AngioJet Rheolytic Thrombectomy in a Thrombotic Free Right Internal Mammary Artery Graft

Introduction

Distal embolization of thrombus material is a known complication of percutaneous coronary intervention (PCI), and is associated with both a larger infarct size and increased mortality.¹ Several devices attempt to address the issue of how to remove a large thrombus burden from vessels while avoiding distal embolization. These include catheters with distal filters, thrombus extraction catheters, and thrombectomy devices,² whose use has mostly been in native coronary arteries and saphenous vein grafts (SVGs). We report a case with a large thrombotic lesion in a free right internal mammary artery (RIMA) treated with mechanical thrombectomy. 

Case Report

A 68-year-old male presented to our emergency department with moderate chest pressure at rest. The troponin I level was 0.32 ng/mL (normal value <0.1 ng/mL). He had a past medical history of hypertension, left ventricular dysfunction with a left ventricular ejection fraction of 35%, and coronary artery disease status post coronary artery bypass grafting (CABG) in 1981 and redo in 1990 (left internal mammary artery [LIMA] to diagonal branch, free RIMA to left anterior descending artery [LAD], and SVG to right coronary artery [RCA]) followed by PCI of the SVG to RCA and RIMA to LAD anastomosis in 2005. Coronary angiography revealed a totally occluded proximal LAD and RCA. The left circumflex showed moderate diffuse disease. The LIMA to diagonal branch was patent and free of significant disease. The SVG to RCA had a 70% in-stent restenosis in the proximal segment. The RIMA to LAD had a severe proximal stenosis with a large thrombus and TIMI (Thrombolysis in Myocardial Infarction) grade 1 flow (Figure 1). Because of the large thrombus burden, the patient was treated with intravenous eptifibatide for 48 hours. 

Repeat coronary angiography still demonstrated a large thrombus in the RIMA. After a transvenous pacemaker was positioned in the apex of the right ventricle, a 300-mm, 0.014-inch Whisper guide wire (Abbott Vascular, Redwood City, Calif.) traversed the lesion and was positioned in the distal vessel. One pass with the AngioJet rheolytic thrombectomy catheter (Medrad Interventional/Possis, Minneapolis, Minn.) led to complete resolution of the thrombus in the RIMA with improvement in TIMI flow to grade 3 (Figure 2). The proximal lesion was predilated with a 2.25 x 12 mm Apex balloon (Boston Scientific, Maple Grove, Minn.). Then a 2.5 x 18 mm everolimus-eluting stent (Xience V stent, Abbott Vascular) was deployed at 12 atm followed by post-dilation with a 2.75 x 15 NC Trek balloon (Abbott Vascular) at 14 atm. Because of TIMI grade 2 flow, an Export aspiration catheter (Medtronic, Santa Rosa, Calif.) was advanced into the distal portion of the RIMA, and a total of 400 mcg of adenosine and 200 mcg of nitroglycerin were administered into the distal RIMA through the aspiration port. Final angiographic images demonstrated excellent angiographic results with TIMI grade 3 flow (Figure 3).

Discussion

This case is the first reported use of the AngioJet rheolytic thrombectomy device in a free RIMA graft to treat a heavily thrombotic lesion to prevent distal embolization and no reflow. Distal embolization of the large thrombus in a graft supplying the LAD in a patient with left ventricular dysfunction could have led to hemodynamic collapse. The AngioJet may be an attractive treatment strategy to treat a thrombotic-free RIMA, as it effectively removed the large thrombus burden without causing significant vasospasm and bradycardia.

The AngioJet rheolytic thrombectomy device

The AngioJet rheolytic thrombectomy device utilizes two lumens — one for inflow and the other for outflow. A high-pressure jet (9,000-10,000 psi) of heparinized saline exits the catheter, and is then re-injected into the center of the catheter at a high velocity, creating a vacuum via the Bernoulli effect.^2,3 This vacuum removes the thrombus material, which is then collected in a bag. The procedure is performed by positioning the catheter tip either proximally or distally to the lesion, activating the device, and crossing the thrombus with the catheter tip. While soft thrombus is removed with the device, organized thrombus is not. Following several passes (average 3-5 passes) across the thrombus with the catheter tip, balloon angioplasty followed by stenting is commonly performed.^2,3

Rheolytic thrombectomy clinical trials

In addition to native coronary artery thrombi, rheolytic thrombectomy has been used in SVGs.⁴ Since atheromas within SVGs are much more diffuse and thrombogenic than those in native coronary arteries, the lesions are not amenable to angioplasty.^5,6 The VeGAS 1 study (Vein Graft AngioJet Study 1), a pilot study of AngioJet thrombectomy in both native coronary arteries and SVGs, demonstrated that the device was safe, and decreased thrombus area (79 mm to 21 mm) and stenosis diameter (77% to 21%).⁴ VeGAS 2 was a randomized trial that compared the efficacy of AngioJet thrombectomy to intracoronary urokinase in 349 patients with evidence of thrombus in a coronary artery or SVG on angiography.⁷ AngioJet treatment had a significantly higher procedural success rate, defined as those procedures in which the residual stenosis diameter is < 50%, with TIMI-3 flow (86% vs. 72%, p = 0.002). While there was no significant difference in the primary endpoint (a composite of combined major adverse cardiac events [MACE] and procedural failure), total MACE at 30 days was lower in those treated with AngioJet, driven mainly by a lower rate of myocardial infarction (MI) (14% vs. 31%, p < 0.001). Additionally, at one-year follow up, freedom from MACE was higher in the AngioJet group (75% vs. 55%, p = 0.001). The AngioJet device itself is expensive, so a study using data from VeGAS 2 was undertaken to determine the cost-effectiveness of the procedure.⁸ The authors found that as a result of reduced periprocedural MI, decreased hemorrhagic complications, and a shorter hospital stay compared to the urokinase group, there was a $3,500 average of cost savings per patient (p < 0.001).

The AIMI (AngioJet Rheolytic Thrombectomy In Patients Undergoing Primary Angioplasty for Acute Myocardial Infarction) trial sought to determine the efficacy of AngioJet thrombectomy as an adjunct to PCI in patients with acute MI in reducing infarct size.⁹ Patients presenting with acute MI (n = 480) were randomized to either AngioJet and PCI or PCI alone. Infarct size, as determined by sestamibi scan, was higher in patients receiving AngioJet treatment (12.5% vs. 9.8%, p = 0.03), as was percent diameter stenosis (23.09% vs. 20.63%, p < 0.05). Within 30 days of follow up, MACE was higher in the AngioJet adjunct group (6.7% vs. 1.7%, p = 0.01), and deaths were higher as well (4.6% vs. 0.8%, p = 0.02). The authors speculated that the delivery of the device itself might have resulted in distal embolization, or that the longer procedure time increases the infarct size. Another factor that may have negatively impacted the AngioJet group is that the technique used in the AIMI trial involved crossing the lesion first before activating the device.^9,10

The results of the AIMI trial are contrary to the results of other randomized trials comparing AngioJet prior to PCI with PCI alone.^10,11 One study of 100 patients presenting with their first MI found that rheolytic thrombectomy was superior to PCI.¹¹ Infarct size by sestamibi scan was smaller in the AngioJet group (13% vs. 21.2%, p = 0.01) and the rate of early ST-segment elevation resolution was higher (90% vs. 72%, p = 0.022). There was no MACE in either group at 30 days. The JETSTENT (AngioJet Rheolytic Thrombectomy Before Direct Infarct Artery Stenting With Direct Stenting Alone in Patients With Acute Myocardial Infarction) trial was the largest AngioJet trial, randomizing 501 patients presenting with acute MI and TIMI thrombus grade 3-5 to either thrombectomy prior to PCI or PCI alone.¹⁰ The technique of thrombectomy used was a single anterograde pass, with additional passes if TIMI flow was not restored. Early ST-segment resolution was higher in the AngioJet group (85.8% vs. 78.8%, p = 0.043), and MACE at 1 month, 6 months, and 12 months was lower in the AngioJet group (at 1 month, 3.1% vs. 6.9%, p = 0.036). Freedom from MACE at one year was higher in those receiving thrombectomy (85.2% vs. 75.0%, p = 0.009), primarily due to lower death and target vessel revascularization rates. The improvement of target vessel revascularization rates in the AngioJet group is thought to be due to more complete apposition of the stent to the vessel wall, and as a result, a lower risk of stent thrombosis. While the difference in infarct size was not significant, this may be due to poor resolution of the sestamibi scan in subendocardial infarcts. In addition to the different techniques used, the JETSTENT trial may have obtained different results than the AIMI trial due to the patient population enrolled. While the AIMI trial enrolled patients without angiographic evidence of a large thrombus burden, the JETSTENT trial enrolled only patients with evidence of thrombus. This may suggest that the ideal candidates for AngioJet are those with angiographic evidence of thrombus. Mount Sinai Medical Center in New York City recommends that all patients with ST-elevation MI with a thrombus grade 4 or higher (using their own grading algorithm) receive AngioJet thrombectomy and abciximab prior to stenting.¹²

Use of rheolytic thrombectomy for stent thrombosis

Another application of the AngioJet thrombectomy device is in the treatment of coronary stent thrombosis.¹³ Patients with stent thrombosis were successfully treated with rheolytic thrombectomy. While there was no control in this study, there was a higher rate of successful recanalization and a lower rate of emergency CABG than was achieved in another retrospective study in which patients were treated with angioplasty and urokinase. Another study utilizing historical controls as a comparison found that thrombectomy with glycoprotein IIb/IIIa inhibitors in this setting resulted in decreased thrombus burden.¹⁴ In patients with stent thrombosis, prospective cohort or randomized trials are needed to better delineate the efficacy of AngioJet thrombectomy.

Complications of rheolytic thrombectomy

Rheolytic thrombectomy is associated with various complications. Bradyarrhythmias include sinus bradycardia to asystole and occur in as high as 79% of patients presenting with MI who are treated with AngioJet thrombectomy.^15,16 There are several theorized mechanisms for this phenomenon. One hypothesis is that hemolysis caused by the device leads to adenosine release, which can result in bradycardia.¹⁷ Another potential mechanism is the Bezold-Jarisch reflex, in which cardiac vagal afferents are activated by stretch receptors or receptors for specific ligands. Aminophylline, an adenosine antagonist, has been used to prevent bradyarrhythmias with mixed success. One study of 44 patients found that aminophylline was not associated with a lower rate of bradyarrhythmias¹⁶, while other studies have found that aminophylline successfully prevents bradyarrhythmias.^18,19 Other recommendations for prevention of this complication include using the single-pass anterograde technique and a shorter duration of device activation.^16,17 Prophylactic pacemaker insertion is beneficial to prevent asystole.¹⁶ Anticholinergic drugs such as glycopyrrolate have also been used in the prevention of bradyarrhythmias.²⁰

Comparison of rheolytic thrombectomy with manual thrombus aspiration

Manual thrombus aspiration is a viable alternative to AngioJet thrombectomy for AMI, being inexpensive and user-friendly.²¹ The DEAR-MI (Dethrombosis to Enhance Acute Reperfusion in Myocardial Infarction) study compared manual aspiration plus PCI to PCI alone, and concluded that thrombus aspiration prior to PCI leads to better myocardial reperfusion and lower risk of distal embolization.²² The TAPAS study (Thrombus Aspiration during Percutaneous Coronary Intervention in Acute Myocardial Infarction Study) also examined the use of manual aspiration.²³ In TAPAS, 1,071 patients with STEMI were randomized to either thrombus aspiration during PCI or to PCI alone. Failed myocardial reperfusion, as defined by postprocedural myocardial blush grade of 0 or 1, occurred in 17.1% in the thrombus aspiration group and in 26.3% in the conventional PCI group (p < 0.001). Furthermore, the blush grade was associated with both death and MACE at 30 days (p = 0.003). There was a benefit observed with manual aspiration both in patients with visible thrombus and no thrombus observed on angiography. Meta-analyses of these studies have also confirmed the benefit of manual aspiration.²⁴ In the absence of randomized data comparing manual aspiration to thrombectomy, some suggest that manual aspiration be used due to the conflicting evidence on AngioJet from the AIMI and JETSTENT trials. The SMART-PCI (CompariSon of Manual Aspiration With Rheolytic Thrombectomy in Patients Undergoing Primary PCI) trial is currently recruiting participants, and is randomizing patients with STEMI to either treatment with manual aspiration or AngioJet thrombectomy. In patients undergoing SVG intervention, aspiration combined with distal embolic protection has also been shown to reduce MACE when compared to PCI alone.²⁵ AngioJet thrombectomy is an alternative to aspiration in SVG intervention, especially in cases where distal embolic protection is not feasible or if thrombus burden is excessive.²⁶

In conclusion, AngioJet rheolytic thrombectomy has been studied extensively in native coronary arteries, SVGs, and non-coronary applications such as in peripheral arteries. AngioJet rheolytic thrombectomy may be a viable treatment option in a free RIMA with a large thrombotic burden.

This article was reviewed by a member of the Cath Lab Digest editorial board.

The authors can be contacted via Dr. Michael S. Lee, UCLA Medical Center, Adult Cardiac Catheterization Laboratory, 10833 Le Conte Avenue, Rm A2-237 CHS, Los Angeles, CA 90095-171715.
Email: mslee@mednet.ucla.edu

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Disclosure: Dr. Lee reports that he consults for Boston Scientific, Bristol-Myers Squibb, Merck, and St. Jude Medical. Mr. Finch reports no conflict of interest regarding the content herein.