Urgent PCI in Patients with Stent Thrombosis: An Observational
Single-Center Study Comparing Thrombus Aspiration and
Standard

Stent thrombosis (ST) is a recognized complication limiting the clinical efficacy of percutaneous coronary interventions (PCI), the incidence reported being between 0.5% and 2.2%.^1–5 Due to the increasing number of stent-based PCI procedures, the absolute number of patients experiencing ST is expected to expand, and the introduction of drug-eluting stents in clinical practice is expected to change the histopathology,⁶ presentation⁷ and possibly the incidence of patients with ST.
Despite the evident clinical relevance associated with ST, its management is not well established. Re-PCI represents the most frequently adopted strategy for ST, but yields unsatisfactory results, as it is associated with a high risk of death and recurrent ST.^3,4,8–11 Recently-developed devices able to remove the thrombus and reduce distal embolization might improve the outcome of patients undergoing PCI for ST.
We report a comparison of the angiographic results obtained with standard PCI (SP) or with PCI associated with thrombus aspiration (TA) using a device that was recently tested successfully in patients undergoing primary PCI.¹²

Methods
Consecutive patients with angiographically-confirmed thrombosis of a previously-implanted stent who underwent urgent PCI at our institution during a 2-year period (from January 2004 to January 2006) were enrolled in the study, irrespective of clinical presentation, type of previously-implanted stent and date of previous stent implantation. Patients with acute ST occurring during the stent implantation procedure were not included in this study.
Patients were treated at the operator’s discretion with either SP or TA using the Diver CE catheter (Invatec, Roncadelle, Italy). The Diver CE is a rapid-exchange, 6 Fr-compatible, TA catheter. It has a central aspiration lumen and a soft, flexible, 0.026 inch, nontraumatic tip with multiple holes (1 large anterior and 3 smaller lateral holes) communicating with the central lumen. A 30 ml luer-lock syringe is connected to the proximal hub of the central lumen for TA. After placement of a 6 Fr guiding catheter (shape chosen by the operator), a 0.014 inch guidewire was advanced through the culprit lesion. Next, TA was performed with the Diver CE catheter by delivering it to the lesion and slowly advancing it as it aspirated through the culprit lesion. When the 30 ml syringe was full (and the aspiration force was consequently abolished), the device was retracted (in aspiration) in the guiding catheter.¹³ The TA procedure was performed 1–6 times according to the operator’s discretion, and immediate angiographic results were obtained. In a few cases after TA, due to the presence of a consistent amount of residual thrombus (thrombus score [TS] ≥ 3) in a large vessel (reference vessel diameter [RVD] ≥ 3.5 mm), some operators decided to use also a distal protection filter device (FilterWire EZ^™, Boston Scientific Corp., Natick, Massachusetts, in 3 patients, and the Spider, eV3, Plymouth, Minnesota, in 1 patient) to avoid distal embolization during inflation of the large balloons and/or deployment of an additional stent. In patients treated with TA, balloon angioplasty was performed after aspiration in all patients to ensure optimal dilatation of the thrombosed stent. In order to achieve optimal angiographic results, an additional stent was implanted in patients in both groups when a dissection or residual stenosis occurred outside of the stent.
All patients were treated with heparin (initial weight-adjusted intravenous [IV] bolus, then additional boluses administered with the aim of obtaining an activated clotting time of 250–300 seconds) and with double antiplatelet therapy with aspirin and clopidogrel (loading dose of 600 mg followed by 75 mg/day). Abciximab (0.25 mg/kg bolus plus infusion of 0.125 μg/kg/minute for 12 hours) was administered unless contraindicated. Beta-blockers, angiotensin-converting enzyme inhibitors and statin drugs were administered as appropriate in the absence of specific contraindication. After the procedure, patients underwent repeated sampling (every 8 hours for 2 days, then daily) for cardiac enzyme assessment (troponin T, creatinekinase [CK]-MB and CK).
Angiographic analyses. Coronary angiograms before intervention, after thrombus aspiration and at the end of the procedure were reviewed (intermediate angiograms were not excluded) and analyzed by 2 independent interventional cardiologists to assess:
• anterograde coronary flow according to the standard TIMI criteria;¹⁴
• corrected TIMI frame count (cTFC) according to Gibson;¹⁵
• thrombus score (TS) according to the TIMI study group¹⁶ (0 = no cineangiographic characteristics of thrombus present; 1 = possible thrombus present, with such angiographic characteristics as reduced contrast density, haziness, irregular lesion contour, or a smooth convex “meniscus” at the site of total occlusion suggestive, but not diagnostic, of thrombus; 2 = definite thrombus, with largest dimensions measuring £ 1/2 the vessel diameter; 3 = definite thrombus, with greatest linear dimension > 1/2 but < 2 vessel diameters; 4 = definite thrombus, with the largest dimension ≥ 2 vessel diameters; 5 = total occlusion);
• angiographic morphologic features of the infarct-related artery identifying the presence of a high thrombus burden (cutoff occlusion pattern, accumulated thrombus > 5 mm proximal to the occlusion, presence of floating thrombus, dye stasis distal to the obstruction, reference lumen diameter of the infarct-related artery 3 4 mm, incomplete obstruction with presence of accumulated thrombus > 3 times the RLD of the infarct-related artery) according to Yip et al.¹⁷
• occurrence of angiographic distal embolization defined as occlusion with an abrupt “cutoff” appearance on angiography of a branch of the infarct-related artery distal to the culprit lesion site;
• myocardial blush grade (MBG) according to van’t Hof et al.¹⁸
Postprocedural adverse angiographic outcome was defined as the occurrence of final TIMI 0–1 flow and/or angiographically evident distal embolization.
In-hospital clinical follow up. The in-hospital clinical outcome was recorded for all patients to assess the occurrence of death, new-onset myocardial infarction (MI) and target lesion revascularization (TLR) (early major adverse coronary events [MACE]). New-onset MI was defined as recurrent chest pain (after its complete resolution) with a new elevation in CK (by 50% over the last measurement, or if normalized, ≥ 2 times the upper limit of normal and/or new electrocardiographic (ECG) changes (ST-segment elevation, new left bundle-branch block, new Q-waves).
Statistical analysis. Continuous variables (presented as mean ± standard deviation) were compared by paired t-, Wilcoxon and Mann-Whitney U-tests, as appropriate. Chisquare tests (Fisher’s corrected when appropriate) were used to compare discrete variables (reported as raw numbers [%]). Analyses were carried out using SPSS for Windows, version 11.0 (SPSS, Inc., Chicago, Illinois). Statistical significance was defined by a two-tailed p-value < 0.05.

Results
During the study period, 35 urgent PCIs were attempted in 30 patients. Two patients presenting in cardiogenic shock died during angiography (1 patient) or during the attempt to cross the lesion with the guidewire (1 patient) and were excluded from the study. Accordingly, the final study population comprised 28 patients with stent thrombosis who underwent 33 percutaneous procedures. Three patients had 2 STs and underwent 2 procedures, and 1 patient had 3 STs (2 in the LCX and 1 in the LAD) and underwent 3 procedures. These 4 patients had a high risk of thrombosis due in 1 case to polycythemia vera and in the other 3 cases to paraneoplastic syndrome.
The study population was divided into two groups: standard PCI (12 patients and 15 procedures), and PCI with TA (16 patients and 18 procedures).

The clinical baseline characteristics of the study population are shown in Table 1 and were similar in the two groups. In particular, the majority of patients presented with ST-elevation myocardial infarction (STEMI), with a mean symptom-to-catheterization laboratory interval of 112 minutes. Most patients had subacute ST (> 24 hours < 30 days from stent implantation) of a previously-implanted bare-metal stent. Baseline angiographic characteristics of the study population were comparable in the two groups (Table 2). The majority of patients had initial TIMI 0–1 with a cutoff occlusion pattern.
In the TA group, the TA catheter was used before balloon dilatation in 16 cases, and after predilatation with an undersized balloon in 2 cases. In only 1 patient, the Diver CE was unsuccessful in completely crossing the thrombosed stent. TA induced a significant increase in coronary flow through the culprit vessel (from 0.71 ± 0.85 TIMI flow to 1.89 ± 0.83 TIMI flow; p < 0.001) and reduced the thrombus burden (from 4.3 ± 0.9 to 3.1 ± 1.1; p < 0.001). Maximal balloon inflation diameter and pressure, as well as the need for additional stent implantation, were similar in the SP and TA groups (14.8 ± 2.5 atm vs. 14.5 ± 2.2 atm; p = 0.74; 2.9 ± 0.5 mm vs. 3.1 ± 0.6; p = 0.22; plain-old balloon angioplasty: 5/15 (33%) vs. 7/18 (39%); p = 0.74, respectively) (Figure 1).

A trend in favor of the TA group compared to the SP group was observed in post-PCI TIMI 3 flow rates (67% vs. 89%; p = 0.10), final cTFC (31 ± 35 vs. 17 ± 21; p = 0.10) and MBG 2–3 rates (40% vs. 67%; p = 0.12). Accordingly, the rate of combination of post-PCI TIMI 0–1 and/or distal embolization was significantly lower in the TA group (33% vs. 5% TA; p = 0.04) (Table 3). In the analysis restricted to the 23 patients with a higher thrombus burden (cutoff occlusion pattern or incomplete obstruction with presence of accumulated thrombus > 3 times the reference lumen diameter [RLD] of the infarct-related artery), the rate of combination of post-PCI TIMI 0–1 and/or distal embolization was 8% (1/13) in the TA group and 40% (4/10) in the SP group (p = 0.08).
In the group of patients treated with TA, there was a small subgroup of 4 patients with large target vessels (reference vessel diameter [RVD] 3 3.5 mm) who, after thrombus aspiration, had a TS ≥ 3 and were also treated with distal filter protection (DFP). Final TIMI 3 flow was achieved in all 4 patients, final MBG of 3 was achieved in 3 out of 4 patients (the other patient had a final MBG of 2), and there were no cases of distal embolization.
In order to separate the effect of DFP from aspiration, we also analyzed the angiographic outcome comparison between the TA group (excluding the 4 patients treated with TA + DFP) and SP groups only. Baseline clinical and angiographic characteristics were similar also in these two groups (data not shown). A trend in favor of only the TA group compared to the SP group was observed in post-PCI TIMI 3 flow rates (67% vs. 86%; p = 0.13), final cTFC (31 ± 35 vs. 18 ± 24; p = 0.13), and final MBG 2–3 rates (40% vs. 57%; p = 0.19). The rate of combined post-PCI TIMI 0–1 rates and/or distal embolization was significantly lower in the TA group only (33% SP vs. 7%; p = 0.05).
In-hospital clinical follow-up data are shown in Table 4. Three patients (1 in the TA group and 2 in the SP group; p = 0.50) experienced 1 or 2 episodes of recurrent ST, with STEMI and need for urgent repeat PCI. Two patients, both in the SP group, died, 1 due to irreversible heart failure, and 1 after another STEMI caused by recurrent ST despite having undergone re- PCI. The rate of in-hospital MACE was lower in the TA group (6% vs. 33%; p = 0.08).

Discussion
Despite the routine use of high-pressure balloon inflation for stent deployment and the use of a thienopyridine in combination with aspirin, ST remains a potentially catastrophic complication of PCI. Moreover, emerging data regarding the possible influence of drug-eluting stent implantation on the risk of late ST, mortality and MI19 make the challenge of preventing and treating this complication even more daunting.
The standard treatment of ST includes repeat angioplasty with or without the use of intracoronary thrombolysis, along with glycoprotein IIb/IIIa inhibitor therapy. However, these treatments have yielded unsatisfactory results with a high rate of mortality, MI, need for emergent bypass surgery and re-ST.^20,21
In this setting, the use of thrombectomy and/or distal protection devices during PCI might improve outcomes. A paucity of data from case reports, case series and substudies report on the feasibility of the use of such devices in patients with ST. In particular, some studies have shown that rheolytic thrombectomy using the AngioJet catheter (Possis Medical, Minneapolis, Minnesota) in patients with ST resulted in high rates of procedural success and final TIMI 3 flow.^23–25 A limited experience involving patients with ST treated with the X-Sizer thrombectomy device (Endi- COR Medical, Inc., San Clemente, California) reported a high rate of final TIMI flow 3, but also reported difficulties in crossing the stent with the device in more than half of the patients.²⁶ Simpler thrombectomy devices such as TA catheters, when compared to the AngioJet and X-Sizer devices, offer greater flexibility to facilitate reaching and crossing previously-implanted stents. Recently, the feasibility of TA using the Diver CE12 and Pronto (Vascular Solutions, Inc., Minneapolis, Minnesota) catheters²⁷ has been shown in a few, highly-selected patient groups.
In the present study, we report our 2-year experience with patients with ST who were treated with the Diver CE catheter compared to those treated with standard PCI. In the Diver CE group, higher rates of final TIMI 3, final MBG 3, and a lower rate of distal embolization and TIMI 0–1 at the end of procedure were observed, thus suggesting an improved overall angiographic result. In-hospital clinical outcomes assessment confirmed the safety of the TA approach, as in-hospital MACE tended to occur less frequently in the patients treated with TA. This is the first study to compare the use of a TA device with standard PCI in the setting of ST, and the encouraging results suggest the need for larger, prospective studies.²⁸
Study limitations. This study had several limitations. First, it was an observational study and was not randomized. Thus, several baseline characteristics differed between the patients treated with or without TA and it is possible that these differences, although not statistically significant, could influence the clinical and angiographic outcomes. Second, the sample size of the study was small. Thus, we used a composite adverse angiographic outcome for comparison of the two groups in order to summarize the trend toward an advantage of TA that was observed for each angiographic endpoint. Third, the clinical follow-up period was brief and limited to the occurrence of in-hospital MACE.

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