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Brugada syndrome phenotype cardiac arrest in a young patient unmasked during the acute phase of amiodarone infusion: disclosure and aggravation of Brugada electrocardiographic pattern
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Journal of Electrocardiology 45 (2012) 411 – 413 www.jecgonline.com
Brugada syndrome phenotype cardiac arrest in a young patient unmasked during the acute phase of amiodarone infusion: disclosure and aggravation of Brugada electrocardiographic pattern Antonio D'Aloia, MD, Enrico Vizzardi, MD,⁎ Silvia Bugatti, MD, Gregoriana Zanini, MD, Luca Bontempi, MD, Antonio Curnis, MD Section of Cardiovascular Diseases, Department of Experimental and Applied Medicine, University of Brescia, Brescia, Italy Received 12 October 2011
Abstract
We report a case of an outpatient cardiac arrest due to ventricular fibrillation and resuscitated with external automated defibrillator shocks in which acute amiodarone infusion unmasked a Brugada phenotype electrocardiographic pattern. Possible interferences by this drug and suitable therapeutic actions are discussed. © 2012 Elsevier Inc. All rights reserved.
A 32-year-old white man was admitted to the intensive care unit after a cardiac arrest episode at home due to ventricular fibrillation aborted by an automated external defibrillator (Fig. 1) . He was not assuming medications. At the admission, he was hemodynamically unstable (blood pressure was 100/64 mm Hg), apyretic, and in normal sinus rhythm. Laboratory tests, cardiac enzyme, and acid-base status were normal. A transthoracic echocardiogram revealed a severe left ventricular systolic dysfunction (ejection fraction of 20%). A 12-lead electrocardiogram (ECG) resulted normal (Fig. 2A). As part of initial treatment, an ventricular antiarrhythmic prophylaxis with intravenous amiodarone infusion was commenced. After few hours of drug infusion (300-mg dose infused over 6 hours) , ECG showed QT lengthening and T-wave inversion from V2 to V6 leads (Fig. 2B). Coronary angiogram and electrolyte status resulted normal. The following ECG (maintenance infusion: 540 mg over the remaining 18 hours) showed ST-segment elevations in leads V1 to V3, which descended with upward convexity into inverted T waves (Fig. 2C), features typical of “coved” type 1 Brugada ECG pattern. Discontinuation of the amiodarone infusion led to a resolution of these ECG changes, and a new echocardiogram revealed a completely ejection fraction recovery. During the hospitalization, an implanted cardioverter/ defibrillator device was implanted at 1 month after neurologic ⁎ Corresponding author. Department of Cardiology, University of Brescia, Brescia, Italy. E-mail address: [email protected] 0022-0736/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.jelectrocard.2012.02.005
recovery. Given his history, the patient was considered at high risk for arrhythmic events, and electrophysiologic study was not pursued. The later course was completely uneventful. No more ventricular tachycardia were noted in the implanted cardioverter/defibrillator's memory, and the ST-segment elevations in the right precordial leads was not evidenced over time at ECG telemetry monitoring during hospitalization.
Discussion and conclusion We report on a case of an outpatient cardiac arrest due to ventricular fibrillation and resuscitated with external automated defibrillator shocks in which acute amiodarone infusion unmasked a Brugada phenotype ECG pattern. Possible interferences by this drug and suitable therapeutic actions are discussed. At presentation, the ECG showed no ST-segment elevations in leads V1 to V3, and a diagnosis of Brugada syndrome was not made at that time. In the patient under discussion, ECG changes typical for Brugada type 1 pattern developed under parenteral amiodarone therapy and regressed after drug interruption. No other medications were made during the observation time, and there was no evidence of cardiac ischemia or acute coronary syndrome, neither serum electrolytes abnormalities. We believe that typical ECG changes of Brugada syndrome in this patient were induced and unmasked by amiodarone. Brugada syndrome is an autosomal-dominant ion channel disorder that predisposes individuals with structurally
412
A. D'Aloia et al. / Journal of Electrocardiology 45 (2012) 411–413
Fig. 1. Electrocardiograms during cardiac arrest. Ventricular fibrillation is detected (note the horizontal bars measure maximum amplitude in millivolts), charging begins (from first to third arrow), a shock is advised (second arrow), and a charge delivered (fourth arrow). An organized rhythm is detected and no further shocks advised.
Fig. 2. A, Twelve-lead ECG at the admission, before amiodarone infusion, demonstrated normal sinus rhythm. B, Twelve-lead ECG undertaken 6 hours after initiation of amiodarone infusion showed QT lengthening and T-wave inversion from V2 to V6 leads. C, Twelve-lead ECG undertaken 18 hours after initiation of amiodarone infusion shows hallmarks of Brugada syndrome: the presence of ST-segment elevation “coved type” in right precordial leads.
A. D'Aloia et al. / Journal of Electrocardiology 45 (2012) 411–413
normal hearts to ventricular arrhythmias and sudden cardiac death. The classic ECG phenotype can be present always or intermittently, so it can be often concealed in affected individuals. Genetic testing is limited to approximately 20% of cases with mutations in the SCN5A gene that is associated with a loss of cardiac sodium channel function. 1 In clinical practice, therefore, the diagnosis of Brugada syndrome is largely based on pharmacologic provocation tests using class Ia antiarrhythmic drugs, notably flecainide, ajmaline, and procainamide, which block sodium ion channels and unmask the key features of Brugada ECG phenotype. 2 Treatment with nonantiarrhythmic agents such as tricyclic antidepressant drugs, lithium, and cocaine as well as increased body temperature may also lead to unmasking of the Brugada ECG phenotype. To our knowledge, however, this is the second ever reported case of unmasking the Brugada ECG phenotype as a result of amiodarone therapy. 3 Amiodarone is predominantly a potassium ion channel–blocking agent (Vaughan Williams class III) but has been shown in vitro to have sodium ion channel–blocking properties, especially in the acute phase of its administration. 4,5 This effect provides a plausible scientific basis as well as another potential mechanism to induce a type I ECG phenotype during amiodarone infusion in patients suspected to have Brugada syndrome responsible for ventricular arrhythmias. 6,7 This case illustrates the critical importance of amiodarone infusion that, despite its original classification, has documen-
413
ted the property to block sodium channel as a class Ia antiarrhythmic drug and to be responsible of the development of ECG Brugada pattern. 8 References 1. Chen PS, Priori S. The Brugada syndrome. JACC 2008;51:1176. 2. Brugada R, Brugada J, Antzelevitch C, et al. Sodium channel blockers identify risk for sudden death in patients with ST-segment elevation and right bundle branch block but structurally normal hearts. Circulation 2000;101:510. 3. Nagele H, Behrens S, Castel A. Ventricular tachycardia and aggravation of Brugada ECG pattern in a patient with coronary artery disease and combined amiodarone and beta-blocker therapy. Clin Res Cardiol 2008;97:56. 4. Sheldon RS, Hill RJ, Cannon NJ, Duff HJ. Amiodarone: biochemical evidence for binding to a receptor for class I drugs associated with the rat cardiac sodium channel. Circ Res 1989;65:477. 5. Lalevee N, Nargeot J, Barrere-Lemaire S, Gautier P, Richard S. Effects of amiodarone and dronedarone on voltage-dependent sodium current in human cardiomyocytes. J Cardiovasc Electrophysiol 2003;14:885. 6. Ikeda T, Watanuki M, Masunaga N, et al. Betablocker subscribed with antiarrhythmic drug for paroxysmal atrial fibrillation was suspected to associate with revealing Brugada syndrome and inducing ventricular fibrillation. Respir Circ 2007;55:473. 7. Sheldon RS, Hill RJ, Cannon NJ, Duff HJ. Amiodarone: biochemical evidence for binding to a receptor for class I drugs associated with the rat cardiac sodium channel. Circ Res 1989;65:477. 8. Lalevee N, Nargeot J, Barrere-Lemaire S, Gautier P, Richard S. Effects of amiodarone and dronedarone on voltage-dependent sodium current in human cardiomyocytes. J Cardiovasc Electrophysiol 2004;14:885.
Journal of Electrocardiology 45 (2012) 411 – 413 www.jecgonline.com
Brugada syndrome phenotype cardiac arrest in a young patient unmasked during the acute phase of amiodarone infusion: disclosure and aggravation of Brugada electrocardiographic pattern Antonio D'Aloia, MD, Enrico Vizzardi, MD,⁎ Silvia Bugatti, MD, Gregoriana Zanini, MD, Luca Bontempi, MD, Antonio Curnis, MD Section of Cardiovascular Diseases, Department of Experimental and Applied Medicine, University of Brescia, Brescia, Italy Received 12 October 2011
Abstract
We report a case of an outpatient cardiac arrest due to ventricular fibrillation and resuscitated with external automated defibrillator shocks in which acute amiodarone infusion unmasked a Brugada phenotype electrocardiographic pattern. Possible interferences by this drug and suitable therapeutic actions are discussed. © 2012 Elsevier Inc. All rights reserved.
A 32-year-old white man was admitted to the intensive care unit after a cardiac arrest episode at home due to ventricular fibrillation aborted by an automated external defibrillator (Fig. 1) . He was not assuming medications. At the admission, he was hemodynamically unstable (blood pressure was 100/64 mm Hg), apyretic, and in normal sinus rhythm. Laboratory tests, cardiac enzyme, and acid-base status were normal. A transthoracic echocardiogram revealed a severe left ventricular systolic dysfunction (ejection fraction of 20%). A 12-lead electrocardiogram (ECG) resulted normal (Fig. 2A). As part of initial treatment, an ventricular antiarrhythmic prophylaxis with intravenous amiodarone infusion was commenced. After few hours of drug infusion (300-mg dose infused over 6 hours) , ECG showed QT lengthening and T-wave inversion from V2 to V6 leads (Fig. 2B). Coronary angiogram and electrolyte status resulted normal. The following ECG (maintenance infusion: 540 mg over the remaining 18 hours) showed ST-segment elevations in leads V1 to V3, which descended with upward convexity into inverted T waves (Fig. 2C), features typical of “coved” type 1 Brugada ECG pattern. Discontinuation of the amiodarone infusion led to a resolution of these ECG changes, and a new echocardiogram revealed a completely ejection fraction recovery. During the hospitalization, an implanted cardioverter/ defibrillator device was implanted at 1 month after neurologic ⁎ Corresponding author. Department of Cardiology, University of Brescia, Brescia, Italy. E-mail address: [email protected] 0022-0736/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.jelectrocard.2012.02.005
recovery. Given his history, the patient was considered at high risk for arrhythmic events, and electrophysiologic study was not pursued. The later course was completely uneventful. No more ventricular tachycardia were noted in the implanted cardioverter/defibrillator's memory, and the ST-segment elevations in the right precordial leads was not evidenced over time at ECG telemetry monitoring during hospitalization.
Discussion and conclusion We report on a case of an outpatient cardiac arrest due to ventricular fibrillation and resuscitated with external automated defibrillator shocks in which acute amiodarone infusion unmasked a Brugada phenotype ECG pattern. Possible interferences by this drug and suitable therapeutic actions are discussed. At presentation, the ECG showed no ST-segment elevations in leads V1 to V3, and a diagnosis of Brugada syndrome was not made at that time. In the patient under discussion, ECG changes typical for Brugada type 1 pattern developed under parenteral amiodarone therapy and regressed after drug interruption. No other medications were made during the observation time, and there was no evidence of cardiac ischemia or acute coronary syndrome, neither serum electrolytes abnormalities. We believe that typical ECG changes of Brugada syndrome in this patient were induced and unmasked by amiodarone. Brugada syndrome is an autosomal-dominant ion channel disorder that predisposes individuals with structurally
412
A. D'Aloia et al. / Journal of Electrocardiology 45 (2012) 411–413
Fig. 1. Electrocardiograms during cardiac arrest. Ventricular fibrillation is detected (note the horizontal bars measure maximum amplitude in millivolts), charging begins (from first to third arrow), a shock is advised (second arrow), and a charge delivered (fourth arrow). An organized rhythm is detected and no further shocks advised.
Fig. 2. A, Twelve-lead ECG at the admission, before amiodarone infusion, demonstrated normal sinus rhythm. B, Twelve-lead ECG undertaken 6 hours after initiation of amiodarone infusion showed QT lengthening and T-wave inversion from V2 to V6 leads. C, Twelve-lead ECG undertaken 18 hours after initiation of amiodarone infusion shows hallmarks of Brugada syndrome: the presence of ST-segment elevation “coved type” in right precordial leads.
A. D'Aloia et al. / Journal of Electrocardiology 45 (2012) 411–413
normal hearts to ventricular arrhythmias and sudden cardiac death. The classic ECG phenotype can be present always or intermittently, so it can be often concealed in affected individuals. Genetic testing is limited to approximately 20% of cases with mutations in the SCN5A gene that is associated with a loss of cardiac sodium channel function. 1 In clinical practice, therefore, the diagnosis of Brugada syndrome is largely based on pharmacologic provocation tests using class Ia antiarrhythmic drugs, notably flecainide, ajmaline, and procainamide, which block sodium ion channels and unmask the key features of Brugada ECG phenotype. 2 Treatment with nonantiarrhythmic agents such as tricyclic antidepressant drugs, lithium, and cocaine as well as increased body temperature may also lead to unmasking of the Brugada ECG phenotype. To our knowledge, however, this is the second ever reported case of unmasking the Brugada ECG phenotype as a result of amiodarone therapy. 3 Amiodarone is predominantly a potassium ion channel–blocking agent (Vaughan Williams class III) but has been shown in vitro to have sodium ion channel–blocking properties, especially in the acute phase of its administration. 4,5 This effect provides a plausible scientific basis as well as another potential mechanism to induce a type I ECG phenotype during amiodarone infusion in patients suspected to have Brugada syndrome responsible for ventricular arrhythmias. 6,7 This case illustrates the critical importance of amiodarone infusion that, despite its original classification, has documen-
413
ted the property to block sodium channel as a class Ia antiarrhythmic drug and to be responsible of the development of ECG Brugada pattern. 8 References 1. Chen PS, Priori S. The Brugada syndrome. JACC 2008;51:1176. 2. Brugada R, Brugada J, Antzelevitch C, et al. Sodium channel blockers identify risk for sudden death in patients with ST-segment elevation and right bundle branch block but structurally normal hearts. Circulation 2000;101:510. 3. Nagele H, Behrens S, Castel A. Ventricular tachycardia and aggravation of Brugada ECG pattern in a patient with coronary artery disease and combined amiodarone and beta-blocker therapy. Clin Res Cardiol 2008;97:56. 4. Sheldon RS, Hill RJ, Cannon NJ, Duff HJ. Amiodarone: biochemical evidence for binding to a receptor for class I drugs associated with the rat cardiac sodium channel. Circ Res 1989;65:477. 5. Lalevee N, Nargeot J, Barrere-Lemaire S, Gautier P, Richard S. Effects of amiodarone and dronedarone on voltage-dependent sodium current in human cardiomyocytes. J Cardiovasc Electrophysiol 2003;14:885. 6. Ikeda T, Watanuki M, Masunaga N, et al. Betablocker subscribed with antiarrhythmic drug for paroxysmal atrial fibrillation was suspected to associate with revealing Brugada syndrome and inducing ventricular fibrillation. Respir Circ 2007;55:473. 7. Sheldon RS, Hill RJ, Cannon NJ, Duff HJ. Amiodarone: biochemical evidence for binding to a receptor for class I drugs associated with the rat cardiac sodium channel. Circ Res 1989;65:477. 8. Lalevee N, Nargeot J, Barrere-Lemaire S, Gautier P, Richard S. Effects of amiodarone and dronedarone on voltage-dependent sodium current in human cardiomyocytes. J Cardiovasc Electrophysiol 2004;14:885.