Challenging pacemaker implantation in a child with aggressive atrial standstill caused by compound heterozygous SCN5A variants

Abstract Introduction: Atrial standstill represents a rare cardiac arrhythmia characterised by the complete absence of atrial electrical and mechanical activity. Early diagnostic recognition coupled with comprehensive genetic counselling assumes paramount importance. Herein, we report a rare case of a patient who presented with bradycardia at an early age and demonstrated aggressive atrial standstill during a pacemaker upgrade, which challenged the therapeutic strategy. Case presentation: A 5-year-old girl was initially diagnosed with bradycardia. Holter monitoring confirmed severe bradycardia with prolonged sinus arrest episodes. Subsequently, the patient underwent single-chamber pacemaker implantation. During a planned dual-chamber upgrade at age 11, despite systematic exploration of multiple anatomical sites within the right atrium, adequate atrial capture could not be achieved. Intracardiac electrophysiological assessment demonstrated a complete absence of electrical activity in the bi-atrium. While speckle-tracking echocardiography revealed mildly reduced global longitudinal strain with impairment noted in the lateral myocardial segments, indicating potential injuries from ventricular demand pacing. Genetic test identified a compound heterozygous variant of SCN5A c.2431C>T and c.2893C>T. The protein structure of SCN5A has been built and named AF-P21333-F1, and the molecular function of the variant site has been annotated. Additionally, murine scRNA-seq data (GSE132658) revealed cardiac Scn5a expression is confined to the conductive bundles and fibres rather than cardiomyocytes, and the loss-of-function caused aggressive atrial standstill. Conclusion: This case provides valuable insights into genotype-phenotype correlations in SCN5A -associated atrial standstill, emphasises the importance of comprehensive electrophysiological assessment during device implantation, and underscores considerations for physiological pacing strategies in paediatric patients requiring lifelong device dependency.