumen CSA <7 mm2. The optimal treatment modalities for such a condition should be further evaluated. This study has several limitations. First, this was a retrospective study. Second, the impact of preintervention IVUS was not evaluated. Third, the results of this study could not be applied to patients with non–IVUSguided stenting because IVUS guidance might be related to a potential for selection bias. Fourth, the number of patients with acute myocardial infarction was small relative to that needed to suggest clinical implications. The groups of stenting for an IRA are in part heterogeneous: primary stenting within 12 hours of symptom onset in 45 of 87 patients and delayed stenting on the IRA within 7 to 10 days after onset in 42 of 87 patients. Finally, various kinds of stents were used in this study. We thank Jae-Yoon Ko, CVT, and other staff of the cardiac catheterization laboratory for their important contributions.
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7. Antoniucci D, Santoro GM, Bolognese L, et al. A clinical trial comparing primary stenting of the infarct-related artery with optimal primary angioplasty for acute myocardial infarction: results from the Florence randomized elective stenting in acute coronary occlusions (FRESCO) trial. J Am Coll Cardiol 1998;31:1234-9. 8. Stone GW, Brodie BG, Griffin JJ, et al. Clinical and angiographic follow-up after primary stenting in acute myocardial infarction: the primary angioplasty in myocardial infarction (PAMI) stent pilot trial. Circulation 1999;99:1548-54. 9. Hong MK, Park SW, Mintz GS, et al. Intravascular ultrasonic predictors of angiographic restenosis after long coronary stenting. Am J Cardiol 2000;85:441-5. 10. Tobis JM, Mallery J, Mahon D, et al. Intravascular ultrasound imaging of human coronary arteries in vivo: analysis of tissue characteristics with comparison to in vivo histologic specimens. Circulation 1991;83:913-26. 11. Nishimura RA, Edwards WD, Warnes CA, et al. Intravascular ultrasound imaging: in vitro validation and pathologic correlation. J Am Coll Cardiol 1990;16:145-54. 12. Hoffmann R, Mintz GS, Mehran R, et al. Intravascular ultrasound predictors of angiographic restenosis in lesions treated with PalmazSchatz stents. J Am Coll Cardiol 1998;31:43-9. 13. Kasaoka S, Tobis JM, Akiyama T, et al. Angiographic and intravascular ultrasound predictors of in-stent restenosis. J Am Coll Cardiol 1998;32:1630-5. 14. Moussa I, Moses J, Di Mario C, et al. Dose the specific intravascular ultrasound criterion used to optimize stent expansion have an impact on the probability of stent restenosis? Am J Cardiol 1999; 83:1012-7. 15. Fitzgerald PJ, Oshima A, Hayase M, et al. Final results of the can routine ultrasound influence stent expansion (CRUISE) study. Circulation 2000;102:523-30. 16. Antoniucci D, Valenti R, Santoro GM, et al. Primary coronary infarct artery stenting in acute myocardial infarction. Am J Cardiol 1999; 84:505-10. 17. Pasterkamp G, Falk E, Woutman H, et al. Techniques characterizing the coronary atherosclerotic plaque: influence on clinical decision making? J Am Coll Cardiol 2000;36:13-21. 18. Falk E. Stable versus unstable atherosclerosis: clinical aspects. Am Heart J 1999;138:S421-5. 19. Akiyama T, Moussa I, Reimers B, et al. Angiographic and clinical outcome following coronary stenting of small vessel: a comparison with coronary stenting of large vessels. J Am Coll Cardiol 1998; 32:1610-8. 20. Savage MP, Fischman DL, Rake R, et al. Efficacy of coronary stenting versus balloon angioplasty in small coronary arteries. J Am Coll Cardiol 1998;31:307-11. 21. Elezi S, Kastrati A, Neumann FJ, et al. Vessel size and long-term outcome after coronary stent placement. Circulation 1998;98:1875-80. 22. Foley DP, Melkert R, Serruys PW. Influence of coronary vessel size on renarrowing process and late angiographic outcome after successful balloon angioplasty. Circulation 1994;90:123951. 23. Park SW, Lee CW, Hong MK, et al. Randomized comparison of coronary stenting with optimal balloon angioplasty for treatment of lesions in small coronary arteries. Eur Heart J 2000;21:1785-9. 24. Neumann FJ, Blasini R, Schmitt C, et al. Effect of glycoprotein IIb/IIIa receptor blockade on recovery of coronary flow and left ventricular function after the placement of coronary-artery stents in acute myocardial infarction. Circulation 1998;98: 2695-701.