Abstract
BackgroundSickle 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.
| Date of Award | 1 Mar 2013 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Ajay Shah (Supervisor) & Narbeh Melikian (Supervisor) |