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

Abstract 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.