Inherited cardiac arrhythmias in the young

This thesis focuses on enhancing the diagnosis and treatment of two inherited cardiac arrhythmias in young individuals: catecholaminergic polymorphic ventricular tachycardia (CPVT) and Brugada syndrome. Since their initial identification in the 1990s, advances in research have enabled the identification of at-risk patients through cascade screening, resulting in a larger patient cohort with different disease characteristics that both enabled and necessitated cohort studies to improve diagnosis and treatment.
Part I centers on CPVT. A significant finding is the assessment of intra-patient variability in ventricular arrhythmia during exercise stress tests, showing moderate repeatability in arrhythmia levels. A review and cohort study of asymptomatic family members with RYR2 variants show a relatively low risk of arrhythmic events, and in the cohort study, the probability of a CPVT phenotype increases after ~6 years of age, and especially between 10 and 15 years of age. A large cohort study in symptomatic children reveals that non-selective β-blockers like nadolol are preferable to β1-selective options, as patients on the latter showed a higher risk of arrhythmic events. Lastly, non-adherence to medication was considerable in a multilingual survey study, with concerns about CPVT treatment associated with non-adherence.
Part II addresses Brugada syndrome in children. It highlights that only children from Brugada families with a SCN5A variant develop a type 1 ECG pattern during fever, indicating that ECG monitoring during fever is warranted only for this group. A consensus statement was developed to standardize the screening and management of children at risk for Brugada syndrome in the Netherlands.