|dc.identifier.citation||Sawhney, V. 2015. Telomere Biology in Ischaemic Cardiomyopathy. Queen Mary University of London.||en_US
|dc.description.abstract||Implantable cardioverter defibrillators (ICDs) reduce mortality in patients with
ischaemic cardiomyopathy at high risk of ventricular arrhythmias (VA).
However, the current indication for ICD prescription needs improvement.
Telomere length and telomerase activity in leukocytes have been shown to
correlate with biological aging and pathogenesis of cardiovascular diseases.
Their role in arrhythmias, however, is unknown.
I examined telomere biology in ischaemic cardiomyopathy patients and
established its association with VA. This study stemmed from the primary
hypothesis that telomere shortening at the time of the index event (myocardial
infarction), results in poor myocardial repair process and predisposes patients
to greater arrhythmic tendency. Hence there would be a correlation between
leukocyte telomere length, load-of-short telomeres and telomerase activity with
VA occurrence in these patients. I also investigated the effect of genetic
variation on telomerase activity and VA. From a basic science perspective,
different mechanisms of telomere shortening were studied by using a novel
method for measuring critically short telomeres.
90 ischaemic cardiomyopathy patients with primary prevention ICDs
were recruited. 35 had received appropriate therapy from the ICD for
potentially-fatal VA while the remaining 55 patients had not. No significant
differences in baseline demographic data were seen between the two groups.
There was no significant difference in the age and sex adjusted mean telomere
length analysed by qPCR between the groups (p=0.66). In contrast, the loadof-
short telomeres assessed by Universal-STELA method and telomerase
activity by TRAP assay were both higher in patients who had appropriate ICD
therapy and were significantly associated with incidence of ICD therapy
(p=0.02, p= 0.02). Genetic variation in telomerase activity was observed with a
significant correlation between telomerase and VA in C/C genotype only.
These data collectively suggest that telomere biology is a promising area
of exploration for further research in risk stratification for ICD prescription.||en_US
|dc.description.sponsorship||Barts and the London Charity Project Grant and
supported by the Barts Cardiovascular Biomedical Research Unit.||en_US
|dc.publisher||Queen Mary University of London||en_US
|dc.title||Telomere Biology in Ischaemic Cardiomyopathy.||en_US
|dc.rights.holder||The copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without the prior written consent of the author||