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Role of AngioJet Rheolytic Thrombectomy Catheter: Mount Sinai Hospital Experience
Percutaneous coronary interventions (PCI) involving balloon angioplasty and stenting are effective in the treatment of acute coronary syndromes but reduced coronary flow and distal embolization frequently complicate interventions when thrombus is present such as in the setting of acute myocardial infarction (AMI). Moreover, PCI on thrombus-containing lesions represents a clinical challenge to the interventionalist since thrombus is a predictor of adverse outcomes. Distal embolization of thrombus, fibrin content and other atherosclerotic plaque particulate matter can lead to a varying degree of consequences ranging from asymptomatic cardiac enzyme leak to flow-limiting microvascular obstruction, which may result in no reflow, abrupt occlusion, peri-procedural MI, emergent coronary artery bypass graft surgery and death.
In recent years it has been demonstrated that restoration of normal coronary flow in the infarct-related artery is not necessarily equivalent to the restoration of normal myocardial perfusion through the coronary microcirculation. After conventional primary PCI for ST-elevation MI with stent implantation and glycoprotein (GP) IIb/IIIa blockade, the normal myocardial perfusion expressed on angiography by the TMP (Tissue Myocardial Perfusion) grade three (TMP-3) is seen in only one-third of patients. In the other two-thirds of cases, impaired microcirculatory perfusion is observed (TMP grade 2–0), accompanied by only partial (30–70%) or no (
It is recognized that complete resolution of ST segment elevation (>70%) in resting ECG is a good indicator of restoration of normal myocardial perfusion. Accordingly, patients with impaired microcirculation have increased early and late mortality, greater irreversible myocardial injury and consequently higher incidence of adverse remodeling of the left ventricle, with higher rates of mortality, congestive heart failure and arrhythmia.
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, platelet/ platelet–leukocyte aggregates and fragmented plaque released in the course of fibrinolytic therapy and/or primary PCI.
Other reasons include increased microcirculatory resistance due to neutrophil obstruction, arteriolar constriction, capillary necrosis, progressive myocardial damage and edema 
following prolonged ischemia or as a result of reperfusion injury. In extreme cases, these phenomena may lead to abrogation of normal rates of epicardial flow despite removal of mechanical obstruction in the infarct-related artery (no reflow) and subsequent attended described adverse sequelae. Thrombus removal may ameliorate the rate of these adverse sequelae (Figure 1).
The optimal treatment for thrombus-containing lesions has yet to be defined. Use of a GP IIb/IIIa inhibitor before PCI has been shown to reduce thrombus burden and subsequent complications.
Devices to treat thrombus-containing lesions include distal protection devices such as the fixed-wire filter devices and the balloon-tipped wire of the PercuSurge system (Medtronic, Sunnyvale, California), and thrombectomy devices (AngioJet Rheolytic Thrombectomy System, Medrad Interventional/Possis, Medical, Minneapolis, Minnesota; X-Sizer thrombectomy system, EndiCOR Medical Inc., San Clementine, California), and other manual aspiration devices.
The AngioJet Rheolytic Thrombectomy System is a catheter-based system for the 
removal of thrombus (Figure 2). This catheter is a relatively novel thrombectomy device, specially designed to remove intravascular thrombus from coronary and peripheral arteries, by applying Bernoulli’s principle relating to a low-pressure zone in the region of a high-velocity jet. The catheter is attached to a drive unit with a piston pump that generates a high-pressure pulsed flow rate of 10,000 psi 
at 40 cc/min through a hypotube. The hypotube ejects its saline at a loop in the catheter tip. The jets of high-velocity saline are directed back into an exhaust lumen. This creates a vortex (Bernoulli effect) that fragments the thrombus while the resulting microparticles are aspirated through the same catheter and removed from the body (Figure 3).
Methods
We studied all AMI consecutive patients with ST segment elevation within 24 hours, who underwent PCI of the native coronary vessels at Mount Sinai Hospital from February 2002 to December 2003 (n=233). Of these patients, those with cardiogenic shock (n=13), thrombus grades 1–2 (n=98) or no thrombus (n=27), were excluded from the analysis. All remaining patients (n=95) included in the study had angiographic thrombus grade 3-5. The AngioJet thrombectomy before stenting was done in 52 patients, and the remaining 43 patients underwent conventional stenting without AngioJet.
Definitions
- Clinical success: procedural success without major complications (re-MI, urgent CABG or death); Procedural success: residual diameter stenosis
- Slow-flow or no flow: delayed distal clearance of the dye in the absence of spasm or dissection;
- Spasm: focal reversible narrowing;
- Thromboembolism: abrupt distal cutoff of a vessel or branch;
- Dissection: intimal dissection zone graded according to NHLBI class from A to F;
- Thrombus grade: defined from 1 to 6 as per TIMI criteria (Figure 3).
Data Collection Demographic, procedural and follow-up mortality data were collected. Primary medical physicians were called and hospital records were analyzed. Mortality data were confirmed through social security death index. These patients were followed for minimum one year.
Statistical analysis Categorical data are expressed as number plus percentage and continuous values are expressed as mean ± standard deviation. Kaplan-Meier curves and log-rank tests were used to evaluate cumulative survival. Univariate and multivariate Cox regression models were used to identify independent predictors of survival. A p value
AngioJet Rheolytic Thrombectomy System — Technical Issues The AngioJet Rheolytic Thrombectomy System includes to components: a disposable thrombectomy catheter and the reusable AngioJet Ultra Console. The integral components of the thrombectomy set are a catheter, a pump, saline delivery and waste tubing, and a collection bag.
- The single-use SpiroFlex catheter is 135 cm in length, 6 Fr guide-compatible, and has a 4 Fr diameter stainless steel rapid-exchange catheter tip designed for use in coronary arteries ≥ 2.0 mm. The catheter contains a dual lumen: one lumen allows for the in-flow of high-velocity saline jets through the catheter tip and the other lumen allows for the evacuation of thrombotic debris and for the passage of a 0.014-inch guidewire. The catheter tip contains 3 orifices, which let the retrograde high-pressure saline jets form toward the opening of the effluent lumen.
- The disposable pump connects to a bag of heparinized saline. Thrombotic debris is directed proximally through the aperture of the catheter and collected in a non-sterile collection bag.
- The Ultra Console pumps pressurized heparinized saline at 10,000 psi at the tip of the catheter, providing the pressurized pulsatile flow at a rate of 40 cc/min, which macerates the thrombus. The Ultra Console will deactivate if air is detected or occlusion occurs at the catheter tip.
The AngioJet catheter is then activated starting at the proximal end of the thrombus. The AngioJet catheter is advanced over a guidewire just until it is proximal to the thrombus. The system is activated by pressing the console foot pedal. The AngioJet catheter is advanced at 1–2 mm/sec to the distal end of the thrombus and then pulled back at the same rate and deactivated. On average, 1 to 2 passes are made on the thrombotic lesion.
Subsequent angioplasty or stenting is performed for definitive treatment of the lesion for optimal results, along with the administration of GP IIb/IIIa antagonists. The AngioJet catheter may feel bulky and somewhat stiffer than conventional angioplasty or stenting equipment. This requires the operator to make careful judgments concerning the likelihood of disruption of the artery in cases of severe tortuosity, especially in small vessels (
This is especially important in the case of total occlusion where the degree of tortuosity distal to the occlusion cannot be ascertained before passing the lesion. In these cases, much information about the potential safety of the AngioJet approach may be gained by injecting dilute contrast into the artery distal to the occlusion through a super low-profile over-the-wire balloon, such as a 1.5 x 9 mm Maverick balloon (Boston Scientific, Maple Grove, Minnesota) passed through the occlusion before proceeding with thrombectomy. Similarly, because of the stiffness of the system, good guide and wire support are essential, especially in situations with severe proximal tortuosity.
Results
Baseline characteristics of the two groups were not different between two groups. 
Glycoprotein IIb/IIIa inhibitor use was at the discretion of the interventionalist (was used in approximately 86% of cases). Procedural characteristics are shown in Table 1. Procedural success was attained in 96% of cases using AngioJet and 91% of conventional stenting (p = 0.31). DES were used approximately equally in both arms of the study (24% in AngioJet and 22% in the conventional stenting group). Major complications, defined as death, re-MI or urgent CABG, were 2% in the AngioJet group and 9% in the conventional stenting arm. There were no re-MI or urgent CABG in the whole study.
Major differences were also obtained in measurements of TMP grade (mean), TMP 2/3 
and cTFC, while the most important results are presented in Table 2. Thirty-day MACE was 6% in AngioJet group and 11% in the conventional stenting group (p = 0.12), while 1-year follow-up showed 5% need for CABG in conventional stenting group (compared to no need for CABG in AngioJet group), and almost double rated for cumulative death and re-MI in the conventional stenting group compared to AngioJet group (death 14.6% compared to 7.4%, p = 0.08; re-MI 9% compared to 4%, p = 0.32). Event-free survival was 86% in the AngioJet group and 74% in the conventional stenting group (p = 0.05).
Discussion
AngioJet thrombectomy appears to be safe and effective in patients with acute MI in the presence of large thrombus burden. Nakagawa et al reported the use of AngioJet thrombectomy in 31 patients with acute MI and angiographic evidence of thrombus in native coronary arteries. AngioJet thrombectomy was planned in 28 patients, while the other 3 patients underwent AngioJet thrombectomy after balloon angioplasty and subsequent no-reflow. All 28 patients who underwent planned AngioJet thrombectomy achieved procedural success with no evidence of no-reflow, as opposed to only one of 3 patients who underwent “bailout” AngioJet thrombectomy. The TIMI grade flow increased from 0.70 ± 0.97 before AngioJet thrombectomy to 2.61 ± 0.88 after AngioJet thrombectomy. The overall procedural success rate was 94%. There was a restenosis rate of 21% at 145 ± 78 days angiographic follow-up. All 31 patients had TIMI 3 coronary flow at follow-up. There were no major adverse in-hospital events and no major adverse events at follow-up.
Similarly, Silva et al reported on 70 acute ST-elevation MI patients (16% with cardiogenic shock) treated with AngioJet thrombectomy. The mean thrombus area was reduced from 73.2 ± 64.6 mm to 15.5 ± 30.1 mm after treatment with AngioJet thrombectomy (p 2 after final treatment) was 93.8%. Final TIMI-3 flow was established in 88%. Clinical success (defined as procedural success without major adverse cardiac events) was achieved in 88%. There were 6 patients who had distal embolization, two patients with perforation and five in-hospital deaths. There were no further major adverse cardiac events at 30-day follow-up. Furthermore, successful reperfusion therapy with AngioJet thrombectomy appears to confer electrical stability to vulnerable myocardium by decreasing QT dispersion after acute MI.
In a single center study from the Mayo Clinic, Singh et al reported the use of AngioJet thrombectomy in 72 high-risk patients with angiographic evidence of thrombus (SVG 45%, acute coronary syndrome 87%, cardiogenic shock 8%). There was 60% TIMI grade 0/1 flow before PCI with the achievement of post-procedural TIMI grade 3 flow in 79% of the patients. AngioJet thrombectomy was associated with a 93% procedural success rate. There was 1 death, 3% Q-wave MI and 7% non-Q-wave MI during hospitalization. At 1-year follow-up of successful PCI with AngioJet thrombectomy, the mortality, death/Q-wave MI, and composite endpoint rate were 10%, 13.3%, and 35.5%, respectively.
Taghizadeh et al studied the use of AngioJet thrombectomy and stenting in a subgroup of patients with acute MI complicated by cardiogenic shock. An intraaortic balloon pump was placed in all 19 patients. Procedural success was achieved in 95%, with final TIMI 3 flow in 89% of the cases. Clinical success was obtained in 68% (13/19 patients). There were 5 in-hospital deaths. No patients experienced stroke or needed emergent CABG. At 30-day follow-up, 2 patients required target vessel revascularization for subacute thrombosis, both of which occurred within 6 hours of the initial treatment. AngioJet thrombectomy may represent a useful treatment modality for patients who present with acute MI complicated by cardiogenic shock.
Although AngioJet thrombectomy appears to be safe and effective in patients with acute MI and a large thrombotic burden, the AngioJet catheter has come under recent criticism since the unexpected adverse outcomes associated with its use in the AiMI Study. The AngioJet Rheolytic Thrombectomy in Patients Undergoing Primary Angioplasty for Acute 
Myocardial Infarction (AiMI) trial is a multicenter randomized prospective trial comparing AngioJet thrombectomy followed by immediate definitive treatment (PCI with stenting) (n = 240) with immediate definitive treatment in patients undergoing primary angioplasty (n = 240). The primary endpoint is the final infarct size as assessed by SPECT imaging with 99 mTc Sestamibi at 14 days after the index procedure (Figure 4).
The secondary endpoints include TIMI grade flow and frame count, TIMI myocardial 
perfusion blush grade, procedural complications, major adverse cardiac events and ST-segment resolution. Mortality rates were higher in the thrombectomy group (4.6% versus 0.8%; p
Among the “believers” in thrombectomy, major barriers to the use of AngioJet include increased procedural time, need for obtaining venous access to insert a temporary pacemaker (when used in the right coronary or dominant left circumflex arteries due to the frequent occurrence of high-grade, hemodynamically significant heart block) and the absence of convincing data regarding benefits of thrombectomy. In contrast to the AiMI data, our study showed better results, both at 30-day follow up and at 1-year follow-up, with the use of AngioJet. In the AngioJet group, 30-day major adverse cardiac events (MACE) was 6% compared to 11% in the conventional stent group (p = 0.12), while death and re-MI rates at 1-year were almost double in the conventional group compared to AngioJet group (7.4% 
compared 14.6% death rates, p = 0.08; 4% compared to 9% for re-MI, p =0.32). The one-year follow-up results showed cumulative death of 6% in AngioJet group and 16% in conventional group (p =0.08) while event-free survival was 89% in AngioJet group and 72% in conventional group (p =0.04) (Figure 6).
This difference between our data and the AiMI study data could be explained by the thrombus size in the patients selected for studies. While the AiMI trial enrolled patients with thrombotic burden of any size, with
Among more recent studies, Burzotta et al showed in a large pooled analysis (ATTEMPT trial) that thrombectomy significantly improves the clinical outcome in patients with STEMI undergoing mechanical reperfusion and that its effect may be additional to that of IIb/IIIa inhibitors. Individual data of 2,686 patients enrolled in 11 trials entered the pooled analysis. Primary endpoint of the study was all-cause mortality. Major adverse cardiac events were considered to be the occurrence of all-cause death and/or target lesion/vessel revascularization and/or myocardial infarction (MI). Kaplan–Meier analysis showed that allocation to thrombectomy was associated with significantly lower all-cause mortality (p = 0.049). Thrombectomy was also associated with significantly reduced MACE (p = 0.011) and
death + MI rate during the follow-up (p = 0.015). Subgroup analysis showed that thrombectomy is associated with improved survival in patients treated with IIb/IIIa-inhibitors (p = 0.045) and that the survival benefit is confined to patients treated in manual thrombectomy trials (p = 0.011) (Figure 7).
It can therefore be concluded that AngioJet thrombectomy is valuable in the setting of MI with large thrombus but should not be used in cases with small or no thrombotic burden, 
because it may cause distal embolization of small, non-visible, adherent thrombus and may add to the procedural time. Figure 8 shows one actual PCI done at Mount Sinai Hospital where AngioJet thrombectomy was successfully done for a thrombotic proximal RCA lesion.
Conclusion
Percutaneous treatment of thrombus containing lesions is associated with higher complication rates compared to non-thrombotic lesions. Adjunct devices such as thrombectomy or distal protection are commonly used as part of the interventional procedure along with the liberal use of GP IIb/IIIa inhibitors and/or vasodilators.
AngioJet thrombectomy in the setting of AMI complicated by a large thrombotic burden represents an important adjunctive technique allowing rapid resolution of thrombus with quick reconstitution of flow and a decrease in the incidence of the no- or slow-reflow phenomenon.
Our current non-randomized study has shown that in carefully selected cases AngioJet thrombectomy for large thrombotic lesions in AMI reduced the distal embolization of intracoronary thrombus, thereby improving infarct-related artery flow as measured by the cTFC, TMP blush grade and TIMI flow. This beneficial effect was translated into a trend 
toward lower 1-year mortality and higher event-free survival at 1-year. In the last 5 years, we at Mount Sinai Hospital used AngioJet thrombectomy devices in ≈ 2% of the PCI cases with 20% of STEMI requiring AngioJet based on our thrombus grade algorithm (Figure 9). The results of the JetStent randomized trial will establish the use of AngioJet device in a definitive manner.
Limitations This is non-randomized registry data and suffers from the inherent bias of the selection of cases. Clearly AngioJet was not used even in STEMI cases with large thrombus burden in the elderly patients and tortuous and small arteries. Although these data are from 2002–2003 with 1 year follow-up, our unpublished data in subsequent years have been consistent with our earlier published results. In addition, our results reflect the outcome in a high-volume PCI center where cath lab staff have been well-trained to set up the AngioJet quickly.
References
1. Koning R, Cribier A, Gerber L, Eltchaninoff H, Tron C, Gupta V, Soyer R, Letac B. A New Treatment for Severe Pulmonary Embolism: Percutaneous Rheolytic Thrombectomy. Circulation 1997;96:2498–2500.
2. Silva JA, Ramee SR, Cohen DJ, et al. Rheolytic thrombectomy during percutaneous revascularization for acute myocardial infarction: Experience with the AngioJet catheter. Am Heart J 2001;141:353–359.
3. Silva JA, White CJ, Ramee SR, Collins TJ, Jenkins JS, et al. Treatment of coronary stent thrombosis with rheolytic thrombectomy: Results from a multicenter experience. Cathet Cardiovasc Invervent 2003:58:11–17.
4. Silva JA, Ramee SR, Collins TJ, et al. Rheolytic thrombectomy in the treatment of acute limb-threatening ischemia: Immediate results and six-month follow-up of the multicenter AngioJet registry. Cathet Cardiovasc Diagn 1998;45:386–393.
5. Hamburger JN, Serruys PW. Treatment of thrombus containing lesions in diseased native coronary arteries and saphenous vein bypass grafts using the AngioJet Rapid Thrombectomy System. Herz 1997;22:318–321.
6. Lee M, Singh V, Wilentz J, Makkar R. AngioJet thrombectomy (review). J Invasive Cardiol 2004;16:587–591.
7. Kim RH, Fischman DL, Dempsey CM, Savage CP. Rheolytic thrombectomy of chronic coronary occlusion. Cathet Cardiovasc Diagn 1998;43:483–489.
8. Nakagawa Y, Matsuo S, Yokoi H, et al. Stenting after thrombectomy with the AngioJet catheter for acute myocardial infarction. Cathet Cardiovasc Diagn 1998;43:327–330.
9. Singh M, Tiede DJ, Mathew V, et al. Rheolytic thrombectomy with Angiojet in thrombus-containing lesions. Cathet Cardiovasc Invervent 2002;56:1–7.
10. Topaz O, Minisi AJ, Bernardo NL, et al. Alterations of platelet aggregation kinetics with ultraviolet laser emission: the stunned platelet phenomenon. Thromb Haemost 2001;86:1087–1093.
11. Rinfret S, Katsiyiannis P, Ho K, et al. Effectiveness of rheolytic coronary thrombectomy with the AngioJet catheter. Am J Cardiol 2002;90:470–96.
12. Kuntz R, Baim D, Cohen D, et al. A trial comparing rheolytic thrombectomy with intracoronary urokinase for coronary and vein graft thrombus (the Vein Graft AngioJet Study [VeGAS 2]). Am J Cardiol 2002;89:326–330.
13. Khan MM, Ellis SG, Aguirre FV, et al. Does intracoronary thrombus influence the outcome of high-risk percutaneous transluminal coronary angioplasty? Clinical and angiographic outcomes in a large multicenter trial. The EPIC Investigators. J Am Coll Cardiol 1998;31:31–36.
14. Safian RD, May MA, Lichtenberg A, et al. Detailed clinical and angiographic analysis of transluminal extraction coronary atherectomy for complex lesions in native coronary arteries. J Am Coll Cardiol 1995;25:848–854.
15. Taghizadeh B, Chiu JA, Papaleo R, et al. AngioJet thrombectomy and stenting for reperfusion in acute MI complicated with cardiogenic shock. Cathet Cardiovasc Intervent 2002;57:79–84.
16. Rinfret S, Cutlip DE, Katsiyiannis PT, et al. Rheolytic thrombectomy and platelet glycoprotein IIb/IIIa blockade for stent thrombosis. Cathet Cardiovasc Intervent 2002;57:24–30.
17. Scott LRP, Silva JA, White C, Collins TJ. Rheolytic thrombectomy: A new treatment for stent thrombosis. Cathet Cardiovasc Intervent 1999;47:97–101.
18. Ali A, Cox D, Dib N, et al. AIMI Investigators Rheolytic thrombectomy with percutaneous coronary intervention for infarct size reduction in acute myocardial infarction: 30-day results from a multicenter randomized study, J Am Coll Cardiol 2006;48:244–252.
19. Kini AS, Moreno P, Mareş A, Kim M, Sharma S. The Improved Outcome with AngioJet Thrombectomy Catheter during Primary Stenting in Acute Myocardial Infarction Patients with High-Grade Thrombus. Circulation 2006;114(Suppl II):II–786.
20. Burzotta F, De Vita M, Gu YL et al. Clinical impact of thrombectomy in acute ST-elevation myocardial infarction: an individual patient-data pooled analysis of 11 trials. Eur Heart J 2009;30:2193–2203.
