Abstract 11509: QT Rate Dependence is Reduced in Brugada Syndrome Independent of Genotypic Status

Abstract

Introduction: Sudden cardiac death in Brugada syndrome (BrS) is most frequent in rest or during sleep suggesting an influence of the autonomic nervous system. Some limited data indicate reduced QT rate dependence and loss of its diurnal variation in BrS. Hypothesis: We evaluated the hypothesis that QT rate dependence and its diurnal variation is reduced in BrS and assessed whether presence of an SCN5A mutation influences this relationship. Methods: In this retrospective single center study we included 4 different groups: patients demonstrating a spontaneous or ajmaline-induced type 1 ECG with (N=17) and without (N=19) SCN5A mutation, carriers of an SCN5A mutation without phenotypic evidence of BrS based on serial ECG’s and provocation with ajmaline (N=22) and finally genotype negative family members of SCN5A mutation carriers as controls (N=25). All patients underwent 24 hour holter recordings. QT/RR analysis of 24 hour, daytime (8AM-9PM) and nighttime (11PM-6AM) data was performed along with manual review. Results: Age and sex were comparable between groups, as was the use of a beta-blocker (9 in the total group). 24 hour QT/RR slope was reduced both in the SCN5A positive (0.141±0.045; p=0.04) and negative BrS group (0.141±0.047; p=0.03) as in the phenotype negative genotype positive group (0.128±0.046; p=0.001) compared to controls (0.183±0.054). Daytime QT rate dependence remained significantly reduced in the 3 pathological states, however nighttime QT rate dependence was not. In controls there was a trend towards a diurnal variation of QT rate dependence (QT/RR slope day 0.152±0.063; night 0.129±0.05; p=0.13), however this was not the case in any of the other groups. There was a clear trend towards lower values in 10 symptomatic BrS patients (0.118±0.045) compared to 26 asymptomatic BrS patients (0.15±0.043; p=0.06). Conclusions: In this large cohort of BrS patients, QT rate dependence was reduced during 24 hour and daytime periods without evidence of diurnal variation and independent of the presence of an SCN5A mutation. This attenuation of QT rate dependency further underscores the role of a pathological response to autonomic nervous system modulation in BrS arrhythmogenesis, irrespective of SCN5A genotypic status.