Emboli Protection Devices in Cardiovascular Medicine

Abstract

Emboli protection devices (EPD) have a solid stand in the modern armamentarium of the interventionalist. However, the use of these devices is associated with a broad range of benefits in different cardiovascular territories. The most compelling data for mechanical emboli protection are available for percutaneous interventions of aortocoronary bypass grafts. In this setting, randomised studies have shown that the use of EPD is associated with a significant reduction in major adverse events. Nevertheless, current registry data suggest that the devices are used only in a minority of those cases. Conversely, in acute myocardial infarction, the routine use of EPD was not found to be beneficial. A strong consensus, though not unanimous, supports the use of these devices for carotid artery stenting. With respect to renal stenting, the experience is still at an early stage and the use of EPD cannot be recommended.

Introduction

Distal embolisation of plaque or thrombotic material may occur spontaneously during the process of plaque rupture and subsequent thrombus formation or may be induced by balloon angioplasty or stenting. The detection of this phenomenon, more frequent than previously believed, has been made possible by imaging technologies such as magnetic resonance, myocardial contrast echocardiography, and transcranial Doppler. The linkage between microvascular obstruction and unfavorable long-term clinical outcomes has been established for multiple vascular beds. Distal embolisation during percutaneous revascularisation may be prevented using a pharmacological (i.e., by periprocedural potent platelet inhibition and/or anticoagulation) or a mechanical approach.

The concept of mechanical emboli protection is based on the placement of a filter device between the lesion treated and the distal vasculature or by a blockage of the blood flow in the vessel – either proximally or distally to the lesion – followed by an aspiration of the blood column prior to allow flow. The different approaches of mechanical emboli protection, in the example of carotid artery stenting, are demonstrated in Figure 1. As a general rule, filter-based emboli protection devices (EPD) are easy to use, allow blood flow throughout the procedure but particles smaller than the pore size (usually 100–150 μm) may reach the distal vasculature. Distal and proximal balloon occlusive devices allow for more complete retrieval of small particles suspended in the blood column at the time of intervention. The disadvantage of these approaches is the potential for ischaemia and the poor visualisation of the lesion (

Table 1. Pros and cons of emboli protection devices (after [23]).

). Protection devices have been tested – with different degree of success – in various arterial beds including the coronary circulation, aortocoronary bypass grafts, the carotid artery, and the renal artery. The purpose of this manuscript is to briefly review the data supporting the use of EPD in cardiovascular interventions.

Acute myocardial infarction

Several small studies have addressed the impact of EPD in the setting of acute myocardial infraction (MI). The largest of them was the EMERALD trial, which randomised 501 patients to conventional treatment or distal balloon protection. No difference was observed in terms of postprocedural ST-segment resolution on ECG, infarct size, or major clinical events at six months [1]. In a meta-analysis of eight randomised studies, for a total of 1467 patients, no difference in terms of post-procedural blood flow normalisation among patients with acute MI treated with protection and those without protection was observed [2]. However, an improvement in myocardial blush grade, suggesting a reduced damage of the microcirculation could be detected. Similarly, in the group treated with protection there was less frequently angiographic evidence of distal embolisation. Nevertheless, these findings were not associated with a survival benefit. In acute MI, the mainstay of distal embolisation prevention is a pharmacologic one based specifically on glycoprotein IIb/IIIa receptor (GP IIb/IIIa) inhibitors. Accordingly, the use of these agents has been associated with improved outcomes in this setting [3]. Adjunctive mechanical emboli protection should be reserved for selected cases with large thrombus burden (Figure 2).

Aortocoronary bypass grafts interventions

Percutaneous coronary intervention (PCI) of saphenous vein grafts (SVG) has been associated with less favorable outcomes compared to procedures involving the native coronary circulation. Acute complications include distal embolisation, “no-reflow”, and higher rate of periprocedural MI. Vein graft and coronary atherosclerosis are to be considered different diseases. Graft atheroma is diffuse, friable, soft, and lipid-rich. The fibrous cap is usually poorly developed or absent and marked calcification is rare [4]. All these features make SVG lesions prone to fragmentation and distal embolisation during PCI.

The use of EPD has been a major breakthrough in SVG PCI. A randomised trial enrolling over 800 patients using distal balloon occlusion demonstrated a 42% relative risk reduction of major adverse cardiac events at one month among patients allocated to emboli protection [5]. Most of the benefit was due to a reduction in periprocedural MI (Figure 3). Comparative studies among different type of EPD have followed. Current data suggests that filter devices, distal balloon occlusion devices and proximal occlusion devices may convey similar benefits [6,7]. Conversely, pharmacologic prevention of distal embolisation by means of glycoprotein IIb/IIIa receptor inhibitors was found of no benefit for SVG PCI. Accordingly, a pooled analysis of five large-scale randomised trials including over 600 patients undergoing bypass graft intervention detected no benefit from active treatment compared with placebo [8]. The likely explanation for this failure is that the amount and/or the composition of the material embolised during the procedure may overwhelm the capacity of these agents to protect the distal vasculature. Data from a large United States registry demonstrated that, despite the strong data supporting its use, EPD are currently deployed in <25% of SVG PCI [9]. In summary, mechanical emboli protection should be applied whenever feasible during PCI of SVG while no GP IIb/IIIa blockade is necessary. Importantly, this does not apply for intervention of arterial grafts (no data).

Carotid artery stenting

Distal embolisation remains the most feared complication of carotid artery stenting (CAS), although its incidence can be reduced by proper technique, adequate antithrombotic therapy, and the use of EPD. Virtually any step of the procedure may be associated with debris formation. The two most critical steps in this respect are the engagement of the common carotid artery with the guiding catheter or sheath and the postinflation of the stent [10]. The initial need for EPD came from transcranial Doppler studies demonstrating that, though in most cases clinically silent, embolic signals could be detected in virtually all cases of surgical and endovascular carotid revascularisation. Accordingly, new lesions on diffusion-weighted MRI following nonprotected CAS may be documented in over half of the patients [11]. A systematic review including 2357 patients undergoing unprotected CAS and 839 patients stented with adjunctive EPD documented a 30-day death or stroke rate of 5.5% and 1.8% (p <0.001), respectively (Figure 4) [12]. A German prospective CAS registry assessing 1483 procedures detected an in-hospital death or stroke rate of 2.1% among 666 patients undergoing CAS with adjunctive EPD and an event rate of 4.9% among 789 patients treated without EPD. Even after correcting for baseline characteristics the use of EPD was identified as independent protective factor (adjusted OR 0.45; 95% CI: 0.2–0.9; p = 0.026) [13]. Similarly, in a multicenter feasibility trial of CAS performed in 261 patients with and without EPD the oneyear major ipsilateral stroke rate was significantly lower among patients undergoing CAS with adjunctive EPD (0% vs 2.3%, p = 0.05) [14].

As a possible confounding factor, EPD have been used more recently and therefore likely at a later stage of the operator’s learning curve. Nevertheless, even in large volume centers, the use of EPD positively impacted outcomes. The placement EPD during CAS has been widely embraced, particularly within the community of interventional cardiologists. In our experience, EPD may be utilised in 95% of cases [15]. As correlated of distal embolisation during filter-based CAS, transient flow obstruction in the internal carotid artery may be observed (Figure 5A,B) [16]. The incidence of this phenomenon may differ according to the type of device used [17]. From a clinical perspective, filter EPD and occlusion-based EPD appear to convey similar efficacy [18]. A broadly shared consensus, though not unanimous, supports the use of EPD during CAS despite the lack of randomised trials based on the efficacy data available and the low device-related complication rate (<1%) [19]. In my opinion, CAS should be routinely performed with EPD. If this is not technically feasible, surgery should be considered.

Renal stenting

In order to prevent decline in renal function following renal revascularisation in patients with renal artery stenosis and renal insufficiency, it is currently being explored whether the use of EPD reduce the incidence of periprocedural atheroembolic renal disease (Figure 6). As opposed to the internal carotid artery or aortocoronary bypass grafts, the renal artery is characterised by a short trunk and early branching. These anatomical features limit the ability to protect the distal vasculature with a device. Although protected renal stenting is feasible, its clinical relevance in terms of preservation of renal function remains to be determined [20]. Encouraging appear the results of a French series showing no deterioration in renal function at six months among 45 patients treated under the protection of distal balloon occlusion [21]. Investigators from New Zealand have reported that among 63 patients with renal artery stenosis and renal dysfunction filter-protected renal stenting was associated with stabilisation or improvement of renal function in 97% of cases at six months, whereas in 3% of the patients renal function further declined [22]. Potentially, the use of this device could have deleterious effects including the need for longer catheter manipulations or the administration of a larger amount of contrast medium. In addition, the effects of microembolisation in the kidney are clearly less devastating than in the brain. Until randomised data assessing the efficacy of EPD become available, embolic mechanical protection cannot be advocated during percutaneous renal interventions.

Conclusions

EPD have a solid stand in the modern armamentarium of the interventionalist. However, the use of these devices is associated with a broad range of benefits in different cardiovascular territories. The most compelling data for mechanical emboli protection are available for percutaneous coronary interventions of aortocoronary vein grafts. In this setting, randomised studies have shown that the use of EPD is associated with a significant reduction in major adverse events. Nevertheless, current registry data suggest that the devices are used only in a minority of those cases. A strong consensus, though not unanimous, supports mechanical emboli protection for carotid artery stenting. In acute MI, the routine use of EPD was not found to be beneficial. Nevertheless, these devices may be considered in selected cases with large thrombus burden. With respect to renal stenting, the experience is still at an early stage and the use of these EPD cannot be recommended.