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Adenosine-Induced Atrial Instability
LETTERS
TO THE
EDITOR
Adenosine-Induced Atrial Instability To the editor, Adenosine (ADO) is a natural ribonucleoside that was approved for therapeutic use by the American Food and Drug Administration at the beginning of the nineties thanks to its excellent pharmacokinetic properties.1 Exogenous ADO interacts with its A1 receptor, present in sinoatrial and atrioventricular (AV) nodes, via a G1 protein. This interaction activates a specific rectifying current (lK-ADO) which hyperpolarizes the cell and induces a diminished response. Adenosine also binds to A2 receptors in the vascular endothelium, thereby reducing concentrations of cyclic adenosine monophosphate. This produces an antiadrenergic effect and may cause hypotension. The reduction in concentration of cyclic adenosine monophosphate is a brief and intense action, and makes ADO the antiarrhythmic therapy of choice for suppression of reentrant supraventricular tachycardias involving the AV node (paroxysmal supraventricular tachycardia [PSVT]). Efficacy is greater than 90%, and adverse effects are few, but not negligible. In this letter to the editor, we report an example of ADOinduced atrial instability (AI). A 72-year-old woman experienced palpitations while she was waiting for an appointment in a clinic. Figure 1 shows ECG traces recorded in the emergency department of the same hospital after adminis-
tration of ADO (trace B was recorded 10 minutes after trace A). A subsequent echocardiogram was normal (left atrial diameter: 4.2 cm). AI manifest as atrial fibrillation (AF) (Figure 1A) or as atrial ectopic beats which, in turn, triggered a new episode of PSVT (Figure 1B). This second form of arrhythmia is common and self-limiting. In contrast, ADO-induced AI wich manifest as AF is uncommon (1%-12% according to studies),2,3 self-limiting, and exceptional at doses of 6 mg. Adenosine is able to induce AF by shortening the atrial refractory periods and increasing the sympathetic tone in response to action at the A2 receptors.4 The self-limited nature of the arrhythmia, which in our case occurred 3 minutes after administration, agrees with the literature. The AI that caused AF occurred during a period of relative bradycardia, in which a single atrial extrasystole (which conforms a long-short activation sequence) appeared in the vulnerable phase of atrial repolarization to trigger fibrillation. We think that this atrial substrate is similar to that in which the ventricle triggers polymorphous ventricular tachycardias (torsades de pointes) associated with prolongation of the QT interval. That is, disparity in action potential duration and voltage of atrial fibers induced by ADO, facilitated by increased sympathetic activity, favored differing responses within the atrium. We think this variation within the atrial substrate allows induction of AF at such a low dose of ADO (6 mg). The possibility of ADO-induced AF should be borne in mind. The effect will often be transient, but if the patient has
Fig. 1. Atrial instability after adenosine. A: 4.4 seconds after administration of 6 mg adenosine (central route), an atrial extrasystole, coinciding with the T wave of the prececling beat, triggers atrial fibrillation instally well organized; please note the relative sinus bradycardia (54 bm) and the long-short sequence of atrial activation (arrows). B: after 12 seconds of sinus depression and atrioventricular block atrial ectopic beats appear one of them reinitiates supraventricular tachycardia in the usual way (reentry by an accuet left accessory pathway). In A, sinus rhythm was restored 3 minutes after onset of atrial fibrillation; in B, 1 minute after. Ten minutes elapsed between A and B (see text).
594
Rev Esp Cardiol 2004;57(6):594-6
152
Letters to the Editor
a rapidly conducting AV accessory pathway, the ventricular response frequency could be dangerous. The mechanism whereby ADO induces AF (and the subsequent restauration of virus rhythm) may be of great electrophysiological and clinical interest.5 Tomás Raviña,a Paula Raviña,b and María L.R. Suáreza a
Sección de Cardiología, Hospital de Cabueñes, Gijón, Asturias, Spain. b Servicio de Farmacia Hospitalaria, Hospital Xeral-Cíes, Vigo, Pontevedra, Spain.
REFERENCES
1. di Marco J, Sellers T, Lerman B, Greenberg M, Berne R, Bellardinelli L. Diagnostic and therapeutic use of adenosine in patients with supraventricular tachyarrhythmias. J Am Coll Cardiol 1985;6: 417-25. 2. Strickberger SA, Man C, Daoud EG, Goyal R, Brinkman K, Knight BP, et al. Adenosine-induced atrial arrhythmia: a prospective analysis. Ann Intern Med 1997;127:417-22. 3. Silverman RT, Machado C, Baga JJ, Meissner MD, Lehman MH, Steinman RT. Adenosine-induced atrial fibrillation. Am J Emerg Med 1996;26:939-43. 4. Nunain OS, Garrat C, Paul V, Debbas N, Camm AJ. Effects of adenosine on atrial and ventricular repolarization. Cardiovasc Res 1992;26:939-43. 5. Raviña T, Batalla A. Adenosina en el síndrome de preexcitación. Rev Esp Cardiol 2001;54:658-9.
density lipoproteins11 and seems to contribute to atherosclerosis progression by increased expression of endothelial adhesion molecules and leukocyte migration.12 It is also possible that it increases the activity of plasminogen inhibitor activator.13 Recently, a relationship has been suggested between endothelial dysfunction, coronary artery calcification and high C-reactive protein values in chronic consumers.14 Coronary vasoconstriction, that occurs after cocaine consumption, may produce repeated injury to the arterial wall that could favor endothelial damage, thus serving as sites of platelet aggregation.6 As a probable result of these pathological mechanisms, and in support of the abovementioned idea, premature coronary arteriosclerosis has been identified in autopsies in young cocaine consumers.15 Although when chest pain occurs after its consumption the percentage of acute coronary events is relatively low (6%-12%),16,17 it may be worthwhile investigating the association between cocaine and chest pains in patients under 45 years old and, in particular, make health workers aware of the need to disseminate knowledge regarding this association and make consumers aware of the potential dangers of chronic consumption regarding the cardiovascular system.15,18 Guillermo Burillo-Putze,a Robert S. Hoffman,b and Antonio Dueñas-Laitac a
Servicio de Urgencias, Hospital Universitario de Canarias, Tenerife, Spain. New York City Poison Control Center, Bellevue Hospital Center, New York University Medical Center, New York, USA. c Unidad Regional de Toxicología Clínica, Hospital Del Río Hortega, Valladolid, Spain. b
Cocaine As a Possible Emerging Cardiovascular Risk Factor To the editor, In Spain the number of cocaine seizures, requests for detoxification treatment and stated consumption of this drug is increasing every year. It has been estimated that 5% of students aged between 14 and 18 years old have consumed it,1 in addition to the fact that, from the cardiological standpoint, its use is worryingly associated with that of tobacco.2 In the Spanish hospital emergency service cocaine represents the leading cause of acute poisoning by illegal substances.3 We have read with great interest the excellent review by Sambola et al on the effect of coronary risk factors on endothelial dysfunction and their thrombotic complications.4 However, we were disappointed that cocaine consumption as a possible emerging vascular risk factor was not referred to, which in our experience probably should be added to the classic factors mentioned in the article.5,6 In addition to its acute effects at the coronary and, in general, cardiovascular levels,5,7 it has been suggested that cocaine consumption increases platelet aggregation,8-10 causes endothelial damage by increasing cell permeability to low153
REFERENCES
1. Observatorio Español sobre Drogas. Informe n.o 5, Julio de 2002. Madrid: Ministerio del Interior, Delegación del Gobierno para el Plan Nacional sobre Drogas; 2002. (Available from: http://www. mir.es/pnd/publica/pdf/oed-5.pdf) 2. Hollander JE, Hoffman RS, Gennis P, Fairweather P, DiSano MJ, Schumb DA, et al. Prospective multicenter evaluation of cocaineassociated chest pain. Cocaine Associated Chest Pain (COCHPA) Study Group. Acad Emerg Med 1994;1:330-9. 3. Burillo-Putze G, Munne P, Duenas A, Pinillos MA, Naveiro JM, Cobo J, et al. National multicentre study of acute intoxication in emergency departments of Spain. Eur J Emerg Med 2003;10:101-4. 4. Sambola A, Fuster V, Badimon JJ. Papel de los factores de riesgo en la trombogenicidad sanguínea y los síndromes coronarios agudos. Rev Esp Cardiol 2003;56:1001-9. 5. Lange R, Hilis LD. Cardiovascular complications of cocaine use. N Engl J Med 2001;345:351-8. 6. Hahn I, Hoffman RS. Cocaine use and acute myocardial infarction. Emerg Med Clin North Am 2001;19:493-510. 7. Freire Castroseiros E, Penas Lado M, Castro Beiras A. Cocaína y corazón. Rev Esp Cardiol 1998;51:396-401. 8. Rezkalla SH, Mazza JJ, Kloner RA, Tillema V, Chang SH. Effects of cocaine on human platelets in healthy subjects. Am J Cardiol 1993;72:243-6. 9. Kugelmass AD, Oda A, Monahan K, Cabral C, Ware JA. Activation of human platelets by cocaine. Circulation 1993;88:876-83. 10. Rinder HM, Ault KA, Jatlow PI, Kosten TR, Smith BR. Platelet alpha-granule release in cocaine users. Circulation 1994;90:1162-7. Rev Esp Cardiol 2004;57(6):594-6
595
TO THE
EDITOR
Adenosine-Induced Atrial Instability To the editor, Adenosine (ADO) is a natural ribonucleoside that was approved for therapeutic use by the American Food and Drug Administration at the beginning of the nineties thanks to its excellent pharmacokinetic properties.1 Exogenous ADO interacts with its A1 receptor, present in sinoatrial and atrioventricular (AV) nodes, via a G1 protein. This interaction activates a specific rectifying current (lK-ADO) which hyperpolarizes the cell and induces a diminished response. Adenosine also binds to A2 receptors in the vascular endothelium, thereby reducing concentrations of cyclic adenosine monophosphate. This produces an antiadrenergic effect and may cause hypotension. The reduction in concentration of cyclic adenosine monophosphate is a brief and intense action, and makes ADO the antiarrhythmic therapy of choice for suppression of reentrant supraventricular tachycardias involving the AV node (paroxysmal supraventricular tachycardia [PSVT]). Efficacy is greater than 90%, and adverse effects are few, but not negligible. In this letter to the editor, we report an example of ADOinduced atrial instability (AI). A 72-year-old woman experienced palpitations while she was waiting for an appointment in a clinic. Figure 1 shows ECG traces recorded in the emergency department of the same hospital after adminis-
tration of ADO (trace B was recorded 10 minutes after trace A). A subsequent echocardiogram was normal (left atrial diameter: 4.2 cm). AI manifest as atrial fibrillation (AF) (Figure 1A) or as atrial ectopic beats which, in turn, triggered a new episode of PSVT (Figure 1B). This second form of arrhythmia is common and self-limiting. In contrast, ADO-induced AI wich manifest as AF is uncommon (1%-12% according to studies),2,3 self-limiting, and exceptional at doses of 6 mg. Adenosine is able to induce AF by shortening the atrial refractory periods and increasing the sympathetic tone in response to action at the A2 receptors.4 The self-limited nature of the arrhythmia, which in our case occurred 3 minutes after administration, agrees with the literature. The AI that caused AF occurred during a period of relative bradycardia, in which a single atrial extrasystole (which conforms a long-short activation sequence) appeared in the vulnerable phase of atrial repolarization to trigger fibrillation. We think that this atrial substrate is similar to that in which the ventricle triggers polymorphous ventricular tachycardias (torsades de pointes) associated with prolongation of the QT interval. That is, disparity in action potential duration and voltage of atrial fibers induced by ADO, facilitated by increased sympathetic activity, favored differing responses within the atrium. We think this variation within the atrial substrate allows induction of AF at such a low dose of ADO (6 mg). The possibility of ADO-induced AF should be borne in mind. The effect will often be transient, but if the patient has
Fig. 1. Atrial instability after adenosine. A: 4.4 seconds after administration of 6 mg adenosine (central route), an atrial extrasystole, coinciding with the T wave of the prececling beat, triggers atrial fibrillation instally well organized; please note the relative sinus bradycardia (54 bm) and the long-short sequence of atrial activation (arrows). B: after 12 seconds of sinus depression and atrioventricular block atrial ectopic beats appear one of them reinitiates supraventricular tachycardia in the usual way (reentry by an accuet left accessory pathway). In A, sinus rhythm was restored 3 minutes after onset of atrial fibrillation; in B, 1 minute after. Ten minutes elapsed between A and B (see text).
594
Rev Esp Cardiol 2004;57(6):594-6
152
Letters to the Editor
a rapidly conducting AV accessory pathway, the ventricular response frequency could be dangerous. The mechanism whereby ADO induces AF (and the subsequent restauration of virus rhythm) may be of great electrophysiological and clinical interest.5 Tomás Raviña,a Paula Raviña,b and María L.R. Suáreza a
Sección de Cardiología, Hospital de Cabueñes, Gijón, Asturias, Spain. b Servicio de Farmacia Hospitalaria, Hospital Xeral-Cíes, Vigo, Pontevedra, Spain.
REFERENCES
1. di Marco J, Sellers T, Lerman B, Greenberg M, Berne R, Bellardinelli L. Diagnostic and therapeutic use of adenosine in patients with supraventricular tachyarrhythmias. J Am Coll Cardiol 1985;6: 417-25. 2. Strickberger SA, Man C, Daoud EG, Goyal R, Brinkman K, Knight BP, et al. Adenosine-induced atrial arrhythmia: a prospective analysis. Ann Intern Med 1997;127:417-22. 3. Silverman RT, Machado C, Baga JJ, Meissner MD, Lehman MH, Steinman RT. Adenosine-induced atrial fibrillation. Am J Emerg Med 1996;26:939-43. 4. Nunain OS, Garrat C, Paul V, Debbas N, Camm AJ. Effects of adenosine on atrial and ventricular repolarization. Cardiovasc Res 1992;26:939-43. 5. Raviña T, Batalla A. Adenosina en el síndrome de preexcitación. Rev Esp Cardiol 2001;54:658-9.
density lipoproteins11 and seems to contribute to atherosclerosis progression by increased expression of endothelial adhesion molecules and leukocyte migration.12 It is also possible that it increases the activity of plasminogen inhibitor activator.13 Recently, a relationship has been suggested between endothelial dysfunction, coronary artery calcification and high C-reactive protein values in chronic consumers.14 Coronary vasoconstriction, that occurs after cocaine consumption, may produce repeated injury to the arterial wall that could favor endothelial damage, thus serving as sites of platelet aggregation.6 As a probable result of these pathological mechanisms, and in support of the abovementioned idea, premature coronary arteriosclerosis has been identified in autopsies in young cocaine consumers.15 Although when chest pain occurs after its consumption the percentage of acute coronary events is relatively low (6%-12%),16,17 it may be worthwhile investigating the association between cocaine and chest pains in patients under 45 years old and, in particular, make health workers aware of the need to disseminate knowledge regarding this association and make consumers aware of the potential dangers of chronic consumption regarding the cardiovascular system.15,18 Guillermo Burillo-Putze,a Robert S. Hoffman,b and Antonio Dueñas-Laitac a
Servicio de Urgencias, Hospital Universitario de Canarias, Tenerife, Spain. New York City Poison Control Center, Bellevue Hospital Center, New York University Medical Center, New York, USA. c Unidad Regional de Toxicología Clínica, Hospital Del Río Hortega, Valladolid, Spain. b
Cocaine As a Possible Emerging Cardiovascular Risk Factor To the editor, In Spain the number of cocaine seizures, requests for detoxification treatment and stated consumption of this drug is increasing every year. It has been estimated that 5% of students aged between 14 and 18 years old have consumed it,1 in addition to the fact that, from the cardiological standpoint, its use is worryingly associated with that of tobacco.2 In the Spanish hospital emergency service cocaine represents the leading cause of acute poisoning by illegal substances.3 We have read with great interest the excellent review by Sambola et al on the effect of coronary risk factors on endothelial dysfunction and their thrombotic complications.4 However, we were disappointed that cocaine consumption as a possible emerging vascular risk factor was not referred to, which in our experience probably should be added to the classic factors mentioned in the article.5,6 In addition to its acute effects at the coronary and, in general, cardiovascular levels,5,7 it has been suggested that cocaine consumption increases platelet aggregation,8-10 causes endothelial damage by increasing cell permeability to low153
REFERENCES
1. Observatorio Español sobre Drogas. Informe n.o 5, Julio de 2002. Madrid: Ministerio del Interior, Delegación del Gobierno para el Plan Nacional sobre Drogas; 2002. (Available from: http://www. mir.es/pnd/publica/pdf/oed-5.pdf) 2. Hollander JE, Hoffman RS, Gennis P, Fairweather P, DiSano MJ, Schumb DA, et al. Prospective multicenter evaluation of cocaineassociated chest pain. Cocaine Associated Chest Pain (COCHPA) Study Group. Acad Emerg Med 1994;1:330-9. 3. Burillo-Putze G, Munne P, Duenas A, Pinillos MA, Naveiro JM, Cobo J, et al. National multicentre study of acute intoxication in emergency departments of Spain. Eur J Emerg Med 2003;10:101-4. 4. Sambola A, Fuster V, Badimon JJ. Papel de los factores de riesgo en la trombogenicidad sanguínea y los síndromes coronarios agudos. Rev Esp Cardiol 2003;56:1001-9. 5. Lange R, Hilis LD. Cardiovascular complications of cocaine use. N Engl J Med 2001;345:351-8. 6. Hahn I, Hoffman RS. Cocaine use and acute myocardial infarction. Emerg Med Clin North Am 2001;19:493-510. 7. Freire Castroseiros E, Penas Lado M, Castro Beiras A. Cocaína y corazón. Rev Esp Cardiol 1998;51:396-401. 8. Rezkalla SH, Mazza JJ, Kloner RA, Tillema V, Chang SH. Effects of cocaine on human platelets in healthy subjects. Am J Cardiol 1993;72:243-6. 9. Kugelmass AD, Oda A, Monahan K, Cabral C, Ware JA. Activation of human platelets by cocaine. Circulation 1993;88:876-83. 10. Rinder HM, Ault KA, Jatlow PI, Kosten TR, Smith BR. Platelet alpha-granule release in cocaine users. Circulation 1994;90:1162-7. Rev Esp Cardiol 2004;57(6):594-6
595