{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:19:24Z","timestamp":1791299964391,"version":"4.1.0"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"13","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2011,9,27]]},"abstract":"<jats:sec>\n                    <jats:title>Background\u2014<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results\u2014<\/jats:title>\n                    <jats:p>\n                      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\u2013Treatment 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 &lt;3.0 m\/s (mean\u00b1SD, 2.8\u00b10.1) in 26% of the subjects and \u22653.0 m\/s (mean\u00b1SD, 3.4\u00b10.4) in 11%. The LV lateral E\/e\u2032 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 \u22652.7 m\/s. Increased hemolysis (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.0001), LV lateral E\/e\u2032 ratio (\n                      <jats:italic>P<\/jats:italic>\n                      =0.0001), blood urea nitrogen (\n                      <jats:italic>P<\/jats:italic>\n                      =0.0002), and erythropoietin (\n                      <jats:italic>P<\/jats:italic>\n                      =0.002) were independently associated with an increased tricuspid regurgitation velocity. Furthermore, female sex (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.0001), older age (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.0001), LV lateral E\/e\u2032 ratio (\n                      <jats:italic>P<\/jats:italic>\n                      =0.014), and tricuspid regurgitation velocity (\n                      <jats:italic>P<\/jats:italic>\n                      =0.019) were independent predictors of a shorter 6-minute walk distance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\u2014<\/jats:title>\n                    <jats:p>Echocardiography-estimated elevated pulmonary artery systolic pressure and LV lateral E\/e\u2032 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration\u2014<\/jats:title>\n                    <jats:p>\n                      URL:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.clinicaltrials.gov\">http:\/\/www.clinicaltrials.gov.<\/jats:ext-link>\n                      Unique identifier: NCT00492531.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.111.032920","type":"journal-article","created":{"date-parts":[[2011,9,7]],"date-time":"2011-09-07T00:17:56Z","timestamp":1315354676000},"page":"1452-1460","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":134,"title":["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"],"prefix":"10.1161","volume":"124","author":[{"given":"Vandana","family":"Sachdev","sequence":"first","affiliation":[{"name":"From the Cardiovascular and Pulmonary Medicine Branch, National Heart, Lung, and Blood Institute, Bethesda, MD (V.S., G.J.K., J.G.T., H.H.); National Heart &amp; Lung Institute, Imperial College London, London, UK (J.S.R.G.); Columbia University, New York, NY (R.J.B., E.B.R.); University of Illinois, Chicago (R.F.M., D.E.S.); Howard University, Washington, DC (M.N., O.L.C., V.R.G.); University of Colorado HSC, Denver (K.L.H., D.B.B.); Albert Einstein College of Medicine, Bronx, NY (J.A.L.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory J.","family":"Kato","sequence":"additional","affiliation":[{"name":"From the Cardiovascular and Pulmonary Medicine Branch, National Heart, Lung, and Blood Institute, Bethesda, MD (V.S., G.J.K., J.G.T., H.H.); National Heart &amp; Lung Institute, Imperial College London, London, UK (J.S.R.G.); Columbia University, New York, NY (R.J.B., E.B.R.); University of Illinois, Chicago (R.F.M., D.E.S.); Howard University, Washington, DC (M.N., O.L.C., V.R.G.); University of Colorado HSC, Denver (K.L.H., D.B.B.); Albert Einstein College of Medicine, Bronx, NY (J.A.L.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Simon R.","family":"Gibbs","sequence":"additional","affiliation":[{"name":"From the Cardiovascular and Pulmonary Medicine Branch, National Heart, Lung, and Blood Institute, Bethesda, MD (V.S., G.J.K., J.G.T., H.H.); National Heart &amp; Lung Institute, Imperial College London, London, UK (J.S.R.G.); Columbia University, New York, NY (R.J.B., E.B.R.); University of Illinois, Chicago (R.F.M., D.E.S.); Howard University, Washington, DC (M.N., O.L.C., V.R.G.); University of Colorado HSC, Denver (K.L.H., D.B.B.); Albert Einstein College of Medicine, Bronx, NY (J.A.L.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robyn J.","family":"Barst","sequence":"additional","affiliation":[{"name":"From the Cardiovascular and Pulmonary Medicine Branch, National Heart, Lung, and Blood Institute, Bethesda, MD (V.S., G.J.K., J.G.T., H.H.); National Heart &amp; Lung Institute, Imperial College London, London, UK (J.S.R.G.); Columbia University, New York, NY (R.J.B., E.B.R.); University of Illinois, Chicago (R.F.M., D.E.S.); Howard University, Washington, DC (M.N., O.L.C., V.R.G.); University of Colorado HSC, Denver (K.L.H., D.B.B.); Albert Einstein College of Medicine, Bronx, NY (J.A.L.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto F.","family":"Machado","sequence":"additional","affiliation":[{"name":"From the Cardiovascular and Pulmonary Medicine Branch, National Heart, Lung, and Blood Institute, Bethesda, MD (V.S., G.J.K., J.G.T., H.H.); National Heart &amp; Lung Institute, Imperial College London, London, UK (J.S.R.G.); Columbia University, New York, NY (R.J.B., E.B.R.); University of Illinois, Chicago (R.F.M., D.E.S.); Howard University, Washington, DC (M.N., O.L.C., V.R.G.); University of Colorado HSC, Denver (K.L.H., D.B.B.); Albert Einstein College of Medicine, Bronx, NY (J.A.L.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Nouraie","sequence":"additional","affiliation":[{"name":"From the Cardiovascular and Pulmonary Medicine Branch, National Heart, Lung, and Blood Institute, Bethesda, MD (V.S., G.J.K., J.G.T., H.H.); National Heart &amp; Lung Institute, Imperial College London, London, UK (J.S.R.G.); Columbia University, New York, NY (R.J.B., E.B.R.); University of Illinois, Chicago (R.F.M., D.E.S.); Howard University, Washington, DC (M.N., O.L.C., V.R.G.); University of Colorado HSC, Denver (K.L.H., D.B.B.); Albert Einstein College of Medicine, Bronx, NY (J.A.L.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn L.","family":"Hassell","sequence":"additional","affiliation":[{"name":"From the Cardiovascular and Pulmonary Medicine Branch, National Heart, Lung, and Blood Institute, Bethesda, MD (V.S., G.J.K., J.G.T., H.H.); National Heart &amp; Lung Institute, Imperial College London, London, UK (J.S.R.G.); Columbia University, New York, NY (R.J.B., E.B.R.); University of Illinois, Chicago (R.F.M., D.E.S.); Howard University, Washington, DC (M.N., O.L.C., V.R.G.); University of Colorado HSC, Denver (K.L.H., D.B.B.); Albert Einstein College of Medicine, Bronx, NY (J.A.L.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane A.","family":"Little","sequence":"additional","affiliation":[{"name":"From the Cardiovascular and Pulmonary Medicine Branch, National Heart, Lung, and Blood Institute, Bethesda, MD (V.S., G.J.K., J.G.T., H.H.); National Heart &amp; Lung Institute, Imperial College London, London, UK (J.S.R.G.); Columbia University, New York, NY (R.J.B., E.B.R.); University of Illinois, Chicago (R.F.M., D.E.S.); Howard University, Washington, DC (M.N., O.L.C., V.R.G.); University of Colorado HSC, Denver (K.L.H., D.B.B.); Albert Einstein College of Medicine, Bronx, NY 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College London, London, UK (J.S.R.G.); Columbia University, New York, NY (R.J.B., E.B.R.); University of Illinois, Chicago (R.F.M., D.E.S.); Howard University, Washington, DC (M.N., O.L.C., V.R.G.); University of Colorado HSC, Denver (K.L.H., D.B.B.); Albert Einstein College of Medicine, Bronx, NY (J.A.L.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico M.","family":"Novelli","sequence":"additional","affiliation":[{"name":"From the Cardiovascular and Pulmonary Medicine Branch, National Heart, Lung, and Blood Institute, Bethesda, MD (V.S., G.J.K., J.G.T., H.H.); National Heart &amp; Lung Institute, Imperial College London, London, UK (J.S.R.G.); Columbia University, New York, NY (R.J.B., E.B.R.); University of Illinois, Chicago (R.F.M., D.E.S.); Howard University, Washington, DC (M.N., O.L.C., V.R.G.); University of Colorado HSC, Denver (K.L.H., D.B.B.); Albert Einstein College of Medicine, Bronx, NY 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London, UK (J.S.R.G.); Columbia University, New York, NY (R.J.B., E.B.R.); University of Illinois, Chicago (R.F.M., D.E.S.); Howard University, Washington, DC (M.N., O.L.C., V.R.G.); University of Colorado HSC, Denver (K.L.H., D.B.B.); Albert Einstein College of Medicine, Bronx, NY (J.A.L.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika Berman","family":"Rosenzweig","sequence":"additional","affiliation":[{"name":"From the Cardiovascular and Pulmonary Medicine Branch, National Heart, Lung, and Blood Institute, Bethesda, MD (V.S., G.J.K., J.G.T., H.H.); National Heart &amp; Lung Institute, Imperial College London, London, UK (J.S.R.G.); Columbia University, New York, NY (R.J.B., E.B.R.); University of Illinois, Chicago (R.F.M., D.E.S.); Howard University, Washington, DC (M.N., O.L.C., V.R.G.); University of Colorado HSC, Denver (K.L.H., D.B.B.); Albert Einstein College of Medicine, Bronx, NY 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London, UK (J.S.R.G.); Columbia University, New York, NY (R.J.B., E.B.R.); University of Illinois, Chicago (R.F.M., D.E.S.); Howard University, Washington, DC (M.N., O.L.C., V.R.G.); University of Colorado HSC, Denver (K.L.H., D.B.B.); Albert Einstein College of Medicine, Bronx, NY (J.A.L.);..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oswaldo L.","family":"Castro","sequence":"additional","affiliation":[{"name":"From the Cardiovascular and Pulmonary Medicine Branch, National Heart, Lung, and Blood Institute, Bethesda, MD (V.S., G.J.K., J.G.T., H.H.); National Heart &amp; Lung Institute, Imperial College London, London, UK (J.S.R.G.); Columbia University, New York, NY (R.J.B., E.B.R.); University of Illinois, Chicago (R.F.M., D.E.S.); Howard University, Washington, DC (M.N., O.L.C., V.R.G.); University of Colorado HSC, Denver (K.L.H., D.B.B.); Albert Einstein College of Medicine, Bronx, NY 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