COGIA – Clinical course, outcome and genetics of inherited arrhythmias in children: a German multicenter study

Background: Clinical management and risk stratification of sudden arrhythmic death remain challenging in children with inherited arrhythmia syndromes, such as long QT syndrome (LQTS), Brugada syndrome (BrS), and catecholaminergic polymorphic ventricular tachycardia (CPVT).

The primary objective was to describe clinical course, molecular genetics, and outcome in children and adolescents with inherited arrhythmia syndromes. The secondary objective was to identify clinical and genetic risk factors for the occurrence of malignant arrhythmias and (aborted) sudden cardiac death.

Method: Retrospective multicenter (12 tertiary care pediatric cardiology centers) data collection from patients with a clinical and/or molecular genetic diagnosis of an inherited arrhythmia syndrome ≤ 18 years. Major arrhythmic event (MAE) was defined as sudden cardiac death (SCD), aborted sudden cardiac death, appropriate discharge of implantable cardioverter-defibrillator (ICD), or documented sustained ventricular tachycardia.

Results: Data from 656 patients (325 male) with inherited arrhythmia syndrome diagnosed in childhood were analyzed. Age at diagnosis was 6.7 ± 5.4 (range: 0–17.99) and age at last follow-up was 13.2 ± 7.8 (range: 0–55) years. Follow-up time since first encounter was 6.5 ± 6.1 (range: 0–48) years. Diagnosis was LQTS in 496 (LQTS1 = 228, LQTS2 = 151, LQTS3 = 44, other LQTS = 73), BrS in 29, CPVT in 59, and other in 72 patients. A (likely) pathogenic genetic variant was identified in 534 of 607 patients tested (88%). An ICD was implanted in 130 patients (19.8%) at 11.9 ± 6.0 (range: 0–30) years of age, with 48 patients (36.9%) receiving an appropriate shock during follow-up. At last follow-up, 543 patients (82.8%) received cardiac medications.

Over a follow-up of 4,100 patient-years, 103 patients (15.7%) experienced a MAE, including sustained ventricular tachycardia (n = 19), aborted sudden death or appropriate ICD discharge (n = 82), and SCD (n = 2). The likelihood of experiencing a MAE was highest in patients with a diagnosis of CPVT (55.9% of CPVT patients).

Conclusion: Major arrhythmic events are not uncommon in children with inherited arrhythmia syndromes, especially in those with the diagnosis of CPVT. Risk stratification and timely initiation of preventive therapies is crucial in this disease entity. This German multicenter dataset will help to identify clinical and genetic factors associated with increased arrhythmic risk in these rare diseases.

Publication History

Article published online:
28 January 2023