title: Telomere shortening and telomerase activity in ischaemic cardiomyopathy patients - Potential markers of ventricular arrhythmia.
abstract: BACKGROUND
  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 and telomerase in leucocytes have been shown to associate with biological ageing and pathogenesis of cardiovascular diseases. We hypothesised that leucocyte telomere length, load-of-short telomeres and/or telomerase activity are associated with VA occurrence in ischaemic cardiomyopathy patients.
  
  
  RESULTS
  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 relevant to telomere biology 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=0.88). In contrast, the load-of-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). ROC analyses demonstrated that the sensitivity and specificity of these telomere dynamics in predicting potentially-fatal VA was higher than the current gold-standard - left ventricular ejection fraction (AUC 0.82 versus 0.47).
  
  
  CONCLUSIONS
  The load-of-short telomeres and telomerase activity had a significant association with ICD therapy (for VA) in ischaemic cardiomyopathy patients. These biomarkers should be tested in prospective studies to assess their clinical utility in predicting VA after myocardial infarction and guiding primary prevention ICD prescription.
authors.affiliation: Cardiology Department, St Bartholomew's Hospital, London, United Kingdom; William Harvey Research Institute, Queen Mary University, London, United Kingdom. Electronic address: sawhneyvin@googlemail.com.
authors.forename: V
authors.initials: V
authors.lastname: Sawhney
authors.affiliation: Cardiology Department, St Bartholomew's Hospital, London, United Kingdom.
authors.forename: N G
authors.initials: NG
authors.lastname: Campbell
authors.affiliation: William Harvey Research Institute, Queen Mary University, London, United Kingdom.
authors.forename: S W
authors.initials: SW
authors.lastname: Brouilette
authors.affiliation: William Harvey Research Institute, Queen Mary University, London, United Kingdom.
authors.forename: S R
authors.initials: SR
authors.lastname: Coppen
authors.affiliation: Department of Clinical Genetics, Vejle Hospital, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Harbo
authors.affiliation: Cardiology Department, St Bartholomew's Hospital, London, United Kingdom.
authors.forename: V
authors.initials: V
authors.lastname: Baker
authors.affiliation: William Harvey Research Institute, Queen Mary University, London, United Kingdom.
authors.forename: C
authors.initials: C
authors.lastname: Ikebe
authors.affiliation: William Harvey Research Institute, Queen Mary University, London, United Kingdom.
authors.forename: Y
authors.initials: Y
authors.lastname: Shintani
authors.affiliation: Cardiology Department, St Bartholomew's Hospital, London, United Kingdom.
authors.forename: R J
authors.initials: RJ
authors.lastname: Hunter
authors.affiliation: Cardiology Department, St Bartholomew's Hospital, London, United Kingdom.
authors.forename: M
authors.initials: M
authors.lastname: Dhinoja
authors.affiliation: William Harvey Research Institute, Queen Mary University, London, United Kingdom.
authors.forename: A
authors.initials: A
authors.lastname: Johnston
authors.affiliation: Cardiology Department, St Bartholomew's Hospital, London, United Kingdom.
authors.forename: M J
authors.initials: MJ
authors.lastname: Earley
authors.affiliation: Cardiology Department, St Bartholomew's Hospital, London, United Kingdom.
authors.forename: S
authors.initials: S
authors.lastname: Sporton
authors.affiliation: Department of Clinical Genetics, Vejle Hospital, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Bendix
authors.affiliation: William Harvey Research Institute, Queen Mary University, London, United Kingdom.
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Cardiology Department, St Bartholomew's Hospital, London, United Kingdom; William Harvey Research Institute, Queen Mary University, London, United Kingdom.
authors.forename: R J
authors.initials: RJ
authors.lastname: Schilling
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D009202:Cardiomyopathies / Q000175:diagnosis / Q000378:metabolism* / Q000628:therapy; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D017147:Defibrillators, Implantable; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000175:diagnosis / Q000378:metabolism* / Q000628:therapy; D012189:Retrospective Studies; D017180:Tachycardia, Ventricular / Q000175:diagnosis / Q000378:metabolism* / Q000628:therapy; D019098:Telomerase / Q000097:blood / Q000378:metabolism*; D059506:Telomere Shortening / Q000502:physiology*
chemical_list: D015415:Biomarkers; D019098:Telomerase
keywords: Implantable cardioverter defibrillator; Telomere biology; Ventricular arrhythmia