TY - JOUR
T1 - Echocardiographic markers of elevated pulmonary pressure and left ventricular diastolic dysfunction are associated with exercise intolerance in adults and adolescents with homozygous sickle cell anemia in the United States and United Kingdom
AU - Sachdev, Vandana
AU - Kato, Gregory J.
AU - Gibbs, J. Simon R.
AU - Barst, Robyn J.
AU - MacHado, Roberto F.
AU - Nouraie, Mehdi
AU - Hassell, Kathryn L.
AU - Little, Jane A.
AU - Schraufnagel, Dean E.
AU - Krishnamurti, Lakshmanan
AU - Novelli, Enrico M.
AU - Girgis, Reda E.
AU - Morris, Claudia R.
AU - Rosenzweig, Erika Berman
AU - Badesch, David B.
AU - Lanzkron, Sophie
AU - Castro, Oswaldo L.
AU - Taylor, James G.
AU - Hannoush, Hwaida
AU - Goldsmith, Jonathan C.
AU - Gladwin, Mark T.
AU - Gordeuk, Victor R.
PY - 2011/9/27
Y1 - 2011/9/27
N2 - Background-Noninvasively assessed pulmonary pressure elevations and left ventricular (LV) diastolic dysfunction are associated with increased mortality in adults with sickle cell disease, but their relationship to exercise intolerance has not been evaluated prospectively. Methods and Results-Echocardiography, 6-minute walk distance, hemolytic rate, and serum concentrations of ferritin and erythropoietin were evaluated in a cohort of 483 subjects with homozygous hemoglobin S in the US and UK Walk-Treatment of Pulmonary Hypertension and Sickle Cell Disease with Sildenafil Therapy (Walk-PHaSST) study. Tricuspid regurgitation velocity, which reflects systolic pulmonary artery pressure, was 2.7 to <3.0 m/s (mean±SD, 2.8±0.1) in 26% of the subjects and 3.0 m/s (mean±SD, 3.4±0.4) in 11%. The LV lateral E/e′ ratio, which has been shown to reflect LV filling pressure in other conditions but has not been studied in sickle cell disease, was significantly higher in the groups with tricuspid regurgitation velocity 2.7 m/s. Increased hemolysis (P<0.0001), LV lateral E/e′ ratio (P=0.0001), blood urea nitrogen (P=0.0002), and erythropoietin (P=0.002) were independently associated with an increased tricuspid regurgitation velocity. Furthermore, female sex (P<0.0001), older age (P<0.0001), LV lateral E/e′ ratio (P=0.014), and tricuspid regurgitation velocity (P=0.019) were independent predictors of a shorter 6-minute walk distance. Conclusions-Echocardiography-estimated elevated pulmonary artery systolic pressure and LV lateral E/e′ ratio were independently associated with poor exercise capacity in a large cohort of patients with sickle cell anemia. Controlled trials investigating whether strategies to prevent or delay pulmonary hypertension and/or LV diastolic dysfunction will improve exercise capacity and long-term outcomes in sickle cell anemia should be considered. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00492531.
AB - Background-Noninvasively assessed pulmonary pressure elevations and left ventricular (LV) diastolic dysfunction are associated with increased mortality in adults with sickle cell disease, but their relationship to exercise intolerance has not been evaluated prospectively. Methods and Results-Echocardiography, 6-minute walk distance, hemolytic rate, and serum concentrations of ferritin and erythropoietin were evaluated in a cohort of 483 subjects with homozygous hemoglobin S in the US and UK Walk-Treatment of Pulmonary Hypertension and Sickle Cell Disease with Sildenafil Therapy (Walk-PHaSST) study. Tricuspid regurgitation velocity, which reflects systolic pulmonary artery pressure, was 2.7 to <3.0 m/s (mean±SD, 2.8±0.1) in 26% of the subjects and 3.0 m/s (mean±SD, 3.4±0.4) in 11%. The LV lateral E/e′ ratio, which has been shown to reflect LV filling pressure in other conditions but has not been studied in sickle cell disease, was significantly higher in the groups with tricuspid regurgitation velocity 2.7 m/s. Increased hemolysis (P<0.0001), LV lateral E/e′ ratio (P=0.0001), blood urea nitrogen (P=0.0002), and erythropoietin (P=0.002) were independently associated with an increased tricuspid regurgitation velocity. Furthermore, female sex (P<0.0001), older age (P<0.0001), LV lateral E/e′ ratio (P=0.014), and tricuspid regurgitation velocity (P=0.019) were independent predictors of a shorter 6-minute walk distance. Conclusions-Echocardiography-estimated elevated pulmonary artery systolic pressure and LV lateral E/e′ ratio were independently associated with poor exercise capacity in a large cohort of patients with sickle cell anemia. Controlled trials investigating whether strategies to prevent or delay pulmonary hypertension and/or LV diastolic dysfunction will improve exercise capacity and long-term outcomes in sickle cell anemia should be considered. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00492531.
KW - anemia, sickle cell
KW - diastole
KW - echocardiography
KW - exercise
KW - hypertension, pulmonary
UR - http://www.scopus.com/inward/record.url?scp=80053300657&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80053300657&partnerID=8YFLogxK
U2 - 10.1161/CIRCULATIONAHA.111.032920
DO - 10.1161/CIRCULATIONAHA.111.032920
M3 - Article
C2 - 21900080
AN - SCOPUS:80053300657
SN - 0009-7322
VL - 124
SP - 1452
EP - 1460
JO - Circulation
JF - Circulation
IS - 13
ER -