Aminophylline for Prevention of Bradyarrhythmias Induced by Rheolytic Thrombectomy

ABSTRACT: In patients with acute ST elevation myocardial infarction or in those with thrombus-containing lesions, percutaneous coronary intervention (PCI) represents a clinical challenge to the interventionist, because coronary thrombus is a predictor of adverse outcomes. Thrombectomy, or the removal of thrombus from the infarct-related vessel prior to PCI, might improve clinical outcomes. The AngioJet® Rheolytic™ Thrombectomy System (Possis Medical, Inc., Minneapolis, Minnesota) is commonly used to treat lesions containing thrombus burden. A complication of rheolytic thrombectomy is transient cardiac rhythm disturbances, specifically bradyarrhythmia requiring temporary pacing. Aminophylline, a methylxanthine and a competitive inhibitor of the adenosine receptor, may prevent rheolytic thrombectomy-associated bradyarrhythmias. This report describes the use of aminophylline alone to prevent rheolytic thrombectomy-induced bradyarrhythmias in a single tertiary care center. J INVASIVE CARDIOL 2008;20:9A–11A Primary percutaneous coronary intervention (PCI) was found to be superior to thrombolytics administration in patients with ST elevation myocardial infarction (STEMI).1 In the setting of acute STEMI or when thrombus-containing lesions are identified, PCI represents a clinical challenge to the interventionist, as coronary thrombus has been considered a predictor of adverse outcomes.2,3 During attempted recannulization of the acute coronary thrombotic occlusion, embolization of debris from thrombus, fibrin content and other plaque substances can lead to microvascular obstruction with subsequent unfavorable events, such as abrupt closure, no-reflow phenomenon, periprocedural MI, emergent coronary artery bypass graft surgery and death.2–6 These facts have led to the belief that thrombectomy (removal of thrombus from the infarct-related artery prior to PCI) might improve myocardial reperfusion, reduce the size of the injury and improve clinical outcomes. Until further data from randomized, controlled trials are available, performing coronary thrombectomy is most appropriate in patients with angiographic presence of large thrombus burden prior to PCI.7–9 One of the commonly used devices to treat thrombus burden-containing lesions is the AngioJet® Rheolytic™ Thrombectomy System (Possis Medical, Inc., Minneapolis, Minnesota). A complication of rheolytic thrombectomy is transient cardiac rhythm disturbances, specifically bradyarrhythmia requiring temporary pacing, such as profound bradycardia, high-grade atrioventricular block, complete heart block and asystole. This complication has been reported in 20–26% of cases involving rheolytic thrombectomy.7 In one report, during AngioJet thrombectomy of the left anterior descending artery, a patient developed asystole for 12 seconds followed by bradycardia for 20 seconds leading to temporary left hemiplegia lasting 2 hours.10 A postulated mechanism of bradyarrhythmias that occur during rheolytic thrombectomy is release of intracellular adenosine from hemolyzed red blood cells.11 Adenosine serves as a coronary vasodilator (A2 receptor subtype mediated) with negative chronotropic and dromotropic effects, as well as anti-beta-adrenergic effects (A1 receptor mediated). A1 receptor stimulation in sinoatrial and atrioventricular nodal cells activates the outward K current through a cAMP-independent mechanism, inhibiting the “slow” Ca/Na mediated action potential of the atrioventricular node.12 Adenosine and other products released from hemolyzed red blood cells are directed to the vessels supplying the sinoatrial and atrioventricular node and impact conduction and heart rate. Intervention on the right coronary artery leads to bradyarrhythmias more frequently due to its arterial supply to the atrioventricular node.12,13 Procedures to prevent significant bradyarrhythmias in patients undergoing rheolytic thrombectomy have not been formally compared. However, a transvenous temporary pacemaker is often inserted prior to rheolytic thrombectomy despite carrying a risk of bleeding from the vascular access site, myocardial perforation and hemopericardium, delay in mechanical reperfusion during primary PCI and increased procedural cost. Aminophylline, a methylxanthine and a competitive inhibitor of the adenosine receptor, may prevent rheolytic thrombectomy-associated bradyarrhythmias.14 This report describes the use of aminophylline alone to prevent AngioJet rheolytic thrombectomy-induced bradyarrhythmias. Materials and Methods Patients. Between 2004 and 2008, charts and procedural Prolog were reviewed for all consecutive patients treated with rheolytic thrombectomy using the AngioJet Rheolytic Thrombectomy System at a single tertiary care center in Albany, New York. All patients had evidence of an occlusive coronary thrombus. Procedure. The standard intraprocedural treatment protocol included intravenous heparin or bivalirudin. Glycoprotein IIb/IIIa receptor inhibitor intravenous infusion and intracoronary nitroglycerin or verapamil were used at the discretion of the operator. Generally, rheolytic thrombectomy was performed for angiographically visible thrombus or if the operator considered there was a high risk of distal embolization. When the decision was made to proceed with rheolytic thrombectomy, 250 mg of aminophylline was placed in 500 cc of heparinized saline/AngioJet flush and aminophylline (250 mg) was administered intravenously to the patient on average 2 to 10 minutes prior to thrombectomy. The infarct-related lesion was crossed with a 0.014" coronary guidewire. The AngioJet catheter was advanced over a guidewire up to the thrombus, activated as it was slowly advanced to the distal part of the thrombus, then slowly withdrawn back to the guiding catheter tip where it was deactivated. The AngioJet catheter also was deactivated at times when symptomatic bradycardia or pauses developed. Thrombectomy was resumed upon return of normal rhythm. It took an average of 2 or 3 and up to 5 passes until angiographic improvement of thrombus appearance was noted. Stenting and occasionally standalone balloon angioplasty were performed after AngioJet treatment to achieve an optimal angiographic result. A temporary pacing wire was not inserted routinely as part of the protocol for rheolytic thrombectomy unless significant bradycardic episodes limited the usage of rheolytic thrombectomy. Endpoints. Baseline clinical, angiographic and procedural data were collected from each patient. The primary endpoint was development of bradycardia after AngioJet passes leading to the insertion of a temporary pacing wire. Other endpoints included death in the catheterization lab and ventricular arrhythmia requiring defibrillation. Results A total of 270 patients were treated with rheolytic thrombectomy: 230 (85%) were men and 40 (15%) were women. Mean patient age was 55 years, with ages varying from 26 to 87 years. Rheolytic thrombectomy in the setting of an acute ST-segment elevation MI was performed in 228 patients (84.4%) and rescue PCI after failed thrombolysis in 5 patients (1.85%). The distribution of the affected vessels is shown in Table 1. Of the 270 patients, 11 (4%) received a temporary transvenous pacemaker. Of those 11 patients, 7 (2.59%) had a pacemaker placed prior to AngioJet use due to symptomatic bradycardia. The 4 other patients (1.48%) had substantial bradyarrhythmias following AngioJet usage requiring placement of a temporary pacing wire. Prior to AngioJet use, 260 patients were premedicated with aminophylline while 10 patients failed to receive it. Out of 260 patients who received aminophylline, 2 (0.77%) met the primary endpoint of symptomatic bradycardia following AngioJet requiring pacing, while out of 10 patients who did not receive aminophylline, 2 (20%) met the primary endpoint. All 4 patients who required pacing post-AngioJet had acute occlusions of the right coronary artery (RCA) in the setting of acute inferior STEMI. Out of the total cohort, 4 patients (1.5%) had ventricular fibrillation or tachycardia that required defibrillation — in 2 instances prior to aminophylline/AngioJet use and in the other 2 after aminophylline/AngioJet use. One patient (0.37%) died of a coronary perforation on the catheterization table. Overall, the complications possibly related to aminophylline occurred in 4 patients out of 260 (1.54%) — 2 bradyarrhythmias requiring pacing and 2 instances of ventricular tachycardia/fibrillation requiring electrical conversion. Bradyarrhythmia post-AngioJet occurred only in patients requiring thrombectomy of the RCA. Discussion Our report shows a low incidence of symptomatic bradyarrhythmia requiring pacing in only 0.77% when aminophylline was administered regularly prior to rheolytic thrombectomy. On the other hand, failure to administer aminophylline resulted in bradycardia in 20% of cases, a finding consistent with prior reports.7 Furthermore, aminophylline does not appear to be proarrhythmic in this setting. Use of rheolytic thrombectomy is physiologically justified in acute myocardial infarction where a large thrombotic burden is present. The most important obstacles to rheolytic thrombectomy include increased procedural time and risk of bradyarrhythmias. Prophylactically inserting a temporary transvenous pacemaker has been considered a safe practice prior to rheolytic thrombectomy. However, transvenous temporary pacemaker insertion carries risk of bleeding from the vascular access site, myocardial perforation and hemopericardium, especially in the era of intensive antiplatelet therapy. It also delays mechanical reperfusion during primary PCI where door-to-balloon time is paramount. The simplified use of aminophylline appears to be a safe alternative based on our data. A recent publication14 showed lack of efficacy of intravenous aminophylline in prevention of serious bradyarrhythmias related to rheolytic thrombectomy. This does not correspond with our data. This discrepancy may be explained by a differing definition of bradyarrhythmia. In our practice, bradycardia was quickly aborted by deactivating the AngioJet thrombectomy, allowing the heart rhythm to return to normal. In our experience, a prophylactic pacemaker is needed only in the hemodynamically unstable patient in whom brief episodes of bradycardia may not be tolerated and in selected RCA interventions. Study Limitations This report represents an observational study of consecutive patients undergoing rheolytic thrombectomy at a single center. Patients were not randomized to aminophylline versus pacemaker. Conclusions Administration of aminophylline safely prevents bradyarrhythmias when used with the rheolytic thrombectomy system, AngioJet, eliminating the need for a transvenous pacer insertion and its potential complications.

1. Dalby M, Bouzamondo A, Lechat P, Montalescot G. Transfer for primary angioplasty versus immediate thrombolysis in acute myocardial infarction: A meta-analysis. Circulation 2003;108:1809–1814.
2. Ellis SG, Roubin GS, King SB 3rd, et al. Angiographic and clinical predictors of acute closure after native vessel coronary angioplasty. Circulation 1988;77:372–379.
3. Mabin TA, Holmes DR Jr, Smith HC, et al. Intracoronary thrombus: Role in coronary occlusion complicating percutaneous transluminal coronary angioplasty. J Am Coll Cardiol 1985;5:198–202.
4. Saber RS, Edwards WD, Bailey KR, et al. Coronary embolization after balloon angioplasty or thrombolytic therapy: An autopsy study of 32 cases. J Am Coll Cardiol 1993;22:1283–1288.
5. Arora RR, Platko WP, Bhadwar K, Simpfendorfer C. Role of intracoronary thrombus in acute complications during percutaneous transluminal coronary angioplasty. Cathet Cardiovasc Diagn 1989;16:226–229.
6. Lincoff AM, Popma JJ, Ellis SG, Hacker JA, Topol EJ. Abrupt vessel closure complicating coronary angioplasty: Clinical, angiographic and therapeutic profile. J Am Coll Cardiol 1992;19:926–935.
7. Ramee SR, Schatz RA, Carrozza P, et al. Results of the VeGAS 1 pilot study of the Possis coronary AngioJet thrombectomy catheter. Circulation 1996;94:3622.
8. Kuntz RE, Baim DS, Cohen DJ, 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.
9. Antoniucci D, Valenti R, Migliorini A, et al. Comparison of rheolytic thrombectomy before direct infarct artery stenting versus direct stenting alone in patients undergoing percutaneous coronary intervention for acute myocardial infarction. Am J Cardiol 2004;93:1033–1035.
10. Nakagawa Y, Matsuo S, Kimura T, et al. Thrombectomy with AngioJet catheter in native coronary arteries for patients with acute or recent myocardial infarction. Am J Cardiol 1999;83:994–999.
11. Henry T, Murad B, Wahlberg MD, et al. Mechanism of heart block of the AngioJet catheter. Circulation 1997;96:1527.
12. Belardinelli L, Linden J, Berne RM. The cardiac effects of adenosine. Prog Cardiovasc Dis 1989;32:73–97.
13. Belardinelli L, Shryock JC, Song Y, Wang D, Srinivas M. Ionic basis of the electrophysiological actions of adenosine on cardiomyocytes. FASEB J 1995;9:359–365.
14. Lee MS, Makkar R, Singh V, et al. Pre-procedural administration of aminophylline does not prevent AngioJet rheolytic thrombectomy-induced bradyarrhythmias. J Invasive Cardiol 2005;17:19–22.