Is there an effect of gender on phenotypical expression of sinus node dysfunction ?

Abstract Introduction Sinus node dysfunction (SND) is a common bradyarrhythmia, usually non-hereditary and typically occuring in older patients. Genetic mutations in ion channel genes such as SCN5A and HCN4 have been implicated. Furthermore, gender can influence phenotypical expression of inherited arrythmia, as it is well described in Brugada syndrome or Long QT syndrome. The influence of gender on the phenotypic expression of genetic SND remains unclear. Objective To evaluate gender-related differences in clinical presentation, arrhythmic burden, and device implantation in patients with genetically confirmed SND. Methods A retrospective multicenter study was conducted across French reference centres for genetic arrythmic diseases and included 43 patients with pathogenic mutations in SCN5A or HCN4 and documented SND. Clinical, electrocardiographic, and imaging data were analyzed, with a focus on gender-based comparisons. Results Among 43 patients (22 men, 21 women), 81.4% carried SCN5A mutations and 18.6% HCN4. No significant gender differences were found in overall phenotypic expression. Women tended to be more symptomatic and bradycardic, especially in the HCN4 subgroup, while men exhibited longer QRS durations. Atrial fibrillation was more prevalent in SCN5A carriers (22.9%) and absent in HCN4 patients. Device implantation was frequent (69%), with high atrial pacing dependency. Conclusion Although no statistically significant gender differences were observed, trends suggest women may present with more symptomatic and bradycardic profiles, while men show more conduction abnormalities. These findings highlight the need for further studies to explore sex-specific mechanisms in genetic SND, and underline the importance of broader use of genetic testing, as genetic SND likely remains underdiagnosed.