NUCLEAR CARDIOLOGY BULLET

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Atrial fibrillation during adenosine pharmacologicstress testing

Matthew Cummings, MD, Jaffar Raza, MD, and Assad Movahed, MD, FACP, FACC

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Adenosine is a naturally occurring nucleoside foundroughout the human body.1 It has both antiarrhythmic

nd vasodilatory properties, making it a useful diagnosticnd therapeutic agent in clinical cardiology. Adenosineas been used in the United States since 1989 for theanagement of reentrant supraventricular tachycardiaVT)1 and is considered to be the initial drug of choicer the acute treatment of this frequently encountered

rrhythmia.2 It is also commonly used off label toifferentiate wide-complex tachycardias and is widelysed as a pharmacologic stress agent in conjunction withyocardial perfusion imaging (MPI).

Adenosine has been reported to have an excellentfety profile,3-5 and serious adverse effects have beenfrequently reported. The most commonly encountered

dverse effects are flushing, chest pain, and shortness ofreath.3,6 Far less common, more serious adverse effectsclude atrioventricular block, bronchospasm, bradycar-

ia, and hemodynamically significant hypotension.3,6,7

ecause of adenosine’s short half-life, these effects aresually rapidly reversed with the termination of itsdministration.3,6

Though not generally recognized, atrial fibrillationa potentially serious adverse effect of adenosine that

as been reported, particularly when used to treatVT. Silverman et al8 reported reproducible adenosine-duced atrial fibrillation in 5 patients undergoing elec-ophysiology testing for SVT. Garratt et al9 reported angle case of nonsustained atrial fibrillation in a patientsinus rhythm who received adenosine. Cases of sus-

ined atrial fibrillation after adenosine administrationave also been reported by McIntosh-Yellin et al10 andriffith et al.11

Atrial fibrillation occurring during adenosine phar-acologic stress testing has been far less frequentlyported. In fact, atrial fibrillation is not listed as a side

rom the Department of Internal Medicine, Brody School of Medicine,East Carolina University, Greenville, NC.a

eprint requests: Matthew Cummings, Department of Internal Medi-cine, Brody School of Medicine, East Carolina University, 600Moye Blvd PCMH, TA Room 340, Greenville, NC 27834;cummingsm@mail.ecu.edu.

Nucl Cardiol 2006;13:576-81.71-3581/$32.00

opyright © 2006 by the American Society of Nuclear Cardiology.i:10.1016/j.nuclcard.2006.05.006

6

ffect of adenosine administration during MPI in themerican Society of Nuclear Cardiology’s guidelines forPI.12 We present 4 patients in whom atrial fibrillation

eveloped during adenosine myocardial perfusion scin-graphy and discuss the possible mechanism of thisequently overlooked but important adverse effect.

CASE REPORTS

Patient 1. A 45-year-old woman with a history oforonary artery disease, hypercholesterolemia, hyperten-on, and stroke was referred for a single-day protocol ofdenosine pharmacologic stress MPI for preoperativeardiac risk stratification for noncardiac surgery. Thesting electrocardiogram (ECG) showed sinus bradycar-

ia and sinus arrhythmia with nonspecific ST changesigure 1).

Adenosine infusion was started at a rate of 140g · kg� · min�. Two minutes into the adenosine infu-on, atrial fibrillation developed with a ventricular ratef 150 to 155 beats/min (Figure 2). The ECG at that timevealed 1-mm horizontal ST depression in leads II, aVF,

nd V5. The adenosine infusion was terminated. Theatient remained in atrial fibrillation for approximately 1our 40 minutes and then spontaneously converted back

having a normal sinus rhythm. Because atrial fibrilla-on developed, the physician performing the stress testecided not to inject technetium 99m sestamibi.

Patient 2. A 61-year-old woman with a history ofiabetes mellitus, hypercholesterolemia, hypertension,nd palpitations was referred for a 2-day protocol ofdenosine pharmacologic stress MPI for the evaluationf chest pain. Her baseline ECG showed sinus rhythmith a short PR segment and nonspecific ST-T changesigure 3).

The patient received an adenosine infusion at a ratef 140 �g · kg� · min� for 6 minutes. Atrial fibrillationeveloped at 1 minute 44 seconds into the adenosinefusion with a ventricular rate of 144 beats/min. Withe development of atrial fibrillation, 0.5- to 1-mm flatT-segment depression developed in electrocardio-raphic leads I, II, III, aVF, and V5 (Figure 4). Theatient’s atrial fibrillation persisted after the adenosinefusion was stopped, and she was admitted to the

ospital for further management. Rest and stress MPI didot reveal any scintigraphic evidence of transient or fixed

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Journal of Nuclear Cardiology Cummings, Raza, and Movahed 577Volume 13, Number 4;576-81 Atrial fibrillation during adenosine pharmacologic stress testing

yocardial perfusion defects. She had a normal-sized leftentricle with normal left ventricular systolic function.

Patient 3. A 51-year-old woman with a history ofypertension, end-stage renal disease, and diabetes mel-tus was referred for adenosine pharmacologic stressPI for preoperative evaluation before renal transplant.er resting ECG showed normal sinus rhythm, left-axiseviation, and slow R-wave progression with a prema-re ventricular contraction (Figure 5).

The patient received an adenosine infusion at a ratef 140 �g · kg� · min�. At 2 minutes 4 seconds into theenosine infusion, atrial fibrillation developed (Figure 6).

Figure 1. Resting ECG with sinus bradycardiapatient 1.

Figure 2. ECG showing atrial fibrillation 2 min150 to 155 beats/min in patient 1.

o significant diagnostic ST-T–wave changes wereoted, although there were occasional premature ventric-lar contractions on the ECG. There was no scintigraphicvidence of a transient or fixed myocardial perfusionefect, and the patient had a normal left ventricular sizeith normal left ventricular function.

Patient 4. An 83-year-old woman with a history ofiabetes mellitus and hypercholesterolemia was referredr adenosine pharmacologic stress MPI for the evalua-

on of chest pain. Her baseline ECG showed sinusythm and slow R-wave progression in leads V1 to V3

igure 7).

arrhythmia, and nonspecific ST changes in

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578 Cummings, Raza, and Movahed Journal of Nuclear CardiologyAtrial fibrillation during adenosine pharmacologic stress testing July/August 2006

The patient received an adenosine infusion at a ratef 140 �g · kg� · min�. At 2 minutes 27 seconds aftere adenosine infusion, atrial fibrillation developed with

.5- to 1.5-mm flat ST depression in leads II, III, aVF,nd V4 to V6 (Figure 8). She spontaneously convertedack to sinus rhythm with premature atrial complexes at

minutes 54 seconds after infusion. There was nointigraphic evidence of a transient or fixed myocardial

erfusion defect. She had a normal left ventricular sizend normal function.

Figure 3. Resting ECG in patient 2 showinnonspecific ST-T changes.

Figure 4. ECG showing atrial fibrillation wpatient 2.

DISCUSSION

Adenosine’s effects on myocardial tissue have beenell described.1-3,8,13,14 Its effectiveness as a pharmaco-gic stress agent in MPI is accomplished by its potent

asodilatory properties, a mechanism mediated throughe activation of A2A receptors located on the arteriolarooth muscle cells.4,7 Its ability to terminate SVT is

xplained by its actions on the atrioventricular nodeVN), where it prolongs the refractory period and

al sinus rhythm, short PR segment, and

ntricular rate of 144 to 151 beats/min in

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Journal of Nuclear Cardiology Cummings, Raza, and Movahed 579Volume 13, Number 4;576-81 Atrial fibrillation during adenosine pharmacologic stress testing

epresses the excitability of the cells, ultimately slowingonduction through the AVN.1,4 This action is mediatedy the activation of A1 receptors found on the cellrface.4 Many of the adverse effects of adenosine are

ccounted for by its nonspecific activation of variousdenosine receptors, including the A1-, A2B-, and A3-ceptor subtypes.7

The mechanism by which adenosine causes atrialbrillation is unknown.8 However, it is known thatholinergic stimulation of atrial tissue shortens the atrialfractory period, and this could result in atrial fibrilla-on.1,5,8 In contrast to AVN tissue, adenosine shortense action potential and the refractory period in the atrialyocytes, resulting in increased conduction velocity in

Figure 5. Resting ECG showing normal sinuscontraction, and slow R-wave progression in pa

Figure 6. ECG showing atrial fibrillation durin

e atrial tissues.1,9,13,14 Adenosine also indirectly short-ns the atrial refractory period by causing an increase inirculating catecholamine levels, which shortens thetrial refractory period.5 This effect on the atrial refrac-ry period is similar to that produced by cholinergicimulation, which suggests that this could be the mech-nism responsible for induction of atrial fibrillation bydenosine. Another plausible explanation is adenosine’sbility to produce atrial premature complexes, resulting

long-short atrial sequences, which have been associ-ted with the development of atrial fibrillation.5

The incidence of atrial fibrillation induced by aden-sine during treatment for supraventricular arrhythmiasunknown,5 but some studies indicate that this is fairly

, left-axis deviation, premature ventricular.

osine infusion in patient 3.

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580 Cummings, Raza, and Movahed Journal of Nuclear CardiologyAtrial fibrillation during adenosine pharmacologic stress testing July/August 2006

ommon. Strickberger et al5 reported the incidence oftrial fibrillation after the administration of 12 mg ofdenosine for treatment of paroxysmal SVT to be 12%.

a retrospective study performed by Glatter et al,13

trial fibrillation occurred in 15% of patients with atrio-entricular reentry, 11% with atrial tachycardia, and 17%ith permanent junctional reciprocating tachycardia.here are few data on the incidence of atrial fibrillationccurring during adenosine pharmacologic stress testing,s presented here.

There is mounting evidence that the incidence oftrial fibrillation induced by adenosine administration

Figure 7. Resting ECG in patient 4 showing sinus

Figure 8. ECG showing development of atrial

grossly underestimated.8,13 Particularly, atrial fibril-tion induced during adenosine pharmacologic stresssting may be even more overlooked. It is importantat the clinicians be aware of this potentially serious

dverse effect of adenosine and take appropriateeasures to identify and treat this condition when it

ccurs.

cknowledgment

The authors have indicated they have no financial conflictsf interest.

and slow R-wave progression in leads V1 to V3.

tion after adenosine infusion in patient 4.

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Journal of Nuclear Cardiology Cummings, Raza, and Movahed 581Volume 13, Number 4;576-81 Atrial fibrillation during adenosine pharmacologic stress testing

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