DISCUSSION
Our study is the first to compare prevalence of CSA in children with and
without HF. Contrary to adults, using the pediatric definition,
prevalence of CSA is similar in children with and without HF. After
adjusting for age, frequency of central apneic events did not differ
between the two groups. Instead, CAI correlated inversely to age at time
of sleep study. Children with elevated CAI were younger and had a higher
prevalence of prematurity. Unlike the adult population, in children, CAI
is not associated with LVEF.
We compared our results with the only other study on sleep disordered
breathing in children with HF5. This was a prospective
observational study, where the prevalence of CSA was 19% in children
with HF secondary to dilated cardiomyopathy. This study used the
pediatric CSA definition of central apnea/hypopnea per hour of sleep
>1 as abnormal. Using similar criteria of pediatric CSA
definition, prevalence of pediatric CSA in the +HF group of our study
was high at 78.9% compared to the den Boer study (19%) (Table 3).
However, the children with +HF in our study were younger with a median
age of 24 months compared to the den Boer study with a median age of
11.1 years. Using the same definition for pediatric CSA as the den Boer
study (CAI+HI >1/hr., with >50% of events
being central), the prevalence of CSA did not differ between children
with and without HF in our study. If we only compared the CAI in the two
groups, it was found to be significantly lower in the +HF group. After
adjusting for age, CAI was no longer different between the two groups.
Thus, we conclude that, unlike the adult population, central apneic
events were not increased in children with HF. Instead, central apneic
events were more commonly seen in younger aged children, regardless of
cardiac function.
Our results support previous findings, which did not show any
correlation between AHI and severity of cardiac dysfunction measured by
LVEF5,13. One study focused on assessing frequency of
sleep disordered breathing and its relationship to cardiac function in
children with cardiomyopathy found significant correlations between
CAI+HI and both LV end diastolic volume index and LV end systolic volume
index13. We did not have data on LV end diastolic
volume or end systolic volume index. 2D LV End-diastolic Septal
Thickness vs BSA z-score and 2D LV End-systolic Dimension vs BSA z-score
were higher in the +HF group. The septal thickness being significantly
higher is not an intuitive result as the assumption is that dilated,
poorly functioning hearts have a thinner septal thickness. With the
presence of a subject with hypertrophic cardiomyopathy in conjunction
with a small n of the +HF group showing a wide range up to a z-score of
19.34, this was most likely enough to skew the average to significance.
However, these parameters did not correlate with CAI or OAI. This
finding contrasts the adult literature, where sleep disordered breathing
is associated with left ventricular remodeling18.
However, this is supported by previous studies in pediatric literature
which suggests that pediatric sleep disordered breathing is not
associated with significant cardiovascular strain and the majority of
cardiovascular parameters in children with sleep disordered breathing
are within the normal range at baseline19.
The relationship between age and CAI demonstrated in our study is
intriguing and a key finding for future research in this field. In the
previous study by den Boer, the median age of the 7 children with
pediatric CSA was 2.9 years compared to 30 patients without CSA who had
a median age of 12.3 years5. One of the biggest
challenges of pediatric CSA is to have a consistent definition. While
some authors have defined CSA as CAI+HI >1/hr., many have
used a cut off of 5/hr. While healthy term infants have an estimated
median CAI of 5.5/hr. at 1 month of age20, older
children aged 7.3 (4) years of age with Chiari 1 malformation had median
CAI of 2.4 (0.63 – 8.95)21. In our cross-sectional
study, we found that CAI is inversely correlated to age. This has
previously been described in children with trisomy
2122. Infants are particularly vulnerable to sleep
apnea due to their upper airway structure23,
ventilatory control 24, arousal threshold25, laryngeal chemoreflex26,
REM-predominant sleep state distribution27 and
physiologically exaggerated laryngeal chemoreflexes that actively induce
protective apneas28. Central respiratory pauses from
immaturity of control of breathing are frequent during REM sleep in
infants20.
While there are no studies exploring the relationship between age and
central apnea, there are a few possible physiologic explanations
involving central and carotid body chemoreception sensitivities. Thus
far, chemoreceptor responsiveness has been evaluated in animal and
cellular models29,30. However, the actual implications
of this as a causative reason for the relationship between age and
central apnea is still grounds for speculation and requires
investigation with future study.
The primary limitation of our study is its retrospective nature.
Hypopneas scored in the study could be obstructive or central in nature,
thereby elevating CAHI and overestimating prevalence of CSA. We did not
have data on medications used in heart failure which could also affect
control of breathing. We did not have data on Cheyne Stoke breathing.
Prospective cohort studies correlating objective measurements of
ejection fraction to polysomnographic parameters are needed to gain a
better understanding of the relationship between heart failure and CSA.
Due to the cross-sectional nature of the study, we were unable to prove
causality. Longitudinal studies can provide insight regarding the
relationship between central apnea index and age. Finally, this is the
experience of a single center, and practices may vary between different
centers. This study is a pilot initiative to gain a better understanding
of this patient population.
Ultimately, unlike adults, after adjusting for age, there is no
difference in frequency of central apneic events in children with and
without HF. CAI appears to be a function of age in children, rather than
a function of ejection fraction, with younger patients demonstrating
higher CAIs. Future studies exploring the relationship between CAI and
age can gain a better understanding of determinants of CSA in children.