Impact of iron overloding on left ventricular torsion in patients with beta-thalassaemia major

Professor Cheung, Yiu Fai   (Principal Investigator (PI))

Professor Chan Godfrey Chi Fung   (Co-Investigator)

24

2006-09-01

60000

Impact of iron overloding on left ventricular torsion in patients with beta-thalassaemia major

iron overload, left ventricle, thalassaemia

Paediatrics

200607176083

Small Project Funding

2006

Completed

While cardiac dysfunction secondary to iron overload in patients with beta-thalassaemia major is well documented, the left ventricular (LV) function usually remains relatively normal as assessed by conventional echocardiograhic imaging until late in the cardiomyopathic process. These echocardiographic indices are derived primarily from the short- and long-axis function of the left ventricle. The relative insensitivity of these conventional, load-dependent indices of systolic and diastolic LV function is in part related to the fact that beta-thalassaemia major represents a high-output anaemic state, being generated by the volume-loaded ventricles to maintain a high cardiac output in the presence of a low systemic vascular resistance. Recent research in cardiac mechanics is moving from short- and long-axis LV function to three-dimensional ventricular deformation, notably LV torsional mechanics. The torsional deformation of the left ventricle is characterized by systolic twisting and diastolic untwisting about its long axis as a result of the opposite rotation of the cardiac apex and base. Left ventricular torsion plays an important role with respect to LV ejection and filling. More important, LV torsion has been shown to relate closely to alterations of sarcomeric proteins in experimental cardiomyopathy models. Ultrastructural alteration of the extracellular matrix proteins may result in subtle changes in myocardial function that are not evident with the conventional global ventricular function measurements. Hence, the effects of free iron increase within the cardimyocytes, which causes oxidative membrane damage and alterations in gene expression, may be reflected by changes in LV twisting and untwisting before the changes are apparent in indices of global LV function. We therefore hypothesized that iron-overloading in patients with beta-thalassaemia major has a negative impact on LV torsional mechanics both at rest and during exercise stress. The proposed study is to test the hypothesis by examining the LV torsion and torsional velocity by speckle tracking echocardiography in patients with beta-thalassaemia major at rest and during exercise stress and comparing the LV torsional mechanics to those of age and sex-matched controls. This proposed study would address the following issues: i) the impact of iron overloading on the resting and exercise-stressed LV torsional mechanics in patients with beta-thalassaemia major, ii) the relation between LV torsional indices and myocardial iron load, iii) the relation between indices of LV torsion and conventional and tissue Doppler indices of LV systolic and diastolic function, and iv) the impact of systemic arterial stiffening, demonstrated to occur in patients with beta-thalassaemia major previously by our group, on LV torsion.