Abstract T P369: Increased Prevalence of Potential Right-to-Left Shunting in Children with Sickle Cell Anemia and Stroke

Abstract

Children with sickle cell anemia (SCA; HbSS and HgbSβ 0 thalassemia) suffer stroke at a rate 220x higher than other children, but are typically less extensively investigated for modifiable risk factors. In patients without SCA, “paradoxical embolization” via intracardiac or intrapulmonary "right-to-left" shunting is a recognized stroke risk factor. Hypercoagulable states and increased right heart pressures predispose to paradoxical embolization and both occur in SCA. We hypothesized that children with SCA and overt stroke have an increased prevalence of potential right-to-left shunting compared to controls. We performed contrasted transthoracic echocardiograms (conventional 2D, color Doppler, and 4 contrast injections with agitated saline, including 2 during Valsalva) on children (ages 2-19y) with SCA and history of overt stroke, and a control group of children with neither SCA nor stroke, at 14 institutions in the US and UK. Potential right-to-left shunting was defined as any potential shunt detected by any method, including “late bubbles” (contrast appearing in the left heart >5 cardiac cycles following injection). Echocardiograms were reviewed locally and centrally, with adjudication of conflicts. We enrolled 153 children with SCA and stroke and 129 controls. There were no significant differences in age or gender between the groups. The prevalence of potential right-to-left shunting was significantly higher in the SCA and stroke group (43.1% vs. 20.0% in controls (p<0.001). There was no significant difference in intracardiac shunting (22.9% vs. 16.2%, p=0.157) but there was a higher proportion with intrapulmonary shunting (“late bubbles” only) in the SCA and stroke group (27.5% vs. 5.5% in controls, p<0.001). Our findings suggest that intracardiac and intrapulmonary shunting could be an independent, potentially modifiable risk factor for stroke or stroke recurrence in children with SCA. Additional therapeutic interventions in patients at risk of stroke or stroke recurrence via paradoxical embolization, including antiplatelet agents or shunt closure, should be evaluated in children with SCA.