Surrogates of Poor Prognostic Signs in Adult Patients with Homozygous Sickle Cell Disease: An Echocardiographic Study

Background: Pulmonary Arterial hypertension (PAH) is a late complication in adult patients with homozygous sickle cell Anaemia (SCA). The early identification of PAH may be of paramount importance.
Aim: This study is aimed at evaluating the usefulness of NT pro BNP in the assessment of diastolic function of RV in adult patients with sickle cell disease. It is also aimed at the assessment of the predictive risk of serum level of NT pro BNP hormone and ferritin with other pulsed and tissue Doppler indices for the development of pulmonary hypertension in patients with SCA. In addition, we measured the usefulness of tissue Doppler velocity of lateral annulus of tricuspid valve in the assessment of diastolic function of RV in adult patients with SCD.
Method: In this cross sectional prospective study, 103 patients with homozygous SCD were studied and compared with age and gender matched healthy control. Every patient had a clinical assessment, pulsed and tissue Doppler evaluation. Blood samples were withdrawn for the level of haemoglobin, ferritin and NT pro BNP hormone. The mean difference between the two groups for echo Doppler and biometric variables were assessed. Multiple regression analysis applied for measuring the odds ratio of different biometric and Doppler variables for risk of PAH in SCD.
Results: The study group consist of 103 patients with SCA, mean age of 28.52±14.11 year, (range 14-42), with 68 male (66.0%) Patients with SCA compared with control had a significantly low diastolic pressure, lower haemoglobin level but high serum level ferritin and pro BNP hormone. Further, there was a significant increment in the left atrium area (LA), higher right ventricle (RV) wall thickness and diameter. The RV tricuspid annular systolic excursion (TAPSE) was high of 1.42±0.21 vs. 1.11±0.23, P<0.05. RV Pulsed Doppler data showed restrictive filling pattern with significant higher E wave velocity, higher early diastolic filling wave (E)/ atria wave velocity (A) ratio and short Deceleration Time (DT). Further, the ratio of upper pulmonary vein for systolic/diastolic Doppler velocity was significantly lower 1.5±0.12 vs.2.4±0.11, p<0.05. The tissue Doppler of lateral annulus of tricuspid valve in SCA patients showed a significantly lower S wave of 6.7±1.7 vs 11.3±1.9, p<0.01, higher pulsed early velocity( E)/ early Tissue velocity (E-) ratio and lower atria wave velocity (A). The incidence of pulmonary hypertension in SCD patients via tricuspid valve velocity defined as ≥2.5 m/s was 28%. There were positive correlation between the serum level of ferritin, NT pro BNP hormone and tricuspid valve velocity of (r= 0.38) and (r=0.43) respectively. The odds ratio for development of PAH was 3.1 for E/E- ratio ≥13, 2.5 for DT of <160msec, 2.2 for Left ventricle mass Index (LVMI)>121 gm/M2, 1.9 for ferritin ≥600μg/l, 1.6cm for left atrial area ≥20cm, 1.3 for pro- BNP ≥150Pmol/L.
Conclusion: Adult patients with SCA have normal Systolic function but increase of LV mass and restrictive diastolic dysfunction. RV has increase wall thickness, systolic and diastolic dysfunction of restrictive pattern. The prevalence of pulmonary hypertension in SCA is 28% with positive correlation between ferritin, pro BNP level and tricuspid valve velocity on echo. The risk of PAH in SCA patients is higher if the patient had on echo DT <160msec, LVMI >121gm/M2, cm, E/E- ratio ≥13 or RV wall thickness >3mm.