Characteristics of cardiovascular dysfunction and pulminory hypertension in patients with sickle cell disease

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

Name dc:type.qualificationname

Doctor of Philosophy

Level dc:type.qualificationlevel

Doctoral Thesis

Grantor dc:publisher.institution

King's College London

Year dc:date.issued

2013

Author dc:creator

• Mushemi-Blake, Sitali

Advisors dc:contributor.advisor

• Shah, Ajay Manmohan
• Melikian, Narbeh

Language dc:language

eng

Identifier

oai:kclpure.kcl.ac.uk:studenttheses/37bb71db-b314-465d-9961-d05eaa676e2d

OAI identifier oai:identifier

oai:kclpure.kcl.ac.uk:studenttheses/37bb71db-b314-465d-9961-d05eaa676e2d