Incidence, Mechanisms, Predictors, and Clinical Impact of Acute and Late Stent Malapposition After Primary Intervention in Patients With Acute Myocardial Infarction
An Intravascular Ultrasound Substudy of the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) Trial
Background—The incidence and mechanisms of acute and late stent malapposition after primary stent implantation in ST-segment elevation myocardial infarction remain unclear.
Methods and Results—The Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial was a dual-arm, factorial, randomized trial comparing paclitaxel-eluting stents (PES) and otherwise equivalent bare metal stents (BMS) in ST-segment elevation myocardial infarction patients. The intravascular ultrasound substudy enrolled 241 patients with 263 native coronary lesions (201 PES, 62 BMS) with baseline and 13-month follow-up imaging. Postintervention acute stent malapposition (ASM) occurred in 34.3% PES- and 40.3% BMS-treated lesions. Of these, 39.1% PES- and 40.0% BMS-treated lesions resolved at follow-up, especially within the stent body (66.7%); complete resolution was accompanied by a reduction in external elastic membrane area. An ASM area >1.2 mm2 best separated persistent from resolved ASM. At follow-up, a higher frequency of late stent malapposition was detected in PES-treated lesions (46.8%) mainly because of more late acquired stent malapposition (30.8%) compared with BMS-treated lesions. Late acquired stent malapposition area correlated to the decrease of peri-stent plaque in the subset of lesions without positive remodeling and only to change in external elastic membrane in the group with positive remodeling. Independent predictors of late acquired stent malapposition were plaque/thrombus protrusion (odds ratio, 5.60; 95% confidence interval [CI], 2.32 to 13.54) and PES use (odds ratio, 6.32; 95% CI, 2.15 to 18.62).
Conclusions—The incidence of ASM was similar in PES- and BMS-treated lesions, but late acquired stent malapposition was more common in PES-treated lesions. The reason for resolved ASM was negative remodeling, with larger ASM areas separating persistent from resolved ASM. Late acquired stent malapposition was due mainly to positive remodeling and plaque/thrombus resolution.
Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00433966.
Received August 31, 2009; accepted June 30, 2010.
The prognosis for patients with acute myocardial infarction (AMI) has been improved by primary percutaneous coronary intervention.1,2 Compared with balloon angioplasty, implantation of bare metal stents (BMS) or drug-eluting stents (DES) during primary percutaneous coronary intervention decreases subsequent target vessel revascularization and restenosis.3–5 However, inconsistent results have been presented on the safety of DES in ST-elevation MI (STEMI) patients.4,5 In particular, there is an increased frequency of stent malapposition after DES implantation that may lead to late stent thrombosis (ST) and other adverse clinical outcomes.6,7 The aims of the present study were to determine the incidence of acute (ASM) and late stent malapposition (LSM) after primary paclitaxel-eluting stent (PES) or BMS implantation in AMI, to identify mechanisms and predictors of ASM progression or resolution in AMI, to identify mechanisms and predictors of late acquired stent malapposition (LASM) in AMI, and to evaluate the 1-year clinical impact of ASM and LSM in AMI.
Clinical Perspective on p 1084
The Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial was a prospective, open-label, multicenter, dual-arm, 2×2 factorial, randomized trial in patients with STEMI presenting <12 hours after symptom onset and undergoing primary percutaneous coronary intervention. The 2 randomization arms consisted of (1) the direct thrombin inhibitor bivalirudin alone versus heparin plus a glycoprotein IIb/IIIa inhibitor (1:1 randomization) and (2) paclitaxel-eluting TAXUS stents versus otherwise equivalent EXPRESS BMS (3:1 randomization; both Boston Scientific Corp, Natick, Mass). This study was performed in accordance with the Code of Federal Regulations and the Declaration of Helsinki with regard to investigation in humans, and the study protocol was approved by the Institutional Review Board or Medical Ethics Committee at each participating center. Written informed consent was obtained from all patients before cardiac catheterization.
Among patients undergoing stent randomization, 13-month angiographic follow-up was prespecified for 1800 patients in whom acute stent implantation was successful (diameter stenosis <10% with Thrombolysis in Myocardial Infarction grade 3 flow and National Heart, Lung, and Blood Institute type A peri-stent dissection or less) and in whom neither ST occurred nor bypass surgery was performed within 30 days. Stent randomization required the presence of ≥1 infarct artery (estimated angiographic reference diameter, 2.25 to 4.0 mm) in which all significant lesions could be treated with study stents. Intravascular ultrasound (IVUS) sites were preselected on the basis of their desire to participate in the IVUS substudy and their agreement to perform baseline (poststent) and follow-up IVUS on consecutive patients in the angiographic follow-up cohort until at least 300 consecutive IVUS cases were completed. Follow-up IVUS was performed at 13 months unless restenosis or ST occurred earlier. The clinical end point of the present study was 1-year safety major adverse cardiac event rate, including death, reinfarction, stroke, or ST. The components of safety major adverse cardiac events have been defined previously.8
IVUS Imaging and Analysis
IVUS was performed after successful, uncomplicated stent implantation. Allowable IVUS systems included iLab, Galaxy, ClearView (all with Atlantis SR Pro, 40-MHz catheters; Boston Scientific, Fremont, Calif), and In Vision Gold with 20-MHz EagleEye catheters (Volcano Therapeutics, Rancho Cordova, Calif). IVUS imaging was performed with motorized pullback at 0.5 mm/s to include the stent and >5 mm segments proximal and distal to the stent. All IVUS studies were archived onto super-VHS tape, CD-ROM, or DVD and sent to the IVUS core laboratory (Cardiovascular Research Foundation, New York, NY) for offline quantitative and qualitative analyses by individuals blinded to treatment allocation. Quantitative analysis was performed with validated planimetry software (EchoPlaque, INDEC Systems, Inc, Mountain View, Calif). IVUS measurements were performed millimeter by millimeter beginning 5 mm distal to the distal stent edge and continuing through the stent to a point 5 mm proximal to the proximal stent edge, including external elastic membrane (EEM), stent, lumen, plaque and media (P&M=EEM−lumen in reference segments and EEM−stent minus malapposition within the stent), neointimal hyperplasia (NIH=stent−intrastent lumen), and malapposition cross-sectional areas (CSA). Volumes were calculated with the Simpson rule and normalized for lengths to calculate mean areas.
Stent malapposition, synonymous with incomplete stent apposition, was blood speckle behind stent struts not overlying a side-branch. Stent malapposition could be ASM (occurring at the time of stent implantation) or LSM (detected at follow-up). If malapposition was noticed after stent implantation but absent at follow-up, it was defined as resolved; otherwise, it was persistent. LSM was classified as LASM if it was not present immediately after the procedure but occurred during follow-up or as persistent if it was present at both baseline and follow-up. The circumferential location of stent malapposition was classified as adjacent to either normal arterial wall (monolayer or P&M thickness <0.5 mm) or atherosclerotic plaque. The longitudinal location of stent malapposition was at or adjacent to the stent edges (<5 mm from the proximal or distal edge of the stent) or within the stent body. Stent malappositions were considered separate if there was a gap of ≥5 mm between them. The follow-up study was reviewed to select the image slice with the largest LSM area; then, the postintervention study was reviewed to identify the corresponding image slice. Similarly, the postintervention study was reviewed independently to select the image slice with the largest ASM area; and the follow-up study was reviewed to identify the corresponding image slice. Thus, each measurement at baseline and follow-up was obtained at the same level of the vessel, the levels corresponding to the maximal malapposition areas at baseline and at follow-up.
Statistical analysis was performed with SAS software, version 9.1 (SAS Institute Inc, Cary, NC). For patient-level data, categorical variables were presented as frequencies and compared with χ2 statistics or the Fisher exact test (if there was an expected cell value <5) and continuous variables were presented as median (quartiles 1 to 3) and compared by use of the Mann–Whitney U test. For malapposition or lesion-level data, a model with generalized estimating equation (GEE) approach was used to compensate for any potential cluster effect of multiple malappositions in the same lesion or multiple lesions in the same patient and presented as least square means with 95% CIs. Receiver-operating curve analysis was used to identify the cutoff value best separating persistent from resolved ASM. To identify independent predictors of LASM, clinical and IVUS variables with values of P<0.2 were entered into the multiple logistic regression model with GEEs. A value of P <0.05 was considered statistically significant.
Baseline Patient Characteristics
Among 389 patients with 429 analyzable lesions in the HORIZONS-AMI IVUS substudy, 245 patients with 268 lesions had paired (both poststenting and follow-up) IVUS images. After exclusion of 5 lesions (4 patients) in which stents were implanted in a bypass graft, 241 patients (184 PES, 57 BMS) with 263 native coronary lesions (201 PES, 62 BMS) were available for this study (Figure 1). There was no difference in use of bivalirudin (50.0% versus 52.7%; P=0.4) or PES (75.1% versus 76.3%; P=0.7) in the overall HORIZONS-AMI population versus IVUS substudy patients. Baseline patient characteristics are shown in Table 1. Patient age, sex, risk factors of coronary artery disease, culprit vessel, and Thrombolysis in Myocardial Infarction flow grade before intervention were similar between PES and BMS recipients.
Acute Stent Malapposition
Postintervention ASM was detected in 69 lesions in 65 patients treated with PES and in 25 lesions in 24 patients treated with BMS (34.3% versus 40.3%; P=0.460). Multiple separate sites of ASM were noticed in 26 lesions (27.7% overall; 29.0% in PES versus 24.0% in BMS; P=0.774).
In 27 PES-treated lesions and 10 BMS-treated lesions, ASM resolved at follow-up (39.1% versus 40.0%; P=0.960). In PES-treated and BMS-treated lesions, complete resolution or reduction in maximum ASM CSA was accompanied by reduction in EEM CSA (BMS, from 21.2 mm2 [17.9 to 25.1 mm2] to 18.8 mm2 [17.7 to 22.5 mm2]; P=0.022; PES, from 18.0 mm2 [16.6 to 22.0 mm2] to 17.6 mm2 [15.5 to 20.3 mm2]; P=0.005) that was not seen at sites of persistent stent malapposition (Figure 2); however, P&M CSA did not change during follow-up in either BMS-treated (from 9.8 mm2 [7.4 to 11.6 mm2] to 10.3 mm2 [7.5 to 11.4 mm2]; P=0.454) or PES-treated lesions (from 8.6 mm2 [6.7 to 10.4 mm2] to 8.5 mm2 [7.2 to 10.2 mm2]; P=0.150). Overall, the change in malapposition CSA correlated with the change in EEM area (r=0.413, P<0.001) but not with the change in P&M (r=−0.174, P=0.057).
As presented in Table 2, compared with the persistent group, intrastent lumen area at the maximal malapposition site significantly decreased during follow-up in the resolved group mainly because of more NIH. Most areas of resolved ASM (66.7%) were located within the stent body, whereas most areas of persistent ASM (67.6%) were located at stent edges (P<0.001). ASM and EEM CSAs at the maximal malapposition site were significantly larger in the persistent than in the resolved group. Receiver-operating curve analysis identified an ASM area >1.2 mm2 (area under the curve, 0.688; 95% CI, 0.598 to 0.779) as separating persistent from resolved ASM.
Late Stent Malapposition
At follow-up, LSM was detected in 94 lesions (46.8%) treated with PES and 18 lesions (29.0%) treated with BMS (P=0.007; Figure 1). Of these, 42 lesions in the PES cohort and 15 lesions in the BMS cohort had ASM that persisted from implantation (P=0.630). LASM was documented in 62 lesions (30.8%) treated with PES and 5 lesions (8.1%) treated with BMS (P=0.023). Both persistent ASM and LASM can be detected within the same lesion if they are at different locations, as was seen in 5.0% of PES-treated and 3.2% of BMS-treated lesions. Among lesions that presented with LSM, there were 148 distinct malapposition sites; 80 late malapposition sites were acquired, and the rest persisted from implantation (BMS, 16; PES, 52). Among the 80 LASM sites, 60 had an increase in EEM CSA, and 20 did not. The malapposition CSAs of these 3 groups were similar (data not shown). Although a malapposition CSA <3.0 mm2 was seen in the LASM sites associated with an increase in EEM area, a malapposition CSA ≥3.0 mm2 was not seen in any of the 20 LASM sites associated with no increase in EEM area (Figure 3).
Late Acquired Stent Malapposition
At follow-up, a single site of LASM was seen in 52 PES- and 5 BMS-treated lesions; multiple sites were seen in 10 PES-treated but in no BMS-treated lesions. Overall, 75% of LASM sites were in stent bodies, and 25% were at stent edges.
Poststenting and follow-up IVUS analyses in PES- and BMS-treated lesions with versus without LASM are shown in Table 3. There was no difference in baseline stent length, proximal or distal reference lumen area, and minimum lumen area between LASM and non-LASM. However, intrastent plaque/thrombus protrusion through stent struts was more common in LASM (88.1% versus 60.2%; P<0.001), as was the percentage of PES implanted (92.5% versus 70.9%; P=0.023). At follow-up, the minimum lumen area was significantly smaller in the non-LASM group mainly because of more NIH.
Patients with LASM were then divided into 2 groups: those with an increase in EEM CSA (positive remodeling) and those with no change or a decrease in EEM CSA (Table 4). LASM and NIH CSAs and the location of the malapposition site (stent body versus edges) were similar between these 2 subgroups. Plaque/thrombus protrusion was more frequent in the group without positive remodeling (55.0% versus 26.7%; P=0.015). Most sites of LASM were circumferentially located adjacent to plaque in the group without positive remodeling (90.0% versus 53.3%; P=0.003), whereas sites of LASM were equally located adjacent to plaque or normal arterial wall in the group with positive remodeling (Table 4 and Figure 2). P&M CSA decreased significantly in the group without positive remodeling; conversely, P&M CSA increased significantly in group with an increase in EEM. Overall, LASM area correlated to the increase in EEM (r=0.324, P=0.004) but not to any change in P&M (r=−0.055, P=0.630). However, LASM CSA did correlate to P&M decrease (r=−0.714, P=0.001) and not to the change in EEM (r=−0.435, P=0.062) but only in the subset of lesions without positive remodeling. Conversely, LASM area correlated only to the increase in EEM (r=0.475, P<0.001) but not to the change in P&M (r=−0.017, P=0.898) in the group with positive remodeling.
Logistic regression analysis was performed to determine independent predictors of LASM. The following clinical and IVUS variables (all P<0.2 in univariate analysis) were tested: diabetes mellitus, stent type (PES), Thrombolysis in Myocardial Infarction flow grade before intervention, intrastent plaque/thrombus protrusion, proximal and distal reference EEM and lumen CSA, and mean stented segment EEM and P&M areas after implantation. Independent predictors of LASM were plaque/thrombus protrusion (P=0.0001; odds ratio, 5.60; 95% CI, 2.32 to 13.54) and PES use (P=0.0008; odds ratio, 6.32; 95% CI, 2.15 to 18.62).
Clinical Outcomes at 1 Year
At the 1-year follow-up, there were no deaths or ST related to the presence of stent malapposition. However, AMI was reported in 2 patients with persistent ASM; 1 patient in the resolved ASM cohort had a stroke. Two lesions with resolved ASM, 1 lesion with persistent ASM, and 2 lesions without any malapposition (at baseline or follow-up) required revascularization.
In this analysis of both postimplantation and follow-up IVUS after primary percutaneous coronary intervention, ASM occurred in 30% to 40% of both PES- and BMS-treated lesions. Of these, ≈40% resolved at 13 months. At follow-up, LSM was more common in PES-treated lesions compared with BMS-treated lesions mainly because of a higher incidence of LASM. LASM was due to positive remodeling and plaque/thrombus resolution, and large LSM areas indicated either persistent ASM or LASM with positive modeling. Independent predictors of LASM were poststent IVUS plaque/thrombus protrusion and randomization to PES rather than BMS.
In previous IVUS studies such as Stent Treatment Region Assessed by Ultrasound Tomography (STRUT), Can Routine Ultrasound Influence Stent Expansion (CRUISE), and Angiography-Directed Versus IVUS-Directed Coronary Stent Placement (AVID), the incidence of ASM was 4% to 22%.9 In the Hong et al10 study, it was 7.2%, similar to the TAXUS-II IVUS substudy (7.5%).11 However, these were not STEMI studies. The only other serial IVUS study in patients with STEMI found ASM in 38.5% of sirolimus-eluting stents and 33.8% of BMS, similar to the present study.12 ASM was mostly technique dependent and occurred after implantation of any stent type.13 However, it was not clear why there appeared to be a higher incidence of ASM in STEMI than in stable angina.
In the present study, 39.1% of PES-associated ASM and 40.0% of BMS-associated ASM resolved at follow-up, especially within the stent body, because of negative remodeling without peri-stent plaque progression (Figure 2). However, the TAXUS-II IVUS substudy showed that >50% of ASM resolved at follow-up because of an increase of peri-stent plaque without any change in EEM.11 Another study showed that most ASM either resolved or became smaller.14 Again, the present study included only patients with STEMI, not focal lesions in stable angina patients as in TAXUS-II. In the present analysis, an immediate poststent ASM area >1.2 mm2 best separated persistent from resolved ASM; Van der Hoeven et al12 also identified a larger ASM area in persistent (versus resolved) ASM. In addition to and similar to previous studies, the present study showed that persistent ASM was associated with less NIH compared with ASM that resolved.10,14
Late Stent Malapposition
LSM can represent either LASM or persistent ASM.13 In the present STEMI study, LASM was more common after PES than after BMS implantation. A meta-analysis showed that the risk of LASM was significantly greater after DES than BMS implantation,6 whereas other studies showed that primary stenting in AMI was an independent predictor of LASM after both BMS and DES implantation.10,15 The limited data on LASM after stenting of patients with STEMI showed a frequency similar to our present findings: ≈25% to 30% after DES and ≈10% after BMS.10,12,15,16
Previous studies have shown that the main cause of LASM was positive remodeling without an equal amount of peri-stent NIH or plaque growth so that the vessel pulled away from the stent without tissue fill-in; thrombus resolution so that a gap formed between the stent and the vessel wall was a potential mechanism only after primary stenting in AMI.10,11,15,17–19 In the present study, 75% of LASM was associated with positive remodeling, a finding similar to that in the study by Van der Hoeven et al.12 LASM CSA correlated only to the increase in EEM (but not to the change in P&M area) in the group with positive remodeling in whom LASM was equally located adjacent to plaque or to an arc of normal arterial wall. Conversely, LASM CSA correlated only to a decrease in P&M (and not to any increase in EEM) in the group without positive remodeling in whom most LASM was located adjacent to plaque (presumably adjacent to thrombus in these patients with AMI) and in whom plaque/thrombus protrusion was more frequent (Figure 2); this cluster of observations supports the importance of thrombus dissolution as a mechanism of LASM in AMI lesions.
Clinical Outcomes of Stent Malapposition
The clinical impact of stent malapposition has been a matter of concern and debate. In previous studies and in the present study, persistent malapposition and acquired stent malapposition were associated with less NIH.10,13,15,19–21 However, although the number of events was small (with no deaths or ST) and follow-up was limited to only 1 year in the present study, there was no difference in safety major adverse cardiac events within the first year between patients with versus without ASM and those with versus without LASM in both the BMS and PES cohorts, similar to many previous studies.10–12,15–17,22,23 Because the development of LASM and the occurrence of clinical events were identified at the same time in the present analysis, ongoing follow-up to 3 years will determine the relationship of longer-term major adverse cardiac events and ASM and especially LASM in both BMS and PES cohorts. Cook et al7 demonstrated that patients with very late ST showed positive arterial remodeling with a high incidence of stent malapposition that was especially apparent when patients with ST were compared with DES control subjects, and a recent meta-analysis suggested an increased frequency of very late ST compared with what should have been expected in these studies.6 The mechanism by which LSM may contribute to ST remains unclear.24 It has been speculated that LSM may serve as a local nidus for thrombus formation by allowing fibrin and platelet deposition.25 LSM may be the consequence of sustained inflammation and delayed healing resulting in tissue necrosis and erosion around the stent.20 LSM may be only a marker for other mechanisms such as delayed reendothelialization, impaired vasomotion, and sustained inflammation allowing platelet adhesion, initiation of the coagulation cascade, and subsequent thrombotic stent occlusion.7 In the study by Cook et al, the malapposition area associated with very late ST was twice as large as in patients without very late ST. Our study indicated that large LSM areas either persisted from stent implantation or were due to positive remodeling, not to thrombus dissolution in patients with AMI.
Not all patients were included in this IVUS substudy, and not all patients enrolled in the IVUS substudy had both baseline and follow-up imaging. The relation between preintervention plaque characteristics and LSM was not evaluated. This study represents a time frame of 13 months and was underpowered to show a difference in major adverse cardiac event rates between patients with and without stent malapposition.
In patients with STEMI, the incidence of ASM was similar in PES- and BMS-treated lesions, whereas LASM was more common in PES-treated lesions; however, neither ASM nor LASM was associated with adverse clinical events within 1 year. The reason for resolved ASM was negative remodeling; larger baseline ASM areas separated persistent from resolved ASM. Conversely, LASM was due mainly to positive remodeling and plaque/thrombus dissolution. Large LSM areas either persisted from stent implantation or were due to positive remodeling.
We thank Celia Castellanos, MD, Takashi Kubo, MD, PhD, Hiroshi Doi, MD, PhD, Kenichi Tsujita, MD, PhD, Jian Liu, MD, Junqing Yang, MD, So-Yeon Choi, MD, PhD, Carlos Oviedo, MD, Harpreet Bharaj, BS, Rasha Aaskar, BS, Lokesh Dani, BA, Sinan Biro, MS for assistance with IVUS image analysis.
Sources of Funding
The HORIZONS-AMI Trial was sponsored by the Cardiovascular Research Foundation, with grant support from Boston Scientific and The Medicines Co.
Drs Lansky, Mintz, Dressler, and Parise report being employed by the Cardiovascular Research Foundation. Dr Stone is a member of the advisory boards for Boston Scientific Corp and Abbott Vascular. Dr Mintz reports receiving consulting fees from Volcano Corp. Dr Guagliumi reports receiving consulting fees from Volcano Corp and Boston Scientific. Drs Maehara, Mintz, Lansky, Guagliumi, and Stone report receiving research grants from Boston Scientific. Drs Maehara, Mintz, and Lansky report receiving research grants from Volcano Corp. Drs Witzenbicher and Mehran report receiving lecture fees from Boston Scientific, Abbott Vascular, and The Medicines Co. Dr Brodie reports receiving lecture fees from The Medicines Co and MedRad/Possis.
Stone GW, Grines CL, Cox DA, Garcia E, Tcheng JE, Griffin JJ, Guagliumi G, Stuckey T, Turco M, Carroll JD, Rutherford BD, Lansky AJ; for Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) Investigators. Comparison of angioplasty with stenting, with or without abciximab, in acute myocardial infarction. N Engl J Med. 2002; 346: 957–966.
Spaulding C, Henry P, Teiger E, Beatt K, Bramucci E, Carrié D, Slama MS, Merkely B, Erglis A, Margheri M, Varenne O, Cebrian A, Stoll HP, Snead DB, Bode C; for TYPHOON Investigators. Sirolimus-eluting versus uncoated stents in acute myocardial infarction. N Engl J Med. 2006; 355: 1093–1104.
Hassan AK, Bergheanu SC, Stijnen T, van der Hoeven BL, Snoep JD, Plevier JW, Schalij MJ, Jukema JW. Late stent malapposition risk is higher after drug-eluting stent compared with bare-metal stent implantation and associates with late stent thrombosis. Eur Heart J. 2010; 31: 1172–1180.
Cook S, Wenaweser P, Togni M, Billinger M, Morger C, Seiler C, Vogel R, Hess OM, Meier B, Windecker S. Incomplete stent apposition and very late stent thrombosis after drug-eluting stent implantation. Circulation. 2007; 115: 2426–2434.
Mehran R, Brodie B, Cox DA, Grines CL, Rutherford B, Bhatt DL, Dangas G, Feit F, Ohman EM, Parise H, Fahy M, Lansky AJ, Stone GW. The Harmonizing Outcomes with RevascularIZatiON and Stents in Acute Myocardial Infarction (HORIZONS-AMI) Trial: study design and rationale. Am Heart J. 2008; 156: 44–56.
Uren NG, Schwarzacher SP, Metz JA, Lee DP, Honda Y, Yeung AC, Fitzgerald PJ, Yock PG. Predictors and outcomes of stent thrombosis: an intravascular ultrasound registry. Eur Heart J. 2002; 23: 124–132.
Hong MK, Mintz GS, Lee CW, Park DW, Park KM, Lee BK, Kim YH, Song JM, Han KH, Kang DH, Cheong SS, Song JK, Kim JJ, Park SW, Park SJ. Late stent malapposition after drug-eluting stent implantation: an intravascular ultrasound analysis with long-term follow-up. Circulation. 2006; 113: 414–419.
Tanabe K, Serruys PW, Degertekin M, Grube E, Guagliumi G, Urbaszek W, Bonnier J, Lablanche JM, Siminiak T, Nordrehaug J, Figulla H, Drzewiecki J, Banning A, Hauptmann K, Dudek D, Bruining N, Hamers R, Hoye A, Ligthart JMR, Disco C, Koglin J, Russell ME, Colombo A; for TAXUS II Study Group. Incomplete stent apposition after implantation of paclitaxel eluting stents or bare metal stents: insights from the randomized TAXUS II trial. Circulation. 2005; 111: 900–905.
Van der Hoeven BL, Liem SS, Dijkstra J, Bergheanu SC, Putter H, Antoni ML, Atsma DE, Bootsma M, Zeppenfeld K, Jukema JW, Schalij MJ. Stent malapposition after sirolimus-eluting and bare-metal stent implantation in patients with ST-segment elevation myocardial infarction: acute and 9-month intravascular ultrasound results of the MISSION! intervention study. J Am Coll Cardiol Interv. 2008; 1: 192–201.
Mintz GS. What to do about late incomplete stent apposition? Circulation. 2007; 115: 2379–2381.
Kimura M, Mintz GS, Carlier S, Takebayashi H, Fujii K, Sano K, Yasuda T, Costa RA, Costa JR Jr, Quen J, Tanaka K, Lui J, Weisz G, Moussa I, Dangas G, Mehran R, Lansky AJ, Kreps EM, Collins M, Stone GW, Moses JW, Leon MB. Outcome after acute incomplete sirolimus-eluting stent apposition as assessed by serial intravascular ultrasound. Am J Cardiol. 2006; 98: 436–442.
Hong MK, Mintz GS, Lee CW, Kim YH, Lee SW, Song JM, Han KH, Kang DH, Song JK, Kim JJ, Park SW, Park SJ. Incidence, mechanism, predictors, and long-term prognosis of late stent malapposition after bare-metal stent implantation. Circulation. 2004; 109: 881–886.
van der Hoeven BL, Liem SS, Jukema JW, Suraphakdee N, Putter H, Dijkstra J, Atsma DE, Bootsma M, Zeppenfeld K, Oemrawsingh PV, van der Wall EE, Schalij MJ. Sirolimus-eluting stents versus bare-metal stents in patients with ST-segment elevation myocardial infarction: 9-month angiographic and intravascular ultrasound results and 12-month clinical outcome results from the MISSION! Intervention Study. J Am Coll Cardiol. 2008; 51: 618–626.
Mintz GS, Shah VM, Weissman NJ. Regional remodeling as the cause of late stent malapposition. Circulation. 2003; 107: 2660–2663.
Shah VM, Mintz GS, Apple S, Weissman NJ. Background incidence of late malapposition after bare-metal stent implantation. Circulation. 2002; 106: 1753–1755.
Finn AV, Nakazawa G, Joner M, Kolodgie FD, Mont EK, Gold HK, Virmani R. Vascular responses to drug eluting stents: importance of delayed healing. Arterioscler Thromb Vasc Biol. 2007; 27: 1500–1510.
Hoffmann R, Morice MC, Moses JW, Fitzgerald PJ, Mauri L, Breithardt G, Schofer J, Serruys PW, Stoll HP, Leon MB. Impact of late incomplete stent apposition after sirolimus-eluting stent implantation on 4-year clinical events: intravascular ultrasound analysis from the multicentre, randomised, RAVEL, E-SIRIUS and SIRIUS trials. Heart. 2008; 94: 322–328.
Colombo A, Latib A. Late incomplete stent apposition after drug-eluting stent implantation: a true risk factor or “an innocent bystander”? Heart. 2008; 94: 253–254.
Waksman R. Late thrombosis after radiation. Circulation. 1999; 100: 780–782.
The prognosis for patients with acute myocardial infarction has been improved by primary percutaneous coronary intervention, especially the implantation of bare-metal stents (BMS) or drug-eluting stents. However, there is an increased frequency of late stent malapposition after drug-eluting stent implantation. In the prospective, multicenter Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial, patients with ST-elevation myocardial infarction within 12 hours of symptom onset were randomized 3:1 to TAXUS EXPRESS paclitaxel-eluting stents (PES) versus EXPRESS BMS. The present intravascular ultrasound substudy included 241 patients with 263 native coronary lesions (201 PES, 62 BMS) with poststenting and 13-month follow-up intravascular ultrasound imaging. Postintervention acute stent malapposition occurred in 34.3% PES- and 40.3% BMS-treated lesions. The reason for resolved acute stent malapposition was negative remodeling with larger acute stent malapposition areas (>1.2 mm2) separating persistent from resolved acute stent malapposition. At follow-up, a higher frequency of late stent malapposition was detected in PES-treated lesions (46.8%) mainly because of more late acquired stent malappositions (30.8%) compared with BMS-treated lesions. Late acquired stent malapposition was attributable to plaque/thrombus resolution in both BMS and PES and to positive remodeling in PES; the largest areas of late stent malapposition either persisted from implantation or were seen in lesions with positive remodeling. However, the number of events related to stent malapposition was small (with no deaths or stent thrombosis), and follow-up was limited to only 1 year; therefore, longer follow-up is required to determine the relationship of long-term major adverse cardiac events (and especially very late stent thrombosis) and late stent malapposition.