Bradycardia progressing to cardiac arrest during adenosine thallium myocardial perfusion imaging in occult sino-atrial disease

EuropeanJournalof

Nuclear Medicine

Case report

Bradycardia progressing to cardiac arrest during adenosine thallium myocardial perfusion imaging in occult sino-atrial disease Dudley J. Pennell, Shahid Mahmood, Peter J. Ell, S. Richard Underwood

Nuclear Medicine Department, Royal Brompton National Heart and Lung Hospital, London, UK Received 28 June and in revised form 15 September 1993

A d e n o s i n e is u s e d i n c r e a s i n g l y as an alternative to d y n a m i c e x e r c i s e d u r i n g m y o c a r d i a l p e r f u s i o n i m a g i n g b e c a u s e it is a p o w e r f u l c o r o n a r y v a s o d i l a t o r with a short half-life. M i n o r side-effects are c o m m o n but l i f e - t h r e a t e n i n g events are rare. We r e p o r t two cases o f p r o v o c a t i o n b y a d e n o s i n e i n f u s i o n o f p r o f o u n d sinus b r a d y c a r d i a p r o g r e s s i n g to atrial and v e n t r i c u l a r a s y s tole. D e s p i t e d i s c o n t i n u a t i o n o f the infusion, a s y s t o l e p e r s i s t e d for up to 1 min in o n e case and was a c c o m p a n i e d b y a g r a n d m a l seizure. N o r m a l sinus r h y t h m r e t u r n e d s p o n t a n e o u s l y in both cases w i t h o u t l o n g - t e r m sequelae. S i n o - a t r i a l d i s e a s e was later s u g g e s t e d in b o t h cases b y 24-h e l e c t r o c a r d i o g r a p h i c m o n i t o r i n g . W e conc l u d e that patients to w h o m a d e n o s i n e is g i v e n m a y h a v e o c c u l t s i n o - a t r i a l d i s e a s e and m a y be s u s c e p t i b l e to l i f e - t h r e a t e n i n g a r r h y t h m i a s . S i g n i f i c a n t sinus b r a d y c a r d i a d u r i n g the i n f u s i o n m a y p r o v i d e a w a r n i n g o f its presence. Abstract.

Key words: A d e n o s i n e - T h a l l i u m - A s y s t o l e - H e a r t - Sino-atrial disease Eur J Nucl Med

(1994) 2 1 : 1 7 0 - 1 7 2

Introduction A d e n o s i n e v a s o d i l a t a t i o n has b e e n u s e d to i n c r e a s e c o r o n a r y flow for v a r i o u s i m a g i n g techniques, m o s t imp o r t a n t l y t h a l l i u m m y o c a r d i a l p e r f u s i o n i m a g i n g [1-5]. W h i l s t its safety is w e l l e s t a b l i s h e d , a d e n o s i n e s h o u l d not be u s e d in a s t h m a [6, 7], after r e c e n t d i p y r i d a m o l e m e d i c a t i o n [8, 9] or in the p r e s e n c e o f h i g h - d e g r e e heart block without a pacemaker. We report a life-threatening c o m p l i c a t i o n d u r i n g a d e n o s i n e i n f u s i o n in two patients with no a p p a r e n t c o n t r a i n d i c a t i o n . In both cases a standard d o s e o f 140 g g / k g / m i n a d e n o s i n e i n f u s i o n was u s e d

Correspondence to: D. J. Pennell, Magnetic Resonance Unit, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK

with separate c a n n u l a e for the a d e n o s i n e i n f u s i o n and the t h a l l i u m injection.

C a s e reports A 60-year-old woman with angina and a previous history of myocardial infarction was referred for thallium imaging. Recent coronary arteriography showed stenosed left circumflex and anterior descending arteries with an occluded circumflex graft and a small patent left anterior descending graft. Three hours before the study she had taken nifedipine 20 mg, isosorbide mononitrate 20 mg and aspirin 150 mg. The patient was lain semi-supine and the baseline heart rate and blood pressure were 75/min and 154/80 mmHg. The electrocardiogram (ECG) showed sinus rhythm with a normal PR interval and non-specific ST segment changes. After 3 min of adenosine infusion, the heart rate was 44/min and the blood pressure was 110/60 mmHg. The patient reported flushing and lightheadedness, and the ECG showed sinus bradycardia with a normal PR interval and no significant change in the ST segment. Because of the symptoms and the change in vital signs, 80 MBq of thallium-201 was given into a second intravenous cannula located in the antecubital fossa, and the adenosine infusion was stopped. Shortly afterwards the patient became unconscious. The ECG showed sinus arrest without ventricular escape. Cardiopulmonary resuscitation was started. There was no spontaneous cardiac activity for 1 min and the patient suffered a grand mal seizure. Sinus rhythm recovered spontaneously and after stabilisation, the patient was able to tolerate planar imaging. This was repeated at 4 h. A fixed apical defect was found with reversible anteroseptal ischaemia. She was admitted for 2 days, but there was no evidence of new infarction and no long-term sequelae. Holter monitoring revealed evidence of sino-atrial disease with sinus pauses of up to 1.8 s and supraventricular dysrhythmias. A 66-year-old woman was prepared for thallium imaging in the same manner as the above patient. The resting blood pressure and heart rate were 160/90 and 58/rain respectively. The ECG showed sinus rhythm, a normal PR interval and left bundle branch block. After 3 min of the adenosine infusion, sinus bradycardia developed at a rate of 28/min with a blood pressure of 70 mmHg systolic. The adenosine was stopped and aminophylline 200 mg was given intravenously, but atrial and ventricular asystole developed. Cardiopulmonary resuscitation was started and sinus rhythm returned after 15 s. The patient recovered, but was kept under observation and scanning only begun at 45 min, by which European Journal of Nuclear Medicine Vol. 21, No. 2, February 1994 - © Springer-Verlag 1994

171

Fig. 1. a Prior to the infusion of adenosine, the ECG showed sinus rhythm with left bundle branch block at a rate of 58/min. b Just prior to the arrest, profound sinus bradycardia developed at a rate of 28/min, and was followed by c atrial and ventricular asystole lasting 15 s. d Recovery began with a nodal escape rhythm, including one normally conducted sinus beat

time the images were normal (Fig. 1). The patient was discharged without long-term sequelae. Subsequent Holter monitoring revealed evidence for sino-atrial disease with frequent atrial premature beats, periods of sinus bradycardia, runs of supraventricular tachycardia and pauses of up to 1.8 s duration.

Discussion Adenosine is usually infused at 140 gg/kg/min over 6 rain with injection of thallium in the 3rd or 4th minute. The adenosine acts on A2 receptors in the heart to cause near maximal coronary hyperaemia in 92% of patients, and the accompanying peripheral vasodilatation usually results in a reflex tachycardia [10]. At least 15 previous imaging studies with a similar infusion protocol in more than 1900 patients have been reported without lifethreatening sequelae. In the largest series of 607 patients, the most serious adverse effect was chest pain requiring nitroglycerin or aminophylline in 1.6% of patients [1]. Hypotension < 80 mmHg occurred in 0.5% and bronchospasm in 0.2% despite previous exclusion of asthmatics. Dysrhythmias usually involved atrioventricular block. Of patients developing a prolonged PR interval, 25.9% subsequently progressed to seconddegree heart block, which occurred in 3.6%. Occasional cases of third-degree heart block have been reported without adverse sequelae. Sinus bradycardia during adenosine infusion is unusual, occurring in less than 3% of patients [1], and typically mild, with a reduction of 3-6 beats per minute [2]. Significant sinus bradycardia leading to prolonged sinus arrest has not previously been recorded in humans at the infusion doses usually used for thallium imaging. The electrophysiological actions of adenosine are mediated predominantly by agonism at the A1 receptors. These actions include prolongation of intra-atrial and atrioventricular conduction, without prolongation of the

European Journal of Nuclear Medicine Vol. 21, No. 2, February 1994

QTc interval [11]. Shortening of the atrial action potential and hyperpolarisation of atrial cells also occurs as a result of increased potassium conductance [12]. The sinus arrest in our patients could have been caused by atrial hyperpolarisation, particularly in the presence of abnormal sino-atrial function. This possibility is supported by the significant sinus bradycardia during the adenosine infusion. This response occurs in sino-atrial disease with dipyridamole [11], which exerts its effects by increasing interstitial levels of adenosine [13], and asystole has been recorded following oral dipyridamole for thallium imaging [14]. There is also evidence that intravenous adenosine exerts a marked bradycardic effect in patients with sino-atrial disease, and cycle lengths of greater than 11 s have been recorded in such patients [15]. Whilst this effect can be demonstrated in normal subjects [16], patients with sino-atrial disease appear to be much more sensitive, and this has led to the hypothesis that adenosine is the specific meditator of the bradycardia and tachycardia of sinoatrial disease [17]. From the clinical viewpoint, every patient attending for adenosine myocardial perfusion imaging should have the following questions confirmed negative: history of asthma, treatment with dipyridamole (Persantin), treatment with theophylline or related respiratory compounds, caffeine ingestion within the last 12 h, and history or electrocardiographic evidence for atrioventricular conduction impairment or sino-atrial disease. The last-mentioned is probably the most difficult, as this report demonstrates, because sino-atrial disease may not be clinically manifest or apparent on the resting electrocardiogram performed prior to adenosine infusion. It might be suggested that an alternative approach to adenosine infusion could be an incremental infusion protocol [2], such that adverse effects might be noticed at lower doses. Unfortunately, however, it is possible that this would be conterproductive, because patients might complain of non-cardiac symptoms which would limit the use of the full infusion rate [2]. The perfusion tracer could then be injected under conditions of submaximal coronary hyperaemia which may potentially lead to reduced sensitivity for the detection and assessment of coronary artery disease. To conclude: The development of significant sinus bradycardia during adenosine infusion is rare. When it occcurs, unsuspected sinoatrial disease may be present and prolonged asystole may develop. Whilst this response may be related to ischaemia, further studies are warranted to establish the safety of the adenosine infusion rates used for coronary vasodilation in patients with sinoatrial disease.

References 1. Abreu A, Mahmarian JJ, Nishimura S, Boyce TM, Verani MS. Tolerance and safety of pharmocologic coronary vasodilation with adenosine in association with thallium-201 scintigraphy

172 in patients with suspected coronary artery disease. J Am Coll Cardiol 1991;18:730-735 2. Verani MS, Mahmarian JJ, Hixson JB, Boyce TM, Staudacher RA. Diagnosis of coronary artery disease by controlled coronary vasodilation with adenosine and thallium-201 scintigraphy in patients unable to exercise. Circulation 1990;82:80-87 3. Nguyen T, Heo J, Ogilby D, Iskandrian AS. Single photon emission computed tomography with thallium-201 during adenosine induced coronary hyperaemia: correlation with coronary arteriography, exercise thallium imaging and two-dimensional echocardiography. J Am Coll Cardiol 1990;16: 13751383 4. Coyne EP, Belvedere DA, Van de Streeke PR, Weiland FL, Evans RB, Spaccavento LJ. Thallium-201 scintigraphy after intravenous infusion of adenosine compared with exercise thallium testing in the diagnosis of coronary artery disease. J Am Coll Cardiol 1991;17:1289-1294 5. Nishimura S, Mahmarian JJ, Boyce TM, Verani MS. Quantitative thallium-201 single photon emission computed tomography during maximal pharmacologic coronary vasodilation with adenosine for assessing coronary artery disease. J Am Coll Cardiol 1991;18:736-745 6. Cushley M J, Tattersfield AE, Holgate ST. Inhaled adenosine and guanosine on airway resistance in normal and asthmatic subjects. Br J Clin Pharmacol 1983;15:161-165 7. Taviot B, Pavheco Y, Coppere B, Pirollet B, Rebaudet R Perrin-Fayolle M. Bronchospasm induced in an asthmatic by the injection of adenosine. Presse Med 1986;15:1103 8. Watt AH, Bernard MS, Webster J, Passani SL, Stephens MR, Routledge PA. Intravenous adenosine in the treatment of supraventricular tachycardia - a dose ranging study and inter-

action with dipyridamole. Br J Clin Pharmacol 1986;21: 277230 9. Belardinelli L, Linden J, Berne RM. The cardiac effects of adenosine. Prog Cardiovasc Dis 1989;32:73-97 10. Wilson RF, Wyche K, Christensen BV, Zimmer S, Laxson DD. Effects of adenosine on human coronary arterial circulation. Circulation 1990;82:1595-1606 11. Bubinski R, Markiewicz K, Cholewa M, Gorski L, Gawor Z, Kus W. Electrophysiologic effects of intravenous dipyridamole. Int J Cardiol 1989;24:327-335 12. Belardinelli L, Isenberg G. Isolated atrial myocytes: adenosine and acetylcholine increase potassium conductance. Am J Physiol 1983;244:H734-737 13. Szegi J, Szentmiklosi AJ, Cseppento A. On the action of specific drugs influencing the adenosine induced activation of cardiac purinoceptors. In: Papp J Gy, ed. Cardiovascular Pharmacology 1987:

results, concepts and perspectives.

Budapest: Akademiai Kiado; 1987:591-599 14. Blumenthal MS, McCauley CS. Cardiac arrest during dipyridamole imaging. Chest 1988;93:1103-1104 15. Benedini G, Cuccia C, Bolognesi R, Affatato A, Gallo G, Renaldi E, Visioli O. Value of purinic compounds in assessing sinus node dysfunction in man: a new diagnostic method. Eur Heart J 1984;5:394-403 16. Wayne EJ, Goodwin JF, Stoner HB. The effect of adenosine triphosphate on the electrocardiogram of man and animals. Br Heart J 1949;11:55-67 17. Watt AH. Sick sinus syndrome: An adenosine mediated disease. Lancet 1985;I: 786-788

European Journal of Nuclear Medicine Vol. 21, No. 2, February 1994