Aminophylline for Preventing Bradyarrhythmias During Orbital or Rotational Atherectomy of the Right Coronary Artery

Abstract: Background. Coronary atherectomy, orbital or rotational, is frequently used for plaque modification in patients with heavily calcified lesions. Atherectomy can be associated with clinically significant bradyarrhythmias or transient atrioventricular block requiring temporary pacemaker insertion, mainly in lesions involving the right coronary artery or a dominant left circumflex artery. Bradyarrhythmias may be mediated by endogenous release of adenosine from red blood cell breakdown. Aminophylline, an adenosine antagonist, can prevent adenosine-mediated bradyarrhythmias. Methods. This retrospective analysis examined 7 patients in whom aminophylline (250-300 mg intravenously over 10 min) was administered before coronary atherectomy. The study endpoint was the occurrence of any bradyarrhythmia. Results. Orbital atherectomy was used in 3 cases, rotational atherectomy was used in 3 cases, and both systems were used in 1 case. Technical success was 100% and all patients had Thrombolysis in Myocardial Infarction 3 flow at the end of the procedure. Preprocedural aminophylline administration successfully prevented bradyarrhythmias or atrioventricular block in all cases. Conclusions. Intravenous aminophylline represents a simple, safe, widely available, and low-cost intervention for preventing bradyarrhythmias during atherectomy of the right coronary artery or a dominant circumflex artery. 

J INVASIVE CARDIOL 2018;30(5):186-189. Epub 2018 February 15.

Key words: atherectomy, bradycardia, aminophylline

Coronary atherectomy can be used for plaque modification in patients with heavily calcified lesions, such as balloon-undilatable and/or balloon-uncrossable lesions.¹ Both rotational and orbital atherectomy are currently available for clinical use in the United States, with an estimated use of rotational atherectomy ranging from <1% to 3% or even 8% in some high-volume centers.² 

Atherectomy can cause bradyarrhythmias and transient atrioventricular block, especially when performed in the right coronary artery (RCA) or in a dominant circumflex (CX) coronary artery. The underlying mechanism may be related to adenosine release from red blood cells that are injured during atherectomy. In cardiac tissues, adenosine binds to type 1 (A1) receptors in the sinoatrial node and atrioventricular node, causing a negative chronotropic and dromotropic effect.³

Aminophylline can potentially antagonize the effects of adenosine on the heart through A1 antagonism. Aminophylline increases cyclic adenosine monophosphate (cAMP), which enhances atrioventricular conduction and prevents adenosine-induced bradyarrhythmias and the ensuing hemodynamic instability.⁴ Aminophylline has been used to prevent or treat adenosine-mediated bradyarrhythmias in various clinical scenarios such as atropine-resistant bradycardia, cardiac arrest, acute inferior myocardial infarction, rheolytic thrombectomy, and rotational atherectomy (Table 1).^5-14 In pharmacodynamics studies, complete A1 receptor antagonism was accomplished with 5 mg/kg aminophylline.⁴ Mader et al described the successful use of 250 mg intravenous (IV) aminophylline for out-of-hospital cardiac arrest.⁹ Abu-Laban et al used aminophylline in doses of 250 mg IV or 500 mg IV for bradysystolic cardiac arrest.¹²

Methods

Based on dosage described across the peer-reviewed literature and aminophylline’s mechanism of action, a protocol was developed for use in the cardiac catheterization laboratory with a single dose of 250-300 mg aminophylline in 50-100 mL dextrose 5%, administered IV over 10 min, approximately 10-15 min prior to atherectomy. There was no re-bolusing or continuous infusion, given aminophylline’s 8-hour half-life.

We retrospectively examined 7 RCA atherectomy cases (Table 2; Figure 1) in whom aminophylline was used prophylactically to reduce the risk of bradyarrhythmias and transient atrioventricular block. All cases were performed at Abbott Northwestern Hospital in Minneapolis, Minnesota, from April 2017 to August 2017. Aminophylline was used according to

the protocol described above.

Results

All patients had complex, de novo, severely calcified RCA lesions. Severe calcification was defined as dense radiopacities noted on both sides of the arterial wall (“tram-track”) without cardiac motion before contrast injection. Mean age was 75 ± 8.2 years and all patients were men. Orbital atherectomy (Diamondback catheter; Cardiovascular Systems, Inc) was used in 3 cases, rotational atherectomy (Rotablator; Boston Scientific) was used in 3 cases, and both systems were used in 1 case (Table 2). Technical success was 100% and all patients had Thrombolysis in Myocardial Infarction (TIMI) 3 flow at the end of the procedure. None of the patients developed clinically significant bradyarrhythmias or atrioventricular block. One patient with a history of atrial fibrillation had transient atrial fibrillation at the end of the procedure that resolved without complications. One patient who had non-sustained ventricular tachycardia prior to the procedure received an implantable cardioverter defibrillator the following day as planned, but did not have any arrhythmias during or after atherectomy. One patient developed a distal vessel perforation due to difficulty delivering stents, which was successfully treated with fat embolization. 

Discussion

Coronary atherectomy is an essential tool for performing complex percutaneous coronary intervention in severely calcified coronary lesions. Atherectomy can, however, cause clinically significant bradyarrhythmias and transient atrioventricular block, primarily when performed in a dominant RCA or CX artery due to adenosine release from injured red blood cells. To prevent bradycardia, some operators often insert a temporary pacemaker before atherectomy, which carries a small risk for right ventricular perforation and tamponade, especially in anticoagulated patients.¹ Another option is pacing over a coronary guidewire,¹⁵ but this also carries risk for coronary spasm and perforation. Thus, many operators seldom use temporary pacemakers, and rely on the use of mechanical maneuvers (eg, coughing) and/or atropine to treat atherectomy-induced bradyarrhythmias.

Methylxanthines, such as theophylline and aminophylline, are competitive antagonists of the adenosine receptor A1 in cardiac tissue, preventing its negative dromotropic effects.⁴ Although aminophylline did not appear to be effective in a non-randomized study in preventing bradyarrhythmias during rheolytic thrombectomy,¹¹ several other studies showed a beneficial effect (Table 1).^5-14 Cha et al showed that preprocedural IV infusion of aminophylline (381.3 ± 38.5 mg) prevented bradyarrhythmias in 38 patients undergoing rotational atherectomy without hemodynamic side effects.⁷ Browne et al studied 39 patients presenting with an acute coronary syndrome who underwent rheolytic thrombectomy. Twenty-one patients received prophylactic aminophylline, while 18 patients did not. Only 3 patients in the aminophylline group experienced bradycardia that required atropine, while 11 patients in the non-aminophylline group received pacemakers prophylactically and another 3 patients required treatment with atropine.⁸ Murad et al studied 20 patients undergoing either atherectomy or rheolytic thrombectomy and showed that intracoronary aminophylline at a dose of 20-40 mg was safe and effective in preventing heart block induced by thrombectomy and rotational atherectomy in 95% of patients.¹⁴ Delago et al examined 270 patients who underwent rheolytic thrombectomy, with aminophylline administered prior to the procedure in 260 patients; symptomatic bradycardia requiring pacing was observed in only 2 of the 260 aminophylline patients (0.77%), whereas it was observed in 2 of the 10 patients (20%) who did not receive aminophylline.¹³

Similar to the above studies, administration of 250-300 mg IV aminophylline over 10 min before coronary atherectomy successfully prevented bradyarrhythmias in all 7 cases performed at our center. Pending validation in larger series, our case series suggests that aminophylline is safe and effective for preventing bradycardia during orbital or rotational atherectomy. The 8-hour half-life negates the need for re-bolusing or continuous infusion. 

Study limitations. Our study has important limitations. First, our observations are based on a small, single-center case series; larger series are needed to further validate its efficacy and safety. Second, our series is limited to atherectomy of the RCA. Third, our observations involve the use of rotational and/or orbital atherectomy and not laser atherectomy, but bradycardia is less common with the latter.

Conclusion

IV aminophylline represents a simple, safe, widely available, and low-cost intervention for preventing bradyarrhythmias during atherectomy of the RCA or a dominant CX artery. 

References

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14.    Murad B. Intracoronary aminophylline for management of bradyarrhythmias during thrombectomy with the AngioJet catheter. J Invasive Cardiol. 2008;20:12A-18A.

15.    Mixon TA, Dehmer GJ, Santos RA, Gantt DS, Lawrence ME, Watson LE. Guidewire pacing safely and effectively treats bradyarrhythmias induced by rheolytic thrombectomy and precludes the need for transvenous pacing: the Scott & White experience. J Invasive Cardiol. 2008;20:5A-8A.

From the ¹Division of Cardiology, Department of Medicine, Hennepin County Medical Center, Minneapolis, Minnesota; ²Minneapolis Heart Institute, Abbott Northwestern Hospital, Minneapolis, Minnesota; and ³Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Brilakis reports personal fees from Abbott Vascular, Acist, Amgen, Asahi Intecc, CSI, Elsevier, GE Healthcare, Medicure, Medtronic, and Nitiloop; he serves on the Board of Directors for the Cardiovascular Innovations Foundation and the Board of Trustees of the Society of Cardiovascular Angiography and Interventions. The remaining authors report no disclosures regarding the content herein.

Manuscript submitted September 2, 2017, provisional acceptance given September 16, 2017, final version accepted September 28, 2017.

Address for correspondence: Emmanouil S. Brilakis, MD, PhD, Minneapolis Heart Institute and Minneapolis Heart Institute Foundation, Abbott Northwestern Hospital, 920 East 28th Street #300, Minneapolis, MN 55407. Email: esbrilakis@gmail.com