Abstract
Introduction:  TheSudden Cardiac Death-Screening of Risk FactOrS survey included a 12-lead ECG plus a digital-based questionnaire and aimed to screen for warning signs of diseases that may course with sudden cardiac death in children and young-adults. We aimed to estimate the prevalence of unexplained syncope (US) and characterize its high-risk features and predictors in this cohort.
Methods and results:  We determined the most probable etiology of the transient loss of consciousness (TLOC) episodes based on clinical criteria. US was an exclusion diagnosis and we analyzed its potential clinical and ECG predictors. Among 11,878 individuals, with a mean age of 21±6 (range 6-40) years-old, the cumulative incidence of TLOC was 26.5%, 76.2% corresponding to females. Reflex syncope was present in 61.0%, orthostatic hypotension in 7.9% and 12.6% of the individuals had US. Unexplained syncope was independently associated with age < 18 years-old (OR1.72; 95%CI 1.27-2.32,p<0.001), male gender (OR1.650; 95%CI 1.22-2.23,p=0.001), participation in competitive sports (OR1.64;95%CI 1.01-2.66,p=0.044), major syncope high-risk features (OR 2.61;95%CI 1.96-3.47,p<0.001), syncope after exertion (OR2.77;95%CI 1.80-4.27,p<0.001), fever context (OR9.58;95%CI 4.12-22.30,p<0.001), lower number of previous syncopal episodes (OR0.36;95%CI 0.37-0.48,p<0.001) and history of palpitations requiring medical care (OR1.98;95%CI 1.16-3.38,p=0.012). We found no ECG predictors of US in this population.
Conclusions:  The cumulative incidence of TLOC in children and young-adults is high and remains unexplained in an important proportion of individuals. We identified eight clinical characteristics that may be useful for the risk stratification of individuals evaluated in a non-acute setting.
Keywords: transient loss of consciousness, unexplained syncope, predictors, children and young-adults, athletes
Introduction
Sudden cardiac death (SCD) in the young population is relatively rare, with an estimated incidence of 0.46–3.7 events per 100 000 person-years among young-adults (1)(2) and of approximately 7.8 per 100 000 persons during a 7-year period among children.(3) Yet, it remains an important health problem that frequently attracts media attention, as it frequently affects previously healthy individuals and carries significant social and psychological consequences to the relatives of the victims. The viability, practicality and efficacy of screening programs is being put in question by some, as nearly two-thirds of the events occur as the first clinical manifestation of cardiac disease. (4)
The SCD – Screening of Risk FactOrS  (SCD-SOS) survey aimed to screen for clinical and electrocardiographic warning signs of potential channelopathies and cardiomyopathies that may course with SCD in children and young-adults. (5) A previous history of syncope is relevant in this setting, although routine assessment of this symptom through questionnaires has only been performed during pre-participation screening of young athletes. (6)
The differential diagnosis of cardiac syncope with other causes of transient loss of consciousness (TLOC) may be challenging, because TLOC is prevalent among young-adults and it frequently has a benign prognosis. While several individuals present with a typical history of syncope with low-risk features that make the diagnosis of a reflex mechanism or orthostatic hypotension (OH) more likely, some syncopal events remain unexplained after initial evaluation. (7) On the other side, the identification of high-risk features in individuals with unexplained syncope (US) may suggest the presence of a serious underlying cause and help to distinguish which patients warrant further investigation and monitoring. Studies assessing high-risk features and clinical predictors of US in the general children and young-adult population are lacking. We aimed to estimate the prevalence of US and characterize its high-risk features and predictors in the SCD-SOS cohort.