Prospective echocardiography assessment of pulmonary hypertension and its potential etiologies in children with sickle cell disease

Abstract

Pulmonary hypertension (PH) is associated with adverse outcomes in adults with sickle-cell disease (SCD), but its importance in children is less clear. The aim of this study was to define the incidence and causes of PH in pediatric patients with SCD. Children with SCD (n = 310) and matched controls (n = 54) were prospectively enrolled under basal conditions. Participants underwent echocardiography, pulse oximetry, 6-minute walk tests, and hematologic testing. Echocardiographic measures were compared between patients with SCD and control subjects before and after adjusting for hemoglobin. Correlations of echocardiographic and clinical parameters were determined. Tricuspid regurgitation velocity (TRV) was elevated compared to controls (2.28 vs 2.10 m/s, p <0.0001). Increased TRV was associated with left ventricular diastolic diameter, hemoglobin, and estimated left atrial pressure. TRV remained elevated when controlling for left ventricular diameter and left atrial pressure. Echocardiographically derived pulmonary resistance was not significantly different between patients with SCD and controls, although it was elevated in the SCD subgroup with elevated TRV. When controlling for hemoglobin, TRV was no longer statistically different, but pulmonary insufficiency velocity, septal wall thickness, and estimated pulmonary resistance were statistically higher. TRV, pulmonary insufficiency end-diastolic velocity, and markers of increased cardiac output were correlated with indicators of adverse functional status, including history of acute chest syndrome, stroke, transfusions, and 6-minute walk distance. In conclusion, children with SCD had mildly increased TRV that was correlated with increased cardiac output and left ventricular filling pressures. Hemoglobin-adjusted analysis also suggested a contribution of primary vascular changes.

Figure 1

Distribution of tricuspid regurgitation velocity in control and sickle cell subjects in unadjusted (left) and adjusted for hemoglobin(right) Crosses show mean values. Abbreviations: TRV - tricuspid regurgitation velocity

Figure 2

Distribution of pulmonary vascular resistance in control and sickle cell subjects in unadjusted (left) and adjusted for hemoglobin (right) Crosses show mean values.

Figure 3

Frequency distribution of pulmonary vascular resistance in sickle cell disease grouped by tricuspid regurgitation velocity category. Abbreviation: TRV – tricuspid regurgitation velocity

Figure 4

Correlation between left ventricular end diastolic dimension Z score and tricuspid valve regurgitation velocity in sickle cell disease Abbreviation: LVIDd – left ventricular internal dimension in diastole.

Figure 4

Correlation between mitral inflow E wave/tissue Doppler E wave ratio and tricuspid regurgitation velocity in sickle cell disease Abbreviation: E/Etdi – mitral inflow E wave/tissue Doppler imaging E wave