Telomere Biology in Ischaemic Cardiomyopathy.

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 3 (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.