Discussion
The cumulative incidence
of TLOC among young-adults (28.8%) and children (18.9%) from the
SCD-SOS survey is high. Unexplained syncope was present in 14.8% of the
individuals and it was independently associated with age<18
years-old, male gender, participation in competitive sports, major
clinical high-risk features, syncope after exertion, fever context,
lower number of syncopal episodes and a history of palpitations
requiring medical care. These may
be regarded as potential warning signs in individuals who are evaluated
in a non-acute setting. Additionally, ECG abnormalities in this
population with TLOC are rare and could not be independently associated
with US.
Syncope is a common medical
problem that affects individuals of all ages and is most frequently
recognized as a benign event. (7) However, most of the previous studies
of syncope were conducted in emergency departments or hospitals, and
evidence about incidence and causes is lacking in the general
population. In Italy, in a cohort of elderly patients admitted to an
emergency department due to TLOC, (10) Rosso et al. found that 67% had
reflex syncope, 10% had orthostatic hypotension and 15% had confirmed
cardiac syncope. Accordingly, in a paper previously published by our
group, (11) the majority of young-adults presenting with a TLOC episode,
reported pre-syncopal symptoms and a context that was suggestive of a
benign (non-cardiac) etiology. (7) In our SCD-SOS cohort, the majority
of TLOC episodes were also benign.
US was present in 14.8% and it
was associated with major and minor high-risk clinical features, thus
suggesting the presence of a serious underlying cause and a higher
likelihood of a cardiac syncope. (7)
Marijon et al. have shown that
warning symptoms are frequent prior to sudden cardiac arrest, but the
vast majority of them are not acted upon. (12) This evidence has
triggered the acknowledgement of a new front in the fight against SCD -
anticipation based on warning symptoms. (13) Therefore, we consider that
early symptoms characterization and identification of the clinical
features associated with US may contribute to improve outcomes related
to SCD.
We found that male gender and less frequent syncopal events were
independent predictors of unexplained syncope. Ungar et al. have
reported that, in patients referred to the emergency department
following a syncopal event, (14) male gender increased and the incidence
of syncopal recurrences decreased mortality. On the other side, coherent
with our results, in the Italian cohort, palpitations preceding syncope,
the absence of autonomic prodromes and syncope during exertion were also
considered independent predictors of cardiac syncope. (10) In our
cohort, the presence of typical symptoms was used to classify other
causes of TLOC, therefore we excluded the high-risk feature absence of
warning symptoms from the multivariate analysis to avoid potential
information bias.
Our findings showing that participation in competitive sports and the
occurrence of syncope during exertion were independent predictors of US,
may be difficult to interpret in the light of the current knowledge.
Previous authors described that syncopal episodes in young athletes are
in most cases non-cardiac and of reflex origin. (6) Additionally, in a
Danish nationwide retrospective study in young-adults, Risgaard et al.
found no differences in the incidence rate of SCD
between competitive and non-competitive athletes aged 12-35 years.(16)
On the other side, coherent with
our results, there is some evidence showing that exertional syncope
tends to be more frequently associated with structural heart disease and
with an unfavorable outcome in adults (17) and mainly with
channelopathies and other rhythm disorders in children. (18) Stronger
evidence supports an association between SCD and sports practice, namely
among athletes in the Veneto region, in whom 91% of the SCDs occurred
during sports activity or immediately afterward. And in a recent British
post-mortem study on the etiology of SD in sports, which included 69%
of competitive-athletes, showing that the majority of athletes died
during exertion (61%). (19)
Another independent predictor of US in our cohort was an history of
fever related-syncope. Some of these individuals had ECG features
potentially suggestive of Brugada patterns. Previous studies suggested a
higher risk of fever-related symptoms and arrhythmic events in children
and young-adults with Brugada Syndrome. (20) Finally, even though the
ECG changes in a cohort of young-adults with a high proportion of
athletes may be difficult to interpret, at least 0.8% of the
participants had abnormalities in the ECG that may require further
assessment to exclude the presence of intrinsic cardiac disease. (9)
There was a negative association between US and Fridericia andBazett QTc, and a positive association with left ventricle
hypertrophy in the baseline ECG in the univariate analysis, but after
adjustment no ECG predictors of US were identified in the multivariate
analysis. We hypothesize that for a cohort composed of predominantly
healthy individuals, a much bigger sample would be necessary to further
explore electrocardiographic predictors of US. More individuals would
likely expand the statistical power of the sample and allow those
analyses. However, this also appears to suggest that the effect size of
frequent ECG traits as predictors of US is low.
We estimate that the costs for the
Portuguese Health Services to screen 11 878 participants in the SCD-SOS
survey would be 79 207,00\euro (2000,00\euro for the software and
for placing online the questionnaires plus 6,50\euro per ECG
(Diário da República 173/2018, Série I de 2018-09-07,https://data.dre.pt/eli/port/254/2018/09/07/p/dre/pt/html)).
Given that the survey allowed the diagnosis of US in 466 individuals and
the identification of relevant ECG abnormalities in 26 participants, the
estimated cost per diagnosis for a diagnostic yield of 4.1% is
160,99\euro. In our opinion, this is an acceptable cost for
identifying patients who are at risk of developing cardiac diseases
and/or have the potential to suffer SCD, thus warranting further
investigations and follow-up.