Long QT syndrome in children and adolescents: risk factors and outcomes in a large German cohort

BACKGROUND AND AIMS: This study describes outcomes in a large contemporary national cohort of children and adolescents with long QT syndrome (LQTS). METHODS: Data analysis of 548 paediatric LQTS patients at 12 German tertiary care centres. Primary outcome was the occurrence of a major arrhythmic event (MAE) defined as sudden cardiac death (SCD), aborted cardiac arrest (ACA) and appropriate implantable cardioverter-defibrillator (ICD) therapy before age 18 years. RESULTS: Patients (48.9% male) presented at a median age of 6.3 (interquartile range 0.5-11.7) years with incidental findings (26.5%), symptoms (31.3%), and for cascade screening (42.2%). Primary outcome was reached in 58 patients (10.6%): SCD in 7 (1.3%), ACA in 40 (7.3%), and appropriate ICD therapy in 11 (2.0%), with an overall event rate of 1.0 per 100 patient-years at risk. During follow-up (before 18 years of age), 92.1% of patients received cardiac medication. An ICD was implanted in 73 patients (13.3%) of whom 25 (34.2%) received appropriate therapy. In multivariate analysis, the likelihood of experiencing a MAE was greater in patients with LQT3 [hazard ratio (HR) 2.5, 95% confidence interval (CI) 1.1-5.6, P = .03], syncope (HR 3.0, 95% CI 1.7-5.5, P < .01), absence of cardiac medication (HR 9.5, 95% CI 5.3-17.3, P < .01), and QTc ≥500 ms (HR 2.9, 95% CI 1.4-6.3, P < .01). In subanalyses, a pathogenic variant in the KCNH2 pore region of LQT2 patients and younger age at symptom presentation were identified as risk factors. CONCLUSIONS: Paediatric LQTS patients are at risk for life-threatening arrhythmias at <18 years of age and require a meticulous personalized clinical approach.