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.
abstract: 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.
  
  
  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 U.S. and U.K. 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.
authors: Cardiovascular and Pulmonary Medicine Branch, National Heart, Lung, and Blood Institute, Bethesda, MD, USA.
authors: Vandana
authors: V
authors: Sachdev
authors: Gregory J
authors: GJ
authors: Kato
authors: J Simon R
authors: JS
authors: Gibbs
authors: Robyn J
authors: RJ
authors: Barst
authors: Roberto F
authors: RF
authors: Machado
authors: Mehdi
authors: M
authors: Nouraie
authors: Kathryn L
authors: KL
authors: Hassell
authors: Jane A
authors: JA
authors: Little
authors: Dean E
authors: DE
authors: Schraufnagel
authors: Lakshmanan
authors: L
authors: Krishnamurti
authors: Enrico M
authors: EM
authors: Novelli
authors: Reda E
authors: RE
authors: Girgis
authors: Claudia R
authors: CR
authors: Morris
authors: Erika Berman
authors: EB
authors: Rosenzweig
authors: David B
authors: DB
authors: Badesch
authors: Sophie
authors: S
authors: Lanzkron
authors: Oswaldo L
authors: OL
authors: Castro
authors: James G
authors: JG
authors: Taylor
authors: Hwaida
authors: H
authors: Hannoush
authors: Jonathan C
authors: JC
authors: Goldsmith
authors: Mark T
authors: MT
authors: Gladwin
authors: Victor R
authors: VR
authors: Gordeuk
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000755:Anemia, Sickle Cell / Q000235:genetics / Q000401:mortality / Q000503:physiopathology*; D002648:Child; D004452:Echocardiography; D005080:Exercise Test / Q000379:methods; D017079:Exercise Tolerance; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D006720:Homozygote; D006801:Humans; D006976:Hypertension, Pulmonary / Q000000981:diagnostic imaging* / Q000401:mortality / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011651:Pulmonary Artery / Q000000981:diagnostic imaging; D014262:Tricuspid Valve Insufficiency / Q000000981:diagnostic imaging / Q000401:mortality / Q000503:physiopathology; D006113:United Kingdom; D014481:United States; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging* / Q000401:mortality / Q000503:physiopathology; D055815:Young Adult