TY - JOUR
T1 - Increased prevalence of potential right-to-left shunting in children with sickle cell anaemia and stroke
AU - the PFAST Investigators
AU - Dowling, Michael M.
AU - Quinn, Charles T.
AU - Ramaciotti, Claudio
AU - Kanter, Julie
AU - Osunkwo, Ifeyinwa
AU - Inusa, Baba
AU - Iyer, Rathi
AU - Kwiatkowski, Janet L.
AU - Johnson, Clarissa
AU - Rhodes, Melissa
AU - Owen, William
AU - Strouse, John J.
AU - Panepinto, Julie A.
AU - Neumayr, Lynne
AU - Sarnaik, Sharada
AU - Plumb, Patricia A.
AU - Dlamini, Nomazulu
AU - Kirkham, Fenella
AU - Hynan, Linda S.
AU - Benton, Melody S.
AU - Cherry, Korin
AU - Ndoro, Sharon
AU - Pushparajah, Kuberan
AU - Majumder, Suvankar
AU - Thomas, Glenda O.
AU - Ware, Hannah
AU - Stanley, Helen
AU - Whaley-Deshotels, Alane
AU - Burns, Patricia
AU - Taylor, Cynthia
AU - Muntz, Devin
AU - Sarnaik, Ingrid
AU - Murphy, Mary
AU - Spranger, Theresa
AU - Wigginton, Sabrina
AU - Coggsdale, Lorrie
AU - Shova, Amy
AU - Farley, Rebecca
AU - Patterson, La Sandra
N1 - Funding Information:
This study was funded by an ‘Innovations in Clinical Research Award’ and a supplemental research grant from the Doris Duke Charitable Foundation (MMD) with additional support from the Children’s Clinical Research Advisory Committee and the Women’s Auxiliary to Children’s Medical Center. Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1TR000003. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We would like to thank George Buchanan, MD, Zora Rogers, MD, Milton Packer, MD and Marie Virginia Moretti for their contributions to this project.
Funding Information:
This study was funded by an ‘Innovations in Clinical Research Award’ and a supplemental research grant from the Doris Duke Charitable Foundation (MMD) with additional support from the Children's Clinical Research Advisory Committee and the Women's Auxiliary to Children's Medical Center. Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1TR000003. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We would like to thank George Buchanan, MD, Zora Rogers, MD, Milton Packer, MD and Marie Virginia Moretti for their contributions to this project.
Publisher Copyright:
© 2016 John Wiley & Sons Ltd
PY - 2017/1/1
Y1 - 2017/1/1
N2 - ‘Paradoxical’ embolization via intracardiac or intrapulmonary right-to-left shunts (RLS) is an established cause of stroke. Hypercoagulable states and increased right heart pressure, which both occur in sickle cell anaemia (SCA), predispose to paradoxical embolization. We hypothesized that children with SCA and overt stroke (SCA + stroke) have an increased prevalence of potential RLS. We performed contrasted transthoracic echocardiograms on 147 children (aged 2–19 years) with SCA + stroke) mean age 12·7 ± 4·8 years, 54·4% male) and a control group without SCA or stroke (n = 123; mean age 12·1 ± 4·9 years, 53·3% male). RLS was defined as any potential RLS detected by any method, including intrapulmonary shunting. Echocardiograms were masked and adjudicated centrally. The prevalence of potential RLS was significantly higher in the SCA+stroke group than controls (45·6% vs. 23·6%, P < 0·001). The odds ratio for potential RLS in the SCA + stroke group was 2·7 (95% confidence interval: 1·6–4·6) vs controls. In post hoc analyses, the SCA + stroke group had a higher prevalence of intrapulmonary (23·8% vs. 5·7%, P < 0·001) but not intracardiac shunting (21·8% vs. 18·7%, P = 0·533). SCA patients with potential RLS were more likely to report headache at stroke onset than those without. Intrapulmonary and intracardiac shunting may be an overlooked, independent and potentially modifiable risk factor for stroke in SCA.
AB - ‘Paradoxical’ embolization via intracardiac or intrapulmonary right-to-left shunts (RLS) is an established cause of stroke. Hypercoagulable states and increased right heart pressure, which both occur in sickle cell anaemia (SCA), predispose to paradoxical embolization. We hypothesized that children with SCA and overt stroke (SCA + stroke) have an increased prevalence of potential RLS. We performed contrasted transthoracic echocardiograms on 147 children (aged 2–19 years) with SCA + stroke) mean age 12·7 ± 4·8 years, 54·4% male) and a control group without SCA or stroke (n = 123; mean age 12·1 ± 4·9 years, 53·3% male). RLS was defined as any potential RLS detected by any method, including intrapulmonary shunting. Echocardiograms were masked and adjudicated centrally. The prevalence of potential RLS was significantly higher in the SCA+stroke group than controls (45·6% vs. 23·6%, P < 0·001). The odds ratio for potential RLS in the SCA + stroke group was 2·7 (95% confidence interval: 1·6–4·6) vs controls. In post hoc analyses, the SCA + stroke group had a higher prevalence of intrapulmonary (23·8% vs. 5·7%, P < 0·001) but not intracardiac shunting (21·8% vs. 18·7%, P = 0·533). SCA patients with potential RLS were more likely to report headache at stroke onset than those without. Intrapulmonary and intracardiac shunting may be an overlooked, independent and potentially modifiable risk factor for stroke in SCA.
KW - cardiology
KW - clinical research
KW - sickle cell anaemia
KW - stroke
UR - http://www.scopus.com/inward/record.url?scp=84995483170&partnerID=8YFLogxK
U2 - 10.1111/bjh.14391
DO - 10.1111/bjh.14391
M3 - Article
C2 - 27766637
AN - SCOPUS:84995483170
VL - 176
SP - 300
EP - 308
JO - British Journal of Haematology
JF - British Journal of Haematology
SN - 0007-1048
IS - 2
ER -