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Abstract
Background The SCN5A gene polymorphism histidine-558-to-arginine (H558R) has been associated with atrial fibrillation (AF) and may affect the therapeutic effects of flecainide. This study aimed to assess the prevalence of the H558R polymorphism in a European cohort of patients with AF and examine its association with flecainide’s effects on AF recurrence and toxicity.
Methods This cohort study included patients diagnosed with AF and prescribed flecainide between 2017 and 2021 in a regional health area. Patients without the polymorphism (H558R−/−) were compared with heterozygous patients (H558R+/−) for a primary outcome of combined 6-month AF recurrence or toxicity. Secondary analyses evaluated the long-term outcomes and compared the prevalence of H558R in the AF cohort to a general population sample (n=3401).
Results A total of 104 patients were enrolled, with 57% H558R−/−, 37% H558R+/− and 6% H558R+/+. The prevalence of the H558R polymorphism was significantly higher in the AF cohort than in the general population (43.27% vs 24.37%, prevalence ratio 1.78, 95% CI 1.41 to 2.23, p<0.01). H558R+/− patients had a significantly lower risk of 6-month AF recurrence or toxicity (p=0.023, risk ratio 0.423, 95% CI 0.189 to 0.947), corresponding to an absolute risk difference of 21.5%. These findings were similar in the multivariable analysis. In long-term follow-up, H558R+/− patients continued to demonstrate a lower risk of AF recurrence or toxicity (p=0.039, HR 0.53, 95% CI 0.276 to 0.999).
Conclusions The H558R polymorphism is more prevalent in patients with AF compared with the general population and its presence is associated with a more favourable response to flecainide treatment.
- Atrial Fibrillation
- Pharmacology, Clinical
- Genetic Association Studies
Data availability statement
Data are available upon reasonable request. The authors of the study are willing to collaborate in future research using the data generated in this work.
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Data availability statement
Data are available upon reasonable request. The authors of the study are willing to collaborate in future research using the data generated in this work.
Footnotes
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Contributors MTA contributed to the conception and design of the work, designed the data collection tools, collected clinical information, wrote the statistical analysis plan, cleaned and analysed the data, and drafted and revised the paper. He is the guarantor. MB directed the genetic study and contributed to the drafting and revision of the paper. AB-V participated in the genetic study and contributed to the drafting and revision of the paper. CT collaborated in the design of the statistical plan and the analysis of the genetic data and contributed to the drafting and revision of the paper. MPH participated in the acquisition of clinical information and in the drafting and revision of the paper. CMC participated in the interpretation of the results and the drafting and revision of the paper. JGS participated in the interpretation of the results and the drafting and revision of the paper. JRG-J participated in the interpretation of the results and the drafting and revision of the paper. MR-M contributed to the conception and design of the work, collaborated in the design of the data collection tools, and drafted and revised the paper. Some authors have used ChatGPT solely as a tool to check if the syntax used was appropriate, as not all authors have English as their first language.
Funding The study has been partially funded by the Instituto de Salud Carlos III (grant number N/A).
Competing interests None declared.
Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.
Provenance and peer review Not commissioned; externally peer reviewed.
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