Abstract
Background: Antithrombotic therapy (ATT) is currently recommended for stroke prevention in pediatric cardioembolic arterial ischemic stroke (CE-AIS) where the risk of recurrence is high. Methods: We conducted a retrospective study of a prospectively enrolled cohort of neonates and children with radiologically-confirmed cardioembolic arterial ischemic stroke (CE-AIS) from January 2003 - December 2017. We evaluated the clinical and radiographic predictors of hemorrhagic transformation (HT) and stroke recurrence to assess the safety and efficacy of ATT. Results: Eighty-two children met inclusion criteria [53.7% males and 28% neonates; median age 0.43 (IQR: 0.08 - 4.23) years]. Stroke recurred in 11 children at a median of 32 days (IQR: 5.5 - 93) from the index event. Most recurrent infarcts were silent (n=6; 54.5%) and found on follow-up neuroimaging with an average follow-up interval of 4.1 ±3 .5 years. Procedure-related recurrence took place in 1 (9.1%) child. Ten (90.9%) children were receiving antithrombotic therapy at the time of recurrence: 8 (72.7%) were on anticoagulant therapy (ACT) and 2 (18.2%) were on a combination of antiplatelet (ATP) and ACT. HT occurred in 20 of 82 children (24.4%), all of whom were receiving ACT, 5 (6.1%) of whom were symptomatic. Four (4.9%) had systemic hemorrhage. There was no difference in the frequency of stroke recurrence between those with and without HT [3 (15.0%) vs. 8 (12.9%); p=1.00]. Children with univentricular physiology were less likely to have HT [15% vs. 43.5%; p=0.03] and had higher rates of recurrent stroke, prior to definitive cardiac repair, despite receiving ATT. Stroke recurrence was highest in those with cyanotic congenital heart disease (CHD) pre-surgery (3/11), cyanotic CHD post-palliative surgery with residual right-to-left-shunt (3/11) and in those with cardiomyopathy (4/11). HT was not associated with ATP vs. ACT use nor combination therapy. Conclusion: ATT appears to be relatively safe in children with CE-AIS. However, ATT warrants further optimization to prevent stroke recurrence, particularly in those with single ventricle physiology and reduced left ventricular function.
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