- Email: [email protected]
Incidence and mechanism of late stent malapposition after phosphorus-32 radioactive stent implantation
Incidence and Mechanism of Late Stent Malapposition After Phosphorus-32 Radioactive Stent Implantation Lukasz Kalinczuk, MD, Jerzy Pregowski, MD, Gary S. Mintz, MD, Christian E. Dilcher, MD, Jun-ichi Kotani, MD, Mariusz Kruk, MD, Vivek M. Shah, Daniel A. Canos, MPH, Rosana C. Chan, PhD, and Neil J. Weissman, MD Late stent malapposition is a potential complication of intracoronary brachytherapy. The aim of our study was to determine the incidence and mechanism of late stent malapposition after implantation of phosphorus-32 radioactive stents. We analyzed 159 patients for de novo lesions after the implantation of phosphorus-32 radioactive stents. There were 15 late stent malappositions. The incidence of malapposition was higher in patients who received Hot-Ends Isostents. External elastic membrane expansion greater than plaque increase in malapposed segments was observed. Late stent malapposition is caused by a localized increase in external elastic membrane that is greater than the increase in plaque area; this is believed to be a dose-dependent phenomenon because it was more common with HotEnds Isostents. 䊚2003 by Excerpta Medica, Inc. (Am J Cardiol 2003;92:970–972)
ate thrombosis and late stent malapposition have been reported after vascular brachytherapy. It L has been speculated that late thrombosis and late stent 1,2
malapposition may be related because struts separated from the vessel wall may provide a nidus for thrombus formation.1 The present report uses serial intravascular ultrasound (IVUS) to evaluate the frequency and mechanisms of late stent malappositon after implantation of radioactive stents. •••
We analyzed 159 patients with complete postinterventional and follow-up IVUS studies after implantation of phosphorus (P)-32 radioactive stents (Isostent, Belmont, California). The Isostent studies were open-label multicenter registries (Isostent for Restenosis Intervention Study [IRIS], European Dose Response Study, HotEnd Study, Cold-End Study, and so forth). Not all patients in these studies had complete serial IVUS; however, the present analysis included all of the patients in these studies who did have complete serial IVUS.2 Patients received P-32 radioactive Palmaz-Schatz or BX (Isostent) stents with activity levels of 0.9 to 20 Ci. At the time of manufacture, the original Isostents were categorized according to activity: 0.75 to 1.5 Ci (“low From the Cardiovascular Research Institute, Washington Hospital Center, Washington, DC; and the Cardiovascular Research Foundation, New York, New York. Drs. Kalinczuk and Pregowski were supported financially by an unrestricted educational travel grant from Guidant, Inc., Poland. Dr. Weissman’s address is: Washington Hospital Center, 110 Irving Street, NW, Suite 4B-1, Washington, DC 20010. E-mail: [email protected]. Manuscript received February 21, 2003; revised manuscript received and accepted June 23, 2003.
970
©2003 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 92 October 15, 2003
MS,
activity”), 3.0 to 6.0 Ci (“medium activity”), or 6.0 to 12.0 Ci (“high activity”). At the time of manufacture, the activity of the 18-mm long “Hot-End” Isostents was 8 Ci within the body and 10 Ci at the ends. IVUS was performed after the intracoronary administration of nitroglycerin 100 to 200 g using a commercially available system (Boston Scientific Corp., Maple Grove, Minnesota) and either 30- or 40-MHz mechanical (rotating) transducer catheter systems. The IVUS catheter was advanced distally to the lesion and withdrawn automatically at the constant speed of 0.5 mm/s. Stent malapposition was defined as separation of at least 1 stent strut from the arterial wall intima, not overlapping a side branch, with evidence of blood speckle behind the strut(s). First, follow-up IVUS studies were examined for the presence of stent malapposition. Afterward, baseline (postirradiation) tapes were reviewed to exclude cases with malapposition immediately or after Isostent implantation. Using perivascular and vascular landmarks and known pullback speeds, baseline and follow-up cross sections were matched, analyzed, and compared. Quantitative IVUS analyses were performed in patients with evidence of late stent malapposition using computerized planimetry (Tape Measure; Indec Systems, Capola, California). Measurements were performed for every 1 mm of the malapposed stent segment, including external elastic membrane, stent, intrastent luminal cross-sectional area, and area of malapposition. Plaque and media area and effective luminal area (intrastent lumen plus area of malapposition) were calculated. Volumetric analyses were performed using Simpson’s rule. The follow-up study was reviewed first to define the areas of late stent malapposition. Then the postimplantation study was reviewed to identify the image slices that corresponded to the area of subsequent late stent malapposition; this was facilitated by motorized transducer pullback because the distance from the edge of the stent could be measured in both studies. Finally, the postimplantation and follow-up image slices were rotated electronically so that circumferential vessel and perivessel landmarks could be aligned. The geometric center of the stent was identified, and the angle of late malapposition was measured with an electronic protractor centered on the geometric center of the stent. Control segments were 5 mm long with complete late stent apposition and were located ⬎5 mm from the edge of the malapposed stent segment, but still within the treated lesion. Control segments were analyzed similarly to malapposition segments. Continuous data are presented as mean ⫾ 1 SD, and categoric data are presented as proportions. We 0002-9149/03/$–see front matter doi:10.1016/S0002-9149(03)00980-9
TABLE 1 Intravascular Ultrasound (IVUS) Measurements in Isostent Patients Variable
Baseline
Follow-up
p Value
Malapposed segments Mean external elastic membrane area (mm2) 15.13 ⫾ 5.10 18.48 ⫾ 6.03 0.001 Mean intrastent luminal area (mm2) 7.40 ⫾ 2.67 6.78 ⫾ 2.36 0.006 Mean stent area (mm2) 7.40 ⫾ 2.67 7.55 ⫾ 2.86 0.3 Mean plaque and media area (mm2) 7.73 ⫾ 2.90 9.84 ⫾ 4.03 0.008 2 Mean effective luminal area (mm ) 7.40 ⫾ 2.67 8.64 ⫾ 2.66 0.001 Control segments* Mean external elastic membrane area (mm2) 16.07 ⫾ 4.00 17.39 ⫾ 5.13 0.075 Mean intrastent luminal area (mm2) 7.91 ⫾ 1.80 6.95 ⫾ 1.86 0.028 Mean stent area (mm2) 7.91 ⫾ 1.80 8.22 ⫾ 2.26 0.6 Mean plaque and media area (mm2) 8.17 ⫾ 2.83 9.17 ⫾ 3.08 0.039 *Segments with complete circumferential apposition ⬎5 mm from the malapposed segments.
used Wilcoxon’s nonparametric test, paired or unpaired Student’s t tests, or correlation coefficients for continuous variables and chi-square statistics or Fisher’s exact test for categoric variables. We identified 15 late stent malappositions (9.4%). There were 12 men, 3 women, and 1 patient with diabetes; patient age was 59.6 ⫾ 9.0 years. The incidence of late stent malapposition was higher in Hot-End Isostent than in original Isostent patients (20% vs 5.9%, p ⫽ 0.024). In the original Isostent patients, there was 1 late stent malapposition in the low-activity group, 4 in the medium-activity group, and 2 in the high-activity group (p ⫽ 0.0258). The location of late stent malapposition was within 5-mm long edges in 2 patients, edge and body in 3, and body alone in 2. In Hot-End Isostent patients, the location of late stent malapposition was at the edges in 2 patients, edge and body in 4, and body alone in 2. In 1 Hot-End Isostent patient, late stent malapposition was circumferential; in another Hot-End Isostent patient, late stent malapposition was nearly circumferential (305°). This extent of late stent malapposition was not seen in any of the regular Isostent patients. The length and volume of late stent malapposition were 5.2 ⫾ 3.36 mm and 12.84 ⫾ 12.79 mm3, respectively. Length and volume did not differ between original Isostents and Hot-End Isostents. Index and follow-up IVUS measurements for the Isostent group are listed in Table 1. Both mean external elastic membrane cross-sectional area and mean plaque and media increased within the malapposed segments; however, ⌬elastic membrane cross-sectional area was significantly larger than ⌬mean plaque and media (3.36 ⫾ 2.01 mm2 vs 2.11 ⫾ 2.46 mm2, p ⫽ 0.008). There was an increase in effective lumen at follow-up, although the intrastent lumen decreased because of intimal hyperplasia that developed over struts that were fully apposed. Change in mean external elastic membrane correlated with ⌬mean plaque and media (r ⫽ 0.81, p ⫽ 0.0002). Control and malapposed segments did not differ with regard to baseline external elastic membrane (p ⫽ 0.6), stent (p ⫽ 1.0), and plaque and media areas (p ⫽ 0.7). There was a tendency for mean elastic membrane cross-sectional area in control segments to increase as well as a statistically significant increase in mean plaque and media area. However, the degree of
positive remodeling (increase in external elastic membrane) was significantly larger for malapposed (24.1 ⫾ 11.3%) versus control segments (7.6 ⫾ 11.6%, p ⫽ 0.004), whereas the difference in plaque and media growth did not reach the level of significance (26.0 ⫾ 37.8% vs 14.3 ⫾ 20.1%, p ⫽ 0.3). There were no differences in baseline minimum and maximum plaque and media thickness comparing the late stent malapposed with fully apposed segments. •••
The present investigation shows that late stent malapposition after implantation of P-32 radioactive stents was more common in patients receiving Hot-End than original Isostents and, therefore, is presumably related to the activity. Potential mechanisms of late stent malapposition include vessel enlargement, stent recoil, thrombus resolution behind the struts, and plaque shrinkage caused by the antiproliferative effects of brachytherapy. We found that late stent malapposition occurred in segments of the vessel that showed more exaggerated positive remodeling in response to brachytherapy. There were no cases of stent recoil. In 3 patients (20%), there was a decrease in plaque and media in association with vessel expansion. Thus, although we identified 2 mechanisms leading to late stent malapposition after irradiation—(1) external elastic membrane enlargement greater than plaque increase or (2) external elastic membrane enlargement and plaque decrease—external elastic membrane enlargement is the common denominator. Compared with controls, intracoronary irradiation after angioplasty in animal models has been shown to inhibit adventitial myofibroblast proliferation in a dose-dependent manner and, therefore, facilitate positive arterial remodeling.3– 6 The present study disagrees somewhat with the article by Kay et al,7 who suggested that positive arterial remodeling occurs only after catheter-based brachytherapy and does not follow radioactive stent implantation. In their report, vessel enlargement was seen in segments with late stent malapposition, but not in control segments. Late stent malapposition segments are only a fraction of total stent length, and only a minority of stents develop late malapposition. Therefore, positive remodeling resulting in late stent malapposition would not be detected in a “global” volumetric IVUS analysis of the entire Isostent experience. This highlights the need to identify patients with unusual manifestations and analyze them separately.2 Recently, the frequency of late malapposition after placement of bare metal stents has been shown to be about 5%.8 The mechanism of late stent malapposition in these patients was positive arterial remodeling. This is consistent with reports by Nakamura et al9 and Hoffman et al,10 who found positive remodeling after bare stent implantation. These findings also indicate that the mechanism of late stent malapposition after brachytherapy is an exaggeration of the normal response. BRIEF REPORTS
971
1. Waksman R. Late thrombosis after radiation. Sitting on a time bomb. Circu-
lation 1999;100:780 –782. 2. Mintz GS, Weissman NJ, Fitzgerald PJ. Intravascular ultrasound assessment of the mechanisms and results of brachytherapy. Circulation 2001;104:1320 –1325. 3. Cottin Y, Kollum M, Chan RC, Kim H, Bhargava B, Vodovotz Y, Waksman R. Differential remodeling after balloon overstretch injury and either beta- or gamma-intracoronary radiation of porcine coronary arteries. Cardiovasc Radiat Med 2001;2:75–82. 4. Scott NA, Cipolla GD, Ross CE, Dunn B, Martin FH, Simonet L, Wilcox JN. Identification of a potential role for the adventitia in vascular lesion formation after balloon overstretch injury of porcine coronary arteries. Circulation 1996; 93:2178 –2187. 5. Waksman R, Rodriguez JC, Robinson KA, Cipolla GD, Crocker IR, Scott NA, King SB III, Wilcox JN. Effect of intravascular irradiation on cell proliferation, apoptosis, and vascular remodeling after balloon overstretch injury of porcine coronary arteries. Circulation 1997;96:1944 –1952. 6. Wilcox JN, Waksman R, King SB, Scott NA. The role of the adventitia in the
arterial response to angioplasty: the effect of intravascular radiation. Int J Radiat Oncol Biol Phy 1996;36:789 –796. 7. Kay IP, Sabate M, Costa MA, Kozuma K, Albertal M, van der Giessen WJ, Wardeh AJ, Ligthart JM, Coen VM, Levendag PC, Serruys PW. Positive geometric vascular remodeling is seen after catheter-based radiation followed by conventional stent implantation but not after radioactive stent implantation. Circulation 2000;102:1434 –1439. 8. Shah V, Mintz GS, Apple S, Weissman NJ. Background incidence of late malapposition after bare-metal stent implantation. Circulation 2002;106:1753– 1755. 9. Nakamura M, Yock PG, Bonneau HN, Kitamura K, Aizawa T, Tamai H, Fitzgerald PJ, Honda Y. Impact of peri-stent remodeling on restenosis: a volumetric intravascular ultrasound study. Circulation 2001;103:2130 –2132. 10. Hoffmann R, Mintz GS, Popma JJ, Satler LF, Pichard AD, Kent KM, Walsh C, Mackell P, Leon MB. Chronic arterial responses to stent implantation: a serial intravascular ultrasound analysis of Palmaz-Schatz stents in native coronary arteries. J Am Coll Cardiol 1996;28:1134 –1139.
Impact of Extracardiac Vascular Disease on Acute Prognosis in Patients Who Undergo Percutaneous Coronary Interventions (Data from the Blue Cross & Blue Shield of Michigan Cardiovascular Consortium [BMC2]) Debabrata Mukherjee, MD, MS, Kim A. Eagle, MD, Dean E. Smith, PhD, Eva M. Kline-Rogers, RN, Stanley Chetcuti, MD, P. Michael Grossman, MD, Brahmajee Nallamothu, MD, Michael O’Donnell, MD, Anthony DeFranco, MD, Ann Maxwell-Eward, PhD, John McGinnity, MS, William M. Meengs, MD, Kirit Patel, MD, and Mauro Moscucci, MD, on behalf of the Blue Cross & Blue Shield of Michigan Cardiovascular Consortium (BMC2) Extracardiac vascular disease is associated with an increased risk of in-hospital mortality and other complications after coronary interventions, independent from other co-morbidities and baseline characteristics. The underlying cause of this significant association is unclear, but it warrants further investigation in an attempt to improve outcome in this high-risk cohort. 䊚2003 by Excerpta Medica, Inc. (Am J Cardiol 2003;92:972–974)
revious studies with small numbers of patients have demonstrated a significantly higher incidence of P periprocedural complications in patients with extracardiac vascular disease (ECVD) undergoing coronary revascularization.1–3 However, it is not well understood if the increased risk is related to ECVD itself or to associated baseline characteristics and co-morbidities. The purpose of the present report was to perform a detailed evaluation of the impact of ECVD on acute outcomes after percutaneous coronary interventions (PCIs) and to determine if the increased risk for periprocedural events From the University of Michigan Health System, Ann Arbor; St. Joseph Mercy Hospital, Ann Arbor; McLaren Regional Medical Center, Flint; Spectrum Health, Grand Rapids; Harper Hospital, Detroit; and Northern Michigan Hospital, Petoskey, Michigan. Dr. Moscucci’s address is: Division of Cardiology, University of Michigan Health System, University Hospital, TC B1-226, 1500 East Medical Center Drive, Ann Arbor, Michigan 48103-0311. E-mail: [email protected]. Manuscript received April 3, 2003; revised manuscript received and accepted June 19, 2003.
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©2003 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 92 October 15, 2003
is secondary to ECVD per se or to increased co-morbid conditions associated with ECVD. •••
The study sample consisted of 25,144 patients who underwent coronary interventions between July 1997 and December 2001 in a consortium of 9 hospitals. The consortium included 3 academic centers, 5 tertiary referral centers, and 1 community hospital. Clinical, procedural, and outcome data were collected prospectively using a standardized data collection form agreed to by the participating centers. ECVD was a clinical diagnosis and made based on the presence of any of the following: history of abnormal ankle– brachial indexes, claudication, amputation for arterial insufficiency, lower extremity revascularization or reconstruction, abdominal aortic aneurysm, history of cerebrovascular accident, reversible ischemic neurologic defect, transient ischemic attack, or documented asymptomatic carotid artery stenosis ⬎75%. Of the 25,144 patients, 4,294 (17.4%) had a history of ECVD. Coronary artery stenoses were classified according to the modified American College of Cardiology/American Heart Association classification.4 The study was approved by the Institutional Review Board of the University of Michigan and by local institutional review boards. The structure of the consortium and the data collection process have been described elsewhere.5,6 Baseline demographics (including age and sex), co-morbidities, and procedural and outcome data were recorded in every case. Among the other data ele0002-9149/03/$–see front matter doi:10.1016/S0002-9149(03)00981-0
ate thrombosis and late stent malapposition have been reported after vascular brachytherapy. It L has been speculated that late thrombosis and late stent 1,2
malapposition may be related because struts separated from the vessel wall may provide a nidus for thrombus formation.1 The present report uses serial intravascular ultrasound (IVUS) to evaluate the frequency and mechanisms of late stent malappositon after implantation of radioactive stents. •••
We analyzed 159 patients with complete postinterventional and follow-up IVUS studies after implantation of phosphorus (P)-32 radioactive stents (Isostent, Belmont, California). The Isostent studies were open-label multicenter registries (Isostent for Restenosis Intervention Study [IRIS], European Dose Response Study, HotEnd Study, Cold-End Study, and so forth). Not all patients in these studies had complete serial IVUS; however, the present analysis included all of the patients in these studies who did have complete serial IVUS.2 Patients received P-32 radioactive Palmaz-Schatz or BX (Isostent) stents with activity levels of 0.9 to 20 Ci. At the time of manufacture, the original Isostents were categorized according to activity: 0.75 to 1.5 Ci (“low From the Cardiovascular Research Institute, Washington Hospital Center, Washington, DC; and the Cardiovascular Research Foundation, New York, New York. Drs. Kalinczuk and Pregowski were supported financially by an unrestricted educational travel grant from Guidant, Inc., Poland. Dr. Weissman’s address is: Washington Hospital Center, 110 Irving Street, NW, Suite 4B-1, Washington, DC 20010. E-mail: [email protected]. Manuscript received February 21, 2003; revised manuscript received and accepted June 23, 2003.
970
©2003 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 92 October 15, 2003
MS,
activity”), 3.0 to 6.0 Ci (“medium activity”), or 6.0 to 12.0 Ci (“high activity”). At the time of manufacture, the activity of the 18-mm long “Hot-End” Isostents was 8 Ci within the body and 10 Ci at the ends. IVUS was performed after the intracoronary administration of nitroglycerin 100 to 200 g using a commercially available system (Boston Scientific Corp., Maple Grove, Minnesota) and either 30- or 40-MHz mechanical (rotating) transducer catheter systems. The IVUS catheter was advanced distally to the lesion and withdrawn automatically at the constant speed of 0.5 mm/s. Stent malapposition was defined as separation of at least 1 stent strut from the arterial wall intima, not overlapping a side branch, with evidence of blood speckle behind the strut(s). First, follow-up IVUS studies were examined for the presence of stent malapposition. Afterward, baseline (postirradiation) tapes were reviewed to exclude cases with malapposition immediately or after Isostent implantation. Using perivascular and vascular landmarks and known pullback speeds, baseline and follow-up cross sections were matched, analyzed, and compared. Quantitative IVUS analyses were performed in patients with evidence of late stent malapposition using computerized planimetry (Tape Measure; Indec Systems, Capola, California). Measurements were performed for every 1 mm of the malapposed stent segment, including external elastic membrane, stent, intrastent luminal cross-sectional area, and area of malapposition. Plaque and media area and effective luminal area (intrastent lumen plus area of malapposition) were calculated. Volumetric analyses were performed using Simpson’s rule. The follow-up study was reviewed first to define the areas of late stent malapposition. Then the postimplantation study was reviewed to identify the image slices that corresponded to the area of subsequent late stent malapposition; this was facilitated by motorized transducer pullback because the distance from the edge of the stent could be measured in both studies. Finally, the postimplantation and follow-up image slices were rotated electronically so that circumferential vessel and perivessel landmarks could be aligned. The geometric center of the stent was identified, and the angle of late malapposition was measured with an electronic protractor centered on the geometric center of the stent. Control segments were 5 mm long with complete late stent apposition and were located ⬎5 mm from the edge of the malapposed stent segment, but still within the treated lesion. Control segments were analyzed similarly to malapposition segments. Continuous data are presented as mean ⫾ 1 SD, and categoric data are presented as proportions. We 0002-9149/03/$–see front matter doi:10.1016/S0002-9149(03)00980-9
TABLE 1 Intravascular Ultrasound (IVUS) Measurements in Isostent Patients Variable
Baseline
Follow-up
p Value
Malapposed segments Mean external elastic membrane area (mm2) 15.13 ⫾ 5.10 18.48 ⫾ 6.03 0.001 Mean intrastent luminal area (mm2) 7.40 ⫾ 2.67 6.78 ⫾ 2.36 0.006 Mean stent area (mm2) 7.40 ⫾ 2.67 7.55 ⫾ 2.86 0.3 Mean plaque and media area (mm2) 7.73 ⫾ 2.90 9.84 ⫾ 4.03 0.008 2 Mean effective luminal area (mm ) 7.40 ⫾ 2.67 8.64 ⫾ 2.66 0.001 Control segments* Mean external elastic membrane area (mm2) 16.07 ⫾ 4.00 17.39 ⫾ 5.13 0.075 Mean intrastent luminal area (mm2) 7.91 ⫾ 1.80 6.95 ⫾ 1.86 0.028 Mean stent area (mm2) 7.91 ⫾ 1.80 8.22 ⫾ 2.26 0.6 Mean plaque and media area (mm2) 8.17 ⫾ 2.83 9.17 ⫾ 3.08 0.039 *Segments with complete circumferential apposition ⬎5 mm from the malapposed segments.
used Wilcoxon’s nonparametric test, paired or unpaired Student’s t tests, or correlation coefficients for continuous variables and chi-square statistics or Fisher’s exact test for categoric variables. We identified 15 late stent malappositions (9.4%). There were 12 men, 3 women, and 1 patient with diabetes; patient age was 59.6 ⫾ 9.0 years. The incidence of late stent malapposition was higher in Hot-End Isostent than in original Isostent patients (20% vs 5.9%, p ⫽ 0.024). In the original Isostent patients, there was 1 late stent malapposition in the low-activity group, 4 in the medium-activity group, and 2 in the high-activity group (p ⫽ 0.0258). The location of late stent malapposition was within 5-mm long edges in 2 patients, edge and body in 3, and body alone in 2. In Hot-End Isostent patients, the location of late stent malapposition was at the edges in 2 patients, edge and body in 4, and body alone in 2. In 1 Hot-End Isostent patient, late stent malapposition was circumferential; in another Hot-End Isostent patient, late stent malapposition was nearly circumferential (305°). This extent of late stent malapposition was not seen in any of the regular Isostent patients. The length and volume of late stent malapposition were 5.2 ⫾ 3.36 mm and 12.84 ⫾ 12.79 mm3, respectively. Length and volume did not differ between original Isostents and Hot-End Isostents. Index and follow-up IVUS measurements for the Isostent group are listed in Table 1. Both mean external elastic membrane cross-sectional area and mean plaque and media increased within the malapposed segments; however, ⌬elastic membrane cross-sectional area was significantly larger than ⌬mean plaque and media (3.36 ⫾ 2.01 mm2 vs 2.11 ⫾ 2.46 mm2, p ⫽ 0.008). There was an increase in effective lumen at follow-up, although the intrastent lumen decreased because of intimal hyperplasia that developed over struts that were fully apposed. Change in mean external elastic membrane correlated with ⌬mean plaque and media (r ⫽ 0.81, p ⫽ 0.0002). Control and malapposed segments did not differ with regard to baseline external elastic membrane (p ⫽ 0.6), stent (p ⫽ 1.0), and plaque and media areas (p ⫽ 0.7). There was a tendency for mean elastic membrane cross-sectional area in control segments to increase as well as a statistically significant increase in mean plaque and media area. However, the degree of
positive remodeling (increase in external elastic membrane) was significantly larger for malapposed (24.1 ⫾ 11.3%) versus control segments (7.6 ⫾ 11.6%, p ⫽ 0.004), whereas the difference in plaque and media growth did not reach the level of significance (26.0 ⫾ 37.8% vs 14.3 ⫾ 20.1%, p ⫽ 0.3). There were no differences in baseline minimum and maximum plaque and media thickness comparing the late stent malapposed with fully apposed segments. •••
The present investigation shows that late stent malapposition after implantation of P-32 radioactive stents was more common in patients receiving Hot-End than original Isostents and, therefore, is presumably related to the activity. Potential mechanisms of late stent malapposition include vessel enlargement, stent recoil, thrombus resolution behind the struts, and plaque shrinkage caused by the antiproliferative effects of brachytherapy. We found that late stent malapposition occurred in segments of the vessel that showed more exaggerated positive remodeling in response to brachytherapy. There were no cases of stent recoil. In 3 patients (20%), there was a decrease in plaque and media in association with vessel expansion. Thus, although we identified 2 mechanisms leading to late stent malapposition after irradiation—(1) external elastic membrane enlargement greater than plaque increase or (2) external elastic membrane enlargement and plaque decrease—external elastic membrane enlargement is the common denominator. Compared with controls, intracoronary irradiation after angioplasty in animal models has been shown to inhibit adventitial myofibroblast proliferation in a dose-dependent manner and, therefore, facilitate positive arterial remodeling.3– 6 The present study disagrees somewhat with the article by Kay et al,7 who suggested that positive arterial remodeling occurs only after catheter-based brachytherapy and does not follow radioactive stent implantation. In their report, vessel enlargement was seen in segments with late stent malapposition, but not in control segments. Late stent malapposition segments are only a fraction of total stent length, and only a minority of stents develop late malapposition. Therefore, positive remodeling resulting in late stent malapposition would not be detected in a “global” volumetric IVUS analysis of the entire Isostent experience. This highlights the need to identify patients with unusual manifestations and analyze them separately.2 Recently, the frequency of late malapposition after placement of bare metal stents has been shown to be about 5%.8 The mechanism of late stent malapposition in these patients was positive arterial remodeling. This is consistent with reports by Nakamura et al9 and Hoffman et al,10 who found positive remodeling after bare stent implantation. These findings also indicate that the mechanism of late stent malapposition after brachytherapy is an exaggeration of the normal response. BRIEF REPORTS
971
1. Waksman R. Late thrombosis after radiation. Sitting on a time bomb. Circu-
lation 1999;100:780 –782. 2. Mintz GS, Weissman NJ, Fitzgerald PJ. Intravascular ultrasound assessment of the mechanisms and results of brachytherapy. Circulation 2001;104:1320 –1325. 3. Cottin Y, Kollum M, Chan RC, Kim H, Bhargava B, Vodovotz Y, Waksman R. Differential remodeling after balloon overstretch injury and either beta- or gamma-intracoronary radiation of porcine coronary arteries. Cardiovasc Radiat Med 2001;2:75–82. 4. Scott NA, Cipolla GD, Ross CE, Dunn B, Martin FH, Simonet L, Wilcox JN. Identification of a potential role for the adventitia in vascular lesion formation after balloon overstretch injury of porcine coronary arteries. Circulation 1996; 93:2178 –2187. 5. Waksman R, Rodriguez JC, Robinson KA, Cipolla GD, Crocker IR, Scott NA, King SB III, Wilcox JN. Effect of intravascular irradiation on cell proliferation, apoptosis, and vascular remodeling after balloon overstretch injury of porcine coronary arteries. Circulation 1997;96:1944 –1952. 6. Wilcox JN, Waksman R, King SB, Scott NA. The role of the adventitia in the
arterial response to angioplasty: the effect of intravascular radiation. Int J Radiat Oncol Biol Phy 1996;36:789 –796. 7. Kay IP, Sabate M, Costa MA, Kozuma K, Albertal M, van der Giessen WJ, Wardeh AJ, Ligthart JM, Coen VM, Levendag PC, Serruys PW. Positive geometric vascular remodeling is seen after catheter-based radiation followed by conventional stent implantation but not after radioactive stent implantation. Circulation 2000;102:1434 –1439. 8. Shah V, Mintz GS, Apple S, Weissman NJ. Background incidence of late malapposition after bare-metal stent implantation. Circulation 2002;106:1753– 1755. 9. Nakamura M, Yock PG, Bonneau HN, Kitamura K, Aizawa T, Tamai H, Fitzgerald PJ, Honda Y. Impact of peri-stent remodeling on restenosis: a volumetric intravascular ultrasound study. Circulation 2001;103:2130 –2132. 10. Hoffmann R, Mintz GS, Popma JJ, Satler LF, Pichard AD, Kent KM, Walsh C, Mackell P, Leon MB. Chronic arterial responses to stent implantation: a serial intravascular ultrasound analysis of Palmaz-Schatz stents in native coronary arteries. J Am Coll Cardiol 1996;28:1134 –1139.
Impact of Extracardiac Vascular Disease on Acute Prognosis in Patients Who Undergo Percutaneous Coronary Interventions (Data from the Blue Cross & Blue Shield of Michigan Cardiovascular Consortium [BMC2]) Debabrata Mukherjee, MD, MS, Kim A. Eagle, MD, Dean E. Smith, PhD, Eva M. Kline-Rogers, RN, Stanley Chetcuti, MD, P. Michael Grossman, MD, Brahmajee Nallamothu, MD, Michael O’Donnell, MD, Anthony DeFranco, MD, Ann Maxwell-Eward, PhD, John McGinnity, MS, William M. Meengs, MD, Kirit Patel, MD, and Mauro Moscucci, MD, on behalf of the Blue Cross & Blue Shield of Michigan Cardiovascular Consortium (BMC2) Extracardiac vascular disease is associated with an increased risk of in-hospital mortality and other complications after coronary interventions, independent from other co-morbidities and baseline characteristics. The underlying cause of this significant association is unclear, but it warrants further investigation in an attempt to improve outcome in this high-risk cohort. 䊚2003 by Excerpta Medica, Inc. (Am J Cardiol 2003;92:972–974)
revious studies with small numbers of patients have demonstrated a significantly higher incidence of P periprocedural complications in patients with extracardiac vascular disease (ECVD) undergoing coronary revascularization.1–3 However, it is not well understood if the increased risk is related to ECVD itself or to associated baseline characteristics and co-morbidities. The purpose of the present report was to perform a detailed evaluation of the impact of ECVD on acute outcomes after percutaneous coronary interventions (PCIs) and to determine if the increased risk for periprocedural events From the University of Michigan Health System, Ann Arbor; St. Joseph Mercy Hospital, Ann Arbor; McLaren Regional Medical Center, Flint; Spectrum Health, Grand Rapids; Harper Hospital, Detroit; and Northern Michigan Hospital, Petoskey, Michigan. Dr. Moscucci’s address is: Division of Cardiology, University of Michigan Health System, University Hospital, TC B1-226, 1500 East Medical Center Drive, Ann Arbor, Michigan 48103-0311. E-mail: [email protected]. Manuscript received April 3, 2003; revised manuscript received and accepted June 19, 2003.
972
©2003 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 92 October 15, 2003
is secondary to ECVD per se or to increased co-morbid conditions associated with ECVD. •••
The study sample consisted of 25,144 patients who underwent coronary interventions between July 1997 and December 2001 in a consortium of 9 hospitals. The consortium included 3 academic centers, 5 tertiary referral centers, and 1 community hospital. Clinical, procedural, and outcome data were collected prospectively using a standardized data collection form agreed to by the participating centers. ECVD was a clinical diagnosis and made based on the presence of any of the following: history of abnormal ankle– brachial indexes, claudication, amputation for arterial insufficiency, lower extremity revascularization or reconstruction, abdominal aortic aneurysm, history of cerebrovascular accident, reversible ischemic neurologic defect, transient ischemic attack, or documented asymptomatic carotid artery stenosis ⬎75%. Of the 25,144 patients, 4,294 (17.4%) had a history of ECVD. Coronary artery stenoses were classified according to the modified American College of Cardiology/American Heart Association classification.4 The study was approved by the Institutional Review Board of the University of Michigan and by local institutional review boards. The structure of the consortium and the data collection process have been described elsewhere.5,6 Baseline demographics (including age and sex), co-morbidities, and procedural and outcome data were recorded in every case. Among the other data ele0002-9149/03/$–see front matter doi:10.1016/S0002-9149(03)00981-0