This commentary refers to the article ‘Brugada syndrome genetics is associated with phenotype severity’ by G. Ciconte et al., doi:10.1093/eurheartj/ehaa942 and the discussion piece ‘Different genotypes of Brugada syndrome may present different clinical phenotypes: electrophysiology from bench to bedside’ by I El-Battrawy et al., doi:10.1093/eurheartj/ehab070.
We thank the authors El-Battrawy et al. 1 for pointing out the studies on human cardiomyocytes from induced pluripotent stem cells, which demonstrate different phenotypes between cells with a mutation in the SCN5A gene vs. mutations in other genes, e.g., SCN10A or SCN1B, which could be in line to confirm our findings on a cellular level. While debated, variants in SCN10A, SCN1B, and other genes may, in fact, result in Brugada syndrome (BrS),2 and their potential causative effects are the subject of current debate possibly only because of the lack of current data.3 However, BrS has a complex pathology, and the effects of variants in these genes have yet to be verified in both additional clinical and functional studies. Results involving these genes were not included in our own present study only because of the low numbers in which they were discovered in the patients, which did not enable the obtainment of a reliable genotype–phenotype relationship, unlike for the SCN5A gene, for which more data were available, due to the higher prevalence of variants that were able to be identified.
Regarding the effects of quinidine or beta-blockers, as we do believe that these drugs could have an effect on the size of the arrhythmogenic substrate and affect the ablation procedure, patients using these drugs were excluded from this particular study. We wrote in our original study, ‘None of the study subjects were taking any antiarrhythmic, antipsychotic, or other drugs known to have a significant effect on cardiac ion channels at the time of SAECG recording’.4
Regarding the effects of anaesthetics that are used during the ablation procedure, we have published a paper5 demonstrating the safety of general anaesthesia using single-bolus propofol and volatile anaesthetics in high-risk patients with BrS, describing how it may exert a modulating effect by reducing the manifestation of the type 1 BrS pattern and arrhythmogenic substrate in the form of epicardial abnormal electrocardiograms. These anaesthetic drugs are used consistently across all patients, regardless of genotype, and thus, while they may affect the presentation of the phenotype as compared to when the patient is not sedated, their consistent use across all patients enabled us to still be able to ascertain differences in the phenotype between patients with or without a variant in the SCN5A gene.
Funding
Ricerca Corrente funding from Italian Ministry of Health to IRCCS Policlinico San Donato, in part.
Conflict of interest: none declared.
Contributor Information
Carlo Pappone, Arrhythmia and Electrophysiology Department, IRCCS Policlinico San Donato, Piazza E. Malan 1, 20097 San Donato Milanese, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.
Giuseppe Ciconte, Arrhythmia and Electrophysiology Department, IRCCS Policlinico San Donato, Piazza E. Malan 1, 20097 San Donato Milanese, Milan, Italy.
Emanuele Micaglio, Arrhythmia and Electrophysiology Department, IRCCS Policlinico San Donato, Piazza E. Malan 1, 20097 San Donato Milanese, Milan, Italy.
Michelle M Monasky, Arrhythmia and Electrophysiology Department, IRCCS Policlinico San Donato, Piazza E. Malan 1, 20097 San Donato Milanese, Milan, Italy.
References
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