056 Leucocyte telomere/telomerase dynamics in patients with implantable cardioverter defibrillator; potential biomarker for ventricular arrhythmias

Introduction Implantable cardioverter defibrillators (ICDs) have been shown to reduce mortality in patients with ischaemic cardiomyopathy at a high risk of ventricular arrhythmias (VA), which are the commonest cause of sudden death. However, ICDs are associated with morbidity and mortality Importantly 67% of patients never receive an appropriate shock after ICD implantation under the current indication, suggesting a need for better risk stratification tools. Telomere and telomerase in leucocytes have recently been shown to correlate with biological aging, health status, and also with pathogenesis/prognosis of various cardiovascular diseases. We hypothesise that the leucocyte telomere length and/or telomerase activity correlate with the incidence of VA in ischaemic cardiomyopathy patients. Methods 73 ischaemic cardiomyopathy Caucasian patients with primary prevention ICDs were recruited to this retrospective study between October 2010 and January 2011 at St Bartholomew9s Hospital. Concentrated leucocyte fraction was obtained from venous blood sample of recruited patients and stored at −80°C in an anonymous manner. Genomic DNA was extracted from these and telomere length measured by telomere PCR. Each telomere length was expressed as a ratio (telomere length: single copy gene). Telomerase activity was measured using Roche Telo TAAGGG ELISA kit. All samples were analysed in duplicate and investigators were semi-blinded to arrhythmia history. Continuous data were compared using unpaired t test and categorical data by χ 2 test. Logistic regression analysis was performed to determine if telomere length/telomerase activity independently predict the likelihood of a shock (fatal VA). A probability value of p Results There were no significant differences between the Shock (patients received appropriate shocks from ICD; n=25) and Non-shock (patients received no shock; n=48) groups in terms of baseline demographics as shown in Abstract 056 table 1. There was no significant difference in the age, sex and WCC adjusted telomere length between the Shock and Non-shock groups (p=0.439). Expected age and WCC turnover related telomere attrition (p=0.031 and 0.031) was observed. In contrast, telomerase activity was significantly higher in the Shock group thank in the Non-shock group (0.5682 vs 0.2105) and co-related to the incidence of shock (p=0.01). This did not appear to be related to an acute response associated with VA. Conclusion This is the first study to characterise the telomere dynamics of patients at high risk of sudden cardiac death and co-relate this with the incidence of VA. Leucocyte telomerase activity independently predicted the likelihood of shock in ischaemic cardiomyopathy patients with primary prevention ICDs. Thus leucocyte telomerase activity may be a potential biomarker for prediction of fatal arrhythmia and guide ICD prescription. To validate these results, a prospective study is now ongoing.