Author + information
- Received February 8, 2008
- Revision received March 7, 2008
- Accepted March 15, 2008
- Published online June 1, 2008.
- Pieter J. Vlaar, MSc⁎,⁎ (, )
- Tone Svilaas, MD⁎,
- Mathijs Vogelzang, MD⁎,
- Gilles F. Diercks, MD, PhD†,
- Bart J. de Smet, MD, PhD⁎,
- Ad F. van den Heuvel, MD, PhD⁎,
- Rutger L. Anthonio, MD, PhD⁎,
- Gillian A. Jessurun, MD, PhD⁎,
- Esjong Tan, MD⁎,
- Albert J. Suurmeijer, MD, PhD† and
- Felix Zijlstra, MD, PhD, FACC⁎
- ↵⁎Reprint requests and correspondence:
Pieter J. Vlaar, MSc, Department of Cardiology, University Medical Center Groningen, P.O. Box 30.001, 9700 RB Groningen, the Netherlands.
Objectives The objective of this study was to compare 2 manual thrombus aspiration catheters in unselected patients with ST-segment elevation myocardial infarction.
Background Distal embolization is common during percutaneous coronary intervention in ST-segment elevation myocardial infarction and can induce impaired myocardial perfusion. Several aspiration thrombectomy devices have been introduced to prevent distal embolization, however, with conflicting clinical results. Currently, it is unclear to what extent this variance in outcome can be explained by device-related factors, such as internal lumen size.
Methods We performed a prospective cohort study in which patients undergoing primary percutaneous coronary intervention were treated with a large-internal-lumen catheter (Diver, Invatec, Roncadelle, Italy). Outcomes were compared with a matched population of the Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction Study (TAPAS) trial, in which patients were treated with a medium-sized catheter (Export, Medtronic, Minneapolis, Minnesota). A histopathological analysis was performed of retrieved material.
Results A total of 160 patients, treated with the Diver (n = 80) or Export (n = 80) aspiration catheter, were enrolled. Effective thrombus aspiration was seen in 70.3% of the patients treated with the Diver catheter versus 81.8% with the Export catheter (p = 0.10) No significant difference was found in myocardial blush grade or electrocardiographic outcome between the 2 devices. Size distribution of retrieved thrombotic particles was similar per device. Erythrocyte-rich thrombi were found in 34.8% of the cases and were predominately seen in patients with low initial Thrombolysis In Myocardial Infarction flow grade (p = 0.008).
Conclusions A larger internal lumen diameter does not result in retrieval of larger thrombotic particles, nor in improved angiographic or electrocardiographic outcomes.
Distal embolization is common during percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI) and can induce impaired myocardial perfusion (1,2). Several aspiration and thrombectomy devices have been introduced to prevent distal embolization. These include the Diver (Invatec, Roncadelle, Italy), Export (Medtronic, Minneapolis, Minnesota), Probing (Boston Scientific, Natick, Massachusetts), Pronto (Vascular Solutions, Minneapolis, Minnesota), and Rescue catheters (Boston Scientific, Natick, Massachusetts) (3–8). The ideal aspiration catheter should be rapidly exchangeable, good deliverable (also in small diameter and tortuous culprit vessels), and at the same time have sufficient lumen size to aspirate thrombus material. Based on internal lumen diameter, aspiration catheters can be subdivided into 3 size groups: large (Diver, 0.062 inch; Pronto, 0.065 inch), medium (Export, 0.041 inch; Rescue, 0.042 inch), and small (Probing, 0.018 inch). Currently, it is unknown whether large-lumen-diameter catheters are able to aspirate larger thrombotic components when compared with smaller sized ones. Retrieval of larger particles could improve the efficacy of thrombus aspiration, leading to better myocardial perfusion after primary PCI. On the other hand, a larger lumen diameter could influence handling characteristics and device safety.
To test the hypothesis that a large-lumen-diameter catheter is capable of aspirating larger thrombotic components, we performed a prospective cohort study in which patients undergoing primary PCI were treated with a large-diameter catheter (Diver catheter). Further, because histopathological analysis of aspirated debris has only been performed in small and selected study populations (8–10), we also performed a histopathological assessment of retrieved material.
Histopathological, angiographic, and clinical outcomes were compared with a matched population of the TAPAS (Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction Study), in which patients were treated with a medium-sized catheter (Export catheter) (3).
Materials and Methods
Enrollment in the TAPAS trial ended December 2006 (3). From January 2007 to March 2007, all patients who underwent PCI in a native vessel for STEMI were included in this prospective study. Inclusion and exclusion criteria were similar to that for the TAPAS trial. In summary, patients were considered eligible for inclusion when they had symptoms suggesting acute myocardial ischemia >30 min, time from symptom onset was <12 h, and ST-segment elevation >0.1 mV in ≥2 contiguous leads was present on the electrocardiogram (ECG). Patients were excluded when they underwent rescue PCI after thrombolysis, had known existence of a disease with life expectancy <6 months, or no informed consent was given.
Consecutive patients treated with the Diver catheter were matched with patients included in the TAPAS study, in which thrombus aspiration with the Export catheter was attempted (3). Matching was based on the following variables: gender, initial Thrombolysis In Myocardial Infarction (TIMI) flow grade ±1, age ±5 years, and segment culprit lesion.
The primary end point is incidence of aspirated thrombotic components >1 mm. Secondary end points are myocardial blush grade, ST-segment elevation resolution, persistent ST-segment elevation, enzymatic infarct size, postprocedural distal embolization, and major adverse cardiac events at 30 days.
The angiographic, histopathological, and electrocardiographic methods used in this study were similar to those used in the TAPAS trial (3).
Description of the thrombus-aspiration catheters
The PCI was performed using standard percutaneous techniques. The Export aspiration catheter (Medtronic) and the Diver Clot Extraction (Invatec) are both 6-F compatible thrombus aspiration catheters. The Export has an oblique aspiration tip design, with an aspiration lumen of 0.041 inch. The Diver has a distal aspiration lumen of 0.062. In both aspiration catheters, suction is provided by hand with a lockable 20-ml syringe. All interventional cardiologists were experienced in the usage of manual thrombus aspiration catheters. In addition, because the usage of both aspiration catheters is similar, no learning curve was expected in the Diver group.
Before PCI, the patient was treated with aspirin (a bolus of 500 mg), intravenous heparin (5000 IU), and clopidogrel (a loading dose of 600 mg). Adjunctive therapy included nitroglycerin intravenously and glycoprotein IIb/IIIa inhibitors. During PCI, additional heparin is administered guided by activated clotting time measurements. Standard therapies after PCI included aspirin 80 mg, clopidogrel 75 mg, beta-blockers, lipid-lowering agents, and angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers.
Angiographic, electrocardiographic, and clinical outcome
Intravenous nitroglycerin was given after the procedure and before the final angiogram in all patients. The TIMI flow grades will be estimated as previously described: grade 0: no perfusion, grade 1: penetration without perfusion, grade 2: partial perfusion, grade 3: complete perfusion (11). The evaluation of myocardial blush grades will be performed as described by van't Hof et al. (1): grade 0: no myocardial blush, grade 1: minimal myocardial blush or contrast density, grade 2, moderate myocardial blush or contrast density but less than that obtained during angiography of a contralateral or ipsilateral non–infarct-related coronary artery, and grade 3, normal myocardial blush or contrast density comparable with that obtained during angiography of a contralateral or ipsilateral non–infarct-related coronary artery. Persisting myocardial blush (staining) suggests leakage of contrast medium into the extravascular space and is graded 0. Distal embolization was considered to have occurred if new circumscribed filling defects and/or abrupt cut-off of the vessel distal to the target lesion appears. Thrombus was assessed according to the criteria summarized by Mabin et al. (12). The coronary angiograms were analyzed offline by 2 experienced observers.
A 12-lead ECG was acquired at presentation and after the PCI procedure. The post-procedural ECG was analyzed by comparison to the ST-segments of the ECG at presentation. ST-segment elevation resolution was categorized as complete (≥70%), partial (30% to 70%), or absent (<30%). Persistent ST-segment deviation, defined as the sum of ST-segment depression and ST-segment elevation, was categorized into <2 mm, 2 to 10 mm, and ≥10 mm.
Clinical status (death, reinfarction, and ischemia-driven target vessel revascularization) was collected from hospital records as well as by telephone interviews at 30 days post-procedure.
Filtered material obtained during aspiration was analyzed using the same method as used in the TAPAS trial. In short, material was placed in formalin and fixed for 24 h. Thereafter, filtered material was pelleted by centrifugation in liquid agar 65°C in an Eppendorf tube. After the agar pellet was solidified at 4°C, it was embedded in paraffin using an automated tissue processor. Paraffin sections were cut at 4 μm and stained with hematoxylin-eosin for microscopical examination (×100). Immunostaining was performed to optimize visualization of endothelial cells, smooth muscle cells, and macrophage foam cells. Samples were classified into effective or no effective aspiration based on the presence of thrombotic material. Identified material was classified into 4 types: thrombus with only platelets, thrombus with an erythrocyte component, thrombus with atheromatous plaque, and thrombus with both erythrocyte and atheromatous plaque and in 5 size groups: residue (very small filter casts of loosely cohesive platelets), well-formed thrombi smaller than 0.5 mm, 0.5 to 1 mm, 1 to 2 mm, and >2 mm.
The primary end point of this study is the incidence of aspirated thrombotic components >1 mm. Based on earlier experience with the Export catheter (3), it was estimated that we needed to enroll 160 patients to achieve a power of 80% (with a 2-sided significance level of 0.05) to detect a increase from 35% to 55% with the Diver catheter.
Values are shown as means ± standard deviations, median (inner quartile range [IQR]), or numbers of patients (percentages). Differences in baseline characteristics and outcomes were tested using either paired sample t test or Wilcoxon signed-rank test. Nonpaired, univariate, and multivariate logistic regression analysis were used to assess independent predictors associated with effective thrombus aspiration and histological subsets. Significant variables at univariate analysis (p < 0.15) were included in multivariate models. The following variables were evaluated: gender, catheter, age, ischemic time, hyperlipidemia, diabetes, current smoking, pre-angina pectoris, body mass index, 3-vessel disease, TIMI flow grade beforehand, thrombus visible beforehand, and severe calcification.
All p values were 2-tailed, with statistical significance set at 0.05. Analyses were performed using SPSS software version 12.0.1 (SPSS Inc., Chicago, Illinois).
A total of 82 consecutive patients were included. Two very young patients had no matching control patient within 5 years and were therefore excluded from the analysis. Baseline characteristics of the 80 enrolled patients are shown in Table 1.
Angiographic and electrocardiographic outcome
No serious complications, such as flow-limiting dissections or air embolization, occurred in the Diver or the Export group. A stent was placed in 91.3% (73 of 80) of the Diver patients and in 93.8% (75 of 80) of the Export patients. Direct stenting (stenting after thrombus aspiration without balloon pre-dilatation) was performed in 42.5% (31 of 73) of the patients treated with the Diver catheter and in 53.3% (40 of 75) treated with the Export (p = 0.39). Distal embolization post PCI was seen in 6.3% (5 of 80) of the patients in the Diver group and in 5.8% (4 of 70) in the Export group (p = 0.74). TIMI flow grade post-procedure and myocardial blush grade were similar in both groups (Table 1, Fig. 1).
The ECGs for persistent ST-segment deviation analysis were available in 92.5% (148 of 160) of the patients and for ST-segment elevation resolution analysis in 91.3% (146 of 160). Median (IQR) time between balloon angioplasty and post-PCI ECG was 0.7 (0.5 to 0.9) h in the Diver group and 0.7 (0.6 to 1.1) h in the Export group (p = 0.37). Persistent ST-segment deviation <2 mm and >70% ST-segment elevation resolution was seen in the majority of the patients treated with thrombus aspiration, respectively 52.0% (77 of 148) and 64.4% (94 of 146). No differences were seen in rates of persistent ST-segment deviation <2 mm, 2 to 10 mm and >10 mm between the Diver (49.3%, 39.7%, and 11.0%) and Export group (54.7%, 33.3%, and 12.0%) (p = 0.38) (Fig. 2). Incidences of ST-segment elevation resolution <30%, 30% to 70% and >70% were also similar in patients treated with the Diver (15.5%, 16,9%, and 67.6%) and the Export patients (14.7%, 24.0%, and 61.3%) (p = 0.97) (Fig. 3).
Short-term clinical outcome
Follow-up was completed in 100% of the patients. Occurrence of death, reinfarction, and target vessel revascularization within 30 days were similar in both groups. One death occurred in the Export group (0% vs 1.3%, p = 0.32). In the Diver group 2 reinfarctions occurred, compared with 1 in the Export group (2.5% vs 1.3%, p = 0.57). Five patients underwent target vessel revascularizations in the Diver group, compared with 4 in the Export group (6.3% vs 5.0%, p = 0.74). The incidence of the combined end point of death, reinfarction, or target vessel revascularization was 7.5% (6 of 80) in the Diver group versus 6.3% (5 of 80) in the Export group (p = 0.76).
Effective thrombus aspiration was seen in 70.3% (52 of 74) of the patients treated with the Diver catheter versus 81.8% (63 of 77) of the Export patients (p = 0.10). Aspirated thrombotic components >1 mm were found in 44.4% (28 of 63) of the Export patients and in 34.6% (18 of 52) of the Diver patients (p = 0.51). The size distribution of retrieved thrombotic particles was also similar for the 2 devices (p = 0.61) (Fig. 4).
Erythrocyte-rich thrombi and thrombi with plaque components were found in respectively 26.9% (14 of 52) and 7.7% (4 of 52) of the patients treated with the Diver and in 22.2% (14 of 63) and 14.3% (9 of 63) of the patients treated with the Export catheter. Thrombi with both plaque and erythrocytes components were seen in 13.5% (7 of 52) of the Diver patients and in 7.9% (5 of 63) of the Export patients. Distribution of histological subsets was similar in the 2 groups (p = 0.47).
The relationship between histopathological findings and baseline characteristics was investigated using logistic regression (Table 2). Thrombus was visible on the initial angiogram in the majority of the patients; however, this was not associated with retrieval of material at univariate logistic regression (p = 0.70). Multivariate analysis showed that thrombus aspiration with the Export catheter was not an independent predictor of effective thrombus aspiration (p = 0.09). Independent predictors for erythrocyte-rich thrombi at multivariate analysis were low initial TIMI flow grade (p = 0.008) and absence of 3-vessel disease (p = 0.026).
This prospective cohort study shows that the Export and Diver catheters are both safe and effective in removing thrombus in an unselected population with ST-segment elevation myocardial infarction. The larger internal lumen diameter of the Diver catheter did not result in retrieval of larger thrombotic particles, nor in improved angiographic or electrocardiographic outcomes.
Primary PCI does not always result in successful reperfusion of the myocardium, despite a patent epicardial vessel. Mechanical crushing and fragmentation of the thrombus-containing lesion during primary PCI is thought to be at least partly responsible for myocardial dysfunction after PCI (13–15). Several devices have been introduced to facilitate removal of thrombus and plaque material, thereby protecting the microvasculature and improving myocardial blood flow. In saphenous vein graft PCI, distal embolic protection devices have proven to be very effective in preventing distal embolization (class I recommendation, level of evidence A) (16). In primary PCI for native coronary lesions, aspiration thrombectomy devices may be most useful because their size allows access to the lesion over a routine wire. The DEAR-MI (Dethrombosis to Enhance Acute Reperfusion in Myocardial Infarction) trial randomized 155 patients to thrombus aspiration with the Pronto catheter or to primary PCI alone (5). Thrombus aspiration in this trial was associated with significantly better ST-segment resolution, better myocardial blush grade, and less distal embolization compared with primary PCI. The results of the TAPAS trial (Export aspiration catheter) and the REMEDIA (Randomized Evaluation of the Effect of Mechanical Reduction of Distal Embolization by Thrombus-Aspiration in Primary and Rescue Angioplasty) trial (Diver aspiration catheter), which compared thrombus aspiration with primary PCI, reported also feasibility and applicability of this approach (3,6). Conflicting results came from the trial of Kaltoft et al. (7), which enrolled 215 patients to thrombus aspiration with the Rescue catheter or primary PCI. This study reported larger final infarct size and a trend toward less myocardial salvage associated with thrombus aspiration. In the abovementioned studies, 4 different aspiration devices were used. It is unclear to what extent these conflicting results can be explained by device-related factors. One major difference between these devices is internal lumen diameter. An aspiration catheter with insufficient capacity to aspirate can theoretically manipulate and dislodge the thrombus, causing an adverse effect on myocardial perfusion. This present study shows that both medium-lumen and large-lumen thrombus aspiration catheters are safe and effective in terms of high rates of myocardial blush grades 2 to 3 and ST-segment normalization.
The size distribution of retrieved particles did not differ significantly between the 2 catheters; however, especially in the range 1 to 2 mm, some difference could be detected in favor of the Export catheter. These differences can be caused by differences in distal tip design between the 2 catheters. The nonsuperiority of a larger-lumen catheter may be explained by the fact that freshly formed thrombi are easily friable. Whether a larger-lumen catheter has a benefit in the context of older occlusions and degenerated saphenous vein grafts, in which particles are less friable, is currently unclear.
Previous angioscopic studies in patients with acute coronary syndromes suppose erythrocyte-rich thrombi to be present in the majority of the patients with acute myocardial infarction (17,18). Our study found a lower incidence of erythrocyte-rich thrombi (34.8%, 40 of 115). Erythrocyte-rich thrombi were predominantly seen in patients with low initial epicardial flow in combination with a trend for longer ischemic time. This supports the thought that erythrocyte-rich thrombi are formed mainly during stasis of blood flow, whereas white thrombi are predominately seen in patients with TIMI flow grade 1 to 3 at presentation (17–20). The lower incidence of erythrocyte-thrombi in our study can be explained by the fact that most previous observations date from the thrombolytic era, whereas nowadays patients are pretreated with heparin, aspirin, and clopidogrel during transportation to a PCI facility. These antithrombotic agents can induce enhancement of lysis and dissolvement of thrombus, causing pharmacological reperfusion before the initial angiogram (21,22).
In our study we compared 2 manual thrombus-aspiration catheters. However, there are several types of adjunctive mechanical devices for reducing distal embolization. Recently a meta-analysis has been published combining the results of 21 randomized trials investigating the impact of adjunctive mechanical devices to prevent distal embolization (4). In this analysis, the benefit in terms of better myocardial perfusion and less distal embolization was more apparent in studies investigating the impact of thrombectomy as compared with distal protection devices. Whether there is a difference in efficacy between different types of adjunctive mechanical devices (for example, mechanical thrombectomy vs manual thrombus aspiration) is currently unclear in the context of STEMI, because no direct comparisons have been performed.
This study has several limitations. Both study groups were followed up prospectively and matched for age, gender, initial TIMI flow grade, and infarct-related segment, but bias of unknown confounders still might exist. Our histopathological analysis provides information on aspiration capacity in terms of presence of thrombotic material and size of aspirated particles. However, no analysis was performed on the total volume of retrieved debris. A distal embolic protection device may be useful for investigating differences in the volume ratio of aspirated versus distal embolic debris, but these devices are only feasible in a selected group of patients.
The present study shows that manual aspiration catheters are safe and effective in removing thrombus in patients with ST-segment elevation myocardial infarction. A larger internal lumen diameter did not result in retrieval of larger thrombotic particles, nor in improved angiographic or electrocardiographic outcomes.
- Abbreviations and Acronyms
- coronary artery bypass grafting
- creatine kinase
- interquartile range
- percutaneous coronary intervention
- ST-segment elevation myocardial infarction
- Thrombolysis In Myocardial Infarction
- Received February 8, 2008.
- Revision received March 7, 2008.
- Accepted March 15, 2008.
- American College of Cardiology Foundation
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