title: The relation of ventricular arrhythmia electrophysiological characteristics to cardiac phenotype and circadian patterns in hypertrophic cardiomyopathy.
abstract: BACKGROUND
  The triggers of ventricular arrhythmias (VAs) leading to sudden cardiac death in hypertrophic cardiomyopathy (HCM) are ill defined. We sought to examine the electrophysiological characteristics of VAs in HCM and study their relation to cardiac phenotype and circadian patterns using stored intracardiac electrocardiograms from implantable cardioverter defibrillators (ICDs).
  
  
  RESULTS
  A single centre, observational cohort study of 230 consecutively evaluated ICD recipients with HCM [median age 42 years, 97% primary prevention, 51% with anti-tachycardia pacing (ATP)]. Fifty-six non-clustered VAs (39 initially treated with ATP and 17 with shocks) from 29 patients were analysed. Monomorphic ventricular tachycardia was the culprit arrhythmia in 86% of cases, ventricular fibrillation/flutter in 9%, and polymorphic ventricular tachycardia in 5%. Prior to the onset of VA the rhythm was sinus in 67%, atrial fibrillation/flutter in 19%, and 15% were paced ventricularly; tachycardia (cycle length <600 ms) was present in 25%. Ventricular arrhythmias were triggered by premature ventricular complexes (PVCs) in 72%, which were late-coupled (84%). Short-long-short initiation was seen in 2% and 26% of VAs were sudden-onset without preceding PVCs. Ventricular arrhythmia peaked at midday (with 20% occurring between 2300 and 0700), on Sundays and in May. The cardiac phenotype and time of the day did not predict the mode of initiation. Age at ICD implantation was the only independent predictor of VA cycle length (linear regression coefficient 0.67, 95% CI 0.02-1.32, P= 0.04). Anti-tachycardia pacing terminated 67% of VAs, but patients with ATP therapy had a similar incidence of appropriate shocks (log-rank test P= 0.25) and syncope (log rank P= 0.23) to patients with shock as initial therapy.
  
  
  CONCLUSIONS
  Most VAs are monomorphic ventricular tachycardias triggered by late-coupled PVCs. They are frequently terminated by ATP, but ATP does not reduce the frequency of ICD shocks. Younger HCM patients have more rapid VAs, which may explain the peak of sudden cardiac death in early adulthood. The circadian periodicity is different from that observed in ischaemic heart disease, and is likely to relate to the distinct character of the arrhythmogenic substrate in HCM and its modulators.
authors.affiliation: Inherited Cardiac Diseases Unit,  The Heart Hospital/University College London, 16-18 Westmoreland Street, London W1G 8PH,  UK.
authors.forename: Constantinos
authors.initials: C
authors.lastname: O'Mahony
authors.forename: Pier D
authors.initials: PD
authors.lastname: Lambiase
authors.forename: Shafiqur M
authors.initials: SM
authors.lastname: Rahman
authors.forename: Montserrat
authors.initials: M
authors.lastname: Cardona
authors.forename: Margherita
authors.initials: M
authors.lastname: Calcagnino
authors.forename: Giovanni
authors.initials: G
authors.lastname: Quarta
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Tsovolas
authors.forename: Shereen
authors.initials: S
authors.lastname: Al-Shaikh
authors.forename: William
authors.initials: W
authors.lastname: McKenna
authors.forename: Perry
authors.initials: P
authors.lastname: Elliott
mesh_terms: D000328:Adult; D002312:Cardiomyopathy, Hypertrophic / Q000453:epidemiology / Q000503:physiopathology*; D002940:Circadian Rhythm / Q000502:physiology*; D015331:Cohort Studies; D016757:Death, Sudden, Cardiac / Q000517:prevention & control; D017147:Defibrillators, Implantable / Q000706:statistics & numerical data; D004562:Electrocardiography; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D008955:Models, Cardiovascular; D012307:Risk Factors; D017180:Tachycardia, Ventricular / Q000453:epidemiology / Q000503:physiopathology* / Q000628:therapy*; D018879:Ventricular Premature Complexes / Q000453:epidemiology / Q000503:physiopathology / Q000628:therapy