Letter to the Editor: Intracoronary Aminophylline for Heart Block with AngioJet Thrombectomy

Thrombectomy in acute myocardial infarction (AMI) makes intuitive sense with positive results from small studies demonstrating benefit. However, the AngioJet (AJC) catheter (Possis Medical, Minneapolis Minnesota) has come under recent criticism since the unexpected adverse outcomes associated with AJC therapy in the AiMI Study.¹ Among the “believers” of thrombectomy, major barriers to the use of AJC include increased procedural time, need for obtaining venous access to insert a temporary pacemaker (TPM) 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. With regard to the first criticism, it is surprising that the extra 3 to 5 minutes it takes for system set-up causes so much concern. With emerging data that transportation of AMI patients to PCI centers for “primary” PCI, even when associated with a delay as long as 120 minutes, is safe and better than administering fibrinolytic therapy at the presenting hospital (thus delaying perfusion of infarcting myocardium), the additional 5 minutes required for thrombectomy should not be clinically important. The need for TPM insertion is a more significant concern because of the time, cost and risks of pacemakers, which include vascular and groin complications in heavily anticoagulated patients. Intravenous (IV) aminophylline has been tried with varying success. A recent publication in this Journal² showed lack of efficacy of IV aminophylline. We have conducted animal studies to test the hypothesis that intracoronary (IC) adenosine released from hemolyzed blood may be the biochemical mediator of heart block during treatment with the AJC.³ Using a porcine model, we showed that the heart block which occurs during treatment with the AJC and injection of hemolyzed blood is prevented by treatment with intravenous theophylline. Aminophylline is a synthetic derivative of theophylline, and also an adenosine receptor blocker. Belardinelli et al. showed that injection of aminophylline into the RCA or AV-nodal artery prevented heart block with subsequent administration of IC adenosine. However, no animal or human studies have previously tested the efficacy or safety of IC aminophylline for treatment of heart block caused by the AJC. Accordingly, we have explored the effects of IC aminophylline. Injection of adenosine into the RCA or AV-nodal artery consistently provoked high-grade heart block. Pre-treatment with atropine was ineffective, while pre-treatment with IC theophylline successfully prevented heart block with subsequent injections of IC adenosine. In unpublished data, we recently completed dose ranging and efficacy studies in 9 pigs. IC aminophylline was administered directly into the RCA via the guide catheter in doses of 1 to 40 mg, with cumulative doses of up to 70 mg (1.3 mg/kg). Aside from mild sinus tachycardia, no significant hemodynamic change or supraventricular or ventricular dysrhythmia occurred. In 5 pigs, AJC operation without pre-treatment produced high-grade bradyarrhythmias with severe hypotension. Pre-treatment with IC aminophylline (2.5 to 20 mg) successfully and consistently prevented heart block in over 90% of subsequent AJC operations. These data will be submitted soon for publication. Thus, a quick, easy pharmacologic alternative may yet exist for TPM insertion. We also have observational experience with 10 patients in whom IC aminophylline was administered emergently for treatment of heart block during AJC operation. All patients had acute inferior myocardial infarction or NSTE-MI with large thrombus in the RCA or SVG to RCA who were not good candidates for TPM insertion. Activation of AJC proximal to clot caused profound heart block with hemodynamic compromise in each patient. In all 10 patients, IC aminophylline in 10 to 20 mg doses (morbidly obese patients may need larger or additional doses), administered via the guide catheter immediately prior to AJC activation, successfully prevented hemodynamically significant bradyarrhythmias without the need for a TPM. Thrombectomy was safely performed in all patients without stopping the AJC. While bradycardia, first or second degree heart block with mild hypotension did occur in 5 patients, AJC operation could continue without interruption or need for TPM insertion. A larger registry and clinical trial are being planned. For interventional cardiologists who believe that thrombectomy is a useful approach and find TPM insertion to be a major barrier to its use, intracoronary aminophylline may provide a quick, easy and effective alternative. More data are needed to rigorously test this approach and studies are underway. Bilal Murad, MD Assistant Professor of Medicine Minneapolis VA Medical Center/University of Minnesota Cardiovascular Consultants, North Memorial Hospital 3300 Oakdale Avenue, Suite 200 Minneapolis, MN 55422

1. Ali and Arshad, for the AiMI Investigators. AngioJet rheolytic thrombectomy in patients undergoing primary angioplasty for acute myocardial infarction: Results of the AIMI Study. Presented at TCT 2004, Late Breaking Clinical Trials. 2. 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. 3. Henry T, Murad B, Murakami M, et al. Adenosine as a mediator of heart block with the AngioJet rheolytic thrombectomy catheter. XIII World Congress of Cardiology 1998; Monduzzi Editore S.p.A. Bologna (Italy), International Proceedings Division.