title: Elevated tricuspid regurgitation velocity and decline in exercise capacity over 22 months of follow up in children and adolescents with sickle cell anemia.
abstract: BACKGROUND
  While in adults with sickle cell disease an elevation of tricuspid regurgitation velocity is associated with increased mortality, the importance of this finding in children has not been established. The role of intravascular hemolysis in the development of this complication is controversial.
  
  
  METHODS
  We conducted a prospective, longitudinal, multi-center study of 160 individuals aged 3-20 years with hemoglobin SS, performing baseline and follow-up determinations of clinical markers, six-minute walk distance less than tricuspid regurgitation velocity and E/Etdi ratio by echocardiography.
  
  
  RESULTS
  At baseline, 14.1% had tricuspid regurgitation velocity of 2.60 m/sec or over, which suggests elevated systolic pulmonary artery pressure, and 7.7% had increased E/Etdi, which suggests elevated left ventricular filling pressure. Over a median of 22 months, baseline elevation in tricuspid regurgitation velocity was associated with an estimated 4.4-fold increase in the odds of a 10% or more decline in age-standardized six-minute-walk distance (P = 0.015). During this interval, baseline values above the median for a hemolytic component derived from four markers of hemolysis were associated with a 9.0-fold increase in the odds of the new onset of elevated tricuspid regurgitation velocity (P = 0.008) and baseline E/Etdi elevation was associated with an estimated 6.1-fold increase in the odds (P = 0.039). In pathway analysis, higher baseline hemolytic component and E/Etdi predicted elevated tricuspid regurgitation velocity at both baseline and follow up, and these elevations in turn predicted decline in six-minute-walk distance.
  
  
  CONCLUSIONS
  Further studies should define the long-term risks of elevated tricuspid regurgitation velocity in childhood and identify potential interventions to prevent increased pulmonary artery pressure and preserve function.
authors.affiliation: Center for Sickle Cell Disease, Howard University, Washington, DC 20060, USA. vgordeuk@howard.edu
authors.forename: Victor R
authors.initials: VR
authors.lastname: Gordeuk
authors.forename: Caterina P
authors.initials: CP
authors.lastname: Minniti
authors.forename: Mehdi
authors.initials: M
authors.lastname: Nouraie
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Campbell
authors.forename: Sohail R
authors.initials: SR
authors.lastname: Rana
authors.forename: Lori
authors.initials: L
authors.lastname: Luchtman-Jones
authors.forename: Craig
authors.initials: C
authors.lastname: Sable
authors.forename: Niti
authors.initials: N
authors.lastname: Dham
authors.forename: Gregory
authors.initials: G
authors.lastname: Ensing
authors.forename: Josef T
authors.initials: JT
authors.lastname: Prchal
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Kato
authors.forename: Mark T
authors.initials: MT
authors.lastname: Gladwin
authors.forename: Oswaldo L
authors.initials: OL
authors.lastname: Castro
mesh_terms: D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000150:complications* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D004452:Echocardiography; D015444:Exercise; D005260:Female; D005500:Follow-Up Studies; D006461:Hemolysis; D006801:Humans; D008297:Male; D008944:Mitral Valve Insufficiency; D011446:Prospective Studies; D014262:Tricuspid Valve Insufficiency / Q000209:etiology* / Q000503:physiopathology; D055815:Young Adult