Letter to the editor Herz 2014 DOI 10.1007/s00059-014-4075-4 © Urban & Vogel 2014
D.D. Anselm · A. Baranchuk Division of Cardiology, Electrophysiology and Pacing, Kingston General Hospital, Queen’s University, Kingston
Confirmed Brugada phenocopy in the setting of hypopituitarism Comment on Dogan M, Ertem AG, Cimen T, Yeter E (2013) Type-1 Brugada-like ECG pattern induced by adrenal crisis. Herz. doi:10.1007/s00059-0133983-z
To the Editor We read the article by Dogan et al. [1] with great interest and noted that this case meets the diagnostic criteria for a Brugada phenocopy (BrP) and will be included in our international registry (http://www. brugadaphenocopy.com). In addition, we would like to direct the authors toward current terminology that distinguishes true congenital Brugada syndrome (BrS) from BrP. As pointed out by the authors, the patient’s electrocardiogram (ECG) is consistent with a type 1 Brugada ECG pattern. Of note is that the most recent consensus report [2] includes only the type 1“coved” and type 2“saddleback” patterns in the formal Brugada ECG pattern definitions. We have published extensively on the subject of BrP [3, 4, 5, 6, 7] and have established the international etiological categories (. Tab. 1, [8]) and diagnostic criteria (. Tab. 2, [4, 9, 10]) for BrP. As such, we direct the authors to our recent paper [5] outlining the terminological distinction between the Brugada ECG pattern, Brugada phenocopy, and true congenital Brugada syndrome. The case presented by Dogan et al. [1] identifies a few salient points. This pa-
Tab. 1 Brugada phenocopy etiological
categories (reproduced with permission [8]) Etiological category i. Metabolic conditions ii. Mechanical compression iii. Ischemia and pulmonary embolism iv. Myocardial and pericardial disease v. ECG modulation vi. Miscellaneous
tient has known hypopituitarism (Sheehan syndrome) and was noncompliant with her medications. Untreated hypopituitarism results in multiple endocrine abnormalities [11, 12] as evidenced by this patient’s concurrent hyponatremia, hypothyroidism, hypoglycemia, and hypocorticoidism. Although this patient was treated appropriately with dextrose, levothyroxine, and prednisolone, it is difficult to ascertain which aspect of her metabolic abnormalities caused the type 1 Brugada ECG pattern. As noted by the authors, the findings may have indeed been due to hyponatremia, which has been associated with the Brugada ECG pattern [13]; however, this remains uncertain. As such, a more appropriate etiology for this case may be attributing the BrP to hypopituitarism. This uncertainty points to an important area of future research. Basic science models that reproduce the Brugada ECG patterns in the setting of common eliciting factors [3] such as hyponatremia, hyperkalemia, hypothermia, and myocardial ischemia are required to advance this field. Herz 2014
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Letter to the editor Tab. 2 Criteria to differentiate between the Brugada ECG pattern, Brugada phenocopy, and true congenital Brugada syndrome (reproduced
with permission [10]) Brugada ECG pattern i. The ECG pattern has a type 1 or type 2 Brugada morphology as currently defined by Bayés de Luna et al. [2] Diagnostic criteria for Brugada phenocopy i. The ECG pattern has a type 1 or type 2 Brugada morphology 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 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 h 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 Brugada syndrome) Features that suggest true congenital Brugada syndrome i. The ECG pattern has a type 1 or type 2 Brugada morphology ii. There is a high clinical pretest probability of true congenital Brugada syndrome determined by presence of symptoms, medical history, and family history iii. Positive provocative testing with sodium channel blockers such as ajmaline, flecainide, or procainamide. This indicates sodium channel dysfunction consistent with true Brugada syndrome iv. Genetic testing is positive in about 20–30% of probands RVOT right ventricular outflow tract, SCN5A sodium channel voltage-gated type V alpha subunit
From a BrP perspective, we must congratulate the authors on meeting all the diagnostic criteria (. Tab. 2). Most importantly they ruled out sodium channel dysfunction with a negative sodium channel blocker provocative challenge. In future cases, we suggest using our systematic diagnostic approach to BrP [9]. As such, this case qualifies as a true BrP under category (i): metabolic conditions (. Tab. 1).
Corresponding address A. Baranchuk Division of Cardiology, Electrophysiology and Pacing, Kingston General Hospital, Queen’s University K7L 2V7 Kingston Ontario Canada [email protected]
Compliance with ethical guidelines Conflict of interest. D.D. Anselm and A. Baranchuk state that there are no conflicts of interest.
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Herz 2014
References 1. Dogan M, Ertem AG, Cimen T et al (2013) Type-1 Brugada-like ECG pattern induced by adrenal crisis. Herz (Epub ahead of print) 2. Bayés de Luna A, Brugada J, Baranchuk A et al (2012) Current electrocardiographic criteria for diagnosis of Brugada pattern: a consensus report. J Electrocardiol 45:433–442 3. Baranchuk A, Nguyen T, Ryu MH et al (2012) Brugada phenocopy: new terminology and proposed classification. Ann Noninvasive Electrocardiol 17:299–314 4. Anselm DD, Baranchuk A (2013) Brugada phenocopy: redefinition and updated classification. Am J Cardiol 111:453 5. Anselm DD, Baranchuk A (2014) 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 171:288 6. Anselm DD, Baranchuk A (2014) About Brugada phenocopy: re: Brugada phenocopy with a Flecainide overdose: a pharmacological dose effect? J Cardiovasc Electrophysiol (Epub ahead of print) 7. Genaro NR, Anselm DD, Cervino N et al (2013) Brugada phenocopy clinical reproducibility demonstrated by recurrent hypokalemia. Ann Noninvasive Electrocardiol (Epub ahead of print) 8. Anselm DD, Baranchuk A (2013) Brugada phenocopy in the context of pulmonary embolism. Int J Cardiol 168:560
9. Anselm DD, Barbosa-Barros R, Sousa Belém L de et al (2013) Brugada phenocopy induced by acute inferior ST-segment elevation myocardial infarction with right ventricular involvement. Inn Card Rhythm Manag 4:1092–1094 10. Anselm DD, Evans JM, Baranchuk A (2014) Brugada phenocopy: a new ECG phenomenon. World J Cardiol (In press) 11. Kovacs K (2003) Sheehan syndrome. Lancet 361:520–522 12. Keleştimur F (2003) Sheehan’s syndrome. Pituitary 6:181–188 13. Tamene A, Sattiraju S, Wang K et al (2010) Brugada-like electrocardiography pattern induced by severe hyponatraemia. Europace 12:905–907
D.D. Anselm · A. Baranchuk Division of Cardiology, Electrophysiology and Pacing, Kingston General Hospital, Queen’s University, Kingston
Confirmed Brugada phenocopy in the setting of hypopituitarism Comment on Dogan M, Ertem AG, Cimen T, Yeter E (2013) Type-1 Brugada-like ECG pattern induced by adrenal crisis. Herz. doi:10.1007/s00059-0133983-z
To the Editor We read the article by Dogan et al. [1] with great interest and noted that this case meets the diagnostic criteria for a Brugada phenocopy (BrP) and will be included in our international registry (http://www. brugadaphenocopy.com). In addition, we would like to direct the authors toward current terminology that distinguishes true congenital Brugada syndrome (BrS) from BrP. As pointed out by the authors, the patient’s electrocardiogram (ECG) is consistent with a type 1 Brugada ECG pattern. Of note is that the most recent consensus report [2] includes only the type 1“coved” and type 2“saddleback” patterns in the formal Brugada ECG pattern definitions. We have published extensively on the subject of BrP [3, 4, 5, 6, 7] and have established the international etiological categories (. Tab. 1, [8]) and diagnostic criteria (. Tab. 2, [4, 9, 10]) for BrP. As such, we direct the authors to our recent paper [5] outlining the terminological distinction between the Brugada ECG pattern, Brugada phenocopy, and true congenital Brugada syndrome. The case presented by Dogan et al. [1] identifies a few salient points. This pa-
Tab. 1 Brugada phenocopy etiological
categories (reproduced with permission [8]) Etiological category i. Metabolic conditions ii. Mechanical compression iii. Ischemia and pulmonary embolism iv. Myocardial and pericardial disease v. ECG modulation vi. Miscellaneous
tient has known hypopituitarism (Sheehan syndrome) and was noncompliant with her medications. Untreated hypopituitarism results in multiple endocrine abnormalities [11, 12] as evidenced by this patient’s concurrent hyponatremia, hypothyroidism, hypoglycemia, and hypocorticoidism. Although this patient was treated appropriately with dextrose, levothyroxine, and prednisolone, it is difficult to ascertain which aspect of her metabolic abnormalities caused the type 1 Brugada ECG pattern. As noted by the authors, the findings may have indeed been due to hyponatremia, which has been associated with the Brugada ECG pattern [13]; however, this remains uncertain. As such, a more appropriate etiology for this case may be attributing the BrP to hypopituitarism. This uncertainty points to an important area of future research. Basic science models that reproduce the Brugada ECG patterns in the setting of common eliciting factors [3] such as hyponatremia, hyperkalemia, hypothermia, and myocardial ischemia are required to advance this field. Herz 2014
| 1
Letter to the editor Tab. 2 Criteria to differentiate between the Brugada ECG pattern, Brugada phenocopy, and true congenital Brugada syndrome (reproduced
with permission [10]) Brugada ECG pattern i. The ECG pattern has a type 1 or type 2 Brugada morphology as currently defined by Bayés de Luna et al. [2] Diagnostic criteria for Brugada phenocopy i. The ECG pattern has a type 1 or type 2 Brugada morphology 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 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 h 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 Brugada syndrome) Features that suggest true congenital Brugada syndrome i. The ECG pattern has a type 1 or type 2 Brugada morphology ii. There is a high clinical pretest probability of true congenital Brugada syndrome determined by presence of symptoms, medical history, and family history iii. Positive provocative testing with sodium channel blockers such as ajmaline, flecainide, or procainamide. This indicates sodium channel dysfunction consistent with true Brugada syndrome iv. Genetic testing is positive in about 20–30% of probands RVOT right ventricular outflow tract, SCN5A sodium channel voltage-gated type V alpha subunit
From a BrP perspective, we must congratulate the authors on meeting all the diagnostic criteria (. Tab. 2). Most importantly they ruled out sodium channel dysfunction with a negative sodium channel blocker provocative challenge. In future cases, we suggest using our systematic diagnostic approach to BrP [9]. As such, this case qualifies as a true BrP under category (i): metabolic conditions (. Tab. 1).
Corresponding address A. Baranchuk Division of Cardiology, Electrophysiology and Pacing, Kingston General Hospital, Queen’s University K7L 2V7 Kingston Ontario Canada [email protected]
Compliance with ethical guidelines Conflict of interest. D.D. Anselm and A. Baranchuk state that there are no conflicts of interest.
2 |
Herz 2014
References 1. Dogan M, Ertem AG, Cimen T et al (2013) Type-1 Brugada-like ECG pattern induced by adrenal crisis. Herz (Epub ahead of print) 2. Bayés de Luna A, Brugada J, Baranchuk A et al (2012) Current electrocardiographic criteria for diagnosis of Brugada pattern: a consensus report. J Electrocardiol 45:433–442 3. Baranchuk A, Nguyen T, Ryu MH et al (2012) Brugada phenocopy: new terminology and proposed classification. Ann Noninvasive Electrocardiol 17:299–314 4. Anselm DD, Baranchuk A (2013) Brugada phenocopy: redefinition and updated classification. Am J Cardiol 111:453 5. Anselm DD, Baranchuk A (2014) 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 171:288 6. Anselm DD, Baranchuk A (2014) About Brugada phenocopy: re: Brugada phenocopy with a Flecainide overdose: a pharmacological dose effect? J Cardiovasc Electrophysiol (Epub ahead of print) 7. Genaro NR, Anselm DD, Cervino N et al (2013) Brugada phenocopy clinical reproducibility demonstrated by recurrent hypokalemia. Ann Noninvasive Electrocardiol (Epub ahead of print) 8. Anselm DD, Baranchuk A (2013) Brugada phenocopy in the context of pulmonary embolism. Int J Cardiol 168:560
9. Anselm DD, Barbosa-Barros R, Sousa Belém L de et al (2013) Brugada phenocopy induced by acute inferior ST-segment elevation myocardial infarction with right ventricular involvement. Inn Card Rhythm Manag 4:1092–1094 10. Anselm DD, Evans JM, Baranchuk A (2014) Brugada phenocopy: a new ECG phenomenon. World J Cardiol (In press) 11. Kovacs K (2003) Sheehan syndrome. Lancet 361:520–522 12. Keleştimur F (2003) Sheehan’s syndrome. Pituitary 6:181–188 13. Tamene A, Sattiraju S, Wang K et al (2010) Brugada-like electrocardiography pattern induced by severe hyponatraemia. Europace 12:905–907
