Current Considerations of Thrombectomy for Acute Myocardial Infarction

Ahmed N. Mahmoud, MD, Islam Y. Elgendy, MD and Anthony A. Bavry, MD, MPH,2

1Department of Medicine, University of Florida, Gainesville, FL, USA

2North Florida/South Georgia Veterans Health System, Gainesville, FL, USA

Introduction

ST-elevation myocardial infarction (STEMI) is due to thrombotic occlusion of an epicardial coronary artery [1, 2]. Without reperfusion there is a high incidence of death and disability [3]. Reperfusion therapy was first successfully achieved with intravenous thrombolytic therapy [4, 5]. While intravenous thrombolytic therapy is still frequently used worldwide, it is limited by incomplete reperfusion in a significant proportion of cases and it is rarely associated with intracranial hemorrhage [6–8]. Primary percutaneous coronary intervention (PCI) represents a significant achievement to safely and more predictably restore flow to the epicardial artery [9,10]. While primary PCI is effective at restoring epicardial flow, myocardial perfusion can still remain compromised at a microvascular level, presumably due to embolization of thrombotic debris [11].Impaired myocardial perfusion is evidenced by poor myocardial blush grade and incomplete ST-segment resolution, both of which are associated with worse outcomes [12–14]. In current day practice, primary PCI is usually performed with adjunctive stent placement. This is done to treat an underlying stenotic lesion or to stabilize an area of disrupted plaque. The immediate goal of thrombectomy is to improve flow in the artery and optimize stent sizing, while the longer-term goal of thrombectomy is to reduce future adverse cardiac events such as repeat revascularization and stent thrombosis. This review will discuss the evolution of thrombectomy devices during acute myocardial infarction, recent clinical trial data on the topic, and what the future of thrombectomy may hold.

Thrombus Removal Devices

A variety of devices have been developed to remove thrombus during PCI. These devices are broadly grouped into (1) embolic protection devices, which capture embolized thrombus during PCI, (2) devices which attempt to break up the thrombus to facilitate removal, and (3) aspiration or suction devices,which rely on vacuum to remove thrombus [15].

Embolic Protection Devices

Embolic protection devices (also referred to as filter devices) were studied as a means to prevent distal embolization during PCI. As such, embolic protection devices only remove thrombus that embolizes into the filter [16]. This strategy has not been found to be effective at preventing adverse events during primary PCI of a native coronary artery [17]. Possible explanations for the lack of benefit include unintended embolization as the un-deployed filter is advanced through the thrombotic lesion. Alternatively, thrombus that remains in place at the site of occlusion, is not removed from the coronary artery, and thus may contribute to sub-optimal PCI and future adverse events [18].These devices are currently only recommended during revascularization of saphenous vein graft lesions [19].

Devices to Breakup Thrombus Prior to Removal

Rheolytic thrombectomy (i.e. Angiojet) is the best-known example of this type of device. With this device, saline jets are forced inside the catheter from the distal end to proximal. Some of the saline exits and then re-enters the catheter. The anticipated effect of the saline flow is to facilitate breakup and removal of thrombus [15]. The amount of thrombus removed by rheolytic thrombectomy appears to be rather modest as evidenced by no improvement in myocardial blush grade and a small improvement in complete ST-segment resolution [17, 20]. These devices also require the need for a temporary pacemaker in a significant proportion of cases [21]. Correspondingly, this device has failed to improve clinical outcomes and may increase the risk of stroke [17, 20]. Therefore,rheolytic thrombectomy is infrequently used in clinical practice.

Aspiration or Suction Devices

Aspiration thrombectomy catheters are simple devices that are advanced into a thrombus-containing artery. The tip of the catheter has an opening, which engages the thrombus. Many brands are available with differences in tip and mouth design. Once the catheter is advanced proximal to the thrombus, vacuum is applied to the catheter which acts to suck thrombus from the artery[15]. These devices are easy to use and are more effective at improving myocardial perfusion than rheolytic thrombectomy [17, 20]. While they extract microscopic thrombotic debris approximately 70% of the time, extraction of visible thrombus (>1 mm) only occurs in 35–44% [22,23]. Although somewhat counterintuitive, angiographic evidence of thrombus has not been shown to predict successful retrieval with aspiration thrombectomy devices [22].

Clinical Evidence

The Thrombus aspiration during primary percutaneous coronary intervention (TAPAS) trial was the first large size trial to compare thrombectomy compared with primary PCI alone [23]. This trial documented a marginally significant reduction in mortality. This outcome was an unexpected finding and not the primary outcome of the trial. While this possible mortality benefit should have been interpreted with caution, it ushered in enthusiasm for widespread thrombectomy use during acute myocardial infarction. Subsequent meta-analyses documented mortality benefit with thrombectomy compared with primary PCI alone [17, 20, 24]. However, the field changed dramatically after documentation of negative findings with the Thrombus Aspiration during ST-segment Elevation Myocardial Infarction(TASTE) (n=7244 patients) and Randomized Trial of Primary PCI with or without Routine Manual Thrombectomy (TOTAL) (n=10,732 patients) trials[25, 26]. An updated meta-analysis including these 2 most recent and largest trials was unable to confirm benefit from a strategy of routine thrombus removal[27]. In that analysis, aspiration thrombectomy was associated with a non-significant reduction in allcause mortality and a non-significant increase in stroke. Current practice guidelines no longer support the routine use of thrombectomy, but still consider it effective in certain circumstances (class IIb recommendation) [28]. Furthermore, the Thrombus Aspiration in Thrombus Containing Culprit Lesions in Non-ST-Elevation Myocardial Infarction(TARTOR-NSTEMI) trial had demonstrated the lack of benefit for aspiration thrombectomy in patients with NSTEMI where there may be smaller thrombus burden [29]. Also, aspiration thrombectomy has not demonstrated benefit on microvascular obstruction among patients with STEMI who present late (i.e.,beyond 12 hours) [30].

Theories Behind the Lack of Improved Cardiovascular Outcomes Following Aspiration Thrombectomy

Intuitively, the concept of thrombus removal during acute myocardial infarction still appears to be valid. During STEMI, stent implantation in a large thrombus significantly increases the risk for subsequent stent thrombosis [31]. Other studies have also confirmed an increased risk of adverse events when thrombus is present during the index PCI procedure[32]. In addition to risk of stent thrombosis, thrombus can make stent sizing difficult and increase the risk of stent malposition resulting in increased revascularization procedures [32–34].

There are multiple reasons why thrombectomy,in its present form, may be ineffective. First, it is possible that sub-optimal technique can result in embolization of thrombus into the aorta and provide a mechanism for stroke [35]. While this complication is rare, the deleterious effects of a neurological ischemic event could negate any benefit from thrombectomy. Good practice with thrombus removal should always be observed [15].

The second consideration is that not all STEMI is due to large thrombus burden [31]. A study in STEMI patients attempted to characterize the size of thrombus. An interesting finding is that approximately 70% of cases were associated with ≤ medium thrombus burden [31]. With non-large thrombus, any benefit from thrombus removal would be expected to be minimal or non-existent. Future study of thrombectomy may need to focus on the approximate 30% of cases with ≥ large thrombus.

The third reason for lack of benefit with thombectomy could be that current thrombectomy devices are not effective enough. In approximately one-third of cases, visible thrombus (>1 mm) is observed in blood that has been aspirated from a coronary artery[22]. Also, while markers of reperfusion are better with aspiration thrombectomy compared with rheolytic thrombectomy, they are still not 100% effective. This is evidenced by the myocardial blush grade≥2 of approximately 59% and complete ST-segment resolution of approximately 68% after aspiration thrombectomy [27]. Aspiration thrombectomy catheters may work best at removing soft thrombus that is small enough to be sucked into the device.In contrast, solid/firm thrombus or large thrombus may be more difficult to remove with this device.Retrievable stents were designed to remove more solid/firm thrombus from the cerebrovascular circulation. They have been studied and approved for use during acute ischemic stroke [36–38]. A meta-analysis of randomized trials documented an improvement in functional outcomes and a non-significant reduction in mortality with retrievable stent devices compared with usual care during acute ischemic stroke [39]. Since these devices have been shown to be beneficial in acute ischemic stroke, they may deserve to be studied in acute myocardial infarction.Another option might be the use of external transthoracic ultra-sound to facilitate coronary thrombolysis,which has been shown in animal models and limited human studies to be associated with improved coronary patency rates [40, 41]. However, the clinical benefit of utilizing such an approach, either alone or as an adjunct to aspiration thrombectomy, still needs to be proven in larger clinical trials.

The final consideration is that stent implantation into thrombus may not be as deleterious as imagined due to a variety of reasons. This could be because of increased use of intravascular ultrasound during STEMicould help to properly size stents [42]. The M-guard stent is an experimental stent which is covered by mesh material intended to capture thrombus between the stent and the wall of the vessel during implantation, thus preventing distal embolization [43]. It is possible that current generation stents may be functioning in a similar fashion and thus minimizing the impact of distal embolization. Also,potent ADP receptor antagonists are likely reducing the overall risk of stent thrombosis and future adverse cardiac events. It is important to note that the 12 month mortality remains at approximately 4–5%, therefore, opportunities remain to further reduce adverse events [44, 45].

Clinical and Angiographic Predictors of Aspiration Thrombectomy Failure

Unsuccessful aspiration thrombectomy occurs due to failure to reach or cross the culprit lesion and/or failure to collect any thrombotic material after crossing the culprit lesion [46]. This occurs in approximately 4–25% of the cases [46, 47]. Older age,marked artery tortuosity, high coronary calcification and bifurcation lesions have all been associated with a higher incidence of failed aspiration thrombectomy[46–48]. However, it is worth mentioning that the impact of aspiration thrombectomy failure on clinical outcomes remains unclear, as the incidence of mortality in those patients was similar to the patients who had successful thrombectomy [46].

Role of Glycoprotein IIb/IIIa Inhibitors Administration Prior to Aspiration Thrombectomy

Although earlier studies had suggested a potential benefit from upstream glycoprotein IIb/IIIa inhibitors during primary PCI, recent studies have demonstrated the lack of clinical benefit with glycoprotein IIb/IIIa inhibitors in the era of potent ADP antagonists [49, 50]. In the intracoronary abciximab and aspiration thrombectomy in patients with large anterior myocardial infarction(INFUSE-AMI) trial evaluated the potential benefit of local intra-coronary delivery of abciximab with a local infusion catheter, there was no clinical outcome benefit in the arm who underwent aspiration thrombectomy compared with no aspiration thrombectomy [51]. In addition, a meta-regression analysis of randomized trials did not illustrate any added clinical benefit with the concomitant use of glycoprotein IIb/IIIa inhibitors with aspiration thrombectomy [27].

Case Examples

Case 1

An 82-year-old male with prior PCI to the right coronary artery (RCA) developed an inferior STEMI when his dual anti-platelet therapy was held before an invasive procedure. Emergent coronary angiography revealed an occluded distal RCA (Figure 1).The area of occlusion was dilated multiple times with 2.5 mm and 3.0 mm balloons; however, this was unsuccessful in restoring coronary flow. At this point, aspiration thrombectomy was performed.The thrombus was too large to be sucked into the device; therefore, constant suction was applied as the device was removed from the body. The thrombus was noted to become dislodged from the catheter tip within the hemostatic valve. It was removed from the guide catheter by aspirating from the side port of the hemostatic valve (Figure 2). Final angiogram revealed a good result after drug-eluting stent implantation (Figure 3). This case illustrates the application of selective thrombectomy after failure to restore flow with initial balloon angioplasty. It also illustrates a possible mechanism for stroke if the thrombus was not recognized to be retained in the guide catheter and/or hemostatic valve.

Case 2

Figure 1 Distal Right Coronary Artery Occlusion.

A 63-year-old male presented with anterior STEMI.Emergent coronary angiography revealed an occluded mid left anterior descending artery (LAD) (Figure 4).After balloon angioplasty, normal coronary flow was restored with no/minimal thrombus burden at a stenotic lesion (Figure 5). The lesion was attempted to be direct stented; however, a stent would not pass due to significant calcium burden. Rotational atherectomy was performed with a 1.25 mm and a 1.5 mm burr.This allowed for optimal implantation of 2 drug-eluting stents (Figure 6). In this case, balloon angioplasty restored normal flow and uncovered no/minimal thrombus burden; therefore, selective thrombectomy was not felt to be indicated.

Figure 2 4.5-centimeter Thrombus Retrieved from the Distal Right Coronary Artery Following Aspiration Thrombectomy.

Figure 3 Good Angiographic Result in the Right Coronary Artery Following Aspiration Thrombectomy and Drug-Eluting Stent Implantation.This case illustrates an application of selective thrombectomy.

Figure 4 Mid Left Anterior Descending Artery Occlusion.

Figure 5 Normal Coronary Flow in the Left Anterior Descending Artery Following Balloon Angioplasty.There is no/minimal thrombus burden associated with the stenosis.

Figure 6 Good Angiographic Result in the Left Anterior Descending Artery Following Rotational Atherectomy and Drug-Eluting Stent Implantation.This case illustrates an example where thrombectomy was not necessary.

Conclusions

In conclusion, thrombus removal still remains a valid concept during acute myocardial infarction. Currently available aspiration thrombectomy devices are recommended for selective, rather than routine use during STEMI. Future studies will need to focus on safe removal of thrombus (i.e. without increasing the risk of stroke), appropriate lesions from which to remove thrombus (i.e. only thrombi of a certain size/characteristic), and more effective thrombus removal devices. Regarding the latter,devices that are more capable of removing solid/firm thrombi (i.e. retrievable stents) deserve study during STEMI. Opportunities still exist with thrombus management to improve future adverse cardiac events in acute myocardial infarction patients.

Conflict of Interest

The authors declare no conflict of interest.

Funding

This research received no specific grant from any funding agency in the public, commercial or notfor-profit sectors.

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