The Potential Mechanisms of Bradyarrhythmias Associated with AngioJet Thrombectomy

ABSTRACT: The AngioJet® Rheolytic™ Thrombectomy System (Possis Medical, Inc., Minneapolis, Minnesota) is an effective thrombectomy device, but it may cause bradycardias ranging from mild bradycardia to asystole and hypotension in some patients. The incidence appears to be higher with the proximity of the device to the heart. Several hypotheses have attempted to explain and attenuate this phenomenon. J INVASIVE CARDIOL 2008;20:2A–4A The AngioJet® Rheolytic™ Thrombectomy System (Possis Medical, Inc., Minneapolis, Minnesota) utilizes a catheter-based technique with a high-velocity saline jet, creating a vacuum at the catheter tip to remove intravascular thrombus. Each treatment time is usually only a few minutes. The reported range of clearance rate1 is 67–95%. Clinical benefits of this technique have been shown for removal of fresh blood clots from 1) native coronary arteries or coronary bypass grafts2 prior to angioplasty or stent placement in patients suffering with acute myocardial infarction beyond ST elevation myocardial infarction; 2) peripheral arteries, such as acute renal artery thrombosis; 3) deep vein thrombosis;3 4) shunts,4 such as dialysis graft thrombosis; 5) pulmonary arteries5 in patients sustaining acute massive pulmonary embolism; and 6) carotid arteries6 in treating stroke caused by blood clots. Transient bradyarrhythmias have been observed when AngioJet thrombectomy is performed in the coronary arteries (especially the right coronary artery) and pulmonary arteries.5 This includes sinus bradycardia, junctional bradycardia, heart block and asystole. Concurrent hypotension is sometimes associated with bradyarrhythmias. Bradyarrhythmias begin within a few seconds after the AngioJet catheter operation, persist as long as the system is operating and resolve within a few seconds after AngioJet is turned off. Bradyarrhythmias have been reported in 20–79% of patients undergoing coronary artery thrombectomy and in 12–20% of patients undergoing pulmonary thrombectomy.3 Bradyarrhythmias also have been reported with AngioJet thrombectomy in the superior and inferior venae cavae and during transjugular intrahepatic portosystemic shunt thrombectomy.3 Little has been published on patients who have undergone thrombectomy in the iliac vein/lower extremity deep vein thrombosis or in dialysis grafts in the arms.3 Based on the literature, it appears that the closer the device is to the heart, the more frequent the incidence of bradyarrhythmias. Potential Mechanisms of AngioJet-Associated Bradyarrhythmias Although several theories have been proposed, the mechanisms for the bradyarrhythmia and hypotension associated with AngioJet thrombectomy remain uncertain. The debris released during AngioJet thrombectomy may cause myocardial ischemia, which may cause arrhythmias.7 This theory, however, does not explain the predominance of bradycardias instead of tachycardias. Also, it does not explain AngioJet-mediated bradyarrhythmias in experimental animals with normal thrombosed coronary arteries, nor does it explain the occurrence of bradycardia in noncoronary thrombectomy. Neither does it account for the rather rapid resolution of bradyarrhythmias when AngioJet is turned off. AngioJet thrombectomy has been shown to cause significant hemolysis. One of the products of hemolysis is adenosine, which can activate the A1 receptor and may be associated with transient bradycardia and hypotension.8 Aminophylline is an adenosine receptor antagonist. When intravenous aminophylline was given before the procedure, however, it did not reduce the incidence of bradyarrhythmias.7 The AngioJet device produces high-pressure pulsatile jets that may activate stretch-sensitive channels present on the vascular endothelium and induce bradyarrhythmias via mechanoelectric feedback.3 Stretching, however, often tends to shorten the refractory period, which would more likely facilitate the occurrence of tachyarrhythmias instead of bradyarrhythmias. Bezold proposed the concept of the Bezold-Jarisch reflex in 1867. In 1937, Jarisch revised it. The Bezold-Jarisch reflex originates in cardiac sensory receptors with nonmyelinated vagal afferent pathways. The left ventricle, particularly the inferoposterior wall, is a principal location for these sensory receptors (Figure 1).9 Stimulation of these inhibitory cardiac receptors by stretch, chemical substances or drugs increases parasympathetic activity and inhibits sympathetic activity.10 These effects promote reflex bradycardia and hypotension secondary to vasodilation. Long regarded as clinical curiosities, it is now clear that reflexes originating in these inhibitory cardiac sensory receptors are important to the pathophysiology of many cardiovascular disorders. These disorders include 1) bradycardia and hypotension with inferoposterior myocardial ischemia and infarction; 2) bradycardia and hypotension during coronary angiogram; 3) exertional syncope in aortic stenosis; and 4) vasovagal syncope. Similar reflexes of bradycardia and hypotension have been reported to be associated with radiofrequency catheter ablation of pulmonary veins for atrial fibrillation.11 These observations provide evidence that the sensory receptors with vagal afferent pathways are also present in the extracardiac vessels in the thoracic cavity and may explain the bradycardia and hypotension associated with some patients undergoing AngioJet thrombectomy in the pulmonary arteries and major thoracic veins. Use of Guidewire Pacing and Aminophylline with AngioJet Operation We performed a pilot animal study in 5 pigs to explore the potential mechanisms of bradyarrhythmias associated with AngioJet operation in the coronary arteries. Bradycardia and heart block could not be provoked in Pig 1 and Pig 2. No data were collectable from Pig 3 due to the premature death of the animal. AngioJet operation initiated sinus bradycardia in Pig 4, which was attenuated by pretreatment with intracoronary aminophylline. In a separate animal study, we demonstrated that intracoronary ventricular pacing via a guidewire is feasible and safe for managing the bradyarrhythmias associated with AngioJet operation in a porcine model. Ventricular pacing, however, was not effective in correcting the associated hypotension (Figure 2). We suggest a shorter activation of the AngioJet device during coronary and pulmonary artery thrombectomy to minimize the occurrence and severity of bradycardia, heart block and hypotension. If necessary, multiple shorter activations (each pass limited to 5 seconds) may be applied to achieve a favorable clinical outcome.12 Insertion of a temporary transvenous ventricular pacemaker is recommended prior to activation to attenuate the potential adverse effects of bradycardia and heart block.13 Temporary ventricular pacing via an intracoronary guidewire can achieve the same effects without the need for a venous puncture; therefore, it may reduce the complication rate and procedure time.14 In an animal study, we demonstrated that the Luge™ guidewire (Boston Scientific, Natick, Massachusetts) and the Wizdom guidewire (Cordis Corporation, Miami Lakes, Florida) had excellent pacing thresholds and impedance due to the presence of an insulation layer over the wire with an exposed tip. The Triumph Guidewire (Lake Region MFG, Inc., Chaska, Minnesota) and Brivant Guidewire (Brivant LTD, Galway, Ireland) had rather high pacing thresholds probably from current leakage due to the absence of an insulation layer. The Whisper guidewire (Abbott Vascular, Redwood City, California) had very high impedance, and capture was not achievable probably due to being covered. It is believed that aminophylline, a methylxanthine and a competitive inhibitor of the adenosine receptor, may prevent AngioJet thrombectomy-associated bradyarrhythmias. Bertolet et al15 reported the administration of another methylxanthine, theophylline, restored sinus rhythm after significant heart block in the setting of an acute inferior myocardial infarction. However, Lee et al7 showed that intravenous aminophylline did not prevent transient bradycardia and heart block and could not obviate the need for temporary pacing. Recently, Murad16 reported that intracoronary aminophylline (10 mg to 20 mg) given via the guide catheter immediately prior to AngioJet activation successfully prevented hemodynamically significant bradyarrhythmias without the need for temporary pacing in 10 patients. No randomized or placebo-controlled studies are available at this time. Conclusion AngioJet is an effective thrombectomy device, but it is associated with bradycardia, heart block and hypotension in some patients. The incidence of bradyarrhythmias appears to increase with the proximity of the device to the heart. The cause of bradycardia and hypotension remains unclear, but it may be associated with the Bezold-Jarisch reflex. Further investigation for simple, safe and effective management of this phenomenon during AngioJet therapy is warranted.

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