Primary Percutaneous Coronary Intervention
Primary Percutaneous Coronary Intervention
Mechanical thrombectomy devices vary in their working mechanism depending on their ability to actively fragment atherosclerotic thrombus material prior to aspiration (Table 1). The AngioJet® (MEDRAD, PA, USA), X-Sizer® (eV3 Inc., MN, USA) and Rinspirator™ System (eV3 Inc.) catheters are capable of such active thrombus fragmentation.
The mechanism in the AngioJet rheolytic thrombectomy (RT) system (Figure 1) involves the delivery of pressurized heparinized saline from the catheter, where saline jets travel backwards creating a low-pressure zone and, thus, a powerful vacuum effect. Thrombus, as a result, is drawn back into the catheter, where it is fragmented by the saline jets prior to being evacuated from the body.
(Enlarge Image)
Figure 1.
The AngioJet® (MEDRAD, PA, USA) rheolytic thrombectomy system. Active thrombus fragmentation by pressurized, heparinized saline. (A) Saline jets travel backwards at high speed to create a negative pressure zone (less than -600 mmHg), causing a powerful vacuum effect. (B) Cross-stream® windows optimize the fluid flow for more effective thrombus removal. (C) Thrombus is drawn into the catheter where it is fragmented by the jets and evacuated from the body.
The use of the AngioJet system as an adjunct in PPCI has been tested in three randomized trials. An initial single-center study enrolling 100 patients demonstrated a reduction of infarct size as assessed by Tc- sestamibi scintigraphy and better STR when compared with standard PPCI. The larger, multicenter, randomized AiMI trial that included 480 patients, however, failed to reproduce these initial findings. Importantly, the MACE rate was higher in the thrombectomy group, driven by an increase in 30-day mortality. The discrepancy between the two studies could be explained to some extent by the complexity of the device and, therefore, the impact of operator experience in its use. This also may explain the higher rate of coronary perforation observed in the AiMI trial. In addition, TIMI 3 flow prior to intervention was encountered significantly more often in the standard PPCI than in the thrombectomy group, potentially biasing the differences in infarct size between the two groups. Finally, angiographic evidence of thrombus was absent in a large percentage of both groups (25%) raising the possibility that the AngioJet device is best suited in cases with significant and visible thrombus burden. Use of the AngioJet device, on the other hand, has been associated with an increased incidence of symptomatic bradycardia, thus requiring positioning of a temporary pacing wire, which, in itself, is not without potential complications. Both of these studies were performed over 7 years ago with suboptimal antiplatelet regimens.
The recently published JETSTENT trial aimed to answer the questions raised by the previous two conflicting studies. It recruited 501 patients, all of whom were treated with dual antiplatelet therapy (300-mg aspirin and 600-mg clopidogrel) and glycoprotein (GP) IIb/IIIa antagonists. Exclusion criteria included TIMI thrombus grade <3 and infarct artery reference diameter <2.5 mm on visual assessment. The presence of thrombus as a prerequisite for entry into the study was an important difference between the JETSTENT and AiMI studies. No significant difference in STR, angiographic end points or myocardial infarct size between the AngioJet and conventional treatment groups were detected by Tc- sestamibi scanning. Interestingly, however, a significant decrease in MACE was noted at 6 and 12 months in the AngioJet group, driven primarily by a lower incidence of death and target-vessel revascularization. This was attributed by the authors to improved myocardial perfusion and better stent length and diameter assessment following RT. The results of the JETSTENT, however, need to be interpreted with caution. In this study, infarct size and STR, both established surrogates of prognosis following MI, showed no benefit with the AngioJet device. It is, therefore, difficult to explain what drives the MACE advantage associated with its use. Owing to this anomaly and the associated costs of the device, it has not gained widespread clinical acceptance in PPCI.
The X-Sizer device consists of a dual-lumen hydrophilic-coated catheter shaft connected to a handheld control module (Figure 2). Once the catheter is engaged, the vacuum captures the thrombus, and the helical cutter present inside the inner lumen and inside the distal tip shears this off. The efficacy of the X-Sizer catheter in STEMI patients has been assessed in three randomized trials, and although it has been shown to improve STR at 60 min post-PCI, achieve better angiographic flow, reduce no reflow and distal embolization of atherosclerotic plaque debris, its use did not provide significant clinical benefit at 1 and 6 months (X-AMINE ST trial). Moreover, the routine use of the X-Sizer catheter in PPCI is limited by its rigidity and, thus, inability to navigate tortuous and heavily calcified vessels, as well as by its bulky size, which limits its use to vessels >2.5 mm and without very tight lesions. In one study, failure of X-Sizer thrombectomy was encountered in 24% of cases, and this was associated with increased incidence of 30-day adverse events. It has also been associated with an increased risk of coronary artery perforation.
(Enlarge Image)
Figure 2.
The X-Sizer system® (eV3 Inc., MN, USA). (A) Helical cutter inside the inner lumen of the catheter. (B) Handheld module.
The Rinspirator system is a newer non-manual thrombectomy device consisting of three lumens. The first is a standard coronary guidewire lumen, whereas the second allows for distal aspiration. The third lumen allows injection of a rinsing solution (heparinized saline) through perforations located proximal to the aspiration lumen and distributed circumferentially along a short length of the catheter. This generates turbulent flow that rinses the vessel wall, detaches any adherent thrombus and simultaneously evacuates the thrombotic material from the vessel. According to the initial data from an international registry, this device is safe and its use does not seem to be associated with higher complication rates. To date, however, no clinical benefit has been established.
The TransVascular Aspiration Catheter® (Nipro, Osaka, Japan) and Rescue™ (Boston Scientific, MA, USA) devices do not offer active thrombus fragmentation, but as they are connected to motorized vacuum units they can be considered mechanical thrombectomy devices. Only the TransVascular Aspiration Catheter system has shown some promise based on the results of a multicenter randomized trial (VAMPIRE). This study showed a marginal benefit of thrombectomy on myocardial perfusion as assessed by final TIMI flow and MBG, with the most benefit observed in patients presenting 6 h after symptom onset. MACE rates were similar at 30 days to standard PPCI, but a significant reduction in MACE was seen at 8 months in the thrombectomy group, mainly as a result of lower rates of revascularization in the treatment group. This was attributed to the better TIMI flow following thrombectomy, which may have facilitated better selection of stent diameter and length, as well as to the removal of inflammatory thrombus material. The use of glycoprotein IIb/IIIa inhibitors and drug-eluting stents were not allowed in the VAMPIRE study and it has been conjectured that in the presence of such adjunctive pharmacological intervention, the rate of future revascularization in the control group may have been more comparable to that of the treatment group.
The Rescue system has not been shown to improve infarct size or myocardial salvage as measured by sestamibi SPECT, nor have a beneficial effect on STR, MBG and left ventricular ejection fraction in randomized trials. Equally important, it has been associated with a high rate of procedural failure in the randomized trial by Kaltoft et al. and other study groups due to failure of the catheter to reach the culprit lesion.
In a meta-analysis including multiple devices, Bavry et al. showed that routine use of mechanical thrombectomy in setting of PPCI appears to significantly increase mortality 5.3 versus 2.8% for PCI alone, whereas the use of embolic protection devices has no impact on survival. Negative results of mechanical thrombectomy in this meta-analysis were driven primarily by the largest study in this category – the AiMI trial (AngioJet system) that showed increased infarct size and 30-day mortality rate in RT group. It must be noted that very low mortality rate was observed in patients treated with PCI alone (0.8 vs 4.6% in patients treated with adjunct RT; p = 0.02). Limitations of this work are described above.
Another meta-analysis, the ATTEMPT study, which included pooled analysis on 2686 individual patients' data from 11 randomized trials, comparing thrombectomy plus PPCI with standard PPCI, showed that allocation to mechanical thrombectomy devices, particularly those which involve thrombus fragmentation prior to aspiration, failed to produce a survival benefit. These data are in agreement with a recent meta-analysis by Costopoulos et al., showing that although mechanical thrombectomy was associated with better STR, it failed to produce any benefit in regarding to MBG, TIMI 3 flow, mortality and MACE. When taken alone, mechanical vacuum aspiration was shown to improve STR and MBG but not TIMI 3 flow. Improvement in clinical outcomes was not seen with mechanical vacuum devices, although this, to some extent, could be the result of low overall patient numbers from the four pooled RCTs.
There are several possible explanations for the disappointing results seen with mechanical thrombectomy. First, they tend to be bulkier and have a longer setup time, resulting in longer procedure times. In fact, all mechanical thrombectomy trials showed longer procedure time compared with conventional PCI, a finding not present in the manual aspiration trials. Such differences in procedure times may have an impact especially in patients presenting within 3 h of the onset of infarction. Second, mechanical thrombectomy devices are more complex to operate than manual aspiration catheters, with resultant less favorable learning curves. Operator and staff experience regarding the use of these complex devices is, thus, important and perhaps limited if one considers that most PPCIs occur out-of-hours when staffing levels are reduced and the likelihood of complications is higher. They are, therefore, best avoided in routine PPCIs, although they may have a role in patients with large vessels and a particularly heavy thrombus burden as some studies suggest.
Mechanical Thrombectomy
Mechanical thrombectomy devices vary in their working mechanism depending on their ability to actively fragment atherosclerotic thrombus material prior to aspiration (Table 1). The AngioJet® (MEDRAD, PA, USA), X-Sizer® (eV3 Inc., MN, USA) and Rinspirator™ System (eV3 Inc.) catheters are capable of such active thrombus fragmentation.
AngioJet
The mechanism in the AngioJet rheolytic thrombectomy (RT) system (Figure 1) involves the delivery of pressurized heparinized saline from the catheter, where saline jets travel backwards creating a low-pressure zone and, thus, a powerful vacuum effect. Thrombus, as a result, is drawn back into the catheter, where it is fragmented by the saline jets prior to being evacuated from the body.
(Enlarge Image)
Figure 1.
The AngioJet® (MEDRAD, PA, USA) rheolytic thrombectomy system. Active thrombus fragmentation by pressurized, heparinized saline. (A) Saline jets travel backwards at high speed to create a negative pressure zone (less than -600 mmHg), causing a powerful vacuum effect. (B) Cross-stream® windows optimize the fluid flow for more effective thrombus removal. (C) Thrombus is drawn into the catheter where it is fragmented by the jets and evacuated from the body.
The use of the AngioJet system as an adjunct in PPCI has been tested in three randomized trials. An initial single-center study enrolling 100 patients demonstrated a reduction of infarct size as assessed by Tc- sestamibi scintigraphy and better STR when compared with standard PPCI. The larger, multicenter, randomized AiMI trial that included 480 patients, however, failed to reproduce these initial findings. Importantly, the MACE rate was higher in the thrombectomy group, driven by an increase in 30-day mortality. The discrepancy between the two studies could be explained to some extent by the complexity of the device and, therefore, the impact of operator experience in its use. This also may explain the higher rate of coronary perforation observed in the AiMI trial. In addition, TIMI 3 flow prior to intervention was encountered significantly more often in the standard PPCI than in the thrombectomy group, potentially biasing the differences in infarct size between the two groups. Finally, angiographic evidence of thrombus was absent in a large percentage of both groups (25%) raising the possibility that the AngioJet device is best suited in cases with significant and visible thrombus burden. Use of the AngioJet device, on the other hand, has been associated with an increased incidence of symptomatic bradycardia, thus requiring positioning of a temporary pacing wire, which, in itself, is not without potential complications. Both of these studies were performed over 7 years ago with suboptimal antiplatelet regimens.
The recently published JETSTENT trial aimed to answer the questions raised by the previous two conflicting studies. It recruited 501 patients, all of whom were treated with dual antiplatelet therapy (300-mg aspirin and 600-mg clopidogrel) and glycoprotein (GP) IIb/IIIa antagonists. Exclusion criteria included TIMI thrombus grade <3 and infarct artery reference diameter <2.5 mm on visual assessment. The presence of thrombus as a prerequisite for entry into the study was an important difference between the JETSTENT and AiMI studies. No significant difference in STR, angiographic end points or myocardial infarct size between the AngioJet and conventional treatment groups were detected by Tc- sestamibi scanning. Interestingly, however, a significant decrease in MACE was noted at 6 and 12 months in the AngioJet group, driven primarily by a lower incidence of death and target-vessel revascularization. This was attributed by the authors to improved myocardial perfusion and better stent length and diameter assessment following RT. The results of the JETSTENT, however, need to be interpreted with caution. In this study, infarct size and STR, both established surrogates of prognosis following MI, showed no benefit with the AngioJet device. It is, therefore, difficult to explain what drives the MACE advantage associated with its use. Owing to this anomaly and the associated costs of the device, it has not gained widespread clinical acceptance in PPCI.
X-Sizer
The X-Sizer device consists of a dual-lumen hydrophilic-coated catheter shaft connected to a handheld control module (Figure 2). Once the catheter is engaged, the vacuum captures the thrombus, and the helical cutter present inside the inner lumen and inside the distal tip shears this off. The efficacy of the X-Sizer catheter in STEMI patients has been assessed in three randomized trials, and although it has been shown to improve STR at 60 min post-PCI, achieve better angiographic flow, reduce no reflow and distal embolization of atherosclerotic plaque debris, its use did not provide significant clinical benefit at 1 and 6 months (X-AMINE ST trial). Moreover, the routine use of the X-Sizer catheter in PPCI is limited by its rigidity and, thus, inability to navigate tortuous and heavily calcified vessels, as well as by its bulky size, which limits its use to vessels >2.5 mm and without very tight lesions. In one study, failure of X-Sizer thrombectomy was encountered in 24% of cases, and this was associated with increased incidence of 30-day adverse events. It has also been associated with an increased risk of coronary artery perforation.
(Enlarge Image)
Figure 2.
The X-Sizer system® (eV3 Inc., MN, USA). (A) Helical cutter inside the inner lumen of the catheter. (B) Handheld module.
Rinspirator
The Rinspirator system is a newer non-manual thrombectomy device consisting of three lumens. The first is a standard coronary guidewire lumen, whereas the second allows for distal aspiration. The third lumen allows injection of a rinsing solution (heparinized saline) through perforations located proximal to the aspiration lumen and distributed circumferentially along a short length of the catheter. This generates turbulent flow that rinses the vessel wall, detaches any adherent thrombus and simultaneously evacuates the thrombotic material from the vessel. According to the initial data from an international registry, this device is safe and its use does not seem to be associated with higher complication rates. To date, however, no clinical benefit has been established.
Vacuum Thrombectomy
The TransVascular Aspiration Catheter® (Nipro, Osaka, Japan) and Rescue™ (Boston Scientific, MA, USA) devices do not offer active thrombus fragmentation, but as they are connected to motorized vacuum units they can be considered mechanical thrombectomy devices. Only the TransVascular Aspiration Catheter system has shown some promise based on the results of a multicenter randomized trial (VAMPIRE). This study showed a marginal benefit of thrombectomy on myocardial perfusion as assessed by final TIMI flow and MBG, with the most benefit observed in patients presenting 6 h after symptom onset. MACE rates were similar at 30 days to standard PPCI, but a significant reduction in MACE was seen at 8 months in the thrombectomy group, mainly as a result of lower rates of revascularization in the treatment group. This was attributed to the better TIMI flow following thrombectomy, which may have facilitated better selection of stent diameter and length, as well as to the removal of inflammatory thrombus material. The use of glycoprotein IIb/IIIa inhibitors and drug-eluting stents were not allowed in the VAMPIRE study and it has been conjectured that in the presence of such adjunctive pharmacological intervention, the rate of future revascularization in the control group may have been more comparable to that of the treatment group.
The Rescue system has not been shown to improve infarct size or myocardial salvage as measured by sestamibi SPECT, nor have a beneficial effect on STR, MBG and left ventricular ejection fraction in randomized trials. Equally important, it has been associated with a high rate of procedural failure in the randomized trial by Kaltoft et al. and other study groups due to failure of the catheter to reach the culprit lesion.
Meta-analyses
In a meta-analysis including multiple devices, Bavry et al. showed that routine use of mechanical thrombectomy in setting of PPCI appears to significantly increase mortality 5.3 versus 2.8% for PCI alone, whereas the use of embolic protection devices has no impact on survival. Negative results of mechanical thrombectomy in this meta-analysis were driven primarily by the largest study in this category – the AiMI trial (AngioJet system) that showed increased infarct size and 30-day mortality rate in RT group. It must be noted that very low mortality rate was observed in patients treated with PCI alone (0.8 vs 4.6% in patients treated with adjunct RT; p = 0.02). Limitations of this work are described above.
Another meta-analysis, the ATTEMPT study, which included pooled analysis on 2686 individual patients' data from 11 randomized trials, comparing thrombectomy plus PPCI with standard PPCI, showed that allocation to mechanical thrombectomy devices, particularly those which involve thrombus fragmentation prior to aspiration, failed to produce a survival benefit. These data are in agreement with a recent meta-analysis by Costopoulos et al., showing that although mechanical thrombectomy was associated with better STR, it failed to produce any benefit in regarding to MBG, TIMI 3 flow, mortality and MACE. When taken alone, mechanical vacuum aspiration was shown to improve STR and MBG but not TIMI 3 flow. Improvement in clinical outcomes was not seen with mechanical vacuum devices, although this, to some extent, could be the result of low overall patient numbers from the four pooled RCTs.
There are several possible explanations for the disappointing results seen with mechanical thrombectomy. First, they tend to be bulkier and have a longer setup time, resulting in longer procedure times. In fact, all mechanical thrombectomy trials showed longer procedure time compared with conventional PCI, a finding not present in the manual aspiration trials. Such differences in procedure times may have an impact especially in patients presenting within 3 h of the onset of infarction. Second, mechanical thrombectomy devices are more complex to operate than manual aspiration catheters, with resultant less favorable learning curves. Operator and staff experience regarding the use of these complex devices is, thus, important and perhaps limited if one considers that most PPCIs occur out-of-hours when staffing levels are reduced and the likelihood of complications is higher. They are, therefore, best avoided in routine PPCIs, although they may have a role in patients with large vessels and a particularly heavy thrombus burden as some studies suggest.
Source...