E2
Letter to the Editor
About Brugada Phenocopy: Brugada Phenocopy with a Flecainide Overdose: A Pharmacological Dose Effect? To the Editor We read the recent paper by Chubb et al.1 with interest and noted that the term Brugada Phenocopy (BrP) was used to refer to a type 1 Brugada ECG pattern induced in the context of flecainide toxicity. This is an intriguing case; however, we would like to clarify salient points regarding the appropriate use of the term Brugada Phenocopy. We have published extensively on the subject of BrP2-4 and have established the international etiological categories5 and diagnostic criteria3,6 for BrP. The etiological categories are: (i) metabolic conditions, (ii) mechanical compression, (iii) ischemia and pulmonary embolism, (iv) myocardial and pericardial disease, (v) ECG modulation, and (vi) miscellaneous. The diagnostic criteria are: (i) the ECG pattern has a type 1 or type 2 Brugada morphology as currently defined by Bay´es de Luna,7 (ii) the patient has an underlying condition that is identifiable, (iii) the ECG pattern resolves after resolution of the underlying condition, (iv) there is a low clinical pretest probability of true Brugada Syndrome (BrS) determined by lack of symptoms, medical history, and family history, (v) negative provocative testing with sodium channel blockers such as ajmaline, flecainide, or procainamide, (vi) provocative testing not mandatory if surgical RVOT manipulation has occurred within the last 96 hours, and (vii) the results of genetic testing are negative (desirable but not mandatory because the SCN5A mutation is identified in only 20–30% of probands affected by true BrS8 ). In addition, we direct the authors to our recent paper9 outlining the terminological distinction between the Brugada ECG Pattern, BrP, and true congenital BrS. In the case presented by Chubb et al., the patient had no reported personal or family history to suggest BrS. However, the type 1 ECG pattern was provoked in the context of supratherapeutic levels of flecainide, a class 1C sodium channel blocker that is known to unmask true congenital BrS. Although the dose in this patient was significantly higher than the therapeutic dose, myocardial sodium channel dysfunction and, therefore, true congenital BrS cannot be completely ruled out since the type 1 Brugada ECG pattern was induced by a sodium channel blocker. We, therefore, suggest to the authors that this patient undergo provocative testing at “controlled” levels with a sodium channel blocking agent (flecainide, ajmaline, procainamide, or pilsicainide)10 after
J Cardiovasc Electrophysiol, Vol. 25, p. E2 Address for correspondence: Adrian Baranchuk, M.D., F.A.C.C., F.R.C.P.C., Division of Cardiology, Electrophysiology and Pacing, Kingston General Hospital, Queen’s University, 76 Stuart Street, Kingston, Ontario, Canada K7L 2V7. Fax: 613-548-1387; E-mail: [email protected] doi: 10.1111/jce.12374
having cleared supratherapeutic flecainide levels from her system. If the test is positive, this would be diagnostic of BrS10 and would not qualify as a BrP. If the test is negative, it would point to an interesting area of further study suggesting that sodium channel dysfunction may occur at varying serum levels of sodium channel blocking agents. Genetic testing remains desirable in this patient but not mandatory, as it is positive in about only 20–30% of true BrS.8
DANIEL D. ANSELM, M.D. and ADRIAN BARANCHUK, M.D., F.A.C.C., F.R.C.P.C From theDivision of Cardiology, Electrophysiology and Pacing, Kingston General Hospital, Queen’s University, Kingston, Ontario, Canada
References 1. Chubb H, Cooklin M, Rosenthal E: Brugada phenocopy with a flecainide overdose: A pharmacological dose effect? J Cardiovasc Electrophysiol 2013; doi:10.1111/jce.12335. 2. Baranchuk A, Nguyen T, Ryu MH, Femen´ıa F, Zareba W, Wilde AA, Shimizu W, Brugada P, P´erez-Riera AR: Brugada phenocopy: New terminology and proposed classification. Ann Noninvasive Electrocardiol 2012;17:299-314. 3. Anselm DD, Baranchuk A: Brugada phenocopy: Redefinition and updated classification. Am J Cardiol 2013;111:453. 4. Genaro NR, Anselm DD, Cervino N, Estevez AO, Perona C, Villamil AM, Kervorkian R, Baranchuk A: Brugada phenocopy clinical reproducibility demonstrated by recurrent hypokalemia. Ann Noninvasive Electrocardiol 2013; doi:10.1111/anec.12101. 5. Anselm DD, Baranchuk A: Brugada phenocopy in the context of pulmonary embolism. Int J Cardiol 2013;168:560. 6. Anselm DD, Barbosa-Barros R, de Sousa Bel´em L, Nogueira de Macedo R, P´erez-Riera AR, Baranchuk A: Brugada phenocopy induced by acute inferior ST-segment elevation myocardial infarction with right ventricular involvement. Inn Card Rhythm Manag 2013;4:1092-1094. 7. Bay´es de Luna A, Brugada J, Baranchuk A, Borggrefe M, Breithardt G, Goldwasser D, Lambiase P, Riera AP, Garcia-Niebla J, Pastore C, Oreto G, McKenna W, Zareba W, Brugada R, Brugada P: Current electrocardiographic criteria for diagnosis of Brugada pattern: A consensus report. J Electrocardiol 2012;45:433-442. 8. Probst V, Wilde AA, Barc J, Sacher F, Babuty D, Mabo P, Mansourati J, Le Scouarnec S, Kyndt F, Le Caignec C, Guicheney P, Gouas L, Albuisson J, Meregalli PG, Le Marec H, Tan HL, Schott JJ: SCN5A mutations and the role of genetic background in the pathophysiology of Brugada syndrome. Circ Cardiovasc Genet 2009;2:552-557. 9. Anselm DD, Baranchuk A: Terminological clarification of Brugada phenocopy, Brugada syndrome, and the Brugada ECG pattern: Re. Early repolarization pattern in patients with provocable Brugada phenocopy: A marker of additional arrhythmogenic cardiomyopathy. Int J Cardiol 2014;171:288. 10. Priori SG, Wilde AA, Horie M, Cho Y, Behr ER, Berul C, Blom N, Brugada J, Chiang CE, Huikuri H, Kannankeril P, Krahn A, Leenhardt A, Moss A, Schwartz PJ, Shimizu W, Tomaselli G, Tracy C: HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: Document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013. Heart Rhythm 2013;10:1932-1963.
Letter to the Editor
About Brugada Phenocopy: Brugada Phenocopy with a Flecainide Overdose: A Pharmacological Dose Effect? To the Editor We read the recent paper by Chubb et al.1 with interest and noted that the term Brugada Phenocopy (BrP) was used to refer to a type 1 Brugada ECG pattern induced in the context of flecainide toxicity. This is an intriguing case; however, we would like to clarify salient points regarding the appropriate use of the term Brugada Phenocopy. We have published extensively on the subject of BrP2-4 and have established the international etiological categories5 and diagnostic criteria3,6 for BrP. The etiological categories are: (i) metabolic conditions, (ii) mechanical compression, (iii) ischemia and pulmonary embolism, (iv) myocardial and pericardial disease, (v) ECG modulation, and (vi) miscellaneous. The diagnostic criteria are: (i) the ECG pattern has a type 1 or type 2 Brugada morphology as currently defined by Bay´es de Luna,7 (ii) the patient has an underlying condition that is identifiable, (iii) the ECG pattern resolves after resolution of the underlying condition, (iv) there is a low clinical pretest probability of true Brugada Syndrome (BrS) determined by lack of symptoms, medical history, and family history, (v) negative provocative testing with sodium channel blockers such as ajmaline, flecainide, or procainamide, (vi) provocative testing not mandatory if surgical RVOT manipulation has occurred within the last 96 hours, and (vii) the results of genetic testing are negative (desirable but not mandatory because the SCN5A mutation is identified in only 20–30% of probands affected by true BrS8 ). In addition, we direct the authors to our recent paper9 outlining the terminological distinction between the Brugada ECG Pattern, BrP, and true congenital BrS. In the case presented by Chubb et al., the patient had no reported personal or family history to suggest BrS. However, the type 1 ECG pattern was provoked in the context of supratherapeutic levels of flecainide, a class 1C sodium channel blocker that is known to unmask true congenital BrS. Although the dose in this patient was significantly higher than the therapeutic dose, myocardial sodium channel dysfunction and, therefore, true congenital BrS cannot be completely ruled out since the type 1 Brugada ECG pattern was induced by a sodium channel blocker. We, therefore, suggest to the authors that this patient undergo provocative testing at “controlled” levels with a sodium channel blocking agent (flecainide, ajmaline, procainamide, or pilsicainide)10 after
J Cardiovasc Electrophysiol, Vol. 25, p. E2 Address for correspondence: Adrian Baranchuk, M.D., F.A.C.C., F.R.C.P.C., Division of Cardiology, Electrophysiology and Pacing, Kingston General Hospital, Queen’s University, 76 Stuart Street, Kingston, Ontario, Canada K7L 2V7. Fax: 613-548-1387; E-mail: [email protected] doi: 10.1111/jce.12374
having cleared supratherapeutic flecainide levels from her system. If the test is positive, this would be diagnostic of BrS10 and would not qualify as a BrP. If the test is negative, it would point to an interesting area of further study suggesting that sodium channel dysfunction may occur at varying serum levels of sodium channel blocking agents. Genetic testing remains desirable in this patient but not mandatory, as it is positive in about only 20–30% of true BrS.8
DANIEL D. ANSELM, M.D. and ADRIAN BARANCHUK, M.D., F.A.C.C., F.R.C.P.C From theDivision of Cardiology, Electrophysiology and Pacing, Kingston General Hospital, Queen’s University, Kingston, Ontario, Canada
References 1. Chubb H, Cooklin M, Rosenthal E: Brugada phenocopy with a flecainide overdose: A pharmacological dose effect? J Cardiovasc Electrophysiol 2013; doi:10.1111/jce.12335. 2. Baranchuk A, Nguyen T, Ryu MH, Femen´ıa F, Zareba W, Wilde AA, Shimizu W, Brugada P, P´erez-Riera AR: Brugada phenocopy: New terminology and proposed classification. Ann Noninvasive Electrocardiol 2012;17:299-314. 3. Anselm DD, Baranchuk A: Brugada phenocopy: Redefinition and updated classification. Am J Cardiol 2013;111:453. 4. Genaro NR, Anselm DD, Cervino N, Estevez AO, Perona C, Villamil AM, Kervorkian R, Baranchuk A: Brugada phenocopy clinical reproducibility demonstrated by recurrent hypokalemia. Ann Noninvasive Electrocardiol 2013; doi:10.1111/anec.12101. 5. Anselm DD, Baranchuk A: Brugada phenocopy in the context of pulmonary embolism. Int J Cardiol 2013;168:560. 6. Anselm DD, Barbosa-Barros R, de Sousa Bel´em L, Nogueira de Macedo R, P´erez-Riera AR, Baranchuk A: Brugada phenocopy induced by acute inferior ST-segment elevation myocardial infarction with right ventricular involvement. Inn Card Rhythm Manag 2013;4:1092-1094. 7. Bay´es de Luna A, Brugada J, Baranchuk A, Borggrefe M, Breithardt G, Goldwasser D, Lambiase P, Riera AP, Garcia-Niebla J, Pastore C, Oreto G, McKenna W, Zareba W, Brugada R, Brugada P: Current electrocardiographic criteria for diagnosis of Brugada pattern: A consensus report. J Electrocardiol 2012;45:433-442. 8. Probst V, Wilde AA, Barc J, Sacher F, Babuty D, Mabo P, Mansourati J, Le Scouarnec S, Kyndt F, Le Caignec C, Guicheney P, Gouas L, Albuisson J, Meregalli PG, Le Marec H, Tan HL, Schott JJ: SCN5A mutations and the role of genetic background in the pathophysiology of Brugada syndrome. Circ Cardiovasc Genet 2009;2:552-557. 9. Anselm DD, Baranchuk A: Terminological clarification of Brugada phenocopy, Brugada syndrome, and the Brugada ECG pattern: Re. Early repolarization pattern in patients with provocable Brugada phenocopy: A marker of additional arrhythmogenic cardiomyopathy. Int J Cardiol 2014;171:288. 10. Priori SG, Wilde AA, Horie M, Cho Y, Behr ER, Berul C, Blom N, Brugada J, Chiang CE, Huikuri H, Kannankeril P, Krahn A, Leenhardt A, Moss A, Schwartz PJ, Shimizu W, Tomaselli G, Tracy C: HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: Document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013. Heart Rhythm 2013;10:1932-1963.
