Prospective Evaluation of the Prevalence of Elevated Tricuspid Regurgitant Jet Velocity and Associated Clinical and Echocardiographic Factors in Children and Adolescents with Sickle Cell Disease.

Abstract

Background: Echocardiography (ECHO)-determined tricuspid regurgitation jet velocity (TRV) ≥2.5 m/s occurs in about 30% of adults with sickle cell disease(SCD)and is associated with increased mortality. The frequency and significance of high TRV in children is not known. We determined the prevalence and risk factors of elevated estimated systolic pulmonary artery pressures in 228 patients with SCD and 39 controls.Methods: Patients with SCD (Hb SS, SC, SB thalassemia or other major sickling phenotypes) aged 3 to 20 years were evaluated clinically and with ECHO and six minute walk tests at their steady state. Healthy, non-SCD controls, matched for ethnicity, sex and age, were also evaluated.Results: A comparison of patients and controls is summarized in Table 1. 184 patients (81%) had hemoglobin SS phenotype and 28 (12%) had hemoglobin SC. TRV was measurable in 214 (94%) of the patients and 34 (87%) of the controls. In a multivariate logistic regression model, each 10 mm Hg increase in systolic blood pressure was associated with an estimated 2.0-fold increase in the odds of TRV≥2.5 m/sec (P = 0.002) and a 10-fold increase in LDH with a 25-fold increase in the odds (P = 0.015).Conclusion: This study of children with SCD who have limited iron overload and limited renal dysfunction compared with the aging SCD population provides a unique window into the early pathogenesis of PH in SCD. TRV and LVMI are significantly higher in children and adolescents with SCD at steady state than age-matched control participants. Among children with SCD, TRV elevation is independently associated with systolic BP and LDH concentration. In this analysis we find a strong association with hemolysis and systemic hypertension and surprisingly no associations with vaso-occlusive events or biomarkers (VOC, ACS, HU use, WBC and platelet counts).Table IComparison of SCD and control subjects. Results in mean (SD) unless otherwise stated.SCD(n=228)Control (n=39)pAge in years12 (5)12 (5)0.7Female (%)48%46%0.8Systolic BP (mm Hg)112 (11)116 (15)0.1Diastolic BP (mm Hg)64 (9)68 (10)0.040Six minute walk in meters454 (76)498 (84)0.006TRV in m/sec2.3 (0.3)2.1 (0.3)0.003TRV 2.5 m/sec (%)21%3%0.012LV intern. diastolic diam Z-score1.2(1.4)−0.3(1.2)<0.001LV mass index88 (25)59 (13)<0.001Table IIComparison of SCD patients according to TRV category. Results in mean (SD) unless otherwise stated.VariablesTRV <2.5 (n= 169)TRV ≥2.5 (n=45)pHistory of acute chest syndrome (%)20%40%0.034Hydroxyurea therapy42%44%0.8Hemoglobin in g/dl9.3 (1.8)8.9 (1.7)0.071LDH in U/L393 (163)474 (170)0.009Total Bilirubin in mg/dL2.7 (1.9)3.8 (2.2)0.004