Temporal Variability of Ventricular Activation in Brugada Syndrome Patients

Sofia Romagnoli1, Alba Isabel Roquero2, Alba Martin3, Flavio Palmieri4, Esther Pueyo5, Pedro Gomis6, Pablo Laguna7, Elena Arbelo Lainez8, Ana Mincholé5
1Universidad de Zaragoza, 2Institut d'Investigació August Pi y Sunyer (IDIBAPS), 3Biomedical Signal Interpretation and Computational Simulation Group (BSICoS), Universidad de Zaragoza, 4Universitat Politècnica de Catalunya, 5University of Zaragoza, 6Universitat Politecnica de Catalunya, 7Zaragoza University, 8Hospital Clinic de Barcelona


Abstract

Introduction: Brugada syndrome (BrS) is a genetic disease associated with increased incidence of ventricular fibrillation events, predominantly between midnight and early morning. This temporal pattern suggests that circadianity may modulate arrhythmogenic susceptibility. The present work evaluates the circadianity of ventricular activation in BrS patients from 24-hour electrocardiographic monitoring with high-precordial leads configuration.

Methods: Ventricular activation is characterized by lead-dependent propagation progression times relative to QRS onset, T(h), which are computed every h-th half hour in each lead as the time along the QRS complex when the QRS energy reaches a percentage of its total energy. The trend of T(h) is characterized in terms of median and standard deviation over 24-hours, as well as MESOR and amplitude from the cosinor fit analysis. The study population is composed of 44 healthy controls and 102 BrS patients. Group comparisons are performed using the Mann-Whitney U test. The association between activation times and heart rate (HR) is estimated by Spearman correlation. To evaluate the discriminative power of T(h), a multivariate logistic regression is conducted with the precordial leads considered as variables.

Results/Discussion: Based on cosinor analysis, T(h) is less affected by circadianity than HR(h). The Spearman correlation of T(h) with HR(h) is lower than 0.5 for both groups. Further, the median and standard deviation of T(h) at different QRS-energy percent distinguish between BrS and controls (AUC≥ 0.80). The standard deviation of T(h) at 70% of QRS energy results higher in symptomatic patients with implanted cardioverter defibrillator than in the asymptomatic group.

Conclusion: The intra-day variability of ventricular activation times is not primarily driven by circadianity or heart rate. Results support the potential role of the temporal variability of T(h) as risk stratification marker in BrS.