Characteristics of cardiovascular dysfunction and pulminory hypertension in patients with sickle cell disease
Background Sickle cell disease (SCD) is a hereditary hemoglobinopathy that causes chronic complications due to repetitive vaso-occlusive events and hemolysis, and can lead to multiorgan failure and shortened life expectancy. Among a spectrum of cardiovascular manifestations in these patients, pulmonary hypertension (PHT) has been stated to pose the highest concern. The exact prevalence of PHT in SCD is controversial; clinical studies using echocardiography have suggested PHT to be highly prevalent and a major determinant of outcome. The contribution of cardiac and endothelial dysfunction to SCD also remains poorly understood. Aims (1) To characterise cardiac function in SCD patients using new 3-dimensional echocardiographic imaging techniques. (2) To determine the prevalence of PHT in SCD patients by using advanced echocardiographic methods and establish mechanisms involved in the development of PHT. (3) To assess whether SCD patients have endothelial dysfunction independent of other vascular risk factors. Methods Detailed 2D, 3D and Doppler echocardiography studies were performed in 122 consecutive unselected SCD patients and 30 healthy age- gender- and ethnicity-matched controls to assess cardiac function and look for PHT. A sub19 group of patients underwent invasive assessment of pulmonary vascular resistance (PVR) by right heart catheterisation. CT lung scan and lung function tests were also performed in patients suspected to have PHT. Vascular endothelial function was assessed by flow-mediated forearm vasodilatation in twenty stable adolescent SCD patients without other risk factors and fifteen healthy age-matched controls. Results Results indicate that patients with SCD have significantly enlarged cardiac dimensions associated with elevated cardiac index (CI) that correlated with the degree of anaemia. Cardiomegaly in SCD patients was not associated with significant contractile dysfunction as assessed by regional myocardial deformation. A high proportion (>30%) of SCD patients had a tricuspid regurgitation jet velocity ! 2.5m/s but non-invasive estimation of PVR revealed that only a minor proportion (<5%) had elevated values. These findings were confirmed by right heart catheterisation. The raised tricuspid regurgitant velocities in SCD patients may be driven more by elevated CI than by elevated PVR. Finally, it was found that young patients with SCD had evidence of subclinical vascular endothelial dysfunction. Taken together, these results provide new information about the prevalence and underlying mechanisms of cardiovascular dysfunction in patients with SCD.
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