International Journal of Cardiology 191 (2015) 301–302
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Association between arrhythmogenic cardiomyopathy and Brugada syndrome — The influence of novel electrocardiographic features of Brugada syndrome Stefan Peters St. Elisabeth Hospital Salzgitter gGmbH, Liebenhaller Str. 20, 38259 Salzgitter, Germany
a r t i c l e
i n f o
Article history: Received 19 April 2015 Accepted 21 April 2015 Available online 23 April 2015 Keywords: Arrhythmogenic cardiomyopathy Brugada syndrome Low amplitude QRS Coved-type STelevation
In 2014 Antonio Bayés de Luna published an article entitled New electrocardiographic features in Brugada syndrome [1] defining some new electrocardiographic criteria: - concave (coved) ST-segment morphology with negative symmetrical T-waves - QRS–ST at least 2 mm high in lead V1 - ST-segment morphology shows progressive decline - the ratio between the peak height of QRS–ST after 80 ms is greater than 1 - the duration of the QRS in leads V1 and V2 is greater than in the middle and left precordial leads - type-1 Brugada syndrome ECG may be seen in a single lead, V1 or V2, but never exclusively in V3. In 2015 Junjie Zhang defined cardiac electrophysiologic substrate underlying the ECG phenotype and electrogram abnormalities in Brugada syndrome patients [2] as follows: - ST-segment elevation and inverted T-waves - delayed RVOT activation - low amplitude and fractionated electrograms, suggesting slow discontinuous conduction - prolonged recovery time and activation-recovery intervals indicating delayed repolarisation - steep repolarisation gradients at RVOT borders.
E-mail address: [email protected].
http://dx.doi.org/10.1016/j.ijcard.2015.04.187 0167-5273/© 2015 Published by Elsevier Ireland Ltd.
Some of these novel criteria were applied to patients with typical arrhythmogenic cardiomyopathy where ajmaline testing was able to detect provocable coved type ST-segment elevation in right precordial leads. In 127 patients with typical arrhythmogenic cardiomyopathy (83 males, mean age 46.6 ± 13.3 years) ajmaline testing was done. In 19 cases (8 males, mean age 52.1 ± 11.6 years) coved-type ST-segment elevation in right precordial leads could be provoked (15%). Some of the novel electrocardiographic criteria were applied to these 19 patients: - QRS–ST at least 2 mm high in lead V1 - the duration of the QRS in leads V1 and V2 is greater than in the middle and left precordial leads - QRS morphology shows progressive decline - low QRS amplitude. This analysis was done to exclude patients with conduction abnormalities in the right ventricular outflow tract not representing as true Brugada syndrome [3]. 19 patients presented with coved-type ST-segment elevation, progressive decline of QRS morphology and symmetrical negative Twaves (100%). Also in all 19 patients the duration of the QRS in leads V1 and V2 was greater than in the middle and left precordial leads (100%). In 16 patients there was low QRS complex amplitude after ajmaline testing in comparison to the ECG before ajmaline administration (84%). In 17 patients the peak of QRS–ST was 2 mm or greater in lead V1 (89%) suggesting that in 2 patients no true Brugada syndrome could be provoked by ajmaline administration (11%). It is an ongoing debate whether Brugada syndrome is associated with arrhythmogenic cardiomyopathy. Since the finding of the so-called connexome [4] – an interaction of sodium channels, desmosomal proteins and gap junctions – a continuum between arrhythmogenic cardiomyopathy and Brugada syndrome is possible and, at least, when plakophilin-2 is the relevant gene mutation an association in likely [5]. Plakophilin-2 is the most relevant finding in arrhythmogenic cardiomyopathy and is in about 2.5% the mutational finding in isolated Brugada syndrome. In this study we could document that provocable coved-type right precordial ST-segment elevation is in most cases a true Brugada
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S. Peters / International Journal of Cardiology 191 (2015) 301–302
Fig. 2. Precordial leads before (right side) and after (left side) ajmaline administration with coved-type ST-segment elevation without other discriminating findings. Fig. 1. Precordial leads before and after ajmaline administration with coved-type ST-segment elevation, QRS–ST height of at least 2 mm in V1, low QRS amplitude after ajmaline administration and increased QRS duration in right precordial leads.
syndrome confirming novel electrocardiographic criteria such as the height of QRS–ST of at least 2 mm in V1, low QRS amplitude, symmetrical negative T-waves, a progressive decline QRS morphology and greater QRS duration in right precordial leads than in left precordial leads. Fig. 1 shows a typical example where all criteria are positive. In at least 2 or 3 patients we can suppose that RVOT conduction abnormalities lead to coved-type ST-segment elevation not to be confused with true Brugada syndrome [3]. Fig. 2 shows a typical ECG before and after ajmaline testing. This study clearly shows that in some patients Brugada syndrome is a variant of arrhythmogenic cardiomyopathy with fibrosis and reduced gap junctions localised at the right ventricular outflow tract [6]. Even in some cases initial Brugada syndrome with aborted sudden death can be supposed in developing arrhythmogenic cardiomyopathy in the course of the disease [7]. Conflict of interest The author reports no relationships that could be construed as a conflict of interest.
References [1] A. Bayes de Luna, J. Garcia-Niebla, A. Baranchuk, New electrocardiographic features in Brugada syndrome, Curr. Cardiol. Rev. 10 (2014) 175–180. [2] J. Zhang, F. Sacher, K. Hoffmayer, T. O'Hara, M. Strom, P. Cuculich, et al., Cardiac electrophysiologic substrate underlying the ECG phenotype and electrogram abnormalities in Brugada syndrome patients, Circulation (2015) pii: CIRCULATIONAHA.114.013698. [3] B.J. Boukens, M. Sylva, C. de Gier-de Vries, C.A. Remme, C. Bezzina, V.M. Christoffels, R. Coronel, Reduced sodium channel function unmasks residual slow conduction in the adult right ventricular outflow tract, Circ. Res. 113 (2013) 137–141. [4] E. Agullo-Pascual, M. Cerrone, M. Delmar, Arrhythmogenic cardiomyopathy and Brugada syndrome: diseases of the connexome, FEBS Lett. 588 (2014) 1322–1330. [5] S. Peters, Arrhythmogenic cardiomyopathy and provocable Brugada ECG in a patient caused by missense mutation in plakophilin-2, Int. J. Cardiol. 173 (2014) 317–318. [6] H. Raju, S.V. de Noronha, S. Rothery, L. Ronbinson, M. Papadakis, S. Sharma, et al., The brugada syndrome and cardiomyopathy: altered collagen and gap junction expression, Europace (2014)http://dx.doi.org/10.1093/europace/euu237.11. [7] S. Peters, Provocable coved-type ST-segment elevation in right precordial leads as initial ECG feature after successful resuscitation with developing arrhythmogenic cardiomyopathy, Int. J. Cardiol. 185 (2015) 136–137.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Association between arrhythmogenic cardiomyopathy and Brugada syndrome — The influence of novel electrocardiographic features of Brugada syndrome Stefan Peters St. Elisabeth Hospital Salzgitter gGmbH, Liebenhaller Str. 20, 38259 Salzgitter, Germany
a r t i c l e
i n f o
Article history: Received 19 April 2015 Accepted 21 April 2015 Available online 23 April 2015 Keywords: Arrhythmogenic cardiomyopathy Brugada syndrome Low amplitude QRS Coved-type STelevation
In 2014 Antonio Bayés de Luna published an article entitled New electrocardiographic features in Brugada syndrome [1] defining some new electrocardiographic criteria: - concave (coved) ST-segment morphology with negative symmetrical T-waves - QRS–ST at least 2 mm high in lead V1 - ST-segment morphology shows progressive decline - the ratio between the peak height of QRS–ST after 80 ms is greater than 1 - the duration of the QRS in leads V1 and V2 is greater than in the middle and left precordial leads - type-1 Brugada syndrome ECG may be seen in a single lead, V1 or V2, but never exclusively in V3. In 2015 Junjie Zhang defined cardiac electrophysiologic substrate underlying the ECG phenotype and electrogram abnormalities in Brugada syndrome patients [2] as follows: - ST-segment elevation and inverted T-waves - delayed RVOT activation - low amplitude and fractionated electrograms, suggesting slow discontinuous conduction - prolonged recovery time and activation-recovery intervals indicating delayed repolarisation - steep repolarisation gradients at RVOT borders.
E-mail address: [email protected].
http://dx.doi.org/10.1016/j.ijcard.2015.04.187 0167-5273/© 2015 Published by Elsevier Ireland Ltd.
Some of these novel criteria were applied to patients with typical arrhythmogenic cardiomyopathy where ajmaline testing was able to detect provocable coved type ST-segment elevation in right precordial leads. In 127 patients with typical arrhythmogenic cardiomyopathy (83 males, mean age 46.6 ± 13.3 years) ajmaline testing was done. In 19 cases (8 males, mean age 52.1 ± 11.6 years) coved-type ST-segment elevation in right precordial leads could be provoked (15%). Some of the novel electrocardiographic criteria were applied to these 19 patients: - QRS–ST at least 2 mm high in lead V1 - the duration of the QRS in leads V1 and V2 is greater than in the middle and left precordial leads - QRS morphology shows progressive decline - low QRS amplitude. This analysis was done to exclude patients with conduction abnormalities in the right ventricular outflow tract not representing as true Brugada syndrome [3]. 19 patients presented with coved-type ST-segment elevation, progressive decline of QRS morphology and symmetrical negative Twaves (100%). Also in all 19 patients the duration of the QRS in leads V1 and V2 was greater than in the middle and left precordial leads (100%). In 16 patients there was low QRS complex amplitude after ajmaline testing in comparison to the ECG before ajmaline administration (84%). In 17 patients the peak of QRS–ST was 2 mm or greater in lead V1 (89%) suggesting that in 2 patients no true Brugada syndrome could be provoked by ajmaline administration (11%). It is an ongoing debate whether Brugada syndrome is associated with arrhythmogenic cardiomyopathy. Since the finding of the so-called connexome [4] – an interaction of sodium channels, desmosomal proteins and gap junctions – a continuum between arrhythmogenic cardiomyopathy and Brugada syndrome is possible and, at least, when plakophilin-2 is the relevant gene mutation an association in likely [5]. Plakophilin-2 is the most relevant finding in arrhythmogenic cardiomyopathy and is in about 2.5% the mutational finding in isolated Brugada syndrome. In this study we could document that provocable coved-type right precordial ST-segment elevation is in most cases a true Brugada
302
S. Peters / International Journal of Cardiology 191 (2015) 301–302
Fig. 2. Precordial leads before (right side) and after (left side) ajmaline administration with coved-type ST-segment elevation without other discriminating findings. Fig. 1. Precordial leads before and after ajmaline administration with coved-type ST-segment elevation, QRS–ST height of at least 2 mm in V1, low QRS amplitude after ajmaline administration and increased QRS duration in right precordial leads.
syndrome confirming novel electrocardiographic criteria such as the height of QRS–ST of at least 2 mm in V1, low QRS amplitude, symmetrical negative T-waves, a progressive decline QRS morphology and greater QRS duration in right precordial leads than in left precordial leads. Fig. 1 shows a typical example where all criteria are positive. In at least 2 or 3 patients we can suppose that RVOT conduction abnormalities lead to coved-type ST-segment elevation not to be confused with true Brugada syndrome [3]. Fig. 2 shows a typical ECG before and after ajmaline testing. This study clearly shows that in some patients Brugada syndrome is a variant of arrhythmogenic cardiomyopathy with fibrosis and reduced gap junctions localised at the right ventricular outflow tract [6]. Even in some cases initial Brugada syndrome with aborted sudden death can be supposed in developing arrhythmogenic cardiomyopathy in the course of the disease [7]. Conflict of interest The author reports no relationships that could be construed as a conflict of interest.
References [1] A. Bayes de Luna, J. Garcia-Niebla, A. Baranchuk, New electrocardiographic features in Brugada syndrome, Curr. Cardiol. Rev. 10 (2014) 175–180. [2] J. Zhang, F. Sacher, K. Hoffmayer, T. O'Hara, M. Strom, P. Cuculich, et al., Cardiac electrophysiologic substrate underlying the ECG phenotype and electrogram abnormalities in Brugada syndrome patients, Circulation (2015) pii: CIRCULATIONAHA.114.013698. [3] B.J. Boukens, M. Sylva, C. de Gier-de Vries, C.A. Remme, C. Bezzina, V.M. Christoffels, R. Coronel, Reduced sodium channel function unmasks residual slow conduction in the adult right ventricular outflow tract, Circ. Res. 113 (2013) 137–141. [4] E. Agullo-Pascual, M. Cerrone, M. Delmar, Arrhythmogenic cardiomyopathy and Brugada syndrome: diseases of the connexome, FEBS Lett. 588 (2014) 1322–1330. [5] S. Peters, Arrhythmogenic cardiomyopathy and provocable Brugada ECG in a patient caused by missense mutation in plakophilin-2, Int. J. Cardiol. 173 (2014) 317–318. [6] H. Raju, S.V. de Noronha, S. Rothery, L. Ronbinson, M. Papadakis, S. Sharma, et al., The brugada syndrome and cardiomyopathy: altered collagen and gap junction expression, Europace (2014)http://dx.doi.org/10.1093/europace/euu237.11. [7] S. Peters, Provocable coved-type ST-segment elevation in right precordial leads as initial ECG feature after successful resuscitation with developing arrhythmogenic cardiomyopathy, Int. J. Cardiol. 185 (2015) 136–137.
