ReplySearch for Evidence-Based Medicine for Brugada Syndrome: The Complex Network of the Brugada Syndrome
Author + information
- Koonlawee Nademanee, MD,
- Hariharan Raju, PhD,
- Sofia De Noronha, PhD,
- Michael Papadakis, MD,
- Laurence Robinson, BSc,
- Stephen Rothery, BSc,
- Naomasa Makita, MD,
- Shinya Kowase, MD,
- Nakorn Boonmee, MD,
- Vorapot Vitayakritsirikul, MD,
- Samrerng Ratanarapee, MD,
- Sanjay Sharma, MD,
- Allard C. van der Wal, MD,
- Michael Christiansen, MD,
- Hanno L. Tan, MD,
- Arthur A. Wilde, MD,
- Akihiko Nogami, MD,
- Mary N. Sheppard, MD,
- Gumpanart Veerakul, MD and
- Elijah R. Behr, MD∗ (ebehr{at}sgul.ac.uk)
- ↵∗Cardiology Clinical Academic Group, St. George's University of London, London SW17 0RE, United Kingdom
We thank Drs. Patanè and Martini for their letters in relation to our paper (1).
Dr. Patanè points out the complexities underlying Connexin-43 expression including regulation by T-box (TBX)–linked transcription factors. Indeed, work from our group and colleagues has associated common variation at the SCN5A-SCN10A locus with the risk for the Brugada syndrome compared with healthy controls (2,3). This locus is associated with a TBX3/5 binding site thought to regulate SCN5A transcription. It is therefore appealing to investigate how TBX3/5 may influence Connexin-43 expression and in turn influence the phenotype of the Brugada syndrome.
Dr. Martini points out the absence of any ante mortem electrocardiographic studies (ECGs) that may support the diagnosis of the Brugada syndrome in the cases of sudden arrhythmic death syndrome included in our study. We recognize this limitation, but a diagnosis of the Brugada syndrome in at least 1 first-degree relative in all our cases makes any other etiology extremely unlikely. This approach forms the basis of current diagnostic guidelines (4). In addition, our own data in sudden arrhythmic death syndrome cases with a familial diagnosis of Brugada syndrome who underwent ECGs ante mortem indicate that a type 1 ECG pattern is usually absent (5).
Dr. Martini also points out work by Nava describing an overt right ventricular structural disorder associated with ECG abnormalities, including the subsequently termed type 1 ECG Brugada pattern. Limitations on reference numbers meant that we were unable to refer to all manuscripts worthy of inclusion. We included only sudden arrhythmic death syndrome cases in our cohort, that is, ostensibly structurally normal hearts. The subsequent finding of subtle fibrosis in the right ventricular outflow tract in these cases represents 1 end of the spectrum of the Brugada syndrome phenotype, the other end being described by Nava.
Footnotes
Please note: Dr. Nademanee has received consulting agreements from and has received research grants and royalties from Biosense Webster. Dr. Wilde is a consultant for Sorin. Dr. Behr has received unrestricted research funds from Biotronik and St. Jude Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- 2016 American College of Cardiology Foundation
