The role of thrombectomy and embolic protection devices

Abstract

In recent years, it has been demonstrated that restoration of normal coronary flow in the infarct-related artery is not equivalent to the restoration of myocardial perfusion through cardiac microcirculation. Among patients with ST-segment elevation myocardial infarction (STEMI) who undergo primary percutaneous coronary intervention (PCI), distal embolization and slow-flow and no-flow phenomenon occur in ∼30% of patients. In these patients, PCI results are less satisfactory, with lower thrombolysis in myocardial infarction (TIMI) or myocardial blush grade (MBG) values, lower rate of a complete resolution of ST-segment elevation, lower left ventricular ejection fraction, and poorer long-term outcome. Studies investigating the usefulness of thrombectomy systems in STEMI showed a similar proportion of patients with TIMI (flow grade 3) in the infarct-related artery in thrombectomy treated patients and control groups. Some small studies with thrombectomy systems or distal protection devices showed encouraging results with preventing slow-flow, no-reflow, and distal embolization, as measured by improved myocardial perfusion by angiography and improved ST-segment elevation resolution after PCI. Large, multi-centre studies did not confirm clinical benefit. New European Society of Cardiology PCI guidelines do not give definitive recommendations regarding the use of embolic protection devices for this group of patients. More randomized trials are needed. However, thrombectomy may be very effective in the situation of large thrombus bulk when present after first balloon catheter inflation. It could be also potentially effective with easy to use thrombectomy system for replacing balloon pre-dilatation before stenting, if studies could prove clinical benefit of such concept for primary PCI.

Introduction

In recent years, it has been demonstrated that restoration of normal coronary flow in the infarct-related artery is not equivalent to the restoration of myocardial perfusion through cardiac microcirculation. After conventional primary percutaneous coronary intervention (PCI) with stent implantation and GPIIb/IIIa blockade, the normal myocardial perfusion expressed on angiography by the myocardial blush grade (MBG) 3 is seen in one-third of patients. In other two-third cases, impaired microcirculatory perfusion is observed (MBG grade 0 to 2), accompanied by only partial (30–70%) or no (<30%) resolution of ST-segment elevation in electrocardiogram.¹ Conversely, it is recognized that complete resolution of ST-segment elevation (>70%) in resting electrocardiogram is a good indicator of restoration of myocardial perfusion. Accordingly, patients with impaired microperfusion have increased early and late mortality, larger irreversible myocardial injury, and consequently higher incidence of adverse remodelling of the left ventricle leading to heart failure.²

One of the main causes of inadequate myocardial reperfusion despite restoration of epicardial flow in the infarct-related artery is embolization of distal artery, side branches, and/or microcirculation by embolic material consisting of fragmented thrombus, fragmented plaque, and lipids released from the plaque core as well as platelet and platelet–leukocyte aggregates released from the culprit lesion in the course of fibrinolytic therapy, and/or primary PCI. Other reasons include increased microcirculatory resistance due to neutrophile obstruction of microcirculation and/or constriction of arterioles, progressing myocardial oedema, and myocardial damage following reperfusion. In extreme cases, these phenomena may lead to epicardial flow stoppage despite removal of mechanical obstruction in the infarct-related artery (no-reflow).³

Distal protection systems in primary PCI for STEMI

Two distal protection devices [PercuSurge GuardWire (Medtronic, Santa Rosa, CA, USA) and FilterWire EX (Boston Scientific, Santa Clara, CA, USA)] have proved their beneficial clinical effect for PCI of saphenous venous bypass graft lesions.^4,5 The hope that the distal protection may improve results of primary PCI for ST-segment elevation myocardial infarction (STEMI) is based on the fact that GuardWire system provides protection against distal embolization during each balloon inflation, whereas thrombectomy is performed only before stent implantation. Consequently, intracoronary thrombectomy does not prevent distal embolization from the material shed during stent implantation or following post-dilatations.

Nakamura et al.⁶ in the rather small group of 42 patients with anterior acute myocardial infarction have shown that application of the GuardWire system during primary PCI leads to better post-PCI epicardial and myocardial perfusions than primary stenting after intracoronary thrombectomy. Use of distal protection device showed greater improvement in left ventricular ejection fraction, left ventricular end-systolic volume index, and regional wall motion abnormalities during follow-up.⁶

Promising initial results with GuardWire have so far not been confirmed by the larger randomized studies like EMERALD (Enhanced Myocardial Efficacy and Removal by Aspiration of Liberated Debris). Despite the fact that thrombotic and plaque debris were found in aspirates of 76% of patients, no differences were found between studied groups in angiographically assessed myocardial reperfusion, ST-segment elevation resolution, or infarct size measured by isotope scan at 30 days. A theoretical difference between study groups, as a result of mechanical protection use, was probably reduced by improvement in results of control group achieved by high (>80%) usage of GPIIb/IIIa inhibitors during PCI.⁷

The results of the EMERALD trial have seriously impeached the concept of mechanical cardioprotection of microcirculation during primary PCI for STEMI. The GuardWire system, however, has important limitations. Aspiration of thrombo-embolic material is performed via an ordinary perfusion catheter without thrombus fragmentation that is the hallmark of AngioJet or X-Sizer. It may result in inability to remove the large fragment of thrombotic debris. Also, the balloon of GuardWire is inflated 3–5 cm beyond occlusion site and as such has no ability to prevent distal embolization of side branches originating in between. Furthermore, if the GuardWire is advanced directly to serve as the so-called ‘buddy wire’, distal embolization is possible by the mobilization of thrombi in the entire arterial segment when device crosses the target lesion. Such technique was used in majority of EMERALD patients and may have accounted for some lack of distal protection efficacy.⁷

Distal protection is also possible with intracoronary filters. Such devices have been demonstrated to improve outcomes in elective PCI in saphenous venous bypass graft.⁵ Limbruno et al.⁸ achieved better corrected thrombolysis in myocardial infarction (TIMI) frame count, myocardial blush, and full ST-segment resolution in patients in whom FilterWire EX device was used during primary PCI for STEMI, when compared with control. However, data from large randomized studies of filters in the setting of primary PCI for STEMI are not yet available. At ACC meeting 2005, the PROMISE (Protection Devices in PCI-Treatment of Myocardial Infarction for Salvage of Endangered Myocardium) trial with FilterWire EZ was announced as a negative one. Average flow velocity (basal and adenosine-induced), which was the primary endpoint of the study, and coronary flow reserve were essentially the same in both groups. There was a slight trend towards a reduced incidence of distal embolization in patients treated with the FilterWire vs. usual care, but the difference did not reach statistical significance. The differences in the infarct size (assessed by percentage of left ventricular mass, as well as peak creatine kinase levels) were also non-significant between the two groups. However, the FLAME (The FilterWire EZ System Used in the Treatment of an Acute Myocardial Infarction for Embolic Protection) large-scale trial utilizing next generation of this device, FilterWire EZ, during primary PCI for STEMI and assessing myocardial necrosis by cardiac magnetic resonance and scintigraphy has been stopped recently. The final FLAME data will be presented at the TCT 2005. In contrast, the effectiveness of intracoronary filters can be reduced by the risk of distal embolization during passage through the lesion with guide wire and relatively high profile of filter before deployment of the system. It is hard to prevent distal embolization of side branches originating between target lesion and open filter basket. Moreover, distal filter devices require also a pore size of ∼100 µm to permit blood flow, but most particles liberated during PCI are <100 µm.⁵

Proximal protection devices in primary PCI for STEMI

The usage of Proxis Embolic Protection System (Velocimed, Maple Grove, MN, USA) is a new concept of reducing distal embolization during primary PCI in STEMI. This catheter deployed proximal to the target lesion, interrupting anterograde blood flow before crossing the lesion. The FASTER (The Feasibility And Safety Trial for its embolic protection device during transluminal intervention in coronary vessels: a European Registry) trial has shown that retrograde blood flow can be achieved during proximal occlusion and that the Proxis system can be used safely during intervention of saphenous venous bypass graft and native coronary arterial lesions to capture embolic material, but experiences with the Proxis system during primary PCI in STEMI are limited.⁹ Unlike distal protection devices, interrupting anterograde blood flow can be achieved with the Proxis system before crossing with guide wire, which may reduce risk of distal embolization. The Proxis system retrieves of embolic material of any size and composition. The Proxis system can also prevent distal embolization of all side branches originating beyond target lesion. Similar to PercuSurge GuardWire, continuous visualization of the target lesion can be limited and it may be essential in the case of complex lesion or coronary artery dissection. Usage of the Proxis system may be unfeasible in the small target vessel <2.5 mm and in the ostial and proximal localization of the target lesion because of the need of ‘landing zone’. It could be an important limitation because many target lesions are located in the proximal segments of native coronary arteries.¹⁰ Large scale, multi-centre trials are needed to confirm feasibility of the Proxis system during primary PCI in STEMI.

Percutaneous intracoronary thrombectomy in STEMI

The main limitation of the distal application of occlusive balloons or filters to the lesion is to look for ‘landing zone’ and need to cross the lesion which may cause distal embolization. To avoid these limitations, thrombectomy devices were developed. Currently, there are several systems for percutaneous intracoronary thrombectomy. The most widely studied systems both in clinical trials and in everyday practice are AngioJet (Possis Medical, Minneapolis, MN, USA), X-Sizer (eV3, Plymouth, MN, USA), and Rescue (Boston Scientific, Maple Grove, MN, USA).^11–18 Furthermore, intracoronary thrombectomy is being performed with perfusion catheters such as Export Catheter (Medtronic, Santa Rosa, CA, USA), Diver CE (Invatec, Roncadelle, Italy), Rinspiration System (Kerberos Proximal Solutions, Cupertino, CA, USA), as well as standard guiding catheters.^19,20 The systems differ considerably in construction and principles of operation.

Several small studies have shown improved outcomes in STEMI patients with large thrombus treated with thrombectomy during primary PCI. These studies showed improved ST-segmentation resolution^13–18 and smaller infarct size assessed by technetium-99m sestamibi scintigraphy.¹⁷ However, the initially encouraging results in small patient populations have so far not been confirmed in large randomized studies. During Transcatheter Therapeutics 2004 (TCT), Arshad Ali has presented for the first time the negative results of the AIMI study (AngioJet Rheolytic Thrombectomy in Patients Undergoing Primary Angioplasty for Acute Myocardial Infarction). This unexpected failure has put the prospects of AngioJet in treatment of STEMI patients in severe doubt. However, serious limitations of that study have to be recognized. Only one-third of patients enrolled in AIMI presented with anterior myocardial infarction. TIMI grade 0 flow was found in baseline angiography of only 55% of patients in the AngioJet group and 53% of patients in the control group. Conversely, absent or minimal thrombus was reported in 23 and 27% of patients, respectively. Furthermore, baseline TIMI grade 3 flow was statistically more frequently observed in the control group (19 vs. 27%, P<0.05). It appears that further studies will be necessary to finally elucidate the utility of AngioJet during primary PCI for STEMI; specifically, higher risk patients should be conceivably studied to find possible benefits.¹²

It has been demonstrated that thrombectomy with X-Sizer prior to stent implantation during primary PCI in STEMI effectively decreases thrombus mass in the culprit lesion, allowing restoration of TIMI grade 3 flow in large proportion of patients and preventing slow-flow, no-reflow, and distal embolization, as measured by improved myocardial perfusion by angiography and improved ST-segment elevation resolution at 60 min post-PCI.^15,16,18 Larger scale studies will be necessary to prove whether these favourable acute effects can result in improvement in left ventricular function and in decrease of adverse coronary events in the long-term follow-up. Furthermore, technical limitations of X-Sizer have to be acknowledged. The significant rigidity of the catheter decreases its ability to cope with tortuosity and excessive calcifications proximal to the culprit lesion. Its large profile disables it from crossing very tight lesions and limits its utility to arteries with reference diameter >2.5 mm. Moreover, X-sizer could be only partially effective in very large vessels. The presence of the cutting blade in conjunction with difficult anatomy increases the probability of vessel perforation.

The thrombectomy by the Rescue system is safe and effective in thrombus removal from the coronary lumen.¹¹ However, shortcomings include difficulties with complex coronary anatomy proximal to the culprit lesion. Some small studies showed improved ST-segment resolution at 60 min post-PCI and trend to improved myocardial perfusion.^14,21 An additional limitation when compared with X-Sizer and AngioJet is the lack of active defragmentation of thrombus before removal. This seems to be the main reason why the Rescue system is less effective than the other two devices in handling massive thrombi in large coronary vessels.²²

Recently, the Diver CE aspiration catheter was introduced into clinical practice. It contains a central aspiration lumen and a soft atraumatic tip with or without multiple side holes (first dedicated for fresh thrombus, second for ‘older’ thrombus) communicating with the central lumen, allowing easy insertion and effective clot removal by blood syringe aspiration from the proximal hub. The experience with the Diver CE aspiration catheter in patients with STEMI undergoing primary PCI showed that it is possible and safe in the majority of patients to re-establish TIMI grade 3 flow in the culprit artery without balloon pre-dilatation.²⁰ In most of these cases, direct stent implantation is the method of choice for a final lesion stabilization. Whether the strategy of intracoronary thrombectomy with Diver CE followed by direct stent implantation is superior to standard balloon pre-dilatation followed by stent implantation should be confirmed in further clinical trials, for example in currently ongoing PIHRATE trial (Polish-Italian-Hungarian Randomized ThrombEctomy Trial). An example of thrombectomy effectiveness during primary PCI in STEMI with the Diver CE catheter is shown in Figure 1.

The Rinspiration System was introduced to optimize thrombus aspiration by changing laminar flow to turbulence assisted aspiration.¹⁹ This system seems to be easy to use, relatively safe, can effectively reduce thrombus bulk, and may be alternative to other thrombectomy systems. Some large randomized studies should check the efficacy of this system.

It seems that thrombectomy systems do not need any adjunctive pharmacotherapy except aspirin, thienopyridine, and heparin. The GPIIb/IIIa blockers should have synergistic action, improving microcirculation by decreasing platelet activity and attenuating inflammatory response in small vessels.^23,24 When compared with placebo, early administration of abciximab in patients with STEMI improves coronary patency before stenting, the success rate of the stenting procedure, the rate of coronary patency at 6 months, left ventricular function, and clinical outcomes.²⁵ Abciximab as adjunctive treatment to routine infarct-related artery stenting for STEMI resulted in improved 1-year survival and lower re-infarction rates.²⁶ Similarly, recent meta-analysis has shown that adjunctive abciximab use during primary PCI for STEMI is associated with a significant reduction in 30-day and long-term mortality.²⁷ Patients treated with GPIIb/IIIa blockers also have better blood flow through infarct-related artery and regional contractility of left ventricle.²⁴

However, a study comparing the combined usage of abciximab and thrombectomy with thrombectomy alone failed to document any significant differences between these two approaches in the long-term improvement in left ventricular systolic function.²⁸ Also in a study in which the X-Sizer system was used in STEMI patients, no significant differences were found in myocardial perfusion between GPIIb/IIIa blockers combined with thrombectomy vs. thrombectomy alone (MBG grade 3: 51.3 vs. 56.6%, P=NS).¹⁵ In addition, the X-Sizer AMI registry did not reveal any additional effects of GPIIb/IIIa blockers on coronary microcirculation.²⁸

Thrombectomy and proximal and distal protection devices are not recommended for routine practice for primary PCI in European Society of Cardiology guidelines (class IIb C).²⁹ Distal embolic protection is recommended only for PCI in saphenous venous bypass grafts (class I A). Distal proximal protection devices or thrombectomy could be considered in acute coronary syndromes patient only when high thrombus load is detected in native vessel (class IIb C). However, in patients with STEMI, percutaneous thrombectomy is safe and is connected with high level of opening infarct-related artery. Use of thrombectomy devices leads to the improvement in ST-segment resolution when compared with standard primary PCI. Some new studies are necessary to answer whether thrombectomy can influence left ventricle function and long-term clinical follow-up in patients with STEMI, to find more convincing arguments for routine recommendations. Many operators expect beneficial clinical impact of easy-to-use manual thrombectomy devices in patients with occluded infarct-related artery. In such case, simple manual aspiration thrombectomy systems could replace standard balloon catheter pre-dilatation and may help to achieve normal coronary flow before direct stent implantation. In contrast, use of thrombectomy systems with active thrombus defragmentation may be very effective in the situation of large thrombus bulk when thrombus was present after first balloon inflation during standard primary PCI procedure.

Conclusions

• Despite achieving TIMI grade 3 flow, myocardial perfusion in STEMI remains suboptimal in a significant number of patients, resulting in larger final infarct size.

• Effective removal of thrombi prior to stenting might reduce distal embolization of thrombus, which could improve myocardial perfusion and salvage.

• Distal embolic protection has not resulted in reduction of infarct size or improvement in event-free survival.

• Randomized studies and guidelines do not support routine use of distal embolic protection or thrombectomy devices with primary PCI in all STEMI patients for reduction of major adverse cardiac event rates.

• Simple aspiration with easy-to-use catheter is able to extract athero-thrombotic material from target lesion, restoring flow and increasing patency rate of infarct-related artery before stenting. Such simple aspiration instead of balloon pre-dilatation and direct stenting following thrombectomy may be the hypothetical option for selected patients during primary PCI.

• Thrombectomy systems with active thrombus defragmentation may be very effective in the situation of large thrombus in large vessels in patients with acute myocardial infarction.

• Additional new studies are necessary to prove the benefit of thrombectomy or distal embolic protection systems on clinical outcome and not to be only focused on better ST-segment resolution or angiographic myocardial perfusion.

Conflict of interest: none declared.

References