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.

Design and 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.

Figures

Figure 1.

Correlation of baseline and follow-up measurements: (A) hemoglobin concentration, (B) hemolytic component, (C) hemoglobin oxygen saturation, (D) tricuspid regurgitation velocity, e) LVIDD z-score, (F) mitral valve E/Etdi, (G) six-minute walk distance.

Figure 2.

Six-minute walk distance at follow up according to baseline tricuspid regurgitation velocity. (A) Mean (SE) distance. (B) Ten percent or more decline in age-standardized six-minute walk distance.

Figure 3.

New development of tricuspid regurgitation velocity 2.60 m/sec or over during follow up according to (A) baseline hemolytic component and (B) mitral valve E/Etdi ratio.

Figure 4.

Pathway analysis of elevated tricuspid regurgitation velocity (TRV) and decline of age-standardized six-minute walk distance. Standardized betas are indicated in the model. χ2= 8.6 (P=0.6). Root Mean Square Error of Approximation of model = 0.0 (90% CI = 0.0–0.08). Each beta represents a positive association with a significance level of less than 0.021. According to this analysis baseline elevations of hemolytic component and E/Etdi were directly related to both baseline and follow up elevations of tricuspid regurgitation velocity. In tandem, baseline elevation of tricuspid regurgitation velocity and duration of follow up were both associated with follow-up elevation in the velocity. In turn, both baseline and follow-up tricuspid regurgitation velocity were directly associated with decline in six-minute walk distance of 10% or more.